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Early surgery for epilepsy: redefining candidacy.

Surgical resection for localization-related epilepsy has recently become a generally accepted treatment in children. Evidence of the poor outcome in natural history studies of temporal lobe epilepsy in childhood initiated consideration of surgical intervention. Subsequent favorable outcome following surgery was encouraging. A number of variables differentiate adults with focal seizures from children. Evolving biologic factors modify the clinical and electroencephalographic expression of seizures in childhood. The pathologic substrate is different, and there is a higher incidence of extratemporal epilepsy. Chronic seizures beginning under age 2 years rarely remit, especially when associated with a demonstrable structural lesion. Behavioral consequences of chronic seizures are significant and become a major problem by adolescence if seizures are not controlled. Early surgery results in superior functional outcome, although subtle deficits persist postoperatively. Surgical outcome is as favorable as in adults with improvements in behavioral status and socialization. Abundant data exist to more adequately assess the benefits and risks of surgery in children so that intervention is not deferred longer than it needs to be.

Adolescent↗

Therapeutics in pediatric epilepsy, Part 2: Epilepsy surgery and vagus nerve stimulation.

When antiepileptic drugs fail to relieve seizures adequately in children and adolescents, more invasive therapies such as epilepsy surgery and an implanted device to stimulate the vagus nerve should be considered. Temporal lobectomy is an effective treatment of complex partial and secondarily generalized tonic-clonic seizures arising in the mesial structures or lateral temporal neocortex. Excellent outcomes (seizure free or rare, nondisabling seizures) are achieved in at least 70% of children. The most common adverse effect is a superior quadrant field cut that is usually asymptomatic. Transient and more long-lasting language difficulties have been reported when the surgery involves the dominant temporal lobe. The excellent outcome rate for extratemporal surgery ranges from approximately 20% to 80%, with better results seen in patients with an identifiable lesion. Potential morbidity is related to the region of resected neocortex. Corpus callosotomy is an excellent procedure for palliation but is not a cure for seizures that cause falls, with substantial improvement seen in more than 80% of patients. Potential adverse effects include more intense focal seizures and dysphasia, depending on the developmental level of the individual. Hemispherectomy provides seizure relief in 60% to 80% of patients with hemispherical pathologies such as Sturge-Weber or Rasmussen syndromes. Operative mortality has been reported in the range of 0% to 6%; other morbidities include infection and hydrocephalus. Stimulation of the vagus nerve has reduced partial seizures by 50% or more in approximately one third of patients. No adverse cognitive or systemic effects are associated with use of the implanted vagus nerve stimulator.

Child↗

Invasive electrographic recording techniques in temporal lobe epilepsy.

The management of uncontrolled partial epilepsy is a process dependent on a multidisciplinary and analytic approach. It is necessary to understand which lesions are epileptogenic, and if they are indeed responsible for the generation of seizures. In addition to localizing seizure onset, the functional and eloquent areas of the brain need to be identified. As in many other centres, we perform resective surgeries on the basis of combined information derived from seizure semiology, EEG abnormalities, neuroimaging and other tests of cerebral function. If surface EEG recording yields inconclusive or ambiguous results, then invasive intracranial techniques using intracerebral depth or subdural electrodes can be used to improve diagnostic or prognostic accuracy. The indications, principles, results and complications of these recording techniques based on extensive experience at two epilepsy surgery centres are reviewed.

Brain↗

Temporal lobe epilepsy in early childhood.

To explore the electroclinical features of temporal lobe epilepsy (TLE) in early childhood, we studied results of video-EEG and other tests of 14 children aged 16 months to 12 years selected by seizure-free outcome after temporal lobectomy. Four children had mesiotemporal sclerosis, 1 had cortical dysplasia, and 9 had low-grade temporal neoplasms. The children had complex partial seizures (CPS) with symptomatology similar to that of adults with TLE, including decreased responsiveness and automatisms. Automatisms tended to be simpler in the younger children, typically limited to lip smacking and fumbling hand gestures. Scalp/sphenoidal EEG showed anterior/inferior temporal interictal sharp waves and unilateral temporal seizure onset in the 4 children with mesiotemporal sclerosis and in the child with cortical dysplasia, but EEG findings in 9 children with low-grade temporal tumors were complex, including multifocal interictal sharp waves or poorly localized or falsely lateralized EEG seizure onset. In children without tumors, video-EEG was critical to localization of the epileptogenic zone for resection, but in patients with tumors video-EEG was less localizing and its main value was to confirm that the reported behaviors were epileptic seizures with semiology typical of temporal lobe onset.

