D-galactose Supplementation for the Treatment of Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE): A Pilot Trial of Precision Medicine After Epilepsy Surgery.

MOGHE is defined as mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Approximately half of the patients with histopathologically confirmed MOGHE carry a brain somatic variant in the SLC35A2 gene encoding a UDP-galactose transporter. Previous research showed that D-galactose supplementation results in clinical improvement in patients with a congenital disorder of glycosylation due to germline variants in SLC35A2. We aimed to evaluate the effects of D-galactose supplementation in patients with histopathologically confirmed MOGHE, with uncontrolled seizures or cognitive impairment and epileptiform activity at the EEG after epilepsy surgery (NCT04833322). Patients were orally supplemented with D-galactose for 6 months in doses up to 1.5 g/kg/day and monitored for seizure frequency including 24-h video-EEG recording, cognition and behavioral scores, i.e., WISC, BRIEF-2, SNAP-IV, and SCQ, and quality of life measures, before and 6 months after treatment. Global response was defined by > 50% improvement of seizure frequency and/or cognition and behavior (clinical global impression of "much improved" or better). Twelve patients (aged 5-28 years) were included from three different centers. Neurosurgical tissue samples were available in all patients and revealed a brain somatic variant in SLC35A2 in six patients (non-present in the blood). After 6 months of supplementation, D-galactose was well tolerated with just two patients presenting abdominal discomfort, solved after dose spacing or reduction. There was a 50% reduction or higher of seizure frequency in 3/6 patients, with an improvement at EEG in 2/5 patients. One patient became seizure-free. An improvement of cognitive/behavioral features encompassing impulsivity (mean SNAP-IV - 3.19 [- 0.84; - 5.6]), social communication (mean SCQ - 2.08 [- 0.63; - 4.90]), and executive function (BRIEF-2 inhibit - 5.2 [- 1.23; - 9.2]) was observed. Global responder rate was 9/12 (6/6 in SLC35A2-positive). Our results suggest that supplementation with D-galactose in patients with MOGHE is safe and well tolerated and, although the efficacy data warrant larger studies, it might build a rationale for precision medicine after epilepsy surgery.

Subjective Evaluation of Mood and Cognitive Functions in a General Neurology Clinic: Patients versus Informants.

BACKGROUND AND PURPOSE: We aimed to determine the correlation between subjective evaluations of mood and cognitive functions by patients and informants, and the findings of a battery of neuropsychological tests. METHODS: We analyzed 74 subjects recruited from a general neurology clinic, comprising 37 patients with cognitive complaints and 37 informants (either relatives or caregivers in close contact with the patients). Four ordinal scales concerning recent memory, verbal expression, initiative, and mood were correlated with the findings of a series of neuropsychological tests and questionnaires using the tau b coefficient. RESULTS: The scores for the patients on the scales were most strongly correlated with scores on the 15-item Geriatric Depression Scale (GDS-15), while the scores for the informants were most strongly correlated with scores on GDS-15, the Informant Questionnaire on Cognitive Decline, and the Functional Activities Questionnaire (FAQ). The most significant correlation was between the initiative scale from informants and FAQ (tau b=-0.591, p<0.001), and it was the only one that remained significant after correcting for multiple testing (p Holm=0.013). CONCLUSIONS: Cognitive complaints from patients mainly reflect their mood, whilst informant reports mainly reflect both the functional ability and mood of the patients.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Occipital lobe epilepsy secondary to ulegyria.

OBJECTIVE: To analyse clinical and therapeutic aspects of epilepsy secondary to ulegyria in adults. PATIENTS: Out of 1,020 consecutive patients studied at a tertiary care epilepsy centre, eight cases of ulegyria were identified. All patients had comprehensive clinical evaluation, neuropsychological testing, interictal EEG, and brain magnetic resonance imaging (MRI). In addition, five patients had video-EEG monitoring. Ulegyria was confirmed by histological analysis in two patients who had successful epilepsy surgery. RESULTS: All patients had a history of perinatal asphyxia. In four of them there was psychomotor developmental delay. Mean age at onset of seizures was 5.8 years (range first week to 21 years). Brain MRI demonstrated predominant involvement of occipito-parietal cortical and subcortical areas. This posterior distribution of lesions was also supported by the presence of auras with occipital and parietal semiology in six patients, and signs of visuospatial dysfunction in five. Four patients had medically refractory epilepsy and two of them had significant improvement with surgical treatment. CONCLUSIONS: In this group of adult epileptic patients with ulegyria brain MRI, ictal semiology, and neurological examination are consistent with occipital lobe epilepsy. Most patients have severe epilepsy, but in some of them epilepsy can be controlled with antiepileptic drugs, while in others surgical treatment can be effective. Brain MRI criteria of ulegyria are well established, and in two cases it was possible to confirm their diagnosis with histological analysis.

Responses to dietary macronutrient distribution of overweight rats under restricted feeding.

Changes in protein and amino acid balance after energy-restricted feeding have scarcely been studied, although it has been suggested that protein utilization may depend on the macronutrient composition of the restricted diet. The aim of this study is to investigate the influence of dietary fat quality and content, during an energy-restricted regime, on body composition and protein metabolism. Therefore, diet-induced overweight rats were divided into three dietary groups: one group was fed on a control diet ad libitum (control) and the other two groups were fed energy-restricted diets (about 60% of control group), which provided a standard amount (20%) of fat (SFR), based on olive oil, or a high amount (60%) of saturated fat (HFR), based on coconut oil. Measurements of body weight, body composition, serum biochemical parameters and the assessment of the hepatic and muscular protein response were performed. Similar results were found comparing weight losses and serum parameters in both deprived groups, although the high-fat-restricted rats (HFR group) showed a greater reduction in the subcutaneous fat depot and of total body fat. After both energy-restricted treatments, the serum amino acid concentration was reduced while the urinary amino acid excretion increased. Muscle and liver protein metabolism was affected by energy restriction, which produced a decrease in protein synthesis capacity (RNA content) in both tissues and a higher muscle proteolysis (catepsin activity), more marked in the SFR group, while no changes were found in liver protein breakdown. Hepatic glycogen and glycogenic amino acid were also altered, reaching significant differences in the HFR group. Thus, dietary macronutrient composition during energy restriction seems to be involved in the metabolic adaptative response.