Biomedical subjects
I Drury
Publications and source records attributed to I Drury.
Seizures induced by intracerebral injection of thrombin: a model of intracerebral hemorrhage.
The coagulation cascade plays an important role in brain edema formation caused by intracerebral blood. In particular, thrombin produces brain injury via direct brain cell toxicity. Seizures and increased cerebral electrical activity are commonly associated with intracerebral blood and are possible effects of thrombin leading to cell injury in the brain. In this study, artificial clots containing concentrations of thrombin found in hematomas were infused intracerebrally in rats. The animals were observed clinically for seizure activity, behavior, and neurological deficits. Several animals underwent video electroencephalographic (EEG) monitoring during intracerebral infusion and for 30 minutes postinfusion. All animals were killed 24 hours after injection, and brain water and ion contents were measured to determine the amount of brain edema. Clinically, thrombin produced focal motor seizures in all animals. None of the control animals or those receiving N[alpha]-(2-Naphthalenesulfonyl-glycyl)-4-amidino-DL-phenylalanine -piperidide (alpha-NAPAP), a thrombin inhibitor added to the thrombin, showed clinical evidence of seizures. Of the rats undergoing EEG monitoring, all animals receiving thrombin showed electrical evidence of seizure activity, whereas none of the control animals exhibited seizure activity. There was no evidence of seizure activity on EEG monitoring when alpha-NAPAP was injected along with the thrombin. In addition, the artificial clots containing thrombin produced agitation and a circling tendency in the rats, along with brain edema. These results indicate that the coagulation cascade is involved in seizure production and increased brain electrical activity, which contribute to the neurological deficits and brain edema formation that are seen with intracerebral hemorrhage.
Intracerebral depth electrode monitoring in partial epilepsy: the morbidity and efficacy of placement using magnetic resonance image-guided stereotactic surgery.
OBJECTIVE: To determine the indications for, efficacy of, and safety of depth electrode placement using magnetic resonance imaging (MRI)-guided stereotactic surgery in patients with intractable epilepsy. METHODS: We analyzed retrospectively the results of depth electrode usage in 50 consecutive patients at the University of Michigan Hospitals studied in the years 1991 through 1994, using MRI-guided stereotactic implantation, in conjunction with simultaneous subdural strip electrode recordings. RESULTS: There were no deaths, no infections, and no new neurological deficits. One small subdural hematoma adjacent to a subdural strip electrode was evacuated to prevent interference with ictal recording. Two cylindrical subdural electrodes were found to be intraparenchymal, as revealed by postoperative MRI, and were removed. One patient was unintentionally left alone briefly, and he pulled out the electrodes while confused postictally, requiring a subsequent operation for replacement. Ictal onset zones were successfully localized in 47 patients. CONCLUSION: We have found intracerebral electrode placement to be as safe as subdural strip electrode placement and have found combined depth and strip electrode monitoring to be highly effective in localizing the onset zones of complex partial seizures. Intracranial monitoring was particularly useful in the detection of a single ictal onset zone in the absence of neuroimaging abnormality and in the definitive diagnosis of bilateral independent ictal onset zones in the temporal lobe epilepsy syndrome. The specific technical aspects of the procedure that contribute to a successful outcome are reviewed. A comparison with earlier reported series suggests that MRI-guided stereotaxy and pial inspection may reduce complications of depth electrode placement.
The gene for progressive myoclonus epilepsy of the Lafora type maps to chromosome 6q.
Progressive myoclonus epilepsy of the Lafora type (Lafora's disease) is an autosomal recessive disease characterized by epilepsy, myoclonus, dementia, and periodic acid-Schiff-positive intracellular inclusion bodies. The inclusion deposits consist of branched polysaccharides (polyglucosans) but the responsible biochemical defect has not been identified. Onset is during late childhood or adolescence and the disease leads to a fatal outcome within a decade of first symptoms. We studied nine families in which Lafora's disease had been proven by biopsy in at least one member. In order to locate the responsible gene, we screened the human genome with microsatellite markers spaced an average of 13 cM. We used linkage analysis in all nine families and homozygosity mapping in four consanguineous families to define the Lafora's disease gene region. Two point linkage analysis resulted in a total peak lod score of 10.54 for marker D6S311. Six additional chromosome 6q23-25 microsatellites yielded lod scores ranging from 5.92 to 9.60 at theta m = f = 0. An extended pedigree with five affected members independently proved linkage with peak lod scores over 3.8 at theta m = f = 0 for D6S292, D6S403, and D6S311. The multipoint one-lod-unit support interval covered a 2.5 cM region surrounding D6S403. Homozygosity mapping defined a 17 cM region in chromosome 6q23-25 flanked by D6S292 and D6S420 that contains the Lafora's disease gene.
Asymmetric hypsarrhythmia: clinical electroencephalographic and radiological findings.
