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Biomedical subjects

I M Najm

Publications and source records attributed to I M Najm.

10 recordsLinked to original sources

Predictors of outcome after temporal lobectomy for the treatment of intractable epilepsy.

To assess short- and long-term seizure freedom, the authors reviewed 371 patients who underwent anterior temporal lobectomy to treat pharmacoresistant epilepsy. The mean follow-up duration was 5.5 years (range 1 to 14.1 years). Fifty-three percent of patients were seizure free at 10 years. The authors identified multiple predictors of recurrence. Results of EEG performed 6 months postoperatively correlated with occurrence and severity of seizure recurrence, in addition to breakthrough seizures with discontinuation of antiepileptic drugs.

Anterior Temporal Lobectomy↗

Localising and lateralising value of ictal piloerection.

BACKGROUND: Piloerection is a rare clinical symptom described during seizures. Previous reports suggested that the temporal lobe is the ictal onset zone in many of these cases. One case series concluded that there is a predominant left hemispheric representation of ictal cold. The aim of this study is to evaluate the localising and lateralising value of pilomotor seizures. METHODS: Medical records of patients who underwent video electroencephalogram (EEG) monitoring at the Cleveland Clinic between 1994 and 2001 were reviewed for the presence of ictal piloerection. The clinical history, physical and neurological examination, video EEG data, neuroimaging data, cortical stimulation results, and postoperative follow ups were reviewed and used to define the epileptogenic zone. Additionally, all previously reported cases of ictal piloerection were reviewed. RESULTS: Fourteen patients with ictal piloerection were identified (0.4%). Twelve out of 14 patients had temporal lobe epilepsy. In seven patients (50%), the ictal onset was located in the left hemisphere. Four out of five patients with unilateral ictal piloerection had ipsilateral temporal lobe epilepsy as compared with the ipsilateral side of pilomotor response. Three patients became seizure free after left temporal lobectomy for at least 12 months of follow up. An ipsilateral left leg pilomotor response with simultaneously recorded after-discharges was elicited in one patient during direct cortical stimulation of the left parahippocampal gyrus. CONCLUSIONS: Ictal piloerection is a rare ictal manifestation that occurs predominantly in patients with temporal lobe epilepsy. Unilateral piloerection is most frequently associated with ipsilateral focal epilepsy. No hemispheric predominance was found in patients with bilateral ictal piloerection.

Adolescent↗

MR imaging in epilepsy.

The advent of MR imaging techniques has immensely improved the ability to evaluate and manage patients with epilepsy. The principles of various MR techniques, the pertinent MRI neuro-anatomic features, and computer based 3D reconstruction post processing methods are discussed. Newer MR-based techniques such as magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) and their applications and potential usefulness in the evaluation of patients with medically intractable epilepsy are also reviewed.

Brain↗

Nerve rootlets to be sectioned for spasticity resolution in selective dorsal rhizotomy.

BACKGROUND: The goal of this study is to confirm the efficacy of the protocol for selective dorsal rhizotomy (SDR). In this protocol, rootlets to be sectioned are selected by palpable responses elicited by intraoperative electrical stimulation, without detailed electromyographic classifications. METHODS: Thirty-six children with spasticity due to cerebral palsy underwent SDR according to our protocol. Priority was given to sectioning rootlets that showed palpable clonic or bilateral responses, which were considered abnormal, over sectioning rootlets that merely had hyperactive responses to intraoperative stimulation. The results of intraoperative monitoring and sectioning amount were analyzed by physical evaluation. RESULTS: Significant improvements were obtained in passive range of motion and muscle tone of the lower extremities. The total percentages of rootlets with abnormal and hyperactive responses at L3 and S1 were bilaterally correlated with preoperative spasticity of the hip adductors and the plantar flexors, respectively. When rootlets with hyperactive responses were excluded from the correlation analysis, no bilateral correlation was observed. From the correlation analyses between the improvement in the physical evaluation and the amount of nerve sectioned, it was concluded that a greater improvement in muscle tone in all examined muscles, except the hamstrings, could be obtained if larger amounts of nerve roots were sectioned. CONCLUSION: The number of rootlets with palpable abnormal and hyperactive responses elicited by intraoperative stimulation reflects the preoperative spasticity of multiple muscles. This implies that only selecting rootlets with palpable responses can be reliable. Because more sectioning leads to better spasticity resolution, our protocol should be reviewed to increase the percentage of rootlets sectioned with hyperactive responses, especially for innervated levels of severely affected muscles.

Adolescent↗

Epileptogenicity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia.

