Progesterone and its derivatives for the treatment of catamenial epilepsy: A systematic review.

OBJECTIVE: Catamenial epilepsy (CE) is defined as an increase in seizure frequency during specific phases of the menstrual cycle in women with epilepsy. The treatment usually includes a combination of non-hormonal and hormonal therapies. This systematic review summarizes the available data on the efficacy of progesterone and its derivates to treat CE. METHODS: We performed a systematic search of the literature to identify studies reporting data on the use of progesterone and its derivatives (any type and dose) for the treatment of CE. The main outcome included the efficacy of progesterone and its derivatives on seizure frequency. RESULTS: Nineteen articles (457 patients) were included; four were randomized controlled trials (two comparing progesterone vs placebo and two comparing norethisterone vs placebo). Progesterone was generally administered during the luteal phase (from day 15 to 25) or during perimenstrual exacerbations (from day 23 to 25), with an average dose of 10-30 mg/day to a maximum of 300 mg/day. The therapy, usually well tolerated, was ineffective in the randomized controlled trials; conversely, it was associated with an overall reduction in seizure frequency in case reports and uncontrolled studies. CONCLUSIONS: Although data from uncontrolled studies suggest that hormone therapy with progesterone may be useful in the treatment of CE, its efficacy has not been demonstrated in controlled trials. The possible antiseizure effect of progesterone could be mediated by its active metabolite allopregnanolone, making the plasmatic measurement of these hormones mandatory to evaluate efficacy. Further randomized controlled trials should investigate the efficacy of progesterone and its derivatives, addressing these pharmacological issues.

Prevalence of comorbidities, and affective disorders in epilepsy: A latent class analysis approach.

OBJECTIVE: Epilepsies are severe chronic neurological diseases that impair several domains in life and are often accompanied by various somatic and psychiatric comorbidities. Associations between epilepsy and its comorbidities remain poorly understood. As epidemiological research mainly relies on cross-sectional designs and descriptive results, homogeneities regarding comorbidities in individuals suffering from epilepsy remain uncovered. Therefore, we aimed to identify clusters of individuals based on selected seizure-related variables and somatic comorbidities, and their respective risk of experiencing affective disorders, using a Latent Class Analysis (LCA). METHODS: Latent class analysis, is a model-driven statistical approach, which aims at latent, unobservable clusters on selected disease features. LCA has therefore the potential for uncovering previously unobservable groups or classes with similar comorbidity patterns. It allows for comparisons between those classes regarding risk or promotive factors - such as affective disorders. Our data derives from the Austrian cohort of the European Study on Burden and Care of Epilepsy (ESBACE; http://www.esbace.eu/). In ESBACE, multiple factors were collected to get a detailed picture on prevalence, epilepsy-related variables and comorbidities in a population-based cohort from the region of Salzburg, Austria. We used LCA to identify epilepsy-somatic-comorbidity-clusters and further, compared them to the observed the risk of suffering from affective disorders. RESULTS: The prevalence of epilepsy in the study region was 9.14/1000 inhabitants. LCA unveiled a three-cluster solution, of which one cluster, mainly consisting of individuals with mixed seizure types, higher age, and discrete somatic comorbidities (stroke, cardiovascular - and respiratory/pulmonary diseases) had a higher risk of experiencing affective disorders. SIGNIFICANCE: To our knowledge, this is the first large scale study that uses LCA to identify epilepsy-related comorbidity phenotypes, and therefore it might open a new way for epidemiological research.

New anti-seizure medication for elderly epilepsy patients - a critical narrative review.

