approach to acute or subacute myelopathy - fk uwks 2012 c · 2015. 4. 18. · william f....
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Approach to acute or subacute myelopathy
William F SchmalstiegMD
Brian G WeinshenkerMD
Neurologyreg Clinical Practice201075(Suppl 1)S2ndashS8
Improved understanding of the differentialdiagnosis and improved investigative tech-niques particularly neuroimaging and sero-
logic testing have facilitated the diagnosis ofpatients with acute and subacute myelopathy andreduced the proportion of patients who are labeledas having ldquoidiopathic transverse myelitisrdquo Addi-tionally these advances have identified subgroupsof patients in whom progression of deficit or fu-ture relapses are anticipated allowing interventionand prophylaxis as appropriate However earlymanagement remains empiric and consists of high-dose corticosteroids for most patients In the eventof an inadequate response to corticosteroids or asubsequent atypical course further investigationsto detect diagnoses other than ldquotransverse myelitisrdquoshould be considered and additional treatmentssuch as plasmapheresis may be appropriate Indi-vidualized diagnosis and treatment is more feasiblenow than in the past
IS IT AN ACUTE MYELOPATHY Localizing anacute neurologic process to the spinal cord is oftenbut not always straightforward (table 1) The as-cending sensory symptoms of acute inflammatorydemyelinating polyradiculoneuropathy (AIDP)may confuse the diagnosis as this complaint is alsohighly associated with acute myelopathy Un-equivocal upper motor neuron signs excludeAIDP but are often not apparent in the early
stages of a spinal cord insult Although not invariably present an unequivocal sensory level on the torsosensory loss indicating involvement of spinal tracts (eg spinothalamic modality impairment contralateral tomotor findings) or urinary retention localize to the spinal cord Myopathy or neuromuscular junction disor-ders may be mistaken for myelopathy particularly if the lower limbs are predominantly affected but theabsence of any sensory abnormality should suggest the correct localization Bilateral mesial frontal lobe lesions(eg bilateral anterior cerebral artery distribution infarcts) could mimic a myelopathy although abulia orother signs of frontal lobe dysfunction typically coexist Autoimmune or paraneoplastic muscle stiffness syn-dromes such as stiff-person syndrome associated with glutamic acid decarboxylase or amphiphysin autoanti-bodies may be confused with spasticity and erroneously lead one to suspect myelopathy
Occasionally patients with chronic myelopathy may present a history that mistakenly suggests an acuteprocess For example patients with primary progressive multiple sclerosis (MS) may experience acute transientworsening (pseudoexacerbation) in the setting of an underlying infection or heat exposure In such casescareful history will uncover symptoms that have been insidiously progressive over a longer interval than first
From the Department of Neurology Mayo Clinic College of Medicine Rochester MN
Disclosure Author disclosures are provided at the end of the article
Illustration by Amy P Collins
Address correspondence andreprint requests to Dr Brian GWeinshenker Department ofNeurology Mayo Clinic Collegeof Medicine 200 1st Street SWRochester MN 55905weinbmayoedu
S2 Copyright copy 2010 by AAN Enterprises Inc
suspected Patients with myelopathy who have noclear lesion on spinal MRI or multiple chronic-appearing lesions should be questioned to uncoversubtle previous symptoms of chronic myelopathyand examined to detect cognitive or bulbar impair-ment localizing elsewhere in the nervous system
WHEN IT IS AN ACUTE MYELOPATHY WHATCAUSES SHOULD BE CONSIDERED In pa-tients with recent onset symptoms particularly onesthat evolve rapidly the initial priority is to exclude asurgical emergency such as epidural metastasis or ab-scess When the index of suspicion for an acute com-pressive lesion is high immediate imaging isrequired ideally with MRI of the entire spine If im-aging demonstrates spinal cord compression due toan acute lesion such as epidural metastasis definitivemanagement (ie surgery) should be pursued with-out delay to prevent rapid and irreversible worsening
Often the cause of an acute or subacute myelopa-thy is inapparent after an initial evaluation In a re-cent French series of patients presenting with acutenoncompressive myelopathy 101170 (594) wereof uncertain cause initially although 55101(544) patients were ultimately diagnosed with ademyelinating or inflammatory disorder After aver-age follow-up of 732 months 49170 (288) had afinal diagnosis of myelopathy of uncertain etiologyThe most commonly identified causes were demyeli-nating disorders (MS and neuromyelitis optica) spi-nal cord infarction parainfectious myelitis and
systemic inflammatory disorders (eg Sjogren syn-drome and lupus)1
Transverse myelitis is the default diagnosis for anunexplained myelopathy evolving over the course ofdays to 3 weeks with subsequent stabilization or im-provement In practice there are no satisfactory waysto distinguish among idiopathic transverse myelitisparainfectious myelitis and postvaccinial myelitisWhen a viral illness occurs in close temporal associa-tion parainfectious myelitis is often diagnosed butthe causal role of the associated infection is difficultto determine for an individual patient One can con-fidently link the two only when myelitis occurs con-currently or within days of an infection known to beassociated with myelitis (eg zoster) or when investi-gation such as CSF PCR demonstrates unequivocalevidence of CNS infection
Nevertheless serologic evidence of recent infectionwith pathogens known to be associated with myelopa-thy (eg enteroviruses Chlamydia Mycoplasma) maylimit the need for further diagnostic investigations in anotherwise unexplained myelopathy Features suggestingan infectious etiology include fever rash (zoster entero-virus Lyme disease) meningismus a history of recenttravel (tuberculosis parasitic infections such as schisto-somiasis with travel to endemic regions) suspected ra-bies exposure or immunosuppression (herpes zostercytomegalovirus) It is particularly important to con-sider treatable infections such as syphilis HIV tubercu-losis Lyme disease and herpesviruses
Occasionally patients withchronic myelopathy maypresent a history thatmistakenly suggests an acuteprocess
Other diagnoses that may be made confidently inmost instances include cord compression vasculardisorders toxicmetabolic syndromes neoplasmparaneoplastic syndromes and sarcoidosis Althoughcompression is often obvious as the cause of myelop-athy on MRI spinal stenosis may cause impressiveand occasionally longitudinally extensive T2 signalabnormalities (3 vertebral segments) on spinalMRI that may lead one to suspect an inflammatorymyelopathy Circumscribed gadolinium enhance-ment at the point of maximal stenosis and a historyof progressive symptoms over many weeks to monthsare consistent findings in such cases (figure 1 A andB)2 Vascular myelopathies include those due to in-farction resulting from arterial embolism or hypo-perfusion hemorrhage or vascular malformationsassociated with venous hypertension Dural arterio-
Table 1 Distinguishing acute myelopathyfrom mimics
Signs strongly indicating myelopathy
Sensory level on torso
Spinal tract crossed findings (eg unilateral pyramidal signswith contralateral spinothalamic findings)
Spinal tract-specific sensory findings (eg selectivespinothalamic findings with preserved dorsal columnfindings suspended band of spinothalamic sensory loss)
Urinary retention
Signs consistent with but not diagnostic of myelopathy
Glove-and-stocking sensory loss (consider peripheralneuropathy)
Hyporeflexiahypotonia (consider peripheral neuropathy)
Unilateral or bilateral upper motor neuron signs (considerbrain or brainstem disorders)
Signs suggesting alternative diagnosis
Spasms rather than spasticity (consider stiff-personsyndrome)
Paratonic rigidity (consider frontal lobe disorder)
Cognitive impairment (consider frontal lobe or diffuse braindisorder)
Dysarthria and dysphagia (consider brainstem disorder suchas motor neuron disease)
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S3
Figure 1 MRI of representative cases of acute and subacute myelopathies
(A B) Sagittal T2 and gadolinium-enhanced T1 MRI showing longitudinally extensive cord signal change (A) and focal signet ringgadolinium enhancement (B) due to severe spinal stenosis (C) Sagittal T2 and axial gadolinium-enhanced T1 (inset) MRI demon-strating longitudinally extensive tract-specific lateral column enhancement due to paraneoplastic disorder in a patient withrenal cell carcinoma (D) Sagittal gadolinium-enhanced T1 and axial T2 (inset) MRI demonstrating focal enhancement and T2signal change in the periphery of the cord in a patient with partial transverse myelitis due to multiple sclerosis (E) Sagittal T2 andaxial gadolinium-enhanced T1 (inset) MRI showing longitudinally extensive transverse myelitis extending rostrally into the me-dulla and central cord enhancement due to neuromyelitis opticandashassociated myelitis (F) Sagittal and axial T2 (inset) MRI showinganterior cord signal change due to anterior spinal artery infarct (G) Sagittal and axial T2 (inset) MRI longitudinally extensivesignal change extending to the conus and flow voids (eccentric to the left side of the cord) characteristic of dural arteriovenous fistula(H) Sagittal and axial gadolinium-enhanced T1 (inset) MRI demonstrating nodular and subpial enhancement due to sarcoidosis
S4 Neurology Clinical Practice 75(Suppl 1) November 2 2010
venous fistula (DAVF)ndashassociated myelopathies maybe distinguished by the distinctive history of stepwiseprogression or transient worsening precipitated bywalking or prolonged standing This myelopathy canbe successfully treated by obliteration of the fistulaand should not be missed Toxic myelopathy due tonitrous oxide abuse is a consideration in younger pa-tients and medical professionals patients with under-lying vitamin B12 deficiency are particularlyvulnerable Vitamin and trace metal deficiencies usu-ally cause chronic myelopathies but as these etiolo-gies are readily treatable vitamin B12 and copperlevels should be tested in unexplained steroid nonre-sponsive myelopathy Spinal cord tumors maypresent subacutely or with apoplectic onset in thecase of hemorrhage into tumor and are usuallyreadily identifiable on MRI although rarely theymay be mistaken radiologically for myelitis Screen-ing for serum paraneoplastic autoantibodies includ-ing collapsin response mediator protein-5 (CRMP-5)antibody3 should be considered in patients withknown cancer constitutional symptoms smokinghistory or suggestive neuroradiology with isolated
tract-specific involvement Sarcoidosis may presentas isolated myelopathy Definitive diagnosis requiresbiopsy evidence of noncaseating granulomatous inflam-mation either from the nervous system or other in-volved organs A high serum angiotensin-convertingenzyme level is suggestive but nonspecific A diagnosisof isolated CNS sarcoidosis should be suspected whensubacute myelopathy is accompanied by patchy asym-metric slowly evolving and persistently enhancing gad-olinium cord lesions A satisfactory therapeutic responseto empiric long-term (months to years) corticosteroidtreatment provides a reasonable basis for a tentative butusually correct diagnosis
WHAT CLINICAL FEATURES SUGGEST A PAR-TICULAR DIAGNOSIS The time course (figure2) specific spinal cord syndrome and symptomsother than those referable to the spinal cord may pro-vide useful clues as to the diagnosis Apoplectic onsetsuggests a cord infarct or spinal hemorrhage both ofwhich may worsen over hours to days Parainfectiousor idiopathic myelitis myelitis related to inflamma-tory demyelinating diseases and some paraneoplastic
Figure 2 Differential diagnosis of acute myelopathy Time course and MRI findings
Relapses upon withdrawal of corticosteroidsimmunosuppression MRI may be normal ADEM acute disseminated en-cephalomyelitis DAVF dural arteriovenous fistula HTLV human T-lymphotropic virus MS multiple sclerosis NMO
neuromyelitis optica SCD subacute combined degeneration SD systemic disease TM transverse myelitis
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S5
syndromes evolve over days to weeks but generallyreach a nadir within 3 weeks after which there iseither improvement or stability4 When a myelopa-thy develops insidiously or continues to progress af-ter 3 weeks transverse myelitis becomes unlikely andthe differential diagnosis includes an intrinsic cordtumor compressive lesion DAVF metabolic de-rangement sarcoidosis or a degenerative process
The clinical syndrome of spinal cord involvementmay suggest a particular etiology although none arespecific Incomplete Brown-Sequard syndrome (lossof pain and temperature sensation contralateral toweakness) may be associated with either compressionor an intrinsic cord lesion such as demyelination Ananterior spinal cord syndrome with bilateral cortico-spinal and spinothalamic involvement sparing dorsalcolumn function is typical of anterior spinal arterydistribution infarction but may also occur in MS Acomplete spinal cord syndrome with bilateral in-volvement of all spinal tracts is rarely caused by anMS relapse or infarct but may occur in idiopathic orneuromyelitis optica (NMO)ndashassociated transversemyelitis or cord compression NMO-associated my-elitis more commonly presents with clinical and im-
aging signs of central cord involvement than doesMS-associated myelitis which more commonly af-fects the periphery of the cord Highly selective tractinvolvement (eg pure corticospinal tract involve-ment) especially when confirmed by MRI evidenceof highly localized enhancing tractopathy is charac-teristic of a paraneoplastic disorder (figure 1C)
Neurologic or constitutional symptoms not refer-able to the spinal cord focus the differential diagno-sis but may be irrelevant and distract one from the truediagnosis Optic neuritis or a prior diagnosis of inter-mediate uveitis may suggest MS Severe optic neuri-tis and an episode of unexplained intractable nauseaor hiccoughs are characteristic of NMO5 Coexist-ing peripheral neuropathy can occur in sarcoidSjogren syndrome lupus metabolic disorders(eg subacute combined degeneration) and para-neoplastic syndromes
