Long term follow-up in advanced Parkinson’s disease treated with DBS of the subthalamic nucleus

Journal of Neurology - Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting both motor and non-motor systems. Deep brain stimulation of the subthalamic...     

Safety and tolerability of fingolimod in patients with relapsing-remitting multiple sclerosis: results of an open-label clinical trial in Italy

The safety profile of fingolimod is well established in clinical trials and post-marketing studies. This study aimed to evaluate the safety and tolerability of fingolimod in a cohort of Italian patients with relapsing-remitting multiple sclerosis (RRMS). This is a non-comparative, open-label, multicentre, interventional study conducted in patients with RRMS with no suitable alternative treatment option. Safety and tolerability of fingolimod 0.5 mg were assessed by recording adverse events (AEs) and serious AEs (SAEs). Of the 906 patients enrolled in the study, 91 % of the patients completed the study. AEs and SAEs were reported in 35.4 and 2.9 % of the patients, respectively. Most common AEs reported were headache (4.1 %), influenza (2.1 %), lymphopenia (1.8 %), asthenia (1.8 %) and pyrexia (1.8 %). Increased alanine aminotransferase levels and hypertension were reported as AE in 1.0 and 1.4 % of the patients, respectively. Macular oedema was reported in three patients. These results emphasize the safety of fingolimod in patients representing the real-world clinical practice in the Italian population. Fingolimod was safe and well tolerated in this population, which, compared to those enrolled in pivotal trials in terms of concomitant diseases and used medications, is broader.Trial registration: EudraCT 2011-000770-60.     

Neurophysiological correlates of cognitive disturbances in multiple sclerosis

Cognitive impairment is common in multiple sclerosis, mostly attributed to involvement of cortico-cortical and cortico-subcortical connections. The latter may be explored using the analysis of bioelectrical activity such as power and coherence of the electroencephalogram at rest and its reactivity to stimulus processing and cognitive activities, such as event-related desynchronization and event-related potentials. Although these methods are very useful for assessing information processing during cognitive tasks and other activities, their value in detecting cognitive impairment concerning sensitivity and specificity needs to be validated and they have been mostly used for understanding the physiopathology of cognitive impairment in different forms and stages of the diseases. Nevertheless, newer applications such as longitudinal monitoring and effects of treatment, although explored only in pilot studies, seem quite promising allowing objective measures potentially useful as secondary endpoints in clinical trials aimed at preserving or improving cognition in MS patients.     

Effects of disease modifying treatments on cognitive dysfunction in multiple sclerosis

Cognitive dysfunctions are frequent in multiple sclerosis and have a negative impact on employment and quality of life. Pathophysiology of impaired mental activities is probably multifactorial including sensory deafferentation, lesion-related disconnection of associative areas (cortico-cortical and cortico-thalamic), involvement of normal appearing white and gray matter, and direct effects of products of inflammation. Available immunomodulatory treatments for multiple sclerosis may have a role in MS-related cognitive dysfunction because they positively impact some of the pathogenetic studies. Pivotal phase III clinical trials have effectively shown some benefit, confirmed by some post marketing studies. However, results of these studies must be interpreted with great caution because many methodological problems may undermine the quality of the studies.     

Interhemispheric Balance in Parkinson's Disease: A Transcranial Magnetic Stimulation Study

