Neuromuscular + Peripheral Neuropathy Flashcards
(113 cards)
1
Q
In terms of NMJ conditions, which are pre-synaptic and which are post-synaptic
A
Presynaptic
- Lambert Eaton Myasthenic Syndrome (voltage gated calcium channel ab)
- Botulism: acetylcholine vesicle
Post synaptic
- Myasthenia gravis: acetylcholine receptors
- Organophosphate poisoning: acetylcholinesterase
2
Q
Main characteristics of MG
A
- Post-synaptic antibody mediated disease (T cells)
- Associated with thymoma or thymic hyperplasia
- Ocular symptoms are the most common presenting symptom (diplopia, ptosis)
- Ptosis can be alternating
- Generalised weakness
- Fatigability
3
Q
What conditions are MG associated with?
A
- Thymoma
- Thymic hyperplasia
- Hashimoto thyroiditis
- RA
- Sarcoidosis
- SLE
thymomas in 15%
autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders, rheumatoid, SLE
thymic hyperplasia in 50-70%
4
Q
What are the main clinical forms of MG
A
- Ocular MG: only the extraocular and/or eyelid muscles
- Generalised MG:
All skeletal muscles may be involved
Especially ocular, bulbar, limb and respiratory muscles - so difficulty standing up, climbing stairs, swallowing or chewing
5
Q
Medications that should be avoided in MG
A
- Beta blockers
- Calcium channel blockers (verapamil)
- Aminoglycosides (eg: gentamicin) - especially out of the abx
- Fluoroquinolones (eg: ciprofloxacin)
- Tetracylcines (eg: doxycycline)
- Macrolides (eg: azithromycin)
- Phenytoin
- Lithium
- Magnesium
penicillamine quinidine, procainamide beta-blockers lithium phenytoin antibiotics: gentamicin, macrolides, quinolones, tetracyclines
6
Q
Clinical features of MG
A
- Eye muscle weakness: most common initial symptom - ptosis, diplopia, blurred vision
- Bulbar muscle weakness: slurred speech, difficulty chewing and/or swallowing
- Proximal limb weakness: rising from chair, climbing stairs, brushing hair. Deep tendon reflexes not affected
- Resp muscle weakness: dyspnoea
- Muscle fatigability
7
Q
Antibodies associated in MG
A
85% of patients have generalised myasthenia
- 85% are acetylcholine receptor (AChR) antibody positive
- 6-10% are muscle specific kinase (MuSK) ab positive
- Small group of seronegative can seroconvert in 1st year
15% of patients have ocular myasthenia
- 50% are ACHR antibody positive
- 66% of patients will progress to generalised within 2 years
- 90% of those who do not generalise within 2 years will remain ocular
(Most people will become generalised but a small subset remain ocular)
- AChR ab correlate with thymoma or thymic hyperplasia
- Antibody titres don’t correlate with clinical severity and no need to conduct follow up serology
- Ocular and generalised
MuSK Ab
- Non white, young, female
- Early onset
- Not related to thymoma/hyperplasia
- Generalised MG
- Severe weakness +/- atrophy
- Severe disease with respiratory and bulbar involvement
- Less fluctuation
- Poor response to treatment, good response to rituximab
LRP4 Ab: mild to mderate disease
MUSK and LRP4 are not associated with thymoma
Titin: late onset, severe thymoma
Titin also associated with myocarditis
Hanna Pearls
Acetylcholine receptor positive in 80% of patients
- 50% would have a thymoma - thymectomy
- 30% have hyperplasia of the thymus - for thymectomy if <55yo
- Can reduce immunotherapy after thymectomy
10-15% patients have MuSK antibody
- Patients do not have a thymoma and do not undergo a thymectomy
Titin Antibodies
- If this is positive, need to check anti-neuronal ab to check for paraneoplastic syndromes
-In patients who are titin ab positive, 100% patients will have a thymoma
Rare: can have seronegative MG so no antibodies
8
Q
Investigations of MG besides Ab
A
- Ice Test: An ice pack is applied to the affected upper eyelid for 2-5 minutes. A positive test is the improvement of ptosis by > 2mm or more. This transient improvement in ptosis is due to the cold decreasing the acetylcholinesterase break-down of acetylcholine at the neuromuscular junction.
Single nerve fibre and repetitive nerve stimulation (electrodiagnostics)
- Single Fibre EMG: Best utilised for ocular MG
High sensitivity, low specificity, false positives
Repetitive Stimulation
- Repeated stimulation of nerve
- 10% decrement in amplitude is diagnostic - a smaller and smaller muscle response with each repetitive stimulus) is abnormal and indicates NMJ dysfunction.
- Greater decrement post exercise
- Generalised MG: Sensitivity 80%
- Ocular MG: 20%
Tensilon Test (edrophonium) 70-95% sensitivity
- Administration of edrophonium which is a short acting acetylcholinesterase inhibitor
- IV bolus given along with atropine at bedside (in case of myasthenia gravis)
- Assess if objective change in signs - normally would get better with repeated doses
- Sensitivity 60%, low specificity
- A patient suffering from myasthenia gravis experiences improvement in muscle strength and endurance with repetitive movements, while healthy persons do not feel any difference. The effects of edrophonium lasts around 10 minutes. The edrophonium allows accumulation of acetylcholine (ACh) in the neuromuscular junctions, and makes more ACh available to the muscle receptors, thereby increasing muscle strength in myasthenia gravis.
CT Chest for thymoma
9
Q
Pathophysiology of MG
A
Normal:
Acetycholine fuse with the presynaptic membrane –> release of Ach in the synaptic cleft –> reversible binding of ACh to the nicotinic ACh receptor –> opening of receptor ion channel –> influx of ions –> depolarisation action potential and contraction of the muscle –> breakdown of Ach by cholinesterase and reuptake in the motor end plate
In MG
- autoantibodies compete with ACh for postsynatpic AChR –> ACh cannot bind –> receptor ion channel does not open –> no neuromuscular transmission
10
Q
Treatment for MG
A
- Thymectomy
- Cholinesterase inhibitors: pyridostigmine (should be avoided in acute resp failure as it can increase resp secretions)
Pyridostigmine is a long-acting acetylcholinesterase inhibitor that reduces the breakdown of acetylcholine in the neuromuscular junction, temporarily improving symptoms of myasthenia gravis - If symptoms persist:
Steroids
Azathioprine: better than pred monotherapy but takes several months to become effective
Mycophenolate, tacrolimus, methotrexate
IVIG, plasma exchange, rituximab in refractory disease
Eculizumab: severe cases (C5 inhibitor)
Efgartigimoid: neonatal Fc receptor (FcRn) molecule that recycle IgG, extending its half life by about 4x that of other immunoglobulins. - For patients with MuSK ab - typically refractory to pyridostigmine, respond well to IVIG and plasmapharesis and rituximab.
11
Q
Characteristics of myasthenia crisis
A
- Severe weakness with respiratory weakness/failure
- Causes: infection, surgery, pregnancy, medications (beta blocker, aminoglycosidesm calcium channel blockers, magnesium fluroquinolones)
- Tx; IVIG for 5 days, plasmapheresis, early intubation
12
Q
Compare myasthenic crisis with cholinergic crisis
A
Myasthenic Crisis (too little acetylcholine) - mydriasis - Tachycardia - Cold and faint - Normal secretions - No fasciculations Tx: IVIG, plasmapheresis
Cholinergic crisis (too much acetylcholine due to too much cholinesterase inhibitors) - Miosis - Bradycardia - Fasciculations - Warm and flushed skin - Increased bronchial secretions - Abdominal cramps Tx; A cholinergic crisis should be treated by withdrawing all anticholinesterase medication, mechanical ventilation if required, and atropine i.v. for muscarinic effects of the overdose. The neuromuscular block is a nicotinic effect and will be unchanged by atropine.
