Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drug-resistant focal epilepsy.

OBJECTIVE: Although many studies have attempted to describe treatment outcomes in patients with drug-resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug-resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria. METHODS: This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug-resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP). RESULTS: A seizure-free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a "treatment failure" as compared to the judgment of the investigator (46.7% vs 62.9%, P < 0.001), because many more patients were rated as "undetermined outcome" (45.6% vs 27.7%, P < 0.001); 19.3% of the recruited patients were not considered drug-resistant by the EP. SIGNIFICANCE: This study validates the use of ILAE treatment outcome criteria in a real-life setting, providing validated estimates of seizure freedom in patients with drug-resistant focal epilepsy in relation to the number of previously failed AEDs. Fewer than one in 10 patients achieved seizure freedom on a newly introduced AED over the study period. Pseudo drug resistance could be identified in one of five cases.

Weight loss and decubitus duodenal ulcer in Parkinson's disease treated with levodopa-carbidopa intestinal gel infusion.

Apparently, unexplained weight loss is a common symptom experienced by patients affected by Parkinson's disease, especially in those treated by levodopa-carbidopa infusion gel (LCIG) with a poor control of dyskinesias. Weight loss is considered part of gastrointestinal dysfunction seen in patients affected by Parkinson's disease, along with gastroparesis and reduced bowel peristalsis. In patients treated with LCIG, weight loss needs to be accurately evaluated, because of possible underlying life-threatening adverse events, like duodenum decubitus ulcer.

A prospective study of direct medical costs in a large cohort of consecutively enrolled patients with refractory epilepsy in Italy.

OBJECTIVE: To evaluate direct medical costs and their predictors in patients with refractory epilepsy enrolled into the SOPHIE study (Study of Outcomes of PHarmacoresistance In Epilepsy) in Italy. METHODS: Adults and children with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers and followed for 18 months. At entry, all subjects underwent a structured interview and a medical examination, and were asked to keep records of diagnostic examinations, laboratory tests, specialist consultations, treatments, hospital admissions, and day-hospital days during follow-up. Study visits included assessments every 6 months of seizure frequency, health-related quality of life (Quality of Life in Epilepsy Inventory 31), medication-related adverse events (Adverse Event Profile) and mood state (Beck Depression Inventory-II). Cost items were priced by applying Italian tariffs. Cost estimates were adjusted to 2013 values. RESULTS: Of 1,124 enrolled individuals, 1,040 completed follow-up. Average annual cost per patient was € 4,677. The highest cost was for antiepileptic drug (AED) treatment (50%), followed by hospital admissions (29% of overall costs). AED polytherapy, seizure frequency during follow-up, grade III pharmacoresistance, medical and psychiatric comorbidities, and occurrence of status epilepticus during follow-up were identified as significant predictors of higher costs. Age between 6 and 11 years, and genetic (idiopathic) generalized epilepsies were associated with the lowest costs. Costs showed prominent variation across centers, largely due to differences in the clinical characteristics of cohorts enrolled at each center and the prescribing of second-generation AEDs. Individual outliers associated with high costs related to hospital admissions had a major influence on costs in many centers. SIGNIFICANCE: Refractory epilepsy is associated with high costs that affect individuals and society. Costs differ across centers in relation to the characteristics of patients and the extent of use of more expensive, second-generation AEDs. Epilepsy-specific costs cannot be easily differentiated from costs related to comorbidities.

Determinants of health-related quality of life in pharmacoresistant epilepsy: results from a large multicenter study of consecutively enrolled patients using validated quantitative assessments.