WHAT INVESTIGATIONS SHOULD BE PER-FORMED MRI scan of the spinal cord with andwithout gadolinium contrast is the initial investiga-tion of choice in the evaluation of acute myelopathyContraindications are limited to MRI-incompatibleferromagnetic medical devices or foreign bodies andincompatibility with the scanner due to habitusWith careful coordination between cardiologists andradiologists MRI can be performed in selected pa-tients with cardiac pacemakers who are not entirelypacemaker-dependent For patients unable to un-dergo MRI CT myelography may be consideredwhen cord compression is suspected CSF evaluationincluding cell count glucose protein oligoclonalbands immunoglobulin G (IgG) index and cytologyis appropriate unless imaging history and examina-tion already suggest a clear diagnosis The results ofspinal MRI and clinical suspicion should guide theselection of additional investigations (table 2)
For noncompressive myelopathy the results ofMRI can be broadly subdivided into 3 categories
1 Short T2 hyperintensity (3 vertebral segmentsin length)
Focal discrete lesions that do not occupy the en-tire cord in axial cross-section are highly sugges-tive of MS (figure 1D) although remotesometimes forgotten trauma can occasionally pro-duce such lesions MRI scan of the brain may helpto clarify the cause detection of 1 or more brainlesions typical of MS (discrete periventricularjuxtacortical or infratentorial T2 hyperintensefoci) correlates with at least an 85ndash90 futurerisk of developing MS6 Oligoclonal bands andelevated CSF IgG index help to confirm a sus-pected MS diagnosis but CSF analysis may be
Table 2 Utility of diagnostic tests in evaluation of myelopathy
Test used to evaluate for Sensitivitya Specificitya
Imaging studies
Spinal MRI Rule out compressiondefine etiology
Brain MRI MS
CT myelogram Cord compression
Spinal angiogram DAVF
CSF studies
Oligoclonal bands MS
IgG index MS
PCR for herpesviruses CNS herpesvirus infection
Cytology Intramedullary neoplasm
Serologic and other bloodtests
NMO IgG NMO
Antinuclear SSanticardiolipin antibodies
Systemic inflammatorydisease NMO
Angiotensin convertingenzyme
Sarcoidosis
Serologies for infectiousagents
Parainfectious or infectiousmyelopathy
Electrodiagnostic studies
EMG Myelopathy associated withperipheral neuropathy (egsarcoid Sjoumlgrenparaneoplastic)
Abbreviations DAVF dural arteriovenous fistula IgG immunoglobulin G MS multiplesclerosis NMO neuromyelitis optica SS Sjoumlgren syndromea The symbols and indicate low intermediate and high sensitivityspecificityrespectively
S6 Neurology Clinical Practice 75(Suppl 1) November 2 2010
superfluous if other clinical and radiographic fea-tures are highly suggestive
2 Longitudinally extensive T2 hyperintensity (3vertebral segments in length)
Longitudinally extensive transverse myelitis oc-curs in idiopathic transverse myelitis NMO (fig-ure 1E) acute disseminated encephalomyelitiscord infarction and myelitis associated with sys-temic diseases such as systemic lupus erythemato-sus Serum NMO IgG testing is indicated beforeassigning a diagnosis of idiopathic transverse my-elitis7 Brain lesions on MRI eventually occur inthe majority of patients with NMO but usuallyNMO does not lead to the discrete Dawson fingerpattern of periventricular lesions characteristic ofMS However confluent and linear lesions encir-cling the ventricles may occur in NMO CSF oligo-clonal bands are usually absent in NMOCertain patterns of signal abnormality on MRIpredict a vascular disorder Anterior and centralcord signal change and swelling with sparing ofthe posterior columns suggest infarct particularlyin patients with a suggestive history (figure 1F)Posterior flow voids on spinal MRI representingdilation of the epidural venous plexus are a fairlyspecific but less sensitive indicator of DAVFwhereas longitudinally extensive gadolinium en-hancement and T2 hyperintensity often extend-ing to the conus are typical but nonspecificfindings (figure 1G) Magnetic resonance angiog-raphy may help to visualize a DAVF but spinalangiography is required for definitive diagnosisand treatment
If symptoms suggestive of recent infection or CSFpleocytosis (50 leukocytesL) are presentCSF PCR testing for herpesviruses (eg herpessimplex cytomegalovirus varicella zoster) and se-rologic testing for HIV syphilis and Lyme dis-ease should be considered Prominent CSFpleocytosis and occasionally neutrophilic pleocy-tosis may occur in myelitis associated with NMOSymptoms and signs of systemic inflammatorydisease such as polyarthritis should prompt auto-immune serologic testing (ie antinuclear anti-bodies SS-A SS-B antibodies) In the absence ofclinical indications of these diseases positive sero-logic tests may be unimportant although they mayindicate NMO a quarter of NMO spectrum disor-der patients have nonspecific serologic evidence ofautoimmunity usually in the absence of clinicalsigns of other autoimmune disorders8 Indiscrimi-nate use of autoantibody testing in all patientswith myelitis is not recommended MRI find-ings including nodular and persisting (2
months) gadolinium enhancement or menin-geal and nerve root enhancement suggest sar-coidosis (figure 1H) or rarely lymphoma
3 Normal MRI
Patients with suspected myelopathy and appar-ently normal MRI should undergo careful reviewof the images for subtle findings of cord signalchange atrophy or extrinsic compression by un-common causes (eg epidural lipomatosis) If ex-amination demonstrates unequivocal evidence ofa spinal cord process and the MRI is normal con-sider and test for degenerative infectious andmetabolic causes of myelopathy EMG and nerveconduction studies occasionally help to identify aprimary peripheral process (eg AIDP) or my-elopathy associated with concomitant peripheralneuropathy as can be seen in sarcoidosis and sub-acute combined degeneration
HOW SHOULD AN ACUTE MYELOPATHY BETREATED Controlled studies of treatment of acutemyelitis are lacking In myelitis due to demyelinat-ing inflammatory or undetermined cause expertconsensus favors high-dose IV corticosteroids typi-cally 1 gram of IV methylprednisolone daily for 5days This treatment should not be withheld in thecase of suspected recent viral infection the role of ste-roid treatment in patients with definitive evidence fordirect viral infection of the cord (eg myelitis occurringsimultaneously with or within days of a zoster eruption)is unclear Plasmapheresis should be considered in pa-tients who continue to have significant impairment af-ter high-dose corticosteroids In a sham-controlled trialof plasma exchange in patients with an acute relapse ofdemyelinating disease unresponsive to corticosteroidtreatment many of whom had acute myelitis 8 of 19(421) treated patients experienced moderate tomarked improvement vs 1 of 17 (59) who receivedsham treatment9 There are no established treatmentsfor patients with cord infarction
Long-term treatment to reduce recurrent attacks orprogression of deficit is required for patients withNMO neurosarcoidosis and systemic inflammatorydisorders Options to be considered for NMO includeazathioprine mycophenolate mofetil mitoxantroneand rituximab Sarcoidosis is usually treated with pro-longed high-dose oral corticosteroids (eg prednisone 1mgkgday for 6ndash12 months) Oral steroids andsteroid-sparing immunosuppressive agents are also typi-cally prescribed when systemic inflammatory processesinvolve the nervous system Immunomodulatory treat-ment should be considered in patients who are at highrisk for developing relapsing-remitting MS by virtue ofhaving additional lesions on MRI of the head
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S7
Ongoing clinical observation is an important partof the care of patients with an unexplained myelopa-thy Subsequent appearance of new neurologic orsystemic symptoms may reveal a demyelinating orsystemic inflammatory disorder Patients with relent-lessly progressive symptoms despite appropriate em-piric treatment may require spinal cord biopsy fordefinitive diagnosis particularly when follow-up im-aging demonstrates worsening
DISCUSSION Acute and subacute myelopathies re-quire urgent medical evaluation Imaging preferablyby MRI should be performed without delay to ex-clude a compressive lesion Subsequently history andphysical examination should guide subsequent inves-tigations to reach a definitive diagnosis As the etiol-ogy is often unclear at initial presentation empirictreatment should be provided while conducting fur-ther investigations to determine the etiology of my-elopathy A thorough evaluation often revealsevidence of a treatable disorder or one that may re-lapse without preventive treatment
DISCLOSURE
Dr Schmalstieg reports no disclosures Dr Weinshenker has served on
data safety monitoring boards for Novartis and Biogen Idec serves on the
editorial boards of Multiple Sclerosis the Canadian Journal of Neurological
Sciences and the Turkish Journal of Neurology receives research support
from the Guthy-Jackson Charitable Foundation and receives license roy-
alties from RSR Ltd and may receive royalties from Mayo Medical Ven-
tures for a patentintellectual property re Aquaporin-4 associated
antibodies for diagnosis of neuromyelitis optica
Received July 14 2010 Accepted in final form September 2 2010
REFERENCES1 Debette S de Seze J Pruvo JP et al Long-term outcome
of acute and subacute myelopathies J Neurol 2009256980ndash988
2 Kelley BJ Erickson BJ Weinshenker BG Compressivemyelopathy mimicking transverse myelitis Neurologist201016120ndash122
3 Keegan BM Pittock SJ Lennon VA Autoimmune my-elopathy associated with collapsin response-mediatorprotein-5 immunoglobulin G Ann Neurol 200863531ndash534
4 Proposed diagnostic criteria and nosology of acute trans-verse myelitis Neurology 200259499ndash505
5 Takahashi T Miyazawa I Misu T et al Intractable hiccupand nausea in neuromyelitis optica with anti-aquaporin-4antibody a herald of acute exacerbations J Neurol Neuro-surg Psychiatry 2008791075ndash1078
6 Brex PA Ciccarelli O OrsquoRiordan JI Sailer M ThompsonAJ Miller DH A longitudinal study of abnormalities onMRI and disability from multiple sclerosis N Engl J Med2002346158ndash164
7 Weinshenker BG Wingerchuk DM Vukusic S et alNeuromyelitis optica IgG predicts relapse after longitudi-nally extensive transverse myelitis Ann Neurol 200659566ndash569
8 Pittock SJ Lennon VA de Seze J et al Neuromyelitisoptica and non organ-specific autoimmunity Arch Neurol20086578ndash83
9 Weinshenker BG OrsquoBrien PC Petterson TM et alA randomized trial of plasma exchange in acute centralnervous system inflammatory demyelinating disease AnnNeurol 199946878ndash886
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Jeremy D Isaacs et al Noncompressive myelopathy associated with violent axial tics of Tourettesyndrome February 23 2010 wwwneurologyorg
David Roshal et al Pearls amp Oy-sters Fibrocartilaginous embolism myelopathy February 162010 wwwneurologyorg
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S8 Neurology Clinical Practice 75(Suppl 1) November 2 2010
DOI 101212WNL0b013e3181fb3638201075S2-S8 Neurology
William F Schmalstieg and Brian G WeinshenkerApproach to acute or subacute myelopathy
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suspected Patients with myelopathy who have noclear lesion on spinal MRI or multiple chronic-appearing lesions should be questioned to uncoversubtle previous symptoms of chronic myelopathyand examined to detect cognitive or bulbar impair-ment localizing elsewhere in the nervous system
WHEN IT IS AN ACUTE MYELOPATHY WHATCAUSES SHOULD BE CONSIDERED In pa-tients with recent onset symptoms particularly onesthat evolve rapidly the initial priority is to exclude asurgical emergency such as epidural metastasis or ab-scess When the index of suspicion for an acute com-pressive lesion is high immediate imaging isrequired ideally with MRI of the entire spine If im-aging demonstrates spinal cord compression due toan acute lesion such as epidural metastasis definitivemanagement (ie surgery) should be pursued with-out delay to prevent rapid and irreversible worsening
Often the cause of an acute or subacute myelopa-thy is inapparent after an initial evaluation In a re-cent French series of patients presenting with acutenoncompressive myelopathy 101170 (594) wereof uncertain cause initially although 55101(544) patients were ultimately diagnosed with ademyelinating or inflammatory disorder After aver-age follow-up of 732 months 49170 (288) had afinal diagnosis of myelopathy of uncertain etiologyThe most commonly identified causes were demyeli-nating disorders (MS and neuromyelitis optica) spi-nal cord infarction parainfectious myelitis and
systemic inflammatory disorders (eg Sjogren syn-drome and lupus)1
Transverse myelitis is the default diagnosis for anunexplained myelopathy evolving over the course ofdays to 3 weeks with subsequent stabilization or im-provement In practice there are no satisfactory waysto distinguish among idiopathic transverse myelitisparainfectious myelitis and postvaccinial myelitisWhen a viral illness occurs in close temporal associa-tion parainfectious myelitis is often diagnosed butthe causal role of the associated infection is difficultto determine for an individual patient One can con-fidently link the two only when myelitis occurs con-currently or within days of an infection known to beassociated with myelitis (eg zoster) or when investi-gation such as CSF PCR demonstrates unequivocalevidence of CNS infection
Nevertheless serologic evidence of recent infectionwith pathogens known to be associated with myelopa-thy (eg enteroviruses Chlamydia Mycoplasma) maylimit the need for further diagnostic investigations in anotherwise unexplained myelopathy Features suggestingan infectious etiology include fever rash (zoster entero-virus Lyme disease) meningismus a history of recenttravel (tuberculosis parasitic infections such as schisto-somiasis with travel to endemic regions) suspected ra-bies exposure or immunosuppression (herpes zostercytomegalovirus) It is particularly important to con-sider treatable infections such as syphilis HIV tubercu-losis Lyme disease and herpesviruses
Occasionally patients withchronic myelopathy maypresent a history thatmistakenly suggests an acuteprocess