13
Q
Characteristics of lambert eaton myasthenic gravis
A
- Can be both autoimmune and paraneoplastic
- Paraneoplastic normally secondary to SCLC
- Non-neoplastic; HLAB8DR3
- Ab against voltage gated calcium channels, proximal weakness improves with exercise, exercise, dysautonomia
14
Q
Clinical features of lambert eaton myasthenic gravis
A
Clinical triad of
- Proximal weakness which improves with exercise
Proximal LL –> proximal UL –> distal muscles –> oculobulbar
- Autonomic features: dry mouth, erectile dysfunction, constipation, urinary issues, orthostatic hypotension
- Areflexia
15
Q
Ix of lambert eaton myasthenic gravis
A
- Voltage gated calcium channel ab
- Malignancy screen
- EMG: repetitive nerve stimulation results in incremental response
16
Q
Tx of lambert eaton MG
A
- Tumour resection
- Amifampridine (3,4-diaminopyridine): blocks presynaptic potassium channel (blocks efflux of potassium ions) –> increase action potential duration/prolong duration of depolarisation –> increased presynaptic calcium concentrations
- Immunosuppression: IVIG, pred (in non paraneoplastic)
17
Q
Contrast MG with LEMG
A
MG
- Associated disease: thymoma
- Starts with weakness of extraocular muscles, proximal weakness worsens with use
- Normal reflexes
- Repetitive nerve stimulation: decremental response
- Autonomic dysfunction: none
- Responds to cholinesterase inhibitors
LEMG
- Associated disease: small cell lung cancer
- Proximal limb muscle weakness that improves throughout the day
- Reduced/absent reflexes
- Repetitive nerve stimulation: incremental response
- Autonomic dysfunction: dry mouth, erectile dysfunction, constipation, urinary issues postural hypotension
- Amifampridine (3,4-diaminopyridine): blocks presynaptic potassium channel (blocks efflux of potassium ions) –> increase action potential duration/prolong duration of depolarisation –> increased presynaptic calcium concentrations
18
Q
Characteristics of botulism
A
- Secondary to clostridium botulinum
- Inhibit presynaptic acetylcholine release
Foodborne Botulism
- Ingestion of botulinum toxin
- Incubation mean 2 days
- N+V
- Symmetric descending flaccid paralysis
- Autonomic involvement: dry eyes, dry mouth, paralytic ileus, urinary retention
- Internal and external ophthalmoplegia
Internal: pupillary muscles, dilation of pupil, and fixed
External: paralysis of extraocular muscles - can’t move eyes
If there is internal + external ophthalmoplegia think toxin! - Mentation and reflexes preserved
Mx
- Removal of unabsorbed toxin only considered if ileus present
- Avoid aminogycoside use as death of clostridum leads to more toxin being produced
- Equine antitoxin
Prognosis
- Recovery over months
- Main complication are immobility and intubation
External ophthalmoplegia means paralysis of the extraocular (extrinsic) muscles that move the eyes. Internal ophthalmoplegia means paralysis of the intrinsic (internal) eye muscles that control pupil size and accommodation (focusing).
19
Q
Characteristics of GBS (AIDP)
Acute idiopathic demyelinating polyradiculoneuropathy
A
- Characterised by ascending symmetrical flaccid paralysis with areflexia
- Albuminocytologic dissociation, characterised by elevated protein levels and normal cell count in CSF
20
Q
Cause of GBS
A
- Occur usually 4 weeks after an upper respiratory tract infection or GIT infection
- Most commonly associated with campylobacter jejuni + CMV
Other causes include: - Bacterial: Mycoplasma pneumoniae Viral: CMV, Zika virus, EBV, HIV, influenza, covid 19 - ZIKA - 2 weeks post COVID 18 - Post immune checkpoint inhibitors - ?vaccinations
21
Q
Pathophysiology of GBS
A
Humorally mediated rather than T cells
- Postinfectious autoimmune reaction that generates cross-reactive antibodies (molecular mimicry)
- Infection triggers humoral response → formation of autoantibodies against gangliosides (e.g., GM1, GD1a) or other unknown antigens of peripheral Schwann cells → immune-mediated segmental demyelination → axonal degeneration of motor and sensory fibers in peripheral and cranial nerves (CN III–XII)
22
Q
Clinical features of GBS
A
- Symmetrical ascending flaccid paralysis
- Reduced/absent reflexes
- Autonomic dysfunction: arrhythmia, void dysfunction, intestinal dysfunction,, postural hypotension
Autonomic symptoms are common in GBS. The most frequently encountered are tachycardia and urinary retention. Although autonomic dysfunction may manifest as hypertension, hypotension, bradycardia, or ileus, these are not as commonly seen. - Respiratory muscle involvement
- Sensory deficit rare
- Lower back pain
- Symptoms peak at 4 weeks
23
Q
Subtypes and variants of GBS
A
- AIDP
- acute variant
- Associated with campylobacter jejuni + CMV
- Ascending flaccid paralysis, autonomic neuropathy, peak at 4 weeks
- IVIG, plasmapheresis - CIDP
- Chronic variant > 8 weeks
- Sensory symptoms and proximal weakness more common - proximal and distal weakness
- Reduced reflexes
- Milder phenotype, rarely have resp involvement/intubation
- Anti-GM1 ganglioside autoantibodies
- Clinical features > 8 weeks
- Glucocorticoids, azathioprine, cyclophosphamide, plasmapharesis, IVIG, ritux for Ab positive disease (better outcomes with early treatment) - Miller Fisher syndrome
- Limited variant of GBS characterised by cranial nerve involvement
- Autoantibodies directed against ganglioside Gq1b, GTa
- Ophthalmoplegia, ataxia, areflexia
- IVIG - Multifocal motor neuropathy (MMN)
- Variant of GBS affecting the motor neurons - asymmetric pure motor weakness
- Onset is usually in the upper extremities
- DDx for AML
- Anti- GM1 ganglioside autoantibodies
- Usually normal protein levels in CSF
- Asymmetric paralysis and areflexia
Deep tendon reflexes are usually decreased but typically intact in unaffected areas
- IVIG
- Steroids can worsen condition. - Acute motor axonal neuropathy
- Abrupt onset variant of GBS
- Affects motor nerve fibres with variable severity and spares sensory fibres
- Typically occurs after campylobacter jejuni, against GM1 ganglioside like epitopes
- Acute paralysis
- Areflexia without sensory loss
- IVIG, plasmapheresis
24
Q
Ix for GBS
A
Bloods
- Elevated LFT in 30%
- Elevated CK
- Serology for C jejuni, HIV, CMV, EBV
CSF
- Albuminocytologic dissociation, high protein levels and normal cell count
- Elevation may be delayed it taken too early
Forced vital capacity, <1L = ICU
NCS
- Decreased nerve conduction velocity due to demyelination /conduction block
- Prolonged F wave latency
EMG: denervation, demyelinating pattern
ECG: autonomic cardiac dysregulation - impaired heart frequency variation
25
Autoantibodies associated with the different variants of GBS
- CIDP: Anti GM1
- Miller Fischer: GQ1b
- Acute motor axonal neuropathy: GD1a, GM1
- Sensory GBS: GD1B
- Bulbar Palsy: GT1a
- Multifocal motor neuropathy (purely motor): GM1
- Bickerstaff Brainste, Encephalitis: GQ1b
- Acute Motor Axonal Neuropathy: GD1a, GM1
26
Tx of GBS
| Tx of CIDP
GBS/AIDP
IVIG
- No benefit of PEX followed by IVIG
Plasmapheresis:
- removes autoantibodies, immune complexes, complement and cytokine
- Within 2-4 weeks of onset
- Should be wary in people with autonomic instability
Steroids DO NOT work well - lead to worse outcome
CIDP
- IVIG, plasmapheresis
- Can use steroids
27
Complications of GBS
- Respiratory paralysis
- Pulmonary infection/embolism
- Cardiac dysfunction
- Unable to walk unaided
28
Difference between small fiber and large fiber neuropathies
Small Fibre Neuropathies
- Involve small, unmyelinated nerve fibres
- Affect pain + temperature sensation and autonomic function
Large fibre neuropathies
- Associated with loss of joint position/proprioception, vibration, pressure and sensory ataxia (touch).
