John D. Putzke

Parkinson disease Handedness predicts asymmetry

Objective: To determine the proportion of individuals in a clinic-based setting that present with asymmetric Parkinson disease (PD) and identify predictive factors associated with asymmetric symptoms. Methods: The authors examined right vs left difference scores on the Unified Parkinson Disease Rating Scale motor subscale in a consecutive clinical series of 1,277 individuals diagnosed with PD. Predictors of asymmetry included sex, symptomatic disease duration, age at onset, initial motor symptom laterality, handedness, and medical history variables (e.g., family history of PD). Results: Nearly half the sample (46%) met criteria for asymmetric disease based on a right vs left difference score of ≥5 points, and 12% of the sample had a difference score of ≥10 (difference score: mean = 4, SD = 3.4). All three cardinal features of PD showed characteristics of asymmetric disease presentation. Multiple regression analyses showed that an increased discrepancy between right- and left-sided symptoms was significantly associated with a shorter disease duration, younger age at symptomatic onset, asymmetric initial symptom onset, hand dominance, and a positive self-reported family history of “other” neurodegenerative disorder. Hand dominance was related to the side of asymmetric disease such that left-handed individuals tended to have more severe disease on the left side of the body. Conclusion: Asymmetric presentation of Parkinson disease features was a common occurrence in the clinical cohort. Asymmetry was reliably predicted by several clinical characteristics, although the moderate level of explained variance (i.e., between 16 and 23%) highlighted the need for additional research examining predictive models of asymmetric disease. Recommendations for the classification and measurement of asymmetric disease are discussed.

Bilateral thalamic deep brain stimulation: midline tremor control

Objectives: To determine the efficacy of bilateral deep brain stimulation (DBS) for management of midline tremor (head, voice, tongue, trunk) in patients with essential tremor. Design: Prospective assessment of tremor at baseline (presurgical), and postoperatively at 1, 3, and 12 months, and annually thereafter. Methods: A clinical series of 22 individuals undergoing staged, bilateral DBS for treatment of essential tremor. The tremor rating scale was the primary outcome measure. Results: Midline tremor showed significant improvement with stimulation “on” at nearly every postoperative interval when compared with stimulation “off” and with baseline tremor. Bilateral stimulation was associated with a significant incremental improvement in midline tremor control compared with unilateral stimulation: average “stimulation on” percentage change in midline tremor from the unilateral to bilateral period was 81%. Head and voice tremor showed the most consistent improvement. Among those requiring a change in stimulation parameters because of side effects, dysarthria, disequilibrium, motor disturbances, and paraesthesiae were the most common. Dysarthria was more common with bilateral (n = 6; 27%) than with unilateral (n = 0) stimulation. Stimulation parameters remained largely unchanged after the first three months. Nine of 44 leads placed (20%) required subsequent repositioning or replacement. Conclusions: Unilateral thalamic stimulation significantly improves midline tremor, and subsequent bilateral thalamic stimulation offers an additional incremental improvement in midline tremor control.

Gender and the Parkinson’s disease phenotype

AbstractObjectivesTo determine whether there are gender differences in the Parkinson’s disease (PD) phenotype using a large clinic–based cohort.MethodsWe examined gender differences in demographic, historical and clinical characteristics in a consecutive clinical series of 1264 individuals diagnosed with PD.ResultsThe majority of individuals in the sample were male (67 %). Comparative analyses showed males and females were not significantly different on most demographic and historical characteristics. For both genders, the mean age and the mean age at symptomatic onset were about 70 and 63 years, respectively and, thus, disease duration was not significantly different between genders. The proportion of individuals with a positive family history of PD (15 %) was similar for both genders. A positive history of depression was significantly higher in females (35 % vs. 24 %). The UPDRS instability score was significantly worse among females, whereas the rigidity score was significantly worse for males. Females showed significantly worse ADL capacity and a more advanced H&Y stage. The proportion of individuals receiving antiparkinsonian medication (about 66 %) and time between the last dose and the clinical evaluation (about 4 hours) was similar for both genders. There was a trend for lower daily levodopa equivalence dosage and more severe dyskinesia score among females but these differences did not reach statistical significance after Bonferroni correction.ConclusionsThe majority of comparisons tended to highlight the commonalities in the PD phenotype between genders, particularly in reference to historical and early disease stage characteristics. However, gender may be an important factor related to the expression of PD features during the symptomatic disease course.

