Peripheral neuropathy

Question 1

Charcot-Marie Tooth disease : Definition

Answer 1

1. Charcot-Marie Tooth disease is an inherited disease
2. Affects the peripheral motor and sensory neurones.
3. It is also known as hereditary motor and sensory neuropathy.

Question 2

Charcot-Marie Tooth disease : Pathophysiology

Answer 2

1. Majority of mutations are inherited in an autosomal dominant pattern.
2. Affect genes responsible for
   * production of proteins in myelin sheath
   * maintenance and axonal structure.

Question 3

Charcot-Marie Tooth disease : Clinical features

Answer 3

Distal lower limb muscles commonly affected ; (Calf + Feet)

1. Muscle weakness (also effects hands)

• Leading to foot deformities such as; high arches (pes cavus) and hammer toes
• Distal muscle wasting : “inverted champagne bottle legs
• Loss of ankle-dorsiflexion : high stepping gait due to foot drop

2. Peripheral sensory loss

3 . LMN symptoms

‘Glove - Stocking’ Distribution

Progression:
* The progression of CMT is typically slow and gradual.
* Symptoms often begin in childhood or adolescence but can appear later in life.

Question 4

Guillian Barre : Definition

Answer 4

1. Triggered by an autoimmune response in which the body’s immune system mistakenly attacks the peripheral nerves
2. acute paralytic polyneuropathy that affects the peripheral nervous system
3. Acute, symmetrical, ascending weakness and can also cause sensory symptoms

Question 5

Guillian Barre : Pathophysiology

Answer 5

1 . Trigger : Infection with Campylobacter jejuni (most common)

2. Autoimmune response :

• B cells produce antibodies against antigens causing infection

3 . Molecular mimicry

• Pathogenic antigens similar to proteins on Myelin Sheath
• Antibody attack nerve cells

4 . Demyelination occurs

Question 6

Peripheral Neuropathy : Definition

Answer 6

Peripheral neuropathy refers to reduced sensory and motor function in the peripheral nerves, typically affecting the feet and hands

Question 7

Peripheral Neuropathy : Causes

Answer 7

1. A – Alcohol
2. B – B12 deficiency
3. C – Cancer (e.g., myeloma) and Chronic kidney disease, Charcot-Marie Tooth disease
4. D – Diabetes and Drugs (e.g., isoniazid, amiodarone, leflunomideand cisplatin)
5. E – Every vasculitis

Question 8

Ulnar nerve palsy

Question 9

Radial nerve : Anatomy

Answer 9

1. Elbow : posterior surface of humerus

2. Forearm

1) Motor innervation-Posterior forearm
* Forearm extension (Brachioradialis)

3. Wrist

1) Motor innervation
* Extends wrists and fingers
* Extension of thumb

2) Sensory innervation
* Skin on dorsum of hand
* Radial 3 1/3 fingers

Question 10

Radial nerve palsy : Clinical features

Answer 10

1. Wrist drop
2. Difficulty in finger + thumb extension
3. Sensory changes
   * Paresthesia/Numbness on dorsum of hand

Question 11

Ulnar nerve palsy : Anatomy

Answer 11

Descends along;

1. Elbow: Medial epicondyle of humerus

2. Forearm :

3. Wrist : Ulnar nerve via pisiform/hamate bone

4. Hand:

Motor

• Hypothenar : Palm muscles
  _MOA _ : Grip strength

5. Fingers

Motor

• interosseous : muscles between metacarpal bones of fingers
  MOA : spreading, bringing together of fingers. Flexing and extending fingers

2) Sensory

• 4th / 5th fingers } dorsal and palmar surface
• Dorsal surface - medial aspect of palm

Question 12

Ulnar palsy : Clinical features

Answer 12

1. Hypothenar muscle wasting
* Weakness in grip strength
2. Sensory
* 4th/5th finger : parenthesia, numbness
3. Claw hand deformity
* Unopposed action of other muscles due to ulnar innervated intrinsic muscle wasting

Question 13

Myasthenia Gravis : Definition

Answer 13

Myasthenia gravis is an autoimmune condition affecting the neuromuscular junction.

