Falls and freezing of gait are two "episodic" phenomena that are common in Parkinson's disease. Both symptoms are often incapacitating for affected patients, as the associated physical and psychosocial consequences have a great impact on the patients' quality of life, and survival is diminished. Furthermore, the resultant loss of independence and the treatment costs of injuries add substantially to the health care expenditures associated with Parkinson's disease. In this clinically oriented review, we summarise recent insights into falls and freezing of gait and highlight their similarities, differences, and links. Topics covered include the clinical presentation, recent ideas about the underlying pathophysiology, and the possibilities for treatment. A review of the literature and the current state-of-the-art suggests that clinicians should not feel deterred by the complex nature of falls and freezing of gait; a careful clinical approach may lead to an individually tailored treatment, which can offer at least partial relief for many affected patients.

https://reylab.bidmc.harvard.edu/pubs/2004/md-2004-19-871.pdf

Falls and freezing of gait in Parkinson's disease : a review of two interconnected, episodic phenomena

background Cholinergic deficits are prominent in patients who have dementia associated with Parkinson’s disease. We investigated the effects of the dual cholinesterase inhibitor rivastigmine in such patients. methods Patients in whom mild-to-moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson’s disease were randomly assigned to receive placebo or 3 to 12 mg of rivastigmine per day for 24 weeks. Primary efficacy variables were the scores for the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) and Alzheimer’s Disease Cooperative Study–Clinician’s Global Impression of Change (ADCS-CGIC). Secondary clinical outcomes were the scores for the Alzheimer’s Disease Cooperative Study–Activities of Daily Living, the 10-item Neuropsychiatric Inventory, the Mini–Mental State Examination, Cognitive Drug Research power of attention tests, the Verbal Fluency test, and the Ten Point Clock-Drawing test. results A total of 541 patients were enrolled, and 410 completed the study. The outcomes were better among patients treated with rivastigmine than among those who received placebo; however, the differences between these two groups were moderate and similar to those reported in trials of rivastigmine for Alzheimer’s disease. Rivastigmine-treated patients had a mean improvement of 2.1 points in the score for the 70-point ADAS-cog, from a baseline score of 23.8, as compared with a 0.7-point worsening in the placebo group, from a baseline score of 24.3 (P<0.001). Clinically meaningful improvements in the scores for the ADCS-CGIC were observed in 19.8 percent of patients in the rivastigmine group and 14.5 percent of those in the placebo group, and clinically meaningful worsening was observed in 13.0 percent and 23.1 percent, respectively (mean score at 24 weeks, 3.8 and 4.3, respectively; P=0.007). Significantly better outcomes were seen with rivastigmine with respect to all secondary efficacy variables. The most frequent adverse events were nausea (affecting 29.0 percent of patients in the rivastigmine group and 11.2 percent of those in the placebo group, P<0.001), vomiting (16.6 and 1.7 percent, P<0.001), and tremor (10.2 and 3.9 percent, P=0.01). conclusions In this placebo-controlled study, rivastigmine was associated with moderate improvements in dementia associated with Parkinson’s disease but also with higher rates of nausea, vomiting, and tremor.

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Rivastigmine for Dementia Associated with Parkinson's Disease

The Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for Parkinson's Disease (PD) was first published in 2002 and was updated in 2005 to cover clinical trial data up to January 2004 with the focus on motor symptoms of PD. In this revised version the MDS task force decided it was necessary to extend the review to non-motor symptoms. The objective of this work was to update previous EBM reviews on treat- ments for PD with a focus on non-motor symptoms. Level-I (randomized controlled trial, RCT) reports of pharmacological and nonpharmacological interventions for the non-motor symptoms of PD, published as full

/pdf/the-movement-disorder-society-evidence-based-medicine-review-2fyuhos0nl.pdf

The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's disease

As there are no biological markers for the antemortem diagnosis of degenerative parkinsonian disorders, diagnosis currently relies upon the presence and progression of clinical features and confirmation depends on neuropathology. Clinicopathologic studies have shown significant false-positive and false-negative rates for diagnosing these disorders, and misdiagnosis is especially common during the early stages of these diseases. It is important to establish a set of widely accepted diagnostic criteria for these disorders that may be applied and reproduced in a blinded fashion. This review summarizes the findings of the SIC Task Force for the study of diagnostic criteria for parkinsonian disorders in the areas of Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. In each of these areas, diagnosis continues to rest on clinical findings and the judicious use of ancillary studies.

/pdf/sic-task-force-appraisal-of-clinical-diagnostic-criteria-for-2mntcoyjd5.pdf

SIC Task Force appraisal of clinical diagnostic criteria for parkinsonian disorders

Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches.

