Neurology

Malignancy and Hydrocephalus

Brachial plexus lesions

Introduction

  • Roots from C5 to T1

Causes

  • Apical lung malignancies (Pancoast tumour)
  • Trauma e.g. motor cycle accident, Birth trauma
  • Cervical rib, Neuralgic amyotrophy

Clinical

  • Pain over the shoulder (in a smoker always CXR)
  • Cervical rib may also impair vascular supply and made worse by carrying or lifting
  • Commoner in women

Investigations

  • CXR, FBC, ESR MRI can help differentiate inflammatory of neoplastic

Brachial neuritis (neuralgic amyotrophy)

Introduction

  • Inflammation of brachial plexus ? infective

Clinical

  • Severe pain in shoulder for 1-3 days followed by weakness and wasting of shoulder as settles.

Investigations

  • CXR and CT may be needed if infiltrative process.
  • Differentiate from other causes of a weak arm

Management

  • Steroids have been used
  • Conservative, physiotherapy

Lumbar plexus

  • Roots from L2 to S2
  • Pelvic malignancies
  • Trauma

Peripheral neuropathy

Aetiology

  • There is a mixed pattern of sensory and/or motor involvement and/or autonomic involvement with many different causes - toxic, metabolic, infective, autoimmune.
  • Divided pathologically into axonal and others demyelinating but divided clinically into motor and sensory or both

Clinical

  • Sensory - Early disease hyperaesthesia and burning sensation
  • paraesthesia, pain in glove(arms) and stocking(legs) distribution
  • Vibration and two point discrimination particularly affected
  • Ataxia due to Severe sensory loss
  • Motor - Lower motor neurone - distal weakness, loss of distal reflexes e.g. ankle jerk first, muscle wasting, fasciculation
  • Trophic changes - muscle atrophy, dry shiny skin reduced sweating, ulcers
  • Autonomic - postural hypotension, loss of normal sinus arrhythmia, reduced sweating, diarrhoea, impotence, sphincter disturbance

Investigations

  • Most suspected cases require Nerve conduction studies - confirms neuropathy and differentiates axonal from demyelinating and Electromyography demonstrates denervation
  • FBC, U&E, Fasting Blood glucose and TFT, PPE, B12 and other tests as appropriate
  • Sural nerve (functionally unimportant) biopsy may be needed - leprosy, vasculitis, amyloid
  • FBC, U&E, LFT, TFT, ESR, Ca, PPE, Bence- Jones protein, B12, Glucose, Autoantibodies, HIV, Syphilis test
  • Urine porphyrins
  • CXR
  • ANCA / ANA, Genetic testing.
  • CSF - raised protein in GBS
  • Genetic assessment for CMTS
  • Lead levels
  • Antiganglioside antibodies

Management

  • Depends on cause
  • Splint and protect affected muscles and joints
  • Neurorehabilitation - OT and PT

Diabetic Neuropathy and others

  • Commonest cause in the developed world - Commoner in men and felt to be a microvascular complication. Marks progression and duration of diabetes. All fibres types may be affected
    • Motor, Sensory and Autonomic fibres with Axonal degeneration with secondary Demyelination
    • Cranial nerves, Can be slowly progressive development of glove and stocking sensory loss and distal motor weakness or sudden onset neuropathy
    • Mild sensory affecting feet and distal limb seen in many diabetics
    • Sensorimotor - affects hands and feet
    • Loss of deep pain - Charcot's joints at knee and ankle, Reduced reflexes
    • Autonomic - erectile impotence, diarrhoea, postural hypotension, tachycardia, gastrointestinal stasis and even bacterial overgrowth, small pupils, decreased response to hypoglycaemia
  • OTHERS
  • Nerve compression palsies e.g carpal tunnel syndrome,
  • Peroneal nerve at fibula neck - Pain down thigh to medial malleolus
  • Diabetic amyotrophy - Type 2 DM : Weakness in quadriceps, Weak hip flexors, Recovery 6-18 months, Optimise diabetic control
  • B12 deficiency - Pernicious anaemia or Terminal ileal disease causes Neuropathy + Subacute degeneration of the cord, Dementia, Megaloblastic anaemia. Gradual onset of a distal symmetrical sensory loss and then weakness. Low vitamin B12, Elevated homocysteine , Elevated methlymalonic acid, Megaloblastic anaemia, Anti Intrinsic factor and parietal antibodies in 70-90%. B12 replacement
  • B1 deficiency - Common Sensorimotor polyneuropathy in alcoholics Toxic effect of alcohol and nutritional deficiencies e.g. thiamine Distal paraesthesia, sensory loss, loss of vibration, absent ankle jerks, autonomic dysfunction
  • B6 deficiency - Isoniazid, Pellagra

