Antiepileptic drug therapy for adult patients with intractable seizures]

Epileptic syndrome, antiepileptic drug (AED) therapy and mental disorder were studied in 223 patients with intractable epilepsy, who were admitted to our epilepsy center between 1992 and 2000. Symptomatic localization-related epilepsy was diagnosed in 86.1% of patients, symptomatic or cryptogenic generalized epilepsy in 7.6%, idiopathic generalized epilepsy in 1.8%, unclassifiable epilepsy in 3.1% and non-epilepsy in 1.3% on discharge. Only 6.3% had diagnoses on discharge that were incongruent with their diagnoses on admission. AED therapy during admission improved markedly in 50% of patients and moderately in 20%, however, 60% had seizures more frequently than 4 a month on discharge. Generalized tonic and clonic seizures were suppressed completely in 82.5% of patients. The number of AEDs used were 2 AEDs in 28.6%, 3 in 39.1% and 4 in 22.3%. Only 6.4% of patients were on monotherapy on discharge. Mental retardation was in 58.7%, schizophrenia-like psychosis in 8.5%, delusional disorder in 1.8%, mood disorder in 3.6%, AED-related disorder in 14.3% and psychogenic disorders in 21.5%. AED therapy is effective for intractable seizures, but it is limited in its effect. Mental disorders also coexisted in most of patients. Therefore comprehensive therapy of epilepsy is necessary for patients with intractable seizures.     

Epilepsy surgery in patients with additional psychogenic seizures.

OBJECTIVE: To assess whether surgery to reduce or control epileptic seizures is safe and effective in patients known to have additional psychogenic seizures. DESIGN: We reviewed our computerized database of 1342 patients examined for epilepsy surgery and identified 13 patients with both epileptic and psychogenic seizures on whom postoperative outcome data were available. Data were gathered from the patients' records. Mean postoperative follow-up was 56 months. RESULTS: Epilepsy surgery led to clinically relevant improvements in 11 of 13 patients. Seven patients became free of epileptic and psychogenic seizures, 2 patients became free of epileptic seizures but continued to have infrequent psychogenic seizures, 1 patient reported more than an 80% improvement in epileptic seizure frequency and an abolishment of psychogenic attacks, and in 1 patient nondisabling epileptic seizures persisted at lower frequency but psychogenic seizures stopped. In 2 of 13 patients, epilepsy surgery failed to produce notable improvements. Although 1 patient became free of epileptic attacks and the other had fewer than 3 epileptic seizures per year, the severity or frequency of psychogenic seizures and pseudo-status epilepticus increased postoperatively. One of these patients had a preoperative diagnosis of somatization disorder; in the other, pathological illness behavior had been noted. CONCLUSION: A diagnosis of additional psychogenic seizures should not be considered an absolute contraindication to epilepsy surgery, although patients should undergo careful preoperative psychiatric evaluation.     

Epilepsy surgery in patients with bilateral temporal lobe seizures: A systematic review

We explored the association between magnetic resonance imaging (MRI) lesion, degree of seizure laterality on intracranial electroencephalography (iEEG), and seizure outcome in patients with ambiguous or presumed bilateral temporal lobe epilepsy (BiTLE) on scalp EEG. We systematically reviewed the literature using Embase and MEDLINE up to May 31, 2012. Patients with bilateral iEEG, temporal lobe surgery, and follow‐up ≥1 year were included. We undertook three separate analyses on patients whose scalp EEG showed ambiguous onset or BiTLE (1) group data of those whose iEEG demonstrated unilateral TLE, (2) group data of those whose iEEG demonstrated BiTLE, (3) individual patient analysis in those with BiTLE for whom iEEG seizure laterality data were provided. Of 1,403 patients with ambiguous or presumed BiTLE on scalp EEG, 1,027 (73%) proved to have unilateral TLE on iEEG and contributed to the first analysis. Of these, 58% had Engel class I and 9% Engel class II outcomes. Of 132 patients in the second analysis (true BiTLE), Engel class I and II outcomes were achieved in 23% and 14%, respectively. Of 41 patients in the third analysis, 66% and 2% had Engel class I and II outcomes, respectively. The median proportion of seizures ipsilateral to the resection on iEEG did not differ between BiTLE patients with Engel class I–II (76%) and Engel III–IV (78%) outcomes (p = 0.87). Patients with ambiguous or independent bitemporal seizure onset on scalp EEG achieved good surgical outcomes. Overall, a significantly higher proportion of patients achieved good outcomes when iEEG showed unilateral TLE (67%) than when it showed true BiTLE (45%). However, the degree of seizure lateralization in those with BiTLE was not associated with seizure outcome, and it has a limited role in selecting the side of surgery.     

