an unusual cause of thenar hypertrophy and carpal tunnel syndrome

LETTERS TO THE EDITOR

AN UNUSUAL CAUSE OF THENARHYPERTROPHY AND CARPAL TUNNELSYNDROME

Carpal tunnel syndrome (CTS) is characterized by classicsymptoms of paresthesias in the median distribution andweakness that is sometimes accompanied by thenar atro-phy.1 We describe an unusual case presenting with the-nar hypertrophy.

A 52-year-old, right-handed man presented with 10years of intermittent paresthesias in the left mediannerve distribution and difficulty snapping his fingers.Driving and typing worsened his symptoms. His exami-nation revealed increased thenar bulk without focalmasses (Fig. 1A). A Tinel sign was present. Sensory ex-amination did not elicit significant abnormalities. Mildthenar weakness was noted. Electrodiagnostic studiesrevealed prolonged distal motor latency (7.9 ms),decreased compound motor action potential amplitudecompared with the right side (left 5.1 mV, right 9.2mV), and absent left median sensory nerve actionpotential. Ulnar studies and F-wave latencies were nor-mal. Needle electromyography of abductor pollicis bre-vis showed increased insertional activity, 1þ fibrillationpotentials, 2þ positive sharp waves, 3þ fasciculationpotentials, increased motor unit potential (MUP) ampli-tude, reduced MUP recruitment, and increased firingrate. Studies were consistent with left median neuropa-thy at the wrist.1

To further elucidate the etiology of thenar hyper-trophy, MRI of the hand and wrist was performed toassess structural detail. MRI revealed linear strands offat infiltrating thenar muscles (Fig. 1B), which wasdifferent from the diffuse fibrofatty change associatedwith advanced muscle atrophy. There was globularenlargement of the median nerve with linear cable-like appearance of the nerve fascicles with surround-ing fat. The enlargement measured 1.2 � 1.6 cm andwas consistent with lipofibromatous hamartoma (LFH)(Fig. 1C).

The patient underwent decompression of thenerve. Nerve enlargement and swelling was noted atthe time of surgery, but fibrofatty change was notappreciated due to intact epineurium. Paresthesias

improved at 3 months postoperatively. However, imag-ing revealed no change in the size of the mediannerve mass (Fig. 1D).

This case is instructive because thenar hypertrophyled to imaging, which revealed LFH. Thenar hypertro-phy could result from either pseudohypertrophy or truehypertrophy related to spontaneous activity, increasedwork of remaining fibers, and fiber stretching.2,3

Chronic denervation and spontaneous activity on needleEMG raises the possibility of true thenar hypertrophy.The focal, band-like pattern of fatty infiltration in thenarmuscles suggests extension of LFH. If the fatty replace-ment were due to severe muscle atrophy, then significantclinical weakness and diffuse fibrofatty change should bepresent. To our knowledge, we have described the firstcase of thenar pseudohypertrophy likely due to exten-sion of median nerve LFH.

Besides LFH, localized hypertrophic neuropathy hasbeen reported in hereditary sensory motor neuropathytype 1, Refsum syndrome, and diabetic neuropathy.4

However, a ‘‘cable-like’’ appearance of the median nerveis pathognomonic for LFH and arguably nullifies theneed for biopsy.5 In addition, LFHs have a predilectionfor the median nerve.6 The etiology of LFH is unknown.There are many proposed mechanisms, including a post-traumatic reactive process, congenital etiology, and asso-ciation with neurofibromatosis.7

Surgical treatment of the tumor is debated. Massexcision can lead to sensory deficits.6 In our case, an ini-tial conservative decompression procedure resulted inimprovement in sensory symptoms. LFH of the mediannerve should be considered in patients who present withCTS and clinical thenar pseudohypertrophy.

Thy Nguyen, MD1

Milan Sen, MD2

Manickam Kumaravel, MD3

Parveen Athar, MD1

Kazim A. Sheikh, MBBS1

1Department of Neurology, University of Texas Medical School atHouston, Houston, Texas

2Department of Orthopedics, University of Texas Medical Schoolat Houston, Houston, Texas

3Department of Radiology, University of Texas Medical School atHouston, Houston, TexasVC 2011 Wiley Periodicals, Inc.

