Richard S. McLachlan

Hippocampal electrical stimulation in mesial temporal lobe epilepsy

Background: Adjustable, reversible therapies are needed for patients with pharmacoresistant epilepsy. Electrical stimulation of the hippocampus has been proposed as a possible treatment for mesial temporal lobe epilepsy (MTLE). Methods: Four patients with refractory MTLE whose risk to memory contraindicated temporal lobe resection underwent implantation of a chronic stimulating depth electrode along the axis of the left hippocampus. The authors used continuous, subthreshold electrical stimulation (90 μsec, 190 Hz) and a double blind, multiple cross-over, randomized controlled design, consisting of three treatment pairs, each containing two 1-month treatment periods. During each treatment pair the stimulator was randomly turned ON 1 month and OFF 1 month. Outcomes were assessed at monthly intervals in a double blind manner, using standardized instruments and accounting for a washout period. The authors compared outcomes between ON, OFF, and baseline periods. Results: Hippocampal stimulation produced a median reduction in seizures of 15%. All but one patient’s seizures improved; however, the results did not reach significance. Effects seemed to carry over into the OFF period, and an implantation effect cannot be ruled out. The authors found no significant differences in other outcomes. There were no adverse effects. One patient has been treated for 4 years and continues to experience substantial long-term seizure improvement. Conclusion: The authors demonstrate important beneficial trends, some long-term benefits, and absence of adverse effects of hippocampal electrical stimulation in mesial temporal lobe epilepsy. However, the effect sizes observed were smaller than those reported in non-randomized, unblinded studies.

Morbidity associated with the use of intracranial electrodes for epilepsy surgery

BACKGROUND Invasive monitoring for the investigation of medically intractable epilepsy may be associated with undesirable morbidity. We performed a review of our recent experience to determine the incidence of major complications. METHODS We reviewed the clinical records of all patients who underwent invasive EEG monitoring at our institution between 2000 and 2004. RESULTS One-hundred and sixteen patients (57 males, 59 females) with a mean age of 32 years of age underwent intracranial placement of electrodes for epilepsy surgery investigation. Subdural strips were placed in 115 patients with a mean of eight strips per patient. Subdural grids were inserted in 11 patients and depth electrodes in five. Fourteen of the 15 patients with grids or depth electrodes also had strips. Coverage was unilateral in 37 patients and bilateral in 79 patients. Electrodes were placed over the frontal lobe in 78 cases, temporal in 93, parietal in 24, and occipital in 27 patients. The average duration of investigation was 12.3 days (range 3-29). The evaluation led to the performance of a surgical resection in 85 patients (74%). Complications were seen in four patients with subdural strips (3%), and in two patients with grids (13%), characterized by clinical infection, intracranial hemorrhage, aseptic meningitis, transient neurological deficits, and status epilepticus. Mortality was nil. CONCLUSIONS In comparison with previously published literature on the topic, the major complication rate in this group of patients appears to be low.

Psychiatric disorders in candidates for surgery for epilepsy.

OBJECTIVE--To provide a descriptive analysis of the prevalence and pattern of psychiatric morbidity among 300 consecutive epileptic patients refractive to treatment and admitted during a six year period for evaluation of their candidature for surgery. METHODS--Patients underwent detailed observation of their seizure and standardised psychiatric assessment. Patients were considered to be refractory to treatment if they continued to manifest seizures with an average frequency of at least once every month even with polytherapy using up to three different anti-convulsants for a period of at least two years. Of the 300 patients, 231 had a temporal lobe focus, 43 had a non-temporal lobe focus, and 26 patients had a generalised and multifocal seizure onset. RESULTS AND CONCLUSIONS--With the DSM-III-R criteria 142 (47.3%) patients emerged as psychiatric cases. A principal axis I diagnosis was made in 88 (29.3%), and an axis II diagnosis (personality disorder) in another 54 (18.0%) patients. The most common axis I diagnosis was anxiety disorders (10.7%). A schizophrenia-like psychosis was seen in 13 (4.3%). Most patients with personality disorders showed dependent and avoidant personality traits. There was a significantly higher psychotic subscore on the present state examination in the temporal than with the non-temporal group of patients. These findings were not significant when compared with patients with a generalised and multifocal seizure disorder. There were no significant findings between the different seizure focus groups on the neurotic subscores. The findings with regard to laterality of seizure focus and the neurotic or psychotic subscores were not significant.

Outcome Assessment in Epilepsy: Comparative Responsiveness of Quality of Life and Psychosocial Instruments

Summary: Purpose: Few data exist on the ability of instruments to detect within‐patient change over time in epilepsy, a property referred to as responsiveness. Our aim was to compare the responsiveness of three instruments [i.e., Epilepsy Surgery Inventory‐55 (ESI‐55) and Washington Psychosocial Inventory (WPSI), both epilepsy specific, and Symptom Checklist‐90–Revised (SCL‐90–R), non‐epilepsy specific].

Psychosis After Resection of Ganglioglioma or DNET : Evidence for an Association

Summary: Purpose: David Taylor and Murray Falconer suggested that some patients may develop a psychotic illness after resection of a ganglioglioma that led to intractable seizures. They implied that the mechanism of this association remained unclear. This concept is currently not universally accepted (M. Trimble, personal communication).

Bilateral hippocampal stimulation for intractable temporal lobe epilepsy: impact on seizures and memory.

