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Biomedical subjects

O Devinsky

Publications and source records attributed to O Devinsky.

At least 109 records · Page 6Linked to original sources
PubMed1993

New antiepileptic medications.

Several new compounds are undergoing extensive investigation in the United States and Europe. The available animal and human studies suggest that these new antiepileptic drugs are very promising. Some or all of them will be approved for clinical use during the next decade. New antiepileptic drugs offer new options in the treatment of epilepsy. Although there already has been considerable testing of these drugs, additional studies that incorporate traditional medical outcome measures and quality of life measures remain to be done to establish the ultimate role of the new antiepileptic drugs in the treatment hierarchy for epilepsy.

Animals↗
PubMed1993

Epilepsy surgery.

Epilepsy surgery is assuming greater importance in treating patients with partial epilepsy whose seizures are uncontrolled with antiepileptic drugs. Many good candidates for surgical treatment are not presented with the option of surgery. The evaluation for epilepsy surgery is extensive and includes several stages of noninvasive and invasive testing. As more sophisticated noninvasive tests develop, fewer patients require invasive monitoring studies such as depth or subdural electrodes. The principal forms of surgical treatment include focal resection, corpus callosotomy, and hemispherectomy. Temporal lobectomy remains the most common and effective form of epilepsy surgery. Frontiers of epilepsy surgery include resective surgery for intractable infantile spasms and multiple subpial transections for patients whose seizure foci are in sensory, motor, or languages cortex. Additional studies are needed to define the safety and efficacy of these new procedures.

Animals↗
PubMed1993

Functional mapping of memory and other nonlinguistic cognitive abilities in adults.

The review of previous research and the studies undertaken at our center suggest an important role for mapping of nonlinguistic cognitive functions with cortical stimulation. Such mapping is usually restricted to language functions, which is understandable given the importance of language to daily activities and the reports of postoperative declines in naming. However, memory functions are also critical to adaptive daily living, and these studies show that memory may be effectively addressed through mapping procedures. Both Ojemann's studies and those at our center suggest an important role for much of the temporal convexity in memory processing, and we believe that postoperative memory declines can be minimized with mapping of the temporal lobe prior to resection. Patients presenting with unique abilities that may be susceptible to postoperative declines can also be effectively mapped with stimulation studies tailored to their unique abilities. We encourage the expansion of mapping paradigms beyond just the language domain and believe that such studies will both improve the quality of our patients' functioning and further our knowledge of brain-behavior relationships.

Adult↗
PubMed1993

Behavioral changes associated with epilepsy.

Epilepsy can be accompanied by changes in cognition, personality, affect, and other elements of behavior. There is no single epileptic constitution or personality complex. A unifying theme to the behavior in epilepsy is diversity. As one looks at the behavioral traits reported in epilepsy, a specific and consistent pattern is lacking. Rather, extremes of behavior are accentuated: sometimes in one direction, often in both directions. Changes in emotional state are prominent among behavioral features in epilepsy. Some authors describe a prominent deepening or increase in emotionality, whereas others identify a global decrease in emotional life and content. Emotional lability is also reported. Sexuality and libido are typically decreased, but fetishism, transvestism, exhibitionism, and hypersexual episodes also occur. Concerns over morality may be lacking or exaggerated. Patients may be irritable and aggressive or timid and apathetic. The impressive list of people with epilepsy in politics, religion, arts, and sciences suggests a positive expression of this behavioral spectrum. Psychosis, depression, paranoia, and personality disorders may represent a negative pole of epilepsy-related behavioral changes. The most important aspect of behavioral changes in epilepsy for physicians is to recognize and treat dysfunctional behavior. Depression is a common problem that is often unrecognized and untreated. Other treatable problems include impotence, anxiety, panic attacks, and psychosis. Identifying risk factors will, it is hoped, assist in developing methods to prevent these disorders.

Anxiety Disorders↗
PubMed1992

Cerebral metabolism and depression in patients with complex partial seizures.

