Polyneuropathy

Background

• Fairly common neurologic condition
• Categorized as sensory (large or small fibre), motor, or autonomic
• Distal symmetric polyneuropathy is the most common subtype
• Mimics of polyneuropathy include cervical myelopathy

Clinical Manifestations

• Manifestations depend on whether it involves sensory, motor, or autonomic fibres
  • Physical examination should include pinprick and temperature (small fibre), vibration and proprioception (large fibre), and mucle bulk, tone, power, and reflexes
• Large fibre sensory dysfunction can cause loss of proprioception and gait impairment, as well as numbness and paresethesias
  • Includes gait ataxia from loss of proprioception
• Small fibre sensory dysfunction can cause pain (most often), hyperesthesia, or allodynia, as well as numbness and paresethesias
  • Can also cause areas of redness and swelling during the episodes of pain
  • Can also cause deep aching, postexertional malaise, and neuropathic itch
• Motor dysfunction can cause weakness, loss of dexterity, gait disturbance
• Autonomic dysfunction can cause orthostatic intolerance, gastroparesis, constipation, diarrhea, neurogenic bladder, sexual dysfunction, pupillomotor symptoms (including burry vision), and vasomotor symptoms (including dry eyes, mouth, and skin, and burning and flushing skin)

Distal Symmetric Polyneuropathy

• Most common subtype
• Length-dependent process
• Symmetric distal weakness with sensory loss and decreased Achilles reflex, ascending from the feet and then once it reaches the mid-calf, also including the fingers (glove and stocking)

Causes

Distal Symmetric Polyneuropathy

• Diabetes mellitus
• Alcohol
• Chronic kidney disease
• Vitamin B12 deficiency
• Adverse effect of medications, including chemotherapy
• Amyloidosis
• MGUS
• HIV

Acute or Subacute Polyneuropathy

• Guillain-Barré syndrome
• Chronic inlammatory demyelinating polyradiculoneuropathy (CIDP) with acute onset
• Vasculitis

• Critical illness polyneuropathy
• Lymphoproliferative disease
• Sarcoidosis
• Organophosphate poisoning
• Diphtheria
• Porphyria

Motor-Predominant Polyneuropathy

• CIDP
• Multifocal motor neuropathy
• Hereditary motor sensory polyneuropathy (e.g. Charcot-Marie-Tooth disease)
• Hereditary motor neuropathy
• Porphyria
• Lead toxicity
• Diphtheria
• Adverse effect of medications, such as dapsone

Mononeuritis Multiplex

• Vasculitis
• Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM)
• Multifocal motor neuropathy
• Amyloidosis
• Sarcoidosis
• Inflammatory bowel disease
• Celiac disease
• Hereditary neuropathy with liability to pressure palsies (HNPP)
• Diabetes mellitus

Autonomic Neuropathy

• Diabetes mellitus
• Alcohol
• Amyloidosis
• Autoimmune autonomic ganglionopathy
• Adverse effect of medications, including amiodarone, vincristine, cisplatin, and paclitaxel
• Sjögren syndrome
• HIV
• Vitamin B12 deficiency
• Heavy metal toxicity, including lead, thallium, mercury
• Hereditary sensory and autonomic neuropathy

Isolated Small-Fibre Polyneuropathy

• Diabetes mellitus
• HIV
• Hepatitis C, with or without cryoglobulinemia
• Cryoglobulinemia
• Amyloidosis
• Fabry disease
• Ehlers-Danlos syndrome
• Hemochromatosis
• Sodium channelopathy
• Sjögren syndrome
• Celiac disease
• Hypertriglyceridemia
• Alcohol

Medication-Induced

• Chemotherapy, including vinca alkaloids (vincirstine, vinblastine), taxanes (paclitaxel, docetaxel, cabazitaxel), platinum analogues (cisplatin, carboplatin, oxaliplatin), proteasome inhibitors (bortezomib), thalidomide, suramin
• Also: metronidazole, amiodarone, phenytoin, pyridoxine, linezolid, colchicine, chloramphenicol, dapsone, nitrofurantoin, isoniazid, disulfiram, lamivudine

Differential Diagnosis

• Mimics include cervical myelopathy, cord compression, ischemic infarction

Investigations

• CBC, electrolytes, creatinine, liver panel, glucose and hemoglobin A1c, SPEP, vitamin B12 (+/- methylmalonic acid)
• EMG studies

Further Reading

• Diagnosis and management of patients with polyneuropathy. CMAJ. 2023;195(6):E227-E233. doi: 10.1503/cmaj.220936. PMID: 36781195; PMCID: PMC9928442.