Diagnosis

Polyneuropathy

Etiology

Cause [kis]

Over 100 different causes of polyneuropathy have been identified

1. Acute polyneuropathy:

   Guillain Barre syndrome, Miller-Fisher syndrome, Acute axonal neuropathy, Critical illness polyneuropathy

2. Acquired:

   • Immune-mediated: GBS, CIDP, ALS

   • Metabolic: Diabetic (microvascular insufficiency), Renal failure (intracellular sodium accumulation), Liver failure, Hypothyroidism, Acromegaly, COPD, Polycythemia, Vitamin deficiencies (B1, B6, B12, and vitamin E)

   • Toxic: Alcohol, Ethylene oxide, Carbon disulfide, Lead, Mercury, Arsenic, Thallium, DMAP, Hexane, Diphtheria, Amiodarone, Chloramphenicol, Dapsone, Disulfiram, Gold, Isoniazide, Lithium, Metronidazole, Nitrofurantoin, Phenytoin, Thalidomide, Vincristine, Cisplatin, Chloroquine

   • Paraproteinemic: MGUS, POEMS syndrome, Amyloidosis, Cryoglobulinemia, Macroglobulinemia

   • Paraneoplastic: Small Cell Lung Cancer, Lymphoma, Multiple myeloma, MGUS

   • Infectious: Lyme disease, Leprosy, Herpes Zoster, EBV, CMV, HIV, HCV, hingles, leprosy, Diphtheria, Trypanosomiasis

   • Vasculitic: Polyarteritis nodosa, Temporal arteritis, Sjogrens syndrome, Rheumatoid arthritis, SLE, Scleroderma, Sarcoidosis

3. Genetic:

   Charcot–Marie–Tooth disease, HSAN, HNPP, Porphyria, Metachromatic leukodystrophy, Tangier disease, Familial amyloid neuropathy, Refsum disease, Friedreichs ataxia, Fabry disease, abetalipoproteinemia

4. Idiopathic

5. Radiculopathy and Mononeuropathy:

   Carpal tunnel syndrome, Cubital tunnel syndrome, Saturday night palsy, Peroneal Mononeuropathy, Meralgia Paresthetica, Brachial/Lumbosacral Plexopathy (radiation, tumor, trauma), Radiculopathy (Spinal disc herniation, tumor, trauma, radiation, infection, immunologic), Neuralgic shoulder amyotrophy

Pathophysiology [kis]

• Segmental demyelination: inflammatory and immune-mediated neuropathy

  • Degeneration of the myelin sheath, with sparing of the nerve axon

• Wallerian degeneration: trauma or infarction of the nerve

  • Nerve axon degenerates due to a lesion or physical compression

  • The portion distal to the axon passively wastes away (ack of nutrients) f

• Axonal degeneration (dying-back phenomenon): symmetrical polyneuropathy in diabetes, HIV, HCV, GBS

  • Weakness in dorsiflexion of the ankles and trophic changes to muscle.

  • Starts distal and progresses proximally

  • The most distal portion of the axon is particularly vulnerable due to its distance from the cell body

  • Insult to the nerve causes impaired delivery of local axonal survival factors

  • Calcium-dependent cytoskeletal breakdown

• Clinical manifestation:

  • Parestesia, weakness, atrophy, pain, hyporeflexia, and autonomic disturbances

Complications [kis]

• Pain, altered sensation, muscle atrophy, and weakness

• Foot ulcers --> gangrenous digits and limbs --> amputation

Epidemiology

Incidence per 100.000 [bwh][9wg][wts][58b][gwo]

Approach

• Blood test: WBC, CRP, SR, glucose, Hemoglobin A1c, electrolytes, creatinine, thyroid, liver, vitamin B12, vitamin E, ANA, Anti-SSA and SSB antibodies, Rheumatoid factor, Paraneoplastic antibodies, folate, alcohol [kis]

• Heavy metal toxicology

• Infectious workup: Lyme disease, Epstein-Barr virus, hepatitis C, HIV, and syphilis

• Antibody testing: Sjögren syndrome, lupus, and rheumatoid arthritis

• Protein electrophoresis

• Lumbar puncture

• Neurography

• Nerve conduction study

• EMG

• Blood smear

• Chest x-ray

• Ultrasound abdomen

• CT/MRI (compression of the nerve)

• Biopsy (rectum/nervus suralis)

• Genetic testing (for inherited neuropathies)

• Urine Test (Bence-Jones proteins)

Treatment

1. Identify and treat the underlying cause: [kis]

   • Glycemic control if diabetes: insulin pump, aldose reductase inhibitors, pancreas transplantation

   • Alcohol cessation if alcoholic neuropathy

   • Vitamin supplementation if nutritional deficiencies

   • Drug toxicity

   • Corticosteroids if inflammatory demyelinating neuropathy

2. Neuropathic Pain Management: [j4e]

   • Pregabalin

   • Gabapentin

   • Sodium valproate

   • Tricyclic antidepressants

   • Selective serotonin reuptake inhibitors (SSRIs)

   • Carbamazepine

   • Lamotrigine

   • Opioids

   • Topical therapy: Capsaicin or transdermal lidocaine

   • Duloxetine

   • Spinal cord stimulators

3. Diabetic Gastroparesis: Erythromycin, metoclopramide, polyethylene glycol, tegaserod, jejunostomy

4. Autonomic Dysfunction:

   • Erectile dysfunction: sildenafil, penile prosthesis

   • Orthostatic hypotension: increase fluid and salt intake, compression stockings

5. Surgery: [ulq]

   • Foot ulcers: debridement or amputaion

   • Release of entrapment neuropathy (CTS)

   • Jejunostomy for severe gastroparesis

   • Pancreatic islet transplants

   • Pancreas-kidney transplantation

Differential diagnoses

Amyotrophic lateral sclerosis, Bell's Palsy, Carpal tunnel syndrome, Diabetes mellitus, Friedreich ataxia, Guillain-Barre syndrome, Herpes zoster, HIV, Lambert-Eaton myasthenic syndrome, Lead toxicity, Leprosy, Meralgia paresthetica, Myasthenia gravis, Neuronal ceroid lipofuscinoses, Polyarteritis nodosa, Radiation, Renal failure, Sarcoidosis, Spinal disc herniation, Syphilis