41 research outputs found
Perampanel as add-on therapy in epilepsies with known etiology: A single center experience with long-term follow-up
We report a retrospective monocentric study performed on 63 patients affected by epilepsy with known
etiology, receiving perampanel as add-on therapy with at least 12-month follow-up. The purpose of our
study was to evaluate efficacy and tolerability of perampanel in this group of epilepsies. Patients were
classified into 2 groups based on the presence/absence of a single focal brain lesion on MRI, as epilepsy
etiology: 48 subjects were affected by focal lesional epilepsy and 15 by non-focal lesional epilepsy. The
retention rate was 76.2% and 53.9% at 12 and 24 months respectively. At 12 months, at least 40% of
patients resulted responders, with a significant reduction in seizure frequency (p = 0.01), confirmed at
24 months. Considering epilepsy etiology, we found a better PER response in patients with focal lesional
epilepsy. A significant correlation was observed between responder rates and EEG pattern. Only 30% of
patients reported mild-moderate adverse events. Efficacy and tolerability of PER, in our study, are in line
with the results reported in other real-world studies. Our data suggest the possibility of better PER
response in patients with focal brain lesions, which indicates that this drug could be a therapeutic option
in this population
An Exploratory Study of Field Failures
Field failures, that is, failures caused by faults that escape the testing
phase leading to failures in the field, are unavoidable. Improving verification
and validation activities before deployment can identify and timely remove many
but not all faults, and users may still experience a number of annoying
problems while using their software systems. This paper investigates the nature
of field failures, to understand to what extent further improving in-house
verification and validation activities can reduce the number of failures in the
field, and frames the need of new approaches that operate in the field. We
report the results of the analysis of the bug reports of five applications
belonging to three different ecosystems, propose a taxonomy of field failures,
and discuss the reasons why failures belonging to the identified classes cannot
be detected at design time but shall be addressed at runtime. We observe that
many faults (70%) are intrinsically hard to detect at design-time
Evaluating the SERCA2 and VEGF mRNAs as Potential Molecular Biomarkers of the Onset and Progression in Huntington's Disease
Abnormalities of intracellular Ca2+ homeostasis and signalling as well as the down-regulation
of neurotrophic factors in several areas of the central nervous system and in peripheral
tissues are hallmarks of Huntington\u2019s disease (HD). As there is no therapy for this hereditary,
neurodegenerative fatal disease, further effort should be made to slow the progression
of neurodegeneration in patients through the definition of early therapeutic interventions.
For this purpose, molecular biomarker(s) for monitoring disease onset and/or progression
and response to treatment need to be identified. In the attempt to contribute to the research
of peripheral candidate biomarkers in HD, we adopted a multiplex real-time PCR approach
to analyse the mRNA level of targeted genes involved in the control of cellular calcium homeostasis
and in neuroprotection. For this purpose we recruited a total of 110 subjects possessing
the HD mutation at different clinical stages of the disease and 54 sex- and agematched
controls. This study provides evidence of reduced transcript levels of sarco-endoplasmic
reticulum-associated ATP2A2 calcium pump (SERCA2) and vascular endothelial
growth factor (VEGF) in peripheral blood mononuclear cells (PBMCs) of manifest and premanifest
HD subjects. Our results provide a potentially new candidate molecular biomarker
for monitoring the progression of this disease and contribute to understanding some early
events that might have a role in triggering cellular dysfunctions in HD
Interpreting signals from the peripheral nerve in amyloidosis: a call for action
Systemic amyloidosis includes a group of disorders, characterized by deposition of insoluble aggregates of amyloid fibrils in various tissues that lead to disruption of normal tissue structure and impaired function. They are currently categorized as hereditary and secondary. Peripheral neuropathy is a frequent complication of systemic amyloidosis. The most common phenotype is a length-dependent sensorimotor polyneuropathy with autonomic dysfunction, but there are many atypical presentations that often lead to delayed diagnosis. In this review, we emphasize the neurological clinical aspects that induce a suspicion of amyloidosis, the possible differential diagnosis and the diagnostic pitfalls. An early diagnosis of the disease is crucial for rapid initiation of appropriate treatment that may change the course and the progression of the disease
Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
The most recent International League Against Epilepsy (ILAE) classification has included âimmune etiologyâ along with other well-known causes of epilepsy. This was possible thanks to the progress in detection of pathogenic neural antibodies (Abs) in a subset of patients, and resulted in an increased interest in identifying potentially treatable causes of otherwise refractory seizures. Most autoimmune encephalitides (AE) present with seizures, but only a minority of cases evolve to long-term epilepsy. The risk of epilepsy is higher for patients harboring Abs targeting intracellular antigens (T cell-mediated and mostly paraneoplastic, such as Hu, CV2/CRMP5, Ma2, GAD65 Abs), compared with patients with neuronal surface Abs (antibody-mediated and less frequently paraneoplastic, such as NMDAR, GABAbR, LGI1, CASPR2 Abs). To consider these aspects, conceptual definitions for two entities were provided: acute symptomatic seizures secondary to AE, and autoimmune-associated epilepsy, which reflect the different pathophysiology and prognoses. Through this manuscript, we provide an up-to-date review on the current state of knowledge concerning diagnosis and management of patients with Ab-mediated encephalitis and associated epilepsy. Special emphasis is placed on clinical aspects, such as brain magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) specificities, electroencephalographic (EEG) findings, cancer screening and suggestions for a rational therapeutic approach
Presurgical cognitive status in patients with lowâgrade glioma and epilepsy: Testing the effects of seizures, antiseizure medications, and tumor localization
Abstract Background Lowâgrade gliomas (LGGs) are frequently associated with epilepsy. There are few studies addressing the impact of seizures, antiseizure medications (ASMs), and lesion localization on presurgery cognitive functioning. Methods We tested the relation between the aboveâmentioned variables in a continuous series of 73 young patients (mean age 38.3 years ± 11.7) affected by LGGs and epilepsy. The anatomical areas, involved in this sample, were the left insula with surrounding cortical and subcortical areas, the right precentral gyrus/rolandic operculum, and the white matter and cortical regions beneath. Results Patientsâ presurgery cognitive status was within the normal range, with borderline performance for some tasks. We tested whether lower scores were related with lesion or with epilepsyârelated factors. Multiple regression identified variables that predict test scores. The Token test score was predicted by a model (p = .0078) containing the DT2T1 MRI, corrected for seizure features. Object naming performance was predicted by a model (p = .0113) containing the localization, the DT2T1 MRI, corrected for sex, EEG, and onset. Verbal fluency score was predicted by a model (p = .0056) containing the localization and the DT2T1 MRI, corrected for AEDs and EEG. Working memory score was predicted by a model (p = .0117) containing Engel class, the DT2T1 MRI, corrected for sex. Clock drawing score was predicted by a model (p < .0001) containing the Engel class, AEDs, and EEG. TMT A score was predicted by a model (p = .0022) containing localization, corrected for EEG. TMT BâA score was predicted by a model (p = .0373) containing localization. Voxel Lesion Symptom Mapping analyses carried out on patientsâ lesion volumes confirmed that patientsâ level of performance correlated with lesionârelated variables. Conclusion This preliminary study indicates that the presurgical level of performance for language tasks and for cognitive flexibility and shifting is mainly predicted by lesionârelated variables, working memory by both lesion and epilepsyârelated variables. Epilepsy clinical and instrumental characteristics predicted performance for visuospatial planning