Magnetic Resonance Imaging and Deep Brain Stimulation

OBJECTIVE To determine whether cranial magnetic resonance imaging (MRI) is associated with deep brain stimulation (DBS) lead displacement or program interference. METHODS In vitro and in vivo studies were performed with the Itrel II implantable pulse generator (IPG) (Model 7424; Medtronic, Minneapolis, MN), Medtronic 3387 and 3389 leads, and a 1.5-T GE Horizon LX scanner (General Electric, Milwaukee, WI). In the in vivo study, two MRI volumetric data sets were compared for each of five patients undergoing staged, bilateral, DBS electrode placement in the thalamic or subthalamic nucleus. The data sets were acquired shortly after the initial implantation and during stereotactic planning for the second implantation (1-8 mo between acquisitions). An additional thalamotomy-treated patient was included as a control patient. Volumetric data were analyzed in a blinded manner, using AnalyzeAVW 3.0 software (Biomedical Imaging Resource, Mayo Clinic, Rochester, MN), to determine lead movement. In the in vitro study, the IPG and leads were positioned in the magnetic field in various configurations and were systematically assessed for movement. RESULTS In vivo, the majority of measured deviations (88%) were within the standard error of measurement (1.4 mm). The maximal measured deviation was 3 mm (2% occurrence). Excellent tremor control with stimulation was demonstrated, which did not change after MRI. In vitro, the DBS leads demonstrated no deflection when introduced into the magnetic field. Similarly, no changes in IPG battery strength, lead impedance, or program settings were observed. CONCLUSION MRI was not associated with significant DBS electrode movement or changes in clinical responses. Other IPG models and components and MRI scanners should be evaluated, to develop specific guidelines for MRI among individuals with implanted DBS systems.

Depression in Parkinson's disease

OBJECTIVE To examine predictive factors associated with onset of depression among individuals diagnosed with Parkinsons disease (PD). BACKGROUND Depression may precede or follow symptomatic parkinsonism in PD. It is frequently treatable but often overlooked. METHODS The clinical series comprised 685 individuals who were diagnosed with PD and followed by one neurologist (RJU) from 1994 to 2007. The primary outcome was time to depression following the onset of PD. Diagnosis of depression was based on clinical assessment of depressive symptoms from patients (and spouse/family/caregiver) and antidepressant usage. A number of demographic, historical and clinical predictive factors were examined, including gender, age at symptomatic onset, disease duration, onset characteristics, clinical ratings, antiparkinsonian medications, cognitive status, depression history, and familial history of PD and other neurodegenerative disorders. RESULTS Seventy-two percent of patients developed depression within ten years of symptomatic PD onset, and the mean time to depression was 7.9 years (median: 5.7 years). Factors associated with depression included longer PD duration, greater impairment in activities of daily living, and positive family history of motor neuron disease (MND). CONCLUSIONS A high rate of individuals with PD develop depressive symptoms during the course of the disease. Based on first clinic visit characteristics, most factors examined were not helpful in identifying individuals with an increased risk of depression. However, disease duration, functional limitations and family history of MND should lead clinicians to an increased vigilance for identifying depression.

Life satisfaction following spinal cord injury: long-term follow-up.

Abstract Objective: T o determine the course of self-reported life satisfaction in a spinal cord injury (SCI) cohort. Design: Prospective study using longitudinal data from the lnjury Control Research Center. Participants: Adult persons with traumatic-onset SCI (n = 207) evaluated at 1, 2, 4, and 5 years postinjury using the Life Satisfaction lndex-A. Results: A nonsignificant (P > 0.0 5) main effect of time was found using a repeated-measures analysis controlling for education and employment status. Several methods were used that provided a range of liberal to conservative estimates for missing data (ie, 3 8% retention rate at year 5). Subsequent missing data analyses tended to corroborate the finding of a nonsignificant effect of time, although the most conservative methods showed a significant decrease in life satisfaction between year 1 and year 5 postinjury (P < 0.05). Examination of numerous demographic, injury, and treatment-related characteristics at each follow-up time point suggested that the main findings of the study were not merely the result of differential dropout rates. Conclusion: Life satisfaction after the first year of injury remains largely the same over the next 4 years. Methodologie and analytic recommendations are discussed.