Hereditary Motor and sensory neuropathies

Charcot Marie Tooth Disease

Introduction

  • Common autosomal dominant inherited distal sensory and motor neuropathy.
  • Most are inherited as Autosomal dominant except Type 3 below
  • Aetiology
    • Most forms show demyelination though some have axonal degeneration
    • The gene on Chromosome 17 encodes a myelin protein PMP
    • Onion skin like Schwann cells appearance on nerve biopsy with CMT
    • Comes on age 10-30 or younger

    Clinical

    • Childhood Pes cavus and Foot drop and Wasting of calf muscles
    • Distal peroneal muscle wasting - as "inverted champagne bottles"
    • Distal "stocking" sensory loss and absent ankle jerks.
    • Patients often recall being bad at sports and difficulty running and a similar family history of limb weakness and atrophy

    Investigations

    • Nerve conduction test : velocities are slow

    Management

    • None be none required
    • Some may need help with prosthetics to help foot drop.
  • HSMN Type III - Dejerine Sottas

    Introduction

    • Autosomal recessive due to faulty metabolism of cerebrosides

    Clinical

    • As CMT above and occurs in young children
    • May be palpable nerve thickening - ulnar and common peroneal nerve Enlarged palpable peripheral nerves

    Investigations

    • CSF protein > 10 g/L
    • Delayed motor conduction velocity
    • Onion skin schwann cells
    • Genetic analysis

    Management

    • Supportive

    Ascending polyneuritis

    Guillain-Barre syndrome

    Introduction

    • Acute inflammatory demyelinating polyneuropathy (AIDP) in 90%
    • Acute motor axonal neuropathy in others (campylobacter)

    Clinical

    • These all present with an acute weakness onset over days with areflexia sometimes following a recent infective illness e.g. of gastroenteritis may precede About 1-3 weeks before - Campylobacter and CMV infections
    • Pathogenesis seems to be an immune response to a foreign substance e.g. CMV, Campylobacter jejuni which excites an immune response against shared epitopes on myelinated cells
    • Other associated infections - CMV, Campylobacter, EBV, Mycoplasma, HIV, HAV, HBV
    • Can lead to a severe flaccid paralysis of all four limbs and arrhythmias and autonomic dysfunction and respiratory failure
    • Back pain - involvement of nerve roots as inflammatory cells have easier access to nerve roots so proximal weakness and back pain can mark onset
    • Paraesthesia in lower limbs , Facial weakness
    • Ascending polyneuritis but often proximal - Difficulty walking and getting out of a chair
    • Decreased sensation distally, Autonomic neuropathy
    • Reduced FVC and respiratory failure are possible serious sequelae
    • Neck weakness suggests respiratory muscle compromise
    • Bradycardia or asystole and swings in blood pressure
    • Urinary retention, Gut Ileus.