296 Letters to the Editor MUSCLE & NERVE February 2012

1. Jablecki CK, Andary MT, Floeter MK, Miller RG, Quartly CA, VennixMJ, et al. Practice parameter: Electrodiagnostic studies in carpal tunnelsyndrome. Report of the American Association of ElectrodiagnosticMedicine, American Academy of Neurology, and the American Acad-emy of Physical Medicine and Rehabilitation. Neurology 2002;58:1589–1592.

2. De Beuckeleer L, Vanhoenacker F, De Schepper A Jr, Seynaeve P,De Schepper A. Hypertrophy and pseudohypertrophy of the lowerleg following chronic radiculopathy and neuropathy: imaging find-ings in two patients. Skeletal Radiol 1999;28:229–232.

3. Gutmann L. AAEM minimonograph #46: Neurogenic muscle hyper-trophy. Muscle Nerve 1996;19:811–818.

4. Carter GT, Kilmer DD, Szabo RM, McDonald CM. Focal posterior in-terosseous neuropathy in the presence of hereditary motor and sen-sory neuropathy, type I. Muscle Nerve 1996;19:644–648.

5. Marom EM, Helms CA. Fibrolipomatous hamartoma: pathogno-monic on MR imaging. Skeletal Radiol 1999;28:260–264.

6. Warhold LG, Urban MA, Bora FW Jr, Brooks JS, Peters SB. Lipofi-bromatous hamartomas of the median nerve. J Hand Surg Am 1993;18:1032–1037.

7. Al-Jabri T, Garg S, Mani GV. Lipofibromatous hamartoma of the me-dian nerve. J Orthop Surg Res 2010;5:71

Published online in Wiley Online Library(wileyonlinelibrary.com). DOI 10.1002/mus.22164

---------------------------------------------------------PURE MONOMELIC SENSORYNEURONOPATHY ASSOCIATEDWITH ANTI-YO ANTIBODIES

A 35-year-old woman presented with paresthesia in thethird finger of the left hand, which extended progressivelyover 8 months to the upper arm. Clinical examinationshowed athetoid movements of the left hand and fingers.There was impaired sensation for all modalities in the leftarm restricted to the C6, C7, and C8 dermatomes. In the

absence of visual feedback, the finger-to-nose test showedleft-sided dysmetria, and prehension was difficult whenthe right hand tried to reach the left thumb. Deep tendonreflexes were absent in the left arm. Magnetic resonanceimaging (MRI) of the brain and spine was normal. Motornerve conduction studies in the median and ulnar nerves(performed up to Erb point) and in the fibular and tibialnerves (up to the popliteal fossa) showed normal com-pound muscle action potential (CMAP) amplitudes andF-wave latencies in all four limbs. Antidromic sensory neu-rography (using surface electrodes) revealed absence ofpotentials in the median, ulnar, and radial nerves on theleft side and no abnormalities in the other limbs. Somato-sensory evoked potentials showed absence of N9, N13,and N20 potentials after left median nerve stimulation,whereas potentials were normal after stimulation of theright median nerve and both tibial nerves. Needle EMGwas normal, particularly in the left arm muscles inner-vated by C6, C7, and C8 roots. Brachial plexus MRI wasnormal. Cerebrospinal fluid analysis showed slightly ele-vated protein levels (0.56 g/L) in the absence of intrathe-cal immunoglobulin synthesis. A left upper limb sensoryneuronopathy was suspected. The patient had no historyof pyridoxine intake. Anti-nuclear and anti-SSA/SSB anti-bodies were in the normal range.

Serologic testing for onconeural antibodies revealedanti-Yo antibodies (using immuno-dot blot assay) andabsence of anti-Hu, anti-amphiphysin, and anti-CV2 anti-bodies. Whole-body fluorodeoxyglucose positron emis-sion tomography (FDG PET) showed increased metabo-lism in the breast and the axillary regions on the right.Breast biopsy revealed invasive ductal carcinoma.

FIGURE 1. (A) Thenar eminence in the symptomatic left hand is appreciably larger compared with the right. (B) MR axial T1-weighted,

non–fat-saturated image reveals linear strands of hyperintense fat (arrow) infiltrating the thenar muscles. (C) MR axial T2-weighted,

fat-saturated preoperative image reveals a globular mass within the median nerve with a ‘‘cable-like’’ (arrow) appearance measuring 1.6

� 1.2 cm. (D) MR axial fat-saturated, T2-weighted postoperative image revealing a globular mass within the median nerve with a

‘‘cable-like’’ appearance without significant change in size (arrow). [Color figure can be viewed in the online issue, which is available at

wileyonlinelibrary.com.]

