Perampanel as only add-on epilepsy treatment in elderly: A subgroup analysis of real-world data from retrospective, multicenter, observational study.

INTRODUCTION: Drug management of epilepsy in the elderly presents unique but data on this population are scarce. This study aimed to assess the effectiveness and tolerability of perampanel (PER) used as only add-on to a background anti-seizure medication (ASM) in the elderly in a real-world setting. METHODS: We performed a subgroup analysis of patients aged ≥65 years included in a previous 12-month multicenter study on adults. Treatment discontinuation, seizure frequency, and adverse events were recorded at 3, 6 and 12 months after PER introduction. Sub-analyses by early (≤1 previous ASM) or late PER add-on were also conducted. RESULTS: The sample included 65 subjects (mean age: 75.7 ± 7.2 years), with mainly focal (73.8%) epilepsy. The mean PER daily dose was ≈4 mg during all follow-up. Retention rates at 3, 6, and 12 months were 90.5%, 89.6%, and 79.4%ly. The baseline median normalized per 28-day seizure number significantly decreased at 3-, 6- and 12-month visits. One year after PER introduction, the responder rate (≥50% reduction in baseline seizure frequency) was 89.7%, with a seizure freedom rate of 72.4%. Adverse events occurred in 22 (34.9%) patients with dizziness and irritability being the most frequent. No major differences between early (41 patients, 63.1%), and late add-on groups were observed. CONCLUSION: Adjunctive PER was effective and well-tolerated when used as only add-on treatment in elderly people with epilepsy in clinical practice, thus representing a suitable therapeutic option in this age category.

Effectiveness of Perampanel as the Only Add-on: Retrospective, Multicenter, Observational Real Life Study on epilepsy patients.

OBJECTIVE: Perampanel (PER) is indicated as adjunctive antiseizure medication (ASM) in adolescents and adults with epilepsy. Data from clinical trials show good efficacy and tolerability, while limited information is available on the routine clinical use of PER, especially when used as only add-on treatment. METHODS: we performed an observational, retrospective, multicenter study on people with focal or generalized epilepsy aged >12 years, consecutively recruited from 52 Italian epilepsy centers. All patients received PER as the only add-on treatment to a background ASM according to standard clinical practice. Retention rate, seizure frequency and adverse events were recorded at 3, 6 and 12 months after PER introduction. Sub-analyses by early or late use of PER and by concomitant ASM were also conducted. RESULTS: 503 patients were included (age 36.5±19.9 years). Eighty-one per cent had focal epilepsy. Overall, the retention rate was very high in the whole group (89% at 12 months) according with efficacy measures. No major differences were observed in the sub-analyses, although patients who used PER as early add-on, as compared with late add-on, more often reached early seizure freedom at 3 months follow-up (66% vs. 53%, p=0.05). Treatment-emergent adverse events occurred in 25%, far less commonly than in PER randomized trials. SIGNIFICANCE: this study confirms the good efficacy and safety of PER for focal or generalized epilepsy in real-life conditions. We provide robust data about its effectiveness as only add-on treatment even in patients with a long-standing history of epilepsy and previously treated with many ASMs.

Effect of Brivaracetam on Efficacy and Tolerability in Patients With Brain Tumor-Related Epilepsy: A Retrospective Multicenter Study.

Background: Epilepsy is a common symptom of brain tumors and is often pharmacoresistent. Among new antiseizure medications (ASMs) Brivaracetam (BRV) has been approved as adjunctive treatment for focal seizures and it was tested in non-oncological patient populations. This is the first study that retrospectively explored efficacy and tolerability of BRV as add-on therapy in brain tumor-related epilepsy (BTRE) patients. Materials and Methods: We reviewed the medical records of 33 BTRE patients from six Italian epilepsy centers; charts included tumor history, diagnosis of BTRE, BRV added as first or second add-on for uncontrolled seizures and/or adverse events (AEs) of the previous ASMs, at least 1-month follow-up, seizure frequency, and AEs assessment. Results: Thirty-three patients (19 males, mean age: 57.6 years; 14 females, mean age: 42.4 years): 11 low grade gliomas, five high grade gliomas, six meningiomas, 10 glioblastomas, one primary cerebral lymphoma. Fourteen patients had focal aware seizures, nine focal unaware, seven focal to bilateral tonic-clonic seizures, three patients presented more than one seizure type: focal unaware with focal to bilateral tonic clonic seizures (two patients) and focal aware and unaware seizures (one patient). Mean seizure frequency in the month preceding BRV introduction: 7.0; at last follow-up: 2.0 (p = 0.001). Seven patients (21.2%) reported AEs (anxiety, agitation, fatigue, vertigo) and three of them (9.0%) required drug withdrawal due to psychiatric adverse events (PAEs). Three other patients withdrew BRV: one for scarce compliance (3.0%), two for uncontrolled seizures (6.0%). Conclusion: Our results showed that BRV could be a new therapeutic option effective in reducing seizures in BTRE patients, taking into account the incidence of PAEs in this particular population. Future and larger prospective studies are needed.

Levetiracetam improves intention tremor in fragile x-associated tremor/ataxia syndrome.

Fragile X-associated tremor/ataxia syndrome is a recently discovered disorder affecting more of one third of older adult male carriers of premutation alleles of fragile X mental retardation 1 (FMR1 gene). There is no established treatment.The 66-year-old right-handed grandfather of a boy with fragile X syndrome, a carrier of premutation alleles of FMR1 gene, developed an action tremor in his right hand when writing. His writing became large and completely illegible. Administration of levetiracetam was associated with subjective and objective improvement, and handwriting became possible again. Levetiracetam was well tolerated, and no adverse effects were reported.

Motor cortex excitability in Alzheimer's disease and in subcortical ischemic vascular dementia.

Twenty Alzheimer's disease (AD) patients, 20 subcortical ischemic vascular dementia (SIVD) patients and 20 neurologically and cognitively normal subjects underwent transcranial magnetic stimulation to study motor cortex excitability changes. Motor threshold (MT), amplitude of motor evoked potentials, silent period and the H/M ratio (amplitude of maximal Hoffman reflex vs. that of maximal motor response) were considered. MT was lower in SIVD patients when compared with AD patients (P = 0.003) and the control group (P < 0.001) and lower in AD patients when compared with the control group (P < 0.001). The increment of motor cortex excitability in AD and SIVD did not lead us to distinguish clearly the two types of dementia. It is likely that the electrophysiological similarity between AD and SIVD could represent another common mechanism shared from these forms of dementia.

Cognitive findings in spinocerebellar ataxia type 2: relationship to genetic and clinical variables.

Several authors have recently reported a broad cognitive impairment in autosomal dominant cerebellar ataxias (ADCAs) patients. However, only a few studies on neuropsychological features in spinocerebellar ataxia type 2 (SCA2) patients are present in the current literature. The aim of this study is to evaluate the cognitive impairment in a wide sample of SCA2 patients and to verify the role of different disease-related factors (age of onset, disease duration, and clinical severity) on intellectual abilities. We administered a battery of neuropsychological tests assessing handedness, attention, short- and long-term verbal and visuo-spatial memory, executive functions, constructive abilities, general intellectual abilities and depression to 18 SCA2 patients belonging to eight families who came to our observation. Evidence of impaired verbal memory, executive functions and attention was found. The cognitive status was partially related to clinical severity rather than to disease duration or age at onset of symptoms. We partially confirmed data on cognitive defects already reported by others but we also found defective attention skills as well as significant lower performances in a nonverbal intelligence task.