Channelopathies: Types & Comparison between Neuropathy & Myopathy

Channelopathies are a group of disorders caused by mutations in ion channel genes, which are essential for the proper functioning of cells in various organ systems. These disorders are increasingly recognized as a cause of many medical conditions, including neurological, cardiac, and muscular disorders.

Channelopathies can be difficult to diagnose due to their varied and often nonspecific clinical presentations. Therefore, medical professionals need a thorough understanding of the underlying pathophysiology and diagnostic tests to identify these disorders accurately.

In this blog we’ll cover Channelopathies, their types and comparison between neuropathy and myopathy. Read on.

• SCN4A channel is located on skeletal muscles 

Loss of function of SCN4A 

• It results in defective depolarization 
• It causes Hypokalemic Periodic Paralysis

Hypokalemic Periodic Paralysis                                   

• Slow depolarization & slow repolarization is seen 

C/F 

• Post high carbohydrate diet weakness is seen 
• Slow depolarization and repolarization is responsible for weakness in the patient.

Work up

1. S. Potassium normal/ decreased
2. NCV (Normal) (N)
3. CPK MM : (N)

• IOC: Genetic studies are required for diagnosis of the patient
• EMG: Reveal weak contractions and weak relaxations
• This patient is told to avoid carbohydrates and to take potassium supplements in the diet. 
• More common in young males
• CALC1A3 channel: Ca⁺⁺ release decreases from sarcoplasmic reticulum→ interaction between actin and myosin also decreases → Muscle weakness is seen 
• Primary defect – Ca channel defect > Sodium channel defect
  (Type 1 Hypokalemic PP) (Type 2 Hypokalemic PP)

Rx

• POTCHLOR (Symptomatic intake of KCL), Coconut water can also be taken.
• For prevention (1°) → Acetazolamide 
  • Opens Ca⁺⁺ activated K⁺ channels
  • Improves K⁺ conductance 

Hyperkalemic Periodic Paralysis

• SCN4A: gain of Function
• This will lead to Fast depolarization and fast repolarization
• The total duration for which the muscle contraction is present will be lesser.
• If we compare the twitch duration, It will be lesser
• Hyperkalemic P. Paralysis is diagnosis of exclusion (Rule out other causes of weakness like electrolyte imbalance, Neuropathies, Myopathies)

C/F

• Myotonia
• Myoclonus: Twitching/ Jerking in. few muscle groups

Management of Hyperkalemic Periodic Paralysis

• High Carbohydrate diet
  (High carbohydrate diet → more sugar will cause more insulin to be produced→ Potassium goes inside cell→ Muscle relax faster, this is symptomatic management)

Rx

• 1°: Acetazolamide
• Mexiletine 

Myokymia: Peri-ocular muscle fluttering

TYPES OF CHANNELOPATHIES

Sodium channel defects is seen in

1. Hypokalemic P. Paralysis – (Loss of function)
2. Hyperkalemic P. Paralysis – (gain of function)
3. Paramyotonia congenita :-
   • Variant of Hyperkalemic P. Paralysis (Gain) 
   • Myotonia ⊕ on Cold Exposure

Calcium Channel defect is seen in

• Hypokalemic P. Paralysis
• Lambert Eaton Syndrome
• Familial hemiplegic migraine

K+ channel defect

• Episodic ataxia

Cl- channel defects 

• Variants of myotonia congenita
  • Thomson disease
  • Becker’s disease

• All these channelopathies are related to the musculoskeletal system.

SCN5A defect → BRUGADA SYNDROME

• Most common cause of death (Nocturnal), In South east Asian Males

• There is Defective inward current in RV epicardium
• Voltage gradient causes V. Tachycardia resulting in Sudden cardiac death
• Asymptomatic/ syncopal attacks are seen

Investigation

• ECG : V₁ V₂ : ST↑ (Asymptomatic), cove pattern, T wave inversion

TOC : I.C.D implantation 

• K⁺ channel defect in cardiac muscle → Andersen Tawil Syndrome

Comparison of Neuropathy versus Myopathy

• Neuropathies are mostly acquired, and present with distal weakness 
• Myopathies present with proximal weakness.

DIABETIC NEUROPATHY

• Sensory involvement:  Distal sensory loss of unmyelinated fibers 
  • It is Earliest finding
  • Vibratory sense is lost 1st 
• Motor involvement 
  • 3rd nerve palsy (Most common cranial nerve involvement) with papillary sparing. 
  • Light reflex is preserved
• Autonomic 
  • Silent MI/ orthostatic hypotension is seen

Charcot MARIE Tooth Disease               

• "Hereditary sensorimotor neuropathy”

C/F

1. Peroneal muscle atrophy is seen
2. Stork leg appearance
3. Thickened nerves
4. Bx nerves shows onion bulb appearance
5. Distal weakness (Flexion Contractures)

DUCHENNE MUSCULAR DYSTROPHY

1. Progressive weakness is seen 
2. Calf muscle involvement is seen 
3. Pseudo hypertrophy is seen
4. XLR: Seen in Boys 
   • Defect is in dystrophin gene
   • Defect is in dystrophin protein (Sarcolemmal protein)
     • 4 yr Boy presents with difficulty in climbing stairs
5. Waddling gait is seen 
6. Gower sign present (+)
7. Wheel chair Bound Patient by 10-12 yrs
8. Death – CHF/ R. Pneumonia

Workup

1. CPK MM
   • Increased during presentation
   • (N) 10-12 yrs: d/t wasting (+) 
   • Decreased around 15 yrs
2. IOC: PCR for dystrophin gene

Rx: Chest Physiotherapy

BECKER’S MUSCULAR DYSTROPHY

• Presentation = 10-12 yrs
• Wheelchair bound at 25 yrs of age 
• Milder disease
• Death may occur at 40 yrs

Q. 10 yrs old boy with large leg muscle CPK MM Ⓝ ds?

A: Duchenne’s muscular Dystrophy

• If CPK-MM ↑ in the same scenario: Dx is Becker’s muscular dystrophy

Myotonic Dystrophy (Type 1 & 2) 

• Myopathic Facies/ hatchet facies are seen 
• Myotonia implies muscle relaxation is defective 
• It results in Weakness 
• If it involves jaw muscles, Partially open mouth and up turned upper lip appearance is seen 
• Rigidity is seen 
• Cataract shows: Christmas tree appearance
• Conduction defects of heart is seen 
• T₂ DM is seen

Ques: A case of calf muscle weakness with toe walking.                  
Defect in Emerin/ Lamin: XLR
Ans: Emery Dreifuss

In cases of gradual weakness, Rule out K↓ (Hypokalemia)         

Workup

• NCV
• CPK MM/ Biopsy of muscle
• Anti Ach (R)/ MUSK/ LRP4/ P/Q
• Repetitive nerve stimulation (RNS) test
• EMG
• Genetic studies
• Dermatomyositis/ Polymyositis: Anti JO-1 

In cases of muscle pain with no weakness

Suspect

• Fibromyalgia
• Polymyalgia rheumatic
  • 50 yr female: Stiffness/ pain in shoulder/ Lower back/ Hips
    • ESR ↑/ CRP++
    • NCV = Ⓝ
    • CPK-MM = Ⓝ

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