Central nervous system neuropathy

Pyriminil toxicity occurs primarily because it inhibits NADH ubiquinone oxidoreductase activity of complex I in mammalian mitochondria resulting in preferential toxicity to high-energy-demanding cells such as nerves and pancreatic jS-cells. However, pyriminil may also act as a nicotinamide antagonist and interfere with the synthesis of NADH/NADPH, furthering neural and jS-cell toxicity. Inhibition of mitochondrial respiration in nerves causes somatic, autonomic, and central nervous system neuropathies while inhibition in jS-cell causes an immediate, irreversible insulin-dependent diabetes mellitus condition. Pyriminil also acts as a noncompetitive inhibitor of rat acetylcholinesterase. 

Etiology Trauma, viral infections, ischemia, inflammation, genetic defects Neuropathy, genetic defects Peripheral inflammation, peripheral neuropathy, trauma, genetic defects, spinal cord injury, inflammation in the central nervous system ... 

Association of Pain, neuropathic pain is defined as pain initiated or caused by a primary lesion, dysfunction in the nervous system". Neuropathy can be divided broadly into peripheral and central neuropathic pain, depending on whether the primary lesion or dysfunction is situated in the peripheral or central nervous system. In the periphery, neuropathic pain can result from disease or inflammatory states that affect peripheral nerves (e.g. diabetes mellitus, herpes zoster, HIV) or alternatively due to neuroma formation (amputation, nerve transection), nerve compression (e.g. tumours, entrapment) or other injuries (e.g. nerve crush, trauma). Central pain syndromes, on the other hand, result from alterations in different regions of the brain or the spinal cord. Examples include tumour or trauma affecting particular CNS structures (e.g. brainstem and thalamus) or spinal cord injury. Both the symptoms and origins of neuropathic pain are extremely diverse. Due to this variability, neuropathic pain syndromes are often difficult to treat. Some of the clinical symptoms associated with this condition include spontaneous pain, tactile allodynia (touch-evoked pain), hyperalgesia (enhanced responses to a painful stimulus) and sensory deficits. 

Neuropathic pain is defined as spontaneous pain and hypersensitivity to pain associated with damage to or pathologic changes in the peripheral nervous system as in painful diabetic peripheral neuropathy (DPN), acquired immunodeficiency syndrome (AIDS), polyneuropathy, post-herpetic neuralgia (PHN) or pain originating in the central nervous system (CNS), that which occurs with spinal cord injury, multiple sclerosis, and stroke. Functional pain, a relatively newer concept, is pain sensitivity due to an abnormal processing or function of the central nervous system in response to normal stimuli. Several conditions considered to have this abnormal sensitivity or hyperresponsiveness include fibromyalgia and irritable bowel syndrome. 

FEATURES COMMON TO THE PERIPHERAL AND CENTRAL NERVOUS SYSTEM IMPORTANT IN THE PATHOGENESIS AND PATHOPHYSIOLOGY OF NEUROPATHIES 620... 

The human leukodystrophies are inherited disorders of central nervous system white matter. These disorders are characterized by a diffuse deficiency of myelin caused by a variety of genetic lesions and often manifest before 10 years of age (Table 38-1). Some are caused by mutations in the PLP gene and resemble the PLP animal mutants described in Chapter 4 [ 1,23]. As with the animal models, depending on the nature of the mutation, they vary from a severe form in connatal Pelizaeus-Merzbacher disease (PMD) through an intermediate phenotype in classical PMD to a mild phenotype in spastic paraplegia. It is noteworthy that some mutations of the PLP gene also cause a peripheral neuropathy [24], very probably related to the expression of low levels of PLP in peripheral nerve (see Ch. 4). 

Peripheral neuropathy has also occurred in humans as the result of solvent abuse of products containing -hexane (Altenkirch et al. 1977 Chang et al. 1998 Spencer et al. 1980). Clinical signs were very similar to those seen after occupational exposure however, signs of central nervous system toxicity may also be present due to other components in the inhaled mixtures, e.g., toluene (Spencer et al. 1980). 