PURPOSE: To evaluate the relative contribution of demographic and epilepsy-related variables, depressive symptoms, and adverse effects (AEs) of antiepileptic drugs (AEDs) to health-related quality of life (HRQOL) in adults with pharmacoresistant epilepsy. METHODS: Individuals with epilepsy whose seizures failed to respond to at least one AED were enrolled consecutively at 11 tertiary referral centers. HRQOL was assessed by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), AEs by the Adverse Event Profile (AEP), and depressive symptoms by the Beck Depression Inventory-II (BDI-II). Multivariate linear regression models were used to identify variables associated with QOLIE-31 total score and subscale scores. KEY FINDINGS: Of 933 enrolled individuals aged 16 years or older, 809 (87%) were able to complete the self-assessment instruments and were included in the analysis. Overall, 61% of the variance in QOLIE-31 scores was explained by the final model. The strongest predictors of HRQOL were AEP total scores (ß = -0.451, p < 0.001) and BDI-II scores (ß = -0.398, p < 0.001). These factors were also the strongest predictors of scores in each of the seven QOLIE-31 subscales. Other predictors of HRQOL were age (ß = -0.060, p = 0.008), lack of a driving license (ß = -0.053, p = 0.018), pharmacoresistance grade, with higher HRQOL in individuals who had failed only one AED (ß = 0.066, p = 0.004), and location of the enrolling center. Epilepsy-related variables (seizure frequency, occurrence of tonic-clonic seizures, age of epilepsy onset, disease duration) and number of AEDs had no significant predictive value on HRQOL. The AEP total score was the strongest negative predictor of HRQOL in the subgroup of 362 patients without depressive symptoms (BDI-II score <10), but even in this subgroup the BDI-II score was retained as a significant predictor. SIGNIFICANCE: In individuals with pharmacoresistant epilepsy, AEs of medication and depressive symptoms are far more important determinants of HRQOL than seizures themselves. When seizure freedom cannot be achieved, addressing depressive comorbidity and reducing the burden of AED toxicity is likely to be far more beneficial than interventions aimed at reducing the frequency of seizures.

Characteristics of a large population of patients with refractory epilepsy attending tertiary referral centers in Italy.

The characteristics of 1,124 consecutive adults and children with refractory epilepsy attending 11 tertiary referral centers in Italy were investigated at enrollment into a prospective observational study. Among 933 adults (age 16-86 years), the most common syndromes were symptomatic (43.7%) and cryptogenic (39.0%) focal epilepsies, followed by idiopathic (8.1%) and cryptogenic/symptomatic generalized (6.2%) epilepsies. The most common syndrome among 191 children was symptomatic focal epilepsy (35.1%), followed by cryptogenic focal (18.8%), cryptogenic/symptomatic generalized (18.3%), undetermined whether focal or generalized (16.8%), and idiopathic generalized (7.3%). Primarily and secondarily generalized tonic-clonic seizures were reported in 27.8% of adults and 16.8% of children. The most commonly reported etiologies were mesial temporal sclerosis (8.0%) and disorders of cortical development (6.2%) in adults, and disorders of cortical development (14.7%) and nonprogressive encephalopathies (6.8%) in children. More than three-fourths of subjects in both age groups were on antiepileptic drug (AED) polytherapy.

Does screening for adverse effects improve health outcomes in epilepsy? A randomized trial.

OBJECTIVE: To determine whether systematic screening for adverse effects of antiepileptic drugs (AEDs) reduces toxicity burden and improves health-related quality of life in patients with epilepsy. METHODS: Consecutive patients with uncontrolled seizures aged ≥16 years and a high Adverse Event Profile (AEP) score were randomized to 2 groups and followed up for 18 months at 11 referral centers. AEP scores were made available to treating physicians at all visits in the intervention group, but not in the control group. Co-primary endpoints were changes in AEP scores and Quality of Life Inventory for Epilepsy-31 (QOLIE-31) scores. RESULTS: Of 809 enrolled patients able to complete the AEP questionnaire, 222 had AEP scores ≥45 and were randomized to the intervention (n = 111) or control group (n = 111). A total of 206 patients completed the 18-month follow-up. Compared with baseline, AEP scores decreased on average by 7.2% at 6 months, 12.1% at 12 months, and 13.8% at 18 months in the intervention group (p < 0.0001), and by 7.7% at 6 months, 9.2% at 12 months, and 12.0% at 18 months in controls (p < 0.0001). QOLIE-31 scores also improved from baseline to final visit, with a mean 20.7% increase in the intervention group and a mean 24.9% increase in the control group (p < 0.0001). However, there were no statistically significant differences in outcomes between groups for the 2 co-primary variables. CONCLUSIONS: Contrary to findings from a previous study, systematic screening for adverse effects of AEDs using AEP scores did not lead to a reduced burden of toxicity over usual physician treatment. ITALIAN MEDICINES AGENCY AIFA IDENTIFIER: FARM52K2WM_003. CLINICALTRIALSGOV IDENTIFIER: NCT03939507 (registered retrospectively in 2019; the study was conducted during the 2006-2009 period and registration of clinical trials was not a widely established practice when this study was initiated). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the additional collection of formal questionnaires regarding adverse effects of AEDs does not reduce toxicity burden over usual physician treatment.

