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

Digoxin-induced chorea in a child.

Jacob’s syndrome (XYY; JS) and Klinefelter syndrome (XXY; KS) are quite common, occurring in 1 and 1.72 per 1000 male births, respectively. Despite this prevalence and the reportedly “frequent” tremors in these patients, there is a paucity of information about the precise phenotype. There is more information available on tremor in KS and XXYY with associated videos. The published characteristics of tremor in JS are lacking in part because most JS men are never diagnosed. To our knowledge, we present the first video case illustrating the neurological features of a patient with JS. A tall, 61-year-old, left-handed man with arthritis and no family history of tremor presented with progressive tremor and twisting movements of the hands. His first noticed tremor when he put together model airplanes as a child with impairment in writing, drinking from a cup, and using utensils by his 20s. In his 50s he required assistance to prepare meals and cut his food. The tremor improved with alcohol. Examination demonstrated a terminal kinetic tremor and “wing-beating” tremor (Video S1). He was unable to perform Archimedes spiral; his pen struck the page numerous times with small straight lines never making a spiral. Writing dystonia and tremor impaired his writing. He compensated for this by bracing his arm to his torso and applying excessive force to the pen (Video S1). When writing or picking up a cup, he had facial grimacing, platysma contraction, anterocollis, and left laterocollis that resolved at rest (Video S1). His gait was wide based with mildly impaired tandem gait and dystonic splaying of his left more than right hand. There was no myoclonus. He was treated with trihexyphenidyl and propranolol without benefit. We offered deep brain stimulation to address his dystonia and tremor, but he declined. A lack of family history of tremor and the patient’s height (6’8”) prompted a karyotype evaluation. We identified a sex chromosome aneuploidy, 47, XYY, or JS. Tall stature and neurological, cognitive, and behavioral abnormalities are common to both KS and JS. There is an increased prevalence of seizures, dental problems, autism spectrum disorder, tremor, and asthma in JS patients, which has been attributed to the presence of the extra Y chromosome. Incoordination, dysdiadochokinesia, rebound, and poorly described synkinesis have also been reported in JS. There have been many case reports/series of resting, postural, and kinetic tremor in KS affecting the bilateral upper extremities and rarely the head and voice. Bardsley and colleagues reported that 43% (39/90) of JS patients had mild action and/or intention tremors without mention of dystonic tremor. The prevalence of dystonia and dystonic tremor in JS is unknown given the possible underrecognition or mislabeling of tremor phenotype. Although the vast majority of tremor reported in KS is action, postural, resting, or intention, Rabin and colleagues reported a KS patient with dystonic tremor and another KS patient with resting tremor and dystonic head movements. Perhaps dystonia and dystonic tremor are uncommon or underrecognized phenotypes in sex chromosome aneuploidies. In a double-blind, population-matched controlled study of KS and JS, there was more irregularity in tremor amplitude and spontaneous abrupt waveform changes in JS subjects. Tremor amplitude was also significantly greater in JS patients when compared with controls and KS patients. The overexpression of pseudoautosomal regions of the X and Y chromosomes is one proposed mechanism for the similarities in kinetic and postural tremor in KS and JS. We hope this case helps to expand the known phenotype of JS to improve clinicians’ recognition of this disorder.

Tremor and Dystonia in Jacob's Syndrome (47,XYY).

Ergotism results from generalized vasoconstriction of small and large blood vessels and can lead to cyanosis and gangrene of affected limbs if not recognized. Ergotism occurs most commonly in the treatment of migraine with ergotamines today; however, ergot-derived drugs are also used in the treatment of restless legs syndrome and …

https://n.neurology.org/content/neurology/67/1/104.full.pdf

Pergolide-induced ergotism.

Neuropsychological Performance in Hallervorden-Spatz Syndrome: A Report of Two Cases

Predominant ataxia, low ceruloplasmin, and absent K–F rings: Hypoceruloplasminemia or Wilson's disease

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