neurology case presentation dr. m. a. sofi md; frcp (london): frcpedin; frcsedin
TRANSCRIPT
Neurology Case Presentation
Dr. M. A. Sofi MD; FRCP (London): FRCPEdin; FRCSEdin
• 19 year old male admitted with acute onset generalized weakness for 1 day duration
• Woke up with diffuse weakness; no anti gravity strength in arms, unable to get out of bed
• Proximal > distal weakness; bilaterally symmetrical
• Denied diplopia, dysphagia, dysarthria, facial droop, drooling or change in level of consciousness
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Case history
• PMH: similar episode in Feb 2013, admitted to local hospital for 4-5 days, ?? Diagnosed with GBS, ?? treated with plasmapheresis, no LP/ EMG
• PMH: nil significant• Home meds: None• FH: Nil for HTN, migraine, DM, asthma, no similar
problem in family members• SH: denies smoking, ETOH or illicit drug use
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Case history
• Vitals stable• General physical exam unremarkable• Neurological exam–Mental status: AAO * 3–Speech : fluent with comprehension
intact–CN 2-12: PERRLA, EOMI, normal
facial sensation and symmetry, normal facial strength, hearing intact, equal palatal elevation and tongue midline
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Physical exam
–Motor: Flaccid tone, motor strength 2/5 proximally and 3-4/5 distally BUE and BLE–DTRs: Normal , planter both down
going–Sensory: Intact to LT/PP/ Vibration
and proprioception –Unable to test for cerebellar
function and gait5
Case history
1. What is the clinical pattern of weakness?
2. What is the anatomical localization?
3. What is the differential diagnosis?
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Case scenario
• Hb - 14.6, WBC 6.1, Plt count 215• Sodium 143, K 1.3, Chloride 110, BUN
13, Creatinine 0.83, Glucose 151, Calcium 9.3, Magnesium 2.0, Phosphorus 2.4
• CK 493, Aldolase 15.7 (on day 3)• TSH: 2.082, free T3 – 3.8, free T4 – 0.9• Urine electrolytes: unremarkable
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Labs
• Aggressive Potassium replacement• Started showing improvement in
muscle strength on day 1• By day 2 – strength was 5/5 BUE and
BLE• Diagnosed with familial hypokalemic
periodic paralysis• Discharged with follow up care
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Hospital course
The skeletal muscle genetic ion channelopathies are a distinct group of diseases caused by mutations which mainly occur in voltage-gated ion channel genes. They can be classified in to 2 categories – non dystrophic myotonias and periodic paralyses.NDMs are a group of conditions characterized by muscle stiffness on voluntary movement due to delayed skeletal muscle relaxation. This group includes :• Myotonia congenita• Paramyotonia congenita • Sodium channel myotonias• (potassium-aggravated myotonias (PAMs)• Myotonia fluctuans• Myotonia permanens • Acetazolamide responsive myotonia
Muscle channelopathies
The NDMs are mainly distinguished clinically from the dystrophic myotonias, myotonic dystrophy types 1 and 2, by the absence of extramuscular systemic involvement.
The periodic paralyses are a group of autosomal-dominant disorders characterized by episodes of flaccid paralysis often triggered by an alteration in serum potassium concentration. They include• hypokalemic periodic paralyses type 1 and 2, • hyperkalemic periodic paralysis and• Anderson Tawil syndrome
Muscle channelopathies
• Hypokalemic:– Thyrotoxic periodic paralysis– hyperaldosteronism– RTA– villous adenoma– cocaine binge– diuretics, licorice, steroids, ETOH
• Hyperkalemic (k>7): – hyporenemic hypoaldosteronism (DM/CRF)– oral K, CRF, chronic heparin, rhabdomyolysis
• Normakalemic: – Guanidine, sleep paralysis, MG, TIA, conversion
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Periodic Paralysis Secondary
• HypoPP is associated with point mutations in both SCN4A and CACNA1S; however, approximately 10–20% of cases remain genetically undefined. Reduced penetrance in women
• HypoKPP 1 is the most frequent form• 1 in 100,000• Autosomal dominant inheritance pattern• M:F – 3 or 4:1 • Onset: first 2 decades of life
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Hypokalemic periodic paralysis
• Flaccid paralysis – mild focal weakness to severe generalized weakness
• Occur anytime of the day; more common in morning• Absence of myotonia• Absence of clinical or electrophysiological myotonia is
helpful in distinguishing this disorder from HyperKPP• Proximal > distal weakness; legs > arms• Sparing of facial, ventilatory and sphincter muscles• Lasts several hours to more than a day
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Clinical features
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Effects of hypokalaemia on the ECGChanges appear when K+ falls below about 2.7 mmol/l
• Increased amplitude and width of the P wave
