Effects of intracerebroventricular injection of histamine on memory deficits induced by hippocampal lesions in rats

This review was conducted to evaluate the long-term prognosis of children responding to vigabatrin by examining the incidence of increased seizure frequency, loss of efficacy, and appearance of new seizures in a cohort of 196 children (mean age, 68.2 months; range, 2 months to 19 years) with drug-resistant epilepsy, who had received vigabatrin as add-on treatment in clinical trials. The results indicate that an increase in seizure frequency was uncommon, occurring in only 10% of children with highly drug-resistant epilepsy and that it usually appears shortly after the initiation of treatment. It was clearly not dose-dependent and most often occurred in patients with nonprogressive myoclonic epilepsy. No specific seizure type was specially involved and usually the problem reversed on discontinuing vigabatrin. Loss of efficacy was also uncommon (12% of patients), and again no specific seizure type was found to be associated. Epilepsy syndrome does seem to be a better predictor of loss of efficacy because it occurred most often in symptomatic generalized epilepsies and cryptogenic infantile spasms. A total of 21 patients (11%) developed genuinely new types of seizures. Fifteen of these patients developed new partial seizures that had little impact on the patients' overall clinical improvement. The new partial seizures were better tolerated than the initial seizure type which in most cases had disappeared. Approximately 3% of patients experienced new generalized seizures that aggravated their initial condition. These occurred most often in patients with nonprogressive myoclonic epilepsy; therefore vigabatrin should be used with particular caution in such patients.     

Clonazepam: a review of its pharmacological properties and therapeutic efficacy in epilepsy

Clonazepam or 5-(2-chlorphenyl)-1, 3-dihydro-7-nitro-2H-1,4benzodiazepin-2-one, is a close structural and pharmacological relative of nitrazepam. It has a broad spectrum of activity against the various types of epilepsy, and is effective in many patients whose condition has proved resistant to other antiepileptic drugs. Its chief uses are in status epilepticus, in which intravenous clonazepam may replace diazepam as the drug of first choice, and in the minor motor seizures of childhood, particularly petit mal absences, the Lennox-Gastaut syndrome and infantile spasms. Clonazepam is also at least as effective as current treatment in psychomotor and myoclonic epilepsies, but seems unlikely to replace phenytoin and the barbiturates in the treatment of grand mal or focal motor seizures except in patients resistant to standard therapy. Initial success with clonazepam can be followed by loss of effect, but benefit can often be restored, at least initially, by temporary interruption and re-institution of treatment. Side-effects are common with clonazepam. Most patients experience drowsiness and fatigue, which are frequent causes of withdrawal, together with lesser incidences of ataxia, dystonia, hypotonia, and hyperactivity. These effects usually disappear with continued therapy, and are minimised by gradual introduction of the drug over 2-4 weeks. Hypersalivation and excessive bronchial secretion may be a problem in children and infants.     

Surgical treatment of extratemporal epilepsy: clinical, radiologic, and histopathologic findings in 60 patients

PURPOSE AND METHODS: The aim of this study was to analyze clinical, radiologic, and histopathologic findings in 60 consecutive patients with medically intractable extratemporal epilepsy who were operated on between November 1987 and May 1993. RESULTS: Histologically, there were distinct structural abnormalities in 50 (83%) of the surgical specimens. Signal abnormalities on magnetic resonance imaging (MRI) were present in all patients with neoplastic lesions (n = 17) and in 94% of patients with nonneoplastic focal lesions (n = 32). Overall, structural abnormalities were detected by MRI in 47 (96%) of 49 patients with focal lesions. During a mean follow-up of 4 years, 30 (54%) patients remained completely seizure free, 11 (20%) had < or = 2 seizures per year, seven (12%) showed a seizure reduction of > or = 75%, and eight (14%) had < 75% reduction in seizure frequency. The fraction of seizure-free patients was 12 (80%) of 15 in patients with neoplastic lesions, 16 (52%) of 31 in patients with nonneoplastic focal lesions, and two (20%) of 10 for those without histopathologic abnormalities. The differences in seizure outcome between patients with and without focal lesions were statistically significant (p < 0.05), if seizure-free outcome was compared with persistent seizures. CONCLUSIONS: Focal lesions and particularly neoplasms are associated with improved postoperative seizure control compared with patients without histopathologic abnormalities. We advise caution in considering surgery to treat extratemporal epilepsy in patients who have normal MRI scans, because the outcome with the approach described in this study is poor in such cases.     