Prevalence of primary focal or segmental dystonia in adults in the district of foggia, southern Italy: a service-based study.

BACKGROUND: Primary focal or segmental dystonia is a rare clinical condition including early-onset dystonia, which has the tendency to generalize, and late-onset dystonia, which may be focal or segmental. The prevalence of late-onset dystonia ranges from 30 to 7,320 cases per million, but no data are available in Italy. METHODS: A service-based study was conducted in the period 1 January 2001 through 31 December 2002 in the administrative district of Foggia, southern Italy (population 541,653). Cases were traced through hospital discharge diagnosis, botulinum toxin services, day hospital access, ear, nose and throat, ophthalmology and orthopedic surgery specialists, and territorial outpatient services. Inclusion criteria were age 17 years or older, residency in the study area and a diagnosis of primary focal/segmental dystonia. RESULTS: A total of 69 patients were included, giving a crude prevalence of 127.4 per 1,000,000 (women: 146.4; men: 107.0; age 18-34 years: 39.2; 35-54 years: 98.7; 55-74 years: 273.6; 75+ years: 163.3). The standardized rate was 137.5 (95% confidence interval 107.0-174.6). Blepharospasm was the commonest clinical condition (prevalence 68.2), followed by cervical dystonia (prevalence 44.8). CONCLUSION: The prevalence of primary focal or segmental dystonia in Italy is in keeping with several other reports, but is lower than in studies performed in northern Europe, Minnesota, USA, and Japan. The difference in our results may be mostly explained by misdiagnosis, underascertainment of cases and a fairly limited observation period.

Italian consensus conference on epilepsy and pregnancy, labor and puerperium.

To facilitate an integrated and rational approach to the care of women with epilepsy of childbearing potential, a group of experts appointed by Italian scientific societies in the fields of epileptology, neonatology, pediatrics, neuropediatrics, child neuropsychiatry, obstetrics, and gynecology held a joint meeting in Santa Trada di Cannitello, Reggio Calabria, Italy, on October 15-16, 2004, with the aim of reaching consensus on the optimal management of these women. An ad hoc system for the classification of available published evidence and the opinions of experts was developed and used to grade recommendations on different aspects related to counseling, diagnostic, and treatment issues. The present document summarizes available evidence on the reciprocal interactions between epilepsy, antiepileptic drugs, fertility, contraception, pregnancy, delivery, breastfeeding, and the offspring. Recommendations are made concerning the information and counseling that should be provided to women with epilepsy with respect to issues related to contraception, conception, pregnancy, labour, and puerperium. More detailed recommendations on the same issues are provided to physicians and other healthcare professionals involved in the care of these women, with special reference to choice of effective contraception, optimization of antiepileptic drug therapy, use of prenatal diagnostic tests and other monitoring procedures, and appropriate management practices in relation to childbirth, puerperium, and the care of the child.

Effects of topiramate and levetiracetam vs placebo on habituation of contingent negative variation in migraine patients.

Migraine is characterized by reduced habituation of multimodal evoked potentials, which in turn reflects an abnormal pattern of cortical excitability. We assessed the effects of a 2-month treatment with topiramate or levetiracetam vs placebo on contingent negative variation (CNV) habituation and amplitude in a cohort of migraine without aura (MO) patients. Forty-five MO patients were selected from a university-based outpatient clinic and randomly assigned to 100mg topiramate or 1000mg levetiracetam or placebo in a double-blind design. Twenty-four control subjects were also recruited. The initial CNV (iCNV) amplitude and habituation were assessed by Cz/A1-A2 derivation recordings in the basal condition (T0) and after 2 months of treatment (T1). Both topiramate and levetiracetam produced a significant reduction in migraine frequency compared to placebo, they also reversed the abnormal iCNV habituation pattern which characterized the MO patients in the basal condition and which was not present in controls. For migraine patients, the reduced migraine frequency and habituation index following treatment were significantly correlated. A lack of habituation of evoked responses is an interictal endophenotypic marker in migraine, the reversion of which may improve disease outcome. These results suggest a role for neurophysiological methods in the management of migraine.

How the cognitive reserve interacts with ß-amyloid deposition in mitigating FDG metabolism: An observational study.

