Peripheral neuropathy Flashcards
Charcot-Marie Tooth disease : Definition
- Charcot-Marie Tooth disease is an inherited disease
- Affects the peripheral motor and sensory neurones.
- It is also known as hereditary motor and sensory neuropathy.
Charcot-Marie Tooth disease : Pathophysiology
- Majority of mutations are inherited in an autosomal dominant pattern.
- Affect genes responsible for
* production of proteins in myelin sheath
* maintenance and axonal structure.
Charcot-Marie Tooth disease : Clinical features
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.
Guillian Barre : Definition
- Triggered by an autoimmune response in which the body’s immune system mistakenly attacks the peripheral nerves
- acute paralytic polyneuropathy that affects the peripheral nervous system
- Acute, symmetrical, ascending weakness and can also cause sensory symptoms
Guillian Barre : Pathophysiology
1 . Trigger : Infection with Campylobacter jejuni (most common)
- 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
Peripheral Neuropathy : Definition
Peripheral neuropathy refers to reduced sensory and motor function in the peripheral nerves, typically affecting the feet and hands
Peripheral Neuropathy : Causes
- A – Alcohol
- B – B12 deficiency
- C – Cancer (e.g., myeloma) and Chronic kidney disease, Charcot-Marie Tooth disease
- D – Diabetes and Drugs (e.g., isoniazid, amiodarone, leflunomideand cisplatin)
- E – Every vasculitis
Ulnar nerve palsy
Radial nerve : Anatomy
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
Radial nerve palsy : Clinical features
- Wrist drop
- Difficulty in finger + thumb extension
- Sensory changes
* Paresthesia/Numbness on dorsum of hand
Ulnar nerve palsy : Anatomy
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
Ulnar palsy : Clinical features
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
Myasthenia Gravis : Definition
Myasthenia gravis is an autoimmune condition affecting the neuromuscular junction.
It causes muscle weakness
progressively worsens with activityand improves with rest
Myasthenia Gravis : Incidence
Women < 40
Men > 60
Myasthenia Gravis : Pathophysiology
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
Myasthenia Gravis : Clinical presentation
**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
Myasthenia Gravis : Associated disease
Strong link with thymomas (thymus gland tumours).
Myasthenia Gravis : Investigations
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
-
Imaging
* A CT or MRI of the thymus gland is used to look for a thymoma.
Myasthenia Gravis : Management
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
Myasthenia Gravis : Complication
Myasthenia Crisis
* Respiratory muscle compromise - respiratory arrest
* May require : Mechanical ventilation
Lambert-Eaton Syndrome : Defintion
Autoimmune disorder associated with small cell lung cancer
Caused by an antibody directed against presynaptic voltage-gated calcium channel in the peripheral nervous system.
Lambert-Eaton Syndrome : Clinical features
- Proximal muscle weakness
- Affects legs first
Repeated muscle contractions -> increased muscle strength (in contrast to myasthenia gravis)
- Autonomic symptoms
- Dry mouth, Impotence, Difficulty micturating
- Hyporeflexia
Lambert-Eaton Syndrome : Investigation
- Electromyography
- R/o Lung Cancer
Lambert-Eaton Syndrome : Management
- Tx of underlying cancer
- Immunosupression : Prednislone/Azathioprine
- 3,4-diaminopyridine : blocking voltage-gated potassium channels in the presynaptic membrane, which in turn prolongs the depolarisation of the cell membrane
Neuropathic pain : Mx
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