The evaluation of patients with intractable complex partial seizures

Conceptual advantages, together with advances in both technique and technology, have considerably altered the approach to intractable epilepsy over the past two decades. Appropriate utilization of these advances allows our evaluation of patients with intractable seizures to be much more precise and specific than was once the case and allows us to improve considerably our ability to treat patients with intractable epilepsy. We propose an algorithm for the evaluation and treatment of patients with intractable complex partial seizures. Other forms of intractable epilepsy may benefit from similar diagnostic and therapeutic approaches.     

Epilepsy surgery in children with seizures arising from the rolandic cortex

Purpose: Medically intractable seizures arising from the sensorimotor (rolandic) cortex present a formidable challenge for epileptologists and epilepsy surgeons. The objective of this study was to evaluate the safety and efficacy of surgical treatment for seizures in this region. Methods: We retrospectively reviewed the medical records of 24 children and adolescents who underwent surgical management of refractory rolandic epilepsy at our institution. Results: Patient age at the time of surgery ranged between 1.9 and 19.2 years, and median postoperative follow‐up was 2.3 years. Three patients had clear lesions on preoperative magnetic resonance imaging (MRI) that correlated with noninvasive electroencephalography (EEG) and underwent single‐stage lesionectomies. Of the 21 patients who underwent invasive monitoring, 19 underwent therapeutic procedures, including lesionectomy, topectomy, and multiple subpial transections. Engel class I and II outcomes were seen in five of six patients (84.0%) after lesionectomy and in seven of nine patients (77.0%) and four of six patients (66.7%) after sensorimotor corticectomy or multiple subpial transections (MSTs), respectively. At last follow‐up, neurologic deficits were observed following 50.0% (n = 3 of 6) of lesionectomies and 67.0% (n = 7 of 9) of topectomies; no neurologic deficits were seen in patients undergoing motor cortex MSTs. No correlation existed between seizure outcome and duration of epilepsy, age at diagnosis, age at surgery, histopathology, or the presence or absence of a discrete lesion. Discussion: Surgery for appropriately selected children with intractable seizures arising from rolandic cortex was effective and associated with minimal neurologic morbidity in many cases. Engel I–II outcome was achieved in 77% of patients overall, and neurologic deficits were often mild and improved over time. Lesionectomy resulted in the best seizure control, followed by topectomy, and then MSTs.     

Epilepsy after early-life seizures can be independent of hippocampal injury

Prolonged early-life seizures are considered potential risk factors for later epilepsy development, but mediators of this process remain largely unknown. Seizure-induced structural damage in hippocampus, including cell loss and mossy fiber sprouting, is thought to contribute to the hyperexcitability characterizing epilepsy, but a causative role has not been established. To determine whether early-life insults that lead to epilepsy result in similar structural changes, we subjected rat pups to lithium-pilocarpine-induced status epilepticus during postnatal development (day 20) and examined them as adults for the occurrence of spontaneous seizures and alterations in hippocampal morphology. Sixty-seven percent of rats developed spontaneous seizures after status epilepticus, yet only one third of these epileptic animals exhibited visible hippocampal cell loss or mossy fiber sprouting in dentate gyrus. Most epileptic rats had no apparent structural alterations in the hippocampus detectable using standard light microscopy methods (profile counts and Timm's staining). These results suggest that hippocampal cell loss and mossy fiber sprouting can occur after early-life status epilepticus but may not be necessary prerequisites for epileptogenesis in the developing brain.     

