Functional inhibitory control dynamics in impulse control disorders in Parkinson's disease.

BACKGROUND: Impulse control disorders related to alterations in the mesocorticolimbic dopamine network occur in Parkinson's disease (PD). Our objective was to investigate the functional neural substrates of reward processing and inhibitory control in these patients. METHODS: Eighteen PD patients with impulse control disorders, 17 without this complication, and 18 healthy controls performed a version of the Iowa Gambling Task during functional magnetic resonance scanning under 3 conditions: positive, negative, and mixed feedback. Whole-brain contrasts, regions of interest, time courses, functional connectivity analyses, and brain-behavior associations were examined. RESULTS: PD patients with impulse control disorders exhibited hyperactivation in subcortical and cortical regions typically associated with reward processing and inhibitory control compared with their PD and healthy control counterparts. Time-course analyses revealed that only PD patients with impulse control disorders exhibited stronger signal intensity during the initial versus final periods of the negative-feedback condition in bilateral insula, and right ventral striatum. Interestingly, hyperactivation of all the examined right-lateralized frontostriatal areas during negative feedback was positively associated with impulse control disorder severity. Importantly, positive associations between impulse control disorder severity and regional activations in the right insula and right inferior frontal gyrus, but not the right subthalamic nucleus, were mediated by functional connectivity with the right ventral striatum. CONCLUSIONS: During a reward-based task, PD patients with impulse control disorders showed hyperactivation in a right-lateralized network of regions including the subthalamic nucleus that was strongly associated with impulse control disorder severity. In these patients, the right ventral striatum in particular played a critical role in modulating the functional dynamics of right-lateralized inhibitory-control frontal regions when facing penalties. © 2019 International Parkinson and Movement Disorder Society.

Nigrostriatal dopamine transporter availability, and its metabolic and clinical correlates in Parkinson's disease patients with impulse control disorders.

PURPOSE: Previous studies in patients with Parkinson's disease (PD) and impulse control disorders (ICDs) have produced heterogeneous results regarding striatal dopamine transporter (DaT) binding and activity in the mesocorticolimbic network. Our aim here was to study the relationship between striatal DaT availability and cortical metabolism, as well as motor, behavioural and cognitive features of PD patients with ICD. METHODS: In a group of PD patients with ICD (PD-ICD, n = 16) and 16 matched PD patients without ICD (PD-noICD, n = 16), DaT single-photon emission computed tomography (SPECT) imaging (DaTSCAN) was used to study DaT availability in predefined striatal volumes of interest (VOIs): putamen, caudate nucleus and ventral striatum (VS). In addition, the specific association of striatal DaT binding with cortical limbic and associative metabolic activity was evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PD-ICD patients and investigated using statistical parametric mapping (SPM8). Finally, associations between DaT availability and motor, behavioural and cognitive features were assessed. RESULTS: PD-ICD patients had a significantly lower DaT density in the VS than PD-noICD patients, which was inversely associated with ICD severity. Lower DaT availability in the VS was associated with lower FDG uptake in several cortical areas belonging to the limbic and associative circuits, and in other regions involved in reward and inhibition processes (p < 0.0001 uncorrected; k > 50 voxels). No significant results were observed using a higher conservative threshold (p < 0.05; FDR corrected). PD-ICD patients also displayed impairment in interference and attentional Stroop Task execution, and more anxiety, all associated with reduced DaT availability in the VS and caudate nucleus. CONCLUSIONS: ICDs in PD patients are related to reduced DaT binding in the VS, which accounts for dysfunction in a complex cortico-subcortical network that involves areas of the mesolimbic and mesocortical systems, being associated with reward evaluation, salience attribution and inhibitory control processes.

Anti-TNF-α therapy in the management of severe neurosarcoidosis: a report of five cases from a single centre and literature review.

Neurologic manifestations are found in 5-15 % of patients with sarcoidosis. This granulomatous disease may affect any part of the peripheral or the central nervous system, being potentially severe and difficult to treat. Corticosteroids are the cornerstone of therapy in sarcoidosis. However, some patients become resistant or experience side effects to corticosteroids. In these patients, second line therapies including immunosuppressive drugs such as methotrexate, azathioprine, mycophenolate, cyclophosphamide and leflunomide have been used. Anti-TNF-α drugs have been proposed as a therapeutic option for those who are refractory to immunosuppressive drugs or initially in cases of severe sarcoidosis. We report on 5 patients with neurosarcoidosis treated with anti-TNF-α drugs in our center. A literature review of patients with neurosarcoidosis treated with anti-TNF-α drugs was conducted. In our series successful response to anti-TNF-α therapy was achieved. However, the high frequency of relapses following anti-TNF-α discontinuation makes necessary a close follow-up of these patients when the biologic agent is stopped.

Clinical spectrum of peripheral facial paralysis in HIV-infected patients according to HIV status.

Although peripheral facial palsy is the most common cranial neuropathy in HIV-infected patients, no series have been reported recently in the literature. In this study we reviewed the clinical records of HIV-infected patients with a diagnosis of peripheral facial palsy between 2000 and 2011 attending the Hospital Marqués de Valdecilla (Infectious Diseases Unit), a 900-bed university hospital in northern Spain. We identified eight patients (4 men, 4 women): median CD4 count and viral load were 232 cells per µL and 130,000 RNA copies per mL, respectively. Most of them presented co-morbidities, including hepatitis C virus in 75%, hepatitis B virus in 15% and tuberculosis in 15%. Aetiologies of palsy were varied: idiopathic Bell's palsy predominated at early stages of the disease, whereas secondary causes, such as lymphoma and infections were frequently the cause of paralysis in advanced HIV/AIDS. At early stages of HIV infection, facial palsy is similar, both in aetiology and prognosis, to cases in the general population. However, in advanced stages the palsy is frequently secondary to underlying complications. Clinicians should be aware of these differences to tailor the diagnostic work-up.