Experience on the use of Vagus Nerve Stimulation during pregnancy.

OBJECTIVE: Vagus Nerve Stimulation (VNS) is a neuromodulation device approved for the treatment of medically refractory epilepsy. Worldwide, only 35 cases of pregnancies that has been described. This study aims to continue to increase the limited knowledge of the use of VNS during pregnancy. METHODS: We interrogated the database of the Epilepsy program at Western University (1998-2018), and identified those patients who were implanted with VNS and became pregnant. RESULTS: From 114 patients implanted with VNS in our centre, four patients had a total of seven pregnancies. This is the first report with one woman implanted with VNS having three pregnancies. Three patients had genetic generalized epilepsy and one focal epilepsy due to periventricular nodular heterotopia. The median duration since implantation was 3.17 years (IQR: 1.33-4.33) and the output was 2.75 mA (IQR: 1.5-3.5). No modifications in stimulation settings were made in any patient during pregnancy. Three patients had obstetric complications, requiring c-sections. All babies were healthy, except one with intellectual disabilities of unclear severity. CONCLUSION: Our small sample suggests VNS could increase the obstetrical complications, but is likely safe for the fetus. However, a larger sample size should be collected to determine safety and potential teratogenicity of VNS.

Prognostic factors in patients with refractory idiopathic generalized epilepsy.

OBJECTIVE: Idiopathic generalized epilepsy (IGE) is an epileptic condition with good response to antiepileptic drugs (AED). Major syndromes are epilepsy with generalized tonic-clonic seizures (GTCS) alone, absence epilepsy and juvenile myoclonic epilepsy. However, clinical practice shows drug-resistant patients. Endpoint is to identify clinical features related with refractoriness in IGE and in its each individual syndrome. METHODS: We retrospectively collected 279 consecutive patients with IGE assessed in the Epilepsy Clinic of our institution. We defined drug-resistant epilepsy as a failure of adequate trials of 2 tolerated and appropriately chosen and used AED schedules. We classified patients in two groups: drug-resistant and drug-responsive. Clinical features were compared among these groups, in the whole IGE group as well as in each syndrome. RESULTS: There were 122 drug-resistant, 105 drug- responsive; 52 were undefined and excluded from the analysis. After multivariate analysis, early seizures onset (age <13), long-time epilepsy, several generalized seizure types, status epilepticus, EEG with generalized epileptiform activity, mainly polyspikes, and side effects with AED brought up as poor outcome factors. Additionally, 50.6% identified modifiable seizure triggers. Regarding syndromes, epilepsy with generalized tonic-clonic seizures alone had the same factors except several seizure types; presence of additional GTCS, polyspikes, history of AED side effects and psychiatric disorder were poor factors for absence epilepsy; only psychiatric comorbidity revealed significance in juvenile myoclonic epilepsy. SIGNIFICANCE: Refractoriness in IGE and its major syndromes is associated with clinical and electrographic parameters. Moreover, lifestyle advices from neurologists to the patients might help them to achieve a better seizure control.

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.

Can I go out for a smoke? A nursing challenge in the epilepsy monitoring unit.

Cigarette smoking is common in patients with intractable epilepsy. As a preliminary assessment of epilepsy and smoking, we evaluated the impact of breaks for smoking on the investigation of epilepsy patients admitted to our epilepsy monitoring unit. Absences from the epilepsy unit at the London Health Sciences Center were monitored for 6 months by nursing personnel. During these absences, events that occurred were registered as well. This is possible using portable EEG recorders (XLTEK) that patients carry with them all the time. A disadvantage is that video recording is not available if the patient has a seizure outside the unit. Information was entered consecutively in a datasheet. Diagnosis, duration of hospital stay, frequency of breaks, and time outside the unit were recorded. Descriptive and statistical analysis was performed. Two thousand two hundred and ninety trips were recorded. Mean duration of stay was 10 days for smokers and 8.5 for non-smokers. Non-smokers had a total of 439 seizures of which 6 (1.4%) were not recorded, while the smokers had 213, of which 11 (5.2%) were not recorded. Five events did not have electroencephalographic correlation, raising a suspicion of non-epileptic events (pseudoseizures). Despite the low number of events missed, precious information may be lost during smoking trips by patients admitted to the epilepsy unit. Ways to avoid such trips should be implemented in epilepsy monitoring units allowing smoking breaks for patients.

