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[Chlormethiazole in the treatment of complex partial epileptic status in childhood].

The authors report on the results of clinical investigations, treatment and follow-up of a 9-year old boy with complex partial status epilepticus (CPSE) which occurred after the first onset of partial secondary generalized epileptic seizures. Electroencephalografic recordings during status epilepticus showed a diffuse, generalized, high-voltage delta dysfunction and bilateral epileptiform activity, with local maximum over the posterior right temporal parietal regions. Parenteral administration of diazepam, phenytoin and phenobarbitone as choice anticonvulsant drugs, failed to stop CPSE in the patient. Only by continuous intravenous infusion of chlormethiazole (Heminevrin) status epilepticus was successfully controlled. Paroxysmal discharges on electroencephalogram disappeared and attenuation of slow wave activity was evident. Memory deficits and the elements of nominal dysphasia and tactile dysgnosia were apparent soon after cessation of CPSE and may be related to the signs of maximal local electroencephalographic dysfunction. Later testings after complete seizure control by chlormethiazole and phenytoin given orally, showed almost normal results. No side effects were encountered. A more common chlormethiazole administration as a useful therapeutic agent in the management of CPSE especially in children with refractory and long-time status, would be mandatory. Since chlormethiazole is free from serious side effects, its earlier use in the control of epileptic status may help to preclude some severe cognitive effects and to evade the use of barbiturate anesthesia as the last therapeutic resort.

Child↗

Vigabatrin dosing during haemodialysis.

The antiepileptic drug vigabatrin has shown efficacy in the treatment of patients with refractory epilepsy. Unlike many other antiepileptics it is not bound to plasma protein and mainly eliminated by the kidney. Although the therapeutic and toxic serum concentration range is not clearly defined and efficacy and toxicity are not closely correlated with the dose, factors decreasing vigabatrin elimination such as advanced age or renal failure may pose risk of untoward effects. Thus far there are no dose recommendations available for patients on haemodialysis. We report on an epileptic patient who experienced severe, partially reversible renal failure as a consequence of near-drowning. In this patient serum concentrations of vigabatrin were measured repeatedly both during haemodialysis and after partial recovery of renal function. The terminal elimination half-life in this patient was 41 hours during the period of severe renal failure (creatinine clearance < 5 ml/min). As about 60% of vigabatrin was removed from the blood pool by haemodialysis in these patients the antiepileptic should be administered after dialysis. To maintain serum concentrations in the usual range and to control seizure activity only 500 mg vigabatrin every 3 days were necessary.

Anticonvulsants↗

No, some types of nonconvulsive status epilepticus cause little permanent neurologic sequelae (or: "the cure may be worse than the disease").

Nonconvulsive status epilepticus (NCSE) is characterized by a cognitive or behavioral change which lasts for at least 30 minutes, with EEG evidence of seizures. Although there is little argument that generalized nonconvulsive status epilepticus (GNSE) does not cause lasting deficits, there is still debate regarding the morbidity of complex partial status epilepticus (CPSE). Because the EEG is used for diagnosis, a strong argument can be made that NCSE is significantly under-recognized and diagnosed. Furthermore, since the documented cases of permanent neurologic sequelae are few, the potential permanent morbidity from CPSE may be significantly exaggerated. The literature indicates that comatose patients have a poor prognosis largely as a result of comorbid conditions and coma, whereas lightly obtunded or slightly confused patients with NCSE have little or no sequelae. Patients with NCSE may suffer (hypotension and respiratory suppression) from iatrogenic 'aggressive' treatment with intravenous anti-epileptic drugs (IV-AEDs), and the findings in the literature indicate that subjects treated with benzodiazepines may have a worse prognosis. The clinician must balance the potential but rare neurologic morbidity associated with NCSE against the not infrequent morbidity caused by IV-AEDs. Better stratification of the level of consciousness and comorbid conditions is needed when evaluating outcomes so as to clearly distinguish among the deficits due to: comorbid conditions; the effects of treatment and the effects of status epilepticus (SE) proper.