Neurological examinations of humans with M-hexanc-induced peripheral neuropathy have not shown clinical signs of central nervous system toxicity (Herskowitz et al. 1971 Yamamura 1969). There have been reports of altered evoked potentials recorded in the brain (increased latency, decreased amplitude) in humans occupationally exposed to -hexane (Mutti et al. 1982c Seppalainen et al. 1979). There has been one report of an individual occupationally exposed to -hexane for 38 years who developed Parkinsonism (Pezzoli et al. 1995), although the etiology of this case is complicated by the fact that the patient had a sister who was probably affected by Parkinsonism. Further studies, particularly prospective... 

The nervous system is the most sensitive target for cyanide toxicity, partly because of its high metabolic demands. High doses of cyanide can result in death via central nervous system effects, which can cause respiratory arrest. In humans, chronic low-level cyanide exposure through cassava consumption (and possibly through tobacco smoke inhalation) has been associated with tropical neuropathy, tobacco amblyopia, and Leber s hereditary optic atrophy. It has been suggested that defects in the metabolic conversion of cyanide to thiocyanate, as well as nutritional deficiencies of protein and vitamin B12 and other vitamins and minerals may play a role in the development of these disorders (Wilson 1965). 

Central nervous system effects predominate in acute exposures at massive doses, whereas peripheral neuropathy is more common with lower doses.After cessation of exposure to acrylamide, most cases recover, although the course of improvement can extend over months to years and depends on the severity of exposure. Because peripheral neurons can regenerate and central axons cannot, severely affected individuals may still experience residual ataxia, distal weakness, reflex loss, or sensory disturbance. 

Toxicology. -Hexane is an upper respiratory irritant and central nervous system depressant chronic exposure causes peripheral neuropathy. 

Toxicology. Methyl butyl ketone (MBK) at high concentrations may produce ocular and respiratory irritation followed by central nervous system depression and narcosis. Chronic inhalation causes peripheral neuropathy. 

Other effects on humans from inhalation of various concentrations are as follows 2000 ppm, mild central nervous system depression within 5 minutes 600 ppm, sensation of numbness around the mouth, dizziness, and some incoordination after 10 minutes. In human experiments, 7-hour exposures at 100 ppm resulted in mild irritation of the eyes, nose, and throat flushing of the face and neck headache somnolence and slurred speech. Prolonged exposure has caused impaired memory, numbness of extremities, and peripheral neuropathy, including impaired vision. ... 

Neurologic effects Convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with nitroimidazole drugs including tinidazole and metronidazole. The appearance of abnormal neurologic signs demands the prompt discontinuation of tinidazole therapy. Administer tinidazole with caution to patients with central nervous system diseases. 

Central nervous system Nervousness hyperkinesia emotional lability Lethargy general slowing of mental processes neuropathies... 

Peripheral neuropathy is observed in 10-20% of patients given dosages greater than 5 mg/kg/d, but it is infrequently seen with the standard 300-mg adult dose. Peripheral neuropathy is more likely to occur in slow acetylators and patients with predisposing conditions such as malnutrition, alcoholism, diabetes, AIDS, and uremia. Neuropathy is due to a relative pyridoxine deficiency. Isoniazid promotes excretion of pyridoxine, and this toxicity is readily reversed by administration of pyridoxine in a dosage as low as 10 mg/d. Central nervous system toxicity, which is less common, includes memory loss, psychosis, and seizures. These may also respond to pyridoxine. 

Dacarbazine Methylates DNA and inhibits DNA synthesis and function Flodgkin s lymphoma, melanoma, soft tissue sarcoma Nausea and vomiting Myelosuppression, central nervous system toxicity with neuropathy, ataxia, lethargy, and confusion... 

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