Evaluating the development of a SPECT protocol in a Canadian epilepsy unit.

BACKGROUND: Functional neuroimaging can address some challenges of seizure localization, and sometimes preclude the need for EEG recording using intracranial electrodes. Ictal Single Photon Emission Computed Tomography (SPECT) has developed into an important tool in the presurgical evaluation of patients with medically-intractable localization-related epilepsy. The purpose of the study was to determine whether the development of a programme using trained nurses to perform ictal injections enabled a more efficient delivery of radiopharmaceuticals and therefore a greater sensitivity and specificity of outcome. METHODS: In our epilepsy unit, nursing staff inject 99mTc-HMPAO at bedside, during or at seizure onset. Brain SPECT is performed later on a gamma camera. RESULTS: Since the implementation of the new protocol (February 2005), 57 scans have been performed: 22 ictal and 35 interictal. Latency of ictal injection was found to be 5-40 seconds (mean 19.7 sec, standard deviation (SD) 10.4). Only 20% of reconstituted radiopharmaceutical vials were not used. Contamination rate was nil. Sixty three percent of SPECT studies were concordant with standard presurgical evaluation. CONCLUSION: The latency of injections and the percentage of unused vials indicated an efficient and effective protocol compared to the literature. Our results show that ictal SPECT can be a safe, noninvasive procedure performed on a routine basis in the epilepsy unit when appropriately trained support staff are incorporated into a structured multidisciplinary programme.

Treating newly diagnosed epilepsy: the Canadian choice.

BACKGROUND: Choosing an antiepileptic medication to treat a patient with epilepsy can be a complicated process during which the treating physician must base her or his decision on efficacy and safety of each of many available drugs. The lack of comparative studies between medications is one of the reasons. METHODS: We conducted a survey on the management of newly diagnosed epilepsy in adult patients. The surveyed were adult and pediatric neurologists with a subspecialty interest in epilepsy who were working in academic institutions or private practice across Canada. Scenarios presented were grouped in categories according to the epilepsy syndrome (absence epilepsy, juvenile myoclonic epilepsy, undetermined idiopathic generalized epilepsy, symptomatic or cryptogenic partial epilepsy, and unclassified epilepsy), the patient's gender and age. First and second step in medical treatment for status epilepticus were surveyed as well. RESULTS: Forty one of 64 experts responded the survey (responder rate of 66%). The results revealed a consensus among Canadian epileptologists that the first choice of antiepileptic medication in generalized epilepsies was between valproate in men (chosen by 88% of respondents) and lamotrigine in women. In localization-related epilepsies, carbamazepine was the preferred drug of choice (chosen by 90% of respondents). In the treatment of status epilepticus, an initial intravenous dose of lorazepam (95% of respondents), followed by a second dose of lorazepam or intravenous phenytoin in case the initial dose of lorazepam failed, were the treatments preferred.

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 microsec, 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.

A genome-wide screen and linkage mapping for a large pedigree with episodic ataxia.

Episodic ataxias are ion channel disorders characterized by attacks of incoordination. The authors performed a genome-wide screen in a large pedigree segregating a novel episodic ataxia and found significant linkage on 1q42 with a multipoint lod score of 3.65. Haplotype analysis and fine mapping yielded a peak 2-point lod score of 4.14 and indicated a 4-cM region on 1q42 that is likely to harbor an episodic ataxia gene.

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).

An autosomal dominant disorder with episodic ataxia, vertigo, and tinnitus.

The authors report an autosomal dominant episodic ataxia that is clinically distinct from the other episodic ataxias. Vestibular ataxia, vertigo, tinnitus, and interictal myokymia are prominent; attacks are diminished by acetazolamide. Linkage analyses of markers flanking the EA1 and EA2 loci demonstrate genetic exclusion from the other autosomal dominant episodic ataxias. The authors suggest EA3 for periodic vestibulocerebellar ataxia and EA4 for the disorder described here.

Does the intracarotid amobarbital procedure predict global amnesia after temporal lobectomy?

