Epileptic seizures of suspected autoimmune origin: a multicentre retrospective study.

OBJECTIVE: To analyse autoantibody status in a well-defined European multicentre cohort of patients with epilepsy of unknown aetiology and to validate the recently proposed Antibody Prevalence in Epilepsy (APE2) and Response to ImmunoTherapy in Epilepsy (RITE2) scores. METHODS: We retrospectively collected clinical and paraclinical data of 92 patients referred to the Neurology Units of Verona and Salzburg between January 2014 and July 2019 with new-onset epilepsy, status epilepticus or chronic epilepsy of unknown aetiology. Fixed and live cell-based assays, tissue-based assays, immunoblot, and live rat hippocampal cell cultures were performed in paired serum/cerebrospinal fluid (CSF) to detect antineuronal and antiglial antibodies. The APE2 and RITE2 scores were then calculated and compared with clinical and laboratory data. RESULTS: Autoantibodies were detected in 29/92 patients (31.5%), with multiple positivity observed in 6/29 cases. The APE2 score (median 5, range 1-15) significantly correlated with antibody positivity (p=0.014), especially for the presence of neuropsychiatric symptoms (p<0.01), movement disorders (p<0.01), dysautonomia (p=0.03), faciobrachial dyskinesias (p=0.03) and cancer history (p<0.01). Status epilepticus was significantly more frequent in antibody-negative patients (p<0.01). Among the items of the RITE2 score, early initiation of immunotherapy correlated with a good treatment response (p=0.001), whereas a cancer history was significantly more common among non-responders (p<0.01). Persistence of neuropsychiatric symptoms and seizures correlated with antiepileptic maintenance after at least 1 year. CONCLUSIONS: This is the first study that independently validates the APE2 and RITE2 scores and includes the largest cohort of patients whose paired serum and CSF samples have been tested for autoantibodies possibly associated with autoimmune epilepsy.

A novel treatment for malignant spasticity: The therapeutic use of stereotactic radiosurgery (SRS).

Spasticity is a clinical condition secondary to central nervous system damage, which impairs patients' mobility and quality of life. Stereotactic radiosurgery (SRS) to the spinal roots responsible of the spasms might represent a non-invasive therapy. The present are the preliminary results of the first clinical use of this novel technique.

Opinion, knowledge, and clinical experience with functional neurological disorders among Italian neurologists: results from an online survey.

BACKGROUND: Functional neurological disorders (FND) are disabling medical conditions commonly seen in neurological practice. Neurologists play an essential role in managing FND, from establishing a diagnosis to coordination of multidisciplinary team-based treatment for patients. With this study, we investigated the knowledge and the clinical experience of Italian neurologists in managing patients with FND. METHODS: Members of the Italian Society of Neurology were invited via e-mail to participate in this ad hoc online survey; 492 questionnaires were returned completed. RESULTS: The term "Functional neurological disorders" in reference to FND was used more frequently than other psychological (e.g., psychogenic or conversion), or descriptive terms (e.g., non-organic or stress-related). When speaking with patients, the respondents stated that they preferred explaining symptoms based on abnormal functioning of the nervous system than discussing mental illness and that they would refer their patient to a psychologist rather than to a psychiatrist. Few considered that physiotherapy and psychiatric interventions are useful approaches to treating FND. Some believed that patients simulate their symptoms. CONCLUSIONS: Overall, the responses suggest that knowledge about scientific advances in FND is somewhat sparse. A psychiatric-centered view of FND opens the way to an approach in which neurobiological and psychological aspects constitute essential factors of the condition. In this context, professional education could improve understanding of FND and optimize patient management.

The Impact of the SARS-CoV-2 Outbreak on the Psychological Flexibility and Behaviour of Cancelling Medical Appointments of Italian Patients with Pre-Existing Medical Condition: The "ImpACT-COVID-19 for Patients" Multi-Centre Observational Study.

Psychological distress imposed by the SARS-CoV-2 outbreak particularly affects patients with pre-existing medical conditions, and the progression of their diseases. Patients who fail to keep scheduled medical appointments experience a negative impact on care. The aim of this study is to investigate the psychosocial factors contributing to the cancellation of medical appointments during the pandemic by patients with pre-existing health conditions. Data were collected in eleven Italian hospitals during the last week of lockdown, and one month later. In order to assess the emotional impact of the SARS-CoV-2 outbreak and the subject's degree of psychological flexibility, we developed an ad hoc questionnaire (ImpACT), referring to the Acceptance and Commitment Therapy (ACT) model. The Impact of Event Scale-Revised (IES-R), the Depression, Anxiety and Stress Scale (DASS) and the Cognitive Fusion Questionnaire (CFQ) were also used. Pervasive dysfunctional use of experiential avoidance behaviours (used with the function to avoid thought, emotions, sensations), feelings of loneliness and high post-traumatic stress scores were found to correlate with the fear of COVID-19, increasing the likelihood of cancelling medical appointments. Responding promptly to the information and psychological needs of patients who cancel medical appointments can have positive effects in terms of psychological and physical health.