Letters to the Editor MUSCLE & NERVE February 2012 297

A diagnosis of probable paraneoplastic monomelic sen-sory neuronopathy was made.1 One year after successfultreatment of her cancer, clinical examination and sen-sory nerve conduction studies remained unchanged withthe persistence of anti-Yo antibodies.

When involuntary movement resembling athetosisresults from proprioceptive sensory dysfunction, the termpseudoathetosis is used. In our case, loss of sensorypotentials in the median, ulnar, and radial nerves on theleft, associated with breast cancer and anti-Yo antibodies,was in favor of a paraneoplastic sensory neuronopathyinvolving the left dorsal root ganglia of cervical levels 6–8.

The main causes of sensory neuronopathy are Sjog-ren syndrome, pyridoxine intoxication, cisplatin, para-neoplastic syndrome, and some inherited disorders (e.g.,Friedreich ataxia).2

Paraneoplastic sensory neuronopathy often has asubacute onset and begins most frequently in the upperlimbs before spreading rapidly to the lower limbs. Themost commonly associated tumor is small cell lung can-cer, and most of the patients have anti-Hu, anti-amphi-physin, or anti-CV2 antibodies. Two cases of very asym-metrical paraneoplastic sensory neuronopathy have beenreported previously. One presented with neuroendocrinetumor and negative antineuronal antibody, and theother had small cell lung cancer accompanied by anti-Hu antibodies. In the latter case, progression was slowlyprogressive, as in our case.3,4 However, sensory neuron-opathy involving only one limb has never been reportedin association with anti-Yo antibodies, suggesting thatanti-Yo antibodies may sometimes be associated with clin-ical syndromes other than cerebellar ataxia.

Guillaume Taieb, MD1

Dimitri Renard, MD1

Marie Deverdal, MD1

Jerome Honnorat, MD, PhD2,3

Pierre Labauge, MD, PhD1

Giovanni Castelnovo, MD1

1Department of Neurology, CHU Nımes, Hopital Caremeau,Nımes, France

2Centre de Reference Maladie Rare ‘‘Syndromes NeurologiquesParaneoplasiques’’, Hospices Civils de Lyon, HopitalNeurologique, Bron, France

3Lyon Neurological Research Center, University of Lyon, Lyon,France

1. Camdessanch JP, Jousserand G, Ferraud K, Vial C, Petiot P, Hon-norat J, et al. The pattern and diagnostic criteria of sensory neuron-opathy: a case–control study. Brain 2009;132:1723–1733.

2. Kuntzer T, Antoine JC, Steck AJ. Clinical features and pathophysio-logical basis of sensory neuronopathies (ganglionopathies). MuscleNerve 2004;30:255–268.

3. Lim A, Scriven A, Knezevic W, Texler M. A predominantly left upperlimb sensory neuronopathy as a manifestation of a metastatic neu-roendocrine malignancy. J Clin Neurosci 2009;16:838–839.

4. Nanetti L, Lauria G, Scaioli V, Marchesi C, Salsano E, Lombardi R,et al. Slowly progressive sensory hemisyndrome: unusual presentationof paraneoplastic sensory neuronopathy. Peripher Nerv Syst 2010;15:73–74.


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AN AUTOPSY CASE OF ADYSFERLINOPATHY PATIENT WITHCARDIAC INVOLVEMENT

In this report we describe an autopsy case of dysferlinop-athy with cardiac involvement. Autopsy revealed disarrayof cardiomyocytes and severe degeneration in cardiacmuscle and diaphragm. Patients with dysferlinopathyshould have careful cardiac and respiratory evaluationduring the long course of this disease.

