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Peripheral nerve disorders Dr Jamie Talbot, ST5 in neurology, Royal Devon and ExeterThe direction of travel • Anatomy, terminology and neurophysiology • Localisation and some cases • Neuropathies not to be missed • Peripheral neuropathy – the daily slog “Demyelinating” “Ganglionopathy” “Axonal” “Neuronopathy” “Length- dependent”The peripheral nervous systemNerve studies/EMG Nerve studies: • Sensory responses – SNAPs and latency/conduction velocity • Motor responses - distal motor latency/conduction velocity and CMAP • F waves EMG: • Spontaneous activity/resting EMG • Smooth contraction (MUAP) • “Interference pattern”/maximal contraction (MUAP) Others; repetitive stimulation, single fibre EMGEMG: Spontaneous activity Positive Fibrillation Neuropathic e.g. MND sharp waves potentialsEMG: Slight effort Long duration, high amplitude, polyphasic Short duration, low amplitudeEMG: Interference patterns (max effort) Normal Neuropathic (reduced units) Myopathic (reduced amplitude)Localisation of nerve problemsNerve root/plexus: • Trauma/disc • Diabetic amyotrophy Dorsal root ganglion: • Inflammatory (sarcoid, Sjogren’s, α 3-ganglionic Ab) Distal axonal/”dying • Paraneoplastic back”: • Diabetes, hypothyroidism • Toxins – alcohol, Anterior horn: vincristine, platinum- • MND (ALS/PMA) based chemotherapy • SMA • Polio Length of nerve: Mononeuritis multiplex: • AIDP/CIDP • Vasculitis, CTDs • HMSNDemyelinating neuropathies • AIDP/CIDP • Inflammatory (vasculitis, sarcoid, SLE) • Infection (HIV, diphtheria) • Paraneoplastic • Toxic (arsenic, amiodarone, TNF blockers) • Paraproteinaemic • Multifocal neuropathy • Other antibody- mediated Acute Subacute : Chronic : Paraneoplastic Metabolic (diabetes, Injury hypothyroidism) Inflammatory (CIDP, CISP) Inflammatory: AIDP Toxic (alcohol, chemotherapy) Inflammatory e.g. vasculitis Inflammatory (vasculitis, SLE, Sjogren’s, sarcoid) Nutritional (B12, copper deficiency) Toxic: Thallium Infectious (hep B/C, HIV) Genetic: Porphyria, HNPP Haematological Metabolic (diabetic (paraproteinaemia, POEMS, amyotrophy) anti-MAG) Infection: Diphtheria Haematological Genetic (CMT, CANVAS, (cryoglobulinaemia, Friedrich’s, Fabry) amyloidosis, other paraproteinaemia) Critical illness polyneuropathy Sensory-predominant Motor-predominant: Autonomic-predominant: Amyloidosis Metabolic (diabetes, B12) AMAN Inflammatory (Sjogren’s Toxic (alcohol, chemotherapy) (MND, myasthenia gravis, neuromuscular disorders) sarcoid, anti-ganglionic AChR) Ganglionopathies Post-chemotherapy (cisplatin) MMN Paraneoplastic (anti-Hu) Lead, porphyria Vitamin B6 toxicity Insulin neuritisCase study • A 53 year old man with type 2 diabetes developed over the course of several days burning pain in the right hip and thigh which slowly spread to the entire leg. A week after the pain began, he developed weakness in the leg which progressed over a couple of months, requiring use of a stick to walk. He continued to suffer with severe pain and was demanding opiate analgesia to manage the pain effectively. Examination revealed weakness throughout the right leg with absent reflexes and mute plantar responses. Sensation was intact. He continued to experience weakness for 18 months before experiencing some slow improvement in symptoms.Diabetic lumbosacral radiculoplexus neuropathy • AKA diabetic amyotrophy • Monophasic neuropathy that typically presents over weeks to months, initially with asymmetric lower extremity pain, weakness and atrophy, often more prominently proximally. • Incidence approx. 4.2 per 100,000 per year • Most common in middle-aged patients with type 2 diabetes; more common in men than women. Often associated with weight loss. Unlike patients with DSPN< those with diabetic amyotrophy generally have better-than-average glycaemic control. • spreads to the entire limb and contralaterally. After the onset of pain, proximal weaknessen develops that can be quite debilitating. • May progress over months (in some cases as long as 18 months), with another 12-24 months for recovery. Recovery is often incomplete. • Less commonly patients may present with a symmetric motor-only form.Case study • A 50 year old man with no medical history presented with worsening postural hypotension, with burning pain in his trunk and limbs. He had lost a significant amount of weight and also complained of erectile dysfunction. His nerve studies were unremarkable and CT TAP did not reveal any malignancy. Serum electrophoresis was negative for any paraproteinaemia, however urinary Bence Jones revealed a significant lambda light chain paraproteinaemia.Neuronopathy secondary to systemic amyloidosis • Differential diagnosis: Inflammatory disorders (Sjogren’s, sarcoid, syndrome; previous chemotherapy (cisplatin); systemic (or familial) amyloidosis (others (even rarer): HSAN, insulin neuritis). • Suggested work up includes: Diverse immune and infection screen, paraneoplastic antibody panel, CT T, electrophoresis and Bence Jones urine. • Management of autonomic dysfunction includes increasing fluid and salt intake, leg and abdominal binders, sleeping with head-up (or antihypertensive at night). Pharmacology options; midodrine, fludrocortisone (and others).Case study A 19 year old woman attended the neurology clinic with a long history of leg symptoms and struggling in relation to her peers. She recalled symptoms since at least the beginning of secondary school, including frequent tripping when walking to and from classes, and poor sporting achievement, including fatigue and calf pain during exercise. Examination revealed high stepping gait bilaterally with weakness of ankle dorsiflexion, reduced ankle reflexes and high arched feet with hammertoes. Nerve studies showed slowing of motor nerve conduction velocities and sensory action potentials in median and sural nerve territories.Charcot-Marie-T ooth =Hereditary