This observational study had the aim to assess the interaction between cognitive reserve (CR) and cerebrospinal fluid ß-amyloid1-42 (Aß1-42) in modulating brain [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) metabolism in patients with moderate Alzheimer disease (AD).Twenty-seven patients with probable AD and 25 neurological normal subjects (NNS) entered the study. All participants had an FDG-PET scan, and AD patients also received a lumbar puncture to measure Aß1-42, 181p-tau, and Tau concentrations. Based on years of formal education, AD patients were classified as highly educated-AD (years of formal education >5) or less educated-AD (years of formal education <5). By using a voxel-wise approach, we first investigated differences in the cerebral glucose uptake between AD and NNS, then we assessed the interaction between level of education (a proxy of CR) and cerebrospinal fluid biomarkers on FDG-PET metabolism in the patient groups.Significantly lower glucose uptake was observed in the posterior cingulate gyrus, in the precuneus, in the inferior and medial temporal gyrus, and in the inferior parietal lobule of AD patients compared with NNS. A significant interaction was found between CR and Aß1-42 values on brain metabolism in the inferior and medial temporal gyrus bilaterally.The AD patients with higher CR level and marked signs of neuropathology showed glucose hypometabolism in regions typically targeted by AD pathology. This finding supports the hypothesis that CR partially compensates for the effect of Aß plaques on cognitive impairment, helps in patients' clinical staging, and opens new possibilities for the development of nonpharmacological interventions.

Open label, long-term, pragmatic study on levetiracetam in the treatment of juvenile myoclonic epilepsy.

PURPOSE: Patients with juvenile myoclonic epilepsy (JME) may be resistant or show adverse effects to valproate. We present a multicenter, prospective, long-term, open-label study evaluating the efficacy and safety of levetiracetam in JME. METHODS: Patients with newly diagnosed (10) or resistant/intolerant to previous AEDs JME (38) were enrolled. After a 8 week baseline period, levetiracetam was titrated in 2 weeks to 500 mg b.i.d. and then increased up to 3000 mg/day according to the patient's response. Efficacy parameters were: number of seizure-free patients, number of days with myoclonus (DWM), and monthly frequency of generalised tonic-clonic (GTC) seizures. Adverse events were recorded. RESULTS: The overall mean dose of levetiracetam was 2208 mg/day. The mean study period was 19 (range 0.3-38) months. Five patients dropped out. 11/38 (28.9%) patients with add-on treatment and 5/10 (50%) newly diagnosed patients were seizure-free for a mean period of 17.2 (+/-8.8) months. Eighteen patients (37.5%) were without myoclonia, and 35 (72.9%) had no GTC seizures over the study period. The mean monthly frequency of DWM and of GTC seizures in the entire group was significantly reduced after levetiracetam. Five patients complained of side effects. CONCLUSIONS: This open-label study suggests levetiracetam may be effective and well tolerated in resistant cases of JME or may become a reasonable alternative to valproate in newly diagnosed patients.

Early recurrence of Tako-Tsubo cardiomyopathy in an elderly woman with amyotrophic lateral sclerosis: different triggers inducing different apical ballooning patterns.

: We report the case of early recurrence of Tako-Tsubo cardiomyopathy in an elderly woman with amyotrophic lateral sclerosis triggered by different stressors. A first episode with typical apical ballooning was anticipated by an emotional stress; a second, characterized by systolic anterior motion of the mitral valve associated with mitral regurgitation and severe intra-ventricular gradient, was precipitated by surgical stress and hypovolemia. We therefore hypothesize both a possible link between amyotrophic lateral sclerosis and Tako-Tsubo cardiomyopathy, and between different stressors and different Tako-Tsubo patterns.

Bilateral putaminal necrosis and bronopol toxicity.

Among alcohols, methanol intoxication is the most frequently associated with cerebral toxicity, causing retinal damage and putaminal necrosis. This consequence is believed to be due to the transformation of methanol into formic acid. We describe the case of a patient who presented with acute impairment of consciousness and tetraparesis after she had been drinking several bottles of a topical antiseptic solution (Lysoform Medical) containing 2-bromo-2-nitro-1,3-propandiol (bronopol) among excipients, in order to lose weight during previous months. Moreover, she had been on a strict slimming diet. Soon after admission, a severe respiratory and metabolic impairment became rapidly evident, requiring an intensive care unit admission. Cerebral MRI showed the presence of bilateral putaminal necrosis. She recovered in 10 days, surprisingly, without any evident clinical neurological signs. Methanol, also bronopol, when diluted in aqueous solution, at warm temperature and/or higher pH, may release formaldehyde, which is converted into formic acid, a basal ganglia toxic compound.