Exploring Emotional Distress, Psychological Traits and Attitudes in Patients with Chronic Migraine Undergoing OnabotulinumtoxinA Prophylaxis versus Withdrawal Treatment.

This explorative cross-sectional study aims at exploring emotional distress, psychological profiles, and the attitude towards receiving psychological support in eighty-seven patients with chronic migraine (CM) undergoing OnabotulinumtoxinA prophylactic treatment (OBT-A, n = 40) or withdrawal treatment (WT, n = 47). The outcomes were explored through a specific battery of questionnaires. 25% of patients undergoing OBT-A and almost half of the patients undergoing WT reported psychological distress of at least moderate-severe level, respectively. Coping strategies, self-efficacy, and perceived social support were similar in the two groups. Patients undergoing OBT-A presented lower psychological inflexibility than patients undergoing WT. Predictors of higher psychological distress were low perceived social support by friends, low self-efficacy, and higher avoidance strategies. In both groups, most of the patients evaluated receiving psychological support to be useful (79%). The potential beneficial effects of OBT-A on the severity of symptoms and psychological distress might further support its role in the multidisciplinary management of patients with CM. Identifying patients with psychological vulnerabilities who may benefit from psychological support is relevant in patients with CM.

Changing therapeutic strategies and persistence to disease-modifying treatments in a population of multiple sclerosis patients from Veneto region, Italy.

BACKGROUND: The availability of new disease-modifying treatments (DMTs) in the last years has changed the therapeutic strategies used in Multiple Sclerosis (MS). We aimed to describe trend in DMTs utilization and persistence to treatment in a large sample of patients attending 10 MS centres from four provinces of Veneto, Italy. METHODS: Demographic, clinical and DMTs information of patients regularly followed from January 2011 to August 2018 were recorded and analysed. Persistence at 12, 24 months and at last follow-up was assessed by Kaplan Meier survival analysis. Multivariable Cox- proportional hazard model was used to identify predictors of persistence. RESULTS: Of 3025 MS patients 65.7% were in treatment al last follow-up. Dimethylfumarate (DMF) was the most prescribed single drug among first-line and fingolimod among second-line DMTs. In the cohort of 1391 cases starting any DMT since 2011 12.9% stopped within 6 months, 24% within 12 and 40.3% within 24 months. Disease duration > 5 years at therapy start was predictive of greater risk of discontinuation, while age and sex were not. DMF use was predictive of higher persistence at 12 and 24 months, but not at last follow-up when azathioprine and glatiramer acetate showed the highest persistence compared to other DMTs. Side effects represented the main reason of discontinuation. CONCLUSION: The use of the new oral DMTs greatly increased since their approval but persistence in the long-term is not better than with old drugs. The treatment choice is still a challenge both for patients and their doctors.

A Prospective Observational Cohort Study on Pharmacological Habitus, Headache-Related Disability and Psychological Profile in Patients with Chronic Migraine Undergoing OnabotulinumtoxinA Prophylactic Treatment.

Chronic Migraine (CM) is a disabling neurologic condition with a severe impact on functioning and quality of life. Successful therapeutic management of patients with CM is complex, and differences in therapeutic response could be attributable to genetically determined factors, sensitivity to pharmacological treatment, psychosocial and relational factors affecting the patient's compliance and approach on the therapeutic treatment. The aim of this prospective observational study was to explore self-efficacy, coping strategies, psychological distress and headache-related disability in a cohort of 40 patients with CM (mean age: 46.73; standard deviation 13.75) treated with OnabotulinumtoxinA and the relationship between these clinical and psychological aspects and acute medication consumption during OnabotulinumtoxinA prophylactic treatment. Patients presented an overall significant reduction in the Headache Index (HI) (p < 0.001), HI with severe intensity (p = 0.009), and total analgesic consumption (p = 0.003) after the prophylactic treatment. These results are in line with the literature. Despite this, higher nonsteroidal anti-inflammatory drugs consumption was associated with higher psychological distress, higher HI with severe and moderate intensity, and worse quality of life. Conversely, triptans consumption was correlated with HI of mild intensity, and problem-focused coping strategies. To conclude, the psychological profile, and in particular, the psychological distress and specific coping strategies might influence the self-management of acute medication.

Does myofascial and trigger point treatment reduce pain and analgesic intake in patients undergoing onabotulinumtoxinA injection due to chronic intractable migraine?