Anticonvulsants↗

Plasma concentrations of vigabatrin in epileptic patients.

OBJECTIVE: To measure plasma concentrations of vigabatrin in a group of 30 adult epileptic patients with complex partial seizures (CPS) refractory to conventional antiepileptic drugs. With a view to better defining the drug's dose-response relationships in the presence of concomitant alternative antiepileptic drugs. METHODS: High-performance liquid chromatographic analysis of blood samples drawn at steady-state trough levels from patients receiving vigabatrin. RESULTS: The steady-state plasma concentrations of vigabatrin showed marked interpatient variability (CV = 59.5%). The mean concentration was 42 +/- 25 micrograms/ml (range 11.5-102.7 micrograms/ml). Nineteen patients (63%) had plasma levels between 20 and 60 micrograms/ml. The plasma clearance of vigabatrin ranged from 0.24 to 1.37 ml/min/kg (mean +/- SD = 0.74 +/- 0.40 ml/min/kg), with a median value of 0.64 ml/min/kg. Concomitant treatment with carbamazepine increased the plasma clearance of vigabatrin from 0.59 ml/min/kg (monotherapy), 0.54 ml/min/kg (co-treated with phenobarbital) and 0.41 ml/min/kg (co-treated with valproic acid) to 0.92 ml/min/kg. CONCLUSION: Vigabatrin plasma levels show wide interpatient variability, and co-administration with carbamazepine increases vigabatrin's clearance. While there is no relationship between plasma level and anti-epileptic effect, abnormally high levels of the drug may increase toxicity.

Adult↗

Reading errors following right hemisphere injection of sodium amobarbital.

The role of the nondominant hemisphere in reading is controversial. We characterized the reading errors made by 64 right-handed adults with complex partial seizures (half with seizure foci on the right and half on the left), after right hemisphere injection of sodium amobarbital. Subjects were presented with 20 six-word sentences and all were found to have speech associated with the left hemisphere only. A variety of reading errors occurred, most of which fell under the syndrome of "neglect dyslexia" including deletions and substitutions of whole words on the left side of a line of text as well as within-word neglect errors. The nature of these errors indicated that they may have been caused by an interaction between a peripheral processing deficit and more centrally located conceptual knowledge of linguistic structure. Other errors could be attributed to a general decrease in attentional mechanisms. Neglect errors at the level of the sentence occurred in the absence of neglect errors at the level of the word although the converse was not true. This suggests that the latter may represent a more severe deficit in the mechanism that causes the former. A double dissociation existed between single word neglect dyslexia errors and "visual" errors, indicating separate processing mechanisms.

Adult↗

Benign idiopathic partial epilepsies in infancy.

In infancy, partial epilepsies have been considered with suspicion for their probable association with brain lesions. Japanese authors first described partial epilepsies in infancy with a favorable outcome and called them benign partial epilepsy in infancy with complex partial seizures. Similar, but familial, cases with onset during the first year of life were described some years later and called benign infantile familial convulsions. Similar familial cases with subsequent choreoathetosis were described in 1997 and called infantile convulsions and choreoathetosis. Benign infantile convulsions have also been described in association with mild gastroenteritis. Interictal electroencephalography (EEG) was always normal in all of these forms. More recently, a new epileptic syndrome characterized by partial seizures with onset between ages 13 and 30 months, a benign outcome, and characteristic EEG abnormalities in the vertex regions during sleep has been described. There is also an early-onset benign childhood occipital seizure susceptibility syndrome that can start in infancy.

Brain↗

Dysembryoplastic neuroepithelial tumors: MR appearance.