Twenty-three patients with complex partial seizures were evaluated with 18F-2-deoxyglucose positron emission tomography and with the Beck Depression Inventory. Five of 10 patients with left and zero of eight with right temporal electroencephalographic foci had depressive symptoms; one of five patients with poorly localized electroencephalographic foci also scored in the depressed range. Temporal, frontal, caudate, and thalamic normalized glucose metabolic rates among five patients with depressive symptoms and well-localized left temporal epileptogenic regions were compared with five patients without depressive symptoms but with similar electroencephalographic characteristics. Multifactorial analysis of variance yielded a significant nonlateralized mood by region interaction. Of nine individual regions compared, only inferior frontal cortex showed a significant difference in normalized regional metabolic rate between depressed and nondepressed patients. Metabolism in this region also distinguished patients with depressive symptoms from normal control subjects. Depressive symptoms in patients with complex partial seizures are associated with a bilateral reduction in inferior frontal glucose metabolism, compared with patients without depressive symptoms and normal control subjects. The frontal lobe hypometabolism observed in patients with depressions associated with epilepsy, Parkinson's disease, and primary affective disorder suggests that similar frontal lobe metabolic disturbances could underlie these conditions.

Adolescent↗
PubMed1992

Viscosity and social cohesion in temporal lobe epilepsy.

Clinical case reports suggest that viscosity, the behavioural tendency to talk repetitively and circumstantially about a restricted range of topics, is common in patients with temporal lobe epilepsy (TLE). Such patients are also reported to exhibit heightened levels of social cohesion, the tendency to become interpersonally "clingy". This "sticky" interpersonal style may be particularly common in TLE patients with a left sided temporal lobe seizure focus. To test this hypothesis, self-report and observer rating scales were developed to assess both viscosity and social cohesion. Subjects consisted of patients with right, left, or bilateral temporal lobe seizure foci, absence or primary generalised tonic-clonic seizures, psychiatric controls (panic disorder patients), and normal controls. Elevations on the viscosity scale were observed primarily in TLE patients with left or bilateral seizure foci. Viscosity scores also correlated with seizure duration and left handedness. No group differences were observed on the social cohesion scale. These findings are consistent with the hypothesis that viscosity results from subtle interictal language disturbances, although other pathogenetic mechanisms are discussed.

Anomia↗
PubMed1992

Aggressive behavior following exposure to cholinesterase inhibitors.

The authors report four instances of significant, essentially unprovoked aggressive behavior, including two homicides, following exposure to cholinesterase inhibitors. No subject had a history of violent behavior, antisocial personality, or major psychiatric or neurologic disorder. After anticholinesterase exposure ceased, all showed sincere remorse for their actions, and none has since engaged in aggressive or psychopathologic behavior. Well-controlled experimentation in animals suggests that enhanced activation of hypothalamic cholinergic receptors may underlie aggressive behavior in humans exposed to cholinesterase inhibitors. A relationship between cholinesterase inhibitors and aggression has important implications for public health, raising the possibility of unappreciated neurotoxic influences on behavior.

Adult↗
PubMed1992

Effects of carbamazepine on pituitary-adrenal function in healthy volunteers.