BACKGROUND: Chronic migraine is a disabling disorder associated with myofascial and trigger point disorders in the neck. Pharmacological management is the first line of treatment; however, rehabilitation procedures aimed at lessening symptoms of myofascial and trigger point disorders may add value in the management of headache symptoms. AIM: The aim of this study was to evaluate the feasibility of myofascial and trigger point treatment in chronic migraine patients receiving prophylactic treatment with onabotulinumtoxinA. To evaluate the treatment effects on headache frequency and intensity, analgesic consumption, cervical range of motion, trigger point pressure pain threshold, quality of life, and disability. DESIGN: Pilot, single-blind randomized controlled trial with two parallel groups. SETTING: Neurorehabilitation Unit. POPULATION: Twenty-two outpatients with chronic migraine. METHODS: Patients were randomly assigned to receive either cervicothoracic manipulative treatment (N.=12) or transcutaneous electrical nerve stimulation (TENS) in the upper trapezius (N.=10). Treatment consisted of 4 sessions (30 min/session, 1 session/week for 4 weeks). A rater blinded to treatment allocation evaluated outcomes before treatment, during treatment, and 1 month after the end of treatment. Consistent with the pilot nature of the study, feasibility was considered the primary outcome and efficacy the secondary outcome. RESULTS: All patients completed the study. No adverse events were reported. No significant between-group differences in pain intensity were observed during the study period. At post-treatment evaluation, the total consumption of analgesics (P=0.02) and non-steroidal anti-inflammatory (P=0.02) drugs was significantly lower in the manipulative treatment group than in the TENS group. These effects paralleled significant improvements in trigger point sensitivity and cervical active range of motion. CONCLUSIONS: Manipulative techniques aimed at reducing peripheral nociceptive triggers might add value in the management of chronic migraine symptoms and lower acute medication use. CLINICAL REHABILITATION IMPACT: An interdisciplinary approach comprising pharmacological and non-pharmacological strategies can reduce analgesic consumption and myofascial dysfunction symptoms in chronic migraine patients.

Robot-assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial.

BACKGROUND: Extensive research on both healthy subjects and patients with central nervous damage has elucidated a crucial role of postural adjustment reactions and central sensory integration processes in generating and "shaping" locomotor function, respectively. Whether robotic-assisted gait devices might improve these functions in Multiple sclerosis (MS) patients is not fully investigated in literature. PURPOSE: The aim of this study was to compare the effectiveness of end-effector robot-assisted gait training (RAGT) and sensory integration balance training (SIBT) in improving walking and balance performance in patients with MS. METHODS: Twenty-two patients with MS (EDSS: 1.5-6.5) were randomly assigned to two groups. The RAGT group (n = 12) underwent end-effector system training. The SIBT group (n = 10) underwent specific balance exercises. Each patient received twelve 50-min treatment sessions (2 days/week). A blinded rater evaluated patients before and after treatment as well as 1 month post treatment. Primary outcomes were walking speed and Berg Balance Scale. Secondary outcomes were the Activities-specific Balance Confidence Scale, Sensory Organization Balance Test, Stabilometric Assessment, Fatigue Severity Scale, cadence, step length, single and double support time, Multiple Sclerosis Quality of Life-54. RESULTS: Between groups comparisons showed no significant differences on primary and secondary outcome measures over time. Within group comparisons showed significant improvements in both groups on the Berg Balance Scale (P = 0.001). Changes approaching significance were found on gait speed (P = 0.07) only in the RAGT group. Significant changes in balance task-related domains during standing and walking conditions were found in the SIBT group. CONCLUSION: Balance disorders in patients with MS may be ameliorated by RAGT and by SIBT.

Occipital nerve stimulation for chronic migraine: a randomized trial.

BACKGROUND: Chronic migraine (CM) and medication overuse headache (MOH) are disabling conditions that may be only partially managed with conservative treatments. Occipital nerve stimulation (ONS) is an innovative treatment for headache disorders. OBJECTIVES: To investigate the safety and efficacy of ONS for CM and MOH patients and to evaluate changes in disability, quality of life, and drug intake in implanted patients. STUDY DESIGN: Prospective, randomized cross-over study. METHODS: Eligible patients who responded to a stimulation trial underwent device implantation and were randomized to "Stimulation On" and "Stimulation Off" arms. Patients crossed over after one month, or when their headaches worsened. Stimulation was then switched On for all patients. Disability as measured by the Migraine Disability Assessment (MIDAS), quality of life (SF-36), and drug intake (patient's diary) were assessed over a one-year follow-up. RESULTS: Thirty-four patients (76% women, 34% men, mean age: 46 ± 11 years) were enrolled; 30 were randomized and 29 completed the study. Headache intensity and frequency were significantly lower in the On arm than in the Off arm (p < 0.05) and decreased from the baseline to each follow-up visit in all patients with Stimulation On (median MIDAS A and B scores: baseline = 70 and 8; one-year follow-up = 14 and 5, p < 0.001). Quality of life significantly improved (p < 0.05) during the study. Triptans and nonsteroidal anti-inflammatory drug use fell dramatically from the baseline (20 and 25.5 doses/month) to each follow-up visit (3 and 2 doses/month at one year, p < 0.001). A total of 5 adverse events occurred: 2 infections and 3 lead migrations. LIMITATIONS: Single-centre study, relatively small number of patients, absence of a control group. CONCLUSIONS: According to the results obtained, ONS appears to be a safe and effective treatment for  carefully selected CM and MOH patients.