29
Peripheral neuropathy Ix
```
FBC, EUC, CMP, LFT, CRP, ESR
Protein electrophoresis with immunofixation
TFT
Glucose
Vitamin B12
```
30
Benefits of EMG
Can confirm presence of neuropathy
Differentiate between axonal or demyelinating
Distinguish neuropathy from myopathy and radiculopathy from plexopathy
31
Types of nerve fibres
A fibres: myelination present, involved in sensory (touch, vibration, pain, temperature)
B fibres: myelinated, preganglionic sympathetic fibres
C fibres: absent myelination, involved in visceral pain, post-ganglionic sympathetic fibres
32
Types of Nerve Damage
Neurapraxia = focal demyelination
- Compression injury causing temporary disruption of nerve conduction
- The whole nerve remains structurally intact
- Good prognosis with complete recovery of nerve function
- Results in focal demyelination, no loss of axonal integrity
- Weakness and sensory loss are due to conduction block which can be confirmed with electrodiagnostic studies (NCS or EMG)
- If axon distal to injury is intact = nerve continuity across the site of injury = excellent recovery days-weeks-maximum months
Axonotmesis = axonopathy
- Caused by crush injury, nerve stretch (MVA, fall) or percussion injuries (eg: gunshot wounds)
- Axon damaged but perineurium and epineurium intact
- The axon is locally but irreversibly damaged and the myelin sheath is similarly involved
- Leads to wallerian degeneration : axon and myeline sheath distal to injury degenerate
- Prognosis depends on many factors with regards to nerve, anatomy, function sensory vs motor = essentially partial recovery, but much longer than neurapraxia
Neurotmesis = complete disruption of entire nerve, irreversible damage of axon and myelin/complete nerve transection
- Caused by severe lesions eg: sharp injuries, traction injuries or exposure to neurotoxic substance
- The axon, myelin sheath and surrounding stroma are all irreversibly damaged
- No regeneration unless surgery re-anastomosis
33
Brachial plexus injuries
- Complete lesions
- Upper Trunk/Erbs/C5-C6
- Lower Trunk/Klumple/C8-T1
Occur rarely only secondary to trauma and malignancy.
Complete lesions
- Motor: LMN weakness affecting the whole limb
- Sensory: sensory loss of the whole limb
- Other: horners
Upper Trunk/Erbs/C5-C6
- Cause: excessive lateral flexion of neck, trauma, birth injury
- Motor: weakness of muscles in C5/6/palsy of axillary, suprascapular and musculocutaneous nerve
- leading flexed wrist with an extended forearm and internally rotated and adducted arm (waiter's tip position)
Weak: biceps brachii, infraspinatus, wrist extensors, deltoid, supraspinatus, waiter's tip posture
imagine BIRDS eating hERBS served by a waiter
- Sensory: loss over lateral aspect of arm and forearm
- Winged scapula
Lower Trunk/Klumple/C8-T1
- Cause: hyperabduction of the arm, compression f the lower trunk of brachial plexus by pancoast tumour, cervical rib
- Motor: true clawhand with paralysis of all intrinsic muscles (thenar, hypothenia, lumbricals, interossei) - median, ulnar
- Sensory: loss along medial aspect of hand and forearm
- Others: Horner's
34
Radial Nerve
- Normal function
- Radial nerve palsy
```
Radial Nerve (C5/T1)
- Motor: extension of everything
```
Radial Nerve Radiculopathy:
Cause
- Axilla: from crutch use, saturday night palsy
- Mid arm: midshaft fracture of humerus
- Wrist: radial fracture, wearing tight bracelets
- Motor: wrist drop due inability to extend at the wrist and fingers
- Sensory:
Dorsal: lateral 2.5 fingers excluding tips of 2nd and 3rd fingers, anatomical snuffbox
Palmar: 1st webspace
```
Proximal Lesion: complete loss of motor and sensory
Distal lesion (radial tunnel syndrome): partial loss of motor function, preservation of sensory function
```
35
Axillary Nerve injury
Axillary C5/6
Cause:
- Anterior shoulder dislocation
- Fracture of surgical neck of humerus
Motor Deficit
- Paralysis of the deltoid muscle --> impaired arm abduction
- Paralysis of the teres minor muscle --> impaired external rotation of the arm
- Deltoid atrophy
Sensory
- Deltoid region
36
Musculocutaneous
Musculocutaneous C5-7
Normal function:
Motor: elbow flexion
Sensory: lateral forearm
Cause: trauma, upper trunk compression (erb balsy)
Motor:
- Paralysis of brachialis: impaired elbow flexion
- Paralysis of biceps brachii: impaired forearm supination
- Reduced biceps reflex
Sensory: lateral forearm from the elbow to the base of the thumb
37
Median Nerve
Median Nerve C5-T1
Normal
Motor: wrist flexion, finger flexion, lumbricals.
- innervates muscles of the anterior foream, supplies almost all the flexors of the wrist and fingers except the flexor carpi ulnaris and medial half of flexor digitorum profundus (ulnar does medial 2 fingers)
- Supplies thenar muscles and lateral 2 lumbricals (LOAF)
Lateral 2 lumbricals: MCPJ flexion, IPJ extension of 2nd and 3rd digits
Opponens pollicis brevis: opposes thumb
Abductor pollicis brevis: abducts thumb
Flexor pollicis brevis: flexes thumb
Injury
- Proximal: supracondylar fracture of humerus above the anterior interosseus nerve origin
- Distal: carpel tunnel compression below the anterior interosseus nerve origin
Motor:
- atrophy of thenar muscles
- Impaired flexion of wrist, thumb, index and middle finger.
- Proximal injury: Hand of benediction (when trying to make a fist) - unable to flex thumb, index and middle finger
- Distal injury: median claw (when extending the fingers) -
Median Claw: paralysis of lateral lumbricals causes permanent flexion of the index and middle finger at the DIP/PIP – can’t EXTEND 2nd and 3rd dingers
- pen touch test for loss of abductor pollicis brevis with lesion at or above wrist
- Deep injury to the wrist or forearm impairing the thenar muscles/superficial palm laceration: ape hand, impaired thenar muscles, impaired flexion/abduction and opposition of thumb.