At the age of 22 years, the patient noticed weaknessin her lower limbs. Two years later the muscle weaknessprogressed to include the distal upper limbs. She wasgiven a diagnosis of limb-girdle muscular dystrophy(LGMD). At the age of 39 years, she could not walk with-out a cane and was subject to falls. At age 40 she beganusing a wheelchair. At age 74, she was admitted to ourhospital with the complaint of palpitations. She hadhypertension. She was unable to stand alone or remainin the sitting position. She could still raise her handsabove her shoulders and flex her neck when supine.Her serum creatine kinase (CK) level was 129 IU/L (45–163 IU/L), and brain natriuretic peptide (BNP) was30.1 pg/ml (<18.4). The cardiothoracic ratio on chestX-ray was 56%. Electrocardiogram revealed inverted Twaves in aVL and ST elevation in II, III, and aVf. Echo-cardiography revealed hypertrophic obstructive cardio-myopathy. She also had paroxysmal supraventriculartachycardia, which was considered an indication for car-diac pacing, but she declined. Her vital capacity (VC)was 700 ml, and %VC was 31.4%, suggesting respiratorydecline late in life. At age 78, she died suddenly of respi-ratory failure.

Mutation analysis was performed1 after informedconsent and upon approval of our local ethics commit-tee. The dysferlin gene of this patient showed homozy-gous c.2643þ1G>A mutations.

An autopsy was performed. The patient’s weight was52.3 kg, and heart weight was 385 g. There was noobvious outflow tract obstruction. In the hematoxylin–eosin-stained sections, skeletal muscle exhibited variationin fiber size with frequent internalized nuclei in an inter-costal muscle (Fig. 1). Iliopsoas muscles were almostreplaced by adipose tissue. Unlike the intercostal muscle,the diaphragm was replaced by adipose tissue, and smallnumbers of myofibers remained. Ischemic heart lesionswere not found. Cardiac muscle exhibited variation infiber size and a disarrayed appearance. There wasenlargement of the interstitial space, and fibrosis wasalso observed. There was deficient sarcolemmal dysferlinin intercostal muscle, cardiac muscle, and diaphragm(Fig. 1).

Dysferlin deficiency causes dysferlinopathy2,3 and hasbeen described as leading to defective membrane reseal-ing in skeletal muscle as well as muscle necrosis.4

Recently, Han et al. demonstrated that dysferlin is alsoinvolved in cardiomyocyte membrane repair and thatdysferlin deficiency leads to cardiomyopathy in dysferlin-null mice.5 However, there have been only a few reportsabout cardiac involvement in human dysferlinopathy.6,7

In this case the disarrayed appearance and fibrosis ofcardiac muscle could not be explained as being the


result of hypertension. Dysferlin deficiency may be thecause of the subclinical involvement in cardiac muscle.As she lived longer than previously reported dysferlinop-athy patients, the effect of dysferlin deficiency may haveaccumulated in her heart and led to cardiac symptoms.Because of the decline in activities of daily living, strainon the heart may have been diminished, leading to thelack of obvious cardiac symptoms. Careful cardiac andrespiratory follow-up is recommended during the longcourse of this disease.

Naoki Suzuki, MD1

Toshiaki Takahashi, MD2

Yasushi Suzuki, MD3

Koichi Narikawa, MD3

Sonoko Kudo, MD3

Hiroyoshi Suzuki, MD4

Maki Tateyama, MD1

Masashi Aoki, MD1

1Department of Neurology, Tohoku University School ofMedicine, Sendai, Japan

2Department of Neurology, Nishitaga National Hospital, Sendai,Japan

3Department of Neurology, Sendai Medical Center, Sendai,Japan

4Department of Pathology, Sendai Medical Center, Sendai,Japan

1. Takahashi T, Aoki M, Tateyama M, Kondo E, Mizuno T, OnoderaY, et al. Dysferlin mutations in Japanese Miyoshi myopathy: relation-ship to phenotype. Neurology 2003;60:1799–1804.

2. Bashir R, Britton S, Strachan T, Keers S, Vafiadaki E, Lako M, et al.A gene related to Caenorhabditis elegans spermatogenesis factor fer-1is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet1998;20:37–42.

3. Liu J, Aoki M, Illa I, Wu C, Fardeau M, Angelini C, et al. Dysferlin, anovel skeletal muscle gene, is mutated in Miyoshi myopathy andlimb girdle muscular dystrophy. Nat Genet 1998;20:31–36.

4. Bansal D, Miyake K, Vogel SS, Groh S, Chen CC, Williamson R, et al.Defective membrane repair in dysferlin-deficient muscular dystrophy.Nature 2003;423:168–172.