PURPOSE: Human cortical dysplasia (CD) is a frequent cause of medically intractable focal epilepsy. The neurotransmitter mechanisms of epileptogenicity in these lesions have been attributed to changes in various glutamate receptor subtypes. Increased N-methyl-D-aspartate (NMDA) receptor (NR) 2A/B coassembled with NR1 subunits has been shown in focal epileptic CD. The purpose of this study is to correlate in situ CD epileptogenicity and the expression of various glutamate receptor subtypes. METHODS: The histopathological, morphological, and immunocytochemical findings in cortical tissue resected from five patients with medically intractable epilepsy and CD were correlated with electroencephalographic data recorded from subdural grids. The NMDA antibodies identified subunits NR1 (splicing variants 1a, 1b, 2a, and 2b) and NR2A/B. RESULTS: Epileptogenic specimens displayed the following common features: (a) widespread histological abnormalities of horizontal and columnar dyslamination, neurons with inverted polarity, and more extensive dendritic changes; (b) significantly higher NR2A/B immunoreactivity in both the dysplastic somata and all their dendritic processes; and (c) no statistically significant change in NR1 subunit expression but a more pronounced staining of the apical dendrites in highly epileptogenic cortex. These abnormalities were either absent or minimal in resected specimens that did not show evidence of severe in vivo epileptogenicity. CONCLUSION: These studies provide direct evidence for a major contribution of the NR2A/B subunit in CD-induced epileptogenicity.

Adolescent↗

Postictal in situ MRS brain lactate in the rat kindling model.

OBJECTIVE: To determine the temporal and spatial extent of the lactate (Lact) changes as correlated with seizure characteristics and EEG changes in the rat kindling model. BACKGROUND: Prior studies using MRS have detected cerebral Lact postictally in animal models of seizures and in patients with intractable focal epilepsy. METHODS: We performed MRS in sham control rats (n = 4) and in rats stimulated in the right hippocampus at two different stages of the kindling and at three time points after the seizures: <2 hours (n = 8 and 5, stage 0 and stage 5), 2 to 3 hours (n = 5 and 6), and >3 hours (n = 4 and 2). Lact/creatine (Cr) and N-acetylaspartate (NAA)/Cr ratios were measured in six contiguous voxels (three left, three right) covering the hippocampi, anterior and posterior regions, and compared with EEG and ictal behavior. Lact/Cr ratios were measured at a very low level in the sham control rats and in the >3-hour group. RESULTS: In the <2-hour group, Lact/Cr increase was higher in stage-5 rats as compared with stage-0 rats (p = 0.001, unpaired t-test) and sham control rats when all the voxels were considered. Lact/Cr ratios were higher in the stimulated area as compared with all other brain areas in stage-0 rats (p = 0.05, paired t-test) but not in the stage-5 rats. Similar results with more inter-animal variability were measured in the 2- to 3-hour group. NAA/Cr ratios increased significantly after stage-0 kindling in the stimulated hippocampus but not after stage-5 kindling. CONCLUSIONS: Postictal Lact increase as assayed by MRS correlates with EEG and behavioral seizures and suggests that it would be an additional noninvasive technique for seizure localization during the presurgical evaluation of patients with intractable focal epilepsy.

Animals↗

A short episode of seizure activity protects from status epilepticus-induced neuronal damage in rat brain.

Kainic acid (KA)-induced status epilepticus (SE) in adult rats results in extensive neuronal damage throughout the limbic system and the loss of selectively vulnerable neuronal populations, particularly CA3 neurons. We investigated the effects of a short episode of seizure activity on neuronal death elicited by a subsequent prolonged SE episode. A short episode of seizure activity was produced by sub-cutaneous (s.c.) injection of KA followed after 1 h by pentobarbital administration. Twenty-four hours later, KA was administered again, and animals were sacrificed 3 days later. Neuronal damage was estimated by visual analysis of neuronal density. Our results show that a short episode of seizure activity did not produce neuronal damage but almost completely protected vulnerable neurons from KA-induced neuronal damage. These results extend to epileptic tolerance the notion of tolerance previously described in the case of ischemia.

Animals↗

MRS metabolic markers of seizures and seizure-induced neuronal damage.

