Polyneuropathies: Causes

Pathogenesis (disease development)

The causes of polyneuropathy (PNP) are manifold:

  • Genetic (hereditary neuropathies).
  • Nutritive (folic acid or vitamin B12 deficiency).
  • Inflammatory/infectious (e.g., Lyme disease)
  • Metabolic (e.g. diabetic polyneuropathy)
  • Immune-mediated (e.g., Guillain-Barré syndrome (GBS)).
  • Vascular (e.g., vasculitides)
  • Tumor-associated (e.g., plasmocytoma)
  • Toxic (e.g., alcohol-associated polyneuropathy or chemotherapy-induced neuropathy (CIN)).
  • Idiopathic

A distinction can be made between noxious agents that primarily attack the nerve cell, i.e., the motor neuron or spinal ganglion neuron, and others that disrupt processes in the nerve fiber (axon and Schwann cell). Alcohol-associated polyneuropathy is due to malnutrition (including deficiency of B vitamins) and the toxic effects of alcohol and its degradation products such as acetaldehydes. Chemotherapy-induced neuropathy (CIN) leads to damage of the spinal ganglia and peripheral nerves and typically starts with sensory loss symptoms as well as pain. For an example of the pathogenesis of polyneuropathy, see diabetic polyneuropathy below.

Etiology (causes)

Biographic causes

  • Genetic diseases
    • Hereditary motor-sensory neuropathy type I (HMSN I; from English “hereditary neuropathy with liability to pressure palsies” (HNPP); synonyms: Charcot-Marie-Tooth disease (CMT), English Charcot-Marie-Tooth disease) – chronic neuropathy inherited in an autosomal dominant manner, resulting in motor and sensory deficits.
    • Fabry disease (synonyms: Fabry disease or Fabry-Anderson disease) – X-linked lysosomal storage disease due to a defect in the gene encoding the enzyme alpha-galactosidase A, leading to progressive accumulation of the sphingolipid globotriaosylceramide in cells; mean age of manifestation: 3-10 years; early symptoms: Intermittent burning pain, decreased or absent sweat production, and gastrointestinal problems; if left untreated, progressive nephropathy (kidney disease) with proteinuria (increased excretion of protein in urine) and progressive renal failure (kidney weakness) and hypertrophic cardiomyopathy (HCM; disease of the heart muscle characterized by thickening of the heart muscle walls).
    • Small fiber neuropathies (SFN) – subgroup of neuropathies in which primarily the so-called “small fibers”, i.e., the small-caliber nerve fibers, are affected.

Behavioral causes

  • Nutrition
    • Foods containing acrylamide (Group 2A carcinogen) – formed during frying, grilling, and baking; used to make polymers and dyes; acrylamide is metabolically activated to glycidamide, a genotoxic (“mutagenic”) metabolite
    • Micronutrient deficiency (vital substances) – see prevention with micronutrients.
  • Consumption of stimulants
    • Alcohol (= alcohol-associated polyneuropathy) → sensitive symptoms, such as numbness, stinging, or gait unsteadiness; prevalence (disease incidence) of 20-70% among chronic alcoholics.
    • Tobacco (smoking); moderate association between smoking and diabetic peripheral neuropathy (DPN).
  • Drug use
  • Poor adjustment of glucose serum levels (blood glucose levels) (in diabetic polyneuropathy).

Disease-related causes

Blood, hematopoietic organs – immune system (D50-D90).

  • Pernicious anemia – anemia due to vitamin B12 deficiency.
  • Porphyria or acute intermittent porphyria (AIP); genetic disease with autosomal dominant inheritance; patients with this disease have a 50 percent reduction in the activity of the enzyme porphobilinogen deaminase (PBG-D), which is sufficient for porphyrin synthesis. Triggers of a porphyria attack, which can last a few days but also months, are infections, drugs or alcohol. The clinical picture of these attacks presents as acute abdomen or neurological deficits, which can take a lethal course. The leading symptoms of acute porphyria are intermittent neurological and psychiatric disturbances.In the foreground is often autonomic neuropathy causing abdominal colic (acute abdomen), nausea (nausea), vomiting or constipation (constipation), as well as tachycardia (heartbeat too fast: > 100 beats per minute) and labile hypertension (high blood pressure).
  • Sarcoidosis (synonyms: Boeck’s disease; Schaumann-Besnier’s disease) – systemic disease of connective tissue with granuloma formation.