Age Factors↗

Persistent sodium current in subicular neurons isolated from patients with temporal lobe epilepsy.

The persistent sodium current is a common target of anti-epileptic drugs and contributes to burst firing. Intrinsically burst firing subicular neurons are involved in the generation and spread of epileptic activity. We measured whole-cell sodium currents in pyramidal neurons isolated from the subiculum resected in drug-resistant epileptic patients and in rats. In half of the cells from both patients and rats, the sodium current inactivated within 500 ms at -30 mV. Others displayed a tetrodotoxin-sensitive slowly or non-inactivating sodium current of up to 53% of the total sodium current amplitude. Compared with the transient sodium current in the same cells, this persistent sodium current activated with normal kinetics but its voltage-dependent activation occurred 7 mV more hyperpolarized. Depolarizing voltage steps that lasted 10 s completely inactivated the persistent sodium current. Its voltage dependence did not differ from that of the transient sodium current but its slope was less steep. The voltage dependence and kinetics of the persistent sodium current in cells from patients were not different from that in subicular cells from rats. The current density and the relative amplitude contribution were 3-4 times greater in neurons from drug-resistant epilepsy patients. The abundant presence of persistent sodium current in half of the subicular neurons could lead to a larger number of neurons with intrinsic burst firing. The extraordinarily large amplitude of the persistent sodium current in this subset of subicular neurons might explain why these patients are susceptible to seizures and hard to treat pharmacologically.

Animals↗

Detection and significance of focal, interictal, slow-wave activity visualized by magnetoencephalography for localization of a primary epileptogenic region.

OBJECT: Magnetoencephalography (MEG) is a novel noninvasive diagnostic tool used to determine preoperatively the location of the epileptogenic zone in patients with epilepsy. The presence of focal slowing of activity recorded by electroencephalography (EEG) is an additional indicator of an underlying pathological condition in cases of intractable mesial temporal lobe epilepsy (MTLE). In the present study the authors examined the significance of focal, slow-wave and interictal spike activity detected using MEG in 29 patients who suffered from MTLE that was not associated with structural brain lesions. METHODS: All patients underwent resective surgery after MEG and EEG monitoring. Equivalent single-dipole modeling was applied to focal low-frequency magnetic activity (LFMA) and interictal paroxysmal activity. Lateralized LFMA was defined as trains of rhythmic activity over the temporal area, with frequencies lower than 7 Hz, which were easily distinguished from background activity. Lateralized LFMA was found in 17 patients (58.6%); it always occurred on the side ipsilateral to the side of resection and displayed a maximum amplitude over the temporal area. Dipolar sources of magnetic flux computed during slow-wave trains were found in the majority of cases in the posterior superior temporal region and, occasionally, in mesial temporal structures that were subsequently resected. With respect to lateralization there was never disagreement between LFMA and MEG interictal spike sources. Thus, in patients with MTLE that is not associated with a mass lesion LFMA is topographically related to the epileptogenic area and, therefore, has value for reliable determination of the side and, possibly, the location of this area. CONCLUSIONS: Although focal slowing of EEG background activity is generally considered to be a nonspecific sign of functional disturbance, interictal LFMA in patients with MTLE should be conceptualized as a distinct electrographic phenomenon that is directly related to the epileptogenic abnormality. Analyzing the interictal MEG distribution of LFMA and sharp activity improves the diagnostic utility of MEG in patients with suspected TLE who are undergoing surgical evaluation.

Adolescent↗

Differential neuronal and glial relations with parameters of ictal discharge in mesial temporal lobe epilepsy.

PURPOSE: EEG recordings of spontaneous seizures should provide clues to epilepsy pathogenesis and pathology. We examined onset, propagation, and termination characteristics of spontaneous seizures recorded by intracranial EEG in temporal lobe (TL) epilepsy in relation to neuronal, glial, and synaptic changes in the same tissue. METHODS: All of our patients with intracranial EEG recordings of spontaneous TL seizure onset, subsequent TL resection, and quantitative pathologic analysis of resected tissue were included. Seizure parameters were mean time to initial propagation, mean total electrical duration, uniformity of seizure-onset distribution and location, and percentage of seizures with spiking onset per patient. Tissue was analyzed for glial and neuronal density in hippocampal fields and presence of sprouting. Outcome was classified as seizure free or not. RESULTS: All seizures with onset in resected TL in 62 patients were analyzed. The percentage of each patient's seizures with spike onsets was significantly correlated with glial density in CA3 (p < 0.01). Initial propagation time was significantly and inversely correlated with neuronal density in CA4 (p < 0.02). Electrical seizure duration was significantly correlated with glial density in CA2 and CA3 (p < 0.02). Neuronal and glial density were significantly (and inversely) related to one another only in CAI (p < 0.001). Outcome was most significantly related to uniform hippocampal seizure onset. Presence or absence of sprouting was not significantly related to outcome or any EEG measure. CONCLUSIONS: These results suggest both glia and neurons exert independent influences on the expression of ictal discharges in seizures of medial TL onset. Glial density influenced interictal-ictal transition, whereas neuronal density influenced seizure propagation. These findings may have implications for pathogenesis.

