Marieke van Rosmalen

General introduction and thesis outline 11 1 POLYNEUROPATHIES The peripheral nervous system consists of the alpha motor neurons in the anterior horn of the spinal cord, ventral and dorsal roots, peripheral nerves, the neuromuscular junction and muscle. Peripheral nerves connect the brain and spinal cord with muscle, skin, joints and sensory organs. Dysfunction of the peripheral nerves has many causes, but is generally described as ‘polyneuropathy’. Complaints caused by polyneuropathies include weakness and sensory deficits including numbness, sensory ataxia and changed or increased pain sensations in hands and feet. Common causes for polyneuropathy are summarized in Table 1.1 and include drugs and alcohol, diabetes, liver or renal insufficiency, (vitamin) deficiencies and idiopathic. Rare causes are of a genetic or inflammatory nature. Discriminating between these multiple causes is of great importance, as treatment opportunities and prognosis can vary between neuropathies. In the diagnostic work-up of patients suspected to have a polyneuropathy, laboratory findings and nerve conduction studies are important tools. Rare causes may be more elusive and require special diagnostic techniques, including genetic testing and nerve imaging by means of ultrasound or magnetic resonance imaging (MRI). Imaging techniques may be particularly helpful for the identification of the rare chronic inflammatory neuropathies. Table 1.1. Causes of polyneuropathy Type of origin Causes Carcinoma Lymphoma Hereditary Charcot-Marie-Tooth disease, hereditary neuropathy with liability to pressure palsies, neurofibromatosis Idiopathic Chronic idiopathic axonal polyneuropathy Infectious Leprosy, Lyme’s disease, HIV Inflammatory Chronic inflammatory demyelinating polyneuropathy (typical and variants), Guillain- Barré syndrome, multifocal motor neuropathy Metabolic Diabetes mellitus, hypothyroidism, liver insufficiency, porphyria, renal insufficiency, vitamin deficiencies Paraneoplastic Small cell lung cancer Paraproteinemic anti-MAG associated polyneuropathy, IgM-monoclonal gammopathy of unknown significance, polyneuropathy organomegaly endocrinopathy M-protein and skin changes syndrome, Waldenström Systemic diseases Amyloidosis, rheumatoid arthritis, sarcoidosis, Sjögren’s syndrome, systemic lupus erythematosus Toxic Alcohol abuse, drug associated (antimicrobials, amiodarone, chemotherapy, digoxin, immunosuppressants), toxins (botulinum toxin, lead, mercury) Vasculitic Microscopic polyangiitis, non-systemic vasculitic neuropathy, polyarteriitis nodosa An overview of causes of peripheral polyneuropathy. Only some examples are shown per type of origin.