Twenty-six children (16 boys and 10 girls) with hypsarrhythmia and infantile spasms (IS) were studied at the University of Michigan EEG Laboratory in a 4-year period. Six (2 boys, 4 girls), had asymmetric hypsarrhythmia with a preponderance of both slowing and epileptiform activity over one hemisphere. All 6 had the symptomatic form of IS, 4 with dysplastic conditions, 1 with porencephaly from a cerebral infarct, and 1 with hypoxicischemic encephalopathy. Five children had focal abnormalities on either physical examination or imaging studies. Four had the highest amplitude slowing and most epileptiform activity ipsilateral to the lesion, in 1, it was contralateral. Asymmetric hypsarrhythmia constituted 23% of cases with hypsarrhythmia examined at our EEG laboratory. The significant success in surgical therapy for some children with IS indicates the importance of identifying focal hemispheric abnormalities even if they are not apparent clinically. EEG may suggest focal changes not detected clinically or radiologically.
Biopsy results in a kindred with Lafora disease.
We studied biopsy results in a kindred with the Lafora form of progressive myoclonic epilepsy. Four members of a family with known consanguinity presented as teenagers with seizures, myoclonus, dementia, and ataxia. After the diagnosis was established by brain biopsy in the first patient, many efforts were made to obtain a tissue diagnosis in the three other patients. Lafora bodies were absent in most of the skin biopsy specimens in three patients and in liver biopsy specimens from two patients. In cases of Lafora disease, where a reasonably certain clinical diagnosis can be established, supported by biopsy proof in some family members, repeated biopsy specimens even at advanced stages of the disease may be negative. These findings suggest that negative skin or liver biopsy specimens in patients with progressive myoclonic epilepsy should not exclude the diagnosis of Lafora disease.
Ictal patterns in generalized epilepsy.
Ictal EEG may be of great benefit in facilitating accurate classification of the underlying seizure disorder in some patients and thus guiding further investigation and management. Ictal recordings in patients with generalized epilepsies are protean in their manifestations and yet may have considerable overlap. Classification is only possible through careful synthesis of all available clinical and electrophysiological data. Although the underlying pathophysiological mechanisms of the generalized epilepsies remain uncertain, evidence from EEG recordings tends to support Gloor's concept of corticoreticular epilepsy.
Correlation of evoked potential and MRI findings in Wilson's disease.
We recorded brainstem auditory evoked potentials (BAEPs) and somatosensory evoked potentials to median nerve stimulation (MSEPs) within 10 days of brain MRI in 20 patients with Wilson's disease (WD). MRI was abnormal in 90% of patients, demonstrating symmetric striatum and brainstem lesions with or without thalamic lesions. MSEPs were abnormal in 65% of patients, usually showing bilaterally prolonged N/P13-N20 latencies. BAEPs were abnormal in 40%, most often with bilateral prolongation of the III-V latency. The III-V and N/P13-N20 interpeak latencies correlated significantly with the severity of MRI lesions in the caudal pons, rostral pons, and caudal midbrain. Our results indicate that subclinical sensory dysfunction is common in WD, and that auditory and somatosensory pathways are most severely affected at the brainstem level. Both the localization and severity of evoked potential abnormalities correspond closely to the morphologic changes in the pons and caudal midbrain shown by MRI.
Pitfalls of EEG interpretation in epilepsy.
Electroencephalogram remains the single most valuable investigation in patients with known or suspected seizure disorders. Errors made in the interpretation of electroencephalogram studies are common and have significant consequences for the patient. This article presents a logical approach to the analysis of electroencephalograms, illustrating the principle pitfalls in each step of this analysis.
Seizure disorders of aging: differential diagnosis and patient management.
The incidence of seizures increases significantly after age 60, mainly because of an associated rise in the prevalence of such etiologies as stroke, brain tumors, and toxic-metabolic disturbances, including alcohol or drug misuse and diabetes. The differential diagnosis must rule out transient ischemic attacks, syncope, and psychiatric disorders, among other conditions. Treatment is based on the underlying cause. Seizures caused by toxic-metabolic disturbances are treated by correcting the underlying condition. Those with other etiologies require single-drug therapy with an anticonvulsant, such as phenytoin, valproic acid, or carbamazepine.
Unilateral 14 and 6 Hz positive bursts.
We describe the unilateral occurrence of 14 and 6 Hz positive bursts in successive EEGs in a 25-year-old woman following surgical resection of a left parietal arteriovenous malformation which had caused a left parieto-temporal intracerebral hematoma. This is only the second reported case of unilateral 14 and 6 Hz positive bursts. This could represent either a normal pattern seen unilaterally because of a skull defect or be a manifestation of neuronal damage.
Myoclonus in adult Huntington's disease.
