Background and Objectives To determine the relative importance of global or regional MRI and blood markers of neurodegeneration and neuroaxonal injury in predicting cognitive performance for recently diagnosed patients with multiple sclerosis (MS). Methods Thirty-five newly diagnosed patients with relapsing-remitting MS (RRMS) and 23 healthy controls (HCs) simultaneously completed a full clinical and neuropsychological assessment, structural brain MRI, and serum neurofilament light chain (sNfL) level test. Linear regression analyses were performed to determine which global or regional measures of gray matter (GM) atrophy and cortical thickness (CT), in combination with sNfL levels and clinical scores, are most strongly related to neuropsychological impairment. Results Compared with HCs, patients with MS showed bilateral thalamic GM atrophy (left, p = 0.033; right, p = 0.047) and diminished CT, particularly in the right superior and transverse temporal gyri (p = 0.045; p = 0.037). Regional atrophy failed to add predictive variance, whereas anxiety symptoms, sNfL, and global CT were the best predictors (R² = 0.404; p < 0.001) of cognitive outcomes, with temporal thickness accounting for greater variance in cognitive deficits than global CT. Discussion Thalamic GM atrophy and thinning in temporal regions represent a distinctive MRI trait in the early stages of MS. Although sNfL levels alone do not clearly differentiate HCs and patients with RRMS, in combination with global and regional CT, sNfL levels can better explain the presence of underlying cognitive deficits. Hence, cortical thinning and sNfL increases can be considered 2 parallel neurodegenerative markers in the pathogenesis of progression in newly diagnosed patients with MS.

Background. Neuropsychiatric symptoms (NPS) are a common and potentially serious manifestation of Parkinsons disease (PD) but are frequently overlooked in favor of a focus on motor symptomatology. Here, we conducted a literature review of the prevalence and type of NPS experienced by PD patients with a clinically defined course of their illness. Methods. We identified reports of NPS in patients with PD and mean disease duration over 3 years. Three databasesPubMed, Scopus, and Dialnetwere searched for relevant literature published between 2010 and 2020. Predefined exclusion criteria were applied prior to a descriptive analysis of the literature base. Results. In all, 87 unique reports were identified and 30 met inclusion and exclusion criteria. These included 7142 patients with PD (male: 67.3; mean age: 66.2 years; mean disease duration: 6.7 years). The most frequent NPS were mood disorders (apathy, depression, and anxiety), psychosis, and impulse control disorders (ICD). Treatment with dopamine agonists was identified as an important risk factor for ICD. Co-occurrence of NPS and cognitive dysfunction was also evidenced in a number of studies. Patients with more significant cognitive deficits and higher levels of NPS appeared to be of older age with a longer disease duration and to have more severe motor symptoms. Conclusions. NPS, most commonly mood disorders (apathy, depression, and anxiety), psychosis, and ICDs are frequent manifestations of PD. The results of this review reflect the need to develop unified validated assessment protocols for NPS in PD, as well as to improve their management in clinical practice.

This study aimed to examine the presence of neuropsychological deficits and their relationships with clinical, pharmacological, and neuropsychiatric characteristics in chronic migraine (CM) patients assessed during a headache-free period. We enrolled 39 CM patients (mean age: 45.4 years; male/female ratio: 3/36) and 20 age-, sex-, and education-matched healthy controls (HCs, mean age: 45.5 years; male/female ratio: 2/18) in a case–control study. All CM patients underwent a full and extensive clinical, neuropsychiatric, and neuropsychological evaluation to evaluate cognitive domains, including sustained attention (SA), information processing speed (IPS), visuospatial episodic memory, working memory (WM), and verbal fluency (VF), as well as depressive and anxiety symptoms. CM patients exhibited higher scores than HCs for all clinical and neuropsychiatric measures, but no differences were found in personality characteristics. Although more than half of the CM patients (54%) showed mild-to-severe neuropsychological impairment (NI), with the most frequent impairments occurring in short- and long-term verbal episodic memory and inhibitory control (in approximately 90% of these patients), almost half of the patients (46%) showed no NI. Moreover, the severity of NI was positively associated with the number of pharmacological treatments received. Remarkably, disease-related symptom severity and headache-related disability explained global neuropsychological performance in CM patients. The presence of cognitive and neuropsychiatric dysfunction during the interictal phase occurred in more than half of CM patients, increasing migraine-related disability and possibly exerting a negative impact on health-related quality of life and treatment adherence.

Introduction Cortico-subcortical dysfunction from dopaminergic depletion is a hallmark of Parkinson’s disease (PD). Modulating primary motor cortex (M1) excitability with intermittent theta burst stimulation (iTBS) may restore network integrity in PD by targeting neurobiological changes at excitatory, structural, and serological levels. This study aimed to demonstrate the clinical and neurobiological effects of bilateral M1 iTBS in patients with PD. Methods Seventeen patients with Hoehn-Yahr stage II–III PD in the on-medication state underwent daily bilateral M1 iTBS sessions for 5 consecutive days in a randomized, double-blind, placebo-controlled, crossover design. The primary clinical outcomes were the relative change from baseline at four follow-up points after the final iTBS session, measured by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II, III, and IV. Changes in corticospinal excitability, structural brain imaging, and serum biomarkers of neurodegeneration, astrocytic activation, and neuroplasticity were also assessed. Results Real iTBS induced a significant improvement in MDS-UPDRS Part III scores, yielding more than twice the therapeutic benefit observed with sham stimulation. Responders (> 20% improvement) showed a mean 9-point improvement. Similarly, real iTBS stimulation resulted in an increase in corticospinal excitability of the clinically most affected hemisphere. In responders, serum brain-derived neurotrophic factor levels increased along with an increase in left ventral diencephalon volume, which was the strongest predictor of clinical response. Conclusion Bilateral M1 iTBS may represent a valuable adjunctive therapeutic option for pharmacological treatment of motor symptoms in patients with PD by promoting structural brain changes and enhancing synaptic plasticity in intermediate disease stages. Clinical Trial Registration https://clinicaltrials.gov/: NCT06840145, retrospectively registered on September 9, 2023.