Postictal symptoms help distinguish patients with epileptic seizures from those with non-epileptic seizures.

The aim of the study was to assess whether post-ictal symptoms can help distinguish patients who have epileptic seizures from those with non-epileptic seizures (NES). We reviewed the spontaneous responses to the question 'What symptoms do you have after a seizure?' in 16 patients with epileptic seizures (predominantly focal with secondary generalization or generalized tonic-clonic) and 23 NES patients. Six of the 16 patients (38%) vs. only one of 23 NES patients (4.3%) noted post-ictal headache (P = 0.008). Nine epilepsy patients (56%) vs. three NES patients (13%) reported post-ictal fatigue (P = 0.004). Confusion or other symptoms did not distinguish epilepsy patients from those with NES. All epilepsy patients had at least one post-ictal symptom while 12 NES patients (52%) had none (P = 0.001). Therefore, patients evaluated for epileptic vs. non-epileptic seizures who have post-ictal fatigue or headache, are more likely to have epileptic seizures. Patients with a diagnosis of NES who note post-ictal fatigue or headache should be investigated further.     

Surgical treatment of patients with low-grade astrocytomas and medically intractable seizures

OBJECTIVE: Low-grade astrocytomas can present with seizures that respond poorly to antiseizure medications, with a consequent reduction in the quality of life, because of both seizures and the medication's side-effects. We report our experience with operative treatment of such patients. SUBJECTS AND METHODS: Five patients (two children and three adults) with supratentorial low-grade astrocytomas associated with severe seizures were operated on. We followed the effects of the operation on post-operative neurological deficit, seizure frequency and the quality of life. RESULTS: No serious neurological complications followed the operations. The patients were followed for a median period of 12 months (6-46). Post-operatively, three of the patients became seizure-free, one experiences only auras, and one had a great reduction in seizure frequency and severity. All patients reported great improvement in their quality of life. CONCLUSION: Resections of low-grade astrocytomas in patients with medically intractable seizures are safe procedures that effectively control seizures in the majority of patients, resulting in significant improvement in the patients' quality of life.     

HIPDM-SPECT in patients with medically intractable complex partial seizures. Ictal study

Both interictal and ictal N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3,propanediamine -single photon emission computed tomography (HIPDM-SPECT) were performed in 16 patients with medically intractable complex partial seizures. Ictal HIPDM-SPECT localized epileptic foci in 13 of 14 patients with unilateral temporal focus and provided confirmative evidence of epileptic focus in 11 patients by demonstrating maximally increased regional cerebral perfusion (rCP) in epileptic foci that had shown decreased rCP in a previous interictal study. Ictal HIPDM-SPECT in two patients with bitemporal foci showed more complicated patterns consisting of slightly increased rCP in bilateral multifocal regions. Ictal HIPDM-SPECT was particularly useful for investigating epileptic foci, and correlation with simultaneously recorded ictal electroencephalograms provided further insight for localizing epileptic foci.     

Valproic acid and intractable seizures in severely brain-damaged patients

We treated 52 mentally retarded patients with intractable seizures by adding valproic acid (VPA) to other drug regimens. Sixty-one percent improved clinically. VPA significantly reduced the frequency of generalized tonic-clonic seizures, generalized myoclonus, absence and atonic seizures. There was a significant correlation between clinical improvement and reduction of EEG paroxysmal activity.     