Other diagnoses that may be made confidently inmost instances include cord compression vasculardisorders toxicmetabolic syndromes neoplasmparaneoplastic syndromes and sarcoidosis Althoughcompression is often obvious as the cause of myelop-athy on MRI spinal stenosis may cause impressiveand occasionally longitudinally extensive T2 signalabnormalities (3 vertebral segments) on spinalMRI that may lead one to suspect an inflammatorymyelopathy Circumscribed gadolinium enhance-ment at the point of maximal stenosis and a historyof progressive symptoms over many weeks to monthsare consistent findings in such cases (figure 1 A andB)2 Vascular myelopathies include those due to in-farction resulting from arterial embolism or hypo-perfusion hemorrhage or vascular malformationsassociated with venous hypertension Dural arterio-
Table 1 Distinguishing acute myelopathyfrom mimics
Signs strongly indicating myelopathy
Sensory level on torso
Spinal tract crossed findings (eg unilateral pyramidal signswith contralateral spinothalamic findings)
Spinal tract-specific sensory findings (eg selectivespinothalamic findings with preserved dorsal columnfindings suspended band of spinothalamic sensory loss)
Urinary retention
Signs consistent with but not diagnostic of myelopathy
Glove-and-stocking sensory loss (consider peripheralneuropathy)
Hyporeflexiahypotonia (consider peripheral neuropathy)
Unilateral or bilateral upper motor neuron signs (considerbrain or brainstem disorders)
Signs suggesting alternative diagnosis
Spasms rather than spasticity (consider stiff-personsyndrome)
Paratonic rigidity (consider frontal lobe disorder)
Cognitive impairment (consider frontal lobe or diffuse braindisorder)
Dysarthria and dysphagia (consider brainstem disorder suchas motor neuron disease)
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S3
Figure 1 MRI of representative cases of acute and subacute myelopathies
(A B) Sagittal T2 and gadolinium-enhanced T1 MRI showing longitudinally extensive cord signal change (A) and focal signet ringgadolinium enhancement (B) due to severe spinal stenosis (C) Sagittal T2 and axial gadolinium-enhanced T1 (inset) MRI demon-strating longitudinally extensive tract-specific lateral column enhancement due to paraneoplastic disorder in a patient withrenal cell carcinoma (D) Sagittal gadolinium-enhanced T1 and axial T2 (inset) MRI demonstrating focal enhancement and T2signal change in the periphery of the cord in a patient with partial transverse myelitis due to multiple sclerosis (E) Sagittal T2 andaxial gadolinium-enhanced T1 (inset) MRI showing longitudinally extensive transverse myelitis extending rostrally into the me-dulla and central cord enhancement due to neuromyelitis opticandashassociated myelitis (F) Sagittal and axial T2 (inset) MRI showinganterior cord signal change due to anterior spinal artery infarct (G) Sagittal and axial T2 (inset) MRI longitudinally extensivesignal change extending to the conus and flow voids (eccentric to the left side of the cord) characteristic of dural arteriovenous fistula(H) Sagittal and axial gadolinium-enhanced T1 (inset) MRI demonstrating nodular and subpial enhancement due to sarcoidosis
S4 Neurology Clinical Practice 75(Suppl 1) November 2 2010
venous fistula (DAVF)ndashassociated myelopathies maybe distinguished by the distinctive history of stepwiseprogression or transient worsening precipitated bywalking or prolonged standing This myelopathy canbe successfully treated by obliteration of the fistulaand should not be missed Toxic myelopathy due tonitrous oxide abuse is a consideration in younger pa-tients and medical professionals patients with under-lying vitamin B12 deficiency are particularlyvulnerable Vitamin and trace metal deficiencies usu-ally cause chronic myelopathies but as these etiolo-gies are readily treatable vitamin B12 and copperlevels should be tested in unexplained steroid nonre-sponsive myelopathy Spinal cord tumors maypresent subacutely or with apoplectic onset in thecase of hemorrhage into tumor and are usuallyreadily identifiable on MRI although rarely theymay be mistaken radiologically for myelitis Screen-ing for serum paraneoplastic autoantibodies includ-ing collapsin response mediator protein-5 (CRMP-5)antibody3 should be considered in patients withknown cancer constitutional symptoms smokinghistory or suggestive neuroradiology with isolated
tract-specific involvement Sarcoidosis may presentas isolated myelopathy Definitive diagnosis requiresbiopsy evidence of noncaseating granulomatous inflam-mation either from the nervous system or other in-volved organs A high serum angiotensin-convertingenzyme level is suggestive but nonspecific A diagnosisof isolated CNS sarcoidosis should be suspected whensubacute myelopathy is accompanied by patchy asym-metric slowly evolving and persistently enhancing gad-olinium cord lesions A satisfactory therapeutic responseto empiric long-term (months to years) corticosteroidtreatment provides a reasonable basis for a tentative butusually correct diagnosis
WHAT CLINICAL FEATURES SUGGEST A PAR-TICULAR DIAGNOSIS The time course (figure2) specific spinal cord syndrome and symptomsother than those referable to the spinal cord may pro-vide useful clues as to the diagnosis Apoplectic onsetsuggests a cord infarct or spinal hemorrhage both ofwhich may worsen over hours to days Parainfectiousor idiopathic myelitis myelitis related to inflamma-tory demyelinating diseases and some paraneoplastic
Figure 2 Differential diagnosis of acute myelopathy Time course and MRI findings
Relapses upon withdrawal of corticosteroidsimmunosuppression MRI may be normal ADEM acute disseminated en-cephalomyelitis DAVF dural arteriovenous fistula HTLV human T-lymphotropic virus MS multiple sclerosis NMO
neuromyelitis optica SCD subacute combined degeneration SD systemic disease TM transverse myelitis
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S5
syndromes evolve over days to weeks but generallyreach a nadir within 3 weeks after which there iseither improvement or stability4 When a myelopa-thy develops insidiously or continues to progress af-ter 3 weeks transverse myelitis becomes unlikely andthe differential diagnosis includes an intrinsic cordtumor compressive lesion DAVF metabolic de-rangement sarcoidosis or a degenerative process
The clinical syndrome of spinal cord involvementmay suggest a particular etiology although none arespecific Incomplete Brown-Sequard syndrome (lossof pain and temperature sensation contralateral toweakness) may be associated with either compressionor an intrinsic cord lesion such as demyelination Ananterior spinal cord syndrome with bilateral cortico-spinal and spinothalamic involvement sparing dorsalcolumn function is typical of anterior spinal arterydistribution infarction but may also occur in MS Acomplete spinal cord syndrome with bilateral in-volvement of all spinal tracts is rarely caused by anMS relapse or infarct but may occur in idiopathic orneuromyelitis optica (NMO)ndashassociated transversemyelitis or cord compression NMO-associated my-elitis more commonly presents with clinical and im-
aging signs of central cord involvement than doesMS-associated myelitis which more commonly af-fects the periphery of the cord Highly selective tractinvolvement (eg pure corticospinal tract involve-ment) especially when confirmed by MRI evidenceof highly localized enhancing tractopathy is charac-teristic of a paraneoplastic disorder (figure 1C)
Neurologic or constitutional symptoms not refer-able to the spinal cord focus the differential diagno-sis but may be irrelevant and distract one from the truediagnosis Optic neuritis or a prior diagnosis of inter-mediate uveitis may suggest MS Severe optic neuri-tis and an episode of unexplained intractable nauseaor hiccoughs are characteristic of NMO5 Coexist-ing peripheral neuropathy can occur in sarcoidSjogren syndrome lupus metabolic disorders(eg subacute combined degeneration) and para-neoplastic syndromes
WHAT INVESTIGATIONS SHOULD BE PER-FORMED MRI scan of the spinal cord with andwithout gadolinium contrast is the initial investiga-tion of choice in the evaluation of acute myelopathyContraindications are limited to MRI-incompatibleferromagnetic medical devices or foreign bodies andincompatibility with the scanner due to habitusWith careful coordination between cardiologists andradiologists MRI can be performed in selected pa-tients with cardiac pacemakers who are not entirelypacemaker-dependent For patients unable to un-dergo MRI CT myelography may be consideredwhen cord compression is suspected CSF evaluationincluding cell count glucose protein oligoclonalbands immunoglobulin G (IgG) index and cytologyis appropriate unless imaging history and examina-tion already suggest a clear diagnosis The results ofspinal MRI and clinical suspicion should guide theselection of additional investigations (table 2)
For noncompressive myelopathy the results ofMRI can be broadly subdivided into 3 categories
1 Short T2 hyperintensity (3 vertebral segmentsin length)
Focal discrete lesions that do not occupy the en-tire cord in axial cross-section are highly sugges-tive of MS (figure 1D) although remotesometimes forgotten trauma can occasionally pro-duce such lesions MRI scan of the brain may helpto clarify the cause detection of 1 or more brainlesions typical of MS (discrete periventricularjuxtacortical or infratentorial T2 hyperintensefoci) correlates with at least an 85ndash90 futurerisk of developing MS6 Oligoclonal bands andelevated CSF IgG index help to confirm a sus-pected MS diagnosis but CSF analysis may be
Table 2 Utility of diagnostic tests in evaluation of myelopathy
Test used to evaluate for Sensitivitya Specificitya
Imaging studies
Spinal MRI Rule out compressiondefine etiology
Brain MRI MS
CT myelogram Cord compression
Spinal angiogram DAVF
CSF studies
Oligoclonal bands MS
IgG index MS
PCR for herpesviruses CNS herpesvirus infection
Cytology Intramedullary neoplasm
Serologic and other bloodtests
NMO IgG NMO
Antinuclear SSanticardiolipin antibodies
Systemic inflammatorydisease NMO
Angiotensin convertingenzyme
Sarcoidosis
Serologies for infectiousagents
Parainfectious or infectiousmyelopathy
Electrodiagnostic studies
EMG Myelopathy associated withperipheral neuropathy (egsarcoid Sjoumlgrenparaneoplastic)
Abbreviations DAVF dural arteriovenous fistula IgG immunoglobulin G MS multiplesclerosis NMO neuromyelitis optica SS Sjoumlgren syndromea The symbols and indicate low intermediate and high sensitivityspecificityrespectively
S6 Neurology Clinical Practice 75(Suppl 1) November 2 2010
superfluous if other clinical and radiographic fea-tures are highly suggestive
2 Longitudinally extensive T2 hyperintensity (3vertebral segments in length)
Longitudinally extensive transverse myelitis oc-curs in idiopathic transverse myelitis NMO (fig-ure 1E) acute disseminated encephalomyelitiscord infarction and myelitis associated with sys-temic diseases such as systemic lupus erythemato-sus Serum NMO IgG testing is indicated beforeassigning a diagnosis of idiopathic transverse my-elitis7 Brain lesions on MRI eventually occur inthe majority of patients with NMO but usuallyNMO does not lead to the discrete Dawson fingerpattern of periventricular lesions characteristic ofMS However confluent and linear lesions encir-cling the ventricles may occur in NMO CSF oligo-clonal bands are usually absent in NMOCertain patterns of signal abnormality on MRIpredict a vascular disorder Anterior and centralcord signal change and swelling with sparing ofthe posterior columns suggest infarct particularlyin patients with a suggestive history (figure 1F)Posterior flow voids on spinal MRI representingdilation of the epidural venous plexus are a fairlyspecific but less sensitive indicator of DAVFwhereas longitudinally extensive gadolinium en-hancement and T2 hyperintensity often extend-ing to the conus are typical but nonspecificfindings (figure 1G) Magnetic resonance angiog-raphy may help to visualize a DAVF but spinalangiography is required for definitive diagnosisand treatment
If symptoms suggestive of recent infection or CSFpleocytosis (50 leukocytesL) are presentCSF PCR testing for herpesviruses (eg herpessimplex cytomegalovirus varicella zoster) and se-rologic testing for HIV syphilis and Lyme dis-ease should be considered Prominent CSFpleocytosis and occasionally neutrophilic pleocy-tosis may occur in myelitis associated with NMOSymptoms and signs of systemic inflammatorydisease such as polyarthritis should prompt auto-immune serologic testing (ie antinuclear anti-bodies SS-A SS-B antibodies) In the absence ofclinical indications of these diseases positive sero-logic tests may be unimportant although they mayindicate NMO a quarter of NMO spectrum disor-der patients have nonspecific serologic evidence ofautoimmunity usually in the absence of clinicalsigns of other autoimmune disorders8 Indiscrimi-nate use of autoantibody testing in all patientswith myelitis is not recommended MRI find-ings including nodular and persisting (2
months) gadolinium enhancement or menin-geal and nerve root enhancement suggest sar-coidosis (figure 1H) or rarely lymphoma
3 Normal MRI
Patients with suspected myelopathy and appar-ently normal MRI should undergo careful reviewof the images for subtle findings of cord signalchange atrophy or extrinsic compression by un-common causes (eg epidural lipomatosis) If ex-amination demonstrates unequivocal evidence ofa spinal cord process and the MRI is normal con-sider and test for degenerative infectious andmetabolic causes of myelopathy EMG and nerveconduction studies occasionally help to identify aprimary peripheral process (eg AIDP) or my-elopathy associated with concomitant peripheralneuropathy as can be seen in sarcoidosis and sub-acute combined degeneration
HOW SHOULD AN ACUTE MYELOPATHY BETREATED Controlled studies of treatment of acutemyelitis are lacking In myelitis due to demyelinat-ing inflammatory or undetermined cause expertconsensus favors high-dose IV corticosteroids typi-cally 1 gram of IV methylprednisolone daily for 5days This treatment should not be withheld in thecase of suspected recent viral infection the role of ste-roid treatment in patients with definitive evidence fordirect viral infection of the cord (eg myelitis occurringsimultaneously with or within days of a zoster eruption)is unclear Plasmapheresis should be considered in pa-tients who continue to have significant impairment af-ter high-dose corticosteroids In a sham-controlled trialof plasma exchange in patients with an acute relapse ofdemyelinating disease unresponsive to corticosteroidtreatment many of whom had acute myelitis 8 of 19(421) treated patients experienced moderate tomarked improvement vs 1 of 17 (59) who receivedsham treatment9 There are no established treatmentsfor patients with cord infarction