Clinico-electroencephalographic observations in epileptic patients during long-term treatment with benzonal

Benzonal was given to 52 epileptics. In 50 cases the duration of treatment ranged from 3 months to 7 years (mean 18 months) in doses of 100-500 mg daily, in 2 cases it had to be withdrawn after a short-term treatment because of intolerance. In all cases the drug was given together with other anticonvulsants: hydantoin, derivatives, mysodin, Tegretol, pheneturid or Ospolot in place of previously administered phenobarbital. It was found that benzonal reduced significantly the frequency of partial simple seizures (in 6 out of 20 cases) and grand mal seizures (in 24 out of 34 cases), while its action on the partial complex seizures was much weaker (improvement in only 7 out of 20 cases). The drug was usually well tolerated, side effects of greater intensity developed in 2 cases only, transient somnolence was observed in another 6 cases. In EEG records a slight favourable effect was exerted on pathological background activity with absent effect in focal changes and increase of seizure activity. The authors believe that in view of its favourable clinical action and good tolerance the drug may be widely used in properly selected cases of epilepsy.     

Epilepsy in early development: the lesson from surgery for early intractable seizures

This report examines the impact on development and the problems involved in assessing development in very young children with early-onset intractable seizures, particularly infantile spasms. A review of studies on medically and surgically treated children with infantile spasms underscores the relationship between seizure control and developmental outcome. About 50% of children with markedly intractable infantile spasms attained seizure control and significant improvement in the use of nonverbal communication, a developmental measure that has been used in other populations of developmentally delayed children. With the exception of duration of illness, clinical measures of age of onset of infantile spasms, type of surgery, and side of surgery did not appear to be related to the postoperative change in nonverbal communication. The neuropathology findings of surgically treated children with infantile spasms suggest that the underlying pathology occurs early in brain development. In conclusion, the cumulative effect of uncontrolled seizures and the underlying pathology might impact the early development of children with intractable infantile spasms.     

Predictors of epilepsy in children who have experienced febrile seizures

We examined the frequency of development of afebrile seizures in 1706 children who had experienced at least one febrile seizure and were followed to the age of seven years. Epilepsy developed by seven years of age in 20 per 1000 (2 per cent), and another 10 per 1000 had at least one afebrile seizure that did not meet our definition of epilepsy. In children whose neurologic or developmental status was suspect or abnormal before any seizure and whose first seizure was complex (longer than 15 minutes, multiple or focal) epilepsy developed at a rate 18 times higher than in children with no febrile seizures (92 vs. 5 per 1000; P less than 0.001). In the largest group with febrile seizures, those previously normal with noncomplex first febrile seizures, epilepsy developed in 11 per 1000; this rate, although moderate, was greater than that for children with no febrile seizures (P = 0.027). Prior neurologic and developmental status and characteristics of the first febrile seizure are important predictors of epilepsy after febrile seizures.     

