Monday, 30 April 2012

Clinical features of Parkinson disease when onset of diabetes came first: A case-control study.

Neurology. 2012 Apr 25. [Epub ahead of print]
Cereda E, Barichella M, Cassani E, Caccialanza R, Pezzoli G.



Recent literature suggests that diabetes is a risk factor for Parkinson disease (PD). We investigated the clinical features of patients with idiopathic PD (IPD) in whom the onset of diabetes came first.


We designed a case-control study. From the cohort of all new patients with IPD free of vascular disease (n = 783) admitted and evaluated at our institute over a 3-year period (2007-2010), we included all the patients with a diagnosis of diabetes prior to PD onset (n = 89) and a control group (n = 89) matched (1:1) for gender, body mass index (±1 kg/m(2)), and duration of PD (±1 year). The Unified Parkinson's Disease Rating Scale (UPDRS) motor score was the primary endpoint.


At study entry, patients with diabetes were similar to controls in terms of most demographic, lifestyle, and general medical features with exception of statins (18% vs 3.4%; p = 0.003). However, diabetes was associated with higher UPDRS motor (22.3 ± 9.0 vs 19.3 ± 7.9; p = 0.019) and activities of daily living (9.7 ± 5.1 vs 8.3 ± 4.3; p = 0.049) scores, more severe Hoehn & Yahr staging (p = 0.009), and higher treatment doses of levodopa (mg/day, 448 ± 265 vs 300 ± 213; p < 0.0001; mg/kg/day, 5.8 ± 4.0 vs 3.8 ± 2.9; p < 0.0001).


Onset of diabetes before the onset of PD appears to be a risk factor for more severe PD symptoms. These findings support the hypothesis that diabetes has a role in the etiopathogenesis of PD. Neurologists should be aware of the potential impact of diabetes on overall PD management.

Friday, 27 April 2012

Accuracy of subjective and objective handwriting assessment for differentiating Parkinson's disease from tremulous subjects without evidence of dopaminergic deficits (SWEDDs): an FP-CIT-validated study

J Neurol. 2012 Apr 25. [Epub ahead of print]
Bajaj NP, Wang L, Gontu V, Grosset DG, Bain PG.


Handwriting examinations are commonly performed in the analysis of tremor and Parkinson's disease (PD). We analyzed the accuracy of subjective and objective assessment of handwriting samples for distinguishing 27 PD cases, 22 with tremulous PD, and five with akinetic-rigid PD, from 39 movement-disorder patients with normal presynaptic dopamine imaging (subjects without evidence of dopamine deficiency or SWEDDs; 31 with dystonic tremor (DT), six indeterminate tremor syndrome, one essential tremor, one vascular parkinsonism). All handwriting analysis was performed blind to clinical details. Subjective classification was made as: (1) micrographia, (2) normal, or (3) macrographia. In addition, a range of objective metrices were measured on standardized handwriting specimens. Subjective assessments found micrographia more frequently in PD than SWEDDs (p = 0.0352) and in akinetic-rigid than tremulous PD (p = 0.0259). Macrographia was predominantly seen in patients with dystonic tremor and not other diagnoses (p = 0.007). Micrographia had a mean sensitivity of 55 % and specificity of 84 % for distinguishing PD from SWEDDs and mean sensitivity of 90 % and specificity of 55 % for distinguishing akinetic-rigid PD from tremulous PD. Macrographia had a sensitivity of 26 % and specificity of 96 % for distinguishing DT from all other diagnoses. The best of the objective metrices increased sensitivity for the distinction of SWEDDs from PD with a reduction in specificity. We conclude that micrographia is more indicative of PD than SWEDDs and more characteristic of akinetic-rigid than tremulous PD. In addition, macrographia strongly suggests a diagnosis of dystonic tremor.

Tuesday, 24 April 2012

Factors contributing to spousal and offspring caregiver burden in Parkinson's disease

Eur Neurol. 2012;67(5):292-6. Epub 2012 Apr 17.
Shin H, Lee JY, Youn J, Kim JS, Cho JW.


