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AIMS Bladder and bowel dysfunction (BBD) have been recognized in children affected by autism spectrum disorder (ASD), but no consistent information exist in adults with the condition. We evaluated the prevalence of BBD and the impact of psychiatric and behavioural profiles in adults affected by ASD. METHODS Twenty-two adults and 13 children/teens with ASD and a matched group of typically developing subjects (TD) were prospectively studied. Patients and TD subjects underwent the evaluation of urinary incontinence (UI: diurnal, continuous or intermittent), nocturnal enuresis (NE), and bowel disturbances with the 3-day voiding and bowel diary. In addition, assessment of intellectual disability (ID) and psychiatric and adaptive behaviours with the Neuropsychiatric Inventory Scale (NPI) and the Vineland Adaptive Behaviour Scale 2nd Edition (Vineland-II), was performed. RESULTS In adults, any type of incontinence was observed in 81.8% of cases, and NE and intermittent UI in 59.0% and 36.3% of patients, respectively. Faecal incontinence and constipation were detected 36.3% and in 68.1% of cases, respectively. ID was severe in 2 cases and profound in 18; NPI and Vineland-II items most affected were "Irritability/Lability," "Motor Activity," and "Agitation," and IQ-Socialization and IQ-Communication. Significant relationships were identified between intermittent UI and greater ID (P

Although amyloid pathology plays a role in epilepsy, little is known about the relationship between beta amyloid and progression to Alzheimer's disease (AD) among patients with late-onset epilepsy of unknown origin (LOEU). This multicenter, observational, prospective study enrolled 40 consecutive nondemented adults diagnosed with LOEU, together with 43 age- and sex-matched healthy controls. All patients completed neuropsychological tests, core CSF AD biomarkers assessment (Aβ1-42, total tau, and phosphorylated tau), and follow-up for a mean of 3 years to verify cognitive decline. Despite age and baseline cognitive performance were similar to healthy controls, patients with LOEU had significant prevalence of CSF pathological Aβ1-42 (

INTRODUCTION AND OBJECTIVE:Bladder and bowel dysfunction (BBD) in pts with autism spectrum disorder (ASD) have been recognized in children/teens but no information exists in adults. Aims of the stu...

Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5-year-old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole-exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen-magnetic resonance spectroscopy (H-MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7-related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth.

Background The impact of adverse events (AEs) of antiepileptic drugs (AEDs) have an impact on compliance and dropouts. We compared tolerability of AEs of AEDs among patients with migraine, epilepsy, or both. Methods Overall, 335 patients (epilepsy (n = 142), migraine (n = 131), and both (n = 62)), were evaluated with the Liverpool Adverse Events Profile (LAEP) to assess the magnitude, profile and occurrence rate of the AEs of valproate, topiramate, and lamotrigine. Results AEs were significantly more common with topiramate treatment (71.0%) and among migraineurs (69.5%), the latter being more prone to discontinue AEDs (46.6%). The profile of AEs with topiramate and valproate differed among groups. Moreover, treatment with both topiramate and valproate was associated, for all groups, with a worse tolerability profile compared to lamotrigine. Conclusion Our data suggest a specific drug and disease AE profile of AEDs. Specifically, migraineurs are the most affected by AEs, even though they receive very low dosages of AEDs. This finding might be considered a clinical implication of central sensitization mechanisms. Both the profile and tolerability of AEs, highly influencing quality of life, depended on the underlying conditions, and deeply impacted on treatment dropout. Therefore, before starting, switching or stopping AED treatment, all options need to be considered.

The efficacy of levetiracetam (LEV) in controlling seizures in patients with brain tumor-related epilepsy (BTRE) depends on tumoral expression of synaptic vesicle protein 2A (SV2A). Although LEV is generally well tolerated, neuropsychiatric adverse events (NPAEs) might occur, limiting compliance and seizure control. We aimed to assess the influence of tumoral SV2A expression on the occurrence of LEV-related NPAEs in patients with glioma.Specimens from patients enrolled in the multicenter COMPO study, with glioma and BTRE treated with LEV, undergoing neurosurgery were retrieved. Immunohistochemistry-based expression of SV2A in tumoral and peritumoral tissue was scored in a four-point scale from absent (score = 0) to strong (score = 3). Low immunoreactivity (IR) corresponded to scores 2. Staining ratios (tumoral SV2A IR/peritumoral SV2A IR) were grouped into low (≤ 0.5) and high ( 0.5). NPAEs were assessed longitudinally with the Neuropsychiatry Inventory 12 test (NPI-12).Overall, 18 patients were eligible for analysis. All received LEV monotherapy, with 67% developing NPAEs. Patients with NPAEs had significantly lower median SV2A intensity score compared to patients without NPAEs (score 1 vs 0, p = 0.025). Low staining ratio (≤ 0.5) associated with higher NPAE occurrence compared to SR 0.5 (85.7% vs 0%, p 0.01). A SR ≤ 0.5 predicted a consistent increase in risk of NPAEs (OR 45.0; 95% CI 1.8-1128; p = 0.02).Our results suggest that SV2A expression in tumoral and peritumoral tissue correlates with the occurrence of LEV-related NPAEs. Thus, considering that SV2A expression also influences LEV effectiveness, SV2A staining might help in tailoring treatment to patients.