Introduction: The number of elderly patients with epilepsy is growing in resource rich countries due to demographic changes and increased longevity. Management in these patients is challenging as underlying etiology, co-morbidities, polypharmacy, age-related pharmacokinetic and pharmacodynamic changes need to be considered.Areas covered: Lacosamide, eslicarbazepine acetate, brivaracetam, and perampanel have been approved in the USA and Europe for monotherapy and/or adjunctive treatment of seizures in the last few years. The authors review the pharmacological properties and safety profile of these drugs and provide recommendations for their use in in the elderly.Expert opinion: There are only limited data available on more recent antiseizure medications (ASMs). Drugs with a low risk of interaction (lacosamide, brivaracetam) are preferred choices. Once daily formulations (perampanel and eslicarbazepine acetate) have the advantage of increased compliance. Intravenous formulations (brivaracetam and lacosamide) are useful in emergency situations and in patients who have difficulties to swallow. Dose adjustments are necessary for all ASMs used in the elderly with slow titration and lower target doses than in the regulatory trials. The adverse event profile does not significantly differ from that found in the general adult population.

HMPAO-SPECT Can Discriminate between Patients with Subjective Cognitive Complaints with and without Cognitive Deficits and those with Mild Cognitive Impairment.

BACKGROUND: Growing evidence suggests that pathological processes leading to Alzheimer's disease occurs gradually and begins to develop decades before the earliest clinical symptoms occur. The use of biomarkers has been proposed to detect evidence of preclinical Alzheimer's pathologic change in asymptomatic subjects. Subjective cognitive complaints (SCC) i.e. self-reported cognitive decline with normal cognition have been reported as an indicator of future cognitive decline, however, this condition is unspecific. OBJECTIVE: In the present study we used the regional brain perfusion measured by HMPAO-SPECT as Biomarker of neurodegeneration to compare the regional brain perfusion of patient with subjective cognitive complaints with and without minimal cognitive dysfunction (SCC+ and SCC- respectively) in respect to patients with mild cognitive impairment (MCI). METHODS: We retrospectively examined 736 Patients who referred to our Memory Clinic because of suspected cognitive dysfunction. After exclusion of patients with overt dementia, automated, quantitatively assessed relative cerebral blood flow of 10 forebrain regions (thalamus, parietotemporal, medial temporal, posterior temporal, posterior cingulate gyrus, each region left hemispheric and right hemispheric) and neuropsychological assessment of 64 SCC (32 SCC+; 32 SCC-) and 28 MCI subjects were analysed. RESULTS: .The most relevant differences between groups in cognitive performance concerned verbal memory. Left hemispheric medial temporal region could significantly discriminate between all three groups, with a progressive decrease n perfusion from SCC towards MCI. Area under the curve of left medial temporal region showed a sensitivity of 0,61 and a specificity of 0,78 for discriminating MCI from SCC. CONCLUSION: Automated analysis of HMPAO-SPECT data of MCI and SCC+ patients showed significant perfusion differences in medial temporal region and impaired verbal memory, both of which are known features of Alzheimer's disease. Perfusion patterns and verbal memory performance in SCC+ are more similar to MCI than SCC-. Thus, SPECT analysis could distinguish those subjects whose perfusion pattern resembles that of an MCI from those who do not. In our opinion, this could identify two populations with a different risk of progression to AD, with SCC+ subjects needing further diagnostic examination and repeated follow-up.

Cannabidiol as adjunctive treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome.

Epilepsy is one of the most common chronic disorders of the brain affecting around 70 million people worldwide. Treatment is mainly symptomatic, and most patients achieve long-term seizure control. Up to one-third of the affected subjects, however, are resistant to anticonvulsant therapy. Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are severe, refractory epilepsy syndromes with onset in early childhood. Currently available interventions fail to control seizures in most cases, and there remains the need to identify new treatments. Cannabidiol (CBD) is the first in a new class of antiepileptic drugs. It is a major chemical of the cannabis plant, which has antiseizure properties in absence of psychoactive effects. This article provides a critical review of the pharmacology of CBD and the most recent clinical studies that evaluated its efficacy and safety as adjunctive treatment of seizures associated with LGS and DS.

Healthier rhythm, healthier brain? Integrity of circadian melatonin and temperature rhythms relates to the clinical state of brain-injured patients.

