pinecone/core-2020-05-10-deduplication huggingface dataset:
Epoetin alfa increases frataxin production in Friedreich's ataxia without affecting hematocrit.

Objective of the study was to test the efficacy, safety, and tolerability of two single doses of Epoetin alfa in patients with Friedreich's ataxia. Ten patients were treated subcutaneously with 600 IU/kg for the first dose, and 3 months later with 1200 IU/kg. Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale. Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted. In addition, no hemoglobin increase was observed, and none of our patients required phlebotomy, indicating lack of erythropoietic effect of single high dose of erythropoietin. © 2010 Movement Disorder Society
Increased cortical hyperexcitability and exaggerated myoclonus with aging in benign adult familial myoclonus epilepsy.

The clinical implications of enlarged early cortical components of somatosensory evoked potentials in benign adult familial myoclonus epilepsy remain unknown. Somatosensory evoked potentials following electrical stimulation of the median nerve at the wrist were studied in 16 patients with a clinical diagnosis of benign adult familial myoclonus epilepsy (7 men and 9 women; mean age, 51 ± 18 years) and 19 age-matched apparently healthy control subjects (11 men and 8 women; mean age, 49 ± 18 years). Giant somatosensory evoked potentials were observed in 13 of the 16 patients. P25 and N35 amplitudes in the patient group were 11.4 ± 6.1 and 19.2 ± 11.5 μV, respectively, and both were significantly larger compared with those in control subjects (P = 0.008 for P25 and P < 0.0001 for N35). There was a significant positive relationship between age at somatosensory evoked potential examination and N20, P25, and N35 amplitudes, both in the patient and in the control groups (P < 0.05). The linear regression gradient of the N35 amplitude with respect to age was significantly larger in the patient group than in the control group (P = 0.04). Furthermore, regression analysis showed a significant positive relationship between the myoclonus rating scale and age at time of somatosensory evoked potential examination (R = 0.645, P = 0.007). Somatosensory evoked potential amplitude increased with age in patients with benign adult familial myoclonus epilepsy to a greater extent than in the control subjects, which suggests a progressive increase in cortical excitability based on progressive pathophysiology in benign adult familial myoclonus epilepsy
Transcranial direct current stimulation for the treatment of focal hand dystonia.

The treatment of writer's cramp, a task-specific focal hand dystonia, needs new approaches. A deficiency of inhibition in the motor cortex might cause writer's cramp. Transcranial direct current stimulation modulates cortical excitability and may provide a therapeutic alternative. In this randomized, double-blind, sham-controlled study, we investigated the efficacy of cathodal stimulation of the contralateral motor cortex in 3 sessions in 1 week. Assessment over a 2-week period included clinical scales, subjective ratings, kinematic handwriting analysis, and neurophysiological evaluation. Twelve patients with unilateral dystonic writer's cramp were investigated; 6 received transcranial direct current and 6 sham stimulation. Cathodal transcranial direct current stimulation had no favorable effects on clinical scales and failed to restore normal handwriting kinematics and cortical inhibition. Subjective worsening remained unexplained, leading to premature study termination. Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp
Long-term neuroprotection and neurorestoration by glial cell-derived neurotrophic factor microspheres for the treatment of parkinson's disease

BACKGROUND:
Glial cell-derived neurotrophic factor is a survival factor for dopaminergic neurons and a promising candidate for the treatment of Parkinson's disease. However, the delivery issue of the protein to the brain still remains unsolved. Our aim was to investigate the effect of long-term delivery of encapsulated glial cell-derived neurotrophic factor within microspheres.
METHODS:
A single dose of microspheres containing 2.5 μg of glial cell-derived neurotrophic factor was implanted intrastriatally in animals 2 weeks after a 6-hydroxydopamine lesion.
RESULTS:
The amphetamine test showed a complete behavioral recovery after 16 weeks of treatment, which was maintained until the end of the study (week 30). This effect was accompanied by an increase in dopaminergic striatal terminals and neuroprotection of dopaminergic neurons.
CONCLUSIONS:
The main achievement was the long-term neurorestoration in parkinsonian animals induced by encapsulated glial cell-derived neurotrophic factor, suggesting that microspheres may be considered as a means to deliver glial cell-derived neurotrophic factor for Parkinson's disease treatment. © 2011 Movement Disorder Society
Long term clinical disease progression in patients with Parkinson’s disease after STN Deep Brain Stimulation

