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R Morawetz

Publications and source records attributed to R Morawetz.

At least 19 recordsLinked to original sources
PubMed1997

Supplementary sensorimotor area epilepsy. Seizure localization, cortical propagation and subcortical activation pathways using ictal SPECT.

We studied clinical signs, EEGs and ictal cerebral blood flow by single-photon emission computed tomography (SPECT) in eight patients with intractable supplementary sensorimotor area (SSMA) seizures. SPECT scans were performed after injection of the regional cerebral blood flow tracer [99mTc]HMPAO (hexametylpropylene amine oxime) early in the ictal phase (2-5 s after seizure onset). Ictal SPECT demonstrated unilateral predominance of hyper-perfusion of the SSMA in all patients, concordant with either lateralizing clinical signs, lateralization of ictal scalp EEG or with the site of ictal onset of seizures, obtained from intracranial electrodes. Two distinctive cortical blood-flow propagation patterns were identified in SSMA seizures. The type I pattern consisted of primary involvement of the ipsilateral SSMA and dorsal premotor and motor cortex. The type II pattern consisted of bilateral but asymmetric mesial frontal propagation. Ictal contraversive head and eye movements were associated with a type I propagation pattern (P < 0.03). Activation of subcortical structures led to variable hyper-perfusion of the basal ganglia and thalamus. Contralateral cerebellar hyperperfusion was observed in all cases. We conclude that ictal SPECT is a useful method for seizure localization in patients with SSMA epilepsy. The observed heterogeneity of clinical features in SSMA epilepsy correlates with propagation to, and activation of, specific cortical structures, and is consistent with known anatomical interconnections between the SSMA, ipsilateral cortical and transcallosal cortical structures.

Adolescent↗
PubMed1997

Occipital lobe developmental malformations and epilepsy: clinical spectrum, treatment, and outcome.

PURPOSE: Cortical developmental malformations (CDM) are increasingly recognized in association with epilepsy. We describe 10 patients (age range 14-35 years) with symptomatic occipital lobe epilepsy and CDM. METHODS: Neurologic, neuroophthalmologic and electrophysiologic studies were performed. Patients had MRI, SPECT, and in some cases intracranial EEG investigators. RESULTS: Mean age of seizure onset was 8 years. We noted strong correlations between the presence of visual auras, the scalp EEG pattern, and the subtype of underlying pathology. Magnetic resonance imaging (MRI) showed CDM in all patients, with polymicrogyria and focal dysplasia being the most frequent malformations. Despite the presence of occipital lobe structural malformations in all patients, visual field deficits were present in only 2. Those who underwent cortical resections were seizure-free or showed major improvement at a mean follow-up of 3.5 years. CONCLUSIONS: Intracranial stimulation studies and the low frequency of pre- and postoperative deficits suggest that some degree of cortical visual reorganization may occur in patients with occipital lobe malformations. Occipital lobe CDM should be sought as a cause of symptomatic occipital lobe epilepsy even though they may become symptomatic after childhood.

Adolescent↗
PubMed1997

Proton spectroscopic imaging at 4.1 tesla in patients with malformations of cortical development and epilepsy.

We used proton magnetic resonance spectroscopic imaging (MRSI) at 4.1 tesla in patients with malformations of cortical development (MCDs) and epilepsy. We compared the spectroscopic results with normative data using 2 SDs (95% confidence) above normal values for detection of significant abnormalities for creatine-N-acetylated compounds (Cr/NA) ratio and choline-N-acetylated compounds (Cho/NA). The results were correlated with clinical, EEG, and histologic findings. Patients with focal cortical dysplasia showed significant metabolic abnormalities in correspondence with the structural lesions, whereas patients with heterotopia and polymicrogyria demonstrated no subcortical MRSI abnormalities. Significant correlations were found between the metabolic abnormalities and the frequency of seizures but not with the degree of interictal EEG discharges. Quantitative neuronal and glial cell counts revealed no statistically significant correlation between cell loss and the abnormal metabolic ratios in those who underwent surgery. These preliminary findings suggest that MRSI-based metabolic abnormalities in patients with MCDs are variable and are likely to be associated with complex cellular mechanisms involving the regulation of NA, total Cr content, and Cho.

