Search

Background: Vitamin D insufficiency has been reported to be more common in patients with Parkinson disease (PD) than in healthy control subjects, but it is not clear whether having a chronic disease causing reduced mobility contributes to this relatively high prevalence., Objective: To examine the prevalence of vitamin D insufficiency in a cohort of untreated patients with early PD (diagnosed within 5 years of study entry). DESIGN, SETTING, AND PATIENTS The Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) cohort is a well-characterized cohort of subjects with early, nondisabling PD. The cohort is well suited for examining the prevalence of vitamin D insufficiency early in the course of the disease. We conducted a survey study of vitamin D status in stored blood samples from patients with PD enrolled in the placebo group of the DATATOP trial. Samples from baseline visits and end point/final visits (mean [SD], 18.9 [13.1] months) were analyzed for 25-hydroxyvitamin D (25[OH]D) concentration in blinded fashion., Main Outcome Measures: The mean vitamin D concentration and the prevalence of vitamin D insufficiency at baseline and end point/final visits., Results: Among 199 subjects, 170 (85.4%) had samples from the baseline and end point visits available for analysis; 13 were excluded (10 with low probability of having PD and 3 with 25[OH]D concentrations>3 SDs above the mean). In the remaining 157 subjects, the mean (SD) 25(OH)D concentrations at the baseline and end point visits were 26.3 (8.6) ng/mL and 31.3 (9.0) ng/mL, respectively (to convert to nanomoles per liter, multiply by 2.496). The prevalence of vitamin D insufficiency (25[OH]D concentration<30.0 ng/mL) was 69.4% at baseline and 51.6% at the end point., Conclusions: The prevalence of vitamin D insufficiency in patients with early PD was similar to or higher than those reported in previous studies. Vitamin D concentrations did not decline during progression of PD. Further studies are needed to elucidate the natural history and significance of vitamin D insufficiency in PD.

Objective: To provide recommendations to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD)., Data Sources and Study Selection: An international consortium of experts organized, reviewed the literature, and attended the workshop. Topics were introduced at the workshop, followed by group discussion., Data Extraction and Synthesis: A draft of a consensus statement was presented and further edited after plenary debate. The final statements were agreed on by all members., Conclusions: (1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients.

Background: A role for vitamin D deficiency in Parkinson disease (PD) has recently been proposed., Objective: To compare the prevalence of vitamin D deficiency in a research database cohort of patients with PD with the prevalence in age-matched healthy controls and patients with Alzheimer disease (AD)., Design: Survey study and blinded comparison of plasma 25-hydroxyvitamin D (25[OH]D) concentrations of stored samples in a clinical research database at Emory University School of Medicine., Setting: Referral center (PD and AD patients), primary care clinics, and community setting (controls)., Participants: Participants were recruited into the study between May 1992 and March 2007. Every fifth consecutively enrolled PD patient was selected from the clinical research database. Unrelated AD (n = 97) and control (n = 99) participants were randomly selected from the database after matching for age, sex, race, APOE genotype, and geographic location., Main Outcome Measures: Prevalence of suboptimal vitamin D and mean 25(OH)D concentrations., Results: Significantly more patients with PD (55%) had insufficient vitamin D than did controls (36%) or patients with AD (41%; P = .02, chi(2)test). The mean (SD) 25(OH)D concentration in the PD cohort was significantly lower than in the AD and control cohorts (31.9 [13.6] ng/mL vs 34.8 [15.4] ng/mL and 37.0 [14.5] ng/mL, respectively; P = .03)., Conclusions: This report of 25(OH)D concentrations in a predominantly white PD cohort demonstrates a significantly higher prevalence of hypovitaminosis in PD vs both healthy controls and patients with AD. These data support a possible role of vitamin D insufficiency in PD. Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of PD.