<p>Background: Parkinson&rsquo;s disease (PD) is a progressive neurodegenerative disorder with severe longterm impact on patients, their caregivers and on the society in general [1]. The treatment of PD is symptomatic. Surgical treatment with chronic high frequency stimulation of the subthalamic nuclei (STN-DBS) has been shown to provide long term symptom relief with few complications in selected patients with PD [2-4].</p>
<p>Aim: The aim of the thesis has been to elucidate the long-term effects of STN-DBS on the development of clinical symptoms in PD.</p>
<p>Materials and methods: All PD patients treated with STN-DBS between 2001-2007 at Rikshospitalet (N=144) and at Stavanger University Hospital (N=28) were prospectively followed with standardized examinations, and all 172 STN-DBS operated PD patients were included in the scientific material for the thesis. As reference we used the patients from a population-based prevalence study conducted with patient recruitment between September 1992 and May 1993, before STN-DBS was available.</p>
<p>Results: We confirm that STN-DBS surgery can be performed with good and stable long time results on dopaminergic motor symptoms. Perioperative mortality was low and the rate of major adverse events low. The non-motor features of PD seem to develop independently of intervention with STN-DBS, as do FOG and falls. Fatigue is observed to develop at a high rate in STN-DBS operated patients after the first year postoperatively.</p>
<p>Conclusions and implications: STN-DBS is a very good treatment option for motor symptoms in selected patients with advanced PD. The benefits of the treatment are limited to motor symptom control as the underlying PD pathology continues to develop in operated patients similar to the natural history of PD. Fatigue seem to develop at a high rate in STN-DBS operated patients after the first year postoperatively. Our findings are relevant to advising patients both about the indication for, and the timing of, STN-DBS surgery in PD</p
Nonmotor versus motor symptoms: How much do they matter to health status in Parkinson's disease?

Evidence suggests that both motor and nonmotor symptoms contribute to health status in Parkinson's disease. Less clear is how much change in health status can be expected if these clinical variables change. In addition, anxiety, separate from depression, has rarely been examined as a predictor of health status. We used hierarchical multiple regression analysis and standardized beta coefficients in a prevalent cohort of 462 patients with Parkinson's disease to explore the relative impact on health status (measured using the Parkinson's Disease Questionnaire) of 5 well-recognized symptom domains in Parkinson's disease: motor signs, depression, anxiety, cognition, and other nonmotor symptoms. In the health status scores, 19.6% of variance was explained by age, number of comorbidities, disease duration, and levodopa equivalent dose. Younger age predicted worse health status. A full regression model containing baseline variables and all 5 symptom domains explained 56% of the variance in health status. The standardized beta coefficient for depression was 2.1, 1.6, and 1.3 times that of motor signs, anxiety, and other nonmotor symptoms, respectively. Our findings provide a ranking order of clinical variables for their relative impact on health status in Parkinson's disease and show that depression has more than twice the impact of motor signs on health status. Anxiety and other nonmotor symptoms are also important separate determinants of poor health status in Parkinson's disease. Our results will help to guide the development of individual care and service planning for patients with Parkinson's disease
Doorway-provoked freezing of gait and its treatment in Parkinson’s disease.