Cell Count↗

Preoperative electroencephalographic investigation in temporal lobe epilepsy: extracranial and intracranial recordings.

Preoperative EEG investigations of patients with temporal lobe seizures include extracranial interictal and ictal recordings during wakefulness and sleep, including long-term EEG and video-monitoring. Interictal epileptiform discharges when evaluated conservatively and in conjunction with other EEG and non-EEG localizing information, provide valuable guidance for the identification of the area to be resected, as do ictal recordings. When extracranial EEG features in conjunction with non-EEG data provide conflicting localizing information, intracranial recordings with stereotaxically implanted depth and epidural electrodes are used. Intracranial recordings must be designed to avoid biasing the exploration strategy in favor of one's preferred localizing hypothesis. Patients with evidence for bitemporal epileptogenic dysfunction in extracranial EEG recordings are suitable candidates for intracranial recordings. The majority of the patients explored in this manner show that all or more than 80% of their seizures arise from one temporal lobe. Excision of that lobe yields satisfactory results in a fair proportion of these patients. The number of satisfactory outcomes is however, still somewhat less than in patients with unilateral temporal foci in extracranial EEG recordings.

Electroencephalography↗

Pleomorphic xanthoastrocytoma: report of a case diagnosed by intraoperative cytopathological examination.

The authors present an unusual case of a 13-yr-old boy with a 3-mo history of seizures. A CT scan showed a contrast-enhancing mass located in the left temporal lobe. The patient underwent a stereotatic-guided craniotomy; intraoperative cytological diagnosis was performed by the smear technique, showing a pleomorphic xanthoastrocytoma. The tumor was totally resected. Definitive diagnosis was established by examination of paraffin-embedded material. Six months after the surgical intervention, the patient is doing well, with no radiological evidence of recurrence. The cytological differential diagnosis of giant cell lesions of the central nervous system is emphasized.

Adolescent↗

Gray-to-white matter ratios of HMPAO in the human brain.

The gray-to-white matter ratio of technetium 99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) in 14 anesthetized patients undergoing partial brain resection for treatment of complex partial seizures. The gray-to-white matter ratio of 99mTc-HMPAO was 1.8:1 (standard deviation 0.6) in the temporal lobe. Many of the biopsied specimens demonstrated histopathological abnormalities.

Adult↗

[A case of fatal herpes encephalitis presenting massive cerebral hematoma].

A 53-year-old woman was admitted to the hospital because of headache and disturbance of consciousness. She was afebrile. No inflammatory reaction was identified on serologic examination. Radiological findings showed acute-subacute, massive intracerebral hemorrhage in the right temporal lobe, compressing the brain stem contra-laterally. On the day of admission, she underwent a right temporal craniotomy for the removal of the mass lesion. The resected brain tissue demonstrated a small hemorrhage and edema accompanied by the infiltration of lymphoid cells into the subarachnoid space. Several days after surgery, the patient became lethargic and showed urinary incontinence. Late onset of fever and CSF findings suggested she was suffering from viral encephalitis. Serological findings, however, disclosed no antibody production against HSV, HZV, or CMV. For the diagnosis, a biopsy of the brain was carried out and herpes encephalitis was subsequently proved. Unfortunately, her condition deteriorated quickly and she died without anti-viral treatment.

Aged↗

An oligo astrocytoma with widespread calcification along axonal fibres.

A rare case of a young man with a diffusely calcified oligo astrocytoma in right parieto occipital region, which spread along the axonal fibres into right temporal lobe and to the left parietal lobe is presented. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated the extent of the lesion. The mass was partially resected.

Adult↗

Lateralising value of ictal features in partial seizures: effect on postsurgical outcome.

We reviewed the videotapes of 49 consecutive patients with a history of medically refractory temporal lobe epilepsy for the presence and laterality of unilateral hand posturing (UHP), unilateral hand automatism (UHA), non-forced head turning (HT), and post-ictal dysphasia (PID). All of these patients underwent temporal resections with follow-up for more than 2 years after the surgery. We examined the correlation of consistency, frequency, and laterality of each of these signs on the postsurgical outcomes. The distribution of these signs was not significantly different between patients with Engel class 1 versus Engel class 2-4. The consistency and laterality of these signs do not correlate with postsurgical outcomes.