- Positive pinch sign in anterior interosseus nerve syndrome
Sensory:
Proximal + Distal
- Thenar eminence
- Palmar aspect of thumb, index, middle finger and lateral ring finger (lateral 3.5)
- Dorsal: loss of sensation over tips of the lateral 3.5 fingers
38
Ulnar nerve
Normal Function
- Motor: finger abduction, finger adduction, digits 4 + 5 ulnar part of flexor digitorum profundus
2 muscles of the anterior forearm:
Flexor carpi ulnaris – flexes and adducts the hand at the wrist
Ulnar (medial) half of flexor digitorum profundus - flexes the 4th and 5th fingers at the distal interphalangeal joint
ntrinsic muscles of the hand except the LOAF muscles which is supplied by the median nerve
Hypothenar muscles (group of muscles associated with the little finger): flexor digiti minimi brevis, abductor digiti minimi, opponens digiti minimi – control movement of the 5th digit
Medial two lumbricals/3rd and 4th lumbricals - MCPJ flexion, IPJ extension for 4th and 5th finger
Adductor pollicis – adducts the thumb
Cause
-Proximal:
Fracture of the medial epicondyle of the humerus (funny bone)
Cubital tunnel syndrome
- Distal
Ulnar tunnel syndrome (from cycling, ganglion cysts)
Injury
Damage at the Elbow
- Motor: All the muscles innervated by the ulnar nerve are affected
- Sensory: All sensory branches are affected
Damage at the Wrist
- Motor: all intrinsic hand muscles affected except LOAF
- Sensory: variable sensory deficit, depending on whether palmar/superficial branch or dorsal branch is affected
Motor
- Atrophy of the hypothenar muscles
- Claw hand deformity/ulnar claw – clawing of the 4th and 5th fingers (mainly in distal nerve injuries)
- Hyperextension of 4th and 5th MCP and flexion of 4th and 5th PIP + DIP
Usually worse when the lesion occurs at the wrist as opposed to the elbow due to greater muscle imbalance. Wrist lesions usually present with weakness of the 3rd and 4th lumbrical muscles while the flexor digitorum profundus is spared (unlike the elbow where both are affected)
Wrist: FDP not affected, medial lumbricals affected - 4th and 5th DIP more flexed
Distal Ulnar Nerve Injury: can’t EXTEND 4th and 5th fingers
Elbow: FDP affected, medial lumbricals affected - less flexion of 4th and 5th DIP
Proximal Ulnar Nerve Injury: can’t FLEX 4th and 5th fingers
- Atrophy of the interosseous muscles
Inability to abduct and adduct fingers (paralysis of interosseous) – patient cannot grip paper placed between fingers
- Inability to adduct thumb leading to positive Froment’s sign (due to paralysis of adductor pollicis)
The patient is asked to hold a piece of paper between the thumb and index finger, as the paper is pulled away
They should be able to hold the paper there with no difficulty (via adduction of the thumb).
A positive test is when the patient is unable to adduct the thumb. Instead, they flex the thumb at the interphalangeal joint to try to maintain a hold on the paper.
-Sensory
Loss of sensation over dorsal and palmar surface of the medial one and half fingers
39
Upper limb reflexes
- Biceps: C5/C6, musculocutaneous
- Brachioradialis: C5/C6, Radial
- Triceps: C7/8, Radial
40
What is the motor function of inferior gluteal
L4/5
| Hip extension
41
Nerve roots of foot inversion and eversion
Inversion: L4/5
Eversion: L5/S1
42
Injury to lateral femoral cutaneous nerve (meralgia paresthetica)
L2/L3
Compressive neuropathy of the lateral femoral cutaneous nerve that causes isolated anterolateral thigh numbness without weakness.
43
What is ramsay hunt syndrome
Ramsay Hunt syndrome (herpes zoster oticus) is caused by the reactivation of the varicella zoster virus in the geniculate ganglion of the seventh cranial nerve.
Features
- auricular pain is often the first feature
- facial nerve palsy
- vesicular rash around the ear
- other features include vertigo and tinnitus
Management
- oral aciclovir and corticosteroids are usually given
44
Treatment of bells palsy
Steroids within 72 hours of symptoms onset
45
Difference between axonal and demyelinating diseases
NCS can help differentiate between axonal and demyelinating conditions
Demyelinating
- Weakness without atrophy
- Length independent distribution - proximal dominant
- Asymmetric/patchy distribution
- Loss of proximal reflexes
- Myokymia of the lid is a unilateral and uncontrollable lid twitch or tic that is not caused by disease or pathology.
- Sensation: usually mild prominent propioception/vibration, pain and temp not lost alone
- Autonomic involvement; only in GBS or autoimmune dysautonomia
- NCS: increase in latency, reduction in conduction velocity
- Recovery: rapid
Causes of Demyelinating
- Genetic: CMT1, HNPP
- Immune mediated: CIDP, GBS, MMN (Multifocal Motor Neuropathy)
- Paraproteinemia
- HIV, leprosy, cryoglobulins (hep C)
- Diphtheria
- amiodarone
- Charcot marie tooth 1
Axonal
- Ankle jerk reduced, knee jerk preserved (length dependent loss)
- Length dependent distribution
- Often symmetric
- Early wasting
- Distal > proximal
- UL affected when symptoms extend to the knees
- Sensation: depending on type of fibres involved, pain/temp/light touch/vibration
- Autosomal involvement: yes with small fibre loss (diabetes, amyloidosis)
- NCS: reduction in amplitude
- Recovery: slow
Causes of Axonal
- Charcot marie tooth type 2
- Diabetes
- Uremic neuropathy
- Toxic, chemotherapy
- Alcohol
- Vasculitis
- Vitamin B 12 deficiency
46
Difference between large and small nerve fibres
Large fibres
- A alpha (motor - muscle) myelinated
- A alpha/beta: proprioception, vibration, light touch, 2 point discrimination
Small fibres
- Crude touch (process of being touched but not being able to localize the site)
- Pain
- Temperature
- Preganglionic autonomic fibres
- Most likely to have autonomic involvement, eg: diabetic neuropathy
Cause: DM, alcohol, fabry, drugs
Note: all nerve fibres are mixed fibres, combination of large and small nerve fibres
47
What is cause of rapidly progressive (within 3 months) neuropathy?
Toxic
Paraneoplastic
Vasculitis
48
Causes of alopecia
Hypothyroidism
SLE
Amyloidosis
Thallium
49
Causes of neuropathy that are:
- Hyperacute (24-72h)
- Acute (<1 month)
- Subacute (<6 months)
- Relapsing Remitting
- Hyperacute (24-72h):
Infections (diphtheria, lyme)
Vasculitis
```
- Acute (<1 month)
GBS
Vasculitis
Porphyria ( think if patient has abdominal pain + neuropathy)
Toxic/Drugs (heavy metals)
```
```
- Subacute (<6 months)
Toxic
Nutritional deficiency
Paraneoplastic
Metabolic
```
- Relapsing Remitting
CIDP
Porphyria
HNPP
50
What is the F wave
Looks at the proximal segment of the nerve
| In GBS, there is prolonged F wave latency
51
NCS
- Distance
- Amplitude
- Latency
- Velocity
- Amplitude: gives an understanding of HOW MANY axons were excited
Amplitude loss = axonal loss
Latency and Conduction Velocity:
Latency - time between the onset of stimulus and peak of the recording.