Freezing of gait in Parkinson's disease can be difficult to study in the laboratory. Here we investigate the use of a variable-width doorway to provoke freeze behavior together with new objective methods to measure it. With this approach we compare the effects of anti-parkinsonian treatments (medications and deep-brain stimulation of the subthalamic nucleus) on freezing and other gait impairments. Ten “freezers” and 10 control participants were studied. Whole-body kinematics were measured while participants walked at preferred speed in each of 4 doorway conditions (no door present, door width at 100%, 125%, and 150% of shoulder width) and in 4 treatment states (offmeds/offstim, offmeds/onstim, onmeds/offstim, onmeds/onstim). With no doorway, the Parkinson's group showed characteristic gait disturbances including slow speed, short steps, and variable step timing. Treatments improved these disturbances. The Parkinson's group slowed further at doorways by an amount inversely proportional to door width, suggesting a visuomotor dysfunction. This was not improved by either treatment alone. Finally, freeze-like events were successfully provoked near the doorway and their prevalence significantly increased in narrower doorways. These were defined clinically and by 2 objective criteria that correlated well with clinical ratings. The risk of freeze-like events was reduced by medication but not by deep-brain stimulation. Freeze behavior can be provoked in a replicable experimental setting using the variable-width doorway paradigm, and measured objectively using 2 definitions introduced here. The differential effects of medication and deep-brain stimulation on the gait disturbances highlight the complexity of Parkinsonian gait disorders and their management
Freezing in PD: a generic motor deficit

Freezing of gait (FOG) is an incapacitating problem in Parkinson's disease that is difficult to manage therapeutically. We tested the hypothesis that impaired rhythm and amplitude control is a common mechanism of freezing which is also present during other rhythmic tasks. Therefore, we compared the occurrence and spatiotemporal profiles of freezing episodes during upper limb motion, lower limb motion, and FOG. Eleven freezers, 12 non-freezers, and 11 controls performed a rhythmic bilateral finger movement task. The triggering effect of movement speed, amplitude, and coordination pattern was evaluated. Regression slopes and spectral analysis addressed the spatial and temporal kinematic changes inherent to freezing episodes. The FOG Questionnaire score significantly predicted severity of upper limb freezing, present in 9 freezers, and of foot freezing, present in 8 freezers. Similar to gait, small-amplitude movements tended to trigger upper limb freezing, which was preceded by hastened movement and a strong amplitude breakdown. Upper limb freezing power spectra were broadband, including increased energy in the "freeze band" (3-8 Hz). Contrary to FOG, unilateral upper limb freezing was common and occurred mainly on the disease-dominant side. The findings emphasize that a core motor problem underlies freezing which can affect various movement effectors. This deficit may originate on the disease-dominant body side and interfere with amplitude and timing regulation during repetitive limb movements. These results may shift current thinking on the origins of freezing as being not exclusively a gait failure. © 2011 Movement Disorder Society.status: publishe
Comparison of enrollees and decliners of Parkinson disease sham surgery trials

Concerns have been raised that persons with serious illnesses participating in high‐risk research, such as PD patients in sham surgery trials, have unrealistic expectations and are vulnerable to exploitation. A comparison of enrollees and decliners of such research may provide insights about the adequacy of decision making by potential subjects. We compared 61 enrollees and 10 decliners of two phase II neurosurgical intervention (i.e., cellular and gene transfer) trials for PD regarding their demographic and clinical status, perceptions and attitudes regarding research risks, potential direct benefit, and societal benefit, and perspectives on the various potential reasons for and against participation. In addition to bivariate analyses, a logistic regression model examined variables regarding risks and benefits as predictors of participation status. Enrollees perceived lower risk of harm while tolerating higher risk of harm and were more action oriented, but did not have more advanced disease. Both groups rated hope for benefit as a strong reason to participate, whereas the fact that the study's purpose was not solely to benefit them was rated as “not a reason” against participation. Hope for benefit and altruism were rated higher than expectation of benefit as reasons in favor of participation for both groups. Enrollees and decliners are different in their views and attitudes toward risk. Although both are attracted to research because of hopes of personal benefit, this hope is clearly distinguishable from an expectation of benefit and does not imply a failure to understand the main purpose of research. © 2012 Movement Disorder Societ
The effects of auditory startle and nonstartle stimuli on step initiation in Parkinson's disease