Objective We performed a systematic review on the comorbidities of familial/sporadic hemiplegic migraine (F/SHM) with seizure/epilepsy in patients with CACNA1A, ATP1A2 or SCN1A mutations, to identify the genotypes associated and investigate for the presence of mutational hot spots. Methods We performed a search in MEDLINE and in the Human Gene Mutation and Leiden Open Variation Databases for mutations in the CACNA1A, ATP1A2 and SCN1A genes. After having examined the clinical characteristics of the patients, we selected those having HM and seizures, febrile seizures or epilepsy. For each gene, we determined both the frequency and the positions at protein levels of these mutations, as well as the penetrance of epilepsy within families. Results Concerning F/SHM-Epilepsy1 (F/SHME1) and F/SHME2 endophenotypes, we observed a prevalent involvement of the transmembrane domains, and a strong correlation in F/SHME1 when the positively charged amino acids were involved. The penetrance of epilepsy within the families was highest for patients carrying mutation in the CACNA1A gene (60%), and lower in those having SCN1A (33.3%) and ATP1A2 (30.9%) mutations. Conclusion Among the HM cases with seizure/epilepsy, we observed mutational hot spots in the transmembrane domains of CACNA1A and ATP1A2 proteins. These findings could lead to a better understanding of the pathological mechanisms underlying migraine and epilepsy, therein guaranteeing the most appropriate therapeutic approach.

Adverse events (AEs) of antiepileptic drugs (AEDs) affect patient compliance and dropout. No questionnaire measuring AEs of AEDs is available for Italian-speaking people with epilepsy. Moreover, no questionnaire has been shown to predict patient dropout.The aim of this study was to provide a validated Italian version of the Liverpool Adverse Events Profile (iLAEP) and to define iLAEP reliability in AE monitoring and dropout risk prediction.The original LAEP was translated and tested for internal consistency and reliability. Patients with epilepsy who are on stable AED regimen completed the questionnaire as well as a 3-month follow-up to assess dropouts.Overall, 204 patients with epilepsy were enrolled (mean age: 47.1±21.5). High internal consistency (Cronbach's α=0.88) was demonstrated, and very quick completion time was registered (mean=9min). A 3-month follow-up was performed to assess treatment discontinuation and potential predictive value of the iLAEP score. Treatment was discontinued in 33.3% of the cohort. Moreover, iLAEP scores (mean=30.71) significantly differed between patients interrupting (39.15±5.66) and those prosecuting treatment (29.4±6.54, p.001). A cutoff of 36.5 had an 85% accuracy in predicting treatment discontinuation (85% sensitivity, 79% specificity). Scores36.5 were associated with a 20.27-fold increase in dropout relative risk (RR), with a 66% positive predictive value.The iLAEP represents a reliable, quick, and inexpensive assessment tool for patient-reported AEs of AEDs. An iLAEP cutoff of 36.5 differentiates patients unlikely to interrupt treatment from those more prone to stop AEDs in the following 3months. The iLAEP might help clinicians in weighting the risk of dropout and better tailor treatment to patients.

Introduction The aim of this paper was to estimate the risk of miscarriage after amniocentesis or chorionic villus sampling (CVS) based on a systematic review of the literature. Evidence acquisition A search of Medline, Embase, and The Cochrane Library (2000-2017) was carried out to identify studies reporting complications following CVS or amniocentesis. The inclusion criteria for the systematic review were studies reporting results from large controlled studies (N.≥1000 invasive procedures) and those reporting data for pregnancy loss prior to 24 weeks' gestation. Data for cases that had invasive procedure and controls were inputted in contingency tables and risk of miscarriage was estimated for each study. Summary statistics were calculated after taking into account the weighting for each study included in the systematic review. Procedure-related risk of miscarriage was estimated as a weighted risk difference from the summary statistics for cases and controls. Evidence snthesis The electronic search from the databases yielded 2465 potential citations of which 2431 were excluded, leaving 34 studies for full-text review. The final review included 10 studies for amniocentesis and 6 studies for CVS, which were used to estimate risk of miscarriage in pregnancies that had an invasive procedure and the control pregnancies that did not. The procedure-related risk of miscarriage following amniocentesis was 0.35% (95% confidence interval [CI]: 0.07 to 0.63) and that following CVS was 0.35% (95% CI: -0.31 to 1.00). Conclusions The procedure-related risks of miscarriage following amniocentesis and CVS are lower than currently quoted to women.

