Rita Nisticò

Computer-Assisted Cognitive Rehabilitation of Attention Deficits for Multiple Sclerosis: A Randomized Trial With fMRI Correlates

Background. Although a growing body of evidence has highlighted the role of cognitive rehabilitation (CR) in the management of cognitive dysfunctions in multiple sclerosis (MS), there is still no evidence for a validated therapeutic approach. Objective. We propose a new therapeutic strategy characterized by a computer-based intensive attention training program in MS patients with predominant attention deficits. We aim to investigate the effectiveness of our rehabilitation procedure, tailored for those with impaired abilities, using functional magnetic resonance imaging (fMRI). Methods. Using a double-blind randomized controlled study, we enrolled 12 MS patients, who underwent a CR program (experimental group), and 11 age-gender–matched MS patients, who underwent a placebo intervention (control group). fMRI was recorded during the execution of a cognitive task broadly used for assessing attention abilities in MS patients (paced visual serial addition test). Results. Significant effects were detected both at a phenotypic and at an intermediate phenotypic level. After CR, the experimental group, in comparison with the control group, showed a specific enhanced performance in attention abilities as assessed by the Stroop task with an effect size of 0.88, which was associated with increased activity in the posterior cerebellar lobule and in the superior parietal lobule. Conclusions. Our study demonstrates that intensive CR tailored for those with impaired abilities affects neural plasticity and improves some aspects of cognitive deficits in MS patients. The reported neurophysiological and behavioral effects corroborate the benefits of our therapeutic approach, which might have a reliable application in the clinical management of cognitive deficits in MS.

Cognitive deficits in multiple sclerosis patients with cerebellar symptoms

Background Cerebellar dysfunction is common in patients with multiple sclerosis (MS). However, neuropsychological studies of this clinical feature are lacking. Objective We investigate the neuropsychological features in relapsing-remitting MS (RR-MS) patients with and without cerebellar dysfunction. Methods Twenty-one RR-MS patients with cerebellar dysfunction (RR-MSc), characterized by prevalent ataxic gait and nystagmus, and 21 RR-MS patients without any cerebellar manifestation (RR-MSnc) pair-matched for demographical and clinical variables were studied. All patients from each group underwent an extensive battery of neuropsychological tests. Magnetic resonance imaging analysis included hyperintense fast fluid-attenuated inversion-recovery lesion load in the whole brain as well as in the four lobes separately. Results Any significant differences were detected in total and regional lesion load measurements between the two groups. RR-MSc group performed equally as well as the RR-MSnc group on many of the cognitive exploration measures. Nevertheless, the RR-MSc group performed more poorly than the RR-MSnc group on attention tests (Symbol Digit Modalities Test) and verbal fluency tests (Controlled Oral Word Association Test); neither of the test results proved to be affected by regional lesion loads. Conclusion These results highlight the importance of considering cognitive deficits associated with the presence of cerebellar symptoms in RR-MS.

Investigating the role of brain‐derived neurotrophic factor in relapsing–remitting multiple sclerosis

Multiple sclerosis (MS) is a common, heterogeneous disorder of the central nervous system with a complex trait composed of both genetic and environmental factors. Recently, scientific interest has increased in defining factors that possibly contribute to brain functional plasticity; the results might be useful to assess the relationship between MS lesion burden and clinical events, as well as explaining the well‐known phenotypic heterogeneity of the disease. In this study, we explored the effect of the Val66Met brain‐derived neurotrophic factor (BDNF) functional polymorphism on cognitive performances and volumetric measurements obtained by magnetic resonance imaging of the brain in a selected population of relapsing–remitting MS (RRMS) patients, with relatively short disease duration and minimal clinical disability, compared to gender, age and educational‐level matched healthy subjects. We found that in the RRMS group, the BDNF Met‐allele was significantly associated with the lower volume of cerebral grey matter (GM) (P = 0.005). Furthermore, a significant (P = 0.013) interaction effect between ‘MS‐status’ and the BDNF genotype was found for GM volumes, with the result that patients carrying the BDNF Met‐allele showed a higher risk of developing global GM atrophy than the homozygous Val/Val. No BDNF‐related impact on global neuropsychological functions resulted in either RRMS patients or controls. Our data seem to be consistent with the reported influence of BDNF in neuronal plasticity, thus suggesting that the Met‐allele might have a negative prognostic effect on cortical morphometry in RRMS patients.

Temporal lobe epilepsy as a unique manifestation of multiple sclerosis

OBJECTIVE To report on five patients with temporal lobe epilepsy (TLE) as the unique manifestation of multiple sclerosis (MS). METHODS Among 350 consecutive MS patients, we identified 16/350 (4.6%) who also had epileptic seizures. Here, we review their electrophysiological and clinical features. RESULTS Five of these 16 patients (four female, one male; mean age 34.2 years; range 31 to 38) with MS and epileptic seizures had an extremely homogeneous clinical picture characterized by TLE as the unique manifestation of MS, even at long follow-up (mean: five years; range 4 to 10). In all patients, seizures started in the second or third decade. Brain MRI revealed at least one juxta-cortical lesion within the temporal region. Antiepileptic medication was always effective. CONCLUSIONS The present study provides the first evidence of a peculiar form of MS characterized by TLE as the unique manifestation of the disease with no disability or MS relapses at long-term follow-up.