Long-term treatment to reduce recurrent attacks orprogression of deficit is required for patients withNMO neurosarcoidosis and systemic inflammatorydisorders Options to be considered for NMO includeazathioprine mycophenolate mofetil mitoxantroneand rituximab Sarcoidosis is usually treated with pro-longed high-dose oral corticosteroids (eg prednisone 1mgkgday for 6ndash12 months) Oral steroids andsteroid-sparing immunosuppressive agents are also typi-cally prescribed when systemic inflammatory processesinvolve the nervous system Immunomodulatory treat-ment should be considered in patients who are at highrisk for developing relapsing-remitting MS by virtue ofhaving additional lesions on MRI of the head
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S7
Ongoing clinical observation is an important partof the care of patients with an unexplained myelopa-thy Subsequent appearance of new neurologic orsystemic symptoms may reveal a demyelinating orsystemic inflammatory disorder Patients with relent-lessly progressive symptoms despite appropriate em-piric treatment may require spinal cord biopsy fordefinitive diagnosis particularly when follow-up im-aging demonstrates worsening
DISCUSSION Acute and subacute myelopathies re-quire urgent medical evaluation Imaging preferablyby MRI should be performed without delay to ex-clude a compressive lesion Subsequently history andphysical examination should guide subsequent inves-tigations to reach a definitive diagnosis As the etiol-ogy is often unclear at initial presentation empirictreatment should be provided while conducting fur-ther investigations to determine the etiology of my-elopathy A thorough evaluation often revealsevidence of a treatable disorder or one that may re-lapse without preventive treatment
DISCLOSURE
Dr Schmalstieg reports no disclosures Dr Weinshenker has served on
data safety monitoring boards for Novartis and Biogen Idec serves on the
editorial boards of Multiple Sclerosis the Canadian Journal of Neurological
Sciences and the Turkish Journal of Neurology receives research support
from the Guthy-Jackson Charitable Foundation and receives license roy-
alties from RSR Ltd and may receive royalties from Mayo Medical Ven-
tures for a patentintellectual property re Aquaporin-4 associated
antibodies for diagnosis of neuromyelitis optica
Received July 14 2010 Accepted in final form September 2 2010
REFERENCES1 Debette S de Seze J Pruvo JP et al Long-term outcome
of acute and subacute myelopathies J Neurol 2009256980ndash988
2 Kelley BJ Erickson BJ Weinshenker BG Compressivemyelopathy mimicking transverse myelitis Neurologist201016120ndash122
3 Keegan BM Pittock SJ Lennon VA Autoimmune my-elopathy associated with collapsin response-mediatorprotein-5 immunoglobulin G Ann Neurol 200863531ndash534
4 Proposed diagnostic criteria and nosology of acute trans-verse myelitis Neurology 200259499ndash505
5 Takahashi T Miyazawa I Misu T et al Intractable hiccupand nausea in neuromyelitis optica with anti-aquaporin-4antibody a herald of acute exacerbations J Neurol Neuro-surg Psychiatry 2008791075ndash1078
6 Brex PA Ciccarelli O OrsquoRiordan JI Sailer M ThompsonAJ Miller DH A longitudinal study of abnormalities onMRI and disability from multiple sclerosis N Engl J Med2002346158ndash164
7 Weinshenker BG Wingerchuk DM Vukusic S et alNeuromyelitis optica IgG predicts relapse after longitudi-nally extensive transverse myelitis Ann Neurol 200659566ndash569
8 Pittock SJ Lennon VA de Seze J et al Neuromyelitisoptica and non organ-specific autoimmunity Arch Neurol20086578ndash83
9 Weinshenker BG OrsquoBrien PC Petterson TM et alA randomized trial of plasma exchange in acute centralnervous system inflammatory demyelinating disease AnnNeurol 199946878ndash886
If you liked this article you may be interested in
Continuum
Spinal Cord Root and Plexus Disorders June 2008 wwwaancomgoelibrarycontinuum
Neurology
Nathan P Staff et al Hypertrophic nerves producing myelopathy in fulminant CIDP August 242010 wwwneurologyorg
Jeremy D Isaacs et al Noncompressive myelopathy associated with violent axial tics of Tourettesyndrome February 23 2010 wwwneurologyorg
David Roshal et al Pearls amp Oy-sters Fibrocartilaginous embolism myelopathy February 162010 wwwneurologyorg
N Duggal et al Brain reorganization in patients with spinal cord compression evaluated usingfMRI March 30 2010 wwwneurologyorg
S8 Neurology Clinical Practice 75(Suppl 1) November 2 2010
DOI 101212WNL0b013e3181fb3638201075S2-S8 Neurology
William F Schmalstieg and Brian G WeinshenkerApproach to acute or subacute myelopathy
This information is current as of November 1 2010
ServicesUpdated Information amp
httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlincluding high resolution figures can be found at
References
ref-list-1httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article cites 9 articles 2 of which you can access for free at
Citations
otherarticleshttpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article has been cited by 2 HighWire-hosted articles
Subspecialty Collections
httpwwwneurologyorgcgicollectiontransverse_myelitisTransverse myelitis
httpwwwneurologyorgcgicollectionmriMRI
httpwwwneurologyorgcgicollectionall_spinal_cordAll Spinal Cord s
httpwwwneurologyorgcgicollectionall_demyelinating_disease_cnAll Demyelinating disease (CNS)following collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpwwwneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2010 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
Figure 1 MRI of representative cases of acute and subacute myelopathies
(A B) Sagittal T2 and gadolinium-enhanced T1 MRI showing longitudinally extensive cord signal change (A) and focal signet ringgadolinium enhancement (B) due to severe spinal stenosis (C) Sagittal T2 and axial gadolinium-enhanced T1 (inset) MRI demon-strating longitudinally extensive tract-specific lateral column enhancement due to paraneoplastic disorder in a patient withrenal cell carcinoma (D) Sagittal gadolinium-enhanced T1 and axial T2 (inset) MRI demonstrating focal enhancement and T2signal change in the periphery of the cord in a patient with partial transverse myelitis due to multiple sclerosis (E) Sagittal T2 andaxial gadolinium-enhanced T1 (inset) MRI showing longitudinally extensive transverse myelitis extending rostrally into the me-dulla and central cord enhancement due to neuromyelitis opticandashassociated myelitis (F) Sagittal and axial T2 (inset) MRI showinganterior cord signal change due to anterior spinal artery infarct (G) Sagittal and axial T2 (inset) MRI longitudinally extensivesignal change extending to the conus and flow voids (eccentric to the left side of the cord) characteristic of dural arteriovenous fistula(H) Sagittal and axial gadolinium-enhanced T1 (inset) MRI demonstrating nodular and subpial enhancement due to sarcoidosis
S4 Neurology Clinical Practice 75(Suppl 1) November 2 2010
venous fistula (DAVF)ndashassociated myelopathies maybe distinguished by the distinctive history of stepwiseprogression or transient worsening precipitated bywalking or prolonged standing This myelopathy canbe successfully treated by obliteration of the fistulaand should not be missed Toxic myelopathy due tonitrous oxide abuse is a consideration in younger pa-tients and medical professionals patients with under-lying vitamin B12 deficiency are particularlyvulnerable Vitamin and trace metal deficiencies usu-ally cause chronic myelopathies but as these etiolo-gies are readily treatable vitamin B12 and copperlevels should be tested in unexplained steroid nonre-sponsive myelopathy Spinal cord tumors maypresent subacutely or with apoplectic onset in thecase of hemorrhage into tumor and are usuallyreadily identifiable on MRI although rarely theymay be mistaken radiologically for myelitis Screen-ing for serum paraneoplastic autoantibodies includ-ing collapsin response mediator protein-5 (CRMP-5)antibody3 should be considered in patients withknown cancer constitutional symptoms smokinghistory or suggestive neuroradiology with isolated
tract-specific involvement Sarcoidosis may presentas isolated myelopathy Definitive diagnosis requiresbiopsy evidence of noncaseating granulomatous inflam-mation either from the nervous system or other in-volved organs A high serum angiotensin-convertingenzyme level is suggestive but nonspecific A diagnosisof isolated CNS sarcoidosis should be suspected whensubacute myelopathy is accompanied by patchy asym-metric slowly evolving and persistently enhancing gad-olinium cord lesions A satisfactory therapeutic responseto empiric long-term (months to years) corticosteroidtreatment provides a reasonable basis for a tentative butusually correct diagnosis
WHAT CLINICAL FEATURES SUGGEST A PAR-TICULAR DIAGNOSIS The time course (figure2) specific spinal cord syndrome and symptomsother than those referable to the spinal cord may pro-vide useful clues as to the diagnosis Apoplectic onsetsuggests a cord infarct or spinal hemorrhage both ofwhich may worsen over hours to days Parainfectiousor idiopathic myelitis myelitis related to inflamma-tory demyelinating diseases and some paraneoplastic
Figure 2 Differential diagnosis of acute myelopathy Time course and MRI findings
Relapses upon withdrawal of corticosteroidsimmunosuppression MRI may be normal ADEM acute disseminated en-cephalomyelitis DAVF dural arteriovenous fistula HTLV human T-lymphotropic virus MS multiple sclerosis NMO
neuromyelitis optica SCD subacute combined degeneration SD systemic disease TM transverse myelitis
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S5
syndromes evolve over days to weeks but generallyreach a nadir within 3 weeks after which there iseither improvement or stability4 When a myelopa-thy develops insidiously or continues to progress af-ter 3 weeks transverse myelitis becomes unlikely andthe differential diagnosis includes an intrinsic cordtumor compressive lesion DAVF metabolic de-rangement sarcoidosis or a degenerative process
The clinical syndrome of spinal cord involvementmay suggest a particular etiology although none arespecific Incomplete Brown-Sequard syndrome (lossof pain and temperature sensation contralateral toweakness) may be associated with either compressionor an intrinsic cord lesion such as demyelination Ananterior spinal cord syndrome with bilateral cortico-spinal and spinothalamic involvement sparing dorsalcolumn function is typical of anterior spinal arterydistribution infarction but may also occur in MS Acomplete spinal cord syndrome with bilateral in-volvement of all spinal tracts is rarely caused by anMS relapse or infarct but may occur in idiopathic orneuromyelitis optica (NMO)ndashassociated transversemyelitis or cord compression NMO-associated my-elitis more commonly presents with clinical and im-
aging signs of central cord involvement than doesMS-associated myelitis which more commonly af-fects the periphery of the cord Highly selective tractinvolvement (eg pure corticospinal tract involve-ment) especially when confirmed by MRI evidenceof highly localized enhancing tractopathy is charac-teristic of a paraneoplastic disorder (figure 1C)
Neurologic or constitutional symptoms not refer-able to the spinal cord focus the differential diagno-sis but may be irrelevant and distract one from the truediagnosis Optic neuritis or a prior diagnosis of inter-mediate uveitis may suggest MS Severe optic neuri-tis and an episode of unexplained intractable nauseaor hiccoughs are characteristic of NMO5 Coexist-ing peripheral neuropathy can occur in sarcoidSjogren syndrome lupus metabolic disorders(eg subacute combined degeneration) and para-neoplastic syndromes
WHAT INVESTIGATIONS SHOULD BE PER-FORMED MRI scan of the spinal cord with andwithout gadolinium contrast is the initial investiga-tion of choice in the evaluation of acute myelopathyContraindications are limited to MRI-incompatibleferromagnetic medical devices or foreign bodies andincompatibility with the scanner due to habitusWith careful coordination between cardiologists andradiologists MRI can be performed in selected pa-tients with cardiac pacemakers who are not entirelypacemaker-dependent For patients unable to un-dergo MRI CT myelography may be consideredwhen cord compression is suspected CSF evaluationincluding cell count glucose protein oligoclonalbands immunoglobulin G (IgG) index and cytologyis appropriate unless imaging history and examina-tion already suggest a clear diagnosis The results ofspinal MRI and clinical suspicion should guide theselection of additional investigations (table 2)
For noncompressive myelopathy the results ofMRI can be broadly subdivided into 3 categories
1 Short T2 hyperintensity (3 vertebral segmentsin length)
Focal discrete lesions that do not occupy the en-tire cord in axial cross-section are highly sugges-tive of MS (figure 1D) although remotesometimes forgotten trauma can occasionally pro-duce such lesions MRI scan of the brain may helpto clarify the cause detection of 1 or more brainlesions typical of MS (discrete periventricularjuxtacortical or infratentorial T2 hyperintensefoci) correlates with at least an 85ndash90 futurerisk of developing MS6 Oligoclonal bands andelevated CSF IgG index help to confirm a sus-pected MS diagnosis but CSF analysis may be
Table 2 Utility of diagnostic tests in evaluation of myelopathy
Test used to evaluate for Sensitivitya Specificitya
Imaging studies
Spinal MRI Rule out compressiondefine etiology
Brain MRI MS
CT myelogram Cord compression
Spinal angiogram DAVF
CSF studies
Oligoclonal bands MS
IgG index MS
PCR for herpesviruses CNS herpesvirus infection
Cytology Intramedullary neoplasm
Serologic and other bloodtests
NMO IgG NMO
Antinuclear SSanticardiolipin antibodies
Systemic inflammatorydisease NMO
Angiotensin convertingenzyme
Sarcoidosis
Serologies for infectiousagents
Parainfectious or infectiousmyelopathy
Electrodiagnostic studies
EMG Myelopathy associated withperipheral neuropathy (egsarcoid Sjoumlgrenparaneoplastic)