Acetylation↗
PubMed1997

Epilepsy surgery outcome: comprehensive assessment in children.

The effect of extratemporal and temporal lobe cortical resection on children with intractable epilepsy is not well understood. We evaluated a comprehensive array of outcome variables in 33 consecutive children who received epilepsy surgery at 12 years of age or younger. Twenty-two (67%) children were seizure-free, three (9%) had a greater than 90% reduction in seizures, and four had no improvement. Antiepileptic drugs (AEDs) were not required in 10 (30%) children and were reduced in number in another 10. Six (29%) of 21 tested children had an improvement of greater than 10 points in Verbal or Performance IQ after surgery, while one (4%) had a decrease greater than 10 points in Verbal IQ. One mild hemiparesis and one inferior quadrantanopsia occurred; both were anticipated. We used the Child Health Questionnaire (CHQ), a valid and reliable instrument for children, to assess health-related quality of life (HRQOL). Six of 12 subscale scores of the CHQ were significantly lower in the surgical group compared with 410 age-matched control subjects. Parents were satisfied with surgical results in 28 (85%) cases. Pathologic tissue diagnosis and site of resection were not associated significantly with any outcome measure. We conclude that surgery eliminates seizures and reduces AED requirements in most children with intractable epilepsy selected by currently available methods. Further investigation is needed to establish the nature and significance of inferior scores in the surgical group in the HRQOL domains of physical function, general health, and self-esteem.

Adolescent↗
PubMed1996

Cytokine-dependent modulation of oral tolerance in a murine model of autoimmune uveitis.

In summary, our data suggest that oral tolerance in the mouse EAU model may occur by anergy/deletion or by suppression, depending on the feeding regimen. Tolerance involving putative regulatory cells appears to require the ability to produce both IL-4 and IL-10, whereas induction of tolerance involving anergy may not require the presence of Il-4 and IL-10. We propose that regulatory cells induced by three feedings of IRBP can be selectively enhanced through the use of cytokines. From the point of view of clinical therapy, it would be worthwhile to explore postimmunization feeding regimens involving administration of IL-4 and IL-10.

Administration, Oral↗
PubMed1996

Cloning and characterisation of genes (pkc1 and pkcA) encoding protein kinase C homologues from Trichoderma reesei and Aspergillus niger.

Oligonucleotides, designed on the basis of conserved flanking amino acid sequence segments within the catalytic domain of eukaryotic protein kinase C (PKC) proteins, were used as primers for polymerase chain reactions to amplify a 427-bp chromosomal DNA fragment from the filamentous fungus Trichoderma reesei. This fragment was then used to isolate genes encoding PKC homologues of T. reesei and Aspergillus niger (pkc1 and pkcA, respectively). The genes contain six (T. reesei) and eight (A. niger) introns, which exhibit notable conservation in position with those found in the corresponding Schizosaccharomyces pombe pkc1+ and Drosophila melanogaster dPKC53Ebr genes. A single 4.2-kb transcript was detected in Northern analyses. The deduced PKC1 (T.reesei, 126 kDa) and PKCA (A. niger, 122 kDa) amino acid sequences reveal domains homologous to the C1 and C3/C4 domains of PKC-related proteins, but lack typical Ca(2+)-binding (C2) domains. Both contain a large, extended N-terminus, which shares a high degree of similarity with the corresponding regions of Saccharomyces cerevisiae PKC1 and S. pombe pkc1+ and pkc2+ proteins, but which is not present in PKCs of Dictyostelium or higher eukaryotes. This extended region can be divided into three subdomains; the N-terminal one contains a hydrophobic helix-turn-helix motif, whereas the C-terminal one contains potential targets for proteolytic processing. A polyclonal antiserum raised against the pseudosubstrate-binding domain of PKC1 recognizes in T. reesei a 115-120 kDa protein in Western blots. Expression of pkc1 cDNA in insect cells directs the synthesis of a PKC1 protein of similar size. The T. reesei PKC1 protein was partially purified and some of its properties examined: it is stimulated about twofold by phospholipids or phorbol esters but is not stimulated by Ca2+. We conclude that these PKC proteins from filamentous fungi represent the Ca(2+)-insensitive fungal homologues of the nPKC family.

