Laura Ferrè

Impact of MS genetic loci on familial aggregation, clinical phenotype, and disease prediction.

Objective: To investigate the role of known multiple sclerosis (MS)-associated genetic variants in MS familial aggregation, clinical expression, and accuracy of disease prediction in sporadic and familial cases. Methods: A total of 1,443 consecutive patients were screened for MS and familial autoimmune history in a hospital-based Italian cohort. Among them, 461 sporadic and 93 familial probands were genotyped for 107 MS-associated polymorphisms. Their effect sizes were combined to calculate the weighted genetic risk score (wGRS). Results: Family history of MS was reported by 17.2% of probands, and 33.8% reported a familial autoimmune disorder, with autoimmune thyroiditis and psoriasis being the most frequent. No difference in wGRS was observed between sporadic and familial MS cases. In contrast, a lower wGRS was observed in probands with greater familial aggregation (>1 first-degree relative or >2 relatives with MS) (p = 0.03). Also, female probands of familial cases with greater familial aggregation had a lower wGRS than sporadic cases (p = 0.0009) and male probands of familial cases (p = 0.04). An inverse correlation between wGRS and age at onset was observed (p = 0.05). The predictive performance of the genetic model including all known MS variants was modest but greater in sporadic vs familial cases (area under the curve = 0.63 and 0.57). Conclusions: Additional variants outside the known MS-associated loci, rare variants, and/or environmental factors may explain disease occurrence within families; in females, hormonal and epigenetic factors probably have a predominant role in explaining familial aggregation. The inclusion of these additional factors in future versions of aggregated genetic measures could improve their predictive ability.

Clinical response to Nabiximols correlates with the down-regulation of immune pathways in Multiple Sclerosis

Nabiximols (Sativex®) is a cannabinoid‐based compound used for the treatment of moderate to severe spasticity in multiple sclerosis (MS). The aim of the study was to investigate the effect of the administration of Nabiximols on blood transcriptome profile of patients with MS and to interpret it in the context of pathways and networks.

Assessing the role of innovative therapeutic paradigm on multiple sclerosis treatment response

Within the last decade, many changes have been made to the management of patients with multiple sclerosis (MS). The aim of our study was to investigate the global impact of all these changes on the diseases course.

Moyamoya disease mimicking the first attack of multiple sclerosis

The spectrum of diseases that must be excluded to make a diagnosis of multiple sclerosis (MS) is wide and the ascertainment of possible alternative conditions is often challenging, but it is a critical aspect in the diagnostic work-up of patients suspected of having MS [1–3]. An early diagnosis has a dramatic influence on patient’s prognosis, since different etiologies require different treatments which have the potential to modify favourably the course of the disease if started promptly. We present the case of a young patient suffering from sensory disturbances occurring over a few days, mimicking a first clinical attack of an inflammatory demyelinating condition, but which eventually proved to have a different origin. In September 2012, a 45-year-old man developed paresthesias involving his left hand and extending to the entire arm in 10 days. Neurological examination revealed hypoesthesia of his left arm. A brain computed tomography (CT) was negative. Blood examinations, including dysimmune and thrombophilic tests, were negative. Cerebrospinal fluid examination was normal and no oligoclonal bands were detected. Visual, motor, and sensory multimodal-evoked potentials were also normal. A brain MRI showed multiple T2-hyperintense cortical/sub-cortical lesions (Fig. 1a), mildly T1-hypointense, which were mainly located in the right hemisphere and were not characterized by a restricted diffusivity (Fig. 1b) nor had contrast-enhancement (Fig. 1c). Periventricular and infratentorial regions were spared. Moreover, asymmetric atrophy of the right fronto-parietal regions (Fig. 1a, c) was evident. Spinal cord MRI was normal. Due to the atypical findings, further non-routine neuroradiological investigations were performed. Both CT angiography (Fig. 1d, e) and MRI angiography (Fig. 1f) revealed a proximal occlusion of the right middle cerebral artery. Angiography (Fig. 1g) confirmed such a finding and also showed the presence of transcortical compensatory mechanisms and lenticulostrialtal anastomoses in the insular region, signs suggestive of a ‘‘Moyamoya syndrome’’ [4, 5]. This condition makes affected patients prone to ischemic cerebrovascular disease due to the progressive stenosis of the intracranial internal carotid arteries and their proximal branches. Due to this chronic and progressive phenomenon, collateral vessels from cortical surface, leptomeninges, and branches of the external carotid artery develop to provide blood flow compensation [4, 5]. Antiplatelet drug was started and a surgical revascularization with a branch of the external carotid artery was proposed, but this procedure was not accepted by the patient. After discharge, brain MRI remained stable (the last one was performed in September 2016) and, until the last clinical evaluation (December 2016), no further clinical manifestation occurred. & Massimo Filippi filippi.massimo@hsr.it