Incidence and spatial distribution of adult-onset primary malignant and other central nervous system tumors in Southern Sardinia, Italy.

PURPOSE: To study for the first time the incidence of adult-onset CNS tumors in Southern Sardinia, Italy. METHODS: Clinical records of patients > 18 years old who were diagnosed with primary CNS tumors during 2016-2019 in the study area were reviewed. Meningiomas, cranial/paraspinal nerve tumors, lymphomas, and pituitary tumors were excluded. Cases were classified according to the 2016 WHO classification of CNS tumors and to the morphology codes from the International Classification of Diseases-Oncology, third edition. Age-adjusted incidence rates were calculated by the direct method to the 2011-2020 European standard population. Kulldorff's spatial scan statistic was used to identify geographic clusters of patients who shared increased/decreased tendency to develop CNS tumors. RESULTS: CNS tumors were diagnosed in 234 incident patients, but histological diagnosis was available in 222/234 patients (95%) aged 64.3 ± 13.5 years at diagnosis. Crude incidence rate was 7.1 per 100,000 persons-year (95% CI, 6.2-8.1), 6.2 per 100,000 persons-year (95% CI, 5.4-7.0) when age-adjusted. CNS tumors were more frequent in men and after age 40. Glioblastoma accounted for 76% of the total (adjusted rate, 4.7 per 100,000 persons-year; 95% CI, 4.0-5.4). Spatial analysis revealed geographic variations of glioblastoma incidence within the study area. CONCLUSION: Although the distribution of tumor diagnoses in Sardinia reflects expected age and gender-related patterns in western populations, our findings would indicate a slightly higher incidence of glial tumors, glioblastoma in particular, in Sardinia than in other European countries. The identification of spatial clusters of high/low risk will serve as a resource for etiological research.

Does the network model fits neurophysiological abnormalities in blepharospasm?

Several neurophysiological abnormalities have been described in blepharospasm, including loss of inhibition in sensorimotor pathways at cortical and brainstem level and abnormalities of sensory processing. These changes have traditionally been linked to a basal ganglia dysfunction. However, this interpretation has recently been questioned and alternative pathophysiological model positing that dystonia is a network disorder has been proposed. On the basis of available information, we can speculate that loss of inhibition at cortical and brainstem level and abnormalities of sensory processing in blepharospasm probably reflect the functional derangement of a network involving frontal and parietal cortical areas, basal ganglia, thalamus, and, possibly, the cerebellum.

Role of dopaminergic neurotransmission in pathophysiology of action tremor in Parkinson's disease.

BACKGROUND: Rest tremor (RT), a tremor that occurs in a body part that is completely supported against gravity, is together with rigidity and bradykinesia among the core features of Parkinson's disease (PD). In addition to classical RT, many PD patients also have action tremor (AT) occurring during sustained postures or voluntary movement. Earlier studies showed a good correlation between striatal dopamine transporter (DAT) binding, measured with [(123)I] FP-CIT SPET and bradykinesia. By contrast, neither rigidity nor rest tremor seems to be closely related to the degree of dopaminergic denervation as measured by DAT imaging. Little is known about the relationship, if any, between the severity of action tremor and striatal DAT binding. SUBJECTS AND METHODS: A cross-sectional study was conducted in 94 patients (57 men and 37 women) with Parkinson's disease staging 1-2 on the Hoehn-Yahr scale. Data on the severity of action tremor and other motor signs were collected using the Unified Parkinson's Disease Rating Scale part III. DAT imaging was performed after injection of 111-185MBq of (123)I-FP-CIT. Images were visualized on Workstation Xeleris 3.0 (GE Healthcare) and reconstructed with dedicated software by a nuclear physician blinded about the clinical information of patients. Spearman correlation coefficient was performed to evaluate the relationship between putamen DAT binding and severity of bradykinesia, severity of rigidity, RT and AT respectively. Multivariable logistic regression analysis was used to assess the association between age, sex, disease duration, and levodopa equivalent daily dose and investigated variables after adjusting for possible confounders. RESULTS: In this group of patients with early PD, DAT binding in the putamen significantly correlated with the severity of bradykinesia (Spearman r=-0.35, P<0.001) but not with the severity of rigidity (Spearman r=0.02, P=0.8), RT (Spearman r=0.05, P=0.6), or AT (Spearman r=-0.03, P=0.7). The findings were confirmed by multivariable regression analysis adjusted by age, sex, disease duration, and levodopa equivalent daily dose. CONCLUSION: Our study confirms the good correlation between putamen DAT binding and bradykinesia and the lack of correlation between putamen DAT binding and rigidity/RT. In addition, we failed to found any significant correlation between putamen DAT binding and severity of action tremor, which suggests a contribution of non-dopaminergic mechanisms to its pathophysiology.

Cerebellar continuous theta burst stimulation reduces levodopa-induced dyskinesias and decreases serum BDNF levels.

Patients with Parkinson's Disease (PD) experience bothersome motor fluctuations and Levodopa-induced Dyskinesias (LIDs). Cerebellar continuous theta burst stimulation (cTBS) was used as an inhibitory protocol of repetitive transcranial magnetic stimulation (rTMS) to reduce LIDs in PD patients. The influence of Val66Met polymorphism of Brain Derived Neurotrophic Factor (BDNF) gene on the therapeutic response to cTBS was investigated and the serum levels of BDNF were measured before and after treatment. Eleven patients were exposed to a session of cTBS and sham stimulation (one week apart) after the administration of 125 % of their usual morning dose of Levodopa and LIDs were video-recorded and evaluated at different time points (0, 15, 30, 45, 60, 90 min after Levodopa). Cerebellar cTBS significantly reduced LIDs with respect to sham stimulation and decreased serum BDNF levels. These effects were evident in the Val66Val group (7 subjects) but not in the Val66Met group (4 subjects). These data confirm the efficacy of cerebellar cTBS in reducing LIDs in PD patients and show that the clinical effect is accompanied by a decrease in serum BDNF levels. Moreover, they suggest that BDNF Val66Met polymorphism may influence the clinical and biological response to cTBS.

Sensory trick in upper limb dystonia.

INTRODUCTION: Sensory trick is a specific maneuver that temporarily improves dystonia that is usually observed in 44%-89% of patients with cranial-cervical dystonia and in 20% of patients with upper limb dystonia. This study aimed to assess the prevalence of sensory trick in a cohort of 37 patients with idiopathic adult-onset upper limb dystonia and to determine whether sensory trick can be a useful tool to distinguish dystonic and non-dystonic tremor. METHODS: Thirty-seven right-handed patients with idiopathic upper limb dystonia and disturbed handwriting and 19 patients with non-dystonic action tremor in the upper limb causing writing disturbances participated into the study. Patients were asked to write a standard sentence twice, before and after applying a standardized sensory trick (gently grabbing right wrist with his left hand). Readability of the two sentences was assessed by three observers blinded to diagnosis. RESULTS: Five/37 patients (13%) self-discovered ST over disease history, while performing the standardized trick maneuver improved handwriting in 14/37 patients (38%). Interobserver agreement on the effectiveness of sensory trick among the three observers yielded a kappa value of 0.86 (p < 0.0001). The standardized trick was effective in 8/19 patients with dystonic tremor (42%) and in 0/19 patients with non-dystonic tremor (p = 0.003). CONCLUSION: The results of applying a standardized non-spontaneous trick demonstrated that, in upper limb dystonia, ST may be more frequent than usually observed. Effective sensory trick, when present, may be a hallmark of idiopathic dystonia. The lack of effective sensory trick may help to identify non dystonic upper limb tremor.