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Disorders of Muscle Membrane Excitability

Muscle membrane excitability is affected in a group of disorders referred to as channelopathies. The heart may also be involved, resulting in life-threatening complications.

 

Channelopathies are diseases caused by disturbed function of ion channel subunits or the proteins that regulate them. These diseases may be either congenital  or acquired.
 

Extra Edge:
All periodic paralysis start before the age of 25 years except thyrotoxicosis periodic paralysis which can start after 25 years of age.

 

Table: Clinical Features of Periodic Paralysis CPP and Non dystrophic Myotonia
(Ref. Hari. 18th ed., Pg- 3504, Table 387.10)

 

Calcium Channel

Sodium Channel

Potassium Channel

Feature

Hypokalemic PP

Hyperkalemic PP

Paramyotonia Congenita

Anderson's Syndrome

Mode of inheritance

AD

AD

AD

AD

Age of onset

Adolescence

Early childhood

Early childhood

Early childhood

Myotonia

No

Yes

Yes

No

Episodic weakness

Yes

Yes

Yes

Yes

Frequency of attacks of weakness

Daily to yearly

May be 2–3/d

With cold, usually rare

Daily to yearly

Duration of attacks of weakness

2–12 h

From 1–2 h to >1 day

2–24 h

2–24 h

Serum K+ level during attacks of weakness

Decreased

Increased or normal

Usually normal

Variable

Effect of K+ loading

No change

Increased myotonia, then weakness

Increased myotonia

No change

Effect of muscle cooling

No change

Increased myotonia

Increased myotonia, then weakness

No change

Fixed weakness

Yes

Yes

Yes

Yes

 

Extra Edge:

  1. Hypokalemic  PP
    1. Attack are precipitated by heavy exercise followed by heavy meals & rest.
    2. Treatment:  a. Potassium  supplement  b. Potassium sparing diuretics (Triamterene, Spironolactone)  
  2. Hyperkalemic PP
    1. Attack are precipitated by heavy exercise followed by no meals & rest.
    2. Treatment acetazolamide  
  3. Paramyotonia Congenita. (PC) (Ref. Hari. 18th ed., Pg- 3506)
    1. In PC, the attacks of weakness are cold-induced or occur spontaneously and are mild.
    2. Myotonia is a prominent feature but worsens with muscle activity (paradoxical myotonia).
    3. This is in contrast to classic myotonia in which exercise alleviates the condition.
    4. Cooling of the muscle often dramatically reduces the amplitude of the compound muscle action potentials.
    5. PC is inherited as an autosomal dominant condition; voltage-gated sodium channel mutations.
    6. Oral administration of glucose or other carbohydrates hastens recovery.
    7. Prophylactic treatment. Thiazide, Mexiletine
  4. Anderson's Syndrome
    1. This rare disease is characterized by episodic weakness, cardiac arrhythmias, and dysmorphic features (short stature, scoliosis, clinodactyly, hypertelorism, small or prominent low-set ears, micrognathia, and broad forehead).
    2. The cardiac arrhythmias are potentially serious and life threatening.
    3. They include long QT, ventricular ectopy, bidirectional ventricular arrhythmias, and tachycardia.
    4. Prophylactic Treatment = Acetazolamide


Other types of Channelopathies

Condition

Channel type

Alternating hemiplegia of childhood

Na+/K+-ATPase

Bartter syndrome, Liddle

Various by type

Cystic fibrosis

Chloride channel

Episodic Ataxia

Voltage-gated potassium channel

Generalized epilepsy with febrile seizures plus

Voltage-gated sodium channel

Familial hemiplegic migraine

Various

Hyperkalemic periodic paralysis

Voltage-gated sodium channel

Hypokalemic periodic paralysis

Voltage-gated sodium channel

or

voltage-dependent calcium channel (calciumopathy)

Long QT syndrome

Various, by type

main type Romano-Ward syndrome

 

Malignant hyperthermia

Ligand-gated calcium channel

Myasthenia Gravis

Ligand-gated sodium channel

Myotonia congenita

Voltage-dependent chloride channel

Neuromyotonia

Voltage-gated potassium channel

Paramyotonia congenita
(a periodic paralysis)

Voltage-gated sodium channel

Retinitis pigmentosa
(some forms)

Ligand-gated non-specific ion channels

Short QT syndrome

Various potassium channels suspected

Seizure

Voltage-dependent potassium channel

 

Extra Edge:  Channelopathy is not feature of TB, spinocerebellar ataxia and Tay Sach’s disease.





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