PURPOSE: Dysembryoplastic neuroepithelial tumor (DNT) is a newly described, pathologically benign tumor arising within the supratentorial cortex and having a 100% association with partial complex seizures. We reviewed the MR appearance of the brains of six patients with DNT, without and with administration of gadolinium-DTPA, emphasizing the clinical and radiologic features. METHODS: The MR images in six patients (five male, one female) with pathologically proved DNT were reviewed. Five had partial complex seizures and one had partial simple seizures. Age at onset of partial seizures ranged from 2 to 19 years. Scans were obtained with conventional T1 and T2 weighting without and with the administration of gadolinium-DTPA. All patients had craniotomies for medically refractory seizures and pathologic examination of all specimens was available for review. RESULTS: MR demonstrated a focal cortical mass in all patients. Five were located in the temporal lobe and one was located within the occipital lobe. Two showed enhancement with gadolinium-DTPA. Calcification occurred in one lesion. Common features included very low signal intensity on T1-weighted images and high signal on T2-weighted images, similar to cerebrospinal fluid. Proton density images demonstrated slightly higher signal intensity in the lesion than cerebrospinal fluid. The margin of the tumor is well-circumscribed and may remodel the adjacent calvarium. CONCLUSIONS: DNT, a newly described pathologic entity resulting in chronic, often medically, intractable seizures, has characteristic features on MR that allow it to be suggested in the differential diagnosis. These lesions may simulate benign cysts; however, increased signal intensity on proton density images should prompt further investigation in the proper clinical setting. Differentiation from low-grade astrocytomas and ganglioglioma is not possible by MR.

Adolescent↗

Mirror focus: function of seizure frequency and influence on outcome after surgery.

The concept of the mirror focus (MF) implies that an actively discharging epileptiform region may induce similar paroxysmal behavior in a homologous site. In a group of patients with complex partial seizures (CPS) we investigated whether occurrence of a MF was influenced by certain clinical factors and whether surgical outcome was influenced by the presence of an MF. Factors studied included age at onset, duration, and total number of seizures. Patients had had CPS for > 3 years and had pathologically proven temporal lobe neoplasms. Seizure frequency was estimated by the history-taking physician. We estimated total seizure number by multiplying frequency by duration. Seven patients had MF, and 15 did not. Mean age at onset of seizures, duration of seizure disorder, and total seizure number did not vary statistically between the two groups of patients. All patients with an MF except 1 were seizure-free at follow-up. Ten of the 15 patients without MF were seizure-free. Three patients who were not seizure-free had had subtotal resection owing to tumor overlap with eloquent cortex. We conclude that an MF is not a contraindication to operation even when the preponderance of interictal spike activity is contralateral to the tumor or when seizures appear to arise from the MF on scalp EEG.

Adolescent↗

Nonconvulsive status epilepticus in rats: impaired responsiveness to exteroceptive stimuli.

An animal model of human complex partial status epilepticus induced by lithium chloride and pilocarpine administration was developed in our laboratory. The objective of the study was to provide a detailed analysis of both ictal and postictal behavior and to quantify seizure-related morphological damage. In order to determine the animal's responsiveness to either visual or olfactory stimuli, adult male rats were submitted to the following behavioral paradigms: the object response test, the social interaction test, and the elevated plus-maze test. The rotorod test was used to evaluate motor performance. Two weeks after status epilepticus, brains were morphologically examined and quantification of the brain damage was performed. Profound impairment of behavior as well as responsiveness to exteroceptive stimuli correlated with the occurrence of epileptic EEG activity. When the epileptic EEG activity ceased, responsiveness of the pilocarpine-treated animals was renewed. However, remarkable morphological damage persisted in the cortical regions two weeks later. This experimental study provides support for the clinical evidence that even nonconvulsive epileptic activity may cause brain damage. We suggest that the model can be used for the study of both functional and morphological consequences of prolonged nonconvulsive seizures.

Animals↗

Lateralisation value of lower limb behaviors in complex partial seizures of temporal lobe origin: a video-EEG analysis.