[Abstract] Background. Auditory external cues enhance step initiation in Parkinson's disease (PD) patients. We wanted to explore whether a startle reaction has a comparable effect on step initiation in PD.
Methods. Thirteen PD patients and 13 aged-matched controls participated in this study. Electromyography pattern and onset toe-off time during a step initiation task were recorded in response to three different stimuli: a visual imperative stimulus; visual stimulus simultaneous with a nonstartle auditory stimulus and with a startle auditory stimulus.
Results. In all subjects, onset of tibialis anterior was faster in the startle auditory condition, compared with the nonstartle auditory condition. However, in the patient group, there was no difference in onset of soleus and toe-off between the startle and nonstartle conditions.
Conclusions. Startle reaction in PD patients demonstrates a disordered coupling between the anticipatory postural adjustments that initiate the weight shift and the movement to initiate toe-off during step initiation.Ministerio de Ciencia e Innovación, Spain (PSI2008-03175
Psychogenic Facial Movement Disorders: Clinical Features and Associated Conditions

The facial phenotype of psychogenic movement disorders has not been fully characterized. Seven tertiary-referral movement disorders centers using a standardized data collection on a computerized database performed a retrospective chart review of psychogenic movement disorders involving the face. Patients with organic forms of facial dystonia or any medical or neurological disorder known to affect facial muscles were excluded. Sixty-one patients fulfilled the inclusion criteria for psychogenic facial movement disorders (91.8% females; age: 37.0 ± 11.3 years). Phasic or tonic muscular spasms resembling dystonia were documented in all patients most commonly involving the lips (60.7%), followed by eyelids (50.8%), perinasal region (16.4%), and forehead (9.8%). The most common pattern consisted of tonic, sustained, lateral, and/or downward protrusion of one side of the lower lip with ipsilateral jaw deviation (84.3%). Ipsi- or contralateral blepharospasm and excessive platysma contraction occurred in isolation or combined with fixed lip dystonia (60.7%). Spasms were reported as painful in 24.6% of cases. Symptom onset was abrupt in most cases (80.3%), with at least 1 precipitating psychological stress or trauma identified in 57.4%. Associated body regions involved included upper limbs (29.5%), neck (16.4%), lower limbs (16.4%), and trunk (4.9%). There were fluctuations in severity and spontaneous exacerbations and remissions (60%). Prevalent comorbidities included depression (38.0%) and tension headache (26.4%). Fixed jaw and/or lip deviation is a characteristic pattern of psychogenic facial movement disorders, occurring in isolation or in combination with other psychogenic movement disorders or other psychogenic features. © 2012 Movement Disorder Societ
Head-pelvis coupling is increased during turning in patients with Parkinson's disease and freezing of gait

Turning is the most important trigger for freezing of gait (FOG). The aim of this study was to investigate the relationship between impaired head-pelvis rotation during turning and FOG. Head, trunk, and pelvic rotation were measured at onset and throughout a 180-degree turn in 13 freezers and 14 nonfreezers (OFF medication). We also studied 14 controls at preferred and slow speed to investigate the influence of turn velocity on axial rotation. Location and duration of FOG episodes were defined during the turn. At turning onset, head rotation preceded thorax and pelvic rotation in all groups, but this craniocaudal sequence disappeared when FOG occurred. Maximum head-pelvis separation was significantly greater in controls, compared to freezers and nonfreezers (35.4 versus 25.7 and 27.3 degrees; P < 0.01), but this finding was speed dependent. Timing of maximum head-pelvis separation was delayed in freezers, compared to nonfreezers and controls, irrespective of turn velocity. This delay was correlated with increased neck rigidity (R = 0.62; P = 0.02) and worsened during FOG trials. FOG occurred more often at the end of the turn, when difference in rotation velocity between head and pelvis was greatest. Even after controlling for speed and disease severity, turning in freezers was characterized by delayed head rotation and a closer coupling between head and pelvis, especially in turns where FOG occurred. These changes may be attributed to delayed preparation for the change in walking direction and, as such, contribute to FOG. © 2013 Movement Disorder Society.status: publishe
Imaging: What can it tell us about parkinsonian gait?