Abbreviations DAVF dural arteriovenous fistula IgG immunoglobulin G MS multiplesclerosis NMO neuromyelitis optica SS Sjoumlgren syndromea The symbols and indicate low intermediate and high sensitivityspecificityrespectively
S6 Neurology Clinical Practice 75(Suppl 1) November 2 2010
superfluous if other clinical and radiographic fea-tures are highly suggestive
2 Longitudinally extensive T2 hyperintensity (3vertebral segments in length)
Longitudinally extensive transverse myelitis oc-curs in idiopathic transverse myelitis NMO (fig-ure 1E) acute disseminated encephalomyelitiscord infarction and myelitis associated with sys-temic diseases such as systemic lupus erythemato-sus Serum NMO IgG testing is indicated beforeassigning a diagnosis of idiopathic transverse my-elitis7 Brain lesions on MRI eventually occur inthe majority of patients with NMO but usuallyNMO does not lead to the discrete Dawson fingerpattern of periventricular lesions characteristic ofMS However confluent and linear lesions encir-cling the ventricles may occur in NMO CSF oligo-clonal bands are usually absent in NMOCertain patterns of signal abnormality on MRIpredict a vascular disorder Anterior and centralcord signal change and swelling with sparing ofthe posterior columns suggest infarct particularlyin patients with a suggestive history (figure 1F)Posterior flow voids on spinal MRI representingdilation of the epidural venous plexus are a fairlyspecific but less sensitive indicator of DAVFwhereas longitudinally extensive gadolinium en-hancement and T2 hyperintensity often extend-ing to the conus are typical but nonspecificfindings (figure 1G) Magnetic resonance angiog-raphy may help to visualize a DAVF but spinalangiography is required for definitive diagnosisand treatment
If symptoms suggestive of recent infection or CSFpleocytosis (50 leukocytesL) are presentCSF PCR testing for herpesviruses (eg herpessimplex cytomegalovirus varicella zoster) and se-rologic testing for HIV syphilis and Lyme dis-ease should be considered Prominent CSFpleocytosis and occasionally neutrophilic pleocy-tosis may occur in myelitis associated with NMOSymptoms and signs of systemic inflammatorydisease such as polyarthritis should prompt auto-immune serologic testing (ie antinuclear anti-bodies SS-A SS-B antibodies) In the absence ofclinical indications of these diseases positive sero-logic tests may be unimportant although they mayindicate NMO a quarter of NMO spectrum disor-der patients have nonspecific serologic evidence ofautoimmunity usually in the absence of clinicalsigns of other autoimmune disorders8 Indiscrimi-nate use of autoantibody testing in all patientswith myelitis is not recommended MRI find-ings including nodular and persisting (2
months) gadolinium enhancement or menin-geal and nerve root enhancement suggest sar-coidosis (figure 1H) or rarely lymphoma
3 Normal MRI
Patients with suspected myelopathy and appar-ently normal MRI should undergo careful reviewof the images for subtle findings of cord signalchange atrophy or extrinsic compression by un-common causes (eg epidural lipomatosis) If ex-amination demonstrates unequivocal evidence ofa spinal cord process and the MRI is normal con-sider and test for degenerative infectious andmetabolic causes of myelopathy EMG and nerveconduction studies occasionally help to identify aprimary peripheral process (eg AIDP) or my-elopathy associated with concomitant peripheralneuropathy as can be seen in sarcoidosis and sub-acute combined degeneration
HOW SHOULD AN ACUTE MYELOPATHY BETREATED Controlled studies of treatment of acutemyelitis are lacking In myelitis due to demyelinat-ing inflammatory or undetermined cause expertconsensus favors high-dose IV corticosteroids typi-cally 1 gram of IV methylprednisolone daily for 5days This treatment should not be withheld in thecase of suspected recent viral infection the role of ste-roid treatment in patients with definitive evidence fordirect viral infection of the cord (eg myelitis occurringsimultaneously with or within days of a zoster eruption)is unclear Plasmapheresis should be considered in pa-tients who continue to have significant impairment af-ter high-dose corticosteroids In a sham-controlled trialof plasma exchange in patients with an acute relapse ofdemyelinating disease unresponsive to corticosteroidtreatment many of whom had acute myelitis 8 of 19(421) treated patients experienced moderate tomarked improvement vs 1 of 17 (59) who receivedsham treatment9 There are no established treatmentsfor patients with cord infarction
Long-term treatment to reduce recurrent attacks orprogression of deficit is required for patients withNMO neurosarcoidosis and systemic inflammatorydisorders Options to be considered for NMO includeazathioprine mycophenolate mofetil mitoxantroneand rituximab Sarcoidosis is usually treated with pro-longed high-dose oral corticosteroids (eg prednisone 1mgkgday for 6ndash12 months) Oral steroids andsteroid-sparing immunosuppressive agents are also typi-cally prescribed when systemic inflammatory processesinvolve the nervous system Immunomodulatory treat-ment should be considered in patients who are at highrisk for developing relapsing-remitting MS by virtue ofhaving additional lesions on MRI of the head
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S7
Ongoing clinical observation is an important partof the care of patients with an unexplained myelopa-thy Subsequent appearance of new neurologic orsystemic symptoms may reveal a demyelinating orsystemic inflammatory disorder Patients with relent-lessly progressive symptoms despite appropriate em-piric treatment may require spinal cord biopsy fordefinitive diagnosis particularly when follow-up im-aging demonstrates worsening
DISCUSSION Acute and subacute myelopathies re-quire urgent medical evaluation Imaging preferablyby MRI should be performed without delay to ex-clude a compressive lesion Subsequently history andphysical examination should guide subsequent inves-tigations to reach a definitive diagnosis As the etiol-ogy is often unclear at initial presentation empirictreatment should be provided while conducting fur-ther investigations to determine the etiology of my-elopathy A thorough evaluation often revealsevidence of a treatable disorder or one that may re-lapse without preventive treatment
DISCLOSURE
Dr Schmalstieg reports no disclosures Dr Weinshenker has served on
data safety monitoring boards for Novartis and Biogen Idec serves on the
editorial boards of Multiple Sclerosis the Canadian Journal of Neurological
Sciences and the Turkish Journal of Neurology receives research support
from the Guthy-Jackson Charitable Foundation and receives license roy-
alties from RSR Ltd and may receive royalties from Mayo Medical Ven-
tures for a patentintellectual property re Aquaporin-4 associated
antibodies for diagnosis of neuromyelitis optica
Received July 14 2010 Accepted in final form September 2 2010
REFERENCES1 Debette S de Seze J Pruvo JP et al Long-term outcome
of acute and subacute myelopathies J Neurol 2009256980ndash988
2 Kelley BJ Erickson BJ Weinshenker BG Compressivemyelopathy mimicking transverse myelitis Neurologist201016120ndash122
3 Keegan BM Pittock SJ Lennon VA Autoimmune my-elopathy associated with collapsin response-mediatorprotein-5 immunoglobulin G Ann Neurol 200863531ndash534
4 Proposed diagnostic criteria and nosology of acute trans-verse myelitis Neurology 200259499ndash505
5 Takahashi T Miyazawa I Misu T et al Intractable hiccupand nausea in neuromyelitis optica with anti-aquaporin-4antibody a herald of acute exacerbations J Neurol Neuro-surg Psychiatry 2008791075ndash1078
6 Brex PA Ciccarelli O OrsquoRiordan JI Sailer M ThompsonAJ Miller DH A longitudinal study of abnormalities onMRI and disability from multiple sclerosis N Engl J Med2002346158ndash164
7 Weinshenker BG Wingerchuk DM Vukusic S et alNeuromyelitis optica IgG predicts relapse after longitudi-nally extensive transverse myelitis Ann Neurol 200659566ndash569
8 Pittock SJ Lennon VA de Seze J et al Neuromyelitisoptica and non organ-specific autoimmunity Arch Neurol20086578ndash83
9 Weinshenker BG OrsquoBrien PC Petterson TM et alA randomized trial of plasma exchange in acute centralnervous system inflammatory demyelinating disease AnnNeurol 199946878ndash886
If you liked this article you may be interested in
Continuum
Spinal Cord Root and Plexus Disorders June 2008 wwwaancomgoelibrarycontinuum
Neurology
Nathan P Staff et al Hypertrophic nerves producing myelopathy in fulminant CIDP August 242010 wwwneurologyorg
Jeremy D Isaacs et al Noncompressive myelopathy associated with violent axial tics of Tourettesyndrome February 23 2010 wwwneurologyorg
David Roshal et al Pearls amp Oy-sters Fibrocartilaginous embolism myelopathy February 162010 wwwneurologyorg
N Duggal et al Brain reorganization in patients with spinal cord compression evaluated usingfMRI March 30 2010 wwwneurologyorg
S8 Neurology Clinical Practice 75(Suppl 1) November 2 2010
DOI 101212WNL0b013e3181fb3638201075S2-S8 Neurology
William F Schmalstieg and Brian G WeinshenkerApproach to acute or subacute myelopathy
This information is current as of November 1 2010
ServicesUpdated Information amp
httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlincluding high resolution figures can be found at
References
ref-list-1httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article cites 9 articles 2 of which you can access for free at
Citations
otherarticleshttpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article has been cited by 2 HighWire-hosted articles
Subspecialty Collections
httpwwwneurologyorgcgicollectiontransverse_myelitisTransverse myelitis
httpwwwneurologyorgcgicollectionmriMRI
httpwwwneurologyorgcgicollectionall_spinal_cordAll Spinal Cord s
httpwwwneurologyorgcgicollectionall_demyelinating_disease_cnAll Demyelinating disease (CNS)following collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpwwwneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2010 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
venous fistula (DAVF)ndashassociated myelopathies maybe distinguished by the distinctive history of stepwiseprogression or transient worsening precipitated bywalking or prolonged standing This myelopathy canbe successfully treated by obliteration of the fistulaand should not be missed Toxic myelopathy due tonitrous oxide abuse is a consideration in younger pa-tients and medical professionals patients with under-lying vitamin B12 deficiency are particularlyvulnerable Vitamin and trace metal deficiencies usu-ally cause chronic myelopathies but as these etiolo-gies are readily treatable vitamin B12 and copperlevels should be tested in unexplained steroid nonre-sponsive myelopathy Spinal cord tumors maypresent subacutely or with apoplectic onset in thecase of hemorrhage into tumor and are usuallyreadily identifiable on MRI although rarely theymay be mistaken radiologically for myelitis Screen-ing for serum paraneoplastic autoantibodies includ-ing collapsin response mediator protein-5 (CRMP-5)antibody3 should be considered in patients withknown cancer constitutional symptoms smokinghistory or suggestive neuroradiology with isolated
tract-specific involvement Sarcoidosis may presentas isolated myelopathy Definitive diagnosis requiresbiopsy evidence of noncaseating granulomatous inflam-mation either from the nervous system or other in-volved organs A high serum angiotensin-convertingenzyme level is suggestive but nonspecific A diagnosisof isolated CNS sarcoidosis should be suspected whensubacute myelopathy is accompanied by patchy asym-metric slowly evolving and persistently enhancing gad-olinium cord lesions A satisfactory therapeutic responseto empiric long-term (months to years) corticosteroidtreatment provides a reasonable basis for a tentative butusually correct diagnosis
WHAT CLINICAL FEATURES SUGGEST A PAR-TICULAR DIAGNOSIS The time course (figure2) specific spinal cord syndrome and symptomsother than those referable to the spinal cord may pro-vide useful clues as to the diagnosis Apoplectic onsetsuggests a cord infarct or spinal hemorrhage both ofwhich may worsen over hours to days Parainfectiousor idiopathic myelitis myelitis related to inflamma-tory demyelinating diseases and some paraneoplastic
Figure 2 Differential diagnosis of acute myelopathy Time course and MRI findings
Relapses upon withdrawal of corticosteroidsimmunosuppression MRI may be normal ADEM acute disseminated en-cephalomyelitis DAVF dural arteriovenous fistula HTLV human T-lymphotropic virus MS multiple sclerosis NMO
neuromyelitis optica SCD subacute combined degeneration SD systemic disease TM transverse myelitis
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S5
syndromes evolve over days to weeks but generallyreach a nadir within 3 weeks after which there iseither improvement or stability4 When a myelopa-thy develops insidiously or continues to progress af-ter 3 weeks transverse myelitis becomes unlikely andthe differential diagnosis includes an intrinsic cordtumor compressive lesion DAVF metabolic de-rangement sarcoidosis or a degenerative process
The clinical syndrome of spinal cord involvementmay suggest a particular etiology although none arespecific Incomplete Brown-Sequard syndrome (lossof pain and temperature sensation contralateral toweakness) may be associated with either compressionor an intrinsic cord lesion such as demyelination Ananterior spinal cord syndrome with bilateral cortico-spinal and spinothalamic involvement sparing dorsalcolumn function is typical of anterior spinal arterydistribution infarction but may also occur in MS Acomplete spinal cord syndrome with bilateral in-volvement of all spinal tracts is rarely caused by anMS relapse or infarct but may occur in idiopathic orneuromyelitis optica (NMO)ndashassociated transversemyelitis or cord compression NMO-associated my-elitis more commonly presents with clinical and im-
aging signs of central cord involvement than doesMS-associated myelitis which more commonly af-fects the periphery of the cord Highly selective tractinvolvement (eg pure corticospinal tract involve-ment) especially when confirmed by MRI evidenceof highly localized enhancing tractopathy is charac-teristic of a paraneoplastic disorder (figure 1C)
