An MRI time course of 512 echo-planar images (EPI) in resting human brain obtained every 250 ms reveals fluctuations in signal intensity in each pixel that have a physiologic origin. Regions of the sensorimotor cortex that were activated secondary to hand movement were identified using functional MRI methodology (FMRI). Time courses of low frequency (< 0.1 Hz) fluctuations in resting brain were observed to have a high degree of temporal correlation (P < 10(-3)) within these regions and also with time courses in several other regions that can be associated with motor function. It is concluded that correlation of low frequency fluctuations, which may arise from fluctuations in blood oxygenation or flow, is a manifestation of functional connectivity of the brain.

Functional connectivity in the motor cortex of resting human brain using echo-planar MRI.

Objective: Parkinson’s disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. Methods: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included “Parkinson’s disease”, “diagnosis” and “signs and symptoms”. Results: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. Conclusions: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

https://jnnp.bmj.com/content/jnnp/79/4/368.full.pdf

Parkinson’s disease: clinical features and diagnosis

This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances.

/pdf/mds-clinical-diagnostic-criteria-for-parkinson-s-disease-74dzuucoq6.pdf

MDS clinical diagnostic criteria for Parkinson's disease

Measuring Health: A Guide to Rating Scales and Questionnaires

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

/pdf/a-randomized-trial-of-deep-brain-stimulation-for-parkinson-s-40jf18b006.pdf

A Randomized Trial of Deep-Brain Stimulation for Parkinson's Disease

Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a common sensorimotor disorder that may be idiopathic (primary) or secondary to a diverse group of conditions. The pathophysiology of primary RLS is only partly understood, but a strong association with brain iron deficiency possibly resulting in impaired dopaminergic function has been recognized. Genomic studies have established a genetic basis for primary RLS as well, and at least 42% of people with primary RLS possess a first-degree relative with the disorder. Secondary RLS is often associated with renal insufficiency, pregnancy, iron deficiency anemia, diabetic neuropathy, and Parkinson's disease. Approximately one-fourth of pregnant women experience RLS, with more intense symptoms experienced during the third trimester, and resolution of symptoms typically occurring within a few months after delivery, though RLS may resolve as early as 2 weeks after delivery. Restless legs syndrome is associated with increased prevalence of mood disturbances, sleep disturbances, and an impaired quality of life. The diagnosis of RLS involves 4 essential criteria related to a compelling urge to move the legs with an accompanying unpleasant sensation in the legs that is worse in the evening and at rest and improved by movement. Treatment of RLS incorporates both pharmacologic and nonpharmacologic approaches. Dopamine agonists are the mainstay of RLS treatment, but other therapies, including gabapentin, benzodiazepines, and low-potency opioids, are also commonly employed.

A clinical primer on restless legs syndrome: what we know, and what we don't know

Prospective study evaluating IncobotulinumtoxinA for cervical dystonia or blepharospasm: Interim results from the first 145 subjects with cervical dystonia

Background : We report the interim results from XCiDaBLE: A large prospective, observational "naturalistic" study evaluating Xeomin ® (incobotulinumtoxinA) for cervical dystonia or blepharospasm in the United States. Methods : Subjects with CD are followed for 2 treatment cycles and monitored via Interactive Voice/Web Response. Subject-reported scales include the Subject Global Impression-Severity and Improvement; Cervical Dystonia Impact Profile (CDIP-58); and Work Productivity and Quality of Life (QoL) are assessed by means of an employment questionnaire and work history and the SF-12v2. Results : This ongoing study includes 145 subjects with a diagnosis of CD. The majority were female (82.3%) and White (91.0%) and had previously been treated with botulinum toxins (77.2%). There were 106 employed at the time of onset of the disease, but 12.6 years later only 44% were still employed at the time of enrolment into the study and 20% were either receiving or seeking disability benefits. However, only 44% were still employed at the time of recruitment for study participation. The mean total dose/treatment of CD was 225.2 units for the 1st injection. The CDIP-58 total score was significantly improved at four weeks post the first injection compared to baseline (p=<0.0001). Most subjects noted improvement in their global impression assessment. No new or unexpected adverse events occurred. Discussion : The results from these interim analyses confirm previous controlled single-dose studies of incobotulinumtoxinA in terms of efficacy and safety.

/pdf/prospective-study-evaluating-incobotulinumtoxina-for-2414hij8tj.pdf

Prospective Study Evaluating IncobotulinumtoxinA for Cervical Dystonia or Blepharospasm: Interim Results from the First 145 Subjects with Cervical Dystonia

Impulse control disorders and dopaminergic drugs.

Visual cueing have been reported to help improve walking in people with Parkinson’s disease. However, many of these studies incorporate instructions and familiarization/practice, making it unclear whether the visual cues themselves were really effective or what parameters of walking are mutable. Here we used a closed-loop virtual visual cueing system to probe the automatic locomotor structures in subjects with idiopathic Parkinson’s disease and no freezing episodes. The cues moved in synchrony to the velocity of each subject’s walking but in the opposite direction, thereby giving rise to the perception of walking across a stationary landscape. In the absence of explicit instructions and practice, the virtual visual cues induced spontaneous changes among various walking kinematics in moderate-severe but not early-stage subjects. The largest effect was seen in the decrease in time to execute the first step (step initiation). Subjects completed the first step faster in the presence of the visual cues. Step length and walking speed on the other hand, decreased with exposure to the cues, i.e. subjects started out fast but then slowed down in the remainder of the walk. We conclude that the novel effects of the closed-loop visual cues produce mixed outcomes in walking performance. While step initiation improved spontaneously, the normalization of speed and step length would require cognitive strategies and practice as indicated in previous studie

Closed-Loop VR-Based Interaction to Improve Walking in Parkinson's Disease

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