EFFECTS OF MUSIC ON SEIZURE FREQUENCY IN INSTITUTIONALIZED SUBJECTS WITH SEVERE/PROFOUND INTELLECTUAL DISABILITY AND DRUG-RESISTANT EPILEPSY

Background: Approximately one-third of patients with epilepsy continue to experience seizures despite adequate therapy with antiepileptic drugs. Drug-resistant epilepsy is even more frequent in subjects with intellectual disability. As a result, several nonpharmacological interventions have been proposed to improve quality of life in patients with intellectual disability and drug-resistant epilepsy. A number of studies have demonstrated that music can be effective at reducing seizures and epileptiform discharges. In particular, Mozart’s sonata for two pianos in D major, K448, has been shown to decrease interictal EEG discharges and recurrence of clinical seizures in patients with intellectual disability and drug-resistant epilepsy as well. The aim of this study is to investigate the influence of Mozart\u27s music on seizure frequency in institutionalized epileptic subjects with profound/severe intellectual disability. Subjects and methods: Twelve patients (10 males and 2 females) with a mean age of 21.6 years were randomly assigned to two groups in a cross-over design; they listened to Mozart K448 once a day for six months. Results: A statistically significant difference was observed between the listening period and both baseline and control periods. During the music period, none of the patients worsened in seizure frequency; one patient was seizure-free, five had a greater than 50% reduction in seizure frequency and the remaining showed minimal (N=2) or no difference (N=4). The average seizure reduction compared to the baseline was 20.5%. Our results are discussed in relation to data in the literature considering differences in protocol investigation. Conclusions: Music may be considered a useful approach as add-on therapy in some subjects with profound intellectual disability and drug-resistant epilepsy and can provide a new option for clinicians to consider, but further large sample, multicenter studies are needed to better understand the characteristics of responders and non-responders to this type of non-pharmacological intervention

MOZART\u27S MUSIC AND MULTIDRUG-RESISTANT EPILEPSY: A POTENTIAL EEG INDEX OF THERAPEUTIC EFFECTIVENESS

Multidrug-resistant epilepsy is a pathological condition that affects approximately one-third of patients with epilepsy, especially those with associated intellectual disabilities. Several non-pharmacological interventions have been proposed to improve quality of life of these patients. In particular, Mozart’s sonata for two pianos in D major, K448, has been shown to decrease interictal electroencephalography (EEG) discharges and recurrence of clinical seizures in these patients. In a previous study we observed that in institutionalized subjects with severe/profound intellectual disability and drug-resistant epilepsy, a systematic music listening protocol reduced the frequency of seizures in about 50% of cases. This study aims to assess electroencephalography as a quantitative (qEEG) predictive biomarker of effectiveness of listening to music on the frequency of epileptic discharges and on background rhythm frequency (BRF)

MOZART\u27S MUSIC AND MULTIDRUG-RESISTANT EPILEPSY: A POTENTIAL EEG INDEX OF THERAPEUTIC EFFECTIVENESS

Multidrug-resistant epilepsy is a pathological condition that affects approximately one-third of patients with epilepsy, especially those with associated intellectual disabilities. Several non-pharmacological interventions have been proposed to improve quality of life of these patients. In particular, Mozart’s sonata for two pianos in D major, K448, has been shown to decrease interictal electroencephalography (EEG) discharges and recurrence of clinical seizures in these patients. In a previous study we observed that in institutionalized subjects with severe/profound intellectual disability and drug-resistant epilepsy, a systematic music listening protocol reduced the frequency of seizures in about 50% of cases. This study aims to assess electroencephalography as a quantitative (qEEG) predictive biomarker of effectiveness of listening to music on the frequency of epileptic discharges and on background rhythm frequency (BRF)

THE EFFECT OF MOZART’S MUSIC IN SEVERE EPILEPSY: FUNCTIONAL AND MORPHOLOGICAL FEATURES

Music is a very important factor in everyday life, involving mood, emotions and memories. The effect of music on the brain is very debated. Certainly, music activates a complex network of neurones in auditory areas, mesolimbic areas, cerebellum and multisensory areas. In particular, music exerts its effects on the brain of patients with epilepsy, having a dichotomous influence: it can either be seizure-promoting in musicogenic epilepsy or antiepileptic. Several studies have shown that seizure-prone neural networks may be stimulated by certain periodicities while other frequencies may prevent seizure activity. There are a lot of data in the literature about the so-called "Mozart effect" (Rauscher et al. 1993). In previous studies we observed that in institutionalized subjects with severe/profound intellectual disability and drug-resistant epilepsy, a systematic music listening protocol reduced the frequency of seizures in about 50% of the cases. In this study we are conducting a survey on the observation of what happens to the brain of patients suffering from drug-resistant epilepsy through electroencephalographic investigations, brain MRI and behavioural analysis before and after six months of listening to Mozart music (Sonata K.448). The first step is to present the data of the first patient under investigation