motor sensory neuropathy (HMSN) • 4 genes account for 90% of cases • Nomenclature: CMT1A (represents 50% all CMT) 1=demyelinating 2=axonal • Clinical features include slow progression, muscle weakness/numbness in the feet, ankles, legs and/or hands, high- arched feet. • Symptoms usually start between 5 and 15, can be earlier or later.Case study • A 40 year old man noticed increasing problems with right hand function over a period of 9 months, with some intermittent cramping sensation. He denied any sensory symptoms and was otherwise well. Clinical examination revealed some fasciculations in the 1 dorsal interosseous muscle of the right hand and weakness of finger/wrist extension and grip. Sensory examination was normal. Nerve studies showed prolonged motor nerve latencies and slowed conduction velocities in the median and radial nerve territories of the right arm, with >50% reduction in compound muscle action potential (CMAP) amplitude between proximal and distal nerve stimulation sites, indicative of conduction block.Multifocal motor neuropathy • common in young adults)athy affecting young patients (mean age 40, • distribution of at least two nerves, for at least 1 month (usually more than 6 months). • No objective sensory abnormalities. • Conduction block is a characteristic feature • syndrometial diagnosis – amyotrophic lateral sclerosis, Lewis-Sumner • Associated with GM1 (anti-ganglioside) antibodies • Does not respond to steroids or plasma exchange. IVIG is the treatment of choice.Neuropathies not to be missed An 18 year old man was brought to the emergency department by his parents after he collapsed at home. He had struggled in a football game 3 days ago, and from there had experienced worsening shooting pains in the arms and legs, and became increasingly weak, today barely able to get out of bed. In the emergency department his pulse was high at 140bpm and he went into urinary retention, requiring catheterisation. He displayed weakness of all 4 limbs (MRC grade 3/5 bilaterally), with associated patchy numbness. Reflexes were globally absent.“Gold standard” management • ABCDE • Heart monitor and hourly FVC measurements (in open bay). Inform nurses to flag any deterioration. • Discuss with neurology. Will likely require IVIG - try and find out body weight and inform blood bank who may advise on protocol (usual dose 2g/kg over 5 days, or 0.4g/kg per day). • Inform ICU given evidence of autonomic involvement. • Auxiliary investigations – LP (albumin-cytological dissociation), anti- Gq1b antibodies, NCS (may be normal in early disease).Differential diagnosis • Lyme or other infections e.g. HIV, diphtheria • Inflammatory disorder e.g. vasculitis • Genetic e.g. porphyria • Toxic - thallium, arsenic, organophosphate, ethylene glycol, (botulism) • NMJ/muscular disorder (myasthenia, rhabdomyolysis, periodic paralysis or Pompe)GBS stats • Acute, symmetrical, radicular pain common, autonomic symptoms. • Mortality associated with dysautonomia (overall mortality 3-10% due to cardiac arrhythmia, blood pressure instability) • 20% pts require mechanical ventilation • 60–80% of patients with GBS are able to walk independently 6 months after disease onset, with or without treatment. • Classically monophasic illness, although relapses of GBS can occur in 2–5% of patients • Subtypes; AMAN, AMSAN.Neuropathies not to be missed A 70 year old woman attended the neurology ambulatory clinic with a 3 week history of weakness and numbness in her hands and feet with associated pain and swelling. She felt generally off sorts and had experienced some night sweats. Her only past medical history was of hypothyroidism. On examination she has significant weakness and numbness of the hands and feet in a glove and stocking distribution. Her bloods revealed an eosinophilia and CRP of 250. pANCA was positive with MPO antibodies.Vasculitic neuropathy • The typical clinical syndrome is mononeuritis multiplex (35-65%) or asymmetric neuropathy, but distal-symmetric neuropathy frequently seen • Includes microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, mixed cryoglobulinaemia, Henoch-Schloein purpura, PAN, giant cell arteritis • Causes of secondary vasculitis include connective tissue diseases (RA, SLE, Sjogren’s, mixed), sarcoidosis, Behcet’s, infection (hep B/C).Suggested work-up in subacute neuropathy Nerve biopsy may be required to confirm the diagnosisPeripheral neuropathy – the daily slog A 67 year old man presents to the neurology clinic with a sensation of walking on sponges for a couple of years. He notices some difficulty with balance when getting up in the night to go to the loo, but is otherwise functioning well. He also describes unpleasant tingling pain in his toes. On examination, Romberg’s test is positive and he has reduced sensation to all modalities up to his mid-shin. Lower limb reflexes are reduced, with absent ankle jerks and equivocal plantar responses.Distal axonal neuropathy • “Dying back” axonopathy • Represent 90% of peripheral neuropathy • Prevalence around 1% in the general population, rising to 7% in the elderly • Idiopathic in 20-30% of cases • Most common causes – diabetes, alcohol. Others include B12 deficiency, hypothyroidism, medications (e.g. chemotherapy), paraprotein-associated, uraemic.Suggested basic screen for peripheral neuropathy • FBC • CRP • HbA1C • TSH • Renal, liver and bone profiles • B12 and folate • Serum electrophoresis/Bence Jones proteinNeuropathic pain • Suggest duloxetine 1 line • Other options include amitriptyline, gabapentin, pregabalinConclusion • Many neuropathies, many causes • Think onset, distribution, motor vs sensory, painful vs non-painful to refine diagnosis • Acute/subacute neuropathies are concerning and often treatable – lumbar punctures can give valuable information. • The peripheral nervous system is complicated even to neurologists – don’t worry!Feedback