Conduction velocity - distance of the recording/latency
- Increase in latency and decreased conduction velocity represents demyelination
- CV can drop in axonal neuropathy as the bigger faster fibres are lost BUT NEVER less than 70% of the normal value
- CV fundamental in localising sites of nerve compression as this leads to focal demyelination --> drop in velocity
- F wave: looks at the proximal segment of nerve, may be the only abnormality in GBS
- SNAP (sensory nerve action potential): sum of all the resultant action potentials
- CMAP (compound muscle action potential): sum of all the action potentials in the muscle fibres
NCS only detect large fibre, cannot test small/autonomic fibres
52
Difference between:
- Mononeuropathy
- Mononeuritis multiplex
- Polyneuropathy
- Plexopathy
- Radiculopathy
- Mononeuropathy: damage to a single peripheral nerve
- Mononeuritis multiplex: damage to >2 peripheral nerves, results in asymmetrical distribution
EG: vasculitis, HNPP, infection, toxic
- Polyneuropathy: damage to terminal branches of multiple nerves, results in symmetrical distal distribution
- Plexopathy: damage to nerve plexus
- Radiculopathy: damage to nerve root, distribution following corresponding dermatome
53
What disease do you think of when someone has trigeminal neuropathy?
Coeliac disease
54
Causes of facial diplegia (bilateral facial paralysis)
GBS (common)
Amyloidosis
Sarcoidosis
Lyme - facial nerve palsy, arthritis, carditis, erythema migrans
Facial Diplegia: they have no facial droop, test for mouth/eye closure in order to pick it up.
High risk of aspiration
55
Investigations of peripheral neuropathy
- BSL
- Vitamin B12 (normally low)
- Methylmalonic acid (MMA) (normally high)
- homocysteine (normally high)
- IEPG/EPG - immunofixation
- TSH
Other:
- FBC/EUC/LFT/CMP
- ANA/ENA/ANCA/dsDNA
- Antineuronal ab
- Coeliac serology
- Cu/Zn
- Vit E
56
Nitrous oxide and peripheral neuropathy
Nitrous oxide use can result in a subacute combined degeneration of the spinal cord and a peripheral neuropathy by converting B12 from an active monovalent to an inactive bivalent (cause b12 deficiency)
57
Causes of peripheral neuropathy
- Diabetes and alcohol are most common
- Hereditary: charcot marie tooth, hereditary neuropathy with liability to pressure palsy (HNPP)
- Diabetes
- Alcohol
- Heave metals: lead poisoning, arsenic, thallium
- Chemotherapeutic agents
- Inflammatory: vasculitis, connective tissue disorders
- Infection: herpes
58
Characteristics of diabetic polyneuropathy
- Small fibre neuropathy - length dependent dysfunction of nerve fibres
- Weakness not a predominant feature till late
- Oculomotor palsy (CNIII): acute onset of pain behind or above the eye and CNIII palsy, pupil sparing
- IV and VI involved
- High prevalence of compression neuropathies - carpal tunnel, ulnar neuropathy
- Mononueritis multiplex - vascular immune mediate
- Tropic skin changes: anhidrosis, edema, ulcers
- Autonomic: postural hypotension, impotence, gastroparesis
Tx
- Amitriptyline (TCA)
- Duloxetine and venlafaxine (SNRI)
- Gabapentin, pregablin
59
Characteristics of alcohol polyneuropathy
- Peripheral nerve injury as a result of thiamine deficiency due to chronic alcohol use disorder
- Impaired joint position
- Burnign feet syndrome
- Atrophy and paresis of distal muscles
Tx: thiamine + stop alcohol
60
Characteristics of hereditary neuropathy with liability to pressure palsy (HNPP)
- Reciprocal deletion of the 1.3Mb segment of chromosome 17p11.2 containing the PMP22 gene
- Autosomal dominant
- Characterised by transient and recurrent + reversible motor and sensory mononeuropathies, typically occurring at entrapment sites such as carpel tunnel, ulnar groove and fibular (elbow/wrist knee)
- Can last hours, days, weeks or occasionally longer
- Tx: avoid compressive positions
61
Characteristics of charcot marie tooth
- Most commonly caused by duplication of the gene PMP22 in chromosome 17
- CMT1: demyelinating, motor predominant, palpable peripheral nerves and uniform slowing of motor nerve conduction velocities on EMG
- CMT2: axonal, sensory predominant
Distal symmetric sensorimotor polyneuropathy (weakness and then sensory occurs late)
- Atrophy of calf muscles (stork legs)
- Pes cavus deformity (elevation of the plantar arch of the foot)
- Hammer toes
- Foot drop
- Reduced reflexes
- Most patients remain ambulatory throughout life and have normal lifespan
Charcot-Marie-Tooth disease is a hereditary sensory and motor peripheral neuropathy. UMN signs are not present in these patients. Patients can present with lower motor neurone signs in all limbs and reduced sensation (more pronounced distally).
62
Characteristics of HIV peripheral neuropathy
Distal, symmetric, sensory -predominant peripheral neuropathy affecting small sensory fibres in isolation or both small and large sensory fibres occur in 20-60%
- Positive and negative symptoms (pain in 50-90%)
- Don't usually have motor symptoms
- Advanced age and comorbidities that predispose patients to neuropathy (eg: diabetes, malnutrition, isoniazid) leads to increased risk
63
Suspicious features for genetic neuropathy
- Symptom onset during infancy
- Long and slowly progressing symptom
- Foot deformities (pes cavus, hammer toes)
- Lack of positive sensory symptoms despite clear sensory involvement
Commonly present as slowly progressive distal weakness, numbness without pain or parasthesia, areflexia and ataxia
64
What deficiencies can cause peripheral neuropathy.
- Copper and vitamin B12 (cobalamin) deficiencies, most often caused by
bariatric surgery, intrinsic factor antibodies, and a restrictive (usually vegetarian) diet, can damage peripheral nerve and
spinal cord structures.
- Vitamin B1 deficiency can lead to an axonal sensorimotor neuropathy and should be treated with aggressive thiamine
supplementation.
- Alcohol abuse can cause a distal axonal neuropathy that is often painful and sometimes complicated
by superimposed nutritional deficiencies.
65
Characteristics of amyloid neuropathy
Immunoglobulin light chain amyloidosis: painful (small fibre) length dependent peripheral neuropathy with generalised autonomic failure (eg: orthostatic hypotension).
Axonal involvement
66
Characteristics of paraproteinemic neuropathies
Waldenstrom macroglobulinaemia and MGUS with IgM gammopathy is linked to an immune mediated neuropathy characterised by distal sensory loss, ataxia, tremor (distal acquired demyelinating symmetric neuropathy) - DADS
- 50% of DADs neuropathy have anti-MAG Ab (myelin associated glycoprotein)
- Can have tremor
- Don't respond well to treatment - normally responds to rituximab
- Otherwise paraprotein neuropathies should respond to steroids, IVIG, plasmapheresis, ritux
IgM MGUS can mimic CIDP - considered atypical CIDP
Suspect paraproteinemia in patients with CIDP that fail to respond to expected immunotherapy.
