Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine of 48 adult patients who underwent orthotopic liver transplantation developed significant clinical neurological abnormalities recognized shortly after operation. Decrease in consciousness occurred with resultant coma, focal and generalized seizures and the occasional appearance of a state of akinetic mutism. Neuropathological abnormalities consisted of multifocal areas of infarction in cerebral cortex and basal ganglia in five patients, central pontine myelinolysis in five (often more extensive than usually reported), Wernicke's encephalopathy in three, glial nodules in two, and fungal abscesses in one. Alzheimer II astrocytosis was found in all brains available for retrospective study. There was direct evidence in two of the patients that air embolization from the homografts had occurred. Correlation of this with the brain infarcts in these and other cases seems reasonable. The ease with which air passed to the systemic circulation is explicable by the right to left venous--arterial shunts that are common in chronic liver disease. With the delination of this cause for the neurologic complications, measures to prevent it in future cases have been described.
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PMID:Acute neurological complications after liver transplantation with particular reference to intraoperative cerebral air embolus. 34 84

A light microscopic study was performed during the preictal period following the administration of methionine sulfoximine (MSO) to adult rats. The principal morphologic observation was the development of Alzheimer II astrocytes in gray matter, suggesting that the metabolic abnormality induced by MSO is initially confined to the astrocyte. In view of the association of the Aizheimer II astrocyte with hyperammonemic states, the drug toxicity may be secondary to the presence of ammonia. A possible mechanism involves astrocytes in the development of seizures produced by MSO.
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PMID:Alzheimer II astrocytosis following methionine sulfoximine. 116 49

Quantitative receptor autoradiography was used to examine the density and distribution of [3H]kainic acid and [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) binding sites in the hippocampal formation and parahippocampal gyrus obtained at autopsy from 10 Alzheimer's disease and eight normal control individuals. In control and Alzheimer's disease individuals, [3H]kainic acid saturation binding analysis in the outer molecular layer of the dentate gyrus fitted a single-site model. Added calcium ions did not alter the density of [3H]kainic acid binding in the human tissues. These results suggest that calcium-sensitive high-affinity kainic acid binding sites are not present in the human brain in contrast to kainic acid receptors in the rat brain. [3H]AMPA binding was also slightly different in the human brain as compared to the rat, being greatest in the inner third as compared to the outer two-thirds of the dentate gyrus molecular layer. In both control and Alzheimer's disease individuals, [3H]kainic acid and [3H]AMPA binding densities were similar at anterior and posterior levels of the hippocampal formation. In Alzheimer's disease patients, there was a significant increase in [3H]AMPA binding in the infragranular layer. In some, but not all Alzheimer's disease patients, there was an increase in [3H]kainic acid binding densities in the outer half of the dentate gyrus molecular layer. The same individuals which exhibited an increase in [3H]kainic acid binding in the outer molecular layer also displayed increased [3H]AMPA binding in the hilar region. Similar alterations in [3H]kainic acid binding have been observed in rats which had received fimbria-fornix lesions, a model of chronic epilepsy and in individuals with temporal lobe epilepsy. Advanced Alzheimer's disease patients are at risk of developing seizures. The results suggest that several factors including cortical and subcortical pathology and seizure activity may contribute to the alterations in [3H]kainic acid and [3H]AMPA binding observed in the hippocampal formation in Alzheimer's disease.
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PMID:Hippocampal excitatory amino acid receptors in elderly, normal individuals and those with Alzheimer's disease: non-N-methyl-D-aspartate receptors. 132 33

Neurologic signs and their neuropathologic correlates were examined in a sample of 56 patients with autopsy-proved Alzheimer's disease (13 men, 43 women; mean age at death, 83.1 years; range, 67 to 96 years) from a prospective longitudinal study. Full-range regular rigidity with cog-wheeling was found in 20 patients and was significantly associated with lower neuron counts in the substantia nigra and with the presence of Lewy bodies in the brain stem and neocortex. Twelve patients with myoclonus had a younger age at onset, a lower age at death (mean, 78.6 years), and lower neuron counts in the serotoninergic dorsal raphe nucleus and in the noradrenergic locus coeruleus than did the patients without myoclonus. Generalized motor seizures were reported in six patients, and they had significantly lower counts of pyramidal cells in cortical layers III through IV of the parietal cortex (area 7) and slightly decreased pyramidal cell numbers in the parahippocampal gyrus (area 28). The 19 patients with a positive grasp reflex had an earlier onset of illness and a significantly inferior performance on the Mini-Mental State examination and Cambridge Cognitive Examination tests. They, and 25 patients with a positive snout reflex, had significantly lower counts of large pyramidal cells in layers III through V of the frontal cortex (area 32). These results indicate that different neurologic symptoms in Alzheimer's disease can be related to disproportionate neuronal degeneration in functionally different brain areas.
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PMID:Neurologic signs in Alzheimer's disease. Results of a prospective clinical and neuropathologic study. 141 11

Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus, particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L-kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy.
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PMID:Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. 142 88