BACKGROUND: Healthy circadian rhythmicity has been suggested to relate to a better state of brain-injured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC). METHODS: Going beyond earlier studies, a systems-level perspective was adopted and, using multilevel modelling, the joint predictive value of three indices of circadian rhythm integrity derived from skin temperature variations, melatoninsulfate secretion, and physical activity (wrist actigraphy) patterns was evaluated for the behaviourally assessed state [Coma Recovery Scale - Revised (CRS-R) score] of DOC patients [13 unresponsive wakefulness syndrome; seven minimally conscious (exit) state]. Additionally, it was assessed in a subset of 16 patients whether patients' behavioural repertoire (CRS-R score) varied (i) with time of day or (ii) offset from the body temperature maximum (BTmax ), i.e. when cognitive performance is expected to peak. RESULTS: The results reveal that better integrity of circadian melatoninsulfate and temperature rhythms relate to a richer behavioural repertoire. Moreover, higher CRS-R scores are, by trend, related to assessments taking place at a later daytime or deviating less from the pre-specified time of occurrence of BTmax . CONCLUSIONS: In conclusion, the results suggest that therapeutic approaches aimed at improving circadian rhythms in brain-injured patients are promising and should be implemented in hospitals or nursing homes. Beyond this, it might be helpful to schedule diagnostic procedures and therapies around the (pre-assessed) BTmax (≈4 pm in healthy individuals) as this is when patients should be most responsive.

Randomized controlled trials of antiepileptic drugs for the treatment of post-stroke seizures: A systematic review with network meta-analysis.

OBJECTIVE: To determine the best available evidence on the efficacy and tolerability of antiepileptic drugs (AEDs) used to treat poststroke seizures and epilepsy. METHODS: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov and Opengrey.eu were searched for RCTs of AEDs used to treat post-stroke epilepsy. The following outcomes were considered: seizure freedom; occurrence of adverse effects (AEs); withdrawal for AEs. The methodological quality was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Adjusted indirect comparisons were made between each AED using controlled-release carbamazepine (CR-CBZ) as common comparator. RESULTS: Only 2 RCTs were included, one comparing levetiracetam (LEV) with CR-CBZ and the other comparing lamotrigine (LTG) with CR-CBZ. No significant difference was found in seizure freedom between either LEV or LTG and CR-CBZ. Occurrence of AEs were lower for LEV and LTG than for CR-CBZ. Indirect comparisons showed no difference between LEV and LTG for seizure freedom (OR 0.86; 95%CI: 0.15-4.89). Occurrence of AEs was higher for LEV than for LTG (OR 6.87; 95%CI: 1.15-41.1). For withdrawal rates due to AEs, we found a large width and asymmetrical distribution of confidence intervals around the obtained OR of 10.8 (95% CI: 0.78-149.71). CONCLUSIONS: Direct and indirect comparisons did not find a difference in seizure freedom between the various AEDs, probably because of the small number of patients included. LEV and LTG appears better tolerated than CR-CBZ and LEV seems associated with more AEs than LTG. Further studies are required to provide robust evidence on efficacy and tolerability of AEDs for treating poststroke epilepsy.

A critical appraisal of randomized controlled trials on intravenous phenytoin in convulsive status epilepticus.

Since the 1970s, intravenous (IV) phenytoin (PHT) has traditionally been used as second-stage treatment for convulsive status epilepticus (SE) after failure of benzodiazepines. The aim of this review was to critically assess the evidence supporting the use of IV PHT as treatment of convulsive SE in patients of any age. In particular, we critically appraised the results of randomized controlled trials (RCTs) evaluating IV PHT as treatment of convulsive SE. A systematic search of the literature was carried out to identify RCTs evaluating IV PHT as treatment of convulsive SE in patients of any age. Eight RCTs (544 patients allocated to IV PHT) were included. The included studies differed in almost every single characteristic considered. Six RCTs (472 patients) used IV PHT without demonstrating refractoriness of SE to benzodiazepines. Only two RCTs (72 patients) used IV PHT as second-line treatment for benzodiazepine-resistant convulsive SE. Overall, most evidence from RCTs supports the use of IV PHT immediately after IV diazepam, even if seizures have not recurred. The recommendation derived from RCTs supporting the use of IV PHT as second-line treatment in benzodiazepine-resistant convulsive SE is weak. This is emblematic of the lack of robust evidence from large RCTs to inform clinical practice on how to treat SE after failure of first-line drugs. IV PHT given immediately after first-line benzodiazepines could prolong their short antiepileptic effect and prevent seizure recurrence.

