Document XOaN8D97118jQGKRwvwmBBoB

618 EXPERIMENTAL AND CLINICAL NEUROTOXICOLOGY $(* 11i< m f swelling and scattered small subarachnoid hemor tion. Definitive ultrastructural studies by rhages. Individuals who survive the acute episode and colleagues (63) have dispelled this notion. u,,| may be left`with residual damage to the CNS indicate that the myelin changes induced in th* resulting from anoxic or hypotensive injury to the corpus callosum of rats by cyanide are second arv brain. to axonal degeneration. Furthermore, Levine (7Ki Chronic has suggested that the localization of degeneration to the corpus callosum may reflect a pattern of There is strong evidence linking chronic exposure hypoxic damage and vascular insufficiency. to dietary cyanide to the development of an ataxic Recent reports by Brierly and colleagues (13) on neuropathy syndrome described in poorer class Ni rats and primates, in which the physiological star, gerians (86, 101). These individuals subsist on food of the animals was carefully monitored, havi* - . that includes large amounts of cassava, the tuber of gested that pure histotoxic damage to neumn> : the manioc shrub, and other plants known to con not occur in cyanide intoxication. As a result ni tain cyanogenetic glycosides. This diet results in Brierley's work, it now seems likely that many of significantly elevated plasma thiocyanate levels. the neuronal changes, previously attributed to a Many are also riboflavin deficient and generally in direct effect of cyanide on nerve cell oxidative me poor health. The disease is slowly progressive and tabolism, may have reflected hypotension and res rarely fatal. Initial complaints are painful paras- piratory depression in moribund animals. thesiae of the feet followed by numbness in the hands. As the illness progresses, visual loss, dimin 2,4-DICHLOROPHENOXY ACETIC ished hearing, weakness of the lower extremities, ACID and a broad-based ataxic gait appear. Loss of sen sation and weakness often have a distal, symmet rical, stocking-glove distribution, and propriocep tive deficits may be severe in the lower extremities. Ataxia is present only in the lower extremities, and probably reflects sensory loss rather than cerebellar involvement. Optic atrophy and visual impairment are prominent features of the illness. Cochlear-type hearing loss is sometimes present but vestibular impairment has not been reported. Nerve conduc tion is abnormal in the lower extremities. Occa sional individuals display signs of corticospinal tract 2,4 0 involvement. There have been no postmortem re 2, 4-Dichlorophenoxy acetic acid (2,4-D) was in ports or experimental animal models of this condi troduced as a herbicide in the early 1950s. In 1959. tion, and the clinical data permit only a limited Goldstein and co-workers (44) described neurotox clinical-pathological correlation. The symmetrical icity in three individuals exposed to the compound polyneuropathy, and resemblance of the CNS signs by skin contact Symmetrical polyneuropathy ap to those of the spinocerebellar degenerations, indi peared approximately 1 week after exposure. Both cate that the Nigerian syndrome most likely is a motor and sensory deficits occurred initially in the distal axonopathy. Plasma thiocyanate levels are extremities. The lower limbs were affected to a significantly elevated in these individuals. Chronic exposure to low levels of cyanide in cigarette smoke has been implicated as causing visual loss in the tobacco-alcohol amblyopia syn drome. However, many of these patients are mal nourished and consume large quantities of ethyl alcohol as well, and the role of cyanide in these conditions remains unproven. greater extent than upper limbs. Partial recovery was observed over a period of many months. Foissac-Gegoux and co-workers (37) described unilmeral sensory loss in the face following 2,4-D exp"sure. No pathological or experimental animal stud ies of 2,4-D neurotoxicity have been performed to dale. EXPERIMENTAL ANIMAL STUDIES MANGANESE There have been many experimental animal studies of the effects on the central nervous system of acute and subchronic cyanide intoxication. Some were undertaken on the premise that, in addition to the classic pattern of hypoxic-ischemic damage to the brain, cyanide induced primary demyelina- Manganese is used in metal alloys and as an antiknock agent in lead-free gasoline. Mining man ganese for these purposes has resulted in a high incidence of chronic manganese poisoning in ex posed workers. Many thousands of workers have developed manganesium neurotoxicity