Peripheral Neuropathy

Question 1

What makes up a peripheral nerve

Answer 1

Peripheral Nerves comprise Neurones (with nucleus and axon) and Myelin sheaths, produced by Schwann cells between each Node of Ranvier; Blood supply by Vaso Nervorum

Question 2

How can damage occur to a peripheral nerve

Answer 2

Damage can be due to Demyelination (showing Conduction Block), Axonal Degeneration (Conduction velocity initially maintained; Occurs in typically toxic and metabolic disorders),
Compression (Focal Myelination), Microinfarction (of the Vaso Nervorum, in Diabetes and Vasculitides) and Infiltration (by Inflammatory cells in Leprosy and Granulomatous disease, as well as Neoplastic disease)

Question 3

How does regeneration happen

Answer 3

Regeneration occurs by Remyelination or by
Axonal Growth down the Sheath from sprouting
Axonal Stump; 1mm/day

Question 4

How can peripheral nerve disease be classified

Answer 4

Peripheral Nerve Disease can be separated into –
Mononeuropathy, Mononeuritis Multiple or
Polyneuropathies (Diffuse, Symmetrical typically
commencing peripherally)
o Polyneuropathies are classified as Motor, Sensory, Sensorimotor or Autonomic;
Widespread loss of Tendon Reflexes, Distal Weakness and Sensory Loss

Question 5

What is Guillain barre Syndrome

Answer 5

Most common acute Polyneuropathy
(3/100,000); Typically, Demyelinating, occasionally Axonal, often Post-infectious
o Spectrum of disease from Acute Motor Axonal Neuropathy to Miller-Fisher Syndrome (Ocular Muscle Palsies and Ataxia)
o Paralysis followed 1 – 3/52 of often minor infection; C jejuni and CMV recognised

Question 6

Pathophysiology of GBS

Answer 6

Molecular Mimicry between Liposaccharides and Nerve Gangliosides

Question 7

Presentation of GBS

Answer 7

Presents with Distal Limb Weakness ± Numbness; Progresses Proximally, over days to weeks;
Loss of Tendon Reflexes almost invariable; Autonomic features often

Question 8

Diagnosis of GBS

Answer 8

Clinical Diagnosis plus Nerve Conduction Studies; CSF protein often raised; In Miller-Fisher Syndrome, Antibodies against GQ1b (sens 90%)

Question 9

How does GBS progress

Answer 9

Paralysis might progress rapidly, requiring Ventilation; LMWH and TEDS to reduce risk of VTE; IVIg given within first 2/52 reduces duration and severity (Screen for IgA Deficiency prior for
risk of Allergy), or Plasma Exchange
o Recovery to Independence might take Months to years and may be incomplete 5 –
8% Mortality, 30% Morbidity

Question 10

Paraproteinemic Neuropathies

Answer 10

• Up to 70% of patients with Serum Paraprotein have Neuropathy; Most associated with MGUS but also seen in Myeloma; Antibody might be Pathogenic (E.g. Anti-MAG) or Coincidental
• IgM Paraproteins typically cause Demyelinating Neuropathy; Often directed against MAG;
Slow, Progressive Distal Neuropathy with Ataxia and Prominent Tremor
• POEMS Syndrome (Polyneuropathy, Organomegaly/Hepatomegaly in 50%, Endocrinopathy
(Reduced Testosterone) and M-protein Band with Skin Changes) – VEFG Release from
Plasmacytoma; Treatment of Underlying Malignancy

Question 11

Diabetic Neuropathy

Answer 11

– Commonest cause of Neuropathy in Developed Countries
o 50% of DM patients after 25yrs
o Distal Symmetrical Sensory Neuropathy – Usually Mild and Asymptomatic
o Acute Painful Sensory Neuropathy – Reversible with Improved Glycaemic Control
o Mononeuropathy and MM – Cranial Nerve Lesions, Carpal Tunnel, etc
o Diabetic Amyotrophy – Vasculitic Plexopathy or Femoral Neuropathy
o Autonomic Neuropathy

Question 12

Uraemic Neuropathy

Answer 12

Progressive Sensorimotor Neuropathy in Chronic Uraemia; Usually
involves after Transplant, might respond to Dialysis

Question 13

Thyroid Neuropathy

Answer 13

Mild, Chronic Sensorimotor Neuropathy in either Hypo or

Hyperthyroidism; Myopathy also occurs in Hyperthyroidism

Question 14

Causes of Toxic Neuropathy

Answer 14

• Alcohol Neuropathy – Mainly in LL after Chronic ETOHXS; Myopathy might accompany
• Lead (Motor Neuropathy), Acrylamide, Arsenic, Thallium, Heavy Metals
• Phenytoin, Chloramphenicol, Metronidazole, Isoniazid, Antiretrovirals, Nitrofurantoin,
Chemotherapy Agents, Amiodarone, Chloroquine

Question 15

Thiamine Deficiency

Answer 15

• Thiamine (B1 Deficiency =Beriberi) – Polyneuropathy and Cardiac Failure; Also leads to Wernicke-Korsakoff Syndrome; ETOHXS most common cause in West
o Eye Signs – Nystagmus, Bilateral LR palsies, Conjugate Gaze palsies
o Ataxia – Broad Gait, Cerebellar Signs, Vestibular Paralysis
o Cognitive – Acute Stupor and Coma, Amnestic Syndrome and Confabulation

Question 16

Vitamin B6 deficiency

Answer 16

Sensory Neuropathy; Limb Numbness, typically when on Anti-TB drugs in patients who are slow Metabolisers of Isoniazid; Prophylactic 10mg Pyridoxine

Question 17

Vitamin B12 deficiency

Answer 17

Subacute Combined Degeneration of Cord
o Combined Cord and Peripheral Neuropathy often in Pernicious Anaemia; Numbness and Tingling of Fingers and Toes, Distal Sensory Loss (especially Dorsal Column), Absent Tendon Reflexes (With Cord involvement, Hyperreflexia and Upgoing Plantars)
o Later stages – Sphincter Disturbance, Severe Generalised Weakness and Dementia
o Macrocytosis with Megaloblastic Anaemia common; B12 Supplementation improves
Neuropathy but rarely have effect on Cord and Brain
o NB: Similar Presentation seen in Copper Deficiency

Question 18

Charcot Marie Tooth

Answer 18

Heterogenous Group of Motor and Sensory Neuropathies; Distal Limb Wasting and Weakness
typically, Slowly Progressive over years; Variable loss of Sensation and Reflexes
o Severe Foot Drop in Advanced disease (but typically Ambulant)

Question 19

CMT1a

Answer 19

Most common (70%); Autosomal Dominant Demyelinating Neuropathy
caused by Duplication or Point Mutation of 1.5Mb portion of 17p11.2, encompassing
Peripheral Myelin Protein 22 gene

Question 20

CMT1b

Answer 20

Second most common; Autosomal Dominant Demyelinating Neuropathy
due to mutations in Myelin Protein Zero gene on 1q22

Question 21

Autonomic Neuropathy

Answer 21

• Postural Hypotension, Urinary Retention, Sexual Dysfunction, Nocturnal Diarrhoea, Diminished Sweating, Impaired Pupillary Reflexes and Cardiac Arrhythmia
• Develops in Diabetes, Amyloidosis (where it might be severe); May complicate Guillain-Barre
Syndrome and Parkinson’s Disease