• Prolongation of the PR interval
• T wave flattening and inversion
• ST depression• Prominent U waves(best
seen in the precordial leads)
Apparent long QT interval due to fusion of the T and U waves (= long QU interval)
• Frequency: highly variable• Frequency decreases after age 30; may
become attack free in 40s and 50s• Permanent fixed weakness or slowly
progressive weakness more common with HypoKPP1
• Attacks may be preceded by sensation of heaviness and or aching in the low back
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Hypokalemic periodic paralysis
• Strenuous physical activity followed by rest or sleep
• High carb diet• ETOH consumption• Emotional stress• Concurrent viral illness• Lack of sleep• Medications like beta agonists,
corticosteroids, and insulin16
Precipitating factors
• Serum K < 3.0mEq/L • Serum CK level elevated • EKG changes – U waves, flattening of T waves• Provocative testing - Intravenous glucose
load/ insulin • Electrophysiology– Sensory and motor NCS normal between
attacks– During attacks – small CMAP. Reduced
insertional activity, fibs and positive sharp waves
– No myotonia on EMG– Short/ long exercise test
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Diagnostic studies
• Reducing exposure to known triggers• Acute treatment – replacement of K• Acetazolamide – prevent attack
recurrence and severity –Acetazolamide may ppt weakness in
HypoK PP2• Dichlorphenamide – no longer
available• Triamterene and spironolactone
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Treatment
A 38-year-old man, feeling poorly after finishing a marathon, was brought to the medical tent near the finish line. He had run three marathons in the past two years.
He was confused, but not hypotensive; pulse was 130 beats/min; his weight was 4.5 kgm higher than at the start of the race. Electrolyte measurements on site included a serum sodium concentration of 118 mEq/L. The most likely proximate reason for the hyponatremia is:
A. Cerebral salt wasting B. NaCl-wasting nephropathy C. Excessive intake of hypotonic fluid D. Excessive sweating
A 60-year-old man with known lung cancer is seen in follow-up with no major symptomatic changes. His BP is 150/90 mmHg, pulse 86 and regular and he has no edema.
Electrolytes reveal a serum sodium concentration of 125 mEq/L; BUN is 6mg/dl, uric acid is 2.8 mg/dl, and the urine osmolality is 280 mosm/kg. The most likely explanation for the hyponatremia is:
A. Cerebral salt wasting B. Diuretic use/abuse C. SIADH D. Psychogenic polydipsia
The most appropriate therapy for patient #2 is: A. Solute-free water restriction B. DDAVP C. Cortisone D. 5% hypertonic saline
60 Year old presented with recurrent attacks of syncope 1.What does ECG rhythm strip show?
_______2.What treatment is recommended?
________
67 year old man presented with left side hemiplegia
1.Describe CT finding? ___
2.What vascular territory is involved? _____
1.What is the diagnosis? _________
2.What blood test has diagnostic value? _______________
Presented with severe acute pain inability to move foot.
On arrival, he is sweaty, distressed and peripherally cyanosedVital Signs:RR 45/min intercostal recessionTempt 38 deg CBP 180/90 mmHg
Upon arrival, arterial blood gases are taken (on 12L / min of O2):pH 7.15 (7.35 – 7.45)PO2 80 mmHg (80 – 95)PCO2 95 mmHg (35 -45)HCO3 42mmol/L (22 – 28)Base Excess + 17 (-3 - +3)SaO2 90%
A 65 year-old man with severe dyspnoea. The patient has a history of Chronic Obstructive Airway Disease (COAD), with regular use of bronchodilators. He is still a heavy smoker, but has no other relevant past history.
Name 2 abnormalities of blood gas analysis above? 1. ___________2. ___________
THANK YOU
History
• 31yo F w/several months progressive BLL weakness; pain greater in LLE
• Bilateral numbness just above breasts & inferiorly• Muscle aches cramps spasms falls• Urinary incontinence & saddle anesthesia• Constipation 2wks (manual dis-impaction)• No history of spinal operation or trauma• No F/C/N/V
Physical Exam
• Sensory deficit inferior to T1 bilaterally• Decreased rectal tone• Motor: LLE 2/5, RLE 5/5• Increased tone/spasticity• Hyper-reflexia• Babinski: Bilateral up going toes• Gait: Able to stand with assistance; drags LLE,
circumduction
LocalizationWhat are the major symptoms and clinical findings ?
What is the anatomical localization of the lesion?
What is the differential diagnosis?
What investigation are requested?
Sag T1 FS MRI Post Sag T2 MRI
Labs/CSF
• Gram stain & culture: rare monocytes, no organisms isolated
• CSF glucose: 69• CSF protein: 31• Elevated levels of IgG antibodies• Oligoclonal bands: negative
Differential Diagnosis
• TumorAstrocytomaEpendymoma
• Demyelinating lesion:Multiple sclerosisNeuromyelitis opticaTransverse myelitisADEM
H&E Stain Hypercellular neural tissue, vessel with perivascular lymphocytic inflammation.
Diagnosis
• Inflammatory demyelinating lesion• Multiple Sclerosis• No further surgical intervention• Neurology for management of MS• Follow up in clinic 2 months postop– Motor LLE improved – MRI Brain & C-spine
Multiple Sclerosis
• Relapsing-remitting MS (RRMS): Most common 85% of MS initially
diagnosed Partial or total
recovery between attacks
• Secondary-progressive MS (SPMS):
RRMS course, but becomes gradually progressive
Attacks & partial recoveries may continue to occur
Over 60% initially RRMS progress to SPMS in 10 yrs
Multiple Sclerosis• Primary-progressive MS
(PPMS): Progressive from onset Symptoms generally do
not remit Progressive disability
w/o acute attacks15% of MS initially
diagnosed
• Primary-relapsing MS (PRMS): Same as PPMS, but with
acute attacks
Multiple Sclerosis • Clinical: Episodic, relapsing-remitting neurologic symptoms in
a young adult (typically)Neurological symptoms disseminated in time & spaceCommon presentations: monocular visual disturbances
(optic neuritis), paresthesias/weakness (myelitis), incoordination (cerebellar), and/or diplopia (brainstem)
• Labs: Oligoclonal bands positive, MBP elevated– Not specific, new tests improving sensitivity/specificity– Early MS vs Clinically definite– MBP elevated in various disease processes
• MRI: T2 intense foci in white matter (UBOs), juxtacortical (G-W junction involving U-fibers), periventricular lesions, involve corpus collosum (perpendicular extensions)
For dissemination in space (DIS) lesions in two out of four typical areas of the CNS are required:
1. Periventricular2. Juxtacortical3. Infratentorial4. spinal cord
For dissemination in time (DIT) there are two possibilities:A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, with reference to a baseline scan, irrespective of the timing of the baseline MRI OR
Simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions at any time
ADEMADEM)is another important differential diagnosis of MS.This is a monophasic, immune-mediated demyelinating disease which often presents in children following an infection or vaccination.On MRI there are often diffuse and relatively symmetrical lesions in the supra-and infratentorial white matter which may enhance simultaneously.
There almost always is preferential involvement of the cortical gray matter and the deep gray matter of the basal ganglia and thalami.Here we have axial FLAIR and T2W-images of a young patient with ADEM - notice the extensive involvement of the cortical and gray matter, including thalamus.
Tumefactive MSTumefactive demyelinating lesion (TDL) is defined as a solitary de-myelinating lesion greater than 2 cm. Mass effect and contrast enhancement on neuroimaging make it difficult to distinguish this type of lesion from high-grade gliomas
This patient was a previously healthy 35-year-old woman who presented with new-onset generalized tonic-clonic seizures and headaches. MRI scans showed a large right frontal mass with surrounding edema and a mild midline shift.The patient underwent a diagnostic stereotactic brain biopsy. Low-grade glioma and reactive gliosis were among the likely differential diagnoses. Permanent section showed a demyelinating lesion.
Tumefactive MS
T1-weighted magnetic resonance imaging scan showed a right frontal lesion with midline shift.
Neuromyelitis OpticaThis is a demyelinating disease in which the optic nerves and spinal cord are usually involved.Often there are few T2-lesions in the brain.Think of NMO when there are extensive spinal cord lesions (more than 3 vertebral segments) with low T1-signalintensity and swelling of the cord.On axial images the lesions often involve most of the cord.This is unlike MS, in which the lesions are usually smaller and peripherally located.The clue to the diagnosis is in the AQP4-AB titer 1:1024.
Borderzone infarctiontypically these lesions are located in only one hemisphere, either in deep watershed area or peripheral watershed area. ADEMMultifocal lesions in WM and basal ganglia 10-14 days following infection or vaccination.As in MS, ADEM can involve the spinal cord, U-fibers and corpus callosum and sometimes show enhancement.Different from MS is that the lesions are often large and in a younger age group. The disease is monophasic.
Lyme2-3mm lesions simulating MS in a patient with skin rash and influenza-like illness. Other findings are high signal in spinal cord and enhancement of CN7 (root entry zone).SarcoidSarcoid is the great mimicker. The distribution of lesions is quite similar to MS.
PMLPML is a demyelinating disease caused by JC virus in immunosuppressed patients.space-occupying, nonenhancing WMLs in the U-fibers (unlike HIV or CMV).PML may be unilateral, but more often it is asymmetrical and bilateral.Virchow Robin spacesBright on T2WI and dark on FLAIR.Small vessel diseaseWMLs in the deep white matter. Not located in corpus callosum, juxtaventricular or juxtacortical.In many cases there are also