    Investigations

    • Antibodies to gangliosides are found
    • CSF protein > 1 g by second week but cells <
    • If cells elevated consider alternative causes.
    • Abnormal nerve conduction studies - marked slowing of conduction
    • Proximal velocities may be more affected than distal
    • There is increased 'F wave' latency.
    • Various antibodies - Anti GD1a (Acute axonal degeneration), GQ1b (Miller-Fisher variant)

    Management

    • Monitor frequently FVC to monitor respiratory function and ECG for arrhythmias
    • Risks of High Dose IVIG - Allergic reactions especially if congenital IgA deficiency which must be screened for first
    • Treatments are either IV Immunoglobulin or Plasmapheresis
    • Steroids are ineffective and not indicated
    • Intensive care if FVC < 1.5 L , Monitor ECG and Pulse BP - autonomic irregularities
    • Physiotherapy to reduce wasting, contractures and encourage positioning to await recovery and LMWH - prevent DVT/PE
    • Temporary pacing for asystole and bradycardia
    • Most make excellent recovery with IVIG and rehabilitation however Campylobacter infection causes a more severe axonal variant and rapid onset suggest poorer outcome

    Miller-Fisher syndrome

    Aetiology

    • Atypical form of GBS causing 3% of causes of Guillain-Barre Syndrome

    Clinical

    • Usually in young men with Ataxia, Ophthalmoplegia, Areflexia

    Investigations

    • anti-GQ1b antibody

    Management

    Chronic inflammatory demyelinating polyneuropathy (CIDP)

    Aetiology

    • Immune mediated peripheral demyelination

    Clinical

    • Weakness and sensory loss
    • Areflexia comes on over weeks and months

    Investigations

    • CSF protein may be elevated
    • NCS shows widespread demyelination and conduction block
    • EMG fibrillation and decreased motor units

    Management

    • Steroids indicated
    • IV Immunoglobulins and plasmapharesis may be useful

    Multifocal motor neuropathy

    Aetiology

    • Treatable autoimmune disorder of peripheral motor nerves
    • Importantly can be misdiagnosed as Motor neuron disease

    Clinical

    • Progressive weakness often asymmetrical with cramps
    • Fasciculations and reflexes lost late
    • Sensation often normal
    • Affects hands and progresses

    Investigations

    • NCS - Demyelination and Conduction block, axonal
    • High titre IgM Anti GM1 Ab seen in 50% (useful but not diagnostic)

    Management

    • IV Immunoglobulins can be very effective
    • Cyclophosphamide
    • Steroids not indicated

    Paraprotein associated polyneuropathy

    Causes

    • Sensory loss mainly in those with IgM and IgG gammopathies
    • Seen in those with myeloma or HGUS, Waldenstroms macroglobulinaemia, lymphoma

    Clinical

    • Seen in older men with Sensory loss, Tremor, Ataxia

    Investigations

    • IgM or IgG Gammopathy
    • Anti MAG antibody, MAG Myelin associated glycoprotein
    • NCS show typically demyelination rather than axonal loss

    Management

    • Myeloma related disease may respond to plasmapheresis
    • Steroids, Cyclophosphamide