Epilepsy surgery in the first three years of life

PURPOSE: Partial seizures in early postnatal life may be catastrophic and associated with poor long-term outcome. Epilepsy surgery can alleviate partial seizures in older children and adults, but there is little experience with surgical therapy in infancy apart from hemispheric epilepsy syndromes. METHODS: We analyzed the results of cortical resection to treat medically refractory partial epilepsy in 31 children (16 boys, 15 girls) aged <3 years (mean, 18.3 months). Subjects were included only if seizure relief was the primary indication for surgery. RESULTS: Follow-up of at least 1 year (mean, 4.6 years) in 26 patients revealed that 16 were seizure-free, 4 had >90% seizure reduction, and 6 had <90% reduction. There was no significant difference in seizure outcome between hemispherectomy/multilobar resections and lobar resections or temporal versus extratemporal resection. Seizure outcome was independent of the amount of cortex removed in nonlesional patients. Only the presence of a discrete lesion on preoperative neuroimaging correlated with a favorable outcome. Family perceptions of accelerated development in seizure-free patients were not confirmed on developmental assessment. CONCLUSIONS: We conclude that cortical resection often benefits very young children with catastrophic partial seizures, but does not guarantee enhanced neurological development. The location and extent of the excised cortex may not be critical as long as the entire epileptogenic region and lesion are removed.     

Complexities of primary generalized epilepsy

Abnormal arousal responses paired with paroxysmal discharges and photosensitivity are the principal mechanisms in the precipitation of seizures in primary generalized epilepsy. The abnormal arousal responses show a consistent maximum over the frontal midline region. An exception from this rule was found in two children with primary generalized epilepsy (petit mal absences, one also with grand mal) with a strongly positive family history. In these patients, the generalized-synchronous bursts showed a maximum over the vertex (Cz electrode). Both of these children also had single spikes over the Rolandic region. A relationship between primary generalized and benign Rolandic epilepsy is demonstrated. Both forms of seizure disorder are based on dysfunction (hyperexcitability) rather than on a structural epileptogenic lesion. A dichotomy of dysfunctional and structural epilepsies is presented but gray zones of overlap indubitably exist. The limitations of the dichotomy concept are pointed out.     

Vigabatrin and lamotrigin: experiences with 2 new anticonvulsants in the Swiss epilepsy clinic

Vigabatrin and lamotrigine are two new antiepileptic drugs which have recently become available. Vigabatrin is a specific and irreversible inhibitor of the enzyme gamma-amino-butyric-acid (GABA) transferase. Its administration leads to a long lasting increase in GABA, the most important inhibitory neurotransmitter. Vigabatrin is effective in both adults and children in the treatment of partial and especially complex-partial seizures. After add-on in vigabatrin to their therapeutic drug regime in 116 of our own patients, 39% of previously therapy resistant patients reported a reduced seizure frequency of at least 50% and 6% of them became seizure free. In secondarily generalized epilepsies the best results were observed in axial (infantile) spasms. In addition there was some improvement in tonic and convulsive seizures. Single patients showed increased myoclonic and clonic seizures. Initial efficacy was not always maintained during follow-up. In the experience of other authors, vigabatrin is also effective in the treatment of infantile spasms. It is not suitable for the treatment of generalized epilepsies with absences and myoclonic seizures. Most patients tolerate vigabatrin very well, although psychotic episodes are sometimes reported. So far there have been no relevant hepatic or hematological side effects. Lamotrigine is also effective in the treatment of partial seizures, for which it is approved. However, uncontrolled studies and our own experience have shown that it is even more effective in generalized seizures. As add-on therapy in absences and tonic or tonic-clonic seizures, a significant reduction in seizure frequency--in individual cases seizure freedom--can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)     

Short-term perioperative anticonvulsant prophylaxis for the surgical treatment of low-risk patients with intracranial aneurysms