Amino Acid Sequence↗
PubMed1996

Qualitative MRI segmentation in mesial temporal sclerosis: clinical correlations.

Magnetic resonance imaging (MRI) is reliable and sensitive in the detection of mesial temporal atrophy in patients with temporal lobe epilepsy. We investigated the MRI patterns of atrophy in 47 patients with histologically confirmed hippocampal sclerosis and correlated the imaging findings to the clinical features and surgical outcome. One hundred percent of patients had hippocampal body atrophy, 70% had hippocampal tail atrophy, 23% had amygdala atrophy, and 10% had focal hippocampal body atrophy without other segmental involvement. Correlative analysis of the segmented MRI findings with other clinical variables, including a previous history of childhood febrile convulsions, showed no significant associations except for younger age of seizure onset associated with hippocampal tail atrophy (p <0.03). No associations between surgical outcome and the patterns of mesial temporal atrophy were detected. Our results demonstrate that variable patterns of atrophy exist in mesial temporal atrophy, but invariably atrophy involves the hippocampal body segment. Segmental MRI analysis in mesial temporal atrophy provides added useful diagnostic information.

Adolescent↗
PubMed1995

Proton nuclear magnetic resonance spectroscopic imaging of human temporal lobe epilepsy at 4.1 T.

We performed proton magnetic resonance spectroscopic imaging (MRSI) at high magnetic field (4.1 T) to study N-acetylaspartate, creatine, and choline levels in the brains of normal control subjects and patients with intractable temporal lobe epilepsy. We compared the results of MRSI to those of other presurgical techniques to determine the sensitivity of this method in the lateralization of the epileptic focus. The normal hippocampal creatine-N-acetylaspartate ratio was 0.71 +/- 0.14 with no differences between left and right. Using the mean control hippocampal creatine-N-acetylaspartate ratio plus 2 standard deviations to identify statistically significant changes, we found lateralizing metabolic abnormalities corresponding to the operated temporal lobe in all patients. Four patients (40%) had contralateral abnormalities, and 2 of them had bilateral independent seizure onset confirmed by intracranial electroencephalographic studies. Statistically significant increases in the choline-N-acetylaspartate ratio in comparison to healthy volunteers were observed in 8 of the 10 patients. With the creatine-N-acetylaspartate ratio, MRSI demonstrated a 100% sensitivity compared to magnetic resonance imaging, which identified pathology in 70% of the patients. These findings suggest that proton MRSI yields a distinctive metabolic profile in patients with temporal lobe epilepsy and is sensitive in detecting bilateral metabolic abnormalities in some patients. These preliminary findings suggest that MRSI is more sensitive than magnetic resonance imaging in the lateralization of epileptic foci in temporal lobe epilepsy.

Adult↗
PubMed1995

Frontal and central lobe focal dysplasia: clinical, EEG and imaging features.

The authors studied 11 patients with developmental malformations and seizures originating from the frontal and central regions. Patients with centrally located seizures had primary involvement of the face or mouth; clonic activity involving the limb was also seen. Seizures among those with frontal lesions were primarily unilateral or bilateral tonic motor. Secondary generalized tonic-clonic seizures preceded by focal manifestations occurred infrequently in those with central localization, but were not rare in the frontal group. MRI revealed abnormalities in 10 patients, nine of whom underwent surgical resection with good results. Focal cortical dysplasia may be the underlying epileptogenic abnormality in young patients with clinical features suggestive of central or frontal cortical involvement.

Adolescent↗
PubMed1994

A protein kinase-encoding gene, pkt1, from Trichoderma reesei, homologous to the yeast YPK1 and YPK2 (YKR2) genes.