67
What are the effects of nitrous oxide
- Nitrous oxide: myeloneuropathy = b12 deficiency
Myeloneuropathy is characterized by simultaneous damage of the tracts of the spinal cord and peripheral nerves in the lower limbs. Clinical manifestations of myeloneuropathy include difficulty in walking, weakness of lower limbs, ataxic gait, and sensory manifestations in glove and stocking distribution.
68
Medications that cause peripheral neuropathy
- Amiodarone
- Colchicine
- Hydralazine
- Chloramphenicol
- Ethambutol, Isoniazid
- Fluroquinolones
69
Chemotherapy that cause peripheral neuropathy
- Platinum based compounds (cisplastin, carboplatin and oxaliplatin): sensory neuropathy
- Taxanes (paclitaxel, docetaxel) and vinca alkaloids (vincristine) produce length dependent sensorimotor peripheral neuropathy
- Bortezomib (Proteasome inhibitor): sensory predominant axonal neuropathy that is frequently dose limiting
70
Treatment for post herpetic neuralgia
- TCA
- Anticonvulsants: gabapentin, pregablin
- Topical lidocaine
- Capsaicin
- Opioids
71
Treatment for facial neuralgia
Carbamazepine
| Gabapentin
72
Characteristics of dorsal root ganglionopathy
- Pure sensory loss
- Consider when upper limbs involved before or at same time as LL (my hands and feet are numb at the same time).
- Can have severe ataxia from complete lack of sensory or proprioceptive input
- Workup for autoimmune (Sjogrens) and paraneoplastic
- B6 toxicity and deficiency can cause ganlionopathy
73
Characteristics of fabry disease
- X linked recessive disease
- a-galactosidase A deficiency
```
Clinical features:
Triad of
- Periodically occurring dysesthesia in the hands and feet caused by small fibre neuropathy (burning pain)
- Anhidrosis, hypohidrosis
- Angiokeratoma
```
Can cause
- Cardiomyopathy
- Cerebovascular lesions (TIA, stroke)
- Fabry nephropathy: progressive renal failure
Tx: Enzyme replacement therapy with a-galactosidase A
FABRYC: foamy urine (fabry nephropathy), a-galactosidase A deficiency/Angiokeratomas, Burning pain in hands and feet, Really sweaty/dry, YX genotype (male), Cardio-Cerebrovascular disease/Ceramide trihexoidase accumulation
74
Characteristics of Porphyria
- Metabolic disorder in which defective enzymes impair the biosynthesis of heme in the liver and/or bone marrow.
- Leads to accumulation of porphyrin
Main Types
1. Porphyria Cutanea Tarda (PCT): most common form and manifest as BLISTERING CUTANEOUS photosensitivity and tea coloured urine
TX: detect prophyrins in urine/serum, photoprotective measures, regular phlebotomy or low dose hydroxychloroquine.
```
2. Acute Intermittent Porphyria
5Ps:
Painful abdomen
Port wine coloured pee
Polyneuropathy
Pscyhological disturbances
Precipitated by medications, infections, fasting.
```
3. Acquired form secondary to lead poisoning
75
Characteristics of acute intermittent porphyria
- Defective enzyme: porphobilinogen deaminase
- Accumulated substrate: porphobilinogen and ALA in blood
5P's
- Painful abdomen
- Polyneuropathy
- Psychologic disturbance: hallucinations
- Port wine coloured pee
- Precipitated by triggers like drugs (eg: phenytoin, sulfonamides)
Skin is not involved.
Ix
- Spot urine sample for heme precursor levlels
High porphobilinogen
High ALA
Tx
Hemin
Glucose loading
76
Characteristics of porphyria cutanea tarda
- Defective enzyme: uroporphyrinogen III decarboxylase
- Accumulated substrate: uroporphyrin in skin and urine
Cause:
PCT can be caused by HEP C, HEMOCHROMATOSIS, HIV, and excessive alcohol consumption. Some drugs containing estrogen, such as oral contraceptive pills or prostate cancer treatments, can also lead to a build-up of porphyrins in the blood, liver, and skin.
Clinical features
- blistering skin lesions on sun-exposed areas
- Possible scarring and/or hyperpigmentation
- Red/brown urine
Ix
Spot urine: Increased uroporphyrins
Blood: increased porphyrins
Tx
- Avoidance of sun
- Phlebotomy
- Hydroxychloroquine
77
Characteristics of ALS
- Characterised by progressive weakness and muscle wasting
- Pathology: oxidative stress caused by free radicals
Clinical Features
- UMN (hyperreflexia, spasticity, extensor plantar response) with LMN (atrophy, fasciculation) with NO sensory involvement
- Asymmetric weakness in proximal or distal aspect of limb (or bulbar), increasing weakness before progressing to another limb
- Fasciculations are rare without weakness
- Split hand: wasting of lateral aspect of hand, thenar and first dorsal interossei wasted compared to hypothenar
- Bulbar dysfunction is usually pseudobulbar (UMN)
Note: Bulbar = LMN
- Resp muscle involvement
Dementia
- Frontotemporal dementia is sometimes present
- TDP-43 positive ubiquinated cytoplasmic inclusions in almost all cases of ALS
- Mainly executive function and verbal fluency loss
Ix
- NCS: decreased CMAP, normal SNAP
- EMG: fasciculation potentials, fibrillation potentials, positive sharp waves and chronic neurogenic changes
- MRI: T2 bright signal in bilateral corticospinal is suggestive of ALS
- DDx: Lyme disease, hyperparathyroidism, thyrotoxicosis, MMN
```
- Treatment is supportive - PEG/resp support
Respiratory Support
- NIV compared to standard care showed:
Improved survival
Maintenance or improved quality of life
```
Riluzole a glutamate release inhibitor may slow progress of ALS by 3 months (need to monitor LFTs)
Disease modifying
Edaravone can be used - potential free radical scavenger to reduce oxidative stress
78
Risk factors of carpel tunnel syndrome
```
Female
Diabetes
Pregnancy
Hypothyroidism
Haemodialysis
Steroid use
RA
```
79
Leprosy
- Myobcaterium leprae
- Consider in patients from low/middle income country with skin lesions, cutaneous sensory loss, thickened nerves on palpation or focal mononeuropathies
- Sparing of tendon jerks, position and vibration and non-cutaneous autonomic function
- Tx: dapsone and rifampicin
80
What do you think of when someone has bilateral 7th nerve involvement
Consider sarcoid
81
What does winging of the scapula indicate?
When the patient is asked to place both palms against a wall and push, the medial border of the right scapula is abnormally prominent.
Scapular winging indicates palsy of the serratus anterior which is most commonly an injury of the long thoracic nerve.
The long thoracic nerve is a proximal branch of the brachial plexus, arising from the proximal C5, C6, and C7 spinal nerves, that innervates the serratus anterior muscle.
82
Sarcoidosis and peripheral neuropathy
- peripheral nerve involvement, specifically granulomatous infiltration of the peripheral nerves is less common than central involvement
- Most common peripheral presentation is polyradiculoneuropathy, peripheral neuropathy, mononeuropathy multiplex
- VII nerve most commonly affected.
83
What conditions should you think of if a person has small fibre peripheral neuropathy and autonomic failure?