The Viral Hypothesis of Mesial Temporal Lobe Epilepsy - Is Human Herpes Virus-6 the Missing Link? A systematic review and meta-analysis.

PURPOSE: Mesial temporal lobe epilepsy (MTLE) is a common epileptic disorder. Although likely multifactorial, the mechanisms underlying the etiology and pathogenesis of the disease remains unknown in majority of patients. Viruses, particularly Human Herpes Virus 6A and B (HHV-6), two neurotropic herpes viruses, have been implicated in MTLE due to their ubiquitous nature and ability to establish lifelong latency with risk of reactivation. However, the results of studies investigating this relationship are conflicting. This systematic review and meta-analysis was conducted to determine the relationship between HHV-6 DNA (not specifying if A or B) in brain tissue and MTLE based on the current evidence. METHOD: Two independent assessors carried out a comprehensive electronic search to identify all relevant studies. Both fixed- and random-effects models were used to determine the overall odds ratio. RESULTS: A total of 10 studies met the inclusion criteria for the systematic review and eight for the meta-analysis. In 19.6% of all MTLE patients HHV-6 DNA was detected in brain tissue compared to 10.3% of all controls (p >0.05). The pooled odds ratio of HHV-6 positive cases in MTLE patients was 2.016 [95%-CI: 1.16-3.50] in the fixed effect model. CONCLUSION: The results of this meta-analysis indicate an association between HHV-6 DNA and MTLE surgically resected tissue samples, unspecified if A or B or both. However, the casual relationship and possible pathological role of HHV-6 in MTLE are yet to be elucidated. This study's results provide a basis for future studies continuing the investigation into pathological implications of HHV-6.

Transcranial magnetic stimulation studies in complex regional pain syndrome type I: A review.

The sensory and motor cortical representation corresponding to the affected limb is altered in patients with complex regional pain syndrome (CRPS). Transcranial magnetic stimulation (TMS) represents a useful non-invasive approach for studying cortical physiology. If delivered repetitively, TMS can also modulate cortical excitability and induce long-lasting neuroplastic changes. In this review, we performed a systematic search of all studies using TMS to explore cortical excitability/plasticity and repetitive TMS (rTMS) for the treatment of CRPS. Literature searches were conducted using PubMed and EMBASE. We identified 8 articles matching the inclusion criteria. One hundred fourteen patients (76 females and 38 males) were included in these studies. Most of them have applied TMS in order to physiologically characterize CRPS type I. Changes in motor cortex excitability and brain mapping have been reported in CRPS-I patients. Sensory and motor hyperexcitability are in the most studies bilateral and likely involve corresponding regions within the central nervous system rather than the entire hemisphere. Conversely, sensorimotor integration and plasticity were found to be normal in CRPS-I. TMS examinations also revealed that the nature of motor dysfunction in CRPS-I patients differs from that observed in patients with functional movement disorders, limb immobilization, or idiopathic dystonia. TMS studies may thus lead to the implementation of correct rehabilitation strategies in CRPS-I patients. Two studies have begun to therapeutically use rTMS. This non-invasive brain stimulation technique could have therapeutic utility in CRPS, but further well-designed studies are needed to corroborate initial findings.

Low-frequency rTMS of the unaffected hemisphere in stroke patients: A systematic review.