5. Han R, Bansal D, Miyake K, Muniz VP, Weiss RM, McNeil PL, et al.Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury. J Clin Invest 2007;117:1805–1813.

6. Kuru S, Yasuma F, Wakayama T, Kimura S, Konagaya M, Aoki M,et al. A patient with limb girdle muscular dystrophy type 2B(LGMD2B) manifesting cardiomyopathy [in Japanese]. Rinsho Shin-keigaku 2004;44:375–378.

7. Miyoshi K, Kawai H, Iwasa M, Kusaka K, Nishino H. Autosomal reces-sive distal muscular dystrophy as a new type of progressive musculardystrophy. Seventeen cases in eight families including an autopsiedcase. Brain 1986;109:31–54.


---------------------------------------------------------ULTRASOUND IN THE DIAGNOSIS ANDTREATMENT OF POSTERIORINTEROSSEOUS NERVE ENTRAPMENT:A CASE REPORT

A 43-year-old woman presented with a 3-week history ofweakness of the finger extensors and pain and swellingin the proximal part of the left forearm. She denied anytrauma, and the rest of her medical history was unre-markable. Physical examination revealed a localized ten-der swelling in the anterolateral forearm, medial anddeep to the brachioradialis muscle. During neurologicalexamination, she was unable to extend the metacarpo-phalangeal joints of all fingers (0/5), and there wasslight weakness (4/5) in wrist extension on the left.Reflex and sensory tests were normal. With a likely diag-nosis of posterior interosseous nerve (PIN) palsy, electro-diagnostic testing was performed. Nerve conduction

FIGURE 1. Skeletal muscle exhibited variation in fiber size with frequent internalized nuclei in intercostal muscle (D). The diaphragm

was almost replaced by adipose tissue, and small numbers of myofibers remained (B). Cardiac muscle exhibited variation in fiber size

and a disarrayed appearance (C). Enlargement of the interstitial space and fibrosis were also observed compared with disease control

(A). Dysferlin was deficient in the sarcolemma of intercostal muscle (H), cardiac muscle (G), and diaphragm (F), compared with dis-

ease control (E). Bar ¼ 100 lm. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]


studies showed that the superficial radial sensory nerveaction potential was normal, but a radial compoundmuscle action potential from the extensor indicis musclecould not be recorded. Electromyographic evaluationdemonstrated acute partial denervation in the extensorcarpi radialis brevis muscle (the most proximal abnormalmuscle) with reduced motor unit potential recruitment,acute complete denervation in the extensor indicis mus-cle, and a normal brachioradialis muscle (the most distalnormal muscle). These findings were considered to beindicative of a severe left PIN palsy.

Ultrasound imaging using a 7–12-MHZ linear probe(Logiq P5; GE Medical Systems, USA) revealed a cysticmass distal to the radial head that indented the PIN frombelow (Fig. 1). Magnetic resonance imaging also showeda well-defined cystic lesion (21 � 14 mm) just anterior–distal to the radiocapitellar joint. In the light of thesefindings, the patient was diagnosed with PIN entrapmentdue to a ganglion cyst in the forearm. The cyst was aspi-rated (3 ml fluid), and corticosteroid injection was per-formed under ultrasound guidance. The patient’s painfulsymptoms improved rapidly, and she started to extendher fingers within a few days. At a 1-month follow-up visitfollowing conservative treatment with rest, activity modifi-cation, and a non-steroidal anti-inflammatory drug, shewas found to be further improved.

The radial nerve bifurcates into the superficial radial sen-sory and PIN just distal to the elbow joint. The PIN passesdeep to the arcade of Frohse and supplies the extensor carpiulnaris, abductor pollicis longus, and finger extensormuscles.1

Entrapment of the nerve usually occurs under the arcade ofFrohse due to either intrinsic (e.g., schwannoma) or extrinsic(e.g., fibrous bands, fractures, ganglion cysts) causes.1,2

Once localized by clinical and electrodiagnostic stud-ies, PIN entrapment syndromes are amenable to furtherinvestigation by imaging studies.3 Ultrasound,4–7 because

of its spatial resolution, safety, and ready availability toclinicians, provides a useful adjunctive tool for the diag-nosis of peripheral nerve entrapment syndromes andsometimes a means for prompt, successful intervention.

