Progressive polyneuropathy

The earliest reports of neurological complications of AIDS described distal symmetrical, painful sensory neuropathy occurring in HIV patients (Snider et al. 1983). Dysimmune inflammatory polyneuropathy was subsequently recognized as a complication of AIDS (Lipkin et al. 1985). Progressive polyneuropathy associated with cytomegalovirus (CMV) infection was documented as the first truly opportunistic infection of the peripheral nerve (Eidelberg et al. 1986). 

Refsum s disease. This disorder, first described nearly 60 years ago, was recently been shown due to a defect in the enzyme phytanoyl-CoA hydroxylase. Phytanic acid is a 3-methyl fatty acid that because of this methyl group cannot be oxidized directly. It is degraded by a peroxisomal a-oxidation to pristanic acid, a 2-methyl fatty acid which can be degraded by P-oxidation. The principal clinical features of Refsum s disease are progressive polyneuropathy, retinal degeneration, hearing loss, cardiomyopathy and ichthyosis, beginning in late childhood or later. 

The most commonly observed disease process leading to death of patients with EMS was progressive polyneuropathy (disease involving the peripheral nerves) and myopathy (disease of muscles) that produced complications of pneumonia and sepsis or respiratory failure due to weakness. Two-thirds of EMS patients died of these complications. Other causes of mortality were cardiomyopathy (disorder affecting the muscles of the heart), primary pulmonary disease, arrhythmia (deviation from the normal rhythm of the heart), and stroke. 

Diabetes mellitus is the most common cause of peripheral neuropathy in the United States. Approximately half of all diabetics demonstrate evidences of neuropathy. The usual clinical pattern is that of a slowly progressive, mixed sensorimotor and autonomic polyneuropathy. More acute, asymmetrical motor neuropathies are also seen, usually affecting the lumbosacral plexus, particularly in older persons with type 2 (non-insulin-dependent) diabetes mellitus. Patients with diabetes mellitus are also prone to develop isolated palsies of cranial nerve III or VII, and there is a high incidence of asymptomatic focal demyelin-ation in the distal median nerve. 

Acute intermittent porphyria is a dominantly inherited partial deficiency of porphobilinogen deaminase, and causes axonal polyneuropathy. Acute intermittent porphyria is caused by partial deficiency of porphobilinogen deaminase, an enzyme required for heme biosynthesis. Patients may present with acute abdominal pain, rapidly progressive sensorimotor axonal polyneuropathy or psychosis, and have elevated concentrations of the heme precursor 8-amino-levulinic acid in their urine. Symptoms may be precipitated by treatment with barbiturates or other drugs and are suppressed by treatment with hematin [59]. 

Friedreich s ataxia is caused by an intronic triplet repeat expansion. Friedreich s ataxia is an autosomal recessive disorder characterized by progressive ataxia, nystagmus, distal sensory polyneuropathy and corticospinal tract degeneration. It is caused by an unstable expanded GAA repeat in intron 1 of the frataxin gene on chromosome 9ql3. This diminishes expression of frataxin, a mitochondrial iron-storage protein that participates in free radical metabolism [71]. 

Delayed neuropathy characterized by distal axonal degeneration is a systemic health effect caused by some organophosphate pesticides and is not due to anticholinesterase inhibition. EPN is neurotoxic to atropine-protected hens, producing polyneuropathy progressing to paralysis and some deaths after ingestion of 5-10mgA g/day. There are no reports, however, of neurotoxicity from EPN in humans. ... 

One type of familial amyloidosis first identified in the Finnish population is caused by deposition of gelsolin (Maury et al., 2000 Maury et al., 2001). This Finnish type familial amyloidosis (FAF) is a hereditable autosomal dominant amyloid polyneuropathy, characterized by corneal lattice dystrophy, progressive cranial and peripheral neuropathy as well as skin changes (Chen et al., 2001 Maury et al., 2001). 

A 36-year-old man developed peripheral polyneuropathy after chronic perianal use of an ammoniated mercury ointment. He had very high blood and urine mercury concentrations. Sural nerve biopsy showed mixed axonal degeneration/demyelination. His symptoms improved progressively over 2 years after withdrawal of the ointment, but neurophysiological recovery was incomplete. 

Peripheral neuropathy with clinical signs and/or symptoms was found in 80% of patients who had received a cumulative dose of 576 mg/m of cisplatin. There was a dose-related reduction in sensory action potential amplitudes (85). The clinical and neurophysiological time progression of the severity of cisplatin polyneuropathy during and after treatment with cisplatin up to a cumulative dose of 600 mg/m has been described (86). 

Certain organophosphates may also induce delayed polyneuropathy, usually 2-3 weeks after a single exposure. The symptoms are tingling of hands and feet, sensory loss, progressive muscle weakness, and ataxia. Also, certain organophosphorus compounds are poor inhibitors of AChE but may, however, bind to another esterase, known as neuropathy target esterase (NTE) and induce delayed neuropathy. 

Benfotiamine has also been shown to improve nerve conduction velocity in patients with diabetic polyneuropathy [58]. Interestingly, benfotiamine improved endothelial function in type 11 diabetic patients when tested in a postprandial state after an AGE-rich meal [59]. Currently ongoing Phase 11 clinical trials will reveal whether benfotiamine influences the progression of microvascular complications in diabetic patients. 

A female adult heart transplant recipient developed reversible progressive symmetrical demyelinating sensorimotor polyneuropathy in the distal muscles of the legs while taking tacrolimus [142 ]. The condition immediately resolved after withdrawal of tacrolimus. 

Characteristic manifestations of the disease include retinitis pigmentosa, cerebellar ataxia, chronic polyneuropathy, and an elevated CSF protein level. Less constant features include sensorineural hearing loss, anosmia, ichthyosis, skeletal malformations, and cardiac abnormalities. The clinical picture of Refsum disease is often that of a slowly developing, progressive peripheral neuropathy manifested by severe motor weakness and muscular wasting, especially of the lower extremities. Onset has occasionally been detected in early childhood but not until the fifth decade in others. Most patients have clear-cut manifestations before 20 years of age. Patients with Refsum disease may die suddenly probably from cardiac arrhythmias [16]. 

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