    Paraneoplastic neuropathy

    Aetiology

    • Seen with
    • Small cell lung cancer
    • Breast cancer
    • Myeloma

    Clinical

    • Usually a distal sensory loss Numbness and pain
    • Autonomic neuropathy

    Investigations

    • Anti-Hu antibodies
    • Anti-Yo antibodies
    • NCS demonstrate neuropathy

    Management

    • IVIG helps some
    • Treat cause if possible

    Other causes of Neuropathy

    • Porphyria
      • Acute hepatic porphyrias with accumulated delta - Aminolaevulinic acid causing Demyelination
      • Acute attacks of abdominal pain followed days later by polyneuropathy mainly motor
    • Amyloidosis
      • Distal Sensory loss followed by weakness
      • Autonomic involvement
      • Rectal, gingival or nerve biopsy for diagnosis
    • Lead
      • Motor neuropathy
      • Bone - lead lines
      • Basophilic stippling
    • Autoimmune
      • SLE, PAN, Rheumatoid, Sjogren's syndrome, Cryoglubulinamia Rx Immunosuppression
    • HIV
      • axonal sensory neuropathy
    • Lyme disease
      • painful radiculopathy
    • Leprosy
      • Sensory or sensorimotor polyneuropathy
      • Palpabe enlarged nerves.
    • Diphtheria
      • demyelinating sensorimotor neuropathy
    • Collagen Vascular disease
      • Rheumatoid arthritis, Systemic lupus erythematosus
      • Polyarteritis nodosa, Glove and stocking sensory loss and distal motor weakness
    • See individual diseases

    Neuromuscular junction

    Myasthenia Gravis

    Introduction

    • Fatiguable weakness
  • Aetiology
    • Autoimmune disease resulting in fatiguable weakness in classically young women and older men.
    • Thymic hyperplasia in young and Thymoma in those over 40
    • Antibodies produced to the Nicotinic Acetyl choline receptor causes a reduced number of receptors
    • Leads to weakness of certain muscle groups
    • Immune mechanism
    • Commoner in women
    • HLA A1, B8 and DR
    • Simimar syndrome can be caused by some drugs eg penicillamine

    Clinical

    • A weakness that fluctuates and is fatigable
    • Worse later in day and after exercise
    • Generalised Motor weakness, Diplopia and Ptosis, Myasthenic weak smile "snarl", Dysphagia, Respiratory weakness, Unable to raise chin, Normal pupils
    • Symptoms may worsens with Gentamicin or Tetracycline

    Investigations

    • EMG - electrodecremental response with repeated stimulation
    • Anti Acetylcholine receptor antibodies in 85% the rest may have antibody to muscle specific receptor tyrosine kinase
    • Tensilon test IV edrophonium improves Symptoms and signs:in 3-5 mins
    • CT or MRI chest to look for thymoma
    • FVC and ABG in acutely ill and weak patients

    Management

    • Long term Pyridostigmine 30-60 mg qds increases Ach in the synaptic cleft
    • Immunosuppression can reduce antibody production and destruction of receptors.
    • Corticosteroids (may cause initial worsening so care must be taken)
    • Azathioprine, Mycophenolate, Cyclosporin A
    • Consider Thymectomy in under 40s whose symptoms are uncontrolled or where there is a thymoma
  • Lambert Eaton syndrome

    Introduction

    • Paraneoplastic disorder with weakness and autonomic
    • Symptoms usually associated with small cell lung cancer
    • Antibodies to voltage gated calcium channels (VGCC) leads to impaired release of Ach

    Clinical

    • Proximal Weakness and fatigue and Difficult climbing stairs and rising from chair and Reduced reflexes Autonomic - dry mouth

    Investigations

    • Antibodies to voltage gated calcium channels (VGCC)
    • NCS and EMG - incremental response to repetitive stimulation
    • CT chest or PET scan to look for lung tumour.

    Management

    • Plasma exchange or IVIG can be used in a crisis
    • Guanidine or 3,4 Diaminopyridine may improve ACh release

    Botulism

    Introduction

    • Botulinum toxin produced by anaerobic clostridium tetani
    • These may exist as heat resistant spores can contaminate improperly preserved foods or wounds
  • Aetiology
    • Toxin binds to presynaptic terminal preventing Ach release causing paralysis

    Clinical

    • Rapid onset weakness with preceding autonomic involvement - nausea, diarrhoea, constipation, dilated pupils
    • bulbar symptoms and respiratory weakness are potentially fatal