Carbamazepine (CBZ) is a widely used therapeutic agent in seizure, pain, and mood disorders. Although CBZ has been shown to inhibit hypothalamic CRH secretion in vitro, limited data suggest that systemic CBZ induces pituitary-adrenal activation. Few data are available to reconcile these effects or clarify their mechanism(s), particularly in healthy human subjects. We report here a study of basal ACTH and cortisol secretion and their responses to ovine CRH administration in nine healthy volunteers, studied both during repeated (2-3 weeks) administration of CBZ and while medication free. CBZ significantly increased mean 24-h urinary free cortisol (mean +/- SE, 197 +/- 17 vs. 137 +/- 24 nmol/day; P less than 0.02) and evening basal total plasma cortisol (113 +/- 17 vs. 83 +/- 14 nmol/L; P less than 0.05) as well as cortisol-binding globulin-binding capacity (497 +/- 36 vs. 433 +/- 28 nmol/L; P less than 0.01). Despite the CBZ-induced hypercortisolism, plasma ACTH responses to CRH during CBZ treatment remained robust, rather than being suppressed by basal hypercortisolism. In fact, during CBZ treatment, we noted a positive correlation between the increase in basal plasma cortisol and the increase in the plasma ACTH response to CRH (r = 0.65; P less than 0.05). We also observed a reduction in cortisol-binding globulin-binding capacity after CRH administration (315 +/- 25 vs. 433 +/- 28 nmol/L; P less than 0.001), which was accentuated by CBZ treatment (342 +/- 19 vs. 497 +/- 36 nmol/L; P less than 0.001; magnitude of fall, -155 +/- 22 nmol/L on CBZ vs. -118 +/- 11 nmol/L off CBZ; P less than 0.05). We conclude that CBZ increases plasma cortisol secretion in healthy volunteers independent of its effect on plasma cortisol-binding capacity. This pituitary-adrenal activation seems to reflect a pituitary, rather than a hypothalamic, effect of CBZ. Hence, despite CBZ-induced hypercortisolism, the ACTH response to CRH remained robust in direct proportion to the CBZ-induced rise in basal plasma cortisol. Thus, we propose that the increased cortisol secretion observed during CBZ treatment reflects a relative inefficacy of glucocorticoid negative feedback at the pituitary. This pituitary-driven increase in cortisol secretion combined with the expected reduction in centrally directed CRH secretion could contribute to the anticonvulsant properties of CBZ.

Adrenocorticotropic Hormone↗
PubMed1991

Herpes zoster myelitis.

We studied the clinical (10 patients) and pathological (9 patients) findings in 13 patients with herpes zoster myelitis, all of whom had systemic illnesses associated with immunosuppression. The median interval between the onset of the herpes zoster rash and myelopathic symptoms was 12 days, and the subsequent median interval to maximal deficit was 10.5 days. Presenting neurological symptoms were characteristically ipsilateral to the rash, with motor dysfunction predominating, followed by a spinothalamic and, less often, posterior column sensory deficit. Pathological involvement was most severe in the dorsal root entry zone and posterior horn of the spinal cord segment corresponding to the involved dermatome. There was variable spread both horizontally and vertically in the spinal cord. Direct varicella-zoster virus (VZV) infection of neuroectodermal cells, particularly oligodendrocytes, was demonstrated by immunostaining viral antigens (8 cases), and by the presence of Cowdry type A intranuclear inclusions (7 cases) and often was associated with focal demyelination (6 cases). In 4 patients a VZV vasculitis was associated with leptomeningitis and haemorrhagic necrosis (spinal cord in 1; brainstem or cerebellum in 3). The protracted evolution in many cases and the pathologically documented direct viral infection of the spinal cord provide a rational basis for the use of antiviral therapy in preventing or attenuating the evolving myelopathy.

Adult↗
PubMed1991

Phenytoin intoxication.

We studied the clinical features of 85 cases of phenytoin toxicity in 76 patients treated at a general hospital. Serum levels of phenytoin on admission ranged from 30.3 to 95.0 micrograms/mL (median, 46.5). Iatrogenic causes of intoxication were common and included increased daily dosage and intravenous loading in the emergency room for single seizures in patients with subtherapeutic serum phenytoin levels. The most frequent neurologic findings were nystagmus (95%), ataxia (88%), lethargy (22%), and seizures (19%). Outcome was usually good, but three patients had serious complications.

Adult↗
PubMed1991

Clozapine-related seizures.