Four unrelated children were thought to have valproate-associated hepatotoxicity. They presented with recurrent partial secondarily generalized status epilepticus and epilepsia partialis continua followed by mental and motor regression. Despite treatment with multiple antiepileptic medications, they continued to have seizures. After initiation of valproic acid (VPA), all 4 manifested liver failure within 3 months. Two of these children each had 1 sibling who was not exposed to VPA, but who developed the same clinical picture including liver failure. At the time of autopsy, all 6 children had similar neuropathological findings with focal areas of spongiosis and neuronal loss, diffuse gliosis, and Alzheimer type II cells. One VPA-treated patient underwent a successful liver transplantation only to die from relentlessly progressive neurological deterioration. We propose that many of the reported patients with VPA-associated hepatotoxicity represent undiagnosed patients with early childhood hepatocerebral degeneration, the Huttenlocher variant of Alpers' syndrome. This disease manifests by obstinate partial seizures, recurrent partial secondarily generalized status epilepticus, epilepsia partialis continua, psychomotor deterioration, and hepatic dysfunction that is exacerbated by VPA administration. The accelerated demise from liver failure in the nontransplanted patients before the central nervous system pathology fully evolves makes the diagnosis of this rare condition difficult. The occurrence of disease in the unexposed siblings suggests recessive inheritance.
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PMID:Early childhood hepatocerebral degeneration misdiagnosed as valproate hepatotoxicity. 147 67

In a 53-year old male suffering from paretic neurosyphilis, SPECT-investigations were performed before and after treatment with high doses of Penicillin G. The patient was admitted for disturbances of speech and concentration, memory disorder and tonic-clonic seizures. Mental examination showed a mild dysphoria and irritability in mood, but no disturbance of orientation, no euphoria or expansive delusions, and no paranoia. Mini-Mental-State examination was within the normal range (28 points); no abnormalities were found on neurologic examination, and CT and MRI investigations showed normal findings. The diagnosis was verified by CSF-examination (pleocytosis, elevated protein, positive Lues reactions). SPECT investigation with Tc 99m HMPAO (20 mCi, single-head rotating camera) revealed a pronounced bilateral parieto-temporal uptake deficiency as observed in patients with dementia of Alzheimer's type. After 18 months the clinical symptoms had remitted, and laboratory findings were improved. On the other hand, the bilateral parieto-temporal uptake deficiency in SPECT remained unchanged. Possible causes of these findings are discussed in relation to neuropathologic findings. It can be concluded that bilateral parieto-temporal uptake deficiency in SPECT is a nonspecific finding and that there is no correlation between clinical improvement and SPECT pattern in paretic neurosyphilis.
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PMID:[Lack of specificity of single photon emission computerized tomography in dementia--results of a case of progressive paralysis]. 163 20

We report the genealogical, clinical and molecular genetic findings of a new family with autosomal dominant early-onset Alzheimer's disease (FAD) discovered in Torino (Italy). Up to now, the pedigree comprises 1500 members, distributed in 8 generations. 22 patients affected with Alzheimer's disease have been identified. The clinical course of the disease was fairly uniform in all the patients. An high incidence of myoclonic jerks and epileptic seizures was found. Molecular genetic studies showed the presence of positive but nonsignificant lod scores between chromosome 21 anonymous DNA markers and the disease. The data obtained from the Torino family were computed together with those of additional 47 pedigrees, with both early-onset and late-onset Alzheimer's disease. A predisposing locus for the disease was found on the pericentromeric region of chromosome 21 only in early-onset FAD pedigrees.
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PMID:Familial Alzheimer's disease. Evidences for clinical and genetic heterogeneity. 180 54

We studied the etiology of seizures in 46 patients who developed seizures after age 65 years. The most frequent cause was cerebrovascular disease, accounting for 41.3% of all cases. Clinical diagnosis of Alzheimer's disease was made in 5 patients (10.8%). Other etiologies were; metabolic encephalopathies in 6.5%, craniocerebral trauma in 4.3% and glioma in 2.1%. The etiology of seizures remained unknown in 34.7%. They had generalized tonic-clonic seizures in 48%. They were partial or partial secondarily generalized in 44.1%. The role of Alzheimer's disease in late onset seizures has not been important enough in previous studies. We believe that a well-designed prospective study will let us know the real frequency of the causes of seizures in the elderly.
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PMID:[Etiology of epileptic crises in the geriatric patient. Results of a retrospective study]. 195 24

Five male patients participated in a pilot open-label study of dose-related aspects of response to intracerebroventricular bethanechol in Alzheimer's disease. No patient had remission of symptoms, but three patients improved symptomatically and on tests of memory. Improvement was evident over a restricted range of doses for each subject, and symptoms were worse at doses below and above the optimal range. There was little overlap in the range of doses producing improvement among these three. Two patients had no consistent improvement in memory, and agitation, depression, paranoia, and seizures developed during treatment. Qualitative differences and variability in dosages producing responses complicate the identification of true drug response in the treatment of Alzheimer's disease.
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PMID:Intracerebroventricular bethanechol for Alzheimer's disease. Variable dose-related responses. 197 38


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