PURPOSE: The intracarotid amobarbital procedure (IAP) is widely used to help predict who might be at risk for postoperative amnesia after unilateral temporal lobectomy for intractable seizures. We describe the memory outcome in 10 patients who underwent standard temporal lobectomy, including mesial temporal structures, despite failing the memory portion of the IAP after injections both ipsilateral and contralateral to the resected seizure focus. METHODS: Data for seven of the study subjects were obtained through a retrospective review of patients assessed on a surgical epilepsy unit during a 15-year period who failed the Montreal Neurological Institute IAP memory protocol after both ipsilateral and contralateral injections and subsequently underwent unilateral temporal lobectomy. More recently, we have studied temporal lobectomy patients who failed the Medical College of Georgia memory protocol after both ipsilateral and contralateral injections (n = 3). Preoperative and postoperative memory test scores were compared, and data regarding seizure outcome and self-perception of postoperative memory were collected. RESULTS: At follow-up, none of the patients presented with a pattern indicative of a global amnesia, and 80% demonstrated >90% improvement in their seizure disorder or were seizure-free. CONCLUSIONS: These findings indicate that bilateral memory failure on the IAP does not preclude the removal of an epileptogenic temporal lobe or a successful surgical outcome. In addition, the findings raise questions regarding the validity of the IAP and the possibility that memory may be reorganized in patients with a long history of temporal lobe epilepsy.

Behaviors induced or disrupted by complex partial seizures.

We reviewed the neural mechanisms underlying some postictal behaviors that are induced or disrupted by temporal lobe seizures in humans and animals. It is proposed that the psychomotor behaviors and automatisms induced by temporal lobe seizures are mediated by the nucleus accumbens. A non-convulsive hippocampal afterdischarge in rats induced an increase in locomotor activity, which was suppressed by the injection of dopamine D(2) receptor antagonist in the nucleus accumbens, and blocked by inactivation of the medial septum. In contrast, a convulsive hippocampal or amygdala seizure induced behavioral hypoactivity, perhaps by the spread of the seizure into the frontal cortex and opiate-mediated postictal depression. Mechanisms underlying postictal psychosis, memory disruption and other long-term behavioral alterations after temporal lobe seizures, are discussed. In conclusion, many of the changes of postictal behaviors observed after temporal lobe seizures in humans may be found in animals, and the basis of the behavioral change may be explained as a change in neural processing in the temporal lobe and the connecting subcortical structures.

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.

Management of antiepileptic drugs following epilepsy surgery: a review.

The favourable impact of surgery for intractable epilepsy on seizures is well documented. However, few studies have determined what changes in antiepileptic drug (AED) therapy occur following surgery. Alterations in AED blood levels in the immediate postoperative period can result in breakthrough seizures. In long term follow-up, one-third to one-half of seizure-free patients after temporal lobectomy, the most common type of epilepsy surgery, still require AED treatment which usually has been reduced from polytherapy to monotherapy. In our study of 93 patients followed two years after temporal lobectomy, polytherapy decreased from 78% before surgery to 14% postoperatively, while medication was discontinued in 44%. Early reduction from polytherapy to monotherapy can often be carried out in the immediate postoperative period but the most appropriate timing of cessation of AED treatment has yet to be determined. Patients undergoing extratemporal resections and other forms of epilepsy surgery associated with less favourable postoperative seizure control may achieve comparatively less reduction in antiepileptic medication. We generally do not recommend stopping AEDs prior to one year after surgery.

Evidence favoring genetic heterogeneity for febrile convulsions.

PURPOSE: Two large Canadian kindreds appearing to segregate febrile convulsions as an autosomal dominant trait were evaluated for linkage to three known FC loci, as well as other epilepsy loci. METHODS: Members of the two families were genotyped with microsatellite markers linked to the previously identified febrile convulsion loci, FEB1, FEB2, and GEFS+, and we performed two-point linkage analyses by assuming an autosomal dominant mode of inheritance. RESULTS: We report the exclusion of the FC trait in our families to FEB1 on 8q13-21 and to a second febrile convulsion locus on 19p13. Furthermore, we also excluded the GEFS+ locus on 19q13.1 as the cause of febrile convulsions in both kindreds. Microsatellite markers linked to juvenile myoclonic epilepsy (EJM1), benign neonatal familial convulsions EBN1 and EBN2, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), idiopathic generalized epilepsy (EGI), progressive myoclonic epilepsy of Unverricht-Lundborg (EPM1), and partial epilepsy with auditory features (EPT), were also excluded as potential loci linked to the FC trait in our families. CONCLUSIONS: These findings favor considerable genetic heterogeneity for febrile convulsions.