PURPOSE: To determine the lateralising value of leg behaviors in complex partial seizures (CPS) of temporal lobe onset. METHODS: Videotapes of 123 seizures from 38 patients who were seizure-free after temporal lobectomy were reviewed. Ictal behaviors including head turning, limb automatisms, tonic/dystonic postures and the latent time for ictal behavior were analysed for their lateralising value. RESULTS: Contralateral versive head turning, ipsilateral arm automatisms, contralateral arm tonic/dystonic posturing, and contralateral arm clonic posturing were found to have high predictive value of lateralisation. As for the lower limbs, meaningful leg behaviors were recorded in 38 (31%) of 123 seizures, far less than behaviors of the upper limbs (79%). The predictive value from leg behaviors were similar to that from upper limbs. Among the leg behaviors, dystonic behaviors were always contralateral to the ictal side. Tonic behaviors were 94% contralateral to the ictal side. Dystonia and clonic movement were always contralateral to the ictal side. Automatisms were 86% ipsilateral to the ictal side. CONCLUSIONS: Although incidences were low, leg behaviors could provide useful lateralising value of the seizure foci. Clinicians as well as investigators should recognize the value of lower limbs behavior in studies of ictal semiology.

Adolescent↗

Psychopathology and pediatric complex partial seizures: seizure-related, cognitive, and linguistic variables.

PURPOSE: This study examined the role of cognition, language, seizure-related, and demographic variables in the psychopathology of children with complex partial seizure disorder (CPS) of average intelligence. METHODS: One-hundred one CPS and 102 normal children, aged 5.1 to 16.9 years, had a structured psychiatric interview and cognitive and language testing. Parents provided demographic, perinatal, and seizure-related information, as well as behavioral information through the Child Behavior Checklist (CBCL) and a structured psychiatric interview about the child. RESULTS: Significantly more CPS patients had psychopathology, cognitive deficits, and linguistic deficits than did those in the normal group. Among the patients, Verbal IQ predicted the presence of a psychiatric diagnosis, as well as CBCL scores in the borderline/clinical range. Seizure, linguistic, and demographic variables were unrelated to psychopathology. The cognitive and linguistic deficits of the CPS group, however, were predicted by seizure factors (e.g., prolonged seizures/febrile convulsions; seizure frequency/number of antiepileptic drugs) and demographic factors (e.g., minority status). CONCLUSIONS: Because subtle verbal cognitive deficits predict behavioral disturbances in pediatric CPSs, the study's findings highlight the importance of assessing behavior, cognition, and language in these children. They also underscore the negative impact of prolonged seizures, febrile convulsions, seizure frequency, and antiepileptic drug polytherapy on cognition and language in pediatric CPSs.

Adolescent↗

Correlations between verbal memory performance and electrocorticographically determined suppression of electrical brain activity in intracarotid amobarbital tests.

As a part of presurgical evaluation, bilateral intracarotid amobarbital procedures (IAPs) were performed in 42 patients (84 tests) with long-standing, medically intractable complex-partial seizures. During the IAPs, electrocorticographic (ECoG) recording was carried out via bilaterally implanted subdural electrodes. Five distinct patterns of suppression of electrical brain activity were observed: (1) an isoelectric line; (2) a burst-suppression pattern; (3) polyphasic waves; (4) high-voltage beta; and (5) low-voltage beta activity. Further, two types of specific reactions of the epileptic focus were detectable: (1) spike-burst-suppression patterns (SBS; 11 left; 7 right; 6 in both IAPs) and amobarbital-induced spikes (7 left; 4 right). ECoG suppression patterns as well as SBS and spike induction showed great variability in duration and overall occurrence. To determine the influence of these amobarbital-induced ECoG changes on results of IAP memory testing, performance in a verbal learning task was analyzed according to the ECoG patterns predominant during encoding. In left IAPs, it was found that SBS at the beginning of or during encoding had a significant negative effect on verbal memory. In right IAPs, verbal memory performance improved significantly with the decline of ECoG suppression. Hence, verbal memory performance in IAPs is significantly affected by specific ECoG suppression patterns and activation of the epileptic focus.

