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.

Influence of head trauma on outcome following anterior temporal lobectomy.

BACKGROUND: There is controversy in the literature regarding the importance of risk factors in developing epilepsy and seizure outcome following anterior temporal lobectomy. Some of the existing studies may be biased because of patient selection and limitations in determining predisposition. OBJECTIVE: To investigate the role of risk factors for epilepsy in determining outcome following anterior temporal lobectomy. PATIENTS AND METHODS: We identified 102 patients in a consecutive surgery series for epilepsy from a tertiary center with a minimum of 1-year postoperative follow-up. Risk factors for epilepsy were determined prospectively on at least 3 occasions before anterior temporal lobectomy. Risk factors investigated were a history of febrile convulsions, family history of epilepsy, significant head trauma, history of meningitis, history of encephalitis, or significant perinatal insult. Foreign tissue lesions on magnetic resonance imaging was also included if an anterior temporal lobectomy was performed for presumed dual pathologic findings (hippocampus and lesion). Outcome was determined using Engel's classification. For statistical analysis we used successive logistic regression analysis, chi(2) test, Fisher exact test, and t test. RESULTS: Of the 102 patients, 13 had no identified risk factor for epilepsy, 49 had 1 identified risk factor, and 40 had more than 1. Frequencies were 39 febrile convulsions (15 complex febrile convulsions), 29 head trauma, 22 with lesions seen on magnetic resonance imaging, 12 history of meningitis, 2 history of encephalitis, 19 family history of epilepsy, and 4 perinatal insult. Seventy-one (70%) were classified as Engel's class I, with 56 patients continuously free of seizures at follow-up. Those without risk factor were as likely to be rendered free of seizures following anterior temporal lobectomy as those with a risk factor (P = .27). No risk factor alone or in combination was correlated with complete freedom from seizures following anterior temporal lobectomy, but the presence of head trauma, alone or in combination, was correlated with continued seizures following anterior temporal lobectomy (P = .03; odds ratio, 2.6). Better outcomes were not seen in those with head trauma before the age of 5 years (P = .57). These findings did not change if all those with lesions on magnetic resonance imaging were excluded in the analysis. Those with a history of head trauma were as likely to have pathologic evidence of mesial temporal sclerosis as others (P = .82). CONCLUSIONS: Patients with a history of significant head trauma are less likely to become free of seizures following anterior temporal lobectomy. No other risk factor correlated with a statistically significant greater or lesser chance of freedom from seizures. This information may be used in preoperative counseling of patients.

Non-epileptic seizures in temporal lobectomy candidates with medically refractory seizures.

Diagnosis of epileptic seizures is often based on temporal lobe epileptiform abnormalities appearing on interictal EEG, when reported ictal semiologies are consistent with temporal lobe seizures. It is unclear how often such patients have non-epileptic seizures. We studied 145 patients who had temporal interictal EEG spikes and reported ictal semiology characteristic of temporal lobe seizures, with long-term EEG-video-monitoring (LTM) for presurgical evaluation of medically refractory seizures. Nonepileptic seizures were unexpectedly recorded in 12 of these patients (8%). Outcomes after LTM in patients who had both epileptic seizures and nonepileptic seizures demonstrated that the epileptic seizures usually were controlled with medications. Our observations support LTM as useful in diagnosis of non-epileptic seizures in this group of patients. We suggest that ictal recordings always should be performed before epilepsy surgery, in part to avoid unintentional surgical treatment of nonepileptic seizures.

The value of pelvic thrusting in the diagnosis of seizures and pseudoseizures.

We evaluated pelvic thrusting as a potential diagnostic sign and localizing indicator of ictal onset. By reviewing the video-EEG results of patients with temporal lobe epilepsy, frontal lobe epilepsy, generalized epilepsy, and pseudoseizures. Pelvic thrusting occurred in 4% of right and 2% of left temporal lobe epilepsy patients, in 24% of frontal lobe epilepsy patients, and in 17% of patients with pseudoseizures. Pelvic thrusting is relatively common in frontal lobe epilepsy and in pseudoseizures, but also occurs in temporal lobe epilepsy.

Primary intracerebral hemorrhage: impact of CT on incidence.

