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.

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.

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.

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.

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.

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.

Interictal psychiatric morbidity and focus of epilepsy in treatment-refractory patients admitted to an epilepsy unit.

Of 71 consecutive patients admitted to an epilepsy unit of a general hospital, 32 (45%) were classified as having psychiatric disorders by using the General Health Questionnaire. No differences were evident to support a specific relationship between the type or focus of epilepsy and psychopathology.

Rasmussen's chronic encephalitis in adults.

OBJECTIVE: Rasmussen's chronic encephalitis, a cause of intractable epilepsy in childhood, is described in three adults. SETTING: Inpatient epilepsy unit. PATIENTS: Of 11 patients with pathological confirmation of Rasmussen's encephalitis, three were adults with intractable seizures, progressive sensorimotor deficits, and cognitive decline beginning at the ages of 36, 24, and 16 years. RESULTS: Clinical, electroencephalographic, and magnetic resonance imaging findings indicated patchy, multifocal involvement of primarily one hemisphere, but the adults had more evidence of disease in the opposite hemisphere than occurs in children. The sensorimotor deficit that the adults developed was greater and the cognitive decline was less than in children. Seizure control following multilobe resection was proportionate to the amount of tissue removed. Cytomegalovirus genome was found in the resected cortical tissue of all three patients. CONCLUSIONS: Rasmussen's encephalitis is a cause of intractable epilepsy with progressive neurological deficit in adults as well as children. Cytomegalovirus may be involved in the pathogenesis of the disease.

The significance of head and eye turning in seizures.

We evaluated the history of ictal versive movement in determining the site of the seizure focus. The focus was in the hemisphere opposite the direction of head or eye turning in more than 90% of patients. Ipsiversive movements were more likely to occur with temporal foci and were never found with occipital foci. Maintenance of awareness during versive movements indicated a contralateral focus in 100% and origin from the frontal lobe in 93%; a temporal focus was more likely if awareness was not maintained. Ictal versive movements, if unequivocal, consistent, and forced, are of reliable lateralizing and localizing value.

Antiepileptic drug treatment following temporal lobectomy.

Antiepileptic drug use was documented before and after temporal lobectomy. Carbamazepine, phenytoin, and clobazam were the most commonly used drugs, both pre- and postoperatively. Preoperatively, polytherapy was used in 78% of patients; at 6 months follow-up, 47%; at 12 months, 18%; and at 24 months, 14%. Preoperatively, monotherapy was used in 20% of patients; at 6 months follow-up, 49%; at 12 months, 55%; and at 24 months, 42%. No medication was used preoperatively by 2% of patients; at 6 months follow-up, 2%; at 12 months, 27%; and at 24 months, 44% (p < 0.001). After 2 years, 53% of patients who were seizure free had stopped taking medication, as had 33% who had some seizures after surgery.

Treatment of Rasmussen's syndrome with ganciclovir.

Since cytomegalovirus (CMV) has been implicated in the pathogenesis of Rasmussen's syndrome, we treated four patients with ganciclovir, a potent anti-CMV drug. A 7-year-old girl with seizures escalating to 60/day over 3 months despite triple antiepileptic drug therapy became seizure-free 5 days after initiation of treatment with no recurrence at 1.5 years follow-up. Focal neurologic signs, cognitive function, and the EEG returned to normal. Two patients treated 34 and 72 months after disease onset in association with epilepsy surgery had a reduction in seizures and one had no response. CMV genome was detected in the brains of two of the three patients in whom it was assessed. The response to antiviral therapy supports a viral etiology for chronic encephalitis of Rasmussen. If the disease is suspected, treatment with ganciclovir should be considered as early as possible.

Temporal lobectomy for intractable epilepsy in patients over age 45 years.

Surgical management of uncontrolled focal epilepsy is most commonly carried out in young adults with good results, but there has been some doubt about the effectiveness of cortical resection in older individuals. We assessed the outcome of temporal lobectomy done after age 45 years in 20 patients with intractable epilepsy followed for more than 2 years after surgery. During a mean follow-up of 5 years, six patients (30%) were seizure-free following surgery and seven (35%) had greater than 90% reduction in seizure frequency. This compares with an outcome of 40% seizure-free and 44% with greater than 90% seizure reduction in 68 younger patients aged 17 to 45 years; the differences do not achieve statistical significance. The outcome was better for complex partial seizures than for secondarily generalized seizures. Complications were no greater than in the younger patients. The findings indicate that surgery is an effective treatment alternative for intractable temporal lobe epilepsy in older patients since two of three of these patients will obtain satisfactory seizure control.

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.

Prospective neuropsychological assessment of nondemented patients with biopsy proven senile plaques.

