Importance Parkinson disease is the second most common neurodegenerative disease worldwide. Although no available therapies alter the underlying neurodegenerative process, symptomatic therapies can improve patient quality of life. Objective To provide an evidence-based review of the initial pharmacological management of the classic motor symptoms of Parkinson disease; describe management of medication-related motor complications (such as motor fluctuations and dyskinesia), and other medication adverse effects (nausea, psychosis, and impulse control disorders and related behaviors); and discuss the management of selected nonmotor symptoms of Parkinson disease, including rapid eye movement sleep behavior disorder, cognitive impairment, depression, orthostatic hypotension, and sialorrhea. Evidence Review References were identified using searches of PubMed between January 1985 and February 2014 for English-language human studies and the full database of the Cochrane Library. The classification of studies by quality (classes I-IV) was assessed using the levels of evidence guidelines from the American Academy of Neurology and the highest-quality data for each topic. Results Although levodopa is the most effective medication available for treating the motor symptoms of Parkinson disease, in certain instances (eg, mild symptoms, tremor as the only or most prominent symptom, aged Conclusions and Relevance Strong evidence supports using levodopa and dopamine agonists for motor symptoms at all stages of Parkinson disease. Dopamine agonists and drugs that block dopamine metabolism are effective for motor fluctuations and clozapine is effective for hallucinations. Cholinesterase inhibitors may improve symptoms of dementia and antidepressants and pramipexole may improve depression. Evidence supporting other therapies for motor and nonmotor features is less well established.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=1861807&pdfFileName=jrv140005.pdf

Pharmacological Treatment of Parkinson Disease: A Review

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)

Introduction Antipsychotics (AP) induce weight gain. However, reviews and meta-analyses generally are restricted to second generation antipsychotics (SGA) and do not stratify for duration of AP use. It is hypothesised that patients gain more weight if duration of AP use is longer. Method A meta-analysis was conducted of clinical trials of AP that reported weight change. Outcome measures were body weight change, change in BMI and clinically relevant weight change (7% weight gain or loss). Duration of AP-use was stratified as follows: ≤6 weeks, 6–16 weeks, 16–38 weeks and >38 weeks. Forest plots stratified by AP as well as by duration of use were generated and results were summarised in figures. Results 307 articles met inclusion criteria. The majority were AP switch studies. Almost all AP showed a degree of weight gain after prolonged use, except for amisulpride, aripiprazole and ziprasidone, for which prolonged exposure resulted in negligible weight change. The level of weight gain per AP varied from discrete to severe. Contrary to expectations, switch of AP did not result in weight loss for amisulpride, aripiprazole or ziprasidone. In AP-naive patients, weight gain was much more pronounced for all AP. Conclusion Given prolonged exposure, virtually all AP are associated with weight gain. The rational of switching AP to achieve weight reduction may be overrated. In AP-naive patients, weight gain is more pronounced.

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Almost All Antipsychotics Result in Weight Gain: A Meta-Analysis

Enormous progress has been made in the treatment of Parkinson’s disease (PD). As a result of advances in experimental therapeutics, many promising therapies for PD are emerging. Levodopa remains the most potent drug for controlling PD symptoms, yet is associated with significant complications such as the “wearing off” effect, levodopa-induced dyskinesias and other motor complications. Catechol-o-methyl-transferase inhibitors, dopamine agonists and nondopaminergic therapy are alternative modalities in the management of PD and may be used concomitantly with levodopa or one another. The neurosurgical treatment, focusing on deep brain stimulation, is reviewed briefly. Although this review has attempted to highlight the most recent advances in the treatment of PD, it is important to note that new treatments are not necessarily better than the established conventional therapy and that the treatment options must be individualized and tailored to the needs of each individual patient.

/pdf/current-approaches-to-the-treatment-of-parkinson-s-disease-4nfxant356.pdf

Current approaches to the treatment of Parkinson’s disease

A systematic review of the literature on disorders of sleep and wakefulness in Parkinson's disease from 2005 to 2015

The present study explores the frequency of RLS in PD and focuses on the clinical differences between patients with and without restless legs syndrome (RLS). A cross-sectional study was designed, comprising 114 patients diagnosed with PD. Those patients positive for RLS were assessed for intensity of the syndrome (IRLS). We compared the clinical characteristics of the patients with and without RLS, using specific scales: Unified Parkinson's Disease Rating Scale (UPDRS I-IV), quality of life (Parkinson's Disease Questionnaire, PDQ 39), sleep symptoms (Parkinson's Disease Sleep Scale, PDSS), and diurnal hypersomnia (Epworth Sleepiness Scale). Twenty-five patients (21.9%) out of a total of 114 subjects diagnosed with PD met the RLS diagnostic criteria. RLS was more frequent in women (68%). The patients with RLS showed poorer scores on the PDSS (PD-RLS+: 102.4 +/- 15.1 vs PD-RLS-: 113.2 +/- 16.4) (P = 0.005) and in the bodily discomfort dimension of the PDQ-39 (PD-RLS+ 6.1 +/- 3.4 vs PD-RLS- 3.8 +/- 2.6) (P = 0.002). Analysis of the subscales of the PDSS showed significant differences (P < 0.001) between both groups of patients in items 4 and 10, and to a lesser degree in items 5 (P = 0.01) and 11 (P = 0.02) There was no increased incidence of diurnal hypersomnia in the group of patients with RLS. There were no differences in the rest of the variables. RLS is frequent in patients with PD, though this condition doesn't apparently affect quality of life or lead to an increased presence of diurnal hypersomnia. It would be advisable to validate the diagnostic criteria of RLS in this specific group of patients.