The long-term use of anticonvulsant medication to prevent postoperative seizures in patients with aneurysms has been accepted medical practice for many years. The low incidence of seizures in more recent aneurysm series makes it appropriate to re-evaluate the use of prophylactic anticonvulsants to prevent postoperative epilepsy, especially in patients at low risk of seizure disorders. On the basis of preoperative presentation, we categorized 387 of the 420 craniotomies for aneurysms over a 4-year period to be at low risk of seizure. Postoperative anticonvulsant medication in this group was restricted to an average of 3 days. A retrospective analysis of the incidence of early postoperative seizures and late postoperative seizure disorders was performed in the populations of patients with ruptured aneurysms and with unruptured aneurysms with an average follow-up of 2.4 years. The overall seizure rate in the study group was 5.4%. Patients with ruptured aneurysms had an early postoperative seizure rate of 1.5% and a long-term seizure disorder rate of 3.0%. Early and long-term seizure rates for unruptured aneurysms were 2.6 and 4.4%, respectively. No patients who had early seizures went on to develop epilepsy, and all seizure disorders were well controlled once anticonvulsants were begun. These data support the idea that anticonvulsant medication may be safely restricted to the immediate perioperative period for most patients with aneurysms.     

Therapeutic efficacy of ACTH in symptomatic infantile spasms with hypsarrhythmia

The records of twenty-six infants with both symptomatic infantile spasms and classic hypsarrhythmia were reviewed to determine the efficacy of various ACTH dosages and time of initiation of therapy. Mean age of infantile spasm onset was 6.4 months. Most patients (13) had sustained perinatal hypoxic-ischemic insults. Seventeen patients (65%) had complete cessation of spasms. Between these responders and the 9 nonresponders there was no difference in duration of spasms prior to treatment (2.6 and 2.0 months) or mean ACTH dose (87.4 and 84.5 U/m2, respectively). Infants treated with high-dose ACTH (> 100 U/m2) did not have an improved response rate. The most favorable outcomes were associated with spasm onset at > 8 months of age (all of whom were responders, regardless of dose) or when treatment was started within 1 month of onset of infantile spasms with > 80 U/m2 ACTH (88% responders). Infants treated more than 2 months after onset often did not respond (57%) regardless of dose. Nonresponders with spasm onset at < 4 months of age had the worst prognoses; all had poorly controlled seizures and regressed developmentally. Although all infants in the study were neurologically abnormal, development either improved or did not deteriorate in most responder infants following spasm resolution and one-half remained seizure free. Nonresponder infants continued to have infantile spasms or other seizure types. These data suggest that ACTH is valuable in the treatment of significantly impaired infants with symptomatic infantile spasms, but the most important determinants of outcome may be age of onset and rapidity of treatment rather than dosage.     

Multilobar polymicrogyria, intractable drop attack seizures, and sleep-related electrical status epilepticus

BACKGROUND AND OBJECTIVE: Patients with cortical malformations often have intractable seizures and are candidates for epilepsy surgery. Within an unselected series of patients with various forms of cortical malformation, nine patients with multilobar polymicrogyria had electrical status epilepticus during sleep (ESES) accompanied by infrequent focal motor seizures. Eight patients also had intractable atonic drop attack seizures. Because ESES usually is accompanied by a good long-term seizure prognosis, the objective of this study was to examine ESES outcome among patients with a structural lesion that is usually highly epileptogenic and has a low seizure remission trend. METHODS: The nine patients had follow-up periods lasting 4 to 19 years. All underwent brain MRI, serial sleep EEG recordings, and cognitive testing during and after ESES. RESULTS: ESES and drop attack seizures appeared between the ages of 2 and 5 years (mean, 4 years) and ceased between the ages of 5 and 12 years (mean, 8 years). At the last visit patients were 8 to 23 years of age (mean, 14.5 years) and were either seizure free or had very infrequent focal motor seizures during sleep. Three patients were free from antiepileptic drugs. In no patient was definite cognitive deterioration apparent after ESES in comparison with earlier evaluations. CONCLUSIONS: Age-related secondary bilateral synchrony underlying ESES may be facilitated in multilobar polymicrogyria. The good seizure outcome contrasts with that usually found in the presence of cortical malformations. For children with polymicrogyria and drop attack seizures, surgical treatment of the epilepsy should be considered cautiously, and sleep EEG recordings should be performed systematically.     

