Late-life terminal seizure freedom in drug-resistant epilepsy: "Burned-out epilepsy".

The course of established epilepsy in late life is not fully known. One key question is whether the resolution of an epileptic diathesis is a natural outcome in some people with long-standing epilepsy. We investigated this with a view to generating a hypothesis. We retrospectively explored whether terminal seizure-freedom occurs in older people with previous drug-resistant epilepsy at the Chalfont Centre for Epilepsy over twenty years. Of the 226 people followed for a median period of 52 years, 39 (17%) achieved late-life terminal seizure-freedom of at least two years before death, which occurred at a median age of 68 years with a median duration of 7 years. Multivariate analysis suggests that a high initial seizure frequency was a negative predictor (p < 0.0005). Our findings indicate that the 'natural' course of long-standing epilepsy in some people is one of terminal seizure freedom. We also consider the concept of "remission" in epilepsy, its definition challenges, and the evolving terminology used to describe the state of seizure freedom. The intersection of ageing and seizure freedom is an essential avenue of future investigation, especially in light of current demographic trends. Gaining mechanistic insights into this phenomenon may help broaden our understanding of the neurobiology of epilepsy and potentially provide targets for therapeutic intervention.

Epilepsy as a systemic condition: Link with somatic comorbidities.

BACKGROUND: People with epilepsy have more concomitant medical conditions than the general population; these comorbidities play an important role in premature mortality. We sought to generate explanatory hypotheses about the co-occurrence of somatic comorbidities and epilepsy, avoiding causal and treatment-resultant biases. METHODS: We collected clinical, demographic and somatic comorbidity data for 2016 consecutive adults with epilepsy undergoing assessment at a tertiary centre and in 1278 people with epilepsy in the community. Underlying causes of epilepsy were not classed as comorbidities. RESULTS: Somatic comorbidities were more frequent in the referral centre (49%) where people more frequently had active epilepsy than in the community (36%). Consistent risk factors for comorbidities were found in both cohorts. Using multivariable ordinal regression adjusted for age, longer epilepsy duration and an underlying brain lesion were independently associated with a smaller burden of somatic conditions. The treatment burden, measured by the number of drugs to which people were exposed, was not an independent predictor. Shorter epilepsy duration was a predictor for conditions that conceivably harbour significant mortality risks. CONCLUSIONS: Somatic comorbidities do not occur randomly in relation to epilepsy; having more severe epilepsy seems to be a risk factor. Independently from age, the early period after epilepsy onset appears to be at particular risk, although it is not clear whether this relates to an early mortality or to a later decrease in the burden of comorbidities. These results suggest that, for some people, epilepsy should be considered a systemic condition not limited to the CNS.

Extended EEG and non-convulsive status epilepticus: Benefit over routine EEG?

OBJECTIVE: EEG monitoring is increasingly used in critically ill patients, but impact on clinical outcome remains unclear. We aimed to investigate the benefit of repeated extended EEG in the prognosis of patients with non-convulsive status epilepticus (SE). MATERIALS & METHODS: We retrospectively collected 29 consecutive patients with non-convulsive SE without coma, who underwent repeated extended EEG between 2013 and 2015. We compared these patients with an historical age-matched group of 58 patients managed between 2011 and 2013 with routine EEG only. We excluded patients treated with therapeutic coma for SE treatment. Outcome at hospital discharge was categorized as return to baseline conditions, new disability, and death. RESULTS: Severity of SE was similar in the two groups, with similar proportion of potential fatal etiologies (58% in the extended EEG group vs 60%, P=.529), similar STESS scores (median was three in both groups, P=.714), and comparable acute hospitalization duration (median of 15 vs 11 days, P=.131). The extended EEG group received slightly more anti-epileptic drugs (median was three in both groups, P=.026). Distribution of the outcome categories at hospital discharge was similar (P=.129). CONCLUSIONS: Extended EEG used for the management of non-convulsive status epilepticus does not seem to improve clinical outcome, but is associated with a higher number of prescribed anti-epileptic drugs. The benefit of continuous EEG monitoring in non-convulsive SE without coma SE should be addressed through a randomized trial.

Refractory and super-refractory status epilepticus in adults: a 9-year cohort study.