Functional neuroimaging has provided new tools to study cerebral gait control in Parkinson's disease (PD). First, imaging of blood flow functions has identified a supraspinal locomotor network that includes the (frontal) cortex, basal ganglia, brainstem tegmentum, and cerebellum. These studies also emphasize the cognitive and attentional dependency of gait in PD. Furthermore, gait in PD and related syndromes like progressive supranuclear palsy may be associated with dysfunction of the indirect, modulatory prefrontal–subthalamic–pedunculopontine loop of locomotor control. The direct, stereotyped locomotor loop from the primary motor cortex to the spinal cord with rhythmic cerebellar input appears to be preserved and may contribute to the unflexible gait pattern in parkinsonian gait. Second, neurotransmitter and proteinopathy imaging studies are beginning to unravel novel mechanisms of parkinsonian gait and postural disturbances. Dopamine displacement imaging studies have shown evidence for a mesofrontal dopaminergic shift from a depleted striatum in parkinsonian gait. This may place additional burden on other brain systems mediating attention functions to perform previously automatic motor tasks. For example, our preliminary cholinergic imaging studies suggest significant slowing of gait speed when additional forebrain cholinergic denervation occurs in PD. Cholinergic denervation of the pedunculopontine nucleus and its thalamic projections have been associated with falls and impaired postural control. Deposition of β‐amyloid may represent another non‐dopaminergic correlate of gait disturbance in PD. These findings illustrate the emergence of dopamine non‐responsive gait problems to reflect the transition from a predominantly hypodopaminergic disorder to a multisystem neurodegenerative disorder involving non‐dopaminergic locomotor network structures and pathologies. © 2013 International Parkinson and Movement Disorder Societ
Emerging common molecular pathways for primary dystonia

The dystonias are a group of hyperkinetic movement disorders whose principal cause is neuron dysfunction at 1 or more interconnected nodes of the motor system. The study of genes and proteins that cause familial dystonia provides critical information about the cellular pathways involved in this dysfunction, which disrupts the motor pathways at the systems level. In recent years study of the increasing number of  DYT  genes has implicated a number of cell functions that appear to be involved in the pathogenesis of dystonia. A review of the literature published in English‐language publications available on PubMed relating to the genetics and cellular pathology of dystonia was performed. Numerous potential pathogenetic mechanisms have been identified. We describe those that fall into 3 emerging thematic groups: cell‐cycle and transcriptional regulation in the nucleus, endoplasmic reticulum and nuclear envelope function, and control of synaptic function. © 2013  Movement  Disorder Societ
Rivastigmine is associated with restoration of left frontal brain activity in Parkinson\u27s disease

The objective of this study was to investigate how acetylcholinesterase inhibitor (ChEI) treatment affects brain function in Parkinson\u27s disease (PD). Twelve patients with PD and either dementia or mild cognitive impairment underwent task-free functional magnetic resonance imaging before and after 3 months of ChEI treatment and were compared with 15 age- and sex-matched neurologically healthy controls. Regional spontaneous brain activity was measured using the fractional amplitude of low-frequency fluctuations. At baseline, patients showed reduced spontaneous brain activity in regions important for motor control (eg, caudate, supplementary motor area, precentral gyrus, thalamus), attention and executive functions (eg, lateral prefrontal cortex), and episodic memory (eg, precuneus, angular gyrus, hippocampus). After treatment, the patients showed a similar but less extensive pattern of reduced spontaneous brain activity relative to controls. Spontaneous brain activity deficits in the left premotor cortex, inferior frontal gyrus, and supplementary motor area were restored such that the activity was increased posttreatment compared with baseline and was no longer different from controls. Treatment-related increases in left premotor and inferior frontal cortex spontaneous brain activity correlated with parallel reaction time improvement on a test of controlled attention. PD patients with cognitive impairment show numerous regions of decreased spontaneous brain function compared with controls, and rivastigmine is associated with performance-related normalization in the left frontal cortex function