Clinical experience with sodium valproate in children

Good control was achieved with sodium valproate (Epilim) in 44 (71%) of a sample of 62 children with severe recurrent epileptic seizures. The medication was most effective in the control of petit mal; good results, however, were also achieved in some patients with previously poorly controlled grand mal epilepsy and psychomotor and myoclonic seizures. Twenty children required no other anti-convulsant and 28 required only one other. Side-effects were infrequent and mild. Only the high cost of sodium valproate in South Africa precludes its more general use in childhood epilepsy.     

Surgical treatment of epilepsy in tuberous sclerosis: strategies and results in 18 patients

BACKGROUND: Seizures in patients with tuberous sclerosis complex (TSC) are often intractable to antiepileptic medications and searching investigation may provide evidence that surgical treatment can be considered. OBJECTIVE: To review the results of investigation and surgical therapy, a treatment modality not generally considered in patients with medically refractory seizures and TSC. METHODS: We report 18 patients (9 male) with TSC who underwent surgical treatment of medically refractory epilepsy. Twelve patients had a well-localized epileptogenic lesion and were treated by lesionectomy or focal resection. Resections were: 7 frontal, 4 temporal, 1 frontotemporal, 1 occipital, and 1 frontoparietal. Four patients underwent more than one operation. Six patients had corpus callosotomy (CC). RESULTS: Follow-up ranged from 1 month to 47 years. Outcome of the patients treated by resection was excellent in 7 (5 were seizure-free and 2 had auras only), good in 1, fair in 3, and 1 was lost to follow-up. Best outcome was obtained in patients who had focal seizures and good imaging and EEG correlation, although they might have multiple seizure types, other imaging abnormalities, and multifocal or generalized EEG findings. When there was no such correlation, CC was found to be an option as five patients had at least some improvement and only one showed no change. CONCLUSION: Surgical treatment of patients with TSC and intractable epilepsy is most effective when a single tuber or epileptogenic area can be identified as the source of seizures and resected. This may be possible even when other tubers or diffuse EEG abnormalities are present. In patients with unlocalizable epileptic abnormalities, palliation may be obtained by CC.     

Single-chain Fv with manifold N-glycans as bifunctional scaffolds for immunomolecules

PURPOSE: To investigate the significance of cortical pathology of tonic spasms in patients with tuberous sclerosis. METHODS: The subjects were 38 patients with epilepsy associated with tuberous sclerosis. We analyzed ictal EEGs of tonic spasms and partial seizures by means of video-EEG monitoring for a total of 763 tonic spasms in 20 patients and 107 partial seizures in 15 patients. We also investigated the relation between partial seizures and magnetic resonance imaging (MRI) findings of these patients. RESULTS: Ictal EEG patterns of tonic spasms were divided into generalized and focal patterns. Thirteen patients had only generalized patterns, whereas seven had both patterns. In five patients who had focal ictal patterns of tonic spasms and partial seizures, the location of focal patterns corresponded with the location of onset of partial seizures. Focal discharges were seen immediately before, after, and in the middle of tonic spasms in series in 13 patients. The location of focal discharges also corresponded with the location of the onset of partial seizures in 10 of the 13 patients. Regarding partial seizures, four patients had multiple active epileptogenic foci during the same period, and two others had shifting epileptogenic foci with increasing age. CONCLUSIONS: These findings indicate that cortical pathology plays an important role in the occurrence not only of partial seizures but also of tonic spasms in patients with tuberous sclerosis.     