PURPOSE: Proton magnetic resonance spectroscopy (MRS) was used to identify specific in situ metabolic markers for seizures and seizure-induced neuronal damage. Kainic acid (KA)-induced seizures lead to histopathologic changes in rat brain. The protective effect of cycloheximide treatment against neuronal damage caused by KA-induced seizures was studied, using in situ proton MRS imaging technique. METHODS: Rats were pretreated with placebo or cycloheximide 1 h before KA injection. Rat brains (n = 25) were scanned at the level of the hippocampus before, during, and 24 h after seizures. Spectra were recorded and the relative ratios of N-acetylaspartate (NAA), choline (cho), and lactate (Lac) to creatine (Cr) were calculated and compared between groups. RESULTS: A significant increase in Lac ratios was observed in KA-treated rats during and 24 h after seizure onset and this increase was prevented by cycloheximide pretreatment. NAA ratios were significantly higher during the ictal phase following KA treatment and this effect was not affected by cycloheximide pretreatment. Nissl staining confirmed previously reported prevention of KA-induced neuronal loss in CA3 and CA1 areas of the hippocampus by cycloheximide pretreatment. CONCLUSIONS: Our results suggest that in situ Lac increase is a marker of seizure-induced neuronal damage, whereas N-acetylaspartate (NAA) changes during and after status epilepticus may be a reflection of neuronal activity and damage, respectively.

Animals↗

Temporal changes in proton MRS metabolites after kainic acid-induced seizures in rat brain.

PURPOSE: In situ 1H-magnetic resonance spectroscopy (MRS) was used to study temporal metabolic changes in a rat model of temporal lobe epilepsy (TLE) by using kainic acid (KA). METHODS: Rat brains were scanned at the level of the hippocampal body for MRS measurements. Relative ratios of N-acetyl groups (NA: N-acetylaspartate and N-acetylaspartyl glutamate), choline, and lactate (Lac) over creatine (Cr) were calculated. RESULTS: NA/Cr ratios increased significantly during the ictal phase. During the postictal and interictal phases, the NA/Cr ratio decreased. There was a significant and prolonged increase of the lactate/Cr ratio in the hippocampi of rats that started 1 h after the onset of KA-induced seizure activity and persisted up to 24 h after the injection. The prolonged lactate/Cr increase in an area susceptible to neuronal damage (e.g., hippocampus) correlated with the onset of seizure activity but remained elevated thereafter. CONCLUSIONS: The ictal and early postictal increase in lactate ratios may reflect increased cellular activity and metabolism resulting from KA excitotoxicity. Assuming that the changes in NA/Cr ratios are due to NAA increase, we speculate that an activation of the N-acetylaspartylglutamate (NAAG) dipeptidase pathway may explain the ictal increase in NA/Cr ratios. The late postictal decrease in NA/Cr ratios is a reflection of KA-induced neuronal cell loss.

Animals↗

Mesial temporal sclerosis. A clinicopathologic study of 27 patients, including 5 with coexistent cortical dysplasia.

OBJECTIVE: Mesial temporal sclerosis (MTS) is a fairly well-recognized cause of intractable epilepsy. Its coexistence with cortical dysplasia is less commonly described. Herein, we describe the clinical and pathologic features of MTS, including cases in which cortical dysplasia was also identified. DESIGN: Retrospective surgical series of 27 patients. SETTING: Tertiary referral center with a high volume of epilepsy surgery. PATIENTS: Patients with medically intractable epilepsy who underwent hippocampal resections and in whom an unequivocal histologic diagnosis of MTS could be made. RESULTS: The patients studied included 18 males and 9 females ranging in age from 15 to 48 years (mean 32 years). Mesial temporal sclerosis was characterized by severe neuronal loss accompanied by gliosis occurring in the CA1/prosubiculum (27 patients, 100%), focally in the dentate gyrus (12 patients, 44%), and in the CA4 region (11 patients, 41%). Five patients (24%) had coexistent cortical dysplasia with increased molecular layer neurons (five patients), gyral fusion (two patients), diffuse architectural disorganization of the cortex (one patient), and clusters of atypical neurons and glial cells within the cortex (one patient). Twenty-five (93%) of the 27 patients had white matter neuronal heterotopia. Follow-up data were available for each patient (mean 23 months). Twenty-two of the patients are free of seizures postoperatively, including all five with coexistent cortical dysplasia; the five remaining patients have fewer seizures. There appeared to be no difference clinically between patients with MTS and no dysplasia and those with coexistent cortical dysplasia. CONCLUSION: We conclude that (1) MTS most severely involves the CA1/prosubiculum and CA4 regions of the hippocampus (the dentate gyrus may also be focally severely involved); (2) MTS and cortical dysplasia do occasionally exist; and (3) surgical outcome for MTS appears to be independent of coexistent cortical dysplasia.

Adolescent↗