The aim of our study was to investigate two inter-related hypotheses about the role of the subthalamic nucleus. First that the subthalamic nucleus plays a role in adjusting response thresholds and speed-accuracy trade-offs and second that it is involved in reactive and proactive inhibition and conflict resolution. These were addressed by comparing the performance of 10 patients with Parkinson's disease treated with right subthalamotomy and 12 patients with left subthalamotomy, to 14 unoperated patients with Parkinson's disease and 23 age-matched healthy control participants on a conditional stop signal task and applying the drift diffusion model. Unilateral subthalamotomy significantly improved Parkinson's disease motor signs. Patients with right subthalamotomy had significantly faster Go reaction times with their contra-lesional hand than the unoperated patients and did not differ from the control participants, indicating their speed of response initiation was 'normalized'. However, operated patients made significantly more discrimination errors than unoperated patients and controls, suggesting that subthalamotomy influenced speed-accuracy trade-offs. This was confirmed by the drift diffusion model, revealing that while the unoperated patients had significantly lower drift rate and higher response thresholds than the control participants, the response thresholds for the operated groups did not differ from the controls and the patients with right subthalamotomy had a significantly higher drift rate than unoperated patients and similar to that of controls. The drift diffusion model further established that unlike the control participants, operated patients failed to show context-dependent strategic modulation of response thresholds. The patients with right subthalamotomy could not engage in late phase, fast inhibition of the response and showed minimal proactive inhibition when tested with the contra-lesional hand. These results provide strong evidence that the subthalamic nucleus is involved in response inhibition, in modulating the rate of information accumulation and the response threshold and influencing the balance between speed and accuracy of performance. Accordingly, the subthalamic nucleus can be considered a key component of the cerebral inhibitory network.
Zolpidem is a non-benzodiazepine drug used for the therapy of insomnia, which has selectivity for stimulating the effect of GABA-A receptors. Recently, a paradoxical arousing effect of zolpidem in patients with severe brain damage has been repeatedly reported.
The present paper shows the result of an open prospective study performed to evaluate the tolerance and efficacy of a program for neurological restoration (PRN) in stroke patients. The PRN is organized 4 weeks cycles - 39 hours per week - and applied by a team of physical, occupational, and speech therapists, physiatrists, psychologists, clinicians and nurses; directed by a neurologist. The first phase of treatment aims to increase the physical capacity and tolerance to exercise. The second phase trains specific abilities (balance, posture, gait and handling). Drugs were only used to modulate physical or mood disorders, spasticity, or pain. The study was performed in 80 stroke patients attended in our institution (2005-2007). Only patients with a confirmed diagnosis of stroke in the carotid territories, over 15 years old, and not least than 6 months post-ictal evolution were included. Tolerance to treatment was very good, with only 4 adverse events not related to treatment. The neurological condition was evaluated using the Scandinavian Stroke Scale (SSS), and the functional condition using the Barthel Index (BI). The results show significant improvements both in the neurological (113.45 ± 1.59%) and functional (130.11 ± 5.17%) condition after one treatment cycle, which improved further when therapy continued for a second cycle (233.71 ± 7.76% and 207.62 ± 27.16% respectively). Severity of the impairment was not a negative predictor of the outcome. Age correlated negatively with the initial condition, but does not prevent improvement. Sex, time of evolution, affected hemisphere or interactions among them did not influence the outcome. These results demonstrate that the PRN is well tolerated and effective promoting recovery even in chronic stroke patients.
Recent imaging studies in healthy controls with a conditional stop signal reaction time (RT) task have implicated the subthalamic nucleus (STN) in response inhibition and the pre-supplementary motor area (pre-SMA) in conflict resolution. Parkinsons disease (PD) is characterized by striatal dopamine deficiency and overactivity of the STN and underactivation of the pre-SMA during movement. We used the conditional stop signal RT task to investigate whether PD produced similar or dissociable effects on response initiation, response inhibition and response initiation under conflict. In addition, we also examined inhibition of prepotent responses on three cognitive tasks: the Stroop, random number generation and Hayling sentence completion. PD patients were impaired on the conditional stop signal reaction time task, with response initiation both in situations with or without conflict and response inhibition all being significantly delayed, and had significantly greater difficulty in suppressing prepotent or habitual responses on the Stroop, Hayling and random number generation tasks relative to controls. These results demonstrate the existence of a generalized inhibitory deficit in PD, which suggest that PD is a disorder of inhibition as well as activation and that in situations of conflict, executive control over responses is compromised.