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Amyloidosis – extracellular (“outside the cell”) deposits of amyloids (degradation-resistant proteins) that can lead to cardiomyopathy (heart muscle disease), neuropathy (peripheral nervous system disease), and hepatomegaly (liver enlargement), among other conditions
  • Folic acid deficiency
  • Hypothyroidism (underactive thyroid gland)
  • Vitamin B12 deficiency

Cardiovascular system (I00-I99)

  • Vasculitis (vascular inflammation)

Infectious and parasitic diseases (A00-B99).

  • Lyme disease – infectious disease caused by bacteria and transmitted to humans by ticks.
  • HIV infection
  • Leprosy – chronic tropical infectious disease caused by the bacterium Mycobacterium leprae.

Musculoskeletal system and connective tissue (M00-M99).

  • Sjögren’s syndrome (SS; sicca syndrome group) (synonyms: sicca syndrome) – autoimmune disease from the collagenosis group that results in chronic inflammatory disease or destruction of the exocrine glands, with the salivary and lacrimal glands most commonly affected; it may also affect the lungs, kidneys, and nervous system

Neoplasms – tumor diseases (C00-D48).

  • Leukemia (blood cancer)
  • Lymphoma – malignant proliferation of lymphoid tissue.
  • Paraneoplastic syndromes (e.g., myeloma, leukemia) – a wide variety of symptoms that may result from a malignant tumor.
  • Plasmocytoma – generalized disease with excessive formation of malignant plasma cells.

Psyche – nervous system (F00-F99; G00-G99)

  • Alcohol abuse (alcohol dependence)
  • Charcot-Marie-Tooth (CMT) – neuromuscular disease (hereditary) leading to degeneration of muscles.
  • Chemotherapy-induced peripheral neuropathy (CIPN).
  • Chronic polyneuritis – inflammatory disease of multiple nerves.
  • Critical illness neuropathy – neuropathy (disease of the peripheral nervous system) that may occur in the course of therapy of critically ill patients.
  • Diabetic neuropathy – damage to multiple nerves (polyneuropathy), which occurs as a complication of existing diabetes mellitus; about 50% of diabetics develop in the course of a polyneuropathy.
  • Bottleneck neuropathy (peripheral nerve disease) due to nerve compression.
  • Guillain-Barré syndrome (GBS; synonyms: Idiopathic polyradiculoneuritis, Landry-Guillain-Barré-Strohl syndrome); two courses: acute inflammatory demyelinating polyneuropathy or chronic inflammatory demyelinating polyneuropathy (peripheral nerve disease); idiopathic polyneuritis (multiple nerve disease) of spinal nerve roots and peripheral nerves with ascending paralysis and pain; usually occurs after infection
  • Neuroborreliosis – disease symptoms of the nervous system caused by Lyme disease.
  • Neuropathy (disease of the peripheral nervous system) with distal symmetrical distribution type:
    • Toxic polyneuropathy due to alcohol or drugs.
    • Deficiency neuropathy due to vitamin B deficiency or malabsorption

Symptoms and abnormal clinical and laboratory findings not elsewhere classified (R00-R99).

  • Uremia (occurrence of urinary substances in the blood above normal levels).

Medication → toxic polyneuropathy

Legend: A = axonal; D = demyelinating; G = mixed axonal-demyelinating.

Operations

Environmental exposures – intoxications (poisonings) → toxic polyneuropathy.

  • Arsenic
  • Hydrocarbons
  • Heavy metals such as lead, thallium, mercury
  • Carbon disulfide
  • Trichloroethylene
  • Triorthocresyl phosphate (TKP)
  • Bismuth (due tobismuth-containing dental material or in the case of long-term treatment with bismuth preparations).