Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies

A registry for Dravet syndrome: The Italian experience

Objectives: We describe the Residras registry, dedicated to Dravet syndrome (DS) and to other phenotypes related to SCN1A mutations, as a paradigm of registry for rare and complex epilepsies. Our primary objectives are to present the tools and framework of the integrative platform, the main characteristics emerging from the patient cohort included in the registry, with emphasis on demographic, clinical outcome, and mortality. / Methods: Standardized data of enrolled pediatric and adult patients were collected in 24 Italian expert centers and regularly updated at least on a yearly basis. Patients were prospectively enrolled, at registry starting, but historical retrospective data were also included. / Results: At present, 281 individuals with DS and a confirmed SCN1A mutation are included. Most patients have data available on epilepsy (n = 263) and their overall neurological condition (n = 255), based on at least one follow-up update. Median age at first clinical assessment was 2 years (IQR 0–9) while at last follow-up was 11 years (IQR 5–18.5). During the 7-year activity of the registry, five patients died resulting in a mortality rate of 1.84 per 1000-person-years. When analyzing clinical changes over the first 5-year follow-up, we observed a significant difference in cognitive function (P < 0.001), an increased prevalence of behavioral disorders including attention deficit (P < 0.001), a significant worsening of language (P = 0.001), and intellectual disability (P < 0.001). / Significance: The Residras registry represents a large collection of standardized national data for the DS population. The registry platform relies on a shareable and interoperable framework, which promotes multicenter high-quality data collection. In the future, such integrated platform may represent an invaluable asset for easing access to cohorts of patients that may benefit from clinical trials with emerging novel therapies, for drug safety monitoring, and for delineating natural history. Its framework makes it improvable based on growing experience with its use and easily adaptable to other rare and complex epilepsy syndromes

EEG findings during "paroxysmal hemiplegia" in a patient with GLUT1-deficiency

A growing number of studies have disclosed the myriad of features that can suggest the diagnosis of a Glucose-transporter-1 deficiency (GLUT1D). The occurrence of paroxysmal movement disorders such as exercise-induced dystonia and non-kinesigenic dyskinesia, received considerable emphasis, while limited attention has been paid to other paroxysmal phenomena, as transitory neurological disorders. These paroxysmal events are roughly and variably described as limb weakness, hemiparesis or ataxia. Their EEG correlate has been never documented

Early-onset head titubation in a child with Poretti-Boltshauser syndrome

Poretti-Boltshauser syndrome (PBS) is a recently described cerebellar disorder characterized by cerebellar dysplasia with cysts and an enlarged and square-like shaped fourth ventricle.1 The clinical phenotype includes nonprogressive cerebellar ataxia, ocular motor apraxia (OMA), intellectual disability, and frequent high myopia or retinal dystrophy.1 Mutations in LAMA1 have been identified as the cause of PBS.2 We report on a 30-month-old girl with genetically confirmed PBS (who has also been included in a recently published series 3), presenting at 2 months of age with head titubation, a movement disorder that has never been reported in association with PBS. To our knowledge, she is the youngest patient with this condition who has been described in the literature

Immunomodulation with Azathioprine therapy in Rasmussen syndrome: A multimodal evaluation

OBJECTIVE: To verify safety and efficacy of the corticosteroid-sparing drug Azathioprine (AZA) in Rasmussen syndrome (RS), we retrospectively analyzed a cohort of RS patients recruited in a single pediatric neuroscience center.METHODS: We compared outcomes in 30 RS patients who received AZA with 23 patients who were not treated with this drug. We used a multimodal approach to correlate therapy with clinical features (seizures, epilepsia partialis continua [EPC], hemiparesis) and neuroimaging markers of progressive brain atrophy.RESULTS: AZA was well tolerated; only one patient discontinued treatment due to pancytopenia. In 27/30 AZA patients, all of whom were corticosteroid responders, corticosteroid therapy could be weaned or reduced without worsening of seizures in 89%. AZA patients had a lower prevalence of EPC (42% vs. 67% in controls) and hemiparesis (64% vs. 92%, respectively). Cox regression showed for the AZA group compared to controls a delayed time to: 1) EPC (of about 2 years, Exp(B)=0.295, 95%CI[0.108, 0.807];p=0.017), 2) hemiparesis (about one year, Exp(B)=0.315, 95%CI[0.137, 0.724];p=0.007), and 3) surgery (about 2 years, Exp(B)=2.068, 95%CI[1.012, 4.227];p=0.046). However, there were no group differences in cognitive decline over time (IQ change per year) or in hemispheric grey matter atrophy on serial MRI scans.CONCLUSION: AZA treatment appears to slow clinical progression of Rasmussen syndrome in steroid responders; this will give most advantage in patients in the early stages of the disease in whom surgical decision-making may require further time.CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for pediatric RS patients AZA is well tolerated and slows hemiparesis and appearance of EPC