DIABETES
| and then think AMYLOID
84
What is diabetic amyotrophy
- Lumbosacral radiculoplexopathy
- Usually >50yo and male
- Severe UNILATERAL pain in the back, hip or thigh that spreads to involve the entire limb and can involve the other leg within weeks to months
- Shortly after the onset of pain, proximal weakness can be detected
- Weakness and atrophy may initially be focal, but they can become widespread and bilateral
- Profound atrophy of the thigh can be seen
- Weakness involves multiple root levels and peripheral nerves
- Frequently associated with weight loss
- Occurrence if often not related to glucose control or duration of diabetes
Diabetic Amyotrophy
- Pain and weakness in quadriceps
- Require steroids for femoral amyotrophy
85
Characteristics of HSV-2 lumbosacral radiculopathy
- Radicular pain, paraesthesia, genital discomfort and lower extremity weakness
- Involvement of conus medullaris or cauda equina may result in associated urinary retention
- MRI: nerve root enlargement with associated T2 hyperintensity and T1 contrast enhancement in nerve roots and spinal cord
- Immunocompetent: valacyclovir
- Immunocompromised: aciclovir
86
Characteristics of parsonage turner syndrome
- Multifocal immune-mediated inflammatory peripheral nervous system disorder
- Brachial neuritis - severe shoulder or arm pain followed by weakness and numbness
- Normally affect middle aged men but can affect anyone
- Most lesions are axonal but occasionally patients recover so quickly because the lesion is likely predominantly demyelinating
- Tx; steroids, analgesics
Brachial neuritis is characterized by acute onset of unilateral (occasionally bilateral) severe pain, followed by shoulder and scapular weakness several days later. Sensory changes are usually minimal. There may be subsequent rapid wasting of the arm muscles in accordance to which nerve is involved. Precipitating factors include recent trauma, infection, surgery, or even vaccination. Rarely it may be hereditary. The prognosis is usually good except when the phrenic nerve is involved since this can result in significant breathlessness.
87
In LP, what can cause a very very very high protein level
- CIDP
- Froin syndrome
coexistence of xanthochromia, high protein level and marked coagulation of cerebrospinal fluid (CSF). It is caused by meningeal irritation (e.g. during spinal meningitis) and CSF flow blockage by tumour mass or abscess
88
What can cause a high opening pressure in LP?
Cryptococcal and TB meningitis
89
In EMG what does spontaneous activity represent?
- A resting muscle should be electrically silent
- Any activity that occurs is known as spontaneous activity
- Spontaneous firing of individual muscle fibres occurs in response to background levels of ACETYLCHOLINE released by denervated fibres
- Spontaneous firing =
ACTIVE DENERVATION
INFLAMFMATORY MYOPATHY - eg: autoimmune, active myositis, statin induced
90
On EMG, difference between neurogenic and myopathic
Neurogenic
- Morphology: large amplitude, increased duration, polyphasic
- Decreased recruitment
Myopathic
- Morphology: small amplitude
- Increased/early recruitment
91
MG and pregnancy
- Can lead to weakness in the newborn
- Improvement of symptoms can occur in 2nd/3rd trimester and sudden severe exacerbation post partum
- Tx:
Mild: cholinesterase inhibitor
Moderate: pred
Severe: IVIG, plex, azathioprine safe
92
Lab findings of of subacute combined degeneration
| Clinical features
In patients with subacute combined degeneration,
results of laboratory studies usually show a LOW B12, ELEVATED METHYLMALONIC ACID, ELEVATED HOMOCYSTEINE, MACROCYTIC ANAEMIA
Patients with subacute combined degeneration of the cord (SCDC) classically have an ataxic gait (due to degeneration of the dorsal columns) and mixed UMN and LMN signs (due to degeneration of lateral motor tracts and peripheral nerves). The history will typically be subacute, occurring over months rather than decades. Patients with SCDC often notice sensory symptoms before weakness.
93
Characteristics of myopathies
Many myopathies are painless
- the presence of pain should prompt investigation of metabolic, toxic, and infectious causes.
- Rapid progression is suggestive of
inflammatory, toxic, or endocrine myopathies, whereas most hereditary myopathies have a stable or slowly progressive course.
- Mitochondrial myopathies may present with fluctuating weakness and ocular and bulbar involvement.
94
Features of myotonic dystrophy
- Myotonic dystrophies are associated with myotonia, an impairment of muscle relaxation causing stiffness and a delayed hand-grip release.
- Myotonic dystrophy type 1 causes DISTAL weakness and is associated with cataracts, frontal balding, and cognitive impairment.
Dystrophia myotonica - DM1
• distal weakness initially
• autosomal dominant
• diabetes
• dysarthria
- Myotonic dystrophy type 2 is milder and causes
proximal weakness.
General features
• myotonic facies (long, 'haggard' appearance)
Long narrow face, hollowed cheeks + high arched palate
• frontal balding
• bilateral ptosis
• cataracts
• dysarthria
Other features
• myotonia (tonic spasm of muscle) - classically manifests as difficult releasing a handshake
• weakness of arms and legs (distal initially)
• mild mental impairment
• diabetes mellitus
• testicular atrophy
• cardiac involvement: heart block, •cardiomyopathy
•dysphagia
95
Features of mitochondrial myopathy
Mitochondrial myopathy can present
with significant variability and may cause fatigue, myalgia, ophthalmoplegia, and various extramuscular manifestations.
The estimated prevalence of mitochondrial myopathies
is between 6 and 16 per 100,000 persons, and their
presence should be suspected in the presence of multiorgan involvement and maternal transmission.
- Organs with a high energy requirement (e.g., retina, brain, inner ear, skeletal, cardiac muscles) are particularly affected.
- Commonly external ophthalmoplegia, ptosis, and/or exertional muscle weakness.
- Muscle biopsy: Immunohistochemistry typically shows ragged red fibers, which are caused by subsarcolemmal and intermyofibrillar accumulation of defective mitochondria in muscles (mitochondria stain red).
Normal CK
Elevated lactate and alanine in serum, urine and/or CSF
Treatment: mainly supportive
96
What are the leptomeninges?
Leptomeninges comprise both the arachnoid mater and the pia mater.
97
Neuropathic Pain Mx
Neuropathic pain may be defined as pain which arises following damage or disruption of the nervous system. It is often difficult to treat and responds poorly to standard analgesia.
```
Examples include:
diabetic neuropathy
post-herpetic neuralgia
trigeminal neuralgia
prolapsed intervertebral disc
```
- first-line treatment*: amitriptyline, duloxetine, gabapentin or pregabalin
if the first-line drug treatment does not work try one of the other 3 drugs
in contrast to standard analgesics, drugs for neuropathic pain are typically used as monotherapy, i.e. if not working then drugs should be switched, not added
- tramadol may be used as 'rescue therapy' - for exacerbations of neuropathic pain
topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)
- pain management clinics may be useful in patients with resistant problems
98
Common peroneal nerve
The sciatic nerve divides into the tibial and common peroneal nerves. Injury often occurs at the neck of the fibula
The most characteristic feature of a common peroneal nerve lesion is foot drop.
Other features include:
weakness of foot dorsiflexion
weakness of foot eversion
weakness of extensor hallucis longus
sensory loss over the dorsum of the foot and the lower lateral part of the leg
wasting of the anterior tibial and peroneal muscles
99
3rd Nerve Palsy
Features
eye is deviated 'down and out'
ptosis
pupil may be dilated (sometimes called a 'surgical' third nerve palsy)
100
Myotonic Dystrophy
```
Dystrophia myotonica - DM1
distal weakness initially
autosomal dominant
diabetes
dysarthria
```
Myotonic dystrophy (also called dystrophia myotonica) is an inherited myopathy with features developing at around 20-30 years old. It affects skeletal, cardiac and smooth muscle. There are two main types of myotonic dystrophy, DM1 and DM2.