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Construction of freezing of gait questionnaire for patients with Parkinsonism.

Balash Y, Mordechovich M, Shabtai H, Giladi N, Gurevich T,Korczyn AD. Subjective memory complaints in elders: depression,anxiety, or cognitive decline?Acta Neurol Scand: 2013: 127: 344–350.© 2012 John Wiley & Sons A/S.Objectives – To study the association of subjective memory complaints(SMC) with affective state and cognitive performance in elders.Materials and methods – We studied community dwelling elderlypersons with normal physical examination. Participants completedquestionnaires regarding memory difﬁculties and lifestyle habits, theGeriatric Depression Scale (GDS) and the Spielberger State-TraitAnxiety Inventory (STAI). Depending on their answers to thequestion about their memory condition, participants were divided intocomplainers and non-complainers and to ﬁve groups according totheir MMSE scores. These data have been compared to objectivecognitive performance according to Mindstreams - a computerizedneuropsychological battery. A logistic regression was performed toevaluate odds ratios (OR) and 95% conﬁdence intervals (CI) for thosefactors, which were associated with SMС (dependent variable).Results – Of 636 consecutive subjects (61% females), 507 participants(79.7%) had SMС. Presence of SMC was inversely correlated withMMSE scores, (r = 0.108; P for trend = 0.007). GDS and STAIscores were higher among subjects with SMC (OR = 1.23: CI 95%:1.1–1.36 and OR = 1.03: CI 95%: 1.01–1.07, respectively). SMC didnot correlate with objective cognitive performance measured byMindstreams. Conclusions – Subjective memory complaints areassociated with sub-syndromal depression and anxiety in healthycognitively normal elders.

Subjective memory complaints in elders: depression, anxiety, or cognitive decline?

Objective To compare the safety and efficacy of quetiapine versus clozapine for the treatment of psychosis in patients with Parkinson's disease (PD). Methods Twenty-seven patients with PD and recent-onset psychosis were randomly allocated to 2 arms of 22 weeks' treatment with quetiapine or clozapine after 2 weeks of adjustment of antiparkinsonian medications. Assessment was done by a blinded neuropsychologist using the Clinical Global Impression of Change (CGIC) questionnaire and the Neuropsychiatric Inventory (NPI). Mixed-effect models were used to compare CGIC and Neuropsychological Inventory scores over time between the 2 groups. Results Both drugs were equally effective based on the CGIC. Clozapine had a trend over quetiapine in controlling the frequency of hallucinations (P = 0.097) and a significant advantage in reducing delusions (P = 0.011). However, one patient in the clozapine arm developed leukopenia. None of the drugs worsened parkinsonism. Conclusions Clozapine and quetiapine are effective atypical neuroleptics for the treatment of psychotic symptoms in PD. Clozapine had greater efficacy in reducing hallucinations and delusions frequency, but its use is associated with an increased risk of leukopenia.

Rater-blinded, prospective comparison: quetiapine versus clozapine for Parkinson's disease psychosis.

Gait festination in Parkinson's disease.

Background. It was commonly assumed that psychotic phenomena in Parkinson’s disease (PD) are mainly drug related. Accumulating evidence suggests the existence of other risk factors for psychosis in PD. Aims. To evaluate the contribution of the drug profile of patients with PD to emergence of hallucinations. Methods. We compared patients with and without hallucinations, using Cox proportional hazards model, concerning drug profile at the time of hallucinations emergence. Results. Of 422 consecutive patients, 113 had dementia, while 90 patients experienced hallucinations (46 had both dementia and hallucinations). The mean levodopa dose for the group of patients with hallucinations was 650 ± 279 mg/day at the time of hallucinations onset, which was not significantly different from the levodopa dose at last visit for the group without hallucinations (621 ± 326 mg/day). Supplementary treatment with amantadine, selegiline, dopamine agonists, entacapone and anticholinergics did not increase the risk for the development of hallucinations. Conclusions. We did not confirm drug treatment as a risk factor for hallucinations in PD. Our study suggests the existence of “endogenic” factors as substantial contributors in the genesis of PD hallucinations. The clinical implications may be earlier administration of antipsychotic treatment and not as traditionally accepted, dose reduction of antiparkinsonian drugs.

H. Shabtai

Papers

Construction of freezing of gait questionnaire for patients with Parkinsonism.

Subjective memory complaints in elders: depression, anxiety, or cognitive decline?

Rater-blinded, prospective comparison: quetiapine versus clozapine for Parkinson's disease psychosis.

Gait festination in Parkinson's disease.

Antiparkinsonian medication is not a risk factor for the development of hallucinations in Parkinson's disease.