The aim of this review was to summarize the evidence for the effectiveness of low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the unaffected hemisphere in promoting functional recovery after stroke. We performed a systematic search of the studies using LF-rTMS over the contralesional hemisphere in stroke patients and reviewed the 67 identified articles. The studies have been gathered together according to the time interval that had elapsed between the stroke onset and the beginning of the rTMS treatment. Inhibitory rTMS of the contralesional hemisphere can induce beneficial effects on stroke patients with motor impairment, spasticity, aphasia, hemispatial neglect and dysphagia, but the therapeutic clinical significance is unclear. We observed considerable heterogeneity across studies in the stimulation protocols. The use of different patient populations, regardless of lesion site and stroke aetiology, different stimulation parameters and outcome measures means that the studies are not readily comparable, and estimating real effectiveness or reproducibility is very difficult. It seems that careful experimental design is needed and it should consider patient selection aspects, rTMS parameters and clinical assessment tools. Consecutive sessions of rTMS, as well as the combination with conventional rehabilitation therapy, may increase the magnitude and duration of the beneficial effects. In an increasing number of studies, the patients have been enrolled early after stroke. The prolonged follow-up in these patients suggests that the effects of contralesional LF-rTMS can be long-lasting. However, physiological evidence indicating increased synaptic plasticity, and thus, a more favourable outcome, in the early enrolled patients, is still lacking. Carefully designed clinical trials designed are required to address this question. LF rTMS over unaffected hemisphere may have therapeutic utility, but the evidence is still preliminary and the findings need to be confirmed in further randomized controlled trials.

Decrease in mortality of adult epilepsy patients since 1980: lessons learned from a hospital-based cohort.

BACKGROUND AND PURPOSE: Data on mortality in patients with epilepsy have been available since the 1800s. They consistently show a 2-3-fold increase compared to the general population. Despite major advances in diagnostic tools and treatment options, there is no evidence for a decrease in premature deaths. The temporal trend of mortality in a hospital-based epilepsy cohort over three decades was assessed. METHODS: A hospital-based incidence cohort was recruited from a specialized epilepsy outpatient clinic at Innsbruck Medical University between 1980 and 2007, divided by decade into three cohorts and followed for 5 years after initial epilepsy diagnosis. Deaths and their primary causes were determined using probabilistic record linkage with the Austrian death registry. Age-, sex- and period-adjusted standardized mortality rates (SMRs) were computed in relation to the general population of the same area and grouped according to time of diagnosis. RESULTS: In all, 122 deaths in 4549.9 person-years (1954.5 women, 2595.2 men) were identified. The overall SMR was 2.2 [95% confidence interval (CI) 1.8-2.6] and decreased from 3.0 (95% CI 2.1-4.3) in 1980-1989, to 2.7 (95% CI 2.0-3.5) in 1990-1999 and to 1.4 (95% CI 1.0-2.0) in 2000-2007. CONCLUSIONS: This study indicates a decrease in mortality in newly diagnosed epilepsy patients over the last three decades. This may be due to advances in diagnosis and treatment over the past three decades, including early identification of drug resistance, introduction of new anti-epileptic drugs and establishment of a comprehensive epilepsy surgery programme in this region.

Eslicarbazepine acetate: its effectiveness as adjunctive therapy in clinical trials and open studies.

Eslicarbazepine acetate (ESL) is a once-daily antiepileptic drug that is approved as adjunctive therapy in adults with focal-onset seizures. Following oral administration, ESL is rapidly metabolized to its active metabolite, eslicarbazepine, which acts primarily by enhancing slow inactivation of voltage-gated sodium channels. The efficacy and safety/tolerability of ESL in the adjunctive setting were established in a comprehensive Phase III program (n = 1702 randomized patients) and this evidence has been supported by several open studies (n = 864). ESL treatment has demonstrated improvements in health-related quality of life, in both randomized clinical trials and open studies. ESL has also been shown to be usually well tolerated and efficacious when used in the adjunctive setting in elderly patients. The effectiveness of ESL as the only add-on to antiepileptic drug monotherapy has been demonstrated in a multinational study (n = 219), subgroup analyses of which have also shown it to be efficacious and generally well tolerated in patients who had previously not responded to carbamazepine therapy. Open studies have also demonstrated improvements in tolerability in patients switched overnight from oxcarbazepine to ESL. Due to differences in pharmacokinetics, pharmacodynamics, and metabolism, there may be clinical situations in which it is appropriate to consider switching patients from oxcarbazepine or carbamazepine to ESL.

rTMS of the prefrontal cortex has analgesic effects on neuropathic pain in subjects with spinal cord injury.

