Changes of protein oxidation, calpain and cytoskeletal proteins (alpha tubulin and pNF-H) levels in rat brain after nerve agent poisoning.

Highly toxic organophosphorus (OP) nerve agents, sarin and soman act by inhibiting acetylcholinesterase (AChE) function at neuronal synapses and cause many toxic effects including death within minutes. The effect of nerve agents on protein oxidation, calpain, and cytoskeletal protein levels was not well known. In the present study we investigated these parameters after subcutaneous injection of sarin (120 µg/kg) and soman (80 µg/kg) in the rat brain. Results indicate that several rat brain proteins were intensely oxidized after nerve agent poisoning. Immunoreactivity levels of µ-calpain were significantly elevated in cerebral cortex and cerebellum regions of rat brain from 2.5 h to 30 days. Alpha tubulin levels reduced from 1 to 7 days in the supernatant and 1 to 3 days in the pellet fractions of cerebellum and cerebral cortex, where as phosphorylation of high molecular weight neurofilament (pNF-H) was increased significantly in nerve agent intoxicated rat brains as compared to control rats. AChE activity was inhibited up to 3 days after nerve agent exposure in plasma and brain. Results suggest that altered protein oxidation, calpain and cytoskeletal protein levels are due to multiple mechanisms of nerve agents actions and these changes might be involved in nerve agent induced complex neurotoxicity.

Use of the intracarotid amobarbital procedure in the evaluation of memory.

The intracarotid amobarbital procedure (IAP) involves the temporary inactivation of one cerebral hemisphere by the injection of sodium amobarbital, which allows independent testing of the contralateral hemisphere. Initially used for lateralization of language, IAP later found a role in the evaluation of memory function in patients with intractable temporal lobe epilepsy being considered for resective surgery. IAP technique varies widely across centers, but, in general, memory is assessed by presenting the patient with a number of items during the period of hemispheric inactivation and testing recall or recognition of these items after the effect of the drug has worn off. Because the medial temporal lobe is not directly perfused by the internal carotid artery, concerns have been raised about the ability of the IAP to test hippocampal memory function. Consequently, a variety of selective procedures have been devised. Findings on both intracranial EEG recordings and pathologic and neuroimaging studies support the association of IAP memory results with hippocampal function. The IAP memory test was originally designed to predict the risk for development of global amnesia following unilateral temporal lobectomy. More recently, it also has been used as an adjunct in lateralizing the seizure focus and for predicting postoperative selective memory deficits and seizure outcome.

Seizure symptomatology in infants with localization-related epilepsy.

The clinical characteristics of seizures in adults and children with localization-related epilepsy have been clearly described and classified, but few data are available based on video EEG studies of postneonatal infants under 2 years of age. We analyzed 125 videotaped seizures from 23 infants aged 2 to 24 months with localization-related epilepsy defined by localized ictal EEG or localized lesion on neuroimaging with seizure-free surgical outcome. Seizure symptomatology was classified based on observable behavioral and motor manifestations and then correlated with location of the epileptogenic zone. Seizures characterized by decrease in behavioral motor activity with indeterminate level of consciousness and minimal or no automatisms ("hypomotor" seizures) arose from temporal, temporoparietal, or parieto-occipital regions (7 patients). Seizures with localized or bilateral clonic, tonic, or atonic motor phenomena arose predominantly from frontal, frontocentral, central, or frontoparietal areas (12 patients). One patient had versive seizures arising from the contralateral occipital lobe, 2 patients had infantile spasms (one with a frontal tumor, one with temporo-parieto-occipital dysplasia), and one patient had unclassifiable seizures. Disruption of temporal or temporoparietal function resulted primarily in diminution of behavioral activity, whereas ictal activation of motor areas during frontal or central onset seizures resulted mainly in localized or generalized motor phenomena. Infantile spasms occurred because of lesions in either location. Using an approach based on easily observable behavioral and motor phenomena, it was possible to classify the seizures in all but one infant.

Familial progressive myoclonus epilepsy: clinical and electrophysiologic observations.

Progressive myoclonus epilepsy (PME) is a syndrome complex encompassing different diagnostic entities. Among the 30 cases of PME studied during 1982 and 1992 at the National Institute of Mental Health and Neurosciences, Bangalore, South India, the specific diagnoses included Lafora disease (LD), neuronal ceroid lipofuscinosis (NCL). Unverricht-Lundborg disease (ULD), and myoclonus epilepsy and ragged-red fibres (MERRF). We discuss the familial nature of PME and the clinical and electrophysiological abnormalities in asymptomatic siblings. Eight cases of LD were in three different families with 3 affected siblings in two families (L1, L2) and 2 siblings in the third family (L3). Occipital seizures and behavioral changes occurred in all 3 members of L1 but were absent in the other two families. Age of onset was similar in two families (L1, 11 years; L2, 14.5 years), but not in the third. Presymptomatic EEG abnormalities were observed as long as 6 years before onset in L2. ULD occurred in 2 sisters in one family. Both had identical clinical features and normal somatosensory evoked potentials (SSEPs). The asymptomatic sister of the patient MERRF had abnormal EEG and giant SSEPs for the past 2 years. Thus, although all variations are evident in the overall clinical pattern in each of the PME, affected member of individuals families tend to be similar. Once an index case is identified, electrophysiologic tests (EEG and SSEP) may be useful in identifying other affected siblings in the presymptomatic stage.

Lafora's disease in south India: a clinical, electrophysiologic, and pathologic study.

Twenty-one cases (12 males, 9 females) of Lafora's disease in 16 families were studied at the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India, from 1982 to 1990. Mean age of onset was 13.5 years (range 9.5-18 years). First symptom was generalized tonic-clonic seizure (17), myoclonus (3), or dementia (1). All patients eventually developed the classical triad, except 1 who has had only myoclonus. Seven had occipital seizures. Other signs included behavioral changes (9), brisk tendon reflexes (11), cerebellar signs (8), and visual impairment (4). Patients from 14 of the 16 families (85%) were products of consanguineous marriage. More than 1 sibling was affected in 6 families. Scalp EEGs showed diffuse background slowing with epileptiform discharges in all and progressive slowing as the disease progressed in 3. Photosensitivity occurred in 4 of the 17 cases studied (23.5%). EEG abnormalities were documented in the presymptomatic stage in 2 cases 6 months and 6 years before clinical symptom onset. Visual evoked responses were abnormal in 4 of the 6 cases studied. Giant somatosensory evoked potentials (SSEP) were observed in all 8 cases studied. Lafora bodies were demonstrated in axillary skin in 14 of 17 (82.4%), in liver in 4 of 10 (40%), and in both brain biopsy specimens. In 2 cases, liver biopsy was positive while axillary skin biopsy was negative. In the brain, inclusions were evident in glial and capillary endothelial cells in addition to neurons. Although our cases were similar to those described earlier, the relative rarity of visual phenomena is emphasized. The clinical pattern was consistent with autosomal recessive inheritance. The high frequency of consanguinity in the South Indian population may be responsible for the many cases observed at our center.