Views of the anatomy and function of the basal ganglia and their role in motor and nonmotor disorders have undergone major revisions during the past decades. The basal ganglia are now appreciated as components of parallel, reentrant cortico-subcortical circuits, which originate from individual cortical areas, traverse the basal ganglia and thalamus, and terminate in their respective areas of origin in the frontal lobe. Further research and clinical experience have resulted in new insights and perspectives on the details of the circuitry and on the role of these structures in Parkinson disease and other basal ganglia disorders. On the basis of anatomical and physiological studies and the striking success of focused surgical interventions, it seems appropriate to view these varied clinical disorders as circuit disorders, resulting from pathologic disturbances in neuronal activity throughout specific cortico-subcortical loops.

Objective: To investigate whether a single daily dose of testosterone replacement gel has beneficial effects on testosterone deficiency symptoms, cognitive function, nonmotor symptoms of Parkinson disease (PD), and motor symptoms of PD., Background: Recently it has been observed that testosterone replacement therapy improves refractory nonmotor symptoms in testosterone-deficient men with PD. Many of the symptoms of testosterone deficiency are nonspecific and overlap with the nonmotor symptoms of PD, such as decreased enjoyment of life, lack of energy, sexual dysfunction, and depression. Replacement therapy for men with PD and comorbid testosterone deficiency may be an important addition to antiparkinsonian management strategies., Methods: A prospective open-labeled pilot study of testosterone topical gel (5 g of AndroGel; Unimed Pharmaceutical Inc, Deerfield, Ill) administered daily to testosterone-deficient (free testosterone <80 pg/mL) men with PD. All 10 patients were followed up for 1 month and 6 patients were followed up for a total of 3 months. Patients were administered a battery of testosterone deficiency questionnaires, cognitive studies, and scales of PD nonmotor and motor function at baseline, 1, and 3 months., Results: With the daily transdermal testosterone gel, patients had an average increase in levels of free testosterone from baseline (53 pg/mL) to a 1-month follow-up visit (131 pg/mL; P =.06) and to a 3-month follow-up visit (98 pg/mL; P =.04). Testosterone deficiency symptoms improved in these patients (St Louis Testosterone Deficiency Questionnaire) from baseline (7.9 deficiency symptoms) to 1 month (5.6 deficiency symptoms, P =.04) and 3 months (5.8 deficiency symptoms, P =.08). The Unified Parkinson's Disease Rating Scale IV showed improvement at 1 month (P =.008). Additionally, there were trends toward improvement in the following scales: Unified Parkinson's Disease Rating Scale I at the 3-month follow-up (P =.09), Letter Fluency at the 3-month follow-up (P =.08), and the Hamilton Anxiety Scale at the 1-month follow-up (P =.09)., Conclusions: A daily dose of transdermal testosterone gel improved testosterone deficiency symptoms in men with PD. Although there were trends in improvement in other nonmotor and motor symptoms of PD, future placebo control studies will need to be powered to answer these important questions. Whether testosterone deficiency is simply a comorbidity in PD or whether it plays a role in the pathogenesis of disease also remains for future study.

Background: Many patients with Parkinson disease (PD) suffer from nonmotor symptoms including depression, anxiety, sexual dysfunction, decreased energy level, and an overall decline in quality of life. Comorbid depression, hypothyroidism, and sleep disorders may account for some, but not all, of these problems. Testosterone deficiency affects 20% to 25% of males over the age of 60 years in the general population and may cause signs and symptoms of the nonmotor symptoms seen in PD. We observed numerous patients with PD whose nonmotor symptoms were refractory to treatment., Objective: To determine whether treatment of comorbid testosterone deficiency in male patients with PD can lead to improvements in refractory nonmotor symptoms., Methods: Case studies were reviewed of the first 5 male patients who had PD with symptoms of testosterone deficiency who were treated in our clinic. All patients had low serum testosterone levels. Screening for testosterone deficiency symptoms using the St Louis Testosterone Deficiency Questionnaire was performed for 4 of the 5 patients. Additionally, to assess the prevalence of PD, total testosterone levels in 68 patients in our PD registry were sent for evaluation., Results: Following testosterone replacement therapy, all 5 patients experienced significant improvements in their refractory nonmotor symptoms. Of 68 male patients with PD enrolled in our PD registry, 24 (35%) had plasma evidence of testosterone deficiency. We also noted that the risk of testosterone deficiency per decade was found to increase 2.8-fold per decade (P<.001), paralleling that which is found in the general elderly male population., Conclusions: The findings from this study reveal the heretofore unrecognized high prevalence of testosterone deficiency in elderly male patients with PD similar to that found in the general population. These symptoms, which may be refractory to antidepressants, anxiolytics, and antiparkinsonian medications, may respond to treatment with testosterone. More rigorous controlled studies will need to be undertaken to examine the treatment of this common comorbidity in male patients with PD.