Senile plaques are characteristic of Alzheimer's disease but also occur as an age-related change in some neurologically normal individuals at autopsy. The significance of these "incidental" senile plaques, with regard to the development of dementia, is unknown and cannot be assessed by postmortem studies. Patients with biopsy proven senile plaques offer an important opportunity for prospective followup. We identified senile plaques in temporal lobectomy specimens, removed in the surgical treatment of intractable epilepsy, from 11 patients. Review of preoperative neuropsychological test results showed no suggestion of dementia in any of the patients with senile plaques and no significant difference compared with controls. Postoperative followup ranged from 2 to 7 years (mean, 3.7 yr). There was no evidence of generalized cognitive deterioration in any of the study patients. These findings indicate that an abundance of senile plaques may be present without associated dementia and without cognitive deterioration for at least several years.

Creutzfeldt-Jakob disease without periodic sharp wave complexes: a clinical, electroencephalographic, and pathologic study.

A comparison of clinical, EEG, and pathologic features was carried out on all cases of autopsy-proven Creutzfeldt-Jakob disease (CJD) studied over the last 10 years. Periodic sharp wave complexes (PSWCs) were present in three but absent in seven patients. Myoclonus was documented in two of the three with and in only one of the seven without PSWCs. The three with PSWCs had severe neocortical and at least mild thalamic involvement; those without PSWCs had more variable disease topography. The diagnosis of CJD should not be rejected if PSWCs are absent.

Microangiopathy with retinopathy, encephalopathy, and deafness (RED-M) and systemic features.

The case of a young woman with a rare syndrome of acute encephalopathy followed by deafness and retinopathy developing over 1 year is reported. Unlike previously described similar cases, she had considerable systemic symptoms and signs including polyarthralgia-arthritis, diffuse myalgia, malar rash, livedo reticularis, night sweats, and fatigue suggestive of systemic lupus erythematosus. However, results of most immunological investigations were repeatedly normal, including antinuclear antibodies. Anticardiolipin antibodies were elevated on one occasion. Cyclophosphamide has been the most effective treatment for exacerbations of the disease, which have continued to occur over 6 years. This microangiopathic syndrome more likely relates to an immunologically mediated vasculitis of small blood vessels than to a thromboembolic etiology.

Spreading depression of Leão in rodent and human cortex.

Spreading depression (SD) has been implicated in the pathophysiology of a number of neurological conditions. The same methodology was used to elicit SD in anesthetized rats and in non-anesthetized patients undergoing cortical resections for intractable epilepsy. A slowly spreading DC potential shift (mean -9 mV) occurred in the cortex of 10 of 15 rats in association with attenuation of the electrocorticogram but this could not be reproduced in any of the human cortices (n = 23) where the mean potential shift was -0.56 mV (P < 0.0001). SD is more difficult to elicit in human than rodent cortex and may not occur in man.

Differential participation of some 'specific' and 'non-specific' thalamic nuclei in generalized spike and wave discharges of feline generalized penicillin epilepsy.

Extracellular single unit and electroencephalographic (EEG) activity during generalized spike and wave discharges (SW) induced by i.m. penicillin was recorded simultaneously in the cortex, in a 'specific' thalamic nucleus (n. lateralis posterior, LP) and in some 'non-specific' thalamic nuclei (n. centralis medialis, NCM; n. centrum medianum, CM; n. centralis lateralis, CL) Computer-generated EEG averages and histograms of single unit activity were triggered by either peaks of EEG transients or action potentials. The time at which cortical neurons (66/66) were most likely to fire was during the 'spike' of the SW complex while absence of firing was the rule during the 'wave'. Most LP neurons (23/26) showed a similar pattern, 3 cells firing preferentially during the 'wave'. In NCM only 17 of 39 neurons fired during the 'spike', 8 of 39 neurons during the 'wave' while the others showed no change in their firing pattern during SWs. Twenty-six of 30 CM and 20 of 24 CL neurons fired during the 'spike' of SW; the other cells in these nuclei did not change their firing pattern during SWs. When present, rhythmic fluctuations in firing linked to SW discharge were less prominent in these 'non-specific' thalamic nuclei than in cortex and LP. Furthermore, participation of NCM, CM and CL neurons in the SW rhythm occurred only after neurons in cortex and LP had become involved in it. Thus, as is the case for cortical neurons, the main firing pattern of thalamic cells during SWs consists of an oscillation between 'excitation' during the 'spike' and 'inhibition' during the 'wave' of the SW complex. However, the coupling between cortical and thalamic neuronal firing is less intimate for cells of the 'non-specific' thalamic nuclei than for a 'specific' nucleus such as LP. Thus, at least some 'specific' thalamic nuclei are more intimately involved in the mechanism of SW discharge than the midline intralaminar nuclei.