Safety and Efficacy of Oxcarbazepine: Results of Randomized, Double‐Blind Trials

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90287/1/phco.20.12.152S.35254.pd

Monotherapy Trials with Gabapentin for Partial Epilepsy

The efficacy and safety of gabapentin as monotherapy for treatment of partial onset seizures were evaluated in three large multicenter, double-blind, parallel-group, dose-controlled trials. In the first trial, 275 outpatients with refractory partial epilepsy maintained on stable doses of one or two antiepileptic drugs (AEDs) were switched to gabapentin (GBP) monotherapy at 600 mg, 1200 mg, or 2400 mg daily. Patients were required to exit the 26-week double-blind phase of the study if they experienced worsening of seizure frequency. With respect to time to exit, there was no statistically significant difference among the three groups; only 3% of patients withdrew from the trial because of adverse events. In the second study, 82 hospitalized patients with medically refractory epilepsy were tapered off baseline AEDs and randomly assigned to GBP monotherapy at 300 mg/day or 3600 mg/day. Patients remained in the trial for a maximum of 8 days but had to exit the trial if they experienced one or more exit events. Time to exit was significantly longer in patients in the 3600-mg group (151 h) compared with those in the 300-mg group (85 h) ( p = 0.0001). None of the patients withdrew from the trial because of side effects. In the third study, 292 patients with newly diagnosed partial seizures were randomized to GBP 300, 900, or 1800 mg/day or to carbamazepine (CBZ) 600 mg/day. Patients remained in the trial for up to 6 months or until they experienced an exit event. Mean time to exit was significantly longer for patients who received GBP 900 mg/day ( p = 0.02) or 1800 mg/day ( p = 0.04) compared with those who received 300 mg/day. The completion rate for the CBZ group (37%) was similar to that of the GBP 900-mg (39%) and 1800-mg (38%) groups. Patients receiving CBZ had a higher withdrawal rate because of adverse events compared with the GBP 900-mg and 1800-mg groups. The results of these trials provide good evidence of the efficacy and safety of GBP as monotherapy for the treatment of partial-onset seizures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65608/1/j.1528-1157.1999.tb00927.x.pd

Generalized Spike-Waves, Multiple Loci, and Clinical Course in Children with EEG Features of Benign Epilepsy of Childhood with Centrotemporal Spikes

In 41 patients with EEG features of benign epilepsy of childhood with centrotemporal spikes (BECCT), we noted associated generalized spike-wave discharges (GSWD) in 14.6% and multiple independent sharp wave foci in 9.8%. The presence or absence of these EEG features was not predictive of the clinical course. The high incidence of GSWD in children with BECCT suggests a possible relation in the expression of these two EEG traits.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66418/1/j.1528-1157.1992.tb01764.x.pd

Longitudinal EEG Studies in a Kindred with Lafora Disease

We reviewed 18 EEG studies in four members of a family with the Lafora form of progressive myoclonic epilepsy. Each patient was the product of a consan-guinous marriage and presented as a teenager with progressive seizures, myoclonus, dementia, and ataxia, and had biopsy proven disease. The EEG early in Lafora disease has spike-wave activity resembling that seen in a primary generalized epilepsy; the background slowing is more typical of a secondary generalized epilepsy. With disease progression, there is increased epileptiform activity, and a striking change in the spike-wave complexes, with a marked increase in frequency up to 6–12 Hz, and many more short duration poly spike components. Unlike some other forms of secondarily generalized epilepsy, the EEG in Lafora disease is distinguished by an increased frequency of the spike-wave complexes with disease progression. RESUME Les auteurs ont revu 18 enregistrements EEG pratiquÉs chez 4 membres d'une famille prÉsentant une maladie de Lafora. Chaque patient Était issu d'un manage consanguin et a prÉsentÉ dans adolescence association progressive de crises, d'un myoclonus, d'une dÉmence et d'une ataxie; le diagnostic de la maladie a ÉtÉ confirmÉ par une biopsie. EEG prÉsente, À la phase initiale de la maladie de Lafora, un aspect comparable À celui de Épilepsie gÉnÉralisÉe idiopathique, mais le ralentissement de activitÉ de fond Évoque davantage EEG des Épilepsies gÉnÉi-alisÉes symptomatiques (EGS). Pendant la progression de la maladie, les auteurs ont constatÉ une augmentation de activitÉÉp-ileptique EEG, avec modification importante de la morphologie des PO, qui ont augmentÉ de frÉquence, jusqu'À 6–12 c/s, avec composantes accrues en Polypointes rapides. Contrairement À d'autres formes d'EGS, EEG de la maladie de Lafora se distingue par une augmentation de frÉquence des PO au cours de Évolution. RESUMEN Se revisan 18 estudios de EEG en 4 miembros de una familia con la forma de Lafora de una epilepsÍa mioclÓnica progresiva. Cada paciente fue producto de un matrimonio consanguÍneo y en su adolescencia presentaron ataques progresivos, mioclonÍas, demencia y ataxia, y se les practiceÓ una biopsia que confirmÓ la enfermedad. Los EEGs practicados precozmente en la enfer-medad de Lafora tienen una actividad de punta-onda que semeja la que se observa en epilepsÍa generalizada primaria y la lentifi-caciÓn de la actividad de fondo es mÁs tÍpica de epilepsÍa generalizada sencundaria. A medida que la enfermedad progresa se observÓ un incremento de la actividad epileptiforme y un cambio sorprendente en los complejos punta-onda con marcado incremento de la frecuencia hasta 6–12 Hz. y muchos mÁs compo-nentes de polipuntas de breve duraciÓn. Contrariamente a otras formas de epilepsÍa generalizada secundaria el EEG en la enfermedad de Lafora se caracteriza por un incremento de la frecuencia de los complejos punta-onda a medida que la enfermedad progresa. ZUSAMMENFASSUNG Wir beurteilten 18 EEG-Untersuchungen bei 4 Mitgliedern einer Familie mit der Lafora-Form der progressiven Myoklonus-Epilepsie. Jeder Patient entstammte einer konsanguinen Ehe und wurde als Teenager mit progressiven AnfÄllen, Myoklonus, De-menz und Ataxie auffÄllig; die Diagnose wurde durch Biopsie bestÄtigt. Das EEG im frÜhen Verlauf einer Lafora-Erkrankung zeigt Spike Wave AktivitÄt, die der bei primÄr generalisierter Epilepsie Ähnelt, wÄhrend die HintergrundaktivitÄt mehr fÜr eine sekundÄr generaliserte Epilepsie typisch ist. Mit fortschreitender Erkrankung tritt vermehrt epileptische AktivitÄt und ein deutli-cher Wechsel der Spike Wave Komplexe mit starkem Ansteigen der Frequenz auf 6–12 Hz und vermehrten kurzdauernden Polyspike-Komponenten auf. Im Gegensatz zu anderen Formen sekundÄr generalisierter Epilepsien zeigt das EEG bei der Lafora-Erkrankung mit Erkrankungsfortgang eine zunehmende Frequenz der Spike Wave Komplexe.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65436/1/j.1528-1157.1991.tb05548.x.pd