Background/Aims: Parkinson's disease (PD) is a common neurodegenerative disease with a chronic disease course. The increase in life expectancy of humans worldwide is expected to increase the prevalence and duration of PD; therefore, it is important to determine factors that contribute to the caregiver burden for both clinical and social reasons. Methods: We surveyed 91 main caregivers of patients, and compared factors contributing to caregiver burden between 50 spouses and 41 offspring of patients. We determined Burden Interview, Depression Scale, Health-Related Quality of Life, and Obligation Scale scores, as well as the degree of functional social support of caregivers. Results: Interestingly, the burden scores of the two groups were not significantly different. Correlation analysis revealed that depression, health-related quality of life, social support, subdivided parts of the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr Scale, score of Mini-Mental State Examination, and Barthel index were correlated with burden in both spouses and offspring. However, in multiple regression, depression score and part 1 of the UPDRS were more significant predictors of burden in the spousal group, whereas social support of community and part 3 of the UPDRS were more important correlated factors in the offspring group. Conclusions: The caregiver burden of spousal and offspring caregivers of PD patients was not significantly different. However, different factors contributed to caregiver burden according to the caregiver's relationship with the patient.

Monday, 23 April 2012

Identifying prodromal Parkinson's disease: Pre-Motor disorders in Parkinson's disease.

Mov Disord. 2012 Apr 15;27(5):617-26. doi: 10.1002/mds.24996.
Postuma RB, Aarsland D, Barone P, Burn DJ, Hawkes CH, Oertel W, Ziemssen T.


Increasing recognition that Parkinson's disease (PD) may start outside of the substantia nigra has led to a rapidly expanding effort to define prodromal stages of PD, before motor signs permit classical diagnosis. Many of these efforts center around the identification of clinical non-motor symptoms and signs of disease. There is now direct evidence that olfaction, rapid eye movement (REM) sleep behavior disorder (RBD), constipation, and depression can be present in prodromal PD. In addition, there is suggestive evidence that visual changes, other autonomic symptoms, and subtle cognitive changes may also be present at prodromal stages. A critical issue in utility of these prodromal markers will be assessment of sensitivity, specificity, and positive and negative predictive values. Although these have yet to be fully defined, olfactory deficits, some visual changes, and autonomic symptoms occur in the majority of PD patients at diagnosis, suggesting good potential sensitivity. However, with the exception of RBD and perhaps some specific autonomic measures, specificity, and positive predictive value of these markers may be insufficient to be used alone as identifiers of prodromal disease. The evidence for the utility of olfaction, RBD, autonomic markers, visual changes, mood disorders, and cognitive loss as markers of prodromal PD and the potential sensitivity and specificity of these markers are summarized. © 2012 Movement Disorder Society.
Copyright © 2012 Movement Disorder Society.

Prerequisites to launch neuroprotective trials in Parkinson's disease: An industry perspective.

Mov Disord. 2012 Apr 15;27(5):651-5. doi: 10.1002/mds.25017.
Streffer JR, Grachev ID, Fitzer-Attas C, Gomez-Mancilla B, Boroojerdi B, Bronzova J, Ostrowitzki S, Victor SJ, Fontoura P, Alexander R.


Realizing that 60% to 80% of dopaminergic nigrostriatal neurons are nonfunctional at the time of clinical diagnosis, there is an emerging consensus that disease-modifying treatments should be initiated in the earliest stages of Parkinson's disease (PD). To date, clinical trial designs and metrics in PD have been focused on motor symptoms as the core feature of the clinical disease. To identify earlier or "pre-motor" populations in PD, new markers have been proposed. We address the prerequisites needed to use these pre-motor markers in clinical trials for the selection of subjects, definition of populations, and monitoring of disease progression. This may require the development of new diagnostic criteria potentially based on non-motor clinical signs, imaging techniques, or biological features, all requiring discussion in a regulatory framework. Questions addressed include: Which steps must be taken to gain a broad consensus in the field from academic opinion leaders, patient advocacy groups, regulatory bodies, and industry? How do we prevent the selection of subgroups, which may not be representative of the full disease spectrum? Is there a way forward in personalized medicine? How do we balance risk and benefit in an at-risk population? While many tools are available, a concerted effort is required to develop integrated data sets, as well as to achieve the necessary standardization for multicenter clinical trials. To this end, public-private consortia (including academic centers, patient advocacy groups, and industry) will be of crucial importance to prospectively investigate and define the best tools and treatment paradigms. © 2012 Movement Disorder Society.