Clozapine is an atypical antipsychotic drug with minimal extrapyramidal toxicity recently approved by the Food and Drug Administration for hard-to-treat schizophrenic patients. We reviewed information on 1,418 patients treated with clozapine in the United States between 1972 and 1988. Forty-one of 1,418 (2.8%) patients had generalized tonic-clonic seizures during treatment with clozapine. Life-table analysis predicts a cumulative 10% risk of seizures after 3.8 years of treatment. Clozapine-related seizures appear to be dose-related. High-dose therapy (greater than or equal to 600 mg/day) was associated with a greater risk of seizures (4.4%) than medium (300 to 600 mg/day; 2.7%) or low doses (less than 300 mg/day; 1.0%). Also, rapid upward titration may increase seizure risk. Thirty-one of 41 patients were successfully continued on clozapine despite seizure occurrence, either with reduction of dose or addition of an antiepileptic medication. Recognition and treatment of clozapine-related seizures will become increasingly important as its use grows in the 1990s.

Adult↗
PubMed1990

Relation of EEG alpha background to cognitive function, brain atrophy, and cerebral metabolism in Down's syndrome. Age-specific changes.

We studied 19 young adults (19 to 37 years old) and 9 older patients (42 to 66 years old) with Down's syndrome (DS) and a control group of 13 healthy adults (22 to 38 years old) to investigate the relation of electroencephalographic (EEG) alpha background to cognitive function and cerebral metabolism. Four of the older patients with DS had a history of mental deterioration, disorientation, and memory loss and were demented. Patients and control subjects had EEGs, psychometric testing, quantitative computed tomography, and positron emission tomography with fludeoxyglucose F 18. A "blinded" reader classified the EEGs into two groups--those with normal alpha background or those with abnormal background. All the control subjects, the 13 young adult patients with DS, and the 5 older patients with DS had normal EEG backgrounds. In comparison with the age-matched patients with DS with normal alpha background, older patients with DS with decreased alpha background had dementia, fewer visuospatial skills, decreased attention span, larger third ventricles, and a global decrease in cerebral glucose utilization with parietal hypometabolism. In the young patients with DS, the EEG background did not correlate with psychometric or positron emission tomographic findings, but the third ventricles were significantly larger in those with abnormal EEG background. The young patients with DS, with or without normal EEG background, had positron emission tomographic findings similar to those of the control subjects. The mechanism underlying the abnormal EEG background may be the neuropathologic changes of Alzheimer's disease in older patients with DS and may be cerebral immaturity in younger patients with DS.

Adult↗
PubMed1990

Depression, anxiety, and temporal lobe epilepsy. Laterality of focus and symptoms.

The association between anxiety, depression, and lateralization of an epileptogenic focus was explored in 18 adult patients with a left temporal lobe focus, 21 with a right focus, 20 with bilateral temporal foci, and 16 individuals with absence seizures. No significant difference in the level of anxiety was found among the groups. However, patients with left-sided temporal lobe epilepsy scored significantly higher than other groups on self-ratings for depression. This could not be accounted for by factors such as duration of epilepsy, employment status, education, age at seizure onset, or medication status. The left temporal lobe epilepsy group had a nonsignificantly larger number of males and left-handed subjects. The possible interactions between gender, handedness, seizure focus, and vulnerability to depression are described.

Adult↗
PubMed1990

General assay for phosphoproteins in cerebrospinal fluid: a candidate marker for paraneoplastic cerebellar degeneration.

The components of protein phosphorylation systems (protein kinases, protein phosphatases, and their phosphoprotein substrates) are highly enriched in neuronal cells compared with other cell types. We exploited this relative neuronal enrichment of protein phosphorylation system components to develop a general assay technique for putative protein kinase substrates (phosphoproteins) in human cerebrospinal fluid. Using this cerebrospinal fluid phosphoprotein assay, we have detected a putative protein kinase C substrate protein of apparent Mr 60 kd in 6 of 14 patients with paraneoplastic cerebellar degeneration but not in any of 55 patients with a variety of other neurological diseases. Phosphoproteins in cerebrospinal fluid may provide novel and unique markers for the diagnosis or staging of neuronal diseases as well as offer potential insights into the biochemical characterization of affected neuronal populations.

Adult↗