Adolescent↗

Dream experience during REM and NREM sleep of patients with complex partial seizures.

This study examined the effectiveness of the cognitive processes underlying dreaming in patients with complex partial seizures (CPS), by assessing the frequency of recall and the structural organization of dreams reported after awakenings provoked alternately during REM and stage 2 NREM sleep on 12 cognitively unimpaired CPS-patients (six with epileptic focus in the right hemisphere and six in the left one). Each patient was recorded for three consecutive nights, respectively, for adaptation to the sleep laboratory context, for polysomnography and for dream collection. The frequency of dream recall was lower after stage 2 NREM sleep than REM sleep, regardless of the side of epileptic focus, while the length and structural organization of dreams did not significantly differ in REM and NREM sleep. However, the length of story-like dreams was influenced by global cognitive functioning during REM sleep. These findings indicate that in CPSs-patients the elaboration of dream experience is maintained in both REM and NREM sleep, while the access to information for conversion into dream contents and the consolidation of dream contents is much less effective during NREM rather than during REM sleep. Further studies may distinguish between these two possibilities and enlighten us as to whether the impaired memory functioning during NREM sleep is a side effect of anticonvulsant treatment.

Adult↗

Measurement of temporal asymmetries of glucose consumption using linear profiles: reproducibility and comparison with visual analysis.

AIM: One approach to regionally analyze temporal glucose consumption consists in drawing linear profiles over the maximal values measured in the temporal cortical ribbon. The aim of our study was to test the reproducibility of this method and to compare its diagnostic performance to that of visual analysis in patients with complex partial seizures (CPS). METHODS: Regional cerebral glucose consumption (rCMRGIc) was measured interictally in 25 CPS patients and 10 controls using F-18-deoxyglucose and the positron emission tomography (PET) camera ECAT EXACT 47. The PET scans were visually analyzed for the occurrence of unilateral temporal hypometabolism. Furthermore, rCMRGIc was quantified on six contiguous coronal planes by manually tracing maximal values of temporal glucose consumption, thus creating line profiles of temporal glucose consumption for each side. Indices of asymmetry (ASY) were then calculated from these line profiles in four temporal regions and compared to the corresponding 95% confidence intervals of the control data. All analyses were performed by two observers independently from each other and without knowledge of the clinical findings. RESULTS: The agreement between the two observers with regard to focus lateralization was 96% (kappa = 0.93) on visual analysis and 100% (kappa = 1) on quantitative analysis. There was an excellent agreement with regard to focus lateralization between visual and quantitative evaluation (kappa = 0.8). CONCLUSION: Quantitation of local temporal rCMRGIc by using linear profile analysis is highly reproducible; for the lateralization of epileptogenic foci, however, this method does not possess significant advantages over the visual evaluation of the scans.

Adult↗

Neuron-specific enolase, a marker of acute neuronal injury, is increased in complex partial status epilepticus.

PURPOSE: To determine whether complex partial status epilepticus (CPSE) causes brain injury in humans. Serum neuron-specific enolase (s-NSE) is an accepted marker of acute brain injury, and increases in s-NSE have been correlated with the duration and outcome of generalized convulsive status epilepticus. s-NSE levels in CPSE are unknown. Increase in s-NSE in CPSE would provide new information about the degree of brain injury in CPSE and would help confirm that CPSE is a medical emergency. METHODS: This was a pilot prospective study of serial levels of s-NSE and outcome in CPSE. Eight patients with confirmed CPSE and no acute neurologic deficit were identified prospectively. Results were compared with those of normal and epileptic control groups, and outcome was assessed at hospital discharge or at 7 days with the Glasgow Oucome Scale (GOS). RESULTS: The mean peak s-NSE was 21.81 ng/ml, which for the 8 patients with CPSE was four times higher than that of normal controls (mean s-NSE = 5.36 SD = 1.66, p = 0.0003) and epileptic controls (mean s-NSE = 4.61 SD = 1.74, p. = 0.001). CONCLUSION: The increase in s-NSE provides new evidence that CPSE causes brain injury in humans.

