Dipika Aggarwal
PGY 4 Neurology
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Teen aged 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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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 four months earlier, 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
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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
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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
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Non dystrophic myotonias
◦ Myotonia congenita (CLCN1)
◦ Paramyotonia congenita (SCN4A)
◦ Sodium channel myotonias (potassium aggravated
myotonias) (SCN4A)
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Periodic paralyses
◦ Hypokalemic (CACNA1S/ SCN4A)
◦ Hyperkalemic (SCN4A)
◦ Anderson Tawil syndrome (KCNJ2)
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Hypokalemic:
◦ Thyrotoxic periodic paralysis
◦ hyperaldosteronism
◦ RTA
◦ villous adenoma
◦ cocaine binge
◦ diuretics, licorice, steroids, ETOH
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Hyperkalemic (k>7):
◦ hyporenemic hypoaldosteronism (DM/CRF)
◦ oral K, CRF, chronic heparin, rhabdomyolysis
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Normakalemic:
◦ Guanidine, sleep paralysis, MG, TIA, conversion
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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
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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
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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
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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
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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)
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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
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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
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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
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R/O secondary forms
Measure K+ during attack
Provocative testing for PP: seldom done!
o Hypo: gluc/insulin
o Hyper: K+
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Muscle Bx – vacuoles/dilated T-tubules
Electrophysiology
o EMG
o Short/long exercise tests
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Genetics
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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
(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
(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
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