Causes of Polyneuropathy: Comprehensive Classification
Yes, your classification of polyneuropathy causes is largely correct, but requires some updates and refinements based on current guidelines.
Metabolic Causes
- Diabetes mellitus (DM) is indeed the most common cause of polyneuropathy in Europe and North America 1
- Vitamin B12 deficiency is a significant nutritional cause 2
- Other nutritional deficiencies including vitamin B1 (thiamine), vitamin B6, folate, and vitamin E 2
- Hypothyroidism can cause polyneuropathy through metabolic disruption 3
- Chronic kidney disease (CKD) and uremic neuropathy are correctly listed 3
- Mitochondrial disorders can cause polyneuropathy through disruption of cellular energy production 2
Inflammatory/Immune-Mediated Causes
- Guillain-Barré syndrome (GBS) - acute inflammatory demyelinating polyneuropathy 3
- Chronic inflammatory demyelinating polyneuropathy (CIDP) 3
- Vasculitic neuropathies associated with systemic conditions (PAN, RA, GPA) 2
- Sarcoidosis can cause polyneuropathy through granulomatous inflammation 3
- Immune checkpoint inhibitor-related polyneuropathy is an emerging cause that should be added to this category 3
Malignancy-Related Causes
- Paraneoplastic syndromes can cause polyneuropathy 3
- Polycythemia vera is correctly listed 2
- Multiple myeloma and other paraproteinemias should be added to this category 3
- Amyloidosis (AL, ATTRv, ATTRwt) causes polyneuropathy in 17-35% of patients with AL amyloidosis and varying percentages in other types 3
Infectious Causes
- Leprosy remains an important cause globally 2
- HIV-associated neuropathy 3
- Syphilis can cause various neuropathies 2
- Lyme disease (neuroborreliosis) 4
- Hepatitis C-associated cryoglobulinemic vasculitis should be added 2
Toxins/Drug-Induced Causes
- Alcohol-associated polyneuropathy has a prevalence of 22-66% among persons with chronic alcoholism 1
- Chemotherapy-induced neuropathies (CIN) from agents like vincristine and cisplatin 1
- Lead and other heavy metal toxicity 2
- Medications including certain antibiotics, antiretrovirals, and anticonvulsants should be added 2
Hereditary Causes
- Charcot-Marie-Tooth (CMT) disease - the most common hereditary neuropathy 5
- Refsum's syndrome 2
- Adrenoleukodystrophy 2
- Familial amyloid polyneuropathy (now classified as ATTRv) 3
- Hereditary sensory and autonomic neuropathies (HSAN) should be added 2
Other Causes
- Amyloidosis is correctly listed but should be specified as primary (AL), hereditary (ATTRv), and wild-type (ATTRwt) 3
- Paraproteinemias including monoclonal gammopathy of undetermined significance (MGUS) 3
- Idiopathic polyneuropathy - accounts for approximately 13.7% of cases 5
- Critical illness polyneuropathy should be added 2
- Multifactorial polyneuropathy (11.1% of cases) should be added 5
Clinical Presentation and Diagnosis
- Polyneuropathy typically presents with distal, symmetric sensory or sensorimotor deficits 2
- Physical examination reveals distal sensory loss, reduced or absent reflexes, and sometimes distal muscle weakness 3
- Diagnostic testing includes nerve conduction studies, electromyography, and sometimes skin biopsy for small fiber neuropathy 3, 2
- Screening for reversible causes should include diabetic screen, B12, folate, TSH, HIV, and serum protein electrophoresis 3
Management Approaches
- Treatment should target the underlying cause when possible 1
- For neuropathic pain, first-line medications include:
- For autonomic symptoms, management may include increased salt/fluid intake, fludrocortisone, midodrine, or droxidopa 3
- Exercise, physiotherapy, and ergotherapy can be beneficial depending on symptoms and functional deficits 1
Patients with severe neuropathy of unidentified cause should be referred to a specialized center for thorough diagnostic evaluation 1.