Synchronous pattern distinguishes resting tremor associated with essential tremor from rest tremor of Parkinson’s disease

Rest tremor associated with essential tremor (ET) is a condition that poses challenges in diagnosing Parkinsons disease (PD). We investigated tremor parameters in PD and ET patients with rest tremor. Fifteen patients with PD and 15 patients with ET underwent electrophysiological examination to evaluate characteristics of muscle bursting in rest postures. Rest tremor amplitude of PD patients was significantly higher than that of patients with ET (p = 0.002), whereas burst duration and frequency were significantly higher in ET than in PD group (p = 0.002, p < 0.001, respectively). Patients with PD, however, showed some overlap of these electrophysiological values with values from patients with ET. By contrast, rest tremor pattern showed no overlap between the two diseases, because all patients with ET presented a synchronous pattern whereas PD patients had an alternating pattern (p < 0.001), a finding that differentiated the patients on an individual basis. The electromyographic pattern of rest tremor may help to differentiate PD from ET.

Characterizing structural neural networks in de novo Parkinson disease patients using diffusion tensor imaging.

Parkinson disease (PD) can be considered as a brain multisystemic disease arising from dysfunction in several neural networks. The principal aim of this study was to assess whether large‐scale structural topological network changes are detectable in PD patients who have not been exposed yet to dopaminergic therapy (de novo patients). Twenty‐one drug‐naïve PD patients and thirty healthy controls underwent a 3T structural MRI. Next, Diffusion Tensor Imaging (DTI) and graph theoretic analyses to compute individual structural white‐matter (WM) networks were combined. Centrality (degree, eigenvector centrality), segregation (clustering coefficient), and integration measures (efficiency, path length) were assessed in subject‐specific structural networks. Moreover, Network‐based statistic (NBS) was used to identify whether and which subnetworks were significantly different between PD and control participants. De novo PD patients showed decreased clustering coefficient and strength in specific brain regions such as putamen, pallidum, amygdala, and olfactory cortex compared with healthy controls. Moreover, NBS analyses demonstrated that two specific subnetworks of reduced connectivity characterized the WM structural organization of PD patients. In particular, several key pathways in the limbic system, basal ganglia, and sensorimotor circuits showed reduced patterns of communications when comparing PD patients to controls. This study shows that PD is characterized by a disruption in the structural connectivity of several motor and non‐motor regions. These findings provide support to the presence of disconnectivity mechanisms in motor (basal ganglia) as well as in non‐motor (e.g., limbic, olfactory) circuits at an early disease stage of PD. Hum Brain Mapp 37:4500–4510, 2016.

Magnetic resonance support vector machine discriminates between Parkinson disease and progressive supranuclear palsy

The aim of the current study was to distinguish patients with Parkinson disease (PD) from those with progressive supranuclear palsy (PSP) at the individual level using pattern recognition of magnetic resonance imaging data.

Blink reflex recovery cycle in patients with dystonic tremor: a cross-sectional study

Dystonic tremor (DT) is defined as a postural/kinetic tremor with irregular amplitude and variable frequency occurring in an extremity or body part affected by dystonia.1 Diagnosing this disorder may be challenging because tremor observed in patients suspected of having DT resembles essential tremor (ET), and dystonia may be subtle and difficult to recognize only on clinical grounds. The recovery cycle of the blink reflex (BRrc) is a measure of brainstem …

Structural 'connectomic' alterations in the limbic system of multiple sclerosis patients with major depression

Background: Major depression (MD) is a common psychiatric disorder in multiple sclerosis (MS). Despite the negative impact of MD on the quality of life of MS patients, little is known about its underlying brain mechanisms. Objective: We studied the whole-brain connectivity patterns that were associated with MD in MS. Alterations were mainly expected within limbic circuits. Methods: Diffusion tensor imaging data were collected in 20 MS patients with MD, 22 non-depressed MS patients and 16 healthy controls. We used deterministic tractography and graph analysis to study the white-matter connectivity patterns that characterized MS patients with MD. Results: We found that MD in MS was associated with increased local path length in the right hippocampus and right amygdala. Further analyses revealed that these effects were driven by an increased shortest distance between both the right hippocampus and right amygdala and a series of regions including the dorsolateral and ventrolateral prefrontal cortex, orbitofrontal cortex, sensory-motor cortices and supplementary motor area. Conclusion: Our data provide strong support for neurobiological accounts positing that MD in MS is mediated by abnormal ‘communications’ within limbic circuits. We also found evidence that MD in MS may be linked with connectivity alterations at the limbic-motor interface, a group of regions that translates emotions into survival-oriented behaviors.

Reduced thalamic volume in Parkinson disease with REM sleep behavior disorder: Volumetric study

INTRODUCTION REM sleep behavior disorder (RBD) is a common non motor feature of Parkinsons Disease (PD) affecting about half the patients with this disease. Distinct structural brain tissue abnormalities have been reported in several regions modulating REM sleep of the patients with idiopathic RBD. At the present time, there are no conventional MRI studies investigating patients with PD associated with RBD. METHODS Herein, we used voxel-based morphometry (VBM) to detect the neuroanatomical profile of PD patients with and without RBD. Optimized VBM was applied to the MRI brain images in 11 PD patients with RBD (PD-RBD), 11 PD patients without RBD (PD) and 18 age-and sex-matched controls. To corroborate VBM findings we used automated volumetric method (FreeSurfer) to quantify subcortical brain regions volumes. Patients and controls also underwent DAT-SPECT and cardiac MIBG scintigraphies. RESULTS The VBM analysis showed markedly reduced gray matter volume in the right thalamus of PD-RBD patients in comparison with PD patients and controls. Automatic thalamic segmentation in PD-RBD patients showed a bilaterally reduced thalamic volume as compared with PD patients or controls. All PD patients (with and without RBD) showed a reduced tracer uptake on DAT-SPECT and cardiac MIBG scintigraphies as compared to controls. CONCLUSIONS Our findings suggest that the presence of RBD symptoms in PD patients is associated with a reduced thalamic volume suggesting a pathophysiologic role of the thalamus in the complex circuit causing RBD.