It causes muscle weakness

progressively worsens with activityand improves with rest

Question 14

Myasthenia Gravis : Incidence

Answer 14

Women < 40
Men > 60

Question 14

Myasthenia Gravis : Pathophysiology

Answer 14

LMN synapse with AcH receptors on Muscle cells
* LMN releases acetylcholine into presynaptic cleft
* AcH binds to post synaptic receptor on muscle cells

1. Acetylcholine receptor antibodies
* Block post synaptic acetylcholine receptors on muscle cell
* Prevent stimulation of muscle by LMN

2 . > Muscle activity increases > AcH antibody blockage
* Exercise -> Less effective stimulation of muscles

3 . Rest
* AcH antibodies cleared from Post-synaptic receptor
* Muscle weakness improves

4 . Over time : Post-synaptic receptor membrane damage
* Antibodies activate complement system, ++ inflammation in neuromuscular junction

Question 14

Myasthenia Gravis : Clinical presentation

Answer 14

**Onset **: Muscle weakness > severe at the end of the day

• Weakness exacerbated with repeated activity - relived at rest

Symptoms
Weakness typically affects the ocular, bulbar, and limb muscles.
1. Proximal muscles of limbs
* Generalised muscle weakness
2. Face and Neck muscles
* Ocular muscles : Ptosis, Diplopia (most common)
* Facial muscles : Slurred speech, facial weakness
* Bulbar muscles : Dysphagia, Dysarthria

Question 15

Myasthenia Gravis : Associated disease

Answer 15

Strong link with thymomas (thymus gland tumours).

Question 16

Myasthenia Gravis : Investigations

Answer 16

1 . Electrophysiological studies
* Single-fiber electromyography (SFEMG): most sensitive test for MG, measures the variability in the time it takes for individual muscle fibres to respond to nerve stimulation.

2 . Serological testing
* Anti-acetylcholine receptor (AChR) antibodies (85% +)
* Anti-muscle-specific kinase (MuSK) antibodies

3. Imaging
   * A CT or MRI of the thymus gland is used to look for a thymoma.

Question 17

Myasthenia Gravis : Management

Answer 17

Symptomatic relief
1. Acetylcholinesterase inhibitors(pyridostigmine)
MOA : inhibiting acetylcholine degradation, thereby increasing its availability at the NMJ

2. IV Plasma exchange / immunoglobulin
MOA : removal of abnormal antibodies or mixture of abx to modify immune response temporarily
Indic : rapid, short-term improvement in severe cases or during myasthenic crisis

Maintaintance therapy
1. Immunosuppressive therapy (Corticosteroids)
MOA : reduce autoantibody production and improve muscle strength.

2. Thymectomy:
MOA : Surgical removal of the thymus is indicated in patients with thymoma

Question 18

Myasthenia Gravis : Complication

Answer 18

Myasthenia Crisis
* Respiratory muscle compromise - respiratory arrest
* May require : Mechanical ventilation

Question 19

Lambert-Eaton Syndrome : Defintion

Answer 19

Autoimmune disorder associated with small cell lung cancer
Caused by an antibody directed against presynaptic voltage-gated calcium channel in the peripheral nervous system.

Question 20

Lambert-Eaton Syndrome : Clinical features

Answer 20

1. Proximal muscle weakness

• Affects legs first
  Repeated muscle contractions -> increased muscle strength (in contrast to myasthenia gravis)

2. Autonomic symptoms

• Dry mouth, Impotence, Difficulty micturating

3. Hyporeflexia

Question 21

Lambert-Eaton Syndrome : Investigation

Answer 21

1. Electromyography
2. R/o Lung Cancer

Question 22

Lambert-Eaton Syndrome : Management

Answer 22

1. Tx of underlying cancer
2. Immunosupression : Prednislone/Azathioprine
3. 3,4-diaminopyridine : blocking voltage-gated potassium channels in the presynaptic membrane, which in turn prolongs the depolarisation of the cell membrane

Question 23

Neuropathic pain : Mx

Answer 23

Trail one neuropathic medication below at one time;
1. Amitriptyline – a tricyclic antidepressant
2. Duloxetine – an SNRI antidepressant
3. Gabapentin – an anticonvulsant
4. Pregabalin – an anticonvulsant

• Tramadol: Short term rescue medication for flares