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EPISODIC MUSCLE WEAKNESS

Comparative features

Andersen syndrome
CIDP
Electrolyte disorders
  Hypophosphatemia
  Barium intoxication
Myasthenia Gravis
    Congenital: ChAT deficiency
Myoglobinuria/ Rhabdomyolysis
Myotonia syndromes
Paramyotonia
Periodic Paralysis
  Hyperkalemic
  Hypokalemic
  Mitochondrial
Porphyria, Acute Intermittent
X-linked episodic weakness

Non-muscle disorders
  Cataplexy
  Relapsing neuropathies
  Spinal: AVM



Hypokalemic Periodic Paralysis

Hereditary
  Ca++ channel: CACNA1S; 1q32
  Na+ channel: SCN4A; 17q23
  K+ channel
    KCNE3: 11q13
    KCNJ2: 17q24
    KCNJ5: 11q24
  Renal tubular acidosis: SLC4A1; 17q21
  Thyrotoxic (TTPP)
    1: CACNA1S; 1q32
    2: KCNJ18; 17p11
    3: 17q24.3
Acquired
  K+ wasting
  Dengue fever
Pathology


Periodic paralysis, K+ sensitive, with Cardiac arrhythmias (Andersen Syndrome)

  KCNJ2 (Kir2.1) ; Chromosome 17q24.3; Dominant

Periodic paralysis, Hypokalemic 15

  KCNJ5 (Kir3.4) ; Chromosome 11q24.3; Dominant

X-linked Episodic Prolonged Muscle Weakness (EMWX) 1

  Chromosome Xp22.3; Recessive

Episodic Muscle Weakness, Mitochondrial & Motor neuropathy 14

  ATP synthase 6 (mtATP6)
  ATP synthase 8 (mtATP8)

HEREDITARY PERIODIC PARALYSIS & MYOTONIA SYNDROMES
  Comparative Features

  Hypo K+
Periodic
Paralysis
Thyrotoxic
Hypo K+ Periodic
Paralysis
Hyper K+
Periodic
Paralysis
K+-
sensitive
Myotonia
*
Para-
myotonia
Myotonia congenita Andersen
syndrome
X-linked
paralysis
Weakness
& Motor PN
Thomsen's Becker's
Channel
  or gene
  defect
Ca++: CACNA1S
    α1-subunit
Other
KCNJ 18
  (Kir 2.6)
Na+: SCN4A
  α-subunit
KCNE3
Na+: SCN4A
  α-subunit
Na+: SCN4A
  α-subunit
Cl-: CLCN1
Cl-: CLCN1
K+: KCNJ2 ? mtAPT6
mtATP8
Inheritance/
Locus
Dominant
1q32.1
Dominant
17p11.2
Dominant
17q23.3
Dominant
17q23.3
Dominant
17q23.3
Dominant
7q34
Recessive
7q34
Dominant
17q23.3
Recessive
Xp22
Maternal or
Sporadic
Functional
 defect
? ? Fast & slow
  Inactivation
Mild Fast
  Inactivation
Fast
  Inactivation
Cl-
  Conduct
Cl-
  Conduct
K+
  Conduct
? ?
Penetrance Females Females High High High High High Variable ? High ?
Onset 5 to 35 years 20 to 40 years < 10 years < 10 years < 10 years Congenital Congenital 2 to
  18 years
0.5 to
  8 years
Childhood
  60 years
Weakness
 duration
2 to 24 hours Hours to Days 1/2 to 4 hours None 2 to 24 hours None Transient 1 to
  36 hours
1 day to
  1 year
1 to 24 hours
Permanent:
  Distal legs
Maximum
 weakness
Severe Mild to Severe Mild to Severe None Mild None Mild Moderate Mild to
  Severe
Moderate
  Distal
Cold ± Paralysis ± Paralysis ± Paralysis Paralysis Paralysis No effect No effect   No effect Occasional
K+-effects Paralysis Paralysis Paralysis Paralysis Paralysis No effect No effect Paralysis No effect No effect
Attack
 precipitants
Carbohydrates
Rest after Activity
Carbohydrates
Rest after Activity
Fasting K+ Cold; K+ None None K+ Viral
  illness
Rest
Myotonia Rare
Eyelids only
None ± Present
Exercise:
Mild to
  Severe
Exercise:
Moderate
Exercise:
Moderate
Constant
Severe
Constant
None None None
Muscles
 large
No No Yes Yes Yes Yes Yes No No No
Sensory
 symptoms
Absent Absent Present ? Absent Absent Absent Absent Absent Absent
Drug
 treatment
K+
Acetazolamide
Dichlor-
  phenamide
Thyrotoxicosis
β-adrenergic
  blockade
Thiazide
Acetazolamide
Dichlor-
  phenamide
Mexiletine
Thiazide
Mexiletine Numerous Numerous ? ? Acetazolamide

  * Includes acetazolamide-responsive myotonia, myotonia fluctuans, & myotonia permanens

Non-Dystrophic Myotonias: General features

Licorice intoxication


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References
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14. Neurology 2013; Online October
15. Neurology 2014; Online Feb

12/23/2015