Murat Kara, MD1

Tulay Tiftik, MD1

Alparslan Yetis�gin, MD1

Gulcin Ural, MD1

Levent Ozcakar, MD2

1Department of Physical Medicine and Rehabilitation, AnkaraPhysical Medicine and Rehabilitation Education and ResearchHospital, Ankara, Turkey

2Department of Physical Medicine and Rehabilitation, HacettepeUniversity Medical School, Ankara, Turkey

1. Lubahn J, Cermak MB. Uncommon nerve compression syndromesof the upper extremity. J Am Acad Orthop Surg 1998;6:378–386.

2. Carr D, Davis P. Distal posterior interosseous nerve syndrome. JHand Surg Am 1985;10:873–878.

3. Ogino T, Minami A, Kato H. Diagnosis of radial nerve palsy causedby ganglion with use of different imaging techniques. J Hand SurgAm 1991;16:230–235.

4. Kılıc E, Ozcakar L. Ulnar nerve compression possibly due to aber-rant veins: sonography is elucidatory for idiopathic cubital tunnelsyndrome. Rheumatol Int 2011;31:139–140.

5. Kara M, Kaymak B, Malas FU, Tiftik T, Yazar F, Erkin G, et al. Thepurview of multifascicle ulnar nerves in cubital tunnel syndrome:single-case sonographic observation. Muscle Nerve 2009;40:664–665.

6. Ozcakar L, Cakar E, Kiralp MZ, Dincer U. Static and dynamic sonog-raphy: a salutary adjunct to electroneuromyography for cubital tun-nel syndrome. Surg Neurol 2009;72:311–312.

7. Kaymak B, Ozcakar L, Cetin A, Candan Cetin M, Akinci A, Hascelik Z. Acomparison of the benefits of sonography and electrophysiologic meas-urements as predictors of symptom severity and functional status inpatients with carpal tunnel syndrome. Arch Phys Med Rehabil 2008;89:743–748.

FIGURE 1. Ultrasonographic imaging of the patient at the level of the anterolateral elbow. (A) Longitudinal view demonstrates the anechoic

cystic lesion (white arrows) with intrinsic heterogeneous echogenicities (white asterisks) over the radial head (R) indenting the posterior interos-

seous nerve (white arrowheads) from below. (B) Axial view demonstrates the superficial radial nerve (white thin arrowhead) and posterior inter-

osseous nerve (thick white arrowhead) in relation to the cyst (white arrows) overlying the radius (R) distal to the bifurcation.


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HOW COMMON IS MISDIAGNOSIS INLATE-ONSET POMPE DISEASE?

Late-onset Pompe disease has become increasingly recog-nized as a cause of proximal muscle weakness in adults.As enzyme replacement therapy (ERT) with alglucosidasealfa holds promise in halting progression of the diseasein adults, early recognition is critical. To aid clinicians,the AANEM recently published (2009) criteria for estab-lishing the diagnosis.1 Despite increasing awareness, thereare anecdotal reports of missed and delayed diagnoses.The exact prevalence of this problem is unknown.

As part of a retrospective review on the electrodiag-nostic findings of infantile and late-onset Pompe dis-ease,2 we examined the incidence of incorrect diagnosisin adults. There were 27 adults with late onset Pompedisease who were treated at the Duke University MedicalCenter during 1999–2010. Information regardingprior diagnosis was available for 23 patients (14 women,9 men). Eleven (48%) had received an incorrectdiagnosis in the past, even when we excluded those whohad a non-specific diagnosis of ‘‘myopathy,’’ ‘‘elevatedliver function tests,’’ or ‘‘possible fatty liver.’’ Table 1 pro-vides more detailed characteristics. There was no differ-ence in time to diagnosis or rate of incorrect diagnosisbetween men and women. The mean time to correct di-agnosis from symptom onset was significantly longer inthose who had previously received an incorrect diagnosis(10.5 vs. 2.5 years). This difference may reflect atypicaldisease features or a decision to defer further testing inpatients who had been given another diagnosis.

Neurologists were equally represented in bothdiagnostic groups. Information on the physician whomade the initial diagnosis was available in 18 of 23patients (10 correct, 8 incorrect). In the patients witha correct initial diagnosis, neurologists were the diag-nosing physician 8 times (80%). The remaining 2patients were siblings diagnosed by a medical geneti-cist. Seven of 8 patients had received their incorrectdiagnosis from a neurologist (88%) and 1 from arheumatologist.