STUDY DESIGN: Repetitive transcranial magnetic stimulation study. OBJECTIVES: The analgesic effects of repetitive transcranial magnetic stimulation (rTMS) in chronic pain have been the focus of several studies. In particular, rTMS of the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC) changes pain perception in healthy subjects and has analgesic effects in acute postoperative pain, as well as in fibromyalgia patients. However, its effect on neuropathic pain in patients with traumatic spinal cord injury (SCI) has not been assessed. SETTING: Merano (Italy) and Salzburg (Austria). METHODS: In this study, we performed PMC/DLPFC rTMS in subjects with SCI and neuropathic pain. Twelve subjects with chronic cervical or thoracic SCI were randomized to receive 1250 pulses at 10 Hz rTMS (n=6) or sham rTMS (n=6) treatment for 10 sessions over 2 weeks. The visual analog scale, the sensory and affective pain rating indices of the McGill Pain Questionnaire (MPQ), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were used to assed pain and mood at baseline (T0), 1 day after the first week of treatment (T1), 1 day (T2), 1 week (T3) and 1 month (T4) after the last intervention. RESULTS: Subjects who received active rTMS had a statistically significant reduction in pain symptoms in comparison with their baseline pain, whereas sham rTMS participants had a non-significant change in daily pain from their baseline pain. CONCLUSION: The findings of this preliminary study in a small patient sample suggest that rTMS of the PMC/DLPFC may be effective in relieving neuropathic pain in SCI patients.

Overnight switching from oxcarbazepine to eslicarbazepine acetate: an observational study.

OBJECTIVES: There are clinical situations where it might be appropriate to switch patients from immediate-release oxcarbazepine (OXC) to eslicarbazepine acetate (ESL). We investigated the effects of transitioning patients overnight from OXC to ESL. MATERIALS AND METHODS: A retrospective, single-center study was conducted in which patients with drug-resistant focal epilepsy on a stable dose of immediate-release OXC for at least 4 weeks were switched overnight to ESL. Patients were switched because they experienced persistent seizures with OXC but were unable to tolerate increased OXC dosing due to adverse events. Tolerability was assessed using the Adverse Events Profile (AEP), quality of life was assessed using the Quality of Life in Epilepsy Inventory 10 (QOLIE-10), and alertness was assessed as reaction time using a subtest of the Test Battery for Attention Performance version 2.3. Assessments were performed immediately prior to and 5 days after switching from OXC to ESL (days 0 and 5, respectively). RESULTS: The analysis included 21 patients (12 women, 9 men; mean age 36 years). After switching from OXC to ESL, there were significant improvements in mean scores for AEP (P<.001), QOLIE-10 (P=.001), and alertness (P<.05). Adverse Events Profile total scores improved for 21/21 (100.0%) patients, QOLIE-10 total scores improved for 17/21 (81.0%) patients, and alertness scores improved for 16/21 (76.2%) patients. CONCLUSIONS: In this short-term, single-center study, an overnight switch from twice-daily OXC to once-daily ESL in patients with drug-resistant focal epilepsies resulted in improvements in side effects, quality of life, and alertness.

The contribution of neurophysiology in the diagnosis and management of cervical spondylotic myelopathy: a review.