Abnormal brain processing of cutaneous pain in patients with chronic migraine.

Syndromes with chronic daily headache include chronic migraine (CM). The reason for the transformation of migraine into chronic daily headache is still unknown. In this study, we aimed to evaluate heat pain thresholds and event-related potentials following CO(2)-laser thermal stimulation (LEPS) in hand and facial regions in patients with CM, to show changes in nociceptive brain responses related to dysfunction of pain elaboration at the cortical level. The results were compared with findings from normal control subjects and from subjects who suffer from migraine without aura. The effects of stimulus intensity, subjective pain perception and attention were monitored and compared with features of the LEPS. Twenty-five CM patients, 15 subjects suffering from migraine without aura and 15 normal control subjects were enrolled in the study. LEPS amplitude variation was reduced in CM patients with respect to the perceived stimulus intensity, in comparison with migraine without aura patients and control subjects. In both headache groups, the distraction from the painful laser stimulus induced by an arithmetic task failed to suppress the LEPS amplitude, in comparison with control subjects. These results suggest an abnormal cortical processing of nociceptive input in CM patients, which could lead to the chronic state of pain. In both headache groups, an inability to reduce pain elaboration during an alternative cognitive task emerged as an abnormal behaviour probably predisposing to migraine.

Insomnia, quality of life and psychopathological features.

Most of the studies about chronic insomnia focused only on specific features, providing in this way a partial outlook of the problem. The aim of this study was to examine a sample of chronic insomniacs from different points of view, by estimating the prevalence of stress, psychopathological symptoms, psychiatric disorders, changes in quality of life and illness behaviour. Forty-three patients (54.4%) experienced some psychosocial stressors in the last 6 months preceding the enrollment in the study. More than 55% of insomniacs reported symptoms of psychopathology. One or more than one psychiatric disorder was diagnosed in 61.5% of insomniacs. Life events could play a role in facilitating the transformation of a psychopathological symptom in a psychiatric disorder, since patients with a psychiatric diagnosis showed a higher percent of stress. The more noticeable disability in the group of insomniacs with psychiatric disorders and the absence of a corresponding worsening in illness behaviour suggests that insomniacs feelings about their health status are so negative to be not fatherly worsen by comorbidity in spite of a worsen disability. The evaluation of insomniacs should be as much detailed as possible, without neglecting tests for the evaluation of disability and illness behaviour, which are important not only for a correct diagnosis but also for monitoring the effects of therapies.

Modulation of trigeminal reflex excitability in migraine: effects of attention and habituation on the blink reflex.

The modulation of trigeminal reflex excitability in migraine patients was evaluated during the asymptomatic phase by studying the effects of attention, habituation and preconditioning stimulus on the R2 and R3 components of the blink reflex (BR). Fifty patients suffering from migraine without aura, 20 affected by migraine with aura and 35 sex- and age-matched controls were selected. In subgroups of migraine with-aura and without-aura patients, and normal controls, the blink reflex was elicited during different cognitive situations: (a) spontaneous mental activity; (b) stimulus anticipation; (c) recognition of target numbers. In the remaining subjects, R2 and R3 habituation was evaluated by repetitive stimulation at 1, 5, 10, 15, 20, 25 and 30 s intervals. The R2 and R3 recovery curves were also computed. A reduced R3 threshold with a normal pain threshold was found in migraine with-aura and without-aura patients; the R3 component was not significantly correlated with the pain thresholds in patients and controls. The R2 and R3 components were less influenced by the warning of the stimulus in migraine without-aura and migraine with-aura patients, in comparison with the control group. A slight increase of both R2 and R3 recovery after preconditioning stimulus was also observed in migraine patients, probably caused by a phenomenon of trigeminal hyperexcitability persisting after the last attack. The abnormal BR modulation by alerting expresses in migraine a dysfunction of adaptation capacity to environmental conditions, probably predisposing to migraine.

Early modifications of auditory event-related potentials in carriers of the Huntington's disease gene.