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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30132/1/0000509.pd

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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29010/1/0000039.pd

Value of Inpatient Diagnostic CCTV-EEG Monitoring in the Elderly

Purpose: To examine the outcome of inpatient diagnostic closed circuit TV-EEG (CCTV-EEG) monitoring in a consecutive series of elderly patients admitted to an adult epilepsy-monitoring unit (EMU) over a continuous 6-year period. Methods: Retrospective review of all admissions to a university hospital adult EMU. Those older than 60 years were identified. Patients who were monitored for status epilepticus were excluded. Data on duration of events, frequency of events, physical examination, medications, preadmission EEG, brain imaging, length of stay, and interictal and ictal EEG were obtained. Results: Of the 18 patients admitted for monitoring only, mean age was 69.5 years (range, 60–90 years). Mean length of stay was 4.3 days (range, 2–9 days). Five patients had complex partial seizures recorded. Three patients, all treated with antiepileptic drugs (AEDs), had no spells recorded, and no additional diagnostic information was gained from the admission. The other 10 patients, eight of whom had been treated with AEDs, were symptomatic during their admission, leading to a variety of neurologic but not epileptic, psychiatric, or other medical disorders, and allowing tapering of AEDs. Conclusions: In elderly patients with suspected epilepsy, CCTV-EEG is a very useful diagnostic tool. In this series of 18, 10 patients were diagnosed with potentially treatable medical illnesses not responsive to AEDs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65172/1/j.1528-1157.1999.tb00825.x.pd

Novel mental retardation–epilepsy syndrome linked to Xp21.1–p11.4

We evaluated a kindred with X-linked mental retardation and epilepsy. Seven affected males with mild to moderate mental retardation developed seizures (primarily generalized, tonic–clonic, and atonic) that began on average at 6.8 months of age (range, 4 to 14 months). These patients did not have a history of infantile spasms. There were no dysmorphic features. Other than mental retardation, the neurological examination was unremarkable, with exception of 2 affected subjects who had mild generalized rigidity and ataxia. We identified tight linkage to a group of markers on Xp21.1–p11.4. A maximum two-point LOD score of +3.83 at θ = 0 was obtained for markers DXS8090, DXS1069, DXS8102, and DXS8085. This locus spans 7.7cM between DXS1049 and DXS8054 and does not overlap the locus for X-linked West syndrome. The tetraspanin gene, implicated in nonspecific mental retardation, is mapped to this region. We sequenced the tetraspanin coding sequence in subjects with X-linked mental retardation and epilepsy and did not identify disease-specific mutations. The syndrome we describe, designated X-linked mental retardation and epilepsy, is clinically and genetically distinct from X-linked West syndrome and other X-linked mental retardation–epilepsy syndromes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34887/1/10051_ftp.pd

The pattern visual evoked potential

The peak latency of the pattern-reversal visual evoked potential is a sensitive measure of conduction delay in the optic nerve caused by demyelination. Despite its clinical utility, the pattern-reversal visual evoked potential has not previously been used in multicenter clinical trials, presumably because of difficulty in standardizing conditions between centers. To establish whether the pattern-reversal visual evoked potential could be adequately standardized for use as a measure in multicenter therapeutic trials for optic neuropathy or multiple sclerosis, stimulus and recording variables were equated at four centers and pattern-reversal visual evoked potentials were recorded from 64 normal subjects and 15 patients with resolved optic neuritis. Results showed equivalent latency and amplitude data from all centers, suggesting that stimulus and recording variables can be satisfactorily standardized for multicenter clinical trials. N70 and P100 peak latencies and N70-P100 interocular amplitude difference were sensitive measures of resolved optic neuritis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42623/1/10633_2005_Article_BF01224629.pd

Human intramuscular and cutaneous pain: psychophysical comparisons

 We used psychophysical methods to compare the central processing of nociceptive inputs from skin and muscle in ten normal humans. Both intramuscular electrical and infrared CO 2 laser cutaneous stimulation showed increasing but decelerating (downward concave) stimulus-response curves and similar temporal summation characteristics. Intramuscular stimulation was rated significantly more unpleasant than cutaneous stimulation. The results are consistent with a common mode of central nociceptive processing for skin and muscle pain intensity but suggest a relatively larger activation of affective mechanisms by muscle afferents.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42009/1/221-114-2-390_71140390.pd