From 1975-1979, the incidence of primary intracerebral hemorrhage (PIH) increased in Rochester, MN, when compared with a previously decreasing incidence. Judging from patients with PIH who were alert at diagnosis, we estimated that 24% of the hemorrhages in earlier years had been mislabeled as infarction. The 30-day survival rate increased from 8% in 1945-1974 to 44% in 1975-1979. The incidence rate was about 45% higher in patients receiving anticoagulant treatment than in those who did not. The increased incidence rate and improved survivorship were attributed to more frequent identification of small PIH by CT.

An acute syndrome with psychiatric symptoms and EEG abnormalities.

Four patients with abrupt onset of psychosis had prominent periodic EEG abnormalities with diffuse sharp waves. Other laboratory studies, including CSF and CT, were normal. The EEG abnormalities disappeared within 1 to 7 days. Clinical improvement was complete and commenced after the EEG showed improvement. The cause remains obscure, but it seems to be a transient organic disturbance of cerebral function that must be distinguished from primary psychiatric disorders.

Increased secondary generalization of partial seizures after temporal lobectomy.

OBJECTIVE: This study tests the primary hypothesis that secondary generalization of partial seizures is more likely after anterior temporal lobectomy (ATL) than before ATL, and the secondary hypothesis that antiepileptic drug withdrawal accounts for increased generalization of seizures postoperatively. BACKGROUND: The authors observed that some patients had generalized tonic-clonic (GTC) seizures after but not before ATL, by using a new classification of outcome that compares preoperative and postoperative seizure frequencies by seizure type. METHODS: Twenty patients with refractory temporal lobe epilepsy had postoperative GTC seizures or nongeneralizing complex partial (CP) seizures in a consecutive ATL series. All had reduced seizure frequency postoperatively and more than 2 years of follow-up on antiepileptic drugs. The authors calculated a generalization fraction, as (number of GTC seizures)/(number of CP and GTC seizures), for 2 years before and 2 years after surgery. RESULTS: Postoperative generalization fractions were greater than preoperative generalization fractions (Wilcoxon signed-rank test, p < 0.01). Most postoperative GTC seizures were not associated with antiepileptic drug withdrawal, and postoperative GTC seizures were not more associated with drug withdrawal than were postoperative CP seizures. Patients with more than two GTC seizures per year preoperatively were more likely than other patients to have postoperative GTC seizures. CONCLUSIONS: Patients with reduced seizure frequency after ATL have a greater tendency for partial seizures to secondarily generalize postoperatively. This phenomenon is not explained by antiepileptic drug withdrawal.

Postictal nose-rubbing in the diagnosis, lateralization, and localization of seizures.

BACKGROUND: Semiology is very useful in the diagnosis and classification of seizures. Some clinical signs occur primarily with specific localization-related epilepsies. OBJECTIVE: To evaluate postictal nose-rubbing as a potential diagnostic sign and a potential lateralizing or localizing indicator. METHODS: We reviewed presurgical prolonged video-EEG results of 50 consecutive patients with right temporal lobe epilepsy (TLE), 50 consecutive patients with left TLE, 50 consecutive patients with frontal lobe epilepsy, 11 consecutive patients with generalized epilepsy, and 100 consecutive patients with nonepileptic events. Videotapes of all events were reviewed independently by two investigators who were blinded to the results of the monitoring. The episodes of nose-rubbing and the hand with which the patient rubbed the nose were recorded. RESULTS: Nose-rubbing occurred in 25 of 50 (50%) right TLE patients and in 21 of 50 (42%) left TLE patients. Approximately 90% of patients rubbed his or her nose with the ipsilateral hand. Nose-rubbing occurred in 5 of 50 (10%) frontal lobe epilepsy patients. Nose-rubbing was not seen in any patient with generalized epilepsy or nonepileptic events. Postictal nose-rubbing did not occur after secondarily generalized seizures. CONCLUSIONS: Nose-rubbing is an easily observed phenomenon, has high interobserver reliability, and provides useful lateralizing information in patients with TLE. It was less frequently seen in extratemporal lobe epilepsy and was not seen after generalized seizures or nonepileptic events.

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.

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.

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.

The continuing decline in the incidence of stroke.

The incidence of stroke has continued to decline in the population of Rochester, Minnesota, up to the end of the last decade. The rate of occurrence of new episodes of stroke in the period 1975-1979 was only 46% of the equivalent rate during the period 1945-1949. The magnitude of the decline in incidence rates was similar in both sexes, but the timing differed. Females showed a progressive decline beginning early in the period of observation, but most of the decline in males occurred in the last 10 years of the study.

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.

Epileptiform patterns of children.