The effect of continuous electrical stimulation of the hippocampus bilaterally on seizures and memory was assessed in two subjects with seizures from both mesial temporal lobes who were not candidates for resective epilepsy surgery. A double blind, randomized, controlled, cross‐over trial design was utilized. Two electrodes with four contacts each were implanted along the axis of the hippocampus bilaterally. Simultaneous stimulation of all electrodes contacts was either on or off during each 3‐month interval. Seizure frequency decreased by 33% in the two patients during stimulation and remained lower by 25% for the 3 months after stimulation was turned off before returning to baseline (p < 0.01). No consistent change in objective or subjective measures of memory occurred. No other adverse effects occurred. Seizure frequency is reduced both during and for a period after bilateral hippocampal stimulation, but the overall impact in this study is not as robust as has been previously reported.

Amygdalar sclerosis: preoperative indicators and outcome after temporal lobectomy.

Isolated amygdalar sclerosis (AS) in the presence of an intact hippocampus has been described in a subset of patients who have undergone a temporal lobectomy for the relief of seizures. Clinical observation suggested that these patients might be distinguishable, before and after operation, from those with typical mesial temporal sclerosis, which implies combined amygdalar and hippocampal sclerosis (AHS). From a three year series, all 11 patients classified as having AS were included in this study. These patients were compared with a group of 20 randomly chosen patients with AHS. The groups were found to be well matched in duration of ongoing seizures, full scale IQ, and duration of follow up (mean 19 months). Compared with patients with AHS, patients in the AS group were less likely to have had a seizure in early childhood, a variety of auras, EEG abnormalities localised to one temporal lobe, or an abnormal MRI before operation. They also performed better on preoperative memory tests. At follow up, patients in the AS group were less likely to be seizure free and more likely to have a deterioration in memory after undergoing anterior temporal lobectomy, including part of the hippocampus. The results show that there are preoperative indicators of mesial temporal pathology that are also of prognostic importance given the differences in outcome between the two pathological groups.

Propofol sedation during awake craniotomy for seizures: electrocorticographic and epileptogenic effects.

This prospective study evaluated the effects of propofol sedation on the incidence of intraoperative seizures and the adequacy of electrocorticographic (ECoG) recordings during awake craniotomy performed for the management of refractory epilepsy.Thirty patients scheduled for temporal or frontal lobectomy for epilepsy under bupivacaine scalp block were randomized to receive patient-controlled propofol sedation (PCS) combined with a basal infusion of propofol (n = 15) or neurolept analgesia using an initial bolus dose of fentanyl (0.7 micro g/kg) and droperidol (0.04 mg/kg) followed by a fentanyl infusion (n = 15). Propofol administration was suspended 15 min before ECoG recording in the PCS group. The occurrence of inappropriate intraoperative seizures was noted and, based on blind review, the adequacy of ECoG recordings was compared. A higher incidence of intraoperative seizures was noted among the neurolept patients (6 vs 0, P = 0.008). Intraoperatively, ECoG recordings were adequate to proceed with resection in both groups. Evidence of low spike activity on ECoG did not correlate with the type of sedation administered. Higher frequency background ECoG activity was noted among patients who received propofol, but this did not interfere with ECoG interpretation. The use of propofol sedation does not appear to interfere with ECoG during epilepsy surgery, provided administration is suspended at least 15 min before recording. (Anesth Analg 1997;84:1280-4)

Seizure identification by clinical description in temporal lobe epilepsy How accurate are we

Objective: To determine the accuracy of the clinical history performed by epileptologists in the identification of seizures in patients with suspected temporal lobe epilepsy. Methods: The clinical and EEG telemetry (EEGT) monitoring data of 88 patients with suspected refractory temporal lobe seizures referred for evaluation of epilepsy surgery were prospectively evaluated. All clinical events obtained by history in these patients were adjudicated as being a seizure or not by two blinded (without access to EEG data) independent epileptologists. Each clinical event was then matched with the corresponding clinical event recorded with EEG telemetry in the epilepsy monitoring unit (gold standard). Sensitivity, specificity, overall accuracy, predictive value, and interrater agreement for the clinical assessment were obtained. Results: Of 357 clinically different events, 175 (49%) were reproduced in the epilepsy monitoring unit. Only 10 events were misidentified by history as being a seizure or not, resulting in an overall clinical accuracy of 94%. Epileptologists’ sensitivity for seizure identification was 96% (95% CI 92, 98%) but specificity was only 50% (95% CI 22, 79%). Accuracy for complex partial seizures and generalized seizures was higher than for simple partial seizures (SPS). Misidentification occurred only with SPS and nonepileptic events. Agreement beyond chance among epileptologists was good. Conclusion: In this selected group of patients with temporal lobe epilepsy, seizure identification by clinical history is highly accurate. Epileptologists rarely miss seizures (high sensitivity) but more often overcall nonepileptic events as seizures (low specificity).

Mefloquine in the treatment of progressive multifocal leukoencephalopathy

Mefloquine, an antimalarial medication with efficacy against JC virus, was used to treat progressive multifocal leukoencephalopathy. A 54-year-old woman with sarcoidosis presented with a progressive cerebellar syndrome. MRI showed lesions affecting the right cerebellum that progressed over time to the brainstem. JC virus was found in the cerebrospinal fluid (CSF), and brain biopsy confirmed the diagnosis of progressive multifocal leukoencephalopathy. Mefloquine 1000 mg/week was initiated 6 months after symptom onset. Clinical progression stopped immediately, and JC virus became undetectable in the CSF. No clinical or imaging evidence of disease progression has occurred over 20 months of follow-up. This is the first report of successful treatment of progressive multifocal leukoencephalopathy with mefloquine.