Neurologic or constitutional symptoms not refer-able to the spinal cord focus the differential diagno-sis but may be irrelevant and distract one from the truediagnosis Optic neuritis or a prior diagnosis of inter-mediate uveitis may suggest MS Severe optic neuri-tis and an episode of unexplained intractable nauseaor hiccoughs are characteristic of NMO5 Coexist-ing peripheral neuropathy can occur in sarcoidSjogren syndrome lupus metabolic disorders(eg subacute combined degeneration) and para-neoplastic syndromes
WHAT INVESTIGATIONS SHOULD BE PER-FORMED MRI scan of the spinal cord with andwithout gadolinium contrast is the initial investiga-tion of choice in the evaluation of acute myelopathyContraindications are limited to MRI-incompatibleferromagnetic medical devices or foreign bodies andincompatibility with the scanner due to habitusWith careful coordination between cardiologists andradiologists MRI can be performed in selected pa-tients with cardiac pacemakers who are not entirelypacemaker-dependent For patients unable to un-dergo MRI CT myelography may be consideredwhen cord compression is suspected CSF evaluationincluding cell count glucose protein oligoclonalbands immunoglobulin G (IgG) index and cytologyis appropriate unless imaging history and examina-tion already suggest a clear diagnosis The results ofspinal MRI and clinical suspicion should guide theselection of additional investigations (table 2)
For noncompressive myelopathy the results ofMRI can be broadly subdivided into 3 categories
1 Short T2 hyperintensity (3 vertebral segmentsin length)
Focal discrete lesions that do not occupy the en-tire cord in axial cross-section are highly sugges-tive of MS (figure 1D) although remotesometimes forgotten trauma can occasionally pro-duce such lesions MRI scan of the brain may helpto clarify the cause detection of 1 or more brainlesions typical of MS (discrete periventricularjuxtacortical or infratentorial T2 hyperintensefoci) correlates with at least an 85ndash90 futurerisk of developing MS6 Oligoclonal bands andelevated CSF IgG index help to confirm a sus-pected MS diagnosis but CSF analysis may be
Table 2 Utility of diagnostic tests in evaluation of myelopathy
Test used to evaluate for Sensitivitya Specificitya
Imaging studies
Spinal MRI Rule out compressiondefine etiology
Brain MRI MS
CT myelogram Cord compression
Spinal angiogram DAVF
CSF studies
Oligoclonal bands MS
IgG index MS
PCR for herpesviruses CNS herpesvirus infection
Cytology Intramedullary neoplasm
Serologic and other bloodtests
NMO IgG NMO
Antinuclear SSanticardiolipin antibodies
Systemic inflammatorydisease NMO
Angiotensin convertingenzyme
Sarcoidosis
Serologies for infectiousagents
Parainfectious or infectiousmyelopathy
Electrodiagnostic studies
EMG Myelopathy associated withperipheral neuropathy (egsarcoid Sjoumlgrenparaneoplastic)
Abbreviations DAVF dural arteriovenous fistula IgG immunoglobulin G MS multiplesclerosis NMO neuromyelitis optica SS Sjoumlgren syndromea The symbols and indicate low intermediate and high sensitivityspecificityrespectively
S6 Neurology Clinical Practice 75(Suppl 1) November 2 2010
superfluous if other clinical and radiographic fea-tures are highly suggestive
2 Longitudinally extensive T2 hyperintensity (3vertebral segments in length)
Longitudinally extensive transverse myelitis oc-curs in idiopathic transverse myelitis NMO (fig-ure 1E) acute disseminated encephalomyelitiscord infarction and myelitis associated with sys-temic diseases such as systemic lupus erythemato-sus Serum NMO IgG testing is indicated beforeassigning a diagnosis of idiopathic transverse my-elitis7 Brain lesions on MRI eventually occur inthe majority of patients with NMO but usuallyNMO does not lead to the discrete Dawson fingerpattern of periventricular lesions characteristic ofMS However confluent and linear lesions encir-cling the ventricles may occur in NMO CSF oligo-clonal bands are usually absent in NMOCertain patterns of signal abnormality on MRIpredict a vascular disorder Anterior and centralcord signal change and swelling with sparing ofthe posterior columns suggest infarct particularlyin patients with a suggestive history (figure 1F)Posterior flow voids on spinal MRI representingdilation of the epidural venous plexus are a fairlyspecific but less sensitive indicator of DAVFwhereas longitudinally extensive gadolinium en-hancement and T2 hyperintensity often extend-ing to the conus are typical but nonspecificfindings (figure 1G) Magnetic resonance angiog-raphy may help to visualize a DAVF but spinalangiography is required for definitive diagnosisand treatment
If symptoms suggestive of recent infection or CSFpleocytosis (50 leukocytesL) are presentCSF PCR testing for herpesviruses (eg herpessimplex cytomegalovirus varicella zoster) and se-rologic testing for HIV syphilis and Lyme dis-ease should be considered Prominent CSFpleocytosis and occasionally neutrophilic pleocy-tosis may occur in myelitis associated with NMOSymptoms and signs of systemic inflammatorydisease such as polyarthritis should prompt auto-immune serologic testing (ie antinuclear anti-bodies SS-A SS-B antibodies) In the absence ofclinical indications of these diseases positive sero-logic tests may be unimportant although they mayindicate NMO a quarter of NMO spectrum disor-der patients have nonspecific serologic evidence ofautoimmunity usually in the absence of clinicalsigns of other autoimmune disorders8 Indiscrimi-nate use of autoantibody testing in all patientswith myelitis is not recommended MRI find-ings including nodular and persisting (2
months) gadolinium enhancement or menin-geal and nerve root enhancement suggest sar-coidosis (figure 1H) or rarely lymphoma
3 Normal MRI
Patients with suspected myelopathy and appar-ently normal MRI should undergo careful reviewof the images for subtle findings of cord signalchange atrophy or extrinsic compression by un-common causes (eg epidural lipomatosis) If ex-amination demonstrates unequivocal evidence ofa spinal cord process and the MRI is normal con-sider and test for degenerative infectious andmetabolic causes of myelopathy EMG and nerveconduction studies occasionally help to identify aprimary peripheral process (eg AIDP) or my-elopathy associated with concomitant peripheralneuropathy as can be seen in sarcoidosis and sub-acute combined degeneration
HOW SHOULD AN ACUTE MYELOPATHY BETREATED Controlled studies of treatment of acutemyelitis are lacking In myelitis due to demyelinat-ing inflammatory or undetermined cause expertconsensus favors high-dose IV corticosteroids typi-cally 1 gram of IV methylprednisolone daily for 5days This treatment should not be withheld in thecase of suspected recent viral infection the role of ste-roid treatment in patients with definitive evidence fordirect viral infection of the cord (eg myelitis occurringsimultaneously with or within days of a zoster eruption)is unclear Plasmapheresis should be considered in pa-tients who continue to have significant impairment af-ter high-dose corticosteroids In a sham-controlled trialof plasma exchange in patients with an acute relapse ofdemyelinating disease unresponsive to corticosteroidtreatment many of whom had acute myelitis 8 of 19(421) treated patients experienced moderate tomarked improvement vs 1 of 17 (59) who receivedsham treatment9 There are no established treatmentsfor patients with cord infarction
Long-term treatment to reduce recurrent attacks orprogression of deficit is required for patients withNMO neurosarcoidosis and systemic inflammatorydisorders Options to be considered for NMO includeazathioprine mycophenolate mofetil mitoxantroneand rituximab Sarcoidosis is usually treated with pro-longed high-dose oral corticosteroids (eg prednisone 1mgkgday for 6ndash12 months) Oral steroids andsteroid-sparing immunosuppressive agents are also typi-cally prescribed when systemic inflammatory processesinvolve the nervous system Immunomodulatory treat-ment should be considered in patients who are at highrisk for developing relapsing-remitting MS by virtue ofhaving additional lesions on MRI of the head
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S7
Ongoing clinical observation is an important partof the care of patients with an unexplained myelopa-thy Subsequent appearance of new neurologic orsystemic symptoms may reveal a demyelinating orsystemic inflammatory disorder Patients with relent-lessly progressive symptoms despite appropriate em-piric treatment may require spinal cord biopsy fordefinitive diagnosis particularly when follow-up im-aging demonstrates worsening
DISCUSSION Acute and subacute myelopathies re-quire urgent medical evaluation Imaging preferablyby MRI should be performed without delay to ex-clude a compressive lesion Subsequently history andphysical examination should guide subsequent inves-tigations to reach a definitive diagnosis As the etiol-ogy is often unclear at initial presentation empirictreatment should be provided while conducting fur-ther investigations to determine the etiology of my-elopathy A thorough evaluation often revealsevidence of a treatable disorder or one that may re-lapse without preventive treatment
DISCLOSURE
Dr Schmalstieg reports no disclosures Dr Weinshenker has served on
data safety monitoring boards for Novartis and Biogen Idec serves on the
editorial boards of Multiple Sclerosis the Canadian Journal of Neurological
Sciences and the Turkish Journal of Neurology receives research support
from the Guthy-Jackson Charitable Foundation and receives license roy-
alties from RSR Ltd and may receive royalties from Mayo Medical Ven-
tures for a patentintellectual property re Aquaporin-4 associated
antibodies for diagnosis of neuromyelitis optica
Received July 14 2010 Accepted in final form September 2 2010
REFERENCES1 Debette S de Seze J Pruvo JP et al Long-term outcome
of acute and subacute myelopathies J Neurol 2009256980ndash988
2 Kelley BJ Erickson BJ Weinshenker BG Compressivemyelopathy mimicking transverse myelitis Neurologist201016120ndash122
3 Keegan BM Pittock SJ Lennon VA Autoimmune my-elopathy associated with collapsin response-mediatorprotein-5 immunoglobulin G Ann Neurol 200863531ndash534
4 Proposed diagnostic criteria and nosology of acute trans-verse myelitis Neurology 200259499ndash505
5 Takahashi T Miyazawa I Misu T et al Intractable hiccupand nausea in neuromyelitis optica with anti-aquaporin-4antibody a herald of acute exacerbations J Neurol Neuro-surg Psychiatry 2008791075ndash1078
6 Brex PA Ciccarelli O OrsquoRiordan JI Sailer M ThompsonAJ Miller DH A longitudinal study of abnormalities onMRI and disability from multiple sclerosis N Engl J Med2002346158ndash164
7 Weinshenker BG Wingerchuk DM Vukusic S et alNeuromyelitis optica IgG predicts relapse after longitudi-nally extensive transverse myelitis Ann Neurol 200659566ndash569
8 Pittock SJ Lennon VA de Seze J et al Neuromyelitisoptica and non organ-specific autoimmunity Arch Neurol20086578ndash83
9 Weinshenker BG OrsquoBrien PC Petterson TM et alA randomized trial of plasma exchange in acute centralnervous system inflammatory demyelinating disease AnnNeurol 199946878ndash886
If you liked this article you may be interested in
Continuum
Spinal Cord Root and Plexus Disorders June 2008 wwwaancomgoelibrarycontinuum
Neurology
Nathan P Staff et al Hypertrophic nerves producing myelopathy in fulminant CIDP August 242010 wwwneurologyorg
Jeremy D Isaacs et al Noncompressive myelopathy associated with violent axial tics of Tourettesyndrome February 23 2010 wwwneurologyorg
David Roshal et al Pearls amp Oy-sters Fibrocartilaginous embolism myelopathy February 162010 wwwneurologyorg
N Duggal et al Brain reorganization in patients with spinal cord compression evaluated usingfMRI March 30 2010 wwwneurologyorg
S8 Neurology Clinical Practice 75(Suppl 1) November 2 2010
DOI 101212WNL0b013e3181fb3638201075S2-S8 Neurology
William F Schmalstieg and Brian G WeinshenkerApproach to acute or subacute myelopathy
This information is current as of November 1 2010
ServicesUpdated Information amp
httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlincluding high resolution figures can be found at
References
ref-list-1httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article cites 9 articles 2 of which you can access for free at
Citations
otherarticleshttpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article has been cited by 2 HighWire-hosted articles
Subspecialty Collections
httpwwwneurologyorgcgicollectiontransverse_myelitisTransverse myelitis
httpwwwneurologyorgcgicollectionmriMRI
httpwwwneurologyorgcgicollectionall_spinal_cordAll Spinal Cord s
httpwwwneurologyorgcgicollectionall_demyelinating_disease_cnAll Demyelinating disease (CNS)following collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpwwwneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2010 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
syndromes evolve over days to weeks but generallyreach a nadir within 3 weeks after which there iseither improvement or stability4 When a myelopa-thy develops insidiously or continues to progress af-ter 3 weeks transverse myelitis becomes unlikely andthe differential diagnosis includes an intrinsic cordtumor compressive lesion DAVF metabolic de-rangement sarcoidosis or a degenerative process
The clinical syndrome of spinal cord involvementmay suggest a particular etiology although none arespecific Incomplete Brown-Sequard syndrome (lossof pain and temperature sensation contralateral toweakness) may be associated with either compressionor an intrinsic cord lesion such as demyelination Ananterior spinal cord syndrome with bilateral cortico-spinal and spinothalamic involvement sparing dorsalcolumn function is typical of anterior spinal arterydistribution infarction but may also occur in MS Acomplete spinal cord syndrome with bilateral in-volvement of all spinal tracts is rarely caused by anMS relapse or infarct but may occur in idiopathic orneuromyelitis optica (NMO)ndashassociated transversemyelitis or cord compression NMO-associated my-elitis more commonly presents with clinical and im-
aging signs of central cord involvement than doesMS-associated myelitis which more commonly af-fects the periphery of the cord Highly selective tractinvolvement (eg pure corticospinal tract involve-ment) especially when confirmed by MRI evidenceof highly localized enhancing tractopathy is charac-teristic of a paraneoplastic disorder (figure 1C)
