Lacosamide in monotherapy in BTRE (brain tumor-related epilepsy): results from an Italian multicenter retrospective study.

PURPOSE: Lacosamide (LCM) is a third-generation anti-seizure medication (ASM) approved for focal onset epilepsy in patients aged ≥ 4.378 Previous studies have reported an efficacy of LCM as add-on treatment in brain tumor-related epilepsy (BTRE). To date, there are no studies in the literature focusing on lacosamide used in monotherapy to treat BTRE. In our retrospective study we investigated efficacy and tolerability of LCM in monotherapy in a multicenter national cohort of primary brain tumor patients. METHODS: We collected from 12 Italian Centers 132 patients with primary brain tumors who were treated with LCM in monotherapy. For each patient we evaluated seizure freedom at 3 and 6 months (primary endpoints), side effects and drop-out rate (secondary endpoints). RESULTS: Overall, LCM led to seizure freedom in 64.4% of patients at 3 months and 55% at 6 months. Patients who used two or more ASMs before LCM had a worse seizure control than patients in monotherapy with LCM as first choice. In 14 patients, we observed seizure control despite tumor progression on magnetic resonance (MRI). Multivariate analysis showed that gross-total resection at diagnosis was significantly associated with higher seizure freedom rate at 6 months. Side effects were mainly mild (grade 1-2 according to CTCAE classification) and drop-out rate was low (1.5%). Main side effects were dizziness and somnolence. CONCLUSIONS: This is the first study showing a good efficacy and tolerability of LCM when used in monotherapy in BTRE. Further prospective studies are needed to confirm these preliminary data, investigating also quality of life and neurocognitive functions.

Rhabdomyolysis caused by tocolytic therapy with ritodrine hydrochloride.

We report a case of rhabdomyolysis with severe generalized weakness and muscle pain after administration of ritodrine hydrochloride, in a pregnant patient without history of neuromuscular disease. Laboratory tests showed an increase of blood CK value and myoglobinuria. An electromyography was performed, revealing a typical myogenic pattern and diffuse denervation activity. Muscular biopsy allowed to rule out inflammatory and metabolic myopathy. After delivery, the patient underwent intensive rehabilitation with progressive improvement of her clinical situation, until complete recovery. Three months later, both neurological assessment and CK levels were normal. This case highlights that rhabdomyolysis has to be considered even in patient treated with ritodrine alone and without history of neuromuscular disease. Therefore, muscular symptoms and CK levels should be monitored in women treated with ritodrine for premature labour.

Oxcarbazepine reduces seizure frequency in a high proportion of patients with both newly diagnosed and refractory partial seizures in clinical practice.

The antiepileptic efficacy and tolerability of oxcarbazepine, used both as monotherapy and adjunctive therapy, were observed for 1 year in 202 adult patients, aged 17-83 years, with newly diagnosed or refractory partial epilepsy in clinical practice in Italy. At first observation, the seizure free rate was 72.2% in newly diagnosed patients given monotherapy, 40% in patients in whom oxcarbazepine replaced another monotherapy and 10.3% in patients given oxcarbazepine as adjunctive therapy. At least 50% reduction in seizure frequency was achieved in 90.7, 72 and 57%, respectively. Efficacy increased with the duration of treatment (p < 0.0001). In the 160 completers the seizure free rate was 61.3% with monotherapy and 28% with adjunctive therapy. 16.3% of patients reported adverse effects, mainly sedation and sleepiness; 5% discontinued oxcarbazepine because of adverse events. OXC is an effective and well-tolerated antiepileptic agent for the long-term treatment of partial epilepsy in adults.

Sleep disorders and extrapyramidal diseases: an historical review.

BACKGROUND AND PURPOSE: Sleep disorders have been mentioned since the first descriptions of extrapyramidal diseases in James Parkinson's Essay on the Shaking Palsy, but only recently they have become the subject of attention, thanks to new acquisitions in clinical knowledge and electroencephalographic technology. In the late 1960s, the introduction of L-dopa permitted comparison of sleep patterns in drug-naive patients before and after therapy in conditions very similar to experimental ones. Historically, we can recognise two major lines of study, one dealing with descriptions of sleep behaviours modified by drugs and the other with polysomnographic sleep research carried out before and after treatment. PATIENTS AND METHODS: The data obtained from the first polysomnographic studies led to the definition of sleep macro- and microstructure in patients suffering from Parkinson's disease, but the interpretation of drug-induced changes was not unequivocal. RESULTS: According to some authors, the improvement in sleep architecture was due mainly to improvement of nocturnal motor impairment. Other researchers suggested a primary sleep dysfunction caused by specific neurodegenerative processes in the brain structures regulating the sleep-wake cycle. CONCLUSIONS: The latter hypothesis has recently been supported by the observation that distinct sleep disorders, such as REM behaviour disorder or restless legs syndrome, often herald extrapyramidal diseases or are a frequent adjunctive complaint for these patients.

Sleep and sleep deprivation as EEG activating methods.

OBJECTIVES: We examined retrospectively 19 patients with a history of clinical seizures, but normal activity or unclear epileptiform abnormalities in wake EEG recordings and obtained preliminary data for a controlled cohort study to evaluate the effects of sleep deprivation (SD) on interictal epileptic activity. METHODS: Nineteen patients referred to our EEG department for diagnostic or follow-up purposes were divided in two groups on the basis of the different EEG protocols applied. The first group (n=5) underwent two laboratory polysomnographies during afternoon naps, after SD, but the patients failed to fall asleep in one of the two occasions. The second group (n=14) was submitted to two polysomnographies, the first without SD and the second after SD. RESULTS: The first group of patients demonstrated focal epileptic discharges in 4 patients in which wake after SD appeared to be less activated that sleep after SD. In the second group the results obtained from the waking part of the recordings suggest a lack of activating effect due to SD. CONCLUSIONS: SD does not seem to offer greater activation than sleep alone. However, a mild SD may be a convenient activating method for inducing sleep and drowsiness without using any drug.