Development of bioactive functions in Hydrangeae Dulcis Folium. VII. Immunomodulatory activities of thunberginol A and related compounds on lymphocyte proliferation

PURPOSE: Vagus nerve stimulation (VNS) has been reported to produce >90% reduction in the number of seizures in children with intractable epilepsy. These encouraging results need confirmation. METHODS: Sixteen children, 10 boys and 6 girls aged 4-19 years, were treated with VNS (Cyberonics, Webster, TX, U.S.A.) for 12-24 months. Seizure frequency, seizure severity, changes in quality of life (QOL: visual analogue scale), and side effects were recorded. Eight children had partial and 8 had generalized seizures; 4 of the latter had Lennox-Gastaut syndrome (LGS). RESULTS: During the tenth to twelfth month of VNS, 6 of 16 children experienced > or =50% reduction in seizure frequency. One girl became seizure-free. Seizure severity showed an average decrease in the score from 15 to 11. After 10 months of treatment, QOL was estimated to have improved > or =50% in 6 of 16 children. Reduction in seizure frequency, decreased seizure severity, and reported improvement in QOL did not entirely coincide. Six children experienced hoarseness, 1 had neck pain, 2 had hypersalivation, 2 experienced tiredness, 2 had aspiration episodes during liquid intake, and 6 had electrical transmission problems; in 4 the problem has been surgically corrected. Five stimulators were turned off due to lack of efficacy. CONCLUSIONS: Six of 16 children with refractory epilepsy treated with VNS improved, with a reduction not only in seizure frequency but also in seizure severity and in QOL.     

Surgical treatment of epilepsy due to cortical dysplasia: clinical and EEG findings

Seventeen patients with cortical dysplasia who had surgical resection for medically intractable partial epilepsy were studied. Compared with two groups of surgically treated patients with intractable epilepsy due to tumour (n = 20) and mesial temporal sclerosis (n = 40), patients with cortical dysplasia showed significantly more frequent extratemporal lesions, more frequent non-epileptiform EEG abnormalities and less favourable surgical outcome for seizure control. Patients with cortical dysplasia were younger at onset of seizures and had a lower detection rate of CT abnormalities compared with the tumour group, and lower IQ compared with the mesial temporal sclerosis group. MRI was abnormal in five of seven patients. Six patients became seizure-free or almost seizure-free but eight did not experience relief of seizures. Surgical outcome related to the extent of pathology but not to the histological abnormality. Lesions outside the temporal and frontal lobes were correlated with poor surgical outcome, as were generalised interictal EEG abnormalities, which may reflect extensive or multiple lesions. Ictal intracranial recordings were not useful for presurgical evaluation of cortical dysplasia.     

Merosin-negative congenital muscular dystrophy, occipital epilepsy with periodic spasms and focal cortical dysplasia. Report of three Italian cases in two families

We report clinical, EEG and neuroimaging findings of three patients in two Italian families with merosin-negative congenital muscular dystrophy (CMD), drug-resistant occipital epilepsy, diffuse persistent cerebral white matter changes and focal cortical dysplasia. Clinical and epilepsy histories, EEG and neuroimaging findings were very similar in all patients. Seizures started in childhood and mainly consisted of periodic spasms, a particular type of partial seizure characterized by clusters of epileptic spasms. The motor expression of the spasms was very mild so that they had been frequently missed or misinterpreted as non-convulsive generalized absence seizures. Interictal EEG showed occipital spike-waves and bilateral synchronous slow spike-wave discharges. Ictal EEG showed prolonged periodic sequences of slow waves with associated fast rhythm complexes, characteristic of periodic spasms. Two patients had normal intelligence, one patient presented moderate mental retardation. Focal cortical dysplasia in the posterior areas of the brain, in addition to marked diffuse white matter alterations, was detected in the magnetic resonance images of all patients. Findings in these patients indicate that in merosin-negative CMD brain involvement can include cortical dysplasia, in addition to white matter changes. In such cases the brain damage can lead to a childhood-onset localization-related symptomatic occipital epilepsy. Epileptic seizures and cortical dysplasia can be, however, difficult to detect in CMD. The clinical semiology of epileptic seizures may in fact be modified because of muscular weakness. This implies that epilepsy may be misdiagnosed or even missed and EEG-polymyographic recordings may be necessary to identify it. Similarly, cortical dysplasia may be very localized and visible by neuroimaging only if it is carefully investigated on the basis of epileptological and EEG-polymyographic findings.