Biomarkers↗

Ictal brain imaging in presurgical evaluation of patients with medically intractable complex partial seizures.

At the Indiana University Medical Center, 99 patients with medically intractable complex partial seizures (MI-CPS) had presurgical evaluation with subsequent anterior temporal lobectomy. The majority of the patients had single photon emission tomography (SPECT) performed interictally as well as during an actual epileptic seizure (ictal scan). Decreased regional cerebral perfusion (rCP) was seen in 54/94 (57%) of the interictal scans corresponding to the eventual site of the surgery. However, ictal scans provided a higher yield; increased rCP in the temporal lobe during an actual seizure was observed in 60/82 (73%) concordant to the side of surgery. SPECT is a useful, noninvasive method of localizing the epileptiform focus in patients with MI-CPS considered for resective surgery. Both interictal and ictal SPECT need to be performed; combined interictal hypoperfusion and ictal hyperperfusion in the same focal area are unique to epileptogenic lesions. Ictal SPECT studies can be performed in the majority of patients during the period of continuous video/EEG monitoring with only a little additional effort. Combining the results of functional brain imaging (interictal and ictal SPECT, PET) with clinical semiology of seizures, surface and sphenoidal EEG, magnetic resonance imaging and other non-invasive tests, anterior temporal lobectomy can be recommended in approximately two-thirds of the patients without resorting to potentially dangerous intracranial EEG monitoring.

Adolescent↗

Valproate-induced coma: case report and literature review.

OBJECTIVE: To report a case of hyperammonemia without hepatic dysfunction as a possible cause of lethargy, stupor, and coma in a woman after valproic acid (VPA) administration, and discuss the possible different mechanisms of ammonia elevation and coma. CASE SUMMARY: A woman diagnosed with complex partial seizures that secondarily generalize was treated with phenytoin (PHT) 250 mg/d for 18 years. Three months before admission, this dosage was increased to 300 mg/d and phenobarbital (PB) 100 mg/d was added because the seizures were incompletely controlled. The patient developed a progressive inability to walk. She was diagnosed as having PHT intoxication. VPA therapy was begun while PHT was being tapered and progressive impairment of consciousness occurred. This evolved into a coma without focal neurologic signs, and was accompanied by isolated hyperammonemia without hepatic failure. DISCUSSION: Adverse effects attributable to VPA were reviewed in the literature. Occasionally, VPA may lead to severe secondary effects such as hepatic failure and coma. In these cases increased blood concentrations of transaminases, bilirubin, and ammonia have been found. Several reports have stressed the existence of hyperammonemic coma without biochemical evidence of hepatic failure, which is what occurred in our patient. This suggests that isolated hyperammonemia and hepatic failure after VPA treatment may have a different biochemical basis. CONCLUSIONS: VPA-induced coma with hyperammonemia and without evidence of hepatic failure should be considered in patients being treated with PHT or PB when VPA is administered concomitantly. This case report shows the importance of clinical monitoring and immediate drug discontinuation when drowsiness, gastrointestinal symptoms, or lethargy occur.

Ammonia↗

[Subarachnoid hemorrhage from the anterior communication artery in a sex offender. Considerations regarding liability].

A 32-year-old man was accused of attempted rape. While urinating at the side of the road he felt an erection. He approached a 9-year-old girl who happened to be coming along and pressed his penis between her legs until ejaculation. Shortly afterwards he was arrested. He confessed, but claimed partial amnesia and had no explanation for the offence, which he normally would never have thought of. Shortly before the event a witness had seen him nearby in a poor state of orientation. Three months later in prison he suffered massive subarachnoidal hemorrhage from an aneurysm of the anterior communicating artery. The evaluation of his legal responsibility must take account of a putative psychomotor seizure at the time of the offence. With regard to the aneurysm diagnosed later, a pathogenetic connection, in terms of a preceding warning leak, might be assumed.

Adult↗