THE EFFECT OF MOZART’S MUSIC IN SEVERE EPILEPSY: FUNCTIONAL AND MORPHOLOGICAL FEATURES

Music is a very important factor in everyday life, involving mood, emotions and memories. The effect of music on the brain is very debated. Certainly, music activates a complex network of neurones in auditory areas, mesolimbic areas, cerebellum and multisensory areas. In particular, music exerts its effects on the brain of patients with epilepsy, having a dichotomous influence: it can either be seizure-promoting in musicogenic epilepsy or antiepileptic. Several studies have shown that seizure-prone neural networks may be stimulated by certain periodicities while other frequencies may prevent seizure activity. There are a lot of data in the literature about the so-called "Mozart effect" (Rauscher et al. 1993). In previous studies we observed that in institutionalized subjects with severe/profound intellectual disability and drug-resistant epilepsy, a systematic music listening protocol reduced the frequency of seizures in about 50% of the cases. In this study we are conducting a survey on the observation of what happens to the brain of patients suffering from drug-resistant epilepsy through electroencephalographic investigations, brain MRI and behavioural analysis before and after six months of listening to Mozart music (Sonata K.448). The first step is to present the data of the first patient under investigation

EVALUATION OF THE QUALITY OF REHABILITATION TREATMENT IN NEURODEVELOPMENTAL DISORDER

Complex disability is very difficult to manage. It usually subtends very serious clinical pictures, because it affect several body systems, or because it is associated with intellectual disability and behavioral disorders. Often affected patients are unable to communicate their basic needs. All these factors combine to make the management of these patients very complex, and those who care for them realize how important it is to find a way to detect their state and to identify their potential capabilities. Developing appropriate rehabilitation programs for these patients requires additional effort and an assessment capacity that is as objective as possible. Few scales cited in the literature are capable of evaluating these aspects in patients with complex disabilities, among them the Barthel Index (Mahoney & Barthel 1965) and the Vineland Adaptive Behavior scale II (Sparrow et al. 2005). The majority of these scales often tend to depict the data regarding the disease to a degree of severity that precludes adequate individual rehabilitation program development. There is a dire need for a more appropriate instrument, an observational grid that is capable of identifying the potential of this patient population and evaluate the effectiveness of rehabilitation interventions provided. The aim of the study is to evaluate the efficacy of rehabilitation interventions in a group of patients with IQ <32 (determined by the Vineland II scale) using an evaluation tool created ad hoc called D-Rubrics, designed with the intent to identify “microdifferences” between baseline (T0) and post-rehabilitation (T1). The goal is part of a more long term-term objective which involves developing an effective assessment tool for patients with complex disabilities. Such an assessment tool should be practical, easy to administer and useful in both clinical and research settings

Efficacy and safety of venous angioplasty of the extracranial veins for multiple sclerosis. Brave Dreams Study (Brain Venous Drainage Exploited Against Multiple Sclerosis): study protocol for a randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a disabling progressive course. Chronic cerebrospinal venous insufficiency (CCSVI) has recently been described as a vascular condition characterized by restricted venous outflow from the brain, mainly due to blockages of the internal jugular and azygos veins. Despite a wide variability among studies, it has been found to be associated with MS. Data from a few small case series suggest possible improvement of the clinical course and quality of life by performing percutaneous balloon angioplasty (PTA) of the stenotic veins.Study design and methodsThis is a multicenter, randomized, parallel group, blinded, sham-controlled trial to assess the efficacy and safety of PTA. Participants with relapsing remitting MS or secondary progressive MS and a sonographic diagnosis of CCSVI will be enrolled after providing their informed consent. Each participant will be centrally randomized to receive catheter venography and PTA or catheter venography and sham PTA. Two primary end points with respect to efficacy at 12 months are (1) a combined end point obtained through the integration of five functional indicators, walking, balance, manual dexterity, bladder control, and visual acuity, objectively measured by instruments; and (2) number of new brain lesions measured by T2-weighted MRI sequences. Secondary end points include annual relapse rate, change in Expanded Disability Status Scale score, proportion of patients with zero, one or two, or more than two relapses; fatigue; anxiety and depression; general cognitive state; memory/attention/calculus; impact of bladder incontinence; and adverse events. Six hundred seventy-nine patients will be recruited. The follow-up is scheduled at 12 months. Patients, treating neurologists, trained outcome assessors, and the statistician in charge of data analysis will be masked to the assigned treatment. DISCUSSION: The study will provide an answer regarding the efficacy of PTA on patients' functional disability in balance, motor, sensory, visual and bladder function, cognitive status, and emotional status, which are meaningful clinical outcomes, beyond investigating the effects on inflammation. In fact, an important part of patients' expectations, sustained and amplified by anecdotal data, has to do precisely with these functional aspects.Trial registrationClinicaltrials.gov NCT01371760

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor