The role of ketamine-induced beta activity in the treatment of refractory status epilepticus. Is the EEG useful to determine responder's rate? A retrospective study.

INTRODUCTION: Multiple investigations have been done to evaluate the possible effect of ketamine in the treatment of status epilepticus (SE). OBJECTIVES: To evaluate the electrographic effect of ketamine on EEG, and its clinical utility following-up refractory and super refractory status epilepticus (SRSE). METHODS: Retrospective review of 24 patients with SE. Clinical record and Video-electroencephalogram (video-EEG) of all included patients were reviewed. The patients' EEGs were then monitored for any immediate changes after administration of the first dose of ketamine as well as at the time patients would be predicted to have peak serum concentration of ketamine. Patients with cessation of electrographic seizures and no SE recurrence within the same admissions were categorized as "Responders". Statistical differences between qualitative variables were analyzed using chi square test. Differences between median were analyzed by Mann-Whitney U test. Difference between groups were considered significant when p < 0.05. RESULTS: We identified 24 patients with SE. Twelve out of 24 (50%) had SRSE and 12 out of 24 (50%) had refractory status epilepticus (RSE). The appearance of superimposed beta activity after ketamine was initiated was associated with a higher responder rate (100% versus 33.3% in the responder group versus the non-responder group respectively). Notably, the presence of a burst suppression pattern had no significant association with one group compared to the other (41.6% versus 33.3%, in the responder group vs the non-responder group respectively). CONCLUSIONS: Background superimposed beta activity induced by ketamine is an early and reliable EEG finding associated with status epilepticus termination.

Double antiglutamatergic treatment in patients with status epilepticus: A case series.

INTRODUCTION: Status epilepticus (SE) continues to be a challenging neurological emergency with high morbidity and mortality. During treatment, different regimens are practiced encompassing all known seizure termination mechanisms. To our knowledge, this is the first case series report describing EEG patterns and clinical outcomes in patients treated with ketamine and perampanel (PER) concomitantly. OBJECTIVE: To assess clinical and electrographic outcomes in patients receiving dual antiglutamatergic therapy in SE. RESULTS: Twenty-one out of twenty five patients were treated with ketamine, and four patients with ketamine were associated with PER. In the ketamine plus PER group, three out of four patients had convulsive SE, and one had non-convulsive status epilepticus (NCSE), whereas eight patients in the ketamine group had NCSE. The incidence of beta pattern appearance on EEG after starting patients on ketamine and PER was achieved in all four patients (100%) compared to (61.9%) in the other group. A burst suppression pattern was recorded in 75% of patients treated with ketamine and PER, in comparison to 28.5% of patients in patients treated with a different regimen. The time to resolution of SE was significantly shorter in the ketamine group (median 24 (24-64) h vs. 6 (05-144) h p > 0.05). Moreover, the average number of days on IV anesthetic was slightly lower in a patient treated with PER concomitantly. In terms of morbidity, the average increase in mRS was also lower in the ketamine and PER group, although it was not statistically significant. CONCLUSIONS: Dual anti-glutamatergic therapy could provide a favorable approach to treating SE, which yet needs to be further investigated through larger randomized control studies.

Reelin, tau phosphorylation and psychiatric complications in patients with hippocampal sclerosis and structural abnormalities in temporal lobe epilepsy.

INTRODUCTION: Temporal lobe epilepsy (TLE) is the most common adult epileptic syndrome. About 30-70% of those cases have neuropsychiatric complications. More than 10% of patients have TLE because of focal cortical dysplasia (FCD) type IIIa. OBJECTIVES: The objective of this study was to review the evidence of reelin (RELN) deficiency and tau phosphorylation role in the histopathological, neuropsychiatric, and hyperexcitability features in TLE because of dysplasia type IIIa. METHODS: The current literature was reviewed using Cochrane, EMBASE, PROSPERO, MEDLINE, and PubMed from 1995 to July 2018. Articles of interest were reviewed by one investigator (RAM). RESULTS: Reelin deficit is related to an abnormal migration of neurons in dentate gyrus, and its deficit causes dentate gyrus abnormalities, which in turn has been associated with memory deficits in patients with TLE. A decreased in the expression of RELN ribonucleic acid (RNA) was found in patients with TLE and dysplasia type IIIa compared with patients with TLE and isolated hippocampal sclerosis (HS). Reelin might affect the distribution and dynamic instability of microtubules within neurons in the cerebral cortex and their phosphorylation. Amyloid pathology, tauopathy, or phosphorylated tau (p-tau) overexpression has been reported in epileptic human brain and in animal models of epilepsy. CONCLUSION: Reelin deficit may determine an abnormal cortical lamination and dentate gyrus dispersion and might be associated with an abnormal tau phosphorylation. These processes can be associated with an abnormal hyperexcitability, neuropsychiatric complications, and a myriad of typical histopathological features seen in patients with TLE because of dysplasia type IIIa.

Gelastic seizures involving the left parietal lobe.

Gelastic seizures have been described in various epilepsies arising from the temporal or frontal lobes, although the most commonly encountered form is related to the presence of a hypothalamic hamartoma. We describe a patient with gelastic seizures involving the left parietal lobe. Our patient, an 8-year-old girl, underwent interictal video/EEG monitoring and MRI. The seizures consisted of brief staring followed by smiling and laughing. Electroencephalography during the gelastic seizures showed rhythmic spikes and waves in the left parietal lobe. MRI revealed the characteristic features of focal cortical dysplasia. Our findings suggest that the left parietal lobe may actively participate in the particular epileptogenic network generating gelastic seizures.

Ictal extension (dorsiflexion) of the toes in a patient with temporal lobe epilepsy: a new ictal lateralizing sign.

Neurologists have analyzed the clinical behaviors that occur during seizures for many years. Several ictal behaviors have been defined in temporal lobe epilepsy (TLE). Ictal behaviors are especially important in the evaluation of candidates for epilepsy surgery. We propose a new ictal lateralizing sign originating from the nondominant hemisphere: extension (dorsiflexion) of the toes (Babinski's, Chaddock's, and Moniz' signs). Our patient is a 16-year-old woman. Her epileptogenic foci were localized to the right neocortical temporal region after noninvasive presurgical investigations. Cranial MRI revealed a right insular lesion compatible with focal cortical dysplasia or cortical tumor. We observed progressive movement of the left leg and, when the patient touched the lateral aspect of the foot to the bed, dorsiflexion of the great toe (Babinski's sign). In other seizures, the patient started a progressive movement of the left leg, rubbing the external border of the left foot on the bed and provoking dorsiflexion of the great toe (Chaddock's sign). The Brissaud reflex component was also observed when the movement was accompanied by internal rotation of the leg and recruitment of the tensor fascia lata, making dorsiflexion more likely to be a reflex response and not voluntary. We also observed forceful passive plantar flexion at the ankle in association with dorsiflexion of the great toe (Moniz' sign). All of these signs were contralateral to ictal seizure onset and to the cerebral epileptogenic lesion. These signs may occur as a result of ictal activation of a specific brain region in this hemisphere.

Cholesterol concentrations and clinical response to sertraline in patients with epilepsy: preliminary results.

OBJECTIVE: Low cholesterol levels are associated with depression and suicide in persons with epilepsy. The goal of this study was to determine whether plasma cholesterol concentration is a predictor of response to sertraline. METHODS: We carried out a prospective open-label study on the efficacy of sertraline as therapy in the treatment of depressive disorder in patients with mesial temporal lobe epilepsy. Patients were treated for 24 weeks at dose levels between 50 and 100mg/day. All patients were evaluated at the beginning of the investigation and 6 months later by two psychiatrists using a structured interview. RESULTS: The mean total cholesterol concentration of nonresponding patients was lower than the mean (SD) cholesterol level of responders [3.2 (0.9) mmol/L vs 5.2 (1.5) mmol/L]; this difference reached statistical significance (P = 0.0000). We found a negative correlation between scores on the Hamilton scale and cholesterol concentrations (r = -33). CONCLUSION: The response to sertraline may depend on the baseline cholesterol concentration.

Efficacy and tolerability of lamotrigine in juvenile myoclonic epilepsy in adults: a prospective, unblinded randomized controlled trial.

PURPOSE: Controlled randomized studies recommending the clinical use of lamotrigine in adult populations with the diagnosis of Juvenile Myoclonic Epilepsy are still lacking. To compare the efficacy and tolerability of lamotrigine versus valproate in adult patients with JME. METHODS: This was a prospective, randomized, controlled, pragmatic, long-term and open-label treatment trial. Patients were randomized to use valproate or lamotrigine. The primary end points of the study were: (1) time from randomization to treatment failure (withdrawal); (2) time from randomization to seizures remission. Secondary ending points were: (1) frequency of clinically important adverse events and (2) change in the QOLIE-31 after randomization. The definition of seizure remission was based on disappearance of all seizure types and EEG discharges. RESULTS: We found that the time to withdraw treatment after randomization was not significantly different in lamotrigine and valproate groups. Long-term seizures freedom was equal in the both groups of the trial; only 8 (19.1%) patients randomized to lamotrigine and 6 (19.4%) randomized to valproate were not seizure free after 4 months of treatment. Between 17.03% (lamotrigine) and 35.3% (valproate) of patients reported adverse reactions at some point in the intention-to treat study (p = 0.07). All subscales of the QOLIE-31 questionnaire, except that related to side effects of medication, improved more than 5 points with respect to baseline period in both groups CONCLUSION: Lamotrigine is effective in adult patients with Juvenile Myoclonic Epilepsy and better tolerated than valproate, although the incidence of idiosyncratic reactions could be a cause of concern.

Suicidal risk and suicide attempts in people treated with antiepileptic drugs for epilepsy.

OBJECTIVE: To determine whether antiepileptic drugs constitute in themselves an independent risk factor for suicidality in patients with epilepsy. METHODS: One hundred and thirty one patients with epilepsy were recruited and followed-up during 5 years. A detailed medical history, neurological examination, EEGs, Mini-International Neuropsychiatric Interview, executive function, and MRI were assessed. Systematically collected data were used to assess suicidality. Multiple regression analysis was carried out to examine predictive associations between clinical variables, psychiatric disorders, antiepileptic drugs and suicidality. RESULTS: We identified two AEDs related with suicide attempts (PHB and LTG) and four with suicidal risk: PHB, PRM, PHT and LTG, but the increased of risk diminished or disappeared when psychiatric comorbidity and other well established risk factors for suicidality were analyzed. We found a significant proportion of patients with depressive episodes associated with Topiramate, Phenitoin, Phenobarbital and Lamotrigine. CONCLUSION: Antiepileptic drugs probably do not have an impact on suicidality.