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

background Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson’s disease have been well documented, the long-term outcomes of the procedure are unknown. methods We conducted a five-year prospective study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus. Patients were assessed at one, three, and five years with levodopa (on medication) and without levodopa (off medication), with use of the Unified Parkinson’s Disease Rating Scale. Seven patients did not complete the study: three died, and four were lost to follow-up. results As compared with base line, the patients’ scores at five years for motor function while off medication improved by 54 percent (P<0.001) and those for activities of daily living improved by 49 percent (P<0.001). Speech was the only motor function for which offmedication scores did not improve. The scores for motor function on medication did not improve one year after surgery, except for the dyskinesia scores. On-medication akinesia, speech, postural stability, and freezing of gait worsened between year 1 and year 5 (P<0.001 for all comparisons). At five years, the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced, as compared with base line (P<0.001 for each comparison). The average scores for cognitive performance remained unchanged, but dementia developed in three patients after three years. Mean depression scores remained unchanged. Severe adverse events included a large intracerebral hemorrhage in one patient. One patient committed suicide. conclusions Patients with advanced Parkinson’s disease who were treated with bilateral stimulation of the subthalamic nucleus had marked improvements over five years in motor function while off medication and in dyskinesia while on medication. There was no control group, but worsening of akinesia, speech, postural stability, freezing of gait, and cognitive function between the first and the fifth year is consistent with the natural history of Parkinson’s disease.

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Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease.

Adequate reporting of randomized, controlled trials (RCTs) is necessary to allow accurate critical appraisal of the validity and applicability of the results. The CONSORT (Consolidated Standards of Reporting Trials) Statement, a 22-item checklist and flow diagram, is intended to address this problem by improving the reporting of RCTs. However, some specific issues that apply to trials of nonpharmacologic treatments (for example, surgery, technical interventions, devices, rehabilitation, psychotherapy, and behavioral intervention) are not specifically addressed in the CONSORT Statement. Furthermore, considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement. Therefore, the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments. A consensus meeting of 33 experts was organized in Paris, France, in February 2006, to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments. The participants extended 11 items from the CONSORT Statement, added 1 item, and developed a modified flow diagram. To allow adequate understanding and implementation of the CONSORT extension, the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting. This extension, in conjunction with the main CONSORT Statement and other CONSORT extensions, should help to improve the reporting of RCTs performed in this field.

/pdf/extending-the-consort-statement-to-randomized-trials-of-39t9d1gijb.pdf

Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration.

Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development.

Two subjects with Parkinson's disease who had long-term survival of transplanted fetal mesencephalic dopaminergic neurons (11-16 years) developed alpha-synuclein-positive Lewy bodies in grafted neurons. Our observation has key implications for understanding Parkinson's pathogenesis by providing the first evidence, to our knowledge, that the disease can propagate from host to graft cells. However, available data suggest that the majority of grafted cells are functionally unimpaired after a decade, and recipients can still experience long-term symptomatic relief.

Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation.

Background Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known. Methods We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or undergo sham surgery; all were to be followed in a double-blind manner for one year. In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally. In the patients who underwent sham surgery, holes were drilled in the skull but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of –3.0 to 3.0 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement. Results The mean (±SD)...

https://www.nejm.org/doi/pdf/10.1056/NEJM200103083441002

Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

Freezing is a common symptom in parkinsonian syndromes, but its association with different causes of parkinsonism as well as with other symptoms has never been investigated. We conducted a database survey of the occurrence of freezing in parkinsonism. Of 347 patients with a clinical diagnosis of parkinsonism other than idiopathic Parkinson's disease and with specific data regarding freezing, 158 patients had freezing (46%). Freezing was significantly associated with progression of the disease as rated on the Hoehn & Yahr scale [odds ratio (OR), 1.69; p < 0.004]. Gender was not a risk factor for the development of freezing. Patients with drug-induced parkinsonism were at a very low risk for developing freezing (p < 0.00001; OR, 0.1). Freezing was found in a high frequency in patients with vascular parkinsonism (57%), normal-pressure hydrocephalus (56%), and generally in the group of patients who had parkinsonism resulting from neurodegenerative diseases (progressive supranuclear palsy, multiple system atrophy, and corticobasal ganglionic degeneration; 45%). Freezing was significantly associated with the presence of dementia, incontinence, and tachyphemia (OR, 2.01, 1.7, and 5.09, respectively).

Richard Kao

Papers

Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

Freezing phenomenon in patients with parkinsonian syndromes