Lorazepam: a controlled trial in patients with intractable partial complex seizures

Lorazepam was studied in a double-blind, placebo-controlled, crossover trial in eight patients with frequent partial complex seizures refractory to therapy with a combination of standard anticonvulsant drugs. Concomitant antiepileptic drugs were maintained at therapeutic serum levels throughout the study, and concentrations of lorazepam were monitored. Following an 8-week baseline observation, patients were randomly assigned to placebo or lorazepam (1 mg BID). The dose was increased biweekly until seizures stopped or unacceptable side effects occurred. Eight weeks later, patients were crossed over, and the same escalating dose paradigm was followed. When seizure frequency during the last 2 weeks of each treatment was compared, seven of eight patients had fewer seizures on lorazepam, and the eighth had decreased seizure duration (a significant difference: p less than 0.01, two-tailed sign test). Blood level data suggest a narrow therapeutic window, with seizure improvement occurring at concentrations of 20-30 ng/ml and side effects at greater than 33 ng/ml. Lorazepam appears to be a useful adjunct in refractory partial complex seizure therapy. It should not be stopped abruptly, as an increase in seizure frequency may result.     

Epilepsy of infancy with migrating focal seizures: Six patients treated with bromide

PurposeWe present six patients with epilepsy of infancy with migrating focal seizures (EIMFS) and provide a comprehensive evaluation of potassium bromide therapy.MethodBetween February 1, 2007 and July 31, 2012, six patients who met the diagnostic criteria of EIMFS were treated with potassium bromide. Potassium bromide was added to other antiepileptic drugs (AEDs) in doses ranging from 30 to 80 mg/kg/day. Plasma bromide concentration was monitored. A therapeutic bromide concentration between 75 and 125 mg/dL was considered to be ideal.ResultsFour of six children responded well to bromide. One of these patients became seizure free, but remained severely mentally impaired. Two boys, currently 4 and 6 years of age, respectively, have monthly seizures as well as axial hypotonia and severe language impairment. The fourth child responded well to bromide, having only weekly seizures and moderate psychomotor retardation. The patient who became seizure free improved visual contact and head control. In the other three patients with good control, the seizures became focal without secondary generalization and status epilepticus and hospital admission was not required. The remaining two patients did not respond well to bromide. Adverse effects were seen in three cases: vomiting in one, drowsiness in another, and acneiform eruption in the face in the remaining patient. Adverse effects resolved with dose reduction.ConclusionEarly treatment with bromides should be considered in EIMFS to control the seizures and status epilepticus and to avoid progressive cognitive impairment. Potassium bromide is an old AED. Plasma concentration monitoring should be considered.     

Results of anterior corpus callosum section in 24 patients with medically intractable seizures

Twenty-four medically refractory seizure patients, who did not qualify for excisional surgery, had anterior two-thirds corpus callosum section. Three to 11 years' postoperative follow-up suggests that this procedure can (1) lateralize a frontal lobe focus, which may lead to subsequent localized excision and (2) significantly reduce seizure frequency and severity in 75% of the patients without giving any permanent neurologic deficits. Patients with an ictal focus confined to one frontal lobe did best (8/8 improved), followed by patients with secondarily generalized seizures and multifocal bilateral foci (5/6 improved). Patients with mental retardation benefited less frequently (5/10 improved), but 4/4 from this group with ictal falls associated with Lennox-Gastaut syndrome did benefit. In this series, the improvements following the anterior partial section were lasting if present at 1 year of follow-up. Anterior corpus callosum section should be considered as a diagnostic (lateralizing) and therapeutic option in appropriately defined medically refractory patients who do not qualify for excisional surgery.     

Magnetic resonance imaging (1.5 tesla) in patients with intractable focal seizures

Magnetic resonance (MR) (1.5 tesla) studies were performed in ten patients with temporal lobe epilepsy and two with temporofrontal epilepsy. Two patients with temporal lobe epilepsy and one with temporofrontal epilepsy exhibited areas of increased signal intensity on T2-weighted images in the mesiobasal portion of the temporal lobe shown by electroencephalography to be the epileptogenic focus; no analogous abnormalities had been found in these patients on computed tomographic scans. Pathologic studies have not revealed a specific ultrastructural correlate for the MR findings in this group of patients. We found MR to be a useful, noninvasive diagnostic adjunct in the presurgical assessment of some patients with temporal lobe epilepsy. Where abnormalities were found, they corresponded with the epileptogenic focus as defined by electroencephalography.