Moderators of the effect of preoperative emotional adjustment on postoperative depression after surgery for temporal lobe epilepsy.

PURPOSE: Other outcome measures besides seizure control must be considered when assessing the benefit of epilepsy surgery. We investigated the effect of preoperative psychosocial adjustment on postoperative depression in epilepsy patients followed up prospectively for 2 years after temporal lobectomy. METHODS: The Washington Psychosocial Seizure Inventory (WPSI) evaluated psychosocial functioning; the Centre for Epidemiological Studies Depression Scale (CES-D) measured depression. Both were completed at baseline and follow-up. RESULTS: Follow-up occurred in 39 temporal lobectomy patients at 2 years after surgery. Greatest improvement in depression scores was limited to patients with good seizure outcomes (seizure free, or marked reduction in seizure frequency), and seizure outcome was a significant predictor of postoperative depression. Despite this, preoperative scores on the emotional adjustment scale of the WPSI were most highly correlated with depression 2 years after surgery. To clarify this relation, moderated hierarchic regression suggested that good preoperative emotional adjustment (WPSI) was generally associated with less depression after surgery. Moreover, poorer preoperative adjustment combined with older age, generalized seizures, the finding of preoperative neurologic deficits, a family history of psychiatric illness, and/or a family history of seizures was related to higher depression scores 2 years after surgery. CONCLUSIONS: Depression after temporal lobectomy is dependent on a complex interaction of variables and can have a significant effect on indices of postoperative adjustment. The WPSI emotional adjustment scale may help to predict which patients are likely to be chronically depressed after surgery.

Auras, seizure focus, and psychiatric disorders.

OBJECTIVE: The goal of this study was to assess the types of auras and their associations with the focus of seizures in 144 consecutive adult patients with partial epilepsy refractory to medical treatment. The association of frequency and type of aura with a psychiatric disorder was also studied. BACKGROUND: The nature of the aura, its association with the seizure focus, and its relation with emotions and behavioral dysfunction have received relatively little attention, and remain controversial. METHODS: Patients were admitted to an epilepsy investigation unit for detailed observation of their seizures and type of aura. Patients underwent standard electroencephalographic telemetry, including implanted subdural electrodes, if necessary, to delineate the seizure focus. The auras were classified into nine categories. All patients had an independent clinical psychiatric interview for a Diagnostic and Statistical Manual, Third Edition-Revised (DSM-III-R)-based diagnosis. RESULTS: Of the 144 patients studied, 111 (77.1%) had one or more symptoms during the aura and 33 (22.9%) had no aura. The most frequent aura types were viscerosensory (47 cases [32.6%]), experiential (44 cases [30.6%]), and cephalic (21 cases [14.6%]). A temporal lobe focus was present in 116 (80.5%) patients. Only experiential auras were significantly associated with a temporal lobe seizure focus (33 of 44 cases). A DSM-III-R psychiatric diagnosis was present in 74 (51.4%) patients. Of the 116 patients with a temporal lobe focus, 60 (50.2%) had a DSM-III-R psychiatric diagnosis. Patients with two or more auras were significantly more likely to have a psychiatric diagnosis (70.2%) compared with those with one aura (39.1%) or no aura (48.5%). A significant association between experiential auras and psychiatric morbidity was seen. CONCLUSIONS: Auras occurred in a majority of patients with a treatment-refractory partial epilepsy who were hospitalized for assessment of their seizure focus for possible surgical candidacy. Two or more auras were associated with a psychiatric diagnosis as was the presence of an experiential aura. Experiential auras were most common in temporal lobe epilepsy. Approximately half the patients, irrespective of seizure focus, had an associated psychiatric morbidity.