Neurologic or constitutional symptoms not refer-able to the spinal cord focus the differential diagno-sis but may be irrelevant and distract one from the truediagnosis Optic neuritis or a prior diagnosis of inter-mediate uveitis may suggest MS Severe optic neuri-tis and an episode of unexplained intractable nauseaor hiccoughs are characteristic of NMO5 Coexist-ing peripheral neuropathy can occur in sarcoidSjogren syndrome lupus metabolic disorders(eg subacute combined degeneration) and para-neoplastic syndromes
WHAT INVESTIGATIONS SHOULD BE PER-FORMED MRI scan of the spinal cord with andwithout gadolinium contrast is the initial investiga-tion of choice in the evaluation of acute myelopathyContraindications are limited to MRI-incompatibleferromagnetic medical devices or foreign bodies andincompatibility with the scanner due to habitusWith careful coordination between cardiologists andradiologists MRI can be performed in selected pa-tients with cardiac pacemakers who are not entirelypacemaker-dependent For patients unable to un-dergo MRI CT myelography may be consideredwhen cord compression is suspected CSF evaluationincluding cell count glucose protein oligoclonalbands immunoglobulin G (IgG) index and cytologyis appropriate unless imaging history and examina-tion already suggest a clear diagnosis The results ofspinal MRI and clinical suspicion should guide theselection of additional investigations (table 2)
For noncompressive myelopathy the results ofMRI can be broadly subdivided into 3 categories
1 Short T2 hyperintensity (3 vertebral segmentsin length)
Focal discrete lesions that do not occupy the en-tire cord in axial cross-section are highly sugges-tive of MS (figure 1D) although remotesometimes forgotten trauma can occasionally pro-duce such lesions MRI scan of the brain may helpto clarify the cause detection of 1 or more brainlesions typical of MS (discrete periventricularjuxtacortical or infratentorial T2 hyperintensefoci) correlates with at least an 85ndash90 futurerisk of developing MS6 Oligoclonal bands andelevated CSF IgG index help to confirm a sus-pected MS diagnosis but CSF analysis may be
Table 2 Utility of diagnostic tests in evaluation of myelopathy
Test used to evaluate for Sensitivitya Specificitya
Imaging studies
Spinal MRI Rule out compressiondefine etiology
Brain MRI MS
CT myelogram Cord compression
Spinal angiogram DAVF
CSF studies
Oligoclonal bands MS
IgG index MS
PCR for herpesviruses CNS herpesvirus infection
Cytology Intramedullary neoplasm
Serologic and other bloodtests
NMO IgG NMO
Antinuclear SSanticardiolipin antibodies
Systemic inflammatorydisease NMO
Angiotensin convertingenzyme
Sarcoidosis
Serologies for infectiousagents
Parainfectious or infectiousmyelopathy
Electrodiagnostic studies
EMG Myelopathy associated withperipheral neuropathy (egsarcoid Sjoumlgrenparaneoplastic)
Abbreviations DAVF dural arteriovenous fistula IgG immunoglobulin G MS multiplesclerosis NMO neuromyelitis optica SS Sjoumlgren syndromea The symbols and indicate low intermediate and high sensitivityspecificityrespectively
S6 Neurology Clinical Practice 75(Suppl 1) November 2 2010
superfluous if other clinical and radiographic fea-tures are highly suggestive
2 Longitudinally extensive T2 hyperintensity (3vertebral segments in length)
Longitudinally extensive transverse myelitis oc-curs in idiopathic transverse myelitis NMO (fig-ure 1E) acute disseminated encephalomyelitiscord infarction and myelitis associated with sys-temic diseases such as systemic lupus erythemato-sus Serum NMO IgG testing is indicated beforeassigning a diagnosis of idiopathic transverse my-elitis7 Brain lesions on MRI eventually occur inthe majority of patients with NMO but usuallyNMO does not lead to the discrete Dawson fingerpattern of periventricular lesions characteristic ofMS However confluent and linear lesions encir-cling the ventricles may occur in NMO CSF oligo-clonal bands are usually absent in NMOCertain patterns of signal abnormality on MRIpredict a vascular disorder Anterior and centralcord signal change and swelling with sparing ofthe posterior columns suggest infarct particularlyin patients with a suggestive history (figure 1F)Posterior flow voids on spinal MRI representingdilation of the epidural venous plexus are a fairlyspecific but less sensitive indicator of DAVFwhereas longitudinally extensive gadolinium en-hancement and T2 hyperintensity often extend-ing to the conus are typical but nonspecificfindings (figure 1G) Magnetic resonance angiog-raphy may help to visualize a DAVF but spinalangiography is required for definitive diagnosisand treatment
If symptoms suggestive of recent infection or CSFpleocytosis (50 leukocytesL) are presentCSF PCR testing for herpesviruses (eg herpessimplex cytomegalovirus varicella zoster) and se-rologic testing for HIV syphilis and Lyme dis-ease should be considered Prominent CSFpleocytosis and occasionally neutrophilic pleocy-tosis may occur in myelitis associated with NMOSymptoms and signs of systemic inflammatorydisease such as polyarthritis should prompt auto-immune serologic testing (ie antinuclear anti-bodies SS-A SS-B antibodies) In the absence ofclinical indications of these diseases positive sero-logic tests may be unimportant although they mayindicate NMO a quarter of NMO spectrum disor-der patients have nonspecific serologic evidence ofautoimmunity usually in the absence of clinicalsigns of other autoimmune disorders8 Indiscrimi-nate use of autoantibody testing in all patientswith myelitis is not recommended MRI find-ings including nodular and persisting (2
months) gadolinium enhancement or menin-geal and nerve root enhancement suggest sar-coidosis (figure 1H) or rarely lymphoma
3 Normal MRI
Patients with suspected myelopathy and appar-ently normal MRI should undergo careful reviewof the images for subtle findings of cord signalchange atrophy or extrinsic compression by un-common causes (eg epidural lipomatosis) If ex-amination demonstrates unequivocal evidence ofa spinal cord process and the MRI is normal con-sider and test for degenerative infectious andmetabolic causes of myelopathy EMG and nerveconduction studies occasionally help to identify aprimary peripheral process (eg AIDP) or my-elopathy associated with concomitant peripheralneuropathy as can be seen in sarcoidosis and sub-acute combined degeneration
HOW SHOULD AN ACUTE MYELOPATHY BETREATED Controlled studies of treatment of acutemyelitis are lacking In myelitis due to demyelinat-ing inflammatory or undetermined cause expertconsensus favors high-dose IV corticosteroids typi-cally 1 gram of IV methylprednisolone daily for 5days This treatment should not be withheld in thecase of suspected recent viral infection the role of ste-roid treatment in patients with definitive evidence fordirect viral infection of the cord (eg myelitis occurringsimultaneously with or within days of a zoster eruption)is unclear Plasmapheresis should be considered in pa-tients who continue to have significant impairment af-ter high-dose corticosteroids In a sham-controlled trialof plasma exchange in patients with an acute relapse ofdemyelinating disease unresponsive to corticosteroidtreatment many of whom had acute myelitis 8 of 19(421) treated patients experienced moderate tomarked improvement vs 1 of 17 (59) who receivedsham treatment9 There are no established treatmentsfor patients with cord infarction
Long-term treatment to reduce recurrent attacks orprogression of deficit is required for patients withNMO neurosarcoidosis and systemic inflammatorydisorders Options to be considered for NMO includeazathioprine mycophenolate mofetil mitoxantroneand rituximab Sarcoidosis is usually treated with pro-longed high-dose oral corticosteroids (eg prednisone 1mgkgday for 6ndash12 months) Oral steroids andsteroid-sparing immunosuppressive agents are also typi-cally prescribed when systemic inflammatory processesinvolve the nervous system Immunomodulatory treat-ment should be considered in patients who are at highrisk for developing relapsing-remitting MS by virtue ofhaving additional lesions on MRI of the head
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S7
Ongoing clinical observation is an important partof the care of patients with an unexplained myelopa-thy Subsequent appearance of new neurologic orsystemic symptoms may reveal a demyelinating orsystemic inflammatory disorder Patients with relent-lessly progressive symptoms despite appropriate em-piric treatment may require spinal cord biopsy fordefinitive diagnosis particularly when follow-up im-aging demonstrates worsening
DISCUSSION Acute and subacute myelopathies re-quire urgent medical evaluation Imaging preferablyby MRI should be performed without delay to ex-clude a compressive lesion Subsequently history andphysical examination should guide subsequent inves-tigations to reach a definitive diagnosis As the etiol-ogy is often unclear at initial presentation empirictreatment should be provided while conducting fur-ther investigations to determine the etiology of my-elopathy A thorough evaluation often revealsevidence of a treatable disorder or one that may re-lapse without preventive treatment
DISCLOSURE
Dr Schmalstieg reports no disclosures Dr Weinshenker has served on
data safety monitoring boards for Novartis and Biogen Idec serves on the
editorial boards of Multiple Sclerosis the Canadian Journal of Neurological
Sciences and the Turkish Journal of Neurology receives research support
from the Guthy-Jackson Charitable Foundation and receives license roy-
alties from RSR Ltd and may receive royalties from Mayo Medical Ven-
tures for a patentintellectual property re Aquaporin-4 associated
antibodies for diagnosis of neuromyelitis optica
Received July 14 2010 Accepted in final form September 2 2010
REFERENCES1 Debette S de Seze J Pruvo JP et al Long-term outcome
of acute and subacute myelopathies J Neurol 2009256980ndash988
2 Kelley BJ Erickson BJ Weinshenker BG Compressivemyelopathy mimicking transverse myelitis Neurologist201016120ndash122
3 Keegan BM Pittock SJ Lennon VA Autoimmune my-elopathy associated with collapsin response-mediatorprotein-5 immunoglobulin G Ann Neurol 200863531ndash534
4 Proposed diagnostic criteria and nosology of acute trans-verse myelitis Neurology 200259499ndash505
5 Takahashi T Miyazawa I Misu T et al Intractable hiccupand nausea in neuromyelitis optica with anti-aquaporin-4antibody a herald of acute exacerbations J Neurol Neuro-surg Psychiatry 2008791075ndash1078
6 Brex PA Ciccarelli O OrsquoRiordan JI Sailer M ThompsonAJ Miller DH A longitudinal study of abnormalities onMRI and disability from multiple sclerosis N Engl J Med2002346158ndash164
7 Weinshenker BG Wingerchuk DM Vukusic S et alNeuromyelitis optica IgG predicts relapse after longitudi-nally extensive transverse myelitis Ann Neurol 200659566ndash569
8 Pittock SJ Lennon VA de Seze J et al Neuromyelitisoptica and non organ-specific autoimmunity Arch Neurol20086578ndash83
9 Weinshenker BG OrsquoBrien PC Petterson TM et alA randomized trial of plasma exchange in acute centralnervous system inflammatory demyelinating disease AnnNeurol 199946878ndash886
If you liked this article you may be interested in
Continuum
Spinal Cord Root and Plexus Disorders June 2008 wwwaancomgoelibrarycontinuum
Neurology
Nathan P Staff et al Hypertrophic nerves producing myelopathy in fulminant CIDP August 242010 wwwneurologyorg
Jeremy D Isaacs et al Noncompressive myelopathy associated with violent axial tics of Tourettesyndrome February 23 2010 wwwneurologyorg
David Roshal et al Pearls amp Oy-sters Fibrocartilaginous embolism myelopathy February 162010 wwwneurologyorg
N Duggal et al Brain reorganization in patients with spinal cord compression evaluated usingfMRI March 30 2010 wwwneurologyorg
S8 Neurology Clinical Practice 75(Suppl 1) November 2 2010
DOI 101212WNL0b013e3181fb3638201075S2-S8 Neurology
William F Schmalstieg and Brian G WeinshenkerApproach to acute or subacute myelopathy
This information is current as of November 1 2010
ServicesUpdated Information amp
httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlincluding high resolution figures can be found at
References
ref-list-1httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article cites 9 articles 2 of which you can access for free at
Citations
otherarticleshttpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article has been cited by 2 HighWire-hosted articles
Subspecialty Collections
httpwwwneurologyorgcgicollectiontransverse_myelitisTransverse myelitis
httpwwwneurologyorgcgicollectionmriMRI
httpwwwneurologyorgcgicollectionall_spinal_cordAll Spinal Cord s
httpwwwneurologyorgcgicollectionall_demyelinating_disease_cnAll Demyelinating disease (CNS)following collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpwwwneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2010 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
superfluous if other clinical and radiographic fea-tures are highly suggestive
2 Longitudinally extensive T2 hyperintensity (3vertebral segments in length)
Longitudinally extensive transverse myelitis oc-curs in idiopathic transverse myelitis NMO (fig-ure 1E) acute disseminated encephalomyelitiscord infarction and myelitis associated with sys-temic diseases such as systemic lupus erythemato-sus Serum NMO IgG testing is indicated beforeassigning a diagnosis of idiopathic transverse my-elitis7 Brain lesions on MRI eventually occur inthe majority of patients with NMO but usuallyNMO does not lead to the discrete Dawson fingerpattern of periventricular lesions characteristic ofMS However confluent and linear lesions encir-cling the ventricles may occur in NMO CSF oligo-clonal bands are usually absent in NMOCertain patterns of signal abnormality on MRIpredict a vascular disorder Anterior and centralcord signal change and swelling with sparing ofthe posterior columns suggest infarct particularlyin patients with a suggestive history (figure 1F)Posterior flow voids on spinal MRI representingdilation of the epidural venous plexus are a fairlyspecific but less sensitive indicator of DAVFwhereas longitudinally extensive gadolinium en-hancement and T2 hyperintensity often extend-ing to the conus are typical but nonspecificfindings (figure 1G) Magnetic resonance angiog-raphy may help to visualize a DAVF but spinalangiography is required for definitive diagnosisand treatment