Background Migraine and epilepsy are chronic disorders, often comorbid, characterized by transient and recurrent neurological disturbances. Sharing pathophysiologic and clinical features, both epilepsy and migraine benefit from antiepileptic drugs (AEDs) treatment. However, despite their overlapping, peculiar differences regarding reported adverse events (AEs) of AEDs seem to emerge in clinical practice. In particular, tolerability and frequency of AEs might depend on the condition from which the patient suffers. Therefore, we interviewed patients treated with AEDs for epilepsy, migraine, and both, in order to compare AEs distribution of frequency among the three groups. Materials and methods We collected AEs of some AEDs - valproic acid (VPA), topiramate (TPM), lamotrigine (LTG) - widely used in prophylactic therapy of migraine, in epilepsy as well as in epileptic migraineurs. All AEs were gathered through the Liverpool Adverse Events Profile (LAEP) [1]. Results Three hundred and thirty-five patients were recruited: 142 suffered from epilepsy (group A), 131 from headache (group B), 62 from both (group C). Mean age was 44.5 in group A, 45.0 in B, 40.5 in C. AEs were significantly more reported in group B (69.5%) and under TPM treatment (71%). The most prescribed AED for group B was TPM, which was more commonly referred to cause paresthesias (68%) and language disorders (42%) among this group than in the other two. Complaints of weight gain were common with VPA in all three groups, with higher frequencies among group B and C. Memory impairment induced by AEDs was reported more frequently for TPM in all three groups, while maximal incidence was reported for VPA and TPM, respectively in group B (5%) and C (9%). Overall, migraineurs were more likely to drop out of treatment (46%) than epileptic patients (29.6%) and patients with epilepsy and migraine (41.9%). Discussion and conclusions Our data confirm the extensive safety and effectiveness of AEDs in clinical practice, and point to patient’s tolerability of AEs as pivotal for a successful treatment [2]. We emphasize the higher prevalence of AEs due to AEDs in migraineurs, suggesting a peculiar susceptibility of their condition to experience AEs. This finding, which emerges despite the average higher dosage of AED used for epilepsy, remains actually unexplained. Our results might be intriguingly considered as a clinical implication of central sensitization mechanisms or, not less intriguingly, they might represent the result of an abnormal network plasticity producing microstructural changes in migraine-affected brain [3]. Written informed consent to publication was obtained from the patient(s).

Background and purpose We assessed the prevalence and magnitude of neuropsychiatric adverse events (NPAEs) associated with antiepileptic drugs (AEDs) among patients with brain tumour-related epilepsy (BTRE). Methods This observational, prospective, multicentre study enrolled 259 patients with BTRE after neurosurgery. All patients received AED monotherapy. Efficacy was assessed through clinical diaries, whereas NPAEs were collected using the Neuropsychiatric Inventory Test-12 questionnaire at baseline and after 5 months. Results Tumour localization in the frontal lobe was associated with a higher prevalence of NPAEs (odds ratio, 7.73; P < 0.001). Independent of tumour localization, levetiracetam (LVT) treatment was associated with higher prevalence and magnitude of NPAEs (odds ratio, 7.94; P < 0.01) compared with other AEDs. Patients with oligodendroglioma reported more NPAEs than patients with other tumour types. NPAEs were not influenced by chemotherapy, radiotherapy or steroid treatment. Evaluating non-neurobehavioural adverse events of AEDs, no significant differences were found among AEDs, although patients treated with old AEDs had a higher prevalence of adverse events than those treated with new AEDs. Conclusions Both tumour localization in the frontal lobe and LVT treatment are associated with a higher risk of NPAEs in patients with BTRE. LVT is regarded as a first-line option in patients with BTRE because of easy titration and few significant drug-to-drug interactions. Thus, as NPAEs lead to poor compliance and a high dropout rate, clinicians need to accurately monitor NPAEs after AED prescription, especially in patients with frontal lobe tumours receiving LVT.

We describe four cases of young men 19, 21, 23 and 25 years old with recurrent episodes of migraine with aura occurring shortly after the end of physical activities (football match, swimming, gym training, physical education activities at school), when they were in the locker room. Since these types of symptoms could mime some important pathologies in approximately 10% of these headaches, it is mandatory, in this kind of patient, to exclude a form of secondary headache [1]. No other subtypes of headache, or head trauma were reported by the patients. It is well known that physical activity can lead to an aggravation of the intensity of the headache, but the pathophysiological relationship between exertion and aura is unknown and still debated. There are anecdotal reports of episodes of migraine preceded by head trauma and visual symptoms (with a past history of non-sports-related migraine) [2, 3], migraine prodrome symptoms after unusually strenuous running with no following head pain [4] or recurrent attacks of hemiplegic migraine induced only by exertion [5]. According to the present version of the International Classification of Headache Disorders, (ICHD-III beta), the headache subtype presented by the four patients fulfilled criteria for “migraine with aura” (ICHD-III beta code: 1.2) and for “primary exertional headache” (pulsating headache, lasting from 5 minutes to 48 hours, brought on by and occurring only during or after physical exertion; ICHD-III beta code: 4.2) [6]. To date, in the IHS Classification (ICHD-III beta), there is no mention of sport/exercise-induced migraine with aura episodes as primary headache, and there is the need of a double diagnosis, although there are anecdotal reports of attacks of migraine with aura shortly after sports. Written informed consent to publish was obtained from the patient(s).