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

Sir, Restless legs syndrome (RLS) is a common sensorimotor disorder with a prevalence of up to 10% in the general population [1]. Despite increasing awareness and education regarding this condition, there remain a sizeable number of patients who suffer from the typical symptoms of RLS but still remain undiagnosed and untreated for this condition [2]. Medications that exacerbate RLS symptoms are generally avoided in a patient diagnosed with RLS [3]. However, these drugs may be inadvertently prescribed for an undiagnosed patient with RLS, leading to a severe worsening and an acute/emergent presentation. We present a previously undiagnosed patient with an explosive presentation of RLS symptoms. A 65-year-old woman was admitted to the neurology intensive care unit (ICU) with sudden onset of uncontrollable movements that were initially diagnosed as biballism. She had undergone laparoscopic pancreatic surgery 10 days prior to her current admission. Upon discharge, she was given promethazine 25 mg as required for nausea, which she was taking two–three times a day. A few days later she started experiencing pain in her right calf, which then spread to both legs and was accompanied by a ‘pins and needles’ type sensation in her legs that subsequently spread to her arms. She continued to take several doses of promethazine for nausea and started having abnormal uncontrolled movements of her legs. She presented to the ER with these symptoms and was diagnosed with acute dystonic reaction due to promethazine and given intravenous diphenhydramine. This lead to a significant worsening of the abnormal movements that led her to be admitted to the ICU. Routine blood tests for hemoglobin, blood glucose, renal and liver function tests were within normal limits. Magnetic resonance imaging of the brain showed no abnormalities. On our evaluation, the patient was in significant distress and appeared very uncomfortable while lying in bed. She was seen having uncontrollable movements in the lower extremities proximal more than distal, with minimal involvement of the upper extremities and the trunk and without orofacial involvement (Video S1). The symptoms improved with walking and mental concentration. When questioned in detail, she admitted having mildly uncomfortable sensations in her legs over the last several years when lying in bed at night. However, they were not bothersome to her and she did not mention it to her physician. She experienced no exacerbations during pregnancy that she was aware of. Her neurological examination was otherwise normal. The symptoms completely abated while awake after i.v. morphine 2 mg (Video S1). She denied having any family history of RLS, and the hemoglobin (14.4 g/dl; range: 12–16 g/dl) and serum ferritin (96.4 ng/ml; range: 7–282 ng/ml) were normal. She was diagnosed with severe exacerbation of RLS and discharged on ropinirole, and has had symptom control for over 2 years. This case illustrates several important points: severe RLS exacerbation can present in a previously undiagnosed patient in an emergency setting. The diagnosis may be missed unless one has a high index of clinical suspicion. Drugs such as dopamine-blocking agents, some antidepressants and antihistaminergics when used in patients with RLS may have a synergistic effect in worsening their RLS symptoms (in this case possibly anesthetics during surgery, diphenhydramine and promethazine) [4]. Also, severe RLS can result in profound involuntary movements that can resemble ballism. It is unlikely that the patient suffered from dopamine-blocking agentsinduced akathisia as she did not complain of inner restlessness and the movements were significantly worse in the lower extremities than other body parts. It must be stressed that RLS is also a focal akathisia and our patient did have a history of mildly uncomfortable sensations in her legs for the last several years, which suggests that she may have been suffering from RLS all along. A detailed clinical history, distribution of abnormal movements, their improvement upon walking and mental concentration, and presence of exacerbating factors such as offending medications should lead the clinician to make the correct diagnosis.

Severe exacerbation of undiagnosed restless legs syndrome presenting as a movement disorder emergency.

Defining the Eye-of-the-Tiger Sign.

International validation of the first united non motor symptoms scale for Parkinson's disease. Results from the first pilot NMSS study

A single-blind trial of bilateral globus pallidus internus deep brain stimulation in medically refractory cervical dystonia

Parkinson’s disease is a progressive, widespread, neurodegenerative disease in which the involvement of the dopaminergic neurons of the substantia nigra results in significant dopamine depletion in the striatum. Newer imaging modalities reviewed here, using various radioligands, positron emission tomography, and single-photon emission computed tomography, have made it possible to assess the in vivo presynaptic and postsynaptic dopaminergic function. This is not only important from a diagnostic standpoint; these tests are being increasingly studied as surrogate markers to assess disease progression and responses to various interventions, including drugs. A brief comment on their role as a putative biomarker of the disease is also included. Because Parkinson’s disease involves multiple neurotransmitter systems, neuroimaging of neurotransmitter systems other than dopamine is also discussed. Lastly, the evidence supporting the use of transcranial ultrasonography and substantia nigra hyperechogenicity in the diagnosis of Parkinson’s disease is presented, along with some controversies that surround this technique.

Neuroimaging and transcranial ultrasonography in Parkinson’s disease

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