Rapid versus slow withdrawal of antiepileptic monotherapy in two-year seizure-free adults patients with epilepsy (RASLOW) study: A pragmatic multicentre, prospective, randomized, controlled study.

PURPOSE: To establish whether a slow or a rapid withdrawal of antiepileptic monotherapy influences relapse rate in seizure-free adults with epilepsy and calculates compliance and differences in the severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries, and death. METHODS: This is a multicentre, prospective, randomized, open label, non-inferiority trial in people aged 16 + years who were seizure-free for more than 2 years. Patients were randomized to slow withdrawal (160 days) or rapid withdrawal (60 days) and were followed for 12 months. The primary outcome was the probability of a first seizure relapse within the 12-months follow-up. The secondary outcomes included the cumulative probability of relapse at 3, 6, 9, and 12 months. A non-inferiority analysis was performed with non-inferiority margin of - 0.15 for the difference between the probabilities of seizure recurrence in slow versus rapid withdrawal. RESULTS: The sample comprised 48 patients, 25 randomized to slow withdrawal and 23 to rapid withdrawal. Median follow-up was 11.9 months. In the intention-to-treat population, 3 patients in the slow-withdrawal group and 1 in the rapid withdrawal group experienced seizure relapses. The corresponding probabilities of seizure recurrence were 0.12 for slow withdrawal and 0.04 for rapid withdrawal, giving a difference of 0.08 (95% CI - 0.12; 0.27), which is entirely above the non-inferiority margin. No patients developed status epilepticus and seizure-related injuries or died. Risks were similar in the Per-Protocol population. CONCLUSIONS: Seizure-relapse rate after drug discontinuation is lower than in other reports, without complications and unrelated to the duration of tapering.

Contraction and nutrition interaction promotes anabolism in cachectic muscle.

PURPOSE OF REVIEW: Cachexia is a disease-related multifactorial syndrome characterized by inflammation, massive muscle protein catabolism and carbohydrate and lipid metabolism disorder.Several studies tried to define the impact of either nutrition or physical exercise (single approach strategy) or their combination (multimodal approach strategy) on prevention and/or treatment of muscle wasting in cachectic patients. RECENT FINDINGS: Single approach strategies (i.e. nutrition or physical exercise) have the potential of preventing and improving features of the cachexia syndrome possibly with a differential impact according to the underlying disease. Limited information is available on the beneficial effect of multimodal approach strategies. SUMMARY: Multimodal approaches appear to be more effective than those based on single interventions in physiological condition and in cachectic patients with COPD or chronic kidney disease. Further studies, however, are required in cachexia induced by heart failure, cancer and critical illness.

Intravenous brivaracetam in status epilepticus: A multicentric retrospective study in Italy.

PURPOSE: to evaluate the use, effectiveness, and adverse events of intravenous brivaracetam (BRV) in status epilepticus (SE). METHODS: a retrospective multicentric study involving 24 Italian neurology units was performed from March 2018 to June 2020. A shared case report form was used across participating centres to limit biases of retrospective data collection. Diagnosis and classification of SE followed the 2015 ILAE proposal. We considered a trial with BRV a success when it was the last administered drug prior the clinical and/or EEG resolution of seizures, and the SE did not recur during hospital observation. In addition, we considered cases with early response, defined as SE resolved within 6 h after BRV administration. RESULTS: 56 patients were included (mean age 62 years; 57 % male). A previous diagnosis of epilepsy was present in 21 (38 %). Regarding SE etiology classification 46 % were acute symptomatic, 18 % remote and 16 % progressive symptomatic. SE episodes with prominent motor features were the majority (80 %). BRV was administered as first drug after benzodiazepine failure in 21 % episodes, while it was used as the second or the third (or more) drug in the 38 % and 38 % of episodes respectively. The median loading dose was 100 mg (range 50-300 mg). BRV was effective in 32 cases (57 %). An early response was documented in 22 patients (39 % of the whole sample). The use of the BRV within 6 h from SE onset was independently associated to an early SE resolution (OR 32; 95 % CI 3.39-202; p = 0.002). No severe treatment emergent adverse events were observed. CONCLUSION: BRV proved to be useful and safe for the treatment of SE. Time to seizures resolution appears shorter when it is administered in the early phases of SE.

Effects of inflammation and/or inactivity on the need for dietary protein.

PURPOSE OF REVIEW: Protein requirement in healthy young and old individuals is traditionally defined as the lowest protein intake sufficient to achieve neutral body protein balance. This concept, however, cannot be applied to those conditions characterized by unavoidable protein catabolism despite optimal nutrition, such as inactivity and diseases associated with systemic inflammation. RECENT FINDINGS: The ability of dietary proteins to promote protein anabolism is reduced by inactivity and inflammatory mediators, whereas physical exercise ameliorates the efficiency in using dietary proteins. Consequently, the protein intake level associated with the lowest rate of catabolism in inactivity and/or inflammation is greater than the minimum protein intake required to achieve neutral protein balance in healthy, physically active individuals. A protein intake of 1.2 g.kg.day is currently recommended for inactive healthy individuals, whereas guidelines recommend up to 1.5 g.kg.day in patients with severe systemic inflammation, such as those affected by critical illness or cancer. High protein intake accelerates progression of renal insufficiency but does not affect renal function in healthy individuals. SUMMARY: In inflammation and/or inactivity a relatively high protein intake may be required to promote synthesis of specific proteins, prevent depletion of selected amino acids (e.g., glutamine or arginine), modulate immune functions, counteract insulin resistance and redox unbalance. Thus, an optimal protein/amino acid intake may be greater than that required to decrease whole body protein wasting.

An atypical Bickerstaff's brainstem encephalitis with involvement of spinal cord.

Bickerstaff brainstem encephalitis (BBE) is a rare neurological disease that generally has a good prognosis. We describe an atypical case of a patient with severe BBE; the presentation was uncommon because of the lack of ophthalmoplegia and because of evidence of both peripheral neuropathy and brainstem encephalitis. The article reports clinical and biochemical evaluation and focuses on magnetic resonance imaging (MRI) findings in diagnosis and management of the patient. Notably, we found a previously unreported dramatic spinal cord involvement on MRI. We believe these findings could add to diagnostic tools, and that this case may represent a new variant of BBE with more aggressive behavior.