The prevalence of acute response to bronchodilator in pulmonary lymphangioleiomyomatosis

Objective:  The objective of this study was to evaluate the prevalence of acute bronchodilator responses in patients who were evaluated for pulmonary lymphangioleiomyomatosis.

Deep brain stimulation lead fixation: a comparative study of the Navigus and Medtronic burr hole fixation device

OBJECTIVES To determine the extent of lead movement based on the type of burr hole fixation device used to secure the lead (Image-Guided Neurologics [IGN], Navigus versus Medtronic [Model 7495-51]). A randomized, blinded design of lead movement measurement was used. METHODS A clinical series of 58 individuals undergoing placement of a deep brain stimulation (DBS) system with a total of 71 operative sides were examined. Lead position was compared between 71 paired, sagital, digitized X-rays of lead position immediately before and after the lead was secured to the basecap. Lead movement was measured in a randomized, blinded fashion using the Siemens measurement tool at an 8x magnification rate. The presurgical planned target centered at the cross hatch of the reticules on a lateral X-ray served as the reference point to determine lead movement. RESULTS The overall mean lead movement was significantly less using the IGN (1.9 mm), as compared to the Medtronic (3.3 mm), fixation device. Moreover, the pattern of lead movement was significantly different between the two devices. That is, the majority of measured movements using IGN device was in the superior direction (74%), whereas the opposite was true for the Medtronic device (i.e., 62% with inferior movement). CONCLUSION The IGN burr hole fixation device is associated with significantly less movement when securing the lead. Probable mechanisms of movement are discussed.

Effect of MAPT and APOE on prognosis of progressive supranuclear palsy.

To assess genetic influence on the clinical presentation of progressive supranuclear palsy (PSP), the genetic effect on disease course was examined for variants in the tau gene (MAPT) and the gene for apolipoprotein E (APOE) in 58 cases of pathologically confirmed PSP. Clinical indicators of disease course included age at symptomatic onset (AAO), age at death (AAD), and disease duration (DD) and the genetic effects examined included MAPT haplotypes and APOE genotypes. From linear regression analysis, the MAPT H1/H1 genotype was associated with significantly earlier AAO (P=0.038). The MAPT genotype did not significantly influence DD or AAD. The APOE epsilon4 allele did not significantly influence AAO, AAD, or DD. Male sex was a predictor for earlier AAO (P=0.015). The interaction between MAPT and APOE was not significant for AAD and DD, but a significant negative coefficient was found for AAO suggesting their combination does not have an additive effect. These results support the assertion that the H1/H1 genotype may contribute to the earlier occurrence of clinical symptoms.

Progressive supranuclear palsy: phenotypic sex differences in a clinical cohort.

We examined sex‐based differences in phenotypic expression among a consecutive clinical series of 121 individuals diagnosed with probable progressive supranuclear palsy (PSP). For both men (44%) and women (56%), the age at symptomatic onset (66.2 and 68.5 years, respectively) and disease duration (4.6 and 4.3 years, respectively) were similar. The overwhelming majority of sex‐based comparisons showed no significant difference on a variety of demographic, historical, and clinical characteristics, as well as measures of disease progression. The only differences observed were that men had significantly worse tremor as measured by the Unified Parkinsons Disease Rating Scale tremor subscore (0.9 for men and 0.3 for women, P < 0.01) and men had a significantly higher mean body mass index (BMI; 28.2 for men and 25.1 for women, P = 0.01), although these differences were not significant after Bonferroni correction. In general, the disease phenotype was similar between men and women, suggesting that sex may have little or no influence on the development, expression, or progression of the PSP phenotype.