If symptoms suggestive of recent infection or CSFpleocytosis (50 leukocytesL) are presentCSF PCR testing for herpesviruses (eg herpessimplex cytomegalovirus varicella zoster) and se-rologic testing for HIV syphilis and Lyme dis-ease should be considered Prominent CSFpleocytosis and occasionally neutrophilic pleocy-tosis may occur in myelitis associated with NMOSymptoms and signs of systemic inflammatorydisease such as polyarthritis should prompt auto-immune serologic testing (ie antinuclear anti-bodies SS-A SS-B antibodies) In the absence ofclinical indications of these diseases positive sero-logic tests may be unimportant although they mayindicate NMO a quarter of NMO spectrum disor-der patients have nonspecific serologic evidence ofautoimmunity usually in the absence of clinicalsigns of other autoimmune disorders8 Indiscrimi-nate use of autoantibody testing in all patientswith myelitis is not recommended MRI find-ings including nodular and persisting (2
months) gadolinium enhancement or menin-geal and nerve root enhancement suggest sar-coidosis (figure 1H) or rarely lymphoma
3 Normal MRI
Patients with suspected myelopathy and appar-ently normal MRI should undergo careful reviewof the images for subtle findings of cord signalchange atrophy or extrinsic compression by un-common causes (eg epidural lipomatosis) If ex-amination demonstrates unequivocal evidence ofa spinal cord process and the MRI is normal con-sider and test for degenerative infectious andmetabolic causes of myelopathy EMG and nerveconduction studies occasionally help to identify aprimary peripheral process (eg AIDP) or my-elopathy associated with concomitant peripheralneuropathy as can be seen in sarcoidosis and sub-acute combined degeneration
HOW SHOULD AN ACUTE MYELOPATHY BETREATED Controlled studies of treatment of acutemyelitis are lacking In myelitis due to demyelinat-ing inflammatory or undetermined cause expertconsensus favors high-dose IV corticosteroids typi-cally 1 gram of IV methylprednisolone daily for 5days This treatment should not be withheld in thecase of suspected recent viral infection the role of ste-roid treatment in patients with definitive evidence fordirect viral infection of the cord (eg myelitis occurringsimultaneously with or within days of a zoster eruption)is unclear Plasmapheresis should be considered in pa-tients who continue to have significant impairment af-ter high-dose corticosteroids In a sham-controlled trialof plasma exchange in patients with an acute relapse ofdemyelinating disease unresponsive to corticosteroidtreatment many of whom had acute myelitis 8 of 19(421) treated patients experienced moderate tomarked improvement vs 1 of 17 (59) who receivedsham treatment9 There are no established treatmentsfor patients with cord infarction
Long-term treatment to reduce recurrent attacks orprogression of deficit is required for patients withNMO neurosarcoidosis and systemic inflammatorydisorders Options to be considered for NMO includeazathioprine mycophenolate mofetil mitoxantroneand rituximab Sarcoidosis is usually treated with pro-longed high-dose oral corticosteroids (eg prednisone 1mgkgday for 6ndash12 months) Oral steroids andsteroid-sparing immunosuppressive agents are also typi-cally prescribed when systemic inflammatory processesinvolve the nervous system Immunomodulatory treat-ment should be considered in patients who are at highrisk for developing relapsing-remitting MS by virtue ofhaving additional lesions on MRI of the head
Neurology Clinical Practice 75(Suppl 1) November 2 2010 S7
Ongoing clinical observation is an important partof the care of patients with an unexplained myelopa-thy Subsequent appearance of new neurologic orsystemic symptoms may reveal a demyelinating orsystemic inflammatory disorder Patients with relent-lessly progressive symptoms despite appropriate em-piric treatment may require spinal cord biopsy fordefinitive diagnosis particularly when follow-up im-aging demonstrates worsening
DISCUSSION Acute and subacute myelopathies re-quire urgent medical evaluation Imaging preferablyby MRI should be performed without delay to ex-clude a compressive lesion Subsequently history andphysical examination should guide subsequent inves-tigations to reach a definitive diagnosis As the etiol-ogy is often unclear at initial presentation empirictreatment should be provided while conducting fur-ther investigations to determine the etiology of my-elopathy A thorough evaluation often revealsevidence of a treatable disorder or one that may re-lapse without preventive treatment
DISCLOSURE
Dr Schmalstieg reports no disclosures Dr Weinshenker has served on
data safety monitoring boards for Novartis and Biogen Idec serves on the
editorial boards of Multiple Sclerosis the Canadian Journal of Neurological
Sciences and the Turkish Journal of Neurology receives research support
from the Guthy-Jackson Charitable Foundation and receives license roy-
alties from RSR Ltd and may receive royalties from Mayo Medical Ven-
tures for a patentintellectual property re Aquaporin-4 associated
antibodies for diagnosis of neuromyelitis optica
Received July 14 2010 Accepted in final form September 2 2010
REFERENCES1 Debette S de Seze J Pruvo JP et al Long-term outcome
of acute and subacute myelopathies J Neurol 2009256980ndash988
2 Kelley BJ Erickson BJ Weinshenker BG Compressivemyelopathy mimicking transverse myelitis Neurologist201016120ndash122
3 Keegan BM Pittock SJ Lennon VA Autoimmune my-elopathy associated with collapsin response-mediatorprotein-5 immunoglobulin G Ann Neurol 200863531ndash534
4 Proposed diagnostic criteria and nosology of acute trans-verse myelitis Neurology 200259499ndash505
5 Takahashi T Miyazawa I Misu T et al Intractable hiccupand nausea in neuromyelitis optica with anti-aquaporin-4antibody a herald of acute exacerbations J Neurol Neuro-surg Psychiatry 2008791075ndash1078
6 Brex PA Ciccarelli O OrsquoRiordan JI Sailer M ThompsonAJ Miller DH A longitudinal study of abnormalities onMRI and disability from multiple sclerosis N Engl J Med2002346158ndash164
7 Weinshenker BG Wingerchuk DM Vukusic S et alNeuromyelitis optica IgG predicts relapse after longitudi-nally extensive transverse myelitis Ann Neurol 200659566ndash569
8 Pittock SJ Lennon VA de Seze J et al Neuromyelitisoptica and non organ-specific autoimmunity Arch Neurol20086578ndash83
9 Weinshenker BG OrsquoBrien PC Petterson TM et alA randomized trial of plasma exchange in acute centralnervous system inflammatory demyelinating disease AnnNeurol 199946878ndash886
If you liked this article you may be interested in
Continuum
Spinal Cord Root and Plexus Disorders June 2008 wwwaancomgoelibrarycontinuum
Neurology
Nathan P Staff et al Hypertrophic nerves producing myelopathy in fulminant CIDP August 242010 wwwneurologyorg
Jeremy D Isaacs et al Noncompressive myelopathy associated with violent axial tics of Tourettesyndrome February 23 2010 wwwneurologyorg
David Roshal et al Pearls amp Oy-sters Fibrocartilaginous embolism myelopathy February 162010 wwwneurologyorg
N Duggal et al Brain reorganization in patients with spinal cord compression evaluated usingfMRI March 30 2010 wwwneurologyorg
S8 Neurology Clinical Practice 75(Suppl 1) November 2 2010
DOI 101212WNL0b013e3181fb3638201075S2-S8 Neurology
William F Schmalstieg and Brian G WeinshenkerApproach to acute or subacute myelopathy
This information is current as of November 1 2010
ServicesUpdated Information amp
httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlincluding high resolution figures can be found at
References
ref-list-1httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article cites 9 articles 2 of which you can access for free at
Citations
otherarticleshttpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article has been cited by 2 HighWire-hosted articles
Subspecialty Collections
httpwwwneurologyorgcgicollectiontransverse_myelitisTransverse myelitis
httpwwwneurologyorgcgicollectionmriMRI
httpwwwneurologyorgcgicollectionall_spinal_cordAll Spinal Cord s
httpwwwneurologyorgcgicollectionall_demyelinating_disease_cnAll Demyelinating disease (CNS)following collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpwwwneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2010 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
Ongoing clinical observation is an important partof the care of patients with an unexplained myelopa-thy Subsequent appearance of new neurologic orsystemic symptoms may reveal a demyelinating orsystemic inflammatory disorder Patients with relent-lessly progressive symptoms despite appropriate em-piric treatment may require spinal cord biopsy fordefinitive diagnosis particularly when follow-up im-aging demonstrates worsening
DISCUSSION Acute and subacute myelopathies re-quire urgent medical evaluation Imaging preferablyby MRI should be performed without delay to ex-clude a compressive lesion Subsequently history andphysical examination should guide subsequent inves-tigations to reach a definitive diagnosis As the etiol-ogy is often unclear at initial presentation empirictreatment should be provided while conducting fur-ther investigations to determine the etiology of my-elopathy A thorough evaluation often revealsevidence of a treatable disorder or one that may re-lapse without preventive treatment
DISCLOSURE
Dr Schmalstieg reports no disclosures Dr Weinshenker has served on
data safety monitoring boards for Novartis and Biogen Idec serves on the
editorial boards of Multiple Sclerosis the Canadian Journal of Neurological
Sciences and the Turkish Journal of Neurology receives research support
from the Guthy-Jackson Charitable Foundation and receives license roy-
alties from RSR Ltd and may receive royalties from Mayo Medical Ven-
tures for a patentintellectual property re Aquaporin-4 associated
antibodies for diagnosis of neuromyelitis optica
Received July 14 2010 Accepted in final form September 2 2010
REFERENCES1 Debette S de Seze J Pruvo JP et al Long-term outcome
of acute and subacute myelopathies J Neurol 2009256980ndash988
2 Kelley BJ Erickson BJ Weinshenker BG Compressivemyelopathy mimicking transverse myelitis Neurologist201016120ndash122
3 Keegan BM Pittock SJ Lennon VA Autoimmune my-elopathy associated with collapsin response-mediatorprotein-5 immunoglobulin G Ann Neurol 200863531ndash534
4 Proposed diagnostic criteria and nosology of acute trans-verse myelitis Neurology 200259499ndash505
5 Takahashi T Miyazawa I Misu T et al Intractable hiccupand nausea in neuromyelitis optica with anti-aquaporin-4antibody a herald of acute exacerbations J Neurol Neuro-surg Psychiatry 2008791075ndash1078
6 Brex PA Ciccarelli O OrsquoRiordan JI Sailer M ThompsonAJ Miller DH A longitudinal study of abnormalities onMRI and disability from multiple sclerosis N Engl J Med2002346158ndash164
7 Weinshenker BG Wingerchuk DM Vukusic S et alNeuromyelitis optica IgG predicts relapse after longitudi-nally extensive transverse myelitis Ann Neurol 200659566ndash569
8 Pittock SJ Lennon VA de Seze J et al Neuromyelitisoptica and non organ-specific autoimmunity Arch Neurol20086578ndash83
9 Weinshenker BG OrsquoBrien PC Petterson TM et alA randomized trial of plasma exchange in acute centralnervous system inflammatory demyelinating disease AnnNeurol 199946878ndash886
If you liked this article you may be interested in
Continuum
Spinal Cord Root and Plexus Disorders June 2008 wwwaancomgoelibrarycontinuum
Neurology
Nathan P Staff et al Hypertrophic nerves producing myelopathy in fulminant CIDP August 242010 wwwneurologyorg
Jeremy D Isaacs et al Noncompressive myelopathy associated with violent axial tics of Tourettesyndrome February 23 2010 wwwneurologyorg
David Roshal et al Pearls amp Oy-sters Fibrocartilaginous embolism myelopathy February 162010 wwwneurologyorg
N Duggal et al Brain reorganization in patients with spinal cord compression evaluated usingfMRI March 30 2010 wwwneurologyorg
S8 Neurology Clinical Practice 75(Suppl 1) November 2 2010
DOI 101212WNL0b013e3181fb3638201075S2-S8 Neurology
William F Schmalstieg and Brian G WeinshenkerApproach to acute or subacute myelopathy
This information is current as of November 1 2010
ServicesUpdated Information amp
httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlincluding high resolution figures can be found at
References
ref-list-1httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article cites 9 articles 2 of which you can access for free at
Citations
otherarticleshttpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article has been cited by 2 HighWire-hosted articles
Subspecialty Collections
httpwwwneurologyorgcgicollectiontransverse_myelitisTransverse myelitis
httpwwwneurologyorgcgicollectionmriMRI
httpwwwneurologyorgcgicollectionall_spinal_cordAll Spinal Cord s
httpwwwneurologyorgcgicollectionall_demyelinating_disease_cnAll Demyelinating disease (CNS)following collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpwwwneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2010 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology
DOI 101212WNL0b013e3181fb3638201075S2-S8 Neurology
William F Schmalstieg and Brian G WeinshenkerApproach to acute or subacute myelopathy
This information is current as of November 1 2010
ServicesUpdated Information amp
httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlincluding high resolution figures can be found at
References
ref-list-1httpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article cites 9 articles 2 of which you can access for free at
Citations
otherarticleshttpwwwneurologyorgcontent7518_Supplement_1S2fullhtmlThis article has been cited by 2 HighWire-hosted articles
Subspecialty Collections
httpwwwneurologyorgcgicollectiontransverse_myelitisTransverse myelitis
httpwwwneurologyorgcgicollectionmriMRI
httpwwwneurologyorgcgicollectionall_spinal_cordAll Spinal Cord s
httpwwwneurologyorgcgicollectionall_demyelinating_disease_cnAll Demyelinating disease (CNS)following collection(s) This article along with others on similar topics appears in the
Permissions amp Licensing
httpwwwneurologyorgmiscaboutxhtmlpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in
Reprints
httpwwwneurologyorgmiscaddirxhtmlreprintsusInformation about ordering reprints can be found online
rights reserved Print ISSN 0028-3878 Online ISSN 1526-632X1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2010 by AAN Enterprises Inc All
reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology