Neurology Case Presentation

August 31st, 2012Dipika AggarwalPGY 4 Neurology

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19 year old RHAAM 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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Denied any sensory complains Denied trouble breathing, urinary or bowel

incontinence Denied any recent illness, trauma, travel or tick bite One episode of non-bloody emesis prior to

admission

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PMH: similar episode in Feb 2012, admitted to OSH for 4-5 days, ?? Diagnosed with GBS, ?? treated with plasmapheresis, no LP/ EMG

PSH: none Home meds: None FH: HTN, migraine, DM, asthma, no similar problem

in family members SH: denies smoking, ETOH or illicit drug use

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Vitals stable General physical exam unremarkable Neurological exam

◦Mental status: AAO * 4◦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

Physical exam

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◦Motor: Flaccid tone, motor strength 2/5 proximally and 3-4/5 distally BUE and BLE

◦DTRs: Areflexic , toes downgoing◦Sensory: Intact to LT/PP/ Vibration and

proprioception ◦Unable to test for cerebellar function and gait

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Where??

What??

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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 lytes: unremarkable

Labs

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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 with Jayhawk clinic

Hospital course

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Non dystrophic myotonias ◦Myotonia congenita (CLCN1)◦Paramyotonia congenita (SCN4A)◦Sodium channel myotonias (potassium aggravated

myotonias) (SCN4A) Periodic paralyses

◦Hypokalemic (CACNA1S/ SCN4A)◦Hyperkalemic (SCN4A)◦Anderson Tawil syndrome (KCNJ2)

Muscle channelopathies

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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

Periodic Paralysis Secondary

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HypoKPP1 and 2 - CACNA1S/ SCN4A gene 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

Hypokalemic periodic paralysis

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Flaccid paralysis – mild focal weakness to severe generalized weakness

Occur anytime of the day; more common in morning Absence of myotonia Proximal > distal weakness; legs > arms Sparing of facial, ventilatory and sphincter muscles Lasts several hours to more than a day

Clinical features

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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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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

insulin

Precipitating factors

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Mutations in voltage sensor segment D2S4 of 1 subunit of skeletal muscle Ca channel gene, chromosome 1q

Arg528His, Arg1239His, Arg1239Gly Less commonly SCN4A mutation enhances Na

inactivation

Hypokalemic Periodic ParalysisGenetics

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The mutation slows the activation rate of L-type Ca current to 30% of NL

Reduced RYR1-mediated Ca release from SER Reduced calcium current density Impaired E-C coupling ? role of K and ? inexcitability Ca homeostasis change reduces ATP-dependent K

channel current and leads to abnormal depolarization (Tricarico D et al 1999)

Hypokalemic Periodic ParalysisPathophysiology

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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

Diagnostic studies

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Muscle biopsy reserved to atypical patients with normal provocative and gene testing

Vacuoles reflect permanent myopathy Vacuoles represent proliferation, degeneration and

autophagic destruction of T-tubules & SR Large central vacuoles in hypokalemic PP

Periodic ParalysisMuscle Pathology

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Hypokalemic Periodic Paralysis

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Reducing exposure to known triggers Acute treatment – replacement of K Acetazolamide – prevent attack recurrence and

severity ◦Acetazolamide may ppt weakness in HypoKPP2

Dichlorphenamide – no longer available Triamterene and spironolactone

Treatment

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R/O secondary forms Measure K+ during attack Provocative testing for PP: seldom done!

o Hypo: gluc/insulino Hyper: K+

Muscle Bx – vacuoles/dilated T-tubules Electrophysiology

o EMGo Short/long exercise tests

Genetics

Diagnosing Muscle Channelopathies

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More useful in MC Baseline CMAP Exercise 10 sec Record CMAP immediately post

exercise, then q 10 sec for 1 min. CMAP in MC and PMC PMC exacerbated by cold No change in CMAP in HypoKPP

Electrophysiology: Short Exercise Test

(Streib. Musc. Nerve. 1982; 5: 719-723)

(Fournier. Ann. Neurol. 2004; 56: 650-661) (Fournier Neurology 2009)

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Record ulnar CMAP Amp baseline Exercise ADM 5 min Check CMAP every 2 min. for 50

min In PP (all types), Amp immed post

ex, over next 10-40 min, grad dec amp

In MC ↓ Amp immed post ex, rapid return to baseline

In PMC sustained ↓ Amp

Long Exercise Test for Periodic Paralysis

(McManis. Musc. Nerve. 1986; 9: 704-710)

(Fournier. Ann. Neurol. 2004; 56: 650-661)

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Dr.Barohn’s presentation on “Muscle Channelopathies” Anthony A.Amato and James A.Russell; Non dystrophic myotonias and

periodic paralysis. Neuromuscular disorders 2008, Mc Graw Hill, Section II Chapter 29; 655-680

Burge JA, Hanna MG. Novel insights into the pathomechanisms of skeletal muscle channelopathies; Curr Neurol Neurosci Rep. 2012 Feb Vol 12:62-69

Hanna, Dipa L Raja Rayan and Michael G. Skeletal Muscle Channelopathies:Non Dystrophic Myotonias and Periodic Paralysis. Current Opinion in Neurology, 2010 Vol. 23: 466-476

neuromuscular.wustl.edu Doreen Fialho and Michael G.Hanna. Periodic paralysis, Handbook of

Clinical Neurology, 2007 Vol. 86 (3rd series), p 89-90

References