The P3 wave is one cognitive component of event-related potentials (ERP) used to investigate various types of dementia. The aim of this study was to use the odd-ball paradigm to evaluate the P3 in Huntington's Disease (HD) gene carriers who showed no symptoms of chorea, compared to a group of mildly affected HD patients. We selected 14 HD patients and six individuals who, despite testing positive for the HD gene, did not show any clinical evidence of the disease. Thirty-six normal subjects were also selected as controls. Statistical evaluation of N1, P2, N2 and P3 latencies and amplitudes was performed in each group. Both the N2 latency and the P3 latency corrected for age (cP3) were significantly correlated with the duration of illness in pooled symptomatic and presymptomatic gene carriers. However, these latencies did not correlate with any clinical scale or psychometric test, including WAIS subtests. As the individual P3 latency of the majority of HD patients and all presymptomatic gene carriers was distributed within normal confidence intervals, and no correlation existed between ERP parameters and the signs of illness progression, the data appear to provide preliminary evidence against the valence of P3 in detecting the early cognitive impairment of HD.

Lentiform fork sign: a magnetic resonance finding in a case of acute metabolic acidosis.

We report a 33 year-old woman addicted to chronic unspecified solvents abuse with stupor, respiratory disorders, tetraplegia and severe metabolic acidosis. On admission an unenhanced cranial CT scan showed symmetrical hypodensities of both lentiform nuclei. MR imaging performed 12 hours after stupor demonstrates bilateral putaminal hemorrhagic necrosis, bilateral external capsule, corona radiata and deep cerebellar hyperintensities with right cingulate cortex involvement. DWI reflected bilateral putaminal hyperintensities with restricted water diffusion as to citotoxic edema and development of vasogenic edema in the external capsule recalling a fork. On day twenty, after specific treatments MRI demonstrated a bilateral putaminal marginal enhancement. Bilateral putaminal necrosis is a characteristic but non-specific radiological finding of methanol poisoning. Lentiform Fork sign is a rare MRI finding reported in literature in 22 patients with various conditions characterized by metabolic acidosis. Vasogenic edema may be due to the differences in metabolic vulnerability between neurons and astrocytes. We postulate that metabolic acidosis could have an important role to generate this sign.

Off-label prescribing of antiepileptic drugs in pharmacoresistant epilepsy: a cross-sectional drug utilization study of tertiary care centers in Italy.

PURPOSE: To assess the extent of off-label prescribing of antiepileptic drugs (AEDs) and associated variables in a large population of patients with pharmacoresistant epilepsy. METHODS: Descriptive analysis of data recorded from consecutively enrolled patients with pharmacoresistant epilepsy attending 11 tertiary referral centers in Italy. Off-label use was stratified by therapeutic indication, dose, and age. Multivariate logistic regression was used to identify variables associated with off-label prescription. RESULTS: Of a total of 1,124 patients enrolled between November 2006 and August 2007, 53 % (101/191) of children and 31 % (287/933) of adults were receiving at least one off-label AED prescription. Among adults, off-label use was related primarily to indication and was highest for clobazam (100 %) and ethosuximide (40 %), followed by lamotrigine (25 %), and vigabatrin (25 %). In children, clobazam (100 %), lamotrigine (79 %), vigabatrin (55 %), ethosuximide (46 %), and levetiracetam (43 %) were most frequently used off-label, with indication or age being the main causes depending on the specific AED. Logistic regression analysis indicated that higher rates of off-label use were associated with a polytherapy regimen (odds ratio [OR] 2.50, 95 % confidence interval [95 % CI], 1.55-4.03), pediatric age (2.49, 1.66-3.76), having failed ≥3 AEDs (2.16, 1.04-4.48), a diagnosis of generalized epilepsy with structural/metabolic or unknown etiology (2.97, 1.25-7.04), and increasing seizure frequency (1.07, 1.01-1.14). CONCLUSIONS: Off-label prescribing of AEDs is common among patients with pharmacoresistant epilepsy and is influenced by demographic and disease-related characteristics. Studies are needed to improve the quality of evidence guiding epilepsy treatment, and to evaluate the risks and benefits of off-label prescribing in epilepsy.

Potential links between neurological disease and Tako-Tsubo cardiomyopathy: a literature review.

Tako-Tsubo cardiomyopathy (TTC), is defined as a fully reversible acute deterioration of left-ventricular (LV) function, which is mainly found in women after an episode of emotional or physical stress (e.g. psychosocial stress, sepsis, surgery). The underlying mechanisms remain unclear. There is evidence suggesting a possible link between neurological disease and TTC. The pathophysiology of the several neurologic diseases has been reviewed searching for possible mechanisms that could lead to TTC in these patients.