Background: Many medical centers throughout the world offer radiosurgery with the gamma knife (GK) for pallidotomy and thalamotomy as a safe and effective alternative to radiofrequency ablative surgery and deep brain stimulation for Parkinson disease (PD). The reported incidence of significant complications varies considerably, and the long-term complication rate remains unknown., Design: We describe 8 patients seen during an 8-month period referred for complications of GK surgery for PD., Results: Of the 8 patients, 1 died as a result of complications, including dysphagia and aspiration pneumonia. Other complications included hemiplegia, homonymous visual field deficit, hand weakness, dysarthria, hypophonia, aphasia, arm and face numbness, and pseudobulbar laughter. In all patients, lesions were significantly off target., Conclusions: The 8 patients with PD seen in referral at our center for complications of GK surgery highlight a spectrum of potential problems associated with this procedure. These include lesion accuracy and size and the delayed development of neurological complications secondary to radiation necrosis. Gamma knife surgery may have a higher complication rate than has been previously appreciated due to delayed onset and underreporting. We believe that the risk-benefit ratio of the GK will require further scrutiny when considering pallidotomy or thalamotomy in patients with PD. Physicians using this technique should carefully follow up patients postoperatively for delayed complications, and fully inform patients of these potential risks.

The objective of this workshop was to provide recommendations on several issues involving pallidotomy for patients with medically intractable Parkinson disease to physicians, patients, and other health care providers. An international consortium of experts in neurology, neurosurgery, and neurophysiology who had extensive experience with pallidotomy were invited to the workshop. Participants were sent background materials from the scientific literature for review-based participant recommendations. A proposed agenda was circulated to all participants before the workshop, and the final agenda was based on their recommendations. Topics were introduced at the workshop by members of the organizing committee, followed by extensive group discussion. A draft of a consensus statement, based on the previous day's discussion, was circulated and further modifications were made. The final statement was agreed on by all members. The conclusions of the participants were: (1) Pallidotomy should be performed only at centers that have a team of physicians with substantial expertise and experience in the field. (2) Patients with disabling idiopathic Parkinson disease, without dementia, and who have exhausted medical therapy should be considered for pallidotomy. (3) All patients should be examined by means of standardized rating scales both preoperatively and postoperatively to ensure quality of care at each center. (4) Symptoms that respond best to pallidotomy include medication-induced dyskinesias, rigidity, and tremor, while balance, gait disorders, and hypophonia are generally less responsive to surgery. Benefits of pallidotomy appear to be long lasting. (5) Each institution's complication rate should be discussed before surgery.

Patients with neurological symptoms and signs of Wilson's disease have been frequently noted to have a worsening of their condition after beginning chelation therapy with D-penicillamine. Presymptomatic patients, however, are not expected to develop neurological manifestations once appropriate therapy is begun. We describe a patient who was seen with hepatic disease and no neurological symptoms who became neurologically incapacitated soon after beginning penicillamine therapy. This case identifies an unexpected complication of penicillamine therapy that should be watched for in the presymptomatic patient who is beginning therapy.