Genetics
autosomal dominant
a trinucleotide repeat disorder
DM1 is caused by a CTG repeat at the end of the DMPK (Dystrophia Myotonica-Protein Kinase) gene on chromosome 19
DM2 is caused by a repeat expansion of the ZNF9 gene on chromosome 3
The key differences are listed in table below:
DM1
- DMPK gene on chromosome 19
- Distal weakness more prominent
DM2
ZNF9 gene on chromosome 3
- Proximal weakness more prominent
- Severe congenital form not seen
```
General features
myotonic facies (long, 'haggard' appearance)
frontal balding
bilateral ptosis
cataracts
dysarthria
```
```
Other features
myotonia (tonic spasm of muscle)
weakness of arms and legs (distal initially)
mild mental impairment
diabetes mellitus
testicular atrophy
cardiac involvement: heart block, cardiomyopathy
dysphagia
```
101
Treatment for post herpetic neuralgia
- first-line treatment*: amitriptyline, duloxetine, gabapentin or pregabalin
if the first-line drug treatment does not work try one of the other 3 drugs
in contrast to standard analgesics, drugs for neuropathic pain are typically used as monotherapy, i.e. if not working then drugs should be switched, not added
- tramadol may be used as 'rescue therapy' for exacerbations of neuropathic pain
- topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)
- pain management clinics may be useful in patients with resistant problem
NOTE: carbamazepine is used first-line for trigeminal neuralgia
102
Features of Miller Fischer
Miller Fisher syndrome
- Variant of Guillain-Barre syndrome
associated with ophthalmoplegia, areflexia and ataxia.
-The eye muscles are typically affected first
- Usually presents as a DESCENDING paralysis rather than ascending as seen in other forms of Guillain-Barre syndrome
- anti-GQ1b antibodies are present in 90% of cases
103
What conditions lead to
- Predominantly motor loss
- Predominantly sensory loss
How does the following present:
- Alcoholic neuropathy
- Vit B12 deficiency
Predominately motor loss
Guillain-Barre syndrome
porphyria
lead poisoning
hereditary sensorimotor neuropathies (HSMN) - Charcot-Marie-Tooth
chronic inflammatory demyelinating polyneuropathy (CIDP)
diphtheria
```
Predominately sensory loss
diabetes
uraemia
leprosy
alcoholism
vitamin B12 deficiency
amyloidosis
```
Alcoholic neuropathy
secondary to both direct toxic effects and reduced absorption of B vitamins
sensory symptoms typically present prior to motor symptoms
Vitamin B12 deficiency
subacute combined degeneration of spinal cord dorsal column usually affected first (joint position, vibration) prior to distal paraesthesia
103
What conditions lead to
- Predominantly motor loss
- Predominantly sensory loss
How does the following present:
- Alcoholic neuropathy
- Vit B12 deficiency
Predominately motor loss
Guillain-Barre syndrome
porphyria
lead poisoning
hereditary sensorimotor neuropathies (HSMN) - Charcot-Marie-Tooth
chronic inflammatory demyelinating polyneuropathy (CIDP)
diphtheria
```
Predominately sensory loss
diabetes
uraemia
leprosy
alcoholism
vitamin B12 deficiency
amyloidosis
```
Alcoholic neuropathy
secondary to both direct toxic effects and reduced absorption of B vitamins
sensory symptoms typically present prior to motor symptoms
Vitamin B12 deficiency
subacute combined degeneration of spinal cord dorsal column usually affected first (joint position, vibration) prior to distal paraesthesia
104
How does uremic neuropathy present?
Present normally as sensory loss
105
Drugs that cause peripheral neuropathy
```
Drugs causing a peripheral neuropathy
amiodarone
isoniazid
vincristine
nitrofurantoin
metronidazole
```
106
Vitamin B12 deficiency
Vitamin B12 deficiency
= subacute combined degeneration of spinal cord dorsal column usually affected first (joint position, vibration) prior to distal paraesthesia
The dorsal column and lateral corticospinal tract are affected. These tracts are responsible for joint position and vibration sense, which are typically lost first in this condition, followed by distal paraesthesia and upper motor neuron signs in the legs.
Note:
Lateral corticospinal: affects legs
Anterior corticospinal: affects axial muscles
107
Before starting folate supplementation, what should be checked
Vitamin B12 deficiency
Vitamin B12 level should be checked and treated before correcting any folate deficiency to avoid subacute combined degeneration of the spinal cord
Always replace vitamin B12 before folate - giving folate to a patient deficient in B12 can precipitate subacute combined degeneration of the cord
108
Characteristics of myotonic dystrophy
Myotonic dystrophy (also called dystrophia myotonica) is an inherited myopathy with features developing at around 20-30 years old. It affects skeletal, cardiac and smooth muscle. There are two main types of myotonic dystrophy, DM1 and DM2.
Genetics
• autosomal dominant
• a trinucleotide repeat disorder
• DM1 is caused by a CTG repeat in the DMPK (Dystrophia Myotonica-Protein Kinase) gene on chromosome 19
- Distal weakness is more prominent
Myotonic dystrophy type I is caused by a CTG nucleotide repeat expansion and results in Cataracts, Toupee (premature hair loss in men), and Gonadal atrophy
• DM2 is caused by a CCTG tetranucleotide repeat expansion of the ZNF9 gene on chromosome 3
- Proximal weakness is more prominent
- Milder disease
General features
• myotonic facies (long, 'haggard' appearance)
Long narrow face, hollowed cheeks + high arched palate
• frontal balding
• bilateral ptosis
• cataracts
• dysarthria
Other features
• myotonia (tonic spasm of muscle) - classically manifests as difficult releasing a handshake
• weakness of arms and legs (distal initially)
• mild mental impairment
• diabetes mellitus
• testicular atrophy
• cardiac involvement: heart block, •cardiomyopathy
•dysphagia
109
Hyperreflexia may be seen in which variant of GBS?
Hyperreflexia may be seen in a GBS variant known as Bickerstaff's encephalitis.
110
MOA of ondansetron
5-HT3 antagonists are antiemetics used mainly in the management of chemotherapy-related nausea. They mainly act in the chemoreceptor trigger zone area of the MEDULLA
Examples
ondansetron
granisetron
Adverse effects
constipation is common
prolonged QT interval
111
Poor prognostic factors for GBS
```
Poor prognostic features
age > 40 years
poor upper extremity muscle strength
previous history of a diarrhoeal illness (specifically Campylobacter jejuni)
high anti-GM1 antibody titre
need for ventilatory support
```
112
What is POEMS?
- POEMS syndrome is a rare, mulitisystem disorder.
- POEMS stands for the disorder's features, which may include Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes.
- Signs and symptoms may include progressive sensorimotor polyneuropathy; enlarged liver, spleen, and/or lymph nodes; a disorder of the endocrine glands (often with multiple abnormalities); a monoclonal plasma cell proliferative disorder; and darkening of the skin (hyperpigmentation).
Elevated VEGF - diagnostic test for POEMs
Require bone marrow transplant to treat the underlying haem malignancy
