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.

Insomnia and daytime sleepiness predict 20-year mortality in older male adults: data from a population-based study.

Data regarding the possible relationship of insomnia and EDS with mortality are inconclusive. The aim of this study was to investigate the association between these sleep complaints and the risk of long-term (20 years) all-cause mortality in older adults. Between April 2000 and March 2001, 750 subjects aged 65 years and older, who resided in the seventh district of Udine, were recruited. Data on sociodemographic characteristics, past medical history, and pharmacological treatment were collected. Dementia was diagnosed using a comprehensive neurological and neuroradiological assessment. Older adults were interviewed by neuropsychologists trained in sleep disturbances in order to assess the presence of sleep complaints. Vital status was followed over 20 years until March 2020. Older male adults affected by insomnia and EDS were significantly more likely to die over the follow-up period. Indeed, males reporting poor sleep and daytime somnolence had a 60% and 48% higher chance of dying than subjects who were not affected by these sleep complaints, respectively. The HR was attenuated after adjusting for confounding variables among insomniacs, whereas that of somnolent men strengthened. Differently from men, insomnia and EDS did not have any impact on mortality in older women. In conclusion, older male adults affected by insomnia and EDS had a significant increased risk of mortality, which is independent of cancer, depression, dementia, cardiovascular diseases, and sleeping pill use.

Amino acid supplementation in l-dopa treated Parkinson's disease patients.

BACKGROUND: The correlation between Parkinson disease and malnutrition is well established, however a protein-restricted diet is usually prescribed because of potentially negative interactions between dietary amino acids and l-dopa pharmacokinetics. This strategy could increase the risk of further nutritional deficits. METHODS: A monocentric, prospective, randomized, double-blind pilot study was performed on two groups of Parkinson-affected, protein-restricted, patients: Intervention (n = 7; amino acid supplementation twice daily) and Placebo (n = 7; placebo supplementation twice daily). At enrolment, after 3- and 6-month supplementation, neurological evaluations (UPDRS III, Hoenh-Yahr scale, l-dopa equivalent dose assessment) were performed and blood sample was collected to define insulin sensitivity (QUICKI index) and oxidative stress (oxidized and reduced glutathione). Repeated measure ANCOVA was applied to define time effect and time × treatment interaction. RESULTS: Participants were comparable at baseline for all assessed parameters. Neurological outcomes and l-dopa requirement were comparable in both group after 6-month of supplementation, without time × treatment interaction. The decrease in insulin sensitivity, as assessed by QUICKI index, observed after 6 months in both groups, was greater in Placebo than in Intervention (time effect p < 0.001; time × treatment interaction p = 0.01). Moreover, despite no changes in total erythrocyte glutathione concentrations, oxidized glutathione levels decreased by 28 ± 17% in the Intervention while increased by 55 ± 38% in Placebo (time effect p = 0.05; time × treatment interaction p = 0.05), after 6-month supplementation. CONCLUSIONS: Amino acid supplementation, assumed with shrewd temporal distribution, did not show detrimental effects on neurological and pharmacological control in protein-restricted Parkinson-affected patients, chronically treated with l-dopa. Furthermore, daily amino acid supplementation partially counteracted insulin resistance development and the loss in antioxidant availability.

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.

Hemifacial spasm due to a tentorial paramedian meningioma: a case report.

Hemifacial spasm (HFS) is a movement disorder characterised by involuntary paroxysmal facial movements that usually involve the orbicularis oculi and then spread to the other facial muscles. A microvascular compression and demyelination of the seventh nerve at its exit from the brain stem is considered to be the main aetiology of HFS. In addition to rare idiopathic (cryptogenetic) cases, others causes of HFS exist: tumours or vascular malformations have been described, of both the ipsilateral and contralateral cerebellopontine angle (CPA). However, space-occupying lesions in locations other than CPA are usually not thought to be responsible for HFS. Here we describe the case of a 45-year-old woman suffering from HFS, who dramatically improved after surgical removal of a tentorial paramedian meningioma.

Case report: subependymal diffuse heterotopia. Clinical, EEG, and neuroimaging findings.

We report the case of a 41 year-old woman with a slight mental retardation and epilepsy. MRI showed a diffuse subependymal heterotopia. The cognitive level supports the view that the ectopic cells are probably not important for the normal cortical functions but that they are likely able to maintain some of the electric properties of normal neurons, even if with altered discharge modalities. The genetic etiology of subependymal neuronal migration disorders is discussed. This is the second reported case of diffuse subependymal heterotopia in a female patient.

Clinical case report: multiple idiosyncratic adverse effects of antiepileptic drugs in trisomy 9p.

We report the case of a mentally retarded 30 y.o. patient with partial trisomy of chromosome 9, affected by epilepsy. Following treatment with antiepileptic drugs (AEDs), the patient developed several rare complications: after beginning therapy with phenytoin, the patient developed pseudolymphoma; after monotherapy with carbamazepine (CBZ), the patient thereafter developed myoclonic jerks of upper and lower limbs upon awakening; after one year of treatment with valproate (VPA) the patient developed clinical and immuno-haematological signs of SLE. Gradual withdrawal of AED, obtained clinical remission. The possibility that the chromosomal abnormality of the patient was responsible for the three rare complications observed during AED therapy is considered.

