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

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

Measuring Health: A Guide to Rating Scales and Questionnaires

The clinical diagnosis of Parkinson's disease rests on the identification of the characteristics related to dopamine deficiency that are a consequence of degeneration of the substantia nigra pars compacta. However, non-dopaminergic and non-motor symptoms are sometimes present before diagnosis and almost inevitably emerge with disease progression. Indeed, non-motor symptoms dominate the clinical picture of advanced Parkinson's disease and contribute to severe disability, impaired quality of life, and shortened life expectancy. By contrast with the dopaminergic symptoms of the disease, for which treatment is available, non-motor symptoms are often poorly recognised and inadequately treated. However, attention is now being focused on the recognition and quantitation of non-motor symptoms, which will form the basis of improved treatments. Some non-motor symptoms, including depression, constipation, pain, genitourinary problems, and sleep disorders, can be improved with available treatments. Other non-motor symptoms can be more refractory and need the introduction of novel non-dopaminergic drugs. Inevitably, the development of treatments that can slow or prevent the progression of Parkinson's disease and its multicentric neurodegeneration provides the best hope of curing non-motor symptoms.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(06)70373-8.pdf

Non-motor symptoms of Parkinson's disease: diagnosis and management

The images are from a 44-year old woman with facial dystonia, chin tremor, and a postural and action-induced dystonic tremor of the right hand. She had severe hypomimia, accompanied by bradykinesia and cogwheel rigidity in both upper and lower extremities. Gait was slow, with small steps. A: Dilated Virchow–Robin spaces along the lenticulostriate vessels in the basal ganglia and the medullary -----------------------------------------------------------*Correspondence to: Dr. Kapil D. Sethi, Professor & Director, Movement Disorders, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA; ksethi@georgiahealth.edu

Dilated Virchow-Robin spaces and parkinsonism.

A 65-year-old dextral woman with hypertension presented with a 5-day history of difficulty writing. On examination, she had impaired adduction of her left eye and micrographia. MRI demonstrated an acute to subacute lacunar infarct involving predominantly the left red nucleus …

https://n.neurology.org/content/neurology/60/12/E10.full.pdf

Midbrain infarct with parkinsonism

A 27-year-old woman presented because of multiple daily episodes of painful “drawing” in her right arm and leg precipitated by hyperventilation (see video, segment 1). These episodes would typically last between 30 seconds and 2 minutes. Brain MRI and CSF analysis were consistent with multiple sclerosis (MS). MS-related paroxysmal hemidystonia was diagnosed because of a typical pattern of limb …

https://n.neurology.org/content/neurology/65/6/E12.full.pdf

Psychogenic paroxysmal dyskinesia following paroxysmal hemidystonia in multiple sclerosis

compared with the first, whereas the prolactin response was unaltered. We now report the endocrine effects of repeated intravenous infusions of RX77368 in MND. Seven patients (six male, one female, age range 43-67) with MND' were given six intravenous infusions of'RX77368 on Mondays and Thursdays of three successive weeks, starting at 9.30 am on each occasion. The dose of RX77368 was 0-2 mg/kg, given over two hours. If side effects were unacceptable,24 the dose was reduced on subsequent infusions. Two patients failed to complete all the infusions, one having five, the other four. Of the other patients, three had dose reductions, to 0 15 or 0 1 mg/kg because of side effects. Blood samples were taken for measurement of T4, T3, TSH and prolactin

https://jnnp.bmj.com/content/jnnp/53/9/804.full.pdf

Carotid dissection: a new false localising sign.

Although hemichorea is often ascribed to a vascular lesion, generalized chorea of adult onset is often thought to be due to degenerative diseases. We describe a 74-year-old woman with generalized chorea that was diagnosed at autopsy as due to multiple lacunar infarcts in the basal ganglia. Generalized chorea in adults may be caused by vascular disease of the basal ganglia.

Kapil D. Sethi

Papers

Dilated Virchow-Robin spaces and parkinsonism.

Midbrain infarct with parkinsonism

Psychogenic paroxysmal dyskinesia following paroxysmal hemidystonia in multiple sclerosis

Carotid dissection: a new false localising sign.

Generalized chorea due to basal ganglia lacunar infarcts.