Although this is a small sample of patients, theycome from a large geographic distribution, representingeight states in the eastern United States and one foreigncountry. Surprisingly, there was no indication thatPompe disease was more likely to be the initial diagnosisin more recent years, as there was no clinically signifi-cant correlation between time to diagnosis and the yearof diagnosis (r ¼ 0.19). This suggests that suspicion ofPompe disease by clinicians is a larger factor in establish-ing the diagnosis than the recent availability of conven-ient blood-based enzymatic diagnostic testing andgenetic sequencing.

Late-onset Pompe disease should be considered inall adults who have slowly progressive limb-girdle and/orrespiratory muscle weakness. In addition, the electrodiag-nostic finding of myotonic discharges isolated to the para-spinal muscles should trigger suspicion, although thisfinding is not pathognomonic.1–4 The availability ofblood-based assays, such as dried blood spot testing,makes screening much easier than in the past.5 Withtreatment now a possibility, the importance of making anaccurate, early diagnosis cannot be overstated.

Table 1. Late-onset Pompe disease: patient characteristics and incorrect diagnosis.

Incorrect diagnosis Correct diagnosis

N 11 (4 males) 12 (5 males)Mean age at symptom

onset (years)33.3 6 16 (95% CI 21–40) 40.4 6 11 (P ¼ 0.35)

(95% CI 33–47)Mean year of symptom onset 1988 (range 1983–2008) 1993 (P ¼ 0.35) (range 1975–2008)Mean time to diagnosis from

symptom onset (years)10.5 6 10.7 (95% CI 2.6–18.6) 2.5 6 2.3 (P ¼ 0.009)

(95% CI 0.24–3.76)Mean maximum CK level

(reference: 30–220 U/L)540 6 415 U/L (95% CI 261–818) 403 6 278 U/L (P ¼ 0.18)

(95% CI 216–590)Prior incorrect diagnosis

and presenting symptomsDeconditioning (1)* Low back pain, leg weaknessLumbar radiculopathy (1)* Dyspnea, leg weaknessLupus (1) Limb weaknessMuscle strain (1) Low back pain, leg weaknessMusculoskeletal disease (1) Difficulty runningObstructive sleep apnea (1)* Exercise intolerance, headachesPolymyalgia rheumatica (1) Leg weakness, myalgiasPolymyositis (1)* Difficulty walkingPolymyositis þ fibromyalgia (1)* Leg weakness, myalgiasPostpolio syndrome (1)* Low back pain, leg weaknessPsychogenic weakness (1)* Leg weakness, myalgias

*Diagnosis made by a neurologist.


Lisa D. Hobson-Webb, MD1

Priya S. Kishnani, MD2

1Division of Neurology/Department of Medicine, Duke UniversityMedical Center, Durham, North Carolina

2Division of Medical Genetics/Department of Pediatrics, DukeUniversity Medical Center, Durham, North Carolina

Disclosure Statement: Priya S. Kishnani has received research/grant support and honoraria from Genzyme Corporation, and is amember of the Pompe and Gaucher Disease Registry AdvisoryBoard for Genzyme Corporation.

1. AANEM. Diagnostic criteria for late-onset (childhood and adult)Pompe disease. Muscle Nerve 2009;40:149–160.

2. Hobson-Webb LD, DeArmey S, Kishnani PK. The clinical and elec-trodiagnostic characteristics of Pompe disease with post-enzyme

replacement therapy findings. Clin Neurophysiol 2011;122:2312–2317.

3. Engel AG. Acid maltase deficiency in adults: studies in four cases ofa syndrome which may mimic muscular dystrophy or other myopa-thies. Brain 1968;91:435–462.

4. Barohn RJ, McVey AL, DiMauro S. Adult acid maltase deficiency.Muscle Nerve 1993;16:672–676.

5. Goldstein JL, Young SP, Changela M, Dickerson GH, Zhang H, DaiJ, et al. Screening for Pompe disease using a rapid dried blood spotmethod: experience of a clinical diagnostic laboratory. Muscle Nerve2009;40:32–36.


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an unusual cause of thenar hypertrophy and carpal tunnel syndrome

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