Restless legs syndrome in Parkinson's disease

Twelve patients with Parkinson disease and psychosis were included in an open-label 12-week trial of ziprasidone. Two patients withdrew from the treatment because of adverse effects. The remaining 10 patients reported a significant improvement in psychiatric symptoms. Altogether, there was no deterioration of motor symptoms (UPDRS III score: basal 40.4 +/- 11.1, first month 41.1 +/- 10.8; final visit, 37.7 +/- 13.3). Two patients (20%) suffered a slight deterioration in motor symptoms and another patient suffered deterioration of gait. No analytic alterations or serious adverse effects that could limit the use of ziprasidone were observed. Although controlled trials are needed, the findings suggest that ziprasidone may be effective in parkinsonian patients with psychosis.

Use of ziprasidone in parkinsonian patients with psychosis.

Introduction Hirayama disease is a rare cervical myelopathy, predominantly affecting young men, and which presents with distal atrophy of the upper limbs as its first and main symptom. It must be differentiated from motor neuron diseases because its natural history is different and because HD tends to stabilise in less than 5 years. Diagnosis is based on clinical findings and dynamic flexion MRI showing segmental spinal muscular atrophy, detachment of the posterior dura mater and venous congestion in the epidural space. The tendency is to indicate conservative treatment and no indications for surgery have been established. Patients We present 4 cases meeting both clinical criteria and dynamic MRI imaging criteria for a diagnosis of Hirayama disease. Two have stabilised spontaneously over the course of many years, and MRI scans show that typical changes have disappeared. Another case also remains stable following a shorter observation time. The fourth case is a young man who developed severe myelopathy in just over a year, and therefore underwent surgery. While his follow-up time is still short, his condition remains stable. Conclusions Our 4 cases suggest that the condition of most patients with Hirayama stabilises naturally; patients should be evaluated for surgery on an individual basis, and surgery should probably be limited to the most severe cases that have progressed quickly.

Hirayama disease: Is surgery an option?

Resumen Introduccion La enfermedad de Hirayama es una rara mielopatia cervical mucho mas frecuente en hombres jovenes, que cursa con atrofia distal en los brazos como primer y principal sintoma. Es importante diferenciarla de las enfermedades de las motoneuronas porque su historia natural es distinta, con tendencia hacia la estabilizacion en menos de 5 anos. El diagnostico se basa en los hallazgos clinicos y en la RM dinamica (en flexion del cuello), que detecta la atrofia medular segmentaria, el despegamiento posterior de la dura madre y la congestion venosa en el espacio epidural. La tendencia es a indicar un tratamiento conservador pero no esta establecido cual puede ser el papel de la cirugia. Pacientes Se presentan 4 casos que cumplen los criterios clinicos y de imagen en RM dinamica para diagnostico de enfermedad de Hirayama. Dos estan en fase de estabilizacion espontanea despues de muchos anos de evolucion y en la RM se demuestra la desaparicion de las alteraciones tipicas. Otro caso tambien permanece estable con menos tiempo de observacion. El cuarto caso corresponde a un joven que en poco mas de un ano presenta una mielopatia grave, por lo que ha sido operado, manteniendose estable tras una observacion todavia corta. Conclusiones Nuestros 4 casos indican que la mayoria de los pacientes con enfermedad de Hirayama se estabilizan de manera natural y que la intervencion quirurgica debe ser una decision individual, probablemente limitada a los casos mas graves con una evolucion muy breve.

Enfermedad de Hirayama: ¿operar o no operar?

We report the case of a 32-year-old man with an epidermoid tumor of the fourth ventricle. About 14 years later, he showed a tumor recurrence which was removed. After this procedure the patient complained of presyncopal and syncopal crisis while attempting to stand or walk. On examination, severe orthostatic hypotension was confirmed and autonomic tests were abnormal. The brain MRI showed a tetraventricular hydrocephalus predominating in the fourth ventricle. A ventriculo-peritoneal shunt was performed, and after surgery the orthostatic intolerance improved. We believe that hydrocephalus has probably been a contributory factor to orthostatic hypotension, and suggest expanding testing for dysautonomia in patients with hydrocephalus.

Joseba Barcena

Papers

Restless legs syndrome in Parkinson's disease

Use of ziprasidone in parkinsonian patients with psychosis.

Hirayama disease: Is surgery an option?

Enfermedad de Hirayama: ¿operar o no operar?

Orthostatic hypotension associated with an epidermoid tumor of the IV ventricle.