OBJECTIVE: While status epilepticus (SE) persisting after two antiseizure agents is called refractory (RSE), super-refractory status epilepticus (SRSE) defines SE continuing after general anaesthesia. Its prevalence and related clinical profiles have received limited attention, and most studies were restricted to intensive care facilities. We therefore aimed at describing RSE and SRSE frequencies and identifying associated clinical variables. METHODS: Between 2006 and 2015, consecutive adult SE episodes were prospectively recorded in a registry. Occurrence of RSE and SRSE and their relationship to clinical variables of interest, including outcome, were analysed. RESULTS: Of 804 SE episodes, 268 (33.3%) were RSE and 33 (4%) SRSE. Coma induction for SE treatment occurred in 79 (9.8%) episodes. Severe consciousness impairment (OR 1.67; 95% CI 1.24-2.46; P = 0.001), increasing age (OR 1.01, 95% CI 1.01-1.02), and lack of remote symptomatic SE aetiology (OR 0.48; 95% CI 0.32-0.72) were independently associated with RSE, while severe consciousness impairment (OR 4.26; 95% CI 1.44-12.60) and younger age (OR 0.96; 95% CI 0.95-0.99) correlated with SRSE; however, most SRSE episodes were not predicted by these variables. Mortality was 15.5% overall, higher in RSE (24.5%) and SRSE (37.9%) than in non-refractory SE (9.8%) (P < 0.001). SIGNIFICANCE: Super-refractory status epilepticus appears clearly less prevalent in this cohort than previously reported, probably as it is not restricted to intensive care unit. SRSE emerges in younger patients with marked consciousness impairment, pointing to the underlying severe clinical background, but these variables do not predict most SRSE developments. There is currently a knowledge gap for prediction of SRSE occurrence that needs to be filled.

Increased prevalence of ECG markers for sudden cardiac arrest in refractory epilepsy.

BACKGROUND AND AIM: People with epilepsy are at increased risk of sudden cardiac arrest (SCA) due to ECG-confirmed ventricular tachycardia/fibrillation, as seen in a community-based study. We aimed to determine whether ECG-risk markers of SCA are more prevalent in people with epilepsy. METHODS: In a cross-sectional, retrospective study, we analysed the ECG recordings of 185 people with refractory epilepsy and 178 controls without epilepsy. Data on epilepsy characteristics, cardiac comorbidity, and drug use were collected, and general ECG variables (heart rate (HR), PQ and QRS intervals) assessed. We analysed ECGs for three markers of SCA risk: severe QTc prolongation (male >450 ms, female >470 ms), Brugada ECG pattern, and early repolarisation pattern (ERP). Multivariate regression models were used to analyse differences between groups, and to identify associated clinical and epilepsy-related characteristics. RESULTS: People with epilepsy had higher HR (71 vs 62 bpm, p<0.001) and a longer PQ interval (162.8 vs 152.6 ms, p=0.001). Severe QTc prolongation and ERP were more prevalent in people with epilepsy (QTc prolongation: 5% vs 0%; p=0.002; ERP: 34% vs 13%, p<0.001), while the Brugada ECG pattern was equally frequent in both groups (2% vs 1%, p>0.999). After adjustment for covariates, epilepsy remained associated with ERP (ORadj 2.4, 95% CI 1.1 to 5.5) and severe QTc prolongation (ORadj 9.9, 95% CI 1.1 to 1317.7). CONCLUSIONS: ERP and severe QTc prolongation appear to be more prevalent in people with refractory epilepsy. Future studies must determine whether this contributes to increased SCA risk in people with epilepsy.

[Systemic enzyme therapy in the treatment of recurrent vulvovaginal candidiasis]. / Systémová enzymoterapie v lécbe recidivující vulvovaginální kandidózy.