Sleep in healthy elderly subjects: a 24-hour ambulatory polysomnographic study.

It is still debated whether the deterioration of the sleep pattern, frequently reported by elderly subjects, is due only to aging per se. Other factors associated with aging or modifications of biological rhythms could also be involved. Elderly subjects frequently complain of daytime sleepiness, but it is not clear whether this actually represents a return to a polyphasic structure of sleep, or only a consequence of a disturbed night sleep. Ten healthy, independent and active elderly subjects (age > 72 years) were elevated by means of 24-hour ambulatory polysomnography. Findings of nocturnal sleep were compared with sleep of the same group in the 24-hour period and with sleep of young healthy controls. We observed a fragmentation of nocturnal sleep, but a fairly good representation of stages and a preservation of cyclicity. Except for three cases, with early or late times of sleep onset and wake-up, sleep disruption did not seem to be related to modification of circadian rhythms. Only three subjects presented undesired daytime naps, whereas the others either did not show daytime sleep at all, or were used to having their siesta after lunch since their young adulthood. In normal aging, daytime sleep does not constitute a social problem. Ambulatory polysomnography is a valid alternative to laboratory recordings in the identification of daytime sleep.

Interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy.

We examined variations in interictal spiking during sleep and wakefulness to assess differences in reliability for localizing epileptic foci. Forty patients were studied prospectively. Spikes were assessed for rates, field, and appearance of new foci. Final localization was determined by surgery, electrocorticography, and seizure onset. Comparison of interictal EEG foci with final localization was made. In 39 patients, slow-wave sleep activated spiking compared with wakefulness. Most patients showed maximal spiking in sleep stages 3 or 4. Restriction of field in rapid eye movement (REM) sleep and wakefulness, and extension of field in slow-wave sleep occurred. New foci appeared in non-rapid eye movement sleep in 53% of patients. Similar but not identical spiking rates, foci, and field distributions were seen in wakefulness and REM sleep. All REM foci were unilateral. Our findings suggest that localization of the primary epileptogenic area is more reliable in REM sleep than in wakefulness, and in wakefulness more than in slow-wave sleep.

Intracerebral metastasis in Ewing's sarcoma.

The evidence of CNS involvement in Ewing's sarcoma is uncommon and very often due to a direct extension of the tumor to extradural space and meninges. We report a case of a 14-year old girl with a primary ischio-pubic localization of Ewing's sarcoma. Body CT scan showed a bone lesion involving the left fronto-temporal region of the skull without affecting the brain. After chemotherapy radiological findings showed complete recovery. Ten months after treatment, the patient had neurological symptoms. Cerebral CT scan evidenced a large tumor mass localized in the right temporal lobe. Following radiotherapy the tumor mass was no longer visible. This case shows that late intraparenchymal CNS metastasis occurs independently from the previous skull lesion. Therefore these data, even through based on a single observation, lead to believe that in some cases prophylactic chemotherapy and radiotherapy of CNS may not be necessary.

Monitoring of subcortical and cortical somatosensory evoked potentials during carotid endarterectomy: comparison with stump pressure levels.

Monitoring of multichannel somatosensory evoked potentials (SEPs) has been performed in 40 cases of carotid endarterectomy (CEA). SEPs were obtained after median nerve stimulation at wrist, recording from 2nd cervical and from the scalp parietal (ipsi- and contralateral) and central (contralateral) positions. The reduction of CBF due to clamping of the carotid artery provoked SEP abnormalities in 10 of the 40 cases. None of the 30 patients with unmodified SEPs developed post-surgical neurological sequelae. SEP alterations were characterized exclusively by amplitude decrements and latency increases of the cortical components, the subcortical ones being unaffected. In 5 of these patients, SEPs returned to normal values before the end of the intervention and no neurological deficit was observed on awakening. In the remaining 5 cases SEPs retained their abnormalities and patients developed post-surgery neurological sequelae (4 immediately, 1 the day after). SEP alterations affected parietal and central components to a similar extent; however, in a few cases cerebral blood flow deficits provoked by carotid clamping modified differently the central P22 and the parietal N20-P25 waves. Comparisons with stump (back) pressure in the carotid artery revealed a higher sensitivity of the SEP technique in detecting vascularization problems due to carotid clamping. The time course of the appearance of SEP abnormalities seems to discriminate alterations secondary to collateral revascularization from those determined by embolization.

On the spinal pathways mediating scalp-SEPs to upper and lower limb nerve stimulation: case report and discussion.

Scalp-SEPs to peroneal nerve stimulation were abnormal in a patient with an intradural meningeoma which was compressing the antero-lateral quadrant of the 1st and, partly, the 2nd cervical myelomers. In contrast, spine and scalp-SEPs were symmetrically normal during the sural, median and ulnar nerve stimulation of either side. On surgery, it was observed that the tumor had left the dorsal columns (DCs) almost unaffected. It is argued, in agreement with the bulk of experimental evidence, that in humans the scalp-SEPs to lower mixed nerve stimulation are also mediated, at the rostral cord level, by fast-propagating tracts ascending outside the DCs.