    Management

    • Supportive + Antitoxin + Antibiotics
  • Mononeuropathies

    Mononeuropathies

    • Long thoracic
      • C5-C7 Supplies serratus anterior
      • Neuralgic shoulder amyotrophy seen in young adults sometimes seen post vaccination
      • Very severe shoulder pain
      • Can take months to settle with rest analgesia and steroids.
      • Displacement of medial edge of scapula away from chest wall "winging" when patient asked to outstretch hands so as to lean against a wall
      • Nerve conduction studies demonstrates neuropathy
    • Ulnar nerve
      • C8-T1
      • Ulnar half of flex dig profundus
      • All small muscles of hand except abductor poll brevis
      • Flexor carpi ulnaris
      • Sensation over ulnar1.5 fingers on palmar side 313 Trauma or arthritis and compression at elbow at ulnar groove, medial epicondyle
      • Sensory loss in medial side of hand
      • Wasting and weakness of small muscles of hand and unable to grip
      • Guttering is seen
      • Hyperextension at MCP and flexion at IP joints especially ring and little fingers give a Claw hand.
      • Froment's sign - paper held between thumb and first finger requires flexor pollicis longus as adductor pollicis is paralysed
      • Nerve conduction studies demonstrates neuropathy
      • If chronic compression then nerve can be transposed with some possible improvement
    • Radial nerve
      • C5-C8
      • Early branches to Triceps
      • Brachioradialis, Wrist dorsiflexors 314 Finger dorsiflexors, Thumb dorsiflexors
      • Thumb abductors
      • Lost supinator jerk
      • Sensory loss radial side of dorsum of hand in 1st interosseous space
      • Proximal lesion due to pressure in axilla with triceps weakening and wrist drop
      • Damaged in spiral groove of humerus may be compressed with arm hung over side of chair or with trauma and humeral fracture.
      • Patient has wrist drop and decreased sensation in first dorsal interosseous space
      • Very proximal lesions can cause weakened triceps
      • Nerve conduction studies demonstrates neuropathy
      • Acute compression heals well but trauma and fracture response is variable
      • The hand should be splinted holding hand in slight extension.
    • Median nerve 315 C5-T1
      • Forearm above carpal tunnel supplies forearm flexors
      • Abductor poll brevis
      • Radial 3.5 fingers palmar side
      • High lesions due to fractures at elbow.
      • Compression in carpal tunnel at wrist between bony carpus and flexor retinaculum
      • Commoner in women as tunnel smaller.
      • Myxoedema, Pregnancy, Diabetes Mellitus, Renal Dialysis with amyloidosis
      • High lesions causes ability to flex only those fingers supplied by ulnar nerve - little and ring fingers
      • Gives "preacher's hand" appearance.
      • Carpal tunnel level lesion causes pain waking patient and paraesthesia in the hand worst usually at night
      • Hand massage or shaking may help temporarily
      • Weakness of thenar eminence muscles - abductor poll brevis and opponens pollicis and flexor pollcis brevis
      • Sensory loss and tingling over the lateral palm of hand recreated by tapping nerve at wrist (tinel's test)
      • Forced extensior or flexion (phalen's test) for 1 minute recreates symptoms
      • Nerve conduction studies demonstrates neuropathy
      • Check U&E, TFT, Glucose
      • Rest and splinting
      • Injection locally of steroids in milder cases
      • Surgical decompression by dividing the flexor retinaculum
    • Common peroneal nerve palsy
      • L4-S2
      • Eversion of foot
      • Foot dorsiflexion
      • Toe dorsiflexion
      • Sensation to dorsum of foot 1st interosseous space
      • Trauma or pressure at head of fibula where the nerve is exposed
      • Foot drop
      • Sensory Symptoms on dorsum of foot
      • Nerve conduction studies demonstrates neuropathy
      • A splint is required to keep the foot and leg at right angle
      • If due to acute compression then outcome typically good
    • Lateral cutaneous nerve of thigh
      • Compression of L2-L3
      • No motor supply purely sensory over front and lateral aspect of thigh
      • Usually compressed under inguinal ligament during pregnancy or obesity
      • Paraesthesia and pain over lateral thigh
      • Nerve conduction studies demonstrates neuropathy
      • Weight loss but in some cases nerve decompression needed