and. ol 618 EXPERIMENTAL AND CLINICAL NEUROTOXICOLOCY S(*f t l r , ,, < swelling and scattered small subarachnoid hemor tion. Definitive ultrastructural studies In rhages. Individuals who survive the acute episode and colleagues (63) have dispelled this notion, itn<i may be left with residual damage to the CNS indicate that the myelin changes induced in ihr resulting from anoxic or hypotensive injury to the corpus callosum of rats by cyanide are secondary brain. to axonal degeneration. Furthermore, Levine {7fii Chronic has suggested that the localization of degeneration to the corpus callosum may reflect a pattern of There is strong evidence linking chronic exposure hypoxic damage and vascular insufficiency. to dietary cyanide to the development of an ataxic Recent reports by Brierly and colleagues (13) on neuropathy syndrome described in poorer class Ni rats and primates, in which the physiological state gerians (86, 101). These individuals subsist on food of the animals was carefully monitored, haw - , th at includes large amounts of cassava, the tuber of gested that pure histotoxic damage to neuron.- : .. the manioc shrub, and other plants known to con not occur in cyanide intoxication. As a result m tain cyanogenetic glycosides. This diet results in Brierley's work, it now seems likely that many of significantly elevated plasma thiocyanate levels. the neuronal changes, previously attributed to a Many are also riboflavin deficient and generally in direct effect of cyanide on nerve cell oxidative me poor health. The disease is slowly progressive and tabolism, may have reflected hypotension and res rarely fatal. Initial complaints are painful paras- piratory depression in moribund animals. thesiae of the feet followed by numbness in the hands. As the illness progresses, visual loss, dimin 2,4-DICHLOROPHENOXY ACETIC ished hearing, weakness of the lower extremities, ACID and a broad-based ataxic gait appear. Loss of sen sation and weakness often have a distal, symmet rical, stocking-glove distribution, and propriocep tive deficits may be severe in the lower extremities. Ataxia is present only in the lower extremities, and probably reflects sensory loss rather than cerebellar involvement. Optic atrophy and visual impairment are prominent features of the illness. Cochlear-type hearing loss is sometimes present but vestibular impairment has not been reported. Nerve conduc tion is abnormal in. the lower extremities. Occa sional individuals display signs of corticospinal tract 1 2,4 D involvement There have been no postmortem re ports or experimental animal models of this condi tion, and the clinical data permit only a limited clinical-pathological correlation. The symmetrical polyneuropathy, and resemblance of the CNS signs to those of the spinocerebellar degenerations, indi cate th at the Nigerian syndrome most likely is a distal axonopathy. Plasma thiocyanate levels are significantly elevated in these individuals. Chronic exposure to low levels of cyanide in cigarette smoke has been implicated as causing visual loss n the tobacco-alcohol amblyopia syn drome. However, many of these patients are mal nourished and consume large quantities of ethyl alcohol as well, and the role of cyanide in these conditions remains unproven. 2, 4-Dichlorophenoxy acetic acid (2,4-D) was in troduced as a herbicide in the early 1950s. In 1959. Goldstein and co-workers (44) described neurotox icity in three individuals exposed to the compound by skin contact Symmetrical polyneuropathy ap peared approximately 1 week after exposure. Both motor and sensory deficits occurred initially in the extremities. The lower limbs were affected to a greater extent than upper limbs. Partial recovery was observed over a period of many months. Foissac-Gegoux and co-workers (37) described unilm* eral sensory loss in the face following 2,4-D expo sure. No pathological or experimental animal stud ies of 2,4-D neurotoxicity have been performed to date. EXPERIMENTAL ANIMAL STUDIES MANGANESE There have been many experimental animal studies of the effects on the central nervous system of acute and subchronic cyanide intoxication. Some were undertaken on the premise that, in addition to the classic pattern of hypoxic-ischemic damage to the brain, cyanide induced primary demyelina- Manganese is used in metal alloys and as an antiknock agent in lead-free gasoline. Mining man ganese for these purposes has resulted in a high incidence of chronic manganese poisoning in ex posed workers. Many thousands of workers m;*> have developed manganesium neurotoxicity and. <'l