The authors report a case of a 55-year-old Caucasian woman who received autologous bone marrow stem cell transplantation 3 years after a subcortical stroke. She exhibited positive cognitive changes 6 months and 1 year after the surgery without rehabilitation. The blood flow changes, measured with SPECT, were statistical significant in prefrontal areas. During the presurgical neuropsychological assessment, the patient presented a critical speech reduction, reflected in impaired performance in verbal fluency, vocabulary and in each task which required overt verbal response. One year later, she showed improvement in mental flexibility, receptive language, phonological fluency, verbal memory and auditory verbal memory. Positive cognitive changes in verbal and executive functions seem to be contingent on increased blood flow in prefrontal areas. Posterior neuropsychological evaluation 3 and 5 years after transplantation did not show deterioration of the cognitive improvement.
Since the advent of deep brain stimulation (DBS) for the treatment of Parkinsons disease (PD), subsequent cognitive and neuropsychiatric effects of this procedure have become well-chronicled. Yet, thermolitic lesion of the subthalamic nucleus (STN) is still a valid option when DBS cannot be applied, and little has been published regarding its impact on cognition and mood. We examined the cognitive and neuropsychiatric functions of 10 consecutive patients with advanced PD undergoing simultaneous bilateral subthalamotomies. With 24 months of follow-up, the patients, three of whom were on anticholinergics prior to surgery, showed no deterioration in cognitive assessments including verbal fluency. Hypoactive behaviors (depression and apathy) showed lasting improvement, while hyperactive behaviors (euphoria and disinhibition) transiently increased after surgery. Improvement in hypoactive behaviors correlated with improvement in hypokinetic movements, and enhanced hyperactive behaviors followed the course of post-operative hyperkinetic movements. Such correlations may support the role of the STN in modulating limbic connections between the basal ganglia and frontal cortex. The results of this proof-of-concept pilot study suggest the need for larger, long-term, randomized controlled studies to assess motor, neuropsychiatric, behavioral and radiologic correlations after subthalamotomies.
Changes of cognitive function in PD have been extensively documented and defined as a frontal type executive dysfunction. One of the main components of this executive dysfunction is the impairment of verbal fluency. The aim of the present study was to assess semantic and phonemic fluency in a large sample of PD patients and to investigate the effect of clinical and sociodemographic variables on verbal fluency in this patient group. Three hundred patients with idiopathic Parkinsons disease who were consecutive referrals to our clinic and 50 age and education matched healthy controls completed the phonemic and semantic verbal fluency tasks. Both phonemic and semantic verbal fluency were significantly impaired in PD patients relative to matched controls. Stage of illness, presence of depression, education and age influenced verbal fluency measures. Regression analyses established that global measures of cognitive ability (MMSE) and executive function (FAB) and side of onset of motor symptoms predicted 36-37% of variance of phonemic or semantic verbal fluency measures. Thus, future studies aimed at assessing cognitive functioning in PD patients treated by deep brain stimulation (DBS) should adequately take into account several factors (stage of illness, depression, executive functioning) which may potentially influence performance on verbal fluency tasks.
The purpose of this study was to assess the effectiveness of a quality improvement (QI) plan aimed at primary healthcare teams (PHCTs) to optimise hypertension control and to compare it with standard clinical care.
Periodic leg movements (PLMs) are a common sleep disorder in spinocerebellar ataxia type 2 (SCA2) being associated to higher disease severity and altered sleep patterns. To assess the efficacy and safety of lisuride for the treatment of PLMs in SCA2 patients, an open-label clinical trial was conducted in 12 SCA2 patients suffering from PLMs associated to other subjective sleep complaints. All subjects received 0.1 mg of oral lisuride daily for 4 weeks. Primary outcome measure was the change of PLMs index. Changes in the subjective sleep quality, other polysomnographical sleep parameters, Scale for the Assessment and Rating of Ataxia score, and saccadic velocity were assessed as secondary outcome parameters. Safety assessments included hemoglobin, hematocrit, cholesterol, creatinine, and TGP. A significant decrease in both the PLMs index and R stage latency were observed during the treatment, associated to subjective improvement of frequent awakenings, early insomnia, restless leg syndrome, and nocturnal limb paresthesias in most cases. Ataxia score and saccadic pathology were unchanged. No significantly adverse events were observed. Our study suggests the efficacy of dopamine agonist therapy in the treatment of PLMs in SCA2, improving various subjective sleep complaints. These findings serve to promote the adequate management of sleep-related disorders in SCA2, which could improve the life quality of the patients.
Recombinant human erythropoietin is used primarily to treat anemia. There is evidence of its neuroprotective capacity from preclinical studies in Parkinsons disease and other neurodegenerative diseases. Recombinant human erythropoietin produced in Cuba (ior-EPOCIM) is registered and approved for use in humans in Cuba and in a number of other countries.
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