STUDY DESIGN: Topical review of the literature. OBJECTIVE: The objective of this review article was to assess indications and usefulness of various neurophysiological techniques in diagnosis and management of cervical spondylogenic myelopathy (CSM). METHODS: The MEDLINE, accessed by Pubmed and EMBASE electronic databases, was searched using the medical subject headings: 'compressive myelopathy', 'cervical spondylotic myelopathy (CSM)', 'cervical spondylogenic myelopathy', 'motor evoked potentials (MEPs)', 'transcranial magnetic stimulation', 'somatosensory evoked potentials (SEPs)', 'electromyography (EMG)', 'nerve conduction studies (NCS)' and 'cutaneous silent period (CSP)'. RESULTS: SEPs and MEPs recording can usefully supplement clinical examination and neuroimaging findings in assessing the spinal cord injury level and severity. Segmental cervical cord dysfunction can be revealed by an abnormal spinal N13 response, whereas the P14 potential is a reliable marker of dorsal column impairment. MEPs may also help in the differential diagnosis between spinal cord compression and neurodegenerative disorders. SEPs and MEPs are also useful in follow-up evaluation of sensory and motor function during surgical treatment and rehabilitation. EMG and NCS improve the sensitivity of cervical radiculopathy detection and may help rule out peripheral nerve problems that can cause symptoms that are similar to those of CSM. CSP also shows a high sensitivity for detecting CSM. CONCLUSION: Neuroimaging, especially magnetic resonance imaging, represents the procedure of choice for the diagnosis of CSM, but a correct interpretation of morphological findings can be achieved only if they are correlated with functional data. The studies reported in this review highlight the crucial role of the electrophysiological studies in diagnosis and management of CSM.

Endovascular mechanical recanalization of acute ischaemic stroke in octogenarians.

BACKGROUND: Multiple studies have shown a clinical benefit of thrombectomy in acute ischaemic stroke, but most of them excluded octogenarians. The purpose of this study was to compare the outcomes between octogenarians and younger patients after thrombectomy. MATERIALS AND METHODS: One hundred and sixty-six patients with large cerebral artery occlusion and consecutive thrombectomy were evaluated and divided into two patient age groups: younger than 80 years and older than 80 years. We compared recanalization rates, complications experienced, disability, death after discharge and at a 90-day follow-up between these age groups. RESULTS: Sixty-eight percent of octogenarians and 72 % of younger patients were registered with successful recanalization (p = 1.0). There was no significant difference in symptomatic intracerebral haemorrhage between the groups (p = 0.32). However, octogenarians had a significantly lower rate of good clinical outcome (24 % vs. 48 %; p = 0.008) and a higher mortality rate (36 % vs. 12 %; p = 0.0013). CONCLUSION: Octogenarians have a lower chance of good clinical outcome and a higher mortality rate despite successful recanalization. Nevertheless, 24 % of octogenarians were documented with mRS ≤2. As this age group of octogenarians will grow prospectively, careful patient selection should be mandatory when considering octogenarians for thrombectomy. KEY POINTS: • Careful patient selection for thrombectomy should be mandatory in octogenarians. • Octogenarians have a higher mortality rate despite successful recanalization. • Nearly one-third of octogenarians were documented with a good clinical outcome.

Perampanel for focal epilepsy: insights from early clinical experience.

Perampanel is approved for adjunctive therapy of focal epilepsy with or without secondarily generalized seizures in patients aged >12 years. This narrative review uses real-world and clinical trial data to elucidate perampanel's role in the clinic. Audit data show good tolerability with perampanel and higher freedom-from-seizure rates in elderly vs younger patients. When using perampanel in elderly patients, special attention should be given to comorbidities and co-medication to avoid potential interactions or adverse events. Slower titration is generally recommended, and seizure control should be reassessed at a dose of 4 mg before further dose increases. Perampanel efficacy is similar in adolescents and adults; however, somnolence, nasopharyngitis, and aggression are more frequent in adolescents vs the overall population. Individualized and slow-dose titration can minimize adverse events. Low serum concentrations of perampanel may occur in patients also receiving some enzyme-inducing anti-epileptic drugs; a perampanel dose increase may be required. Adverse events of importance with perampanel include dizziness; anger, aggression, and hostile behavior (particularly in adolescents); and falls (particularly in patients >65 years). An individualized approach to dosing, including slower up-titration and bedtime dosing, reduces dizziness risk. Other drugs may cause or aggravate dizziness; reducing concomitant drugs may be necessary when up-titrating perampanel. It would seem clinically appropriate to give due consideration to avoiding use in patients with a history of anger or hostile/aggressive behavior. The possibility of such behaviors should be discussed with patients before starting perampanel, with monitoring during up-titration. Slower up-titration of perampanel in older patients helps reduce fall risk.