BackgroundParkinson's disease (PD) is characterized by various changes in motor excitability.ObjectiveTo examine through Transcranial Magnetic Stimulation (TMS) cortical excitability, specifically addressing interhemispheric connections in PD.MethodsNineteen PD patients with a predominant involvement of the left hemibody (7 females, age 61.7 years,) and 13 controls (6 females, age 61.5 years) entered the study. Patients were subdivided into two groups (early and advanced) according to the time from PD diagnosis. Participants underwent evaluation of Resting Motor Threshold (RMT) and ipsilateral Silent Period (iSP), induced by suprathreshold TMS on the ipsilateral-M1, measured as suppression of voluntary EMG activity. Mirror Movements (MM) were EMG-recorded and scored, in three upper limb muscles, during unilateral voluntary hand movement. Patients were studied at baseline (OFF drug) and after acute levodopa challenge (ON).ResultsPD patients showed a general reduction in RMT vs controls (P < 0.01 for right and left hemisphere) in both drug conditions. Early PD had a significantly lower RMT over the right vs the left hemisphere (P = 0.027); this difference was no longer significant after levodopa. In early PD patients, MM were mainly observed in the right arm during voluntary activation of the left, more affected side both in OFF (P = 0.033) and in ON (P = 0.046). In PD, RMT of the left, less affected M1 was significantly correlated with the right lateralized motor score (P = 0.011; Spearman's coefficient = ?0.585), as well as with disease duration. In PD patients, a shorter (P = 0.039) and smaller (P = 0.037) iSP was detected when the stimulus was applied to the worse M1 (right) compared with the contralateral side. This asymmetry was significant only OFF drug. In the PD group iSP-duration from the right, less affected APB was negatively correlated with the MM recorded from the same side during the voluntary movement of the worse side (Spearman's coefficient = ?0.498; P = 0.035).ConclusionsIncreased cortical motor excitability in PD, consistent with previous findings, is more evident in the worse hemisphere, particularly in early PD. Asymmetric motor involvement is also associated with excessive involuntary mirroring and defective interhemispheric inhibition, both unfavoring the more affected side. Altogether, these findings suggest that asymmetric motor involvement in PD, particularly in the earlier phases of the disease, affects the interhemispheric balance of cortical excitability, movement lateralization and transcallosal inhibition.     

Multiple sclerosis associated with pembrolizumab in a patient with non-small cell lung cancer

Journal of Neurology -     

Identification of potentially druggable molecular alterations in skin adnexal malignancies

Skin adnexal cancers (SAC) are a heterogeneous group of rare malignancies with histological differentiation towards epithelial adnexa, which lack effective systemic treatments. The aim of this work is to identify any potentially druggable genomic alterations for possible targeted therapies. Cases of primary or recurrent/metastatic (RM) SAC between 2002 and 2014 were identified by searching the institutional cancer registration database. Histological sections of all referral cases were reviewed by a dedicated pathologist to confirm diagnosis. Immunohistochemistry was performed to assess the expression of androgen receptors (AR) and human epidermal growth factor receptor type 2 (HER2). Targeted next‐generation sequencing (T‐NGS) was performed to identify targetable mutations (panel of 50 genes analyzed by Cancer Hotspot Panel, Ion‐Torrent Personal Genome Machine). Mutational analysis of the PTCH1 gene not present in the T‐NGS panel was assessed by Sanger sequencing. A total of 45 cases with available histological samples were identified (35 primary, 10 RM). The most frequent histological type was porocarcinoma (n = 12). Globally, 14 cases (31%) were AR+ (6/10 RM, 60%; 8/35 primary, 23%). HER2 was shown as 2+ in eight of 42 (19%) cases (2/9 RM, 22%; 6/33 primary, 18%). DNA was adequate for T‐NGS analysis in 25 cases. In the majority of cases (17 cases, 68%) at least one mutation in oncogenes or tumor suppressor genes was found: the most frequent ones involved TP.53 (13 cases, 76% of mutated SAC) and PIK3CA (three cases, 18%). The rate of PTCH1 mutation was 30%. These findings support the use of molecular screening in patients with advanced SAC.     

Intraoperative sonography for nonpalpable breast lesions: Additional indications for a consolidate technique

This prospective study evaluated the intraoperative ultrasound scan (IUSS) for nonpalpable breast lesions’ detection. A total of 108 consecutive female patients underwent surgery using IUSS: Frozen sections demonstrated clear margins in 95.5% of neoplastic patients. Only four (4.5%) patients underwent local re‐excision in the same operation. IUSS demonstrated to be quick, accurate, useful, effective, and safe for the intraoperative management of neoplastic nonpalpable breast lesions when performed by a surgeon who has undergone US training, particularly for people in whom alternative approaches can show some limitations due to contraindications or because of scheduling constraints, costs, and patient discomfort.