Infants and children display almost the entire range of interictal and ictal epileptiform patterns, exclusive of those seen in the neonatal period. This paper reviews patterns seen in the idiopathic and secondary forms of epilepsies, both generalized and partial, as well as periodic patterns and benign epileptiform variants as they appear in childhood. The discussion focuses on interictal activities, the abnormalities most commonly seen in the EEG laboratory. Special attention is paid to differential diagnostic features; the distinctions between significant epileptiform patterns and normal background features of the maturing child's EEG can be particularly challenging. A large number of illustrations are provided to demonstrate not only the classic epileptiform patterns but also many of the less typical presentations, since children's EEGs show a greater number of atypical waveforms.

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.

Understanding dynamic state changes in temporal lobe epilepsy.

The authors review their work in applying nonlinear dynamics to predict onset of seizures in patients with medically refractory temporal lobe epilepsy. The underlying mathematical methodology is presented in some detail. To illustrate their approach, they present an extensive discussion of the analysis of preictal data from two seizures of one patient, and from one disease-free subject. They find similar behavior in some nonlinear measures across seizures, which suggests the possibility of forming a robust method of seizure prediction. However, despite clinical and electrographic preictal and ictal similarity, they have also found marked heterogeneity in other nonlinear measures of preictal activity across seizures arising out of stage 2 nonrapid eye movement sleep. The underlying basis for this variation remains uncertain and needs to be the subject of further intense study to gain a better understanding of the dynamic basis of epilepsy. The origin of these heterogeneities may or may not be related to the much larger differences in nonlinear measures between patients and disease-free subjects. To understand these differences, the authors think it is crucial to pay close attention to potentially confounding factors such as behavioral and other state changes, and to study and report in detail the ways in which relevant nonlinear measures behave in the presence of such changes, independent of seizure onset.

Indications and outcome of ictal recording with intracerebral and subdural electrodes in refractory complex partial seizures.

Intracranial electrophysiologic recording has often been used to localize ictal onset zones in presurgical evaluation of refractory complex partial seizures. Specific indications for intracranial ictal monitoring have not been analyzed in detail, however. The authors designed this study to test the utility of intracranial monitoring in specific indications and considered six specific indications for intracranial monitoring. They compared prospectively determined indications and outcomes of chronic intracerebral and subdural electrophysiologic recording in 50 consecutive patients whose ictal onset zones had been inadequately localized with interictal and ictal EEG using extracranial electrodes, magnetic resonance imaging, interictal[18F]fluorodeoxyglucose positron emission tomography, and neuropsychological testing. In 47 patients ictal onset zones were localized with intracranial recordings, leading to resections in 38 patients. Each indication for intracranial monitoring selected a group in which the majority went on to have efficacious epilepsy surgery (5-year follow-up). Definitive diagnosis of bilateral independent ictal onset zones in temporal lobe epilepsy required intracranial ictal EEG. Intracranial EEG localization supported efficacious resection in most patients, despite contradictory or nonlocalizing extracranial ictal EEG and neuroimaging abnormalities. Critical analysis of these specific indications for intracranial monitoring may be useful in multicenter evaluation of these techniques.

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.

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.

EEG abnormalities aid diagnosis of Rett syndrome.

Nine girls with Rett syndrome had 22 electroencephalographic studies performed over 5 years. Nineteen walking tracings demonstrated moderate background slowing. Focal epileptiform activity was observed in 13 studies, 10 of which had bilateral independent foci. Spikes were invariably maximal in central regions, diphasic or triphasic, and of very short duration. In 3 patients, epileptiform activity preceded clinical seizures by up to 2 years. Two children had spontaneous hyperpnea preceding apnea during wakefulness with further background slowing. Video monitoring of 2 children revealed that episodic behavioral changes were not seizures. Ten of 12 sleep recordings had abnormal background activity with absent or rudimentary spindles. Normal activity occurred only in girls younger than 2 1/2 years of age. Epileptiform activity was markedly increased during sleep in 8 tracings in which both wakefulness and sleep were obtained. It was characterized by bilaterally independent and bisynchronous spike-and-wave activity, maximal in parasagittal areas. One patient had bursts of high-voltage slow-wave activity followed by attenuation. No apneic episodes were recorded during sleep. In Rett syndrome, electroencephalographic abnormalities include background slowing, centrally located short-duration spikes, and increased epileptiform activity during sleep. This activity commonly preceded clinical seizures in patients studied at initial presentation.