A gene (pkt1) was isolated from the filamentous fungus Trichoderma reesei, which exhibits high homology with the yeast YPK1 and YKR2 (YPK2) genes. It contains a 2123-bp ORF that is interrupted by two introns, and it encodes a 662-amino-acid protein with a calculated M(r) of 72,820. During active growth, pkt1 is expressed as two mRNAs of 3.1 and 2.8 kb which differ in the 3' untranslated region due to the use of two different polyadenylation sites.

Amino Acid Sequence↗
PubMed1993

Predictive value of magnetic resonance imaging in temporal lobe epilepsy surgery.

The predictive value of magnetic resonance imaging (MRI) was assessed by a prospective study of 34 patients selected for surgical treatment of temporal lobe epilepsy. The MRIs were interpreted using standardized visual diagnostic criteria and the imaging findings were correlated with the surgical outcome. Lateralized MRI abnormalities were found in 25 (74%) of 34 patients. Significant associations were found between either the presence of a restricted foreign-tissue lesion or hippocampal atrophy and an excellent surgical outcome. An abnormal MRI had an 82% predictive value and a normal MRI had a 56% predictive value for surgical success. A history of febrile convulsions and the presence of hippocampal atrophy best predicted outcome (predictive value, 86%). These results suggest that specific MRI findings in candidates for temporal lobe epilepsy surgery are predictive of surgical outcome. The information provided by MRI may be of value for counseling patients prior to surgical intervention.

Adolescent↗
PubMed1993

Ictal single-photon emission computed tomography demonstrates localized epileptogenesis in cortical dysplasia.

We investigated the use of ictal single-photon emission computed tomography (SPECT) in 2 children with intractable epilepsy. Ictal scalp electroencephalographic studies failed to localize the epileptic focus and interictal data demonstrated widespread lateralized abnormalities. Ictal SPECT studies with technetium 99m-hexamethylpropyleneamineoxime demonstrated focal areas of hyperperfusion in the frontal lobes. Resection of the abnormal areas shown by SPECT was carried out despite evidence of large areas of epileptogenesis demonstrated by scalp and subdural electroencephalographic studies. Pathological material revealed cortical dysplasia. Ictal SPECT provides functional evidence for localized epileptogenesis in focal cortical dysplasia.

Cerebral Cortex↗
PubMed1993

Randomized comparison of diaziquone and carmustine in the treatment of adults with anaplastic glioma.

PURPOSE: We conducted a phase III trial comparing intravenous (IV) diaziquone (AZQ) and carmustine (BCNU) as single agents in patients with cerebral anaplastic gliomas who had received surgery and radiotherapy. Its purpose was to compare the efficacy of AZQ with that of BCNU, the standard agent for brain tumor chemotherapy. PATIENTS AND METHODS: Randomization between the two regimens occurred 8 weeks after completion of radiotherapy. A total of 251 patients were randomized to receive either AZQ or BCNU, and there were no significant differences between the two treatment arms in any of the known prognostic variables, including age, histologic grade, and Karnofsky performance status (KPS). RESULTS: There was no significant difference in either time to tumor progression or survival between the two treatment arms. Age and histology were strong predictors of outcome, whereas KPS had relatively less effect. Three groups of patients with distinctly different outcomes could be identified: (1) older age (45+) and glioblastoma/gliosarcoma (GBM/GS) patients had a median survival of 37 weeks after randomization; (2) patients with either older age or GBM/GS had a median survival of 61 weeks; and (3) younger age (< 45) and non-GBM/GS (usually anaplastic astrocytoma) patients had a median survival of 147 weeks. Toxicity was primarily hematologic, although acute gastrointestinal toxicity and chronic pulmonary toxicity were more common with BCNU. Patients randomized to AZQ who had significant hematologic toxicity that required dose reduction after the first treatment cycle had significantly longer time to tumor progression and survival than those who did not require dose reduction (P = .011 and .016, respectively). CONCLUSION: There was no significant difference in efficacy between AZQ and BCNU in patients with anaplastic gliomas as tested in this study, although AZQ was somewhat better tolerated.

Adult↗
PubMed1993

Magnetic resonance imaging in childhood intractable partial epilepsies: pathologic correlations.