Aphasia↗

Surgical management of intractable epilepsy associated with cerebral neurocytoma.

Neuronal neoplasms of the CNS constitute a rarely encountered group of tumors. This report concerns the surgical management of seizures encountered in four cases (ranging from 2 to 10 years-of-age at onset; consisting of two males and two females) of a recently recognized morphologically unique tumor, called 'cerebral neurocytoma'. All patients were associated solely with intractable complex partial seizures. The tumor involved the temporal lobe in two cases, and the frontal in two. Magnetoencephalography (MEG) clearly demonstrated an accumulation of equivalent current dipoles originating from the interictal spikes on the cortex around the tumor. On intra-operative electrocorticography (ECoG), the epileptogenic zone was topographically distinct from the region of the tumor. No definite ECoG activities were observed at the tumor site, although this tumor did consist of small mature neuronal cells. Either a complete or a subtotal resection of the tumor and the epileptogenic cortex was performed and, post-operatively, universal freedom from seizures was demonstrated in all patients. A histological examination of the epileptogenic cortex revealed the presence of minute cortical dysplasia or tumor involvement in the hippocampus. A resection of the epileptogenic cortex along with the tumor was thus found to improve the seizure outcome in patients with neurocytoma-associated epilepsy without inducing any identifiable neurological deficits attributable to the incremental resection.

Adult↗

Normative data on 372 stimuli for descriptive naming.

Naming problems are common in patients with dominant temporal lobe epilepsy (TLE) and anterior temporal lobectomy (ATL). Descriptive naming may be an especially useful procedure for the presurgical workup of candidates for ATL, given its sensitivity for detecting subtle naming problems in TLE and its localization to anterior temporal regions that are commonly targeted for resection in ATL. This study provides normative data pertaining to difficulty level (accuracy and reaction time) on 372 descriptive naming items in four conceptual categories: common non-living, common living, unique non-living, and unique living things. These data will be useful to investigators who wish to develop protocols for clinical assessment or stimuli for functional imaging paradigms aimed at assessing the function of the anterior temporal lobes.

Adolescent↗

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↗

Changes in intelligence following temporal lobectomy: relationship to EEG activity, seizure relief, and pathology.

Pre- and posttemporal lobectomy measures of intelligence and memory in 36 patients with medically refractory complex partial seizures were compared with (1) various aspects of presurgical ictal and interictal EEG activity derived from surface and deep electrodes, (2) postlobectomy seizure relief, and (3) pathological findings in the resected lobe. With respect to interictal EEG data, bilaterally synchronous surface spikes (accompanied or unaccompanied by simultaneous deep spikes) and sharp waves were significantly correlated with lower prelobectomy intelligence scores and a drop in these scores following lobectomy. With respect to ictal EEG data, bilaterally synchronous and multifocal onsets were significantly correlated with a postlobectomy drop in intelligence scores. Patients with poor postlobectomy seizure relief tended to have lower presurgical intelligence scores and a drop in intelligence scores following lobectomy. The patients most likely to show a postlobectomy drop in intelligence were those demonstrating some combination of poor seizure relief, an absence of pathology in the resected specimen, or EEG signs indicative of poor seizure relief. Postlobectomy changes in intellectual status are therefore not necessarily exclusively attributable to the amount of postlobectomy seizure relief experienced by these patients, but might be due to a combination of factors.

Adult↗

Diagnosis and treatment of temporal lobe epilepsy.

Of the 1,200,000 Americans with partial epilepsy, temporal lobe epilepsy (TLE) occurs in more than 400,000. Temporal lobe seizures are usually stereotypic in their symptoms and duration. A typical sequence is an aura followed by arrest of motor behavior, blank stare, and automatisms. Patients with TLE often show impairments in attention, memory, mental processing speed, executive functions, mood, personality, and drive-related behaviors. Interictal depression occurs in approximately one third of TLE patients. TLE is diagnosed by a history of characteristic partial seizure symptoms. The diagnosis is confirmed by the capture of a typical episode during an electroencephalogram (EEG) or video-EEG, with epileptiform activity over one or both temporal regions. Video-EEG monitoring has revolutionized diagnosis and should be considered in patients in whom diagnosis is uncertain. TLE is treated with medications, resective surgery, and vagus nerve stimulation. Epilepsy surgery should be considered in all patients with refractory partial epilepsy.

Epilepsy, Temporal Lobe↗