OBJECTIVE: Phase I: A prospective evaluation of long-term systemic enzyme therapy (Wobenzym; WE) effects on the frequency of recurrent vulvovaginal candidiasis (RVVC) episodes. Phase II: A retrospective analysis of possible positive effects remaining in the next 3 years. TRIAL DESIGN: Original work - pilot project consisting of prospective phase I and retrospective phase II trials. METHODS: Composition of animal and plant proteo-lytic enzymes (WE) is a common component in the treatment of chronic or recurrent inflammatory diseases and has been also shown to have immunomodulatory effects. Project involving 7 gynecology practices has been started in 2005 - 2007 to evaluate the effectiveness of WE in the complex treatment of RVVC. The trial involved 62 women with at least 4 microscopically confirmed episodes of RVVC in the last 12 months (year 1; 4-9 episodes, mean 4.4 episodes per patient-year). From the beginning of the trial, participants took WE in the dose of 2× 8 tbl/day for 10 weeks and were monitored for 12 months (year +1). All infections of RVVC were treated according to usual practice of the particular gynecologist. The number of RVVC episodes during the year -1 was compared to the number of RVVC during the year +1. To evaluate possible long-term effects of the WE treatment, retrospective analysis of the data from 3 years following the phase I (year +2, +3, +4) was performed. Complete data for 54 women were collected (87.1% of the former group of patients). All data were processed with regular statistics methods. RESULTS: Mean number of RVVC in the year +1 has decreased from 4.4 to 0.5 per patient-year (i.e. by 88.5%; p < 0.001). All women experienced an improvement, 63% of them experienced no recurrence. The lower incidence of RVVC remained also for the phase II (year +2: 0.91; year +3: 0.57; year +4: 0.52 episodes of RVVC per patient-year). The difference, as compared to the mean incidence of RVVC before the treatment (year -1), remains significant (p < 0.001) although women, who became pregnant during the trial, were not excluded from the observed population. If only non-pregnant women were analyzed (41 women), the mean incidence of RVVC was even lower (year +2: 0.69; year +3: 0.39; year +4: 0.44 episodes of RVVC per patient-year). CONCLUSION: 10 weeks of systemic enzyme therapy (WE) in women with RVVC significantly reduced recurrence of this disease not only for the first year following the treatment, but also for the next 3 years. An explanation of the basis for this effect needs further research.

[Epilepsy surgery: the curative approach]. / Chirurgie de l'épiepsie: l'approche curative.

Epilepsy surgery is possible in specific cases of localisation-related pharmaco-resistant epilepsy and can often lead to seizure-freedom condition. A presurgical diagnostic workup is necessary to localise the epileptic focus and assess the risks of post-operative neurological or cognitive deficits. Even when the brain MRI does not reveal any lesion, other imaging techniques and in some cases intracranial EEG recordings can lead to successful surgery. All patients suffering from pharmaco-resistant epilepsy should be referred to an expert centre to confirm the diagnosis and evaluate the possibility of epilepsy surgery. In children, early epilepsy surgery can allow better continuation of cognitive development and education.

["Palliative" surgical procedures in refractory epilepsy]. / Approches chirurgicales "palliatives" de l'épilepsie.

In some patients with refractory epilepsy, no resective surgery of the epileptogenic zone can be offered. This is the case when for instance the epileptogenic zone is located in an eloquent region (motor, language or visual) or when there are several epileptogenic zones. When disabling seizures persist despite the medical treatment, several surgical procedures can be proposed with the aim of decreasing the seizure frequency. Among these procedures, we review briefly here vagus nerve stimulation, the various brain stimulations procedures, multiples subpial transsections, and the corpus callosotomy. For each procedure, we will discuss its indication and outcome.

Medicinal plants of the eastern region of Madagascar.

Sixty-eight plants used in the traditional medicinal practices of the Betsimisaraka and Tanala peoples of the eastern region of Madagascar are reported. Preparations and utilizations of these medicinal plants are as varied as the plants themselves. Some of the plants discussed are known to science, but because of the diversity of tribal groups in Madagascar, new preparations and utilizations of these plants were based on the ethnobotanical data collected from the Betsimisaraka and Tanala. Many of the plants discussed remain to be chemically tested. Ethnopharmacological information is in danger of being lost in Madagascar as slash and burn agriculture destroys much of the forest, and the elder traditional healers, often illiterate, pass away without handing down their knowledge.

[Zona pellucida antibody detection using the passive hemagglutination reaction. II. Clinical part]. / Protilátky proti zona pellucida vysetrované pasivní hemaglutinacní reakcí--II. Klinická cást.

The authors examined sera of patients suffering from idiopathic infertility, unsuccessful IVF, the diagnosis of habitual abortion and endometriosis, using the test of the passive haemagglutination reaction with sheep erythrocytes sensitized by 11 antigenic fractions of pig zona pellucida, molecular weights from 13.3-114 kilodaltons. The authors analyze the assembled results with regard to individual antigenic fractions and with regard to the diagnoses. The frequency of positive reactions in patients is investigated in particular in the area of higher molecular weights, as compared with the control group of healthy fertile women.

Screwworm eradication in North and Central America.

Screwworms, Cochliomyia hominivorax (Fig. 1), have been eradicated from the USA and now have a tenuous hold only in the Yucatan peninsula of Mexico, where control programmes based on massive release of sterile males have recently been initiated. Sterile male release operations are now underway in Guatemala and proposals have been made to extend the eradication procedures south to the Darien Gap in Panama. It is planned to extend the barrier zone to Belize and Guatemala later this year. This article reviews the progress and operational obstacles of the screwworm eradication programme.