We conducted a retrospective single-blind study assessing the value of MRI in 44 children surgically treated for partial epilepsy, and correlated the MRI findings with the pathology in all cases. MRI revealed abnormalities in concordance with the clinical and electroencephalographic data in 84% of patients. Developmental neuronal migration pathology was present in 25% of patients and was relatively more common in the sensorimotor cortex. There was hippocampal sclerosis in 50% of patients with temporal lobe resection; however, only two of the 10 children with hippocampal sclerosis were below the age of 12 years. Similarly, ganglio-glial tumors were more common than astrocytomas in children below age 12. These results indicate that MRI is sensitive in the detection of pathologic abnormalities in most pediatric candidates for epilepsy surgery, and that the distribution and type of pathology appear to be age related in this population.

Adolescent↗
PubMed1992

Lyme neuroborreliosis manifesting as an intracranial mass lesion.

Lyme neuroborreliosis is one of the chronic manifestations of Lyme disease and is caused by the neurotropic spirochete, Borrelia burgdorferi. Two of the three stages of Lyme disease potentially involve the central nervous system: a second stage that may manifest as meningitis, cranial neuritis, or radiculoneuritis; and a third stage, or chronic neuroborreliosis, with parenchymal involvement. The tertiary stage may mimic many conditions, including multiple sclerosis, polyneuropathy, viral encephalitis, brain tumor, vasculitis, encephalopathy, psychiatric illness, and myelopathy. We report a 10-year-old child with signs, symptoms, and radiological manifestations of intracranial mass lesions, without previously recognized manifestations of Lyme disease. This proved to be Lyme neuroborreliosis, documented by histological and serological examination, which responded well to antibiotic therapy. The need to establish a tissue diagnosis of intracranial mass lesions is emphasized, and the utility of a computed tomographic-guided stereotactic system for this purpose is discussed.

Biopsy↗
PubMed1990

Surgical treatment of epilepsy: initial results based upon epidural electroencephalographic recordings.

We describe our initial results in 50 consecutive patients who had investigation for possible surgical treatment of intractable focal epilepsy. Forty-three were investigated using intracranial epidural or foramen ovale electrodes. Forty-five had cortical resection (43 temporal, one frontal, and one parietal). Thirty-two patients who had resection have been followed up for 6 months to 4 years, and 29 (90%) have had good results. Our findings suggest that epidural recordings are valuable in patients with epilepsy who are being considered for surgical resection. They offer an alternative to depth intracerebral investigations in the majority of patients.

Adolescent↗
PubMed1990

[Infusion or repetitive bolus injection? A clinical study of midazolam/fentanyl and diazepam/fentanyl combination anesthesia in neurosurgical operations].

The objectives of this study were to compare two narcotic/benzodiazepine combinations given either as continuous infusion or intermittent bolus injections in neurosurgical patients. 24 patients scheduled for elective craniotomy were investigated. They were assigned randomly to four different groups for treatment. Groups 1 and 2 received a combination of midazolam and fentanyl, groups 3 and 4 a combination of diazepam and fentanyl. Anaesthesia was maintained either by continuous infusion (groups 1 and 3) or intermittent bolus injections (groups 2 and 4). At six key intervals cardiovascular variables were compared. Furthermore, total drug dosage requirements were measured and compared. Except for measurement 3 (skin incision), cardiovascular dynamics were not markedly different between bolus and infusion groups. Haemodynamic response to skin incision was less in both bolus groups. Furthermore, the bolus technique revealed a non-significant reduction in total drug dosage requirements in the bolus groups. Our data indicate that for neurosurgical anaesthesia conventional bolus injection of intravenous anaesthetics is superior to continuous infusion with respect to intraoperative haemodynamics. The typically reduced level of pain with short peaks only, characteristic for neurosurgical operations, is one of the factors contributing to these surprising results. Furthermore, the simple method of infusion chosen influences the results decisively. Certain advantages might be achieved by the use of sophisticated pharmacokinetic infusion models. Total drug dosage requirements were reduced in the bolus groups mainly because of the typical anaesthetic requirements of craniotomy, disposing it for bolus technique.

Adult↗