Two brothers with clinically definite adult Huntington's disease developed disabling myoclonus years after the first signs of the disease. Their electroencephalograms were consistent with a primary generalized epilepsy, although neither man had seizures. The myoclonus was controlled with valproic acid therapy.
Variance of interburst intervals in burst suppression.
Each EEG performed over a 3 year period at the University of Michigan with a diagnosis of generalized burst-suppression (BS) was reviewed. Ten EEGs from 10 patients with hypoxic-ischemic encephalopathy (HIE-BS) and 21 records from 8 patients with pentobarbital induced burst-suppression for treatment of status epilepticus (SE-BS) were reviewed. For each EEG, the mean duration of 40 interburst intervals (IBIs) as well as their coefficient of variability were calculated. We found that in the SE-BS group the coefficient of variability of IBI duration was highly correlated with the logarithm of mean IBI duration while in the HIE-BS group, there was no significant correlation between these 2 variables. This suggests that the underlying mechanism causing BS is different in the 2 groups and might be related to a uniform and progressive affection of similar brain structures in the SE-BS group and a more patchy and variable pathology in the HIE-BS group.
Triphasic waves in coma from brainstem infarction.
There have been reports on patients in stupor or coma from a variety of disorders that affect the brain diffusely, notably hepatic failure, whose EEGs showed triphasic waves. We describe a patient in coma with neurologic signs localizing to the brainstem who had triphasic waves on EEG. This case further confirms the nonspecific nature of triphasic waves.
Allele-specific sequencing confirms novel prion gene polymorphism in Creutzfeldt-Jakob disease.
We analyzed the prion protein coding sequence in a familial Creutzfeldt-Jakob disease patient who did not have any of the currently recognized prion protein mutations. Denaturing gradient gel electrophoresis indicated that the prion protein coding sequence was heterozygous at least one location. We isolated each allele by denaturing gradient gel electrophoresis and directly sequenced. We found a DNA polymorphism at codon 178 that predicted the amino acid substitution, aspartate----asparagine. Whether this represents a benign polymorphism or pathogenic mutation will depend on analysis of the functional consequences of this change. Denaturing gradient gel electrophoresis and allele-specific sequencing proved to be efficient means of analyzing sequence polymorphisms in this gene.
Felbamate for partial seizures: results of a controlled clinical trial.
Felbamate (2-phenyl-1,3-propanediol dicarbamate) has a favorable preclinical profile in animal models of epilepsy. We present the results of a double-blind, randomized, placebo-controlled clinical trial in patients with partial seizures. Criteria for entry included a requirement for four or more partial seizures per month despite concomitant therapeutic blood levels of phenytoin and carbamazepine. Fifty-six patients (mean age, 31.4 years; 32 men, 24 women) completed the trial. The mean seizure frequencies for the 8-week periods analyzed were felbamate = 34.9, placebo = 40.2. Felbamate was statistically superior to placebo in seizure reduction, percent seizure reduction, and truncated percent seizure reduction. The mean felbamate dosage was 2,300 mg/d. Plasma felbamate concentrations ranged from 18.4 to 51.9 mg/l, mean = 32.5 mg/l. Adverse experiences during felbamate therapy were minor and consisted primarily of nausea and CNS effects. This trial indicates that felbamate is safe and effective in the treatment of comedicated patients with severely refractory epilepsy.
Familial Creutzfeldt-Jakob disease without periodic EEG activity.
Four members of a kindred with Creutzfeldt-Jakob disease are reported, in whom myoclonus did not develop and in whom serial electroencephalograms performed late in their illness failed to show periodic sharp wave complexes. Otherwise, the patients' disease duration, clinical features, and neuropathological findings were similar to those described in sporadic cases of Creutzfeldt-Jakob disease. Our findings and those reported by others suggest that periodic electroencephalographic activity may be rare in familial forms of Creutzfeldt-Jakob disease, as it is in other slow transmissible encephalopathies.
Epileptiform abnormalities during sleep in Rett syndrome.
We recorded all-night electroencephalograms (EEGs)/polysomnograms on 2 consecutive nights from 4 children (ages 4-11 years) with Rett syndrome. The first 10 sec of each 60 sec epoch were analyzed with counts of left and right hemisphere spikes and correlated with sleep stage. Spike counts were lowest during wakefulness. Spikes were most frequent over parasagittal regions during all sleep stages and varied from 0.28 +/- 0.03 to 40.4 +/- 0.7 (mean +/- S.E.M.) spikes/hemisphere/min. Spike counts were 51-109% higher during NREM sleep than during REM sleep. In 3 of 4 subjects, spikes were most frequent during light NREM sleep. Spikes increased in frequency during the second half of the night. We conclude that in Rett syndrome, epileptiform activity is maximally expressed in stage 1-2 NREM sleep and during the early morning hours. Sleep EEG features may be useful in the diagnosis of Rett syndrome.