Sunday, 8 April 2012

Dihydropyridine calcium channel blockers and the progression of parkinsonism.

Ann Neurol. 2012 Mar;71(3):362-9. doi: 10.1002/ana.22616.
Marras C, Gruneir A, Rochon P, Wang X, Anderson G, Brotchie J, Bell CM, Fox S, Austin PC.

A study was undertaken to test the association between dihydropyridine calcium channel blocker use and the time to important milestones of disease progression among patients with parkinsonism.

Data were obtained from Ontario's health care administrative databases. Within a cohort of hypertensive individuals older than 65 years who developed parkinsonism, we examined the effect of the length of exposure to less brain-penetrant dihydropyridines (amlodipine) and more brain-penetrant dihydropyridines (eg, nifedipine, felodipine) on parkinsonism milestones as measured by time to requiring drug treatment for parkinsonism, nursing home admission, and death.

Among 4,733 hypertensive individuals with parkinsonism, longer treatment with any dihydropyridine was associated with a decreased risk of each of the 3 outcomes. There was no difference, however, between amlodipine (adjusted hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.42-0.50 for initiation of drug treatment; HR, 0.68; 95% CI, 0.63-0.73 for application for nursing home admission; and HR, 0.75; 95% CI, 0.70-0.80 for death) and nonamlodipine dihydropyridines (adjusted HRs [95% CIs], 0.45 [0.39-0.53], 0.74 [0.67-0.81], and 0.74 [0.64-0.85] for the 3 milestones, respectively).

We found no specific beneficial effect of treatment with brain-penetrant dihydropyridines on delaying parkinsonism progression milestones. Dihydropyridine calcium channel blockers are unlikely to have a clinically significant effect on the course of parkinsonism, particularly Parkinson disease, in the doses used to treat hypertension.

High school football and risk of neurodegeneration: a community-based study.

Mayo Clin Proc. 2012 Apr;87(4):335-40.
Savica R, Parisi JE, Wold LE, Josephs KA, Ahlskog JE.


To assess whether high school football played between 1946 and 1956, when headgear was less protective than today, was associated with development of neurodegenerative diseases later in life.

All male students who played football from 1946 to 1956 in the high schools of Rochester, Minnesota, plus a non-football-playing referent group of male students in the band, glee club, or choir were identified. Using the records-linkage system of the Rochester Epidemiology Project, we reviewed (from October 31, 2010, to March 30, 2011) all available medical records to assess later development of dementia, Parkinson disease (PD), or amyotrophic lateral sclerosis (ALS). We also compared the frequency of dementia, PD, or ALS with incidence data from the general population of Olmsted County, Minnesota.

We found no increased risk of dementia, PD, or ALS among the 438 football players compared with the 140 non-football-playing male classmates. Parkinson disease and ALS were slightly less frequent in the football group, whereas dementia was slightly more frequent, but not significantly so. When we compared these results with the expected incidence rates in the general population, only PD was significantly increased; however, this was true for both groups, with a larger risk ratio in the non-football group.

Our findings suggest that high school students who played American football from 1946 to 1956 did not have an increased risk of later developing dementia, PD, or ALS compared with non-football-playing high school males, despite poorer equipment and less regard for concussions compared with today and no rules prohibiting head-first tackling (spearing).

Amantadine: The journey from fighting flu to treating Parkinson disease.

Neurology. 2012 Apr 3;78(14):1096-9.
Hubsher G, Haider M, Okun MS.

To explore how amantadine transitioned from an anti-flu drug to antiparkinsonian agent.

A review of the historical literature on the use of amantadine from 1966 to the present was performed.

Amantadine was originally introduced and utilized as an antiviral medication. A single patient noticed relief in her Parkinson disease (PD) symptoms after taking amantadine for a flu infection, and this observation sparked an interest, and several important studies that eventually led to a new drug indication.

Amantadine has over the years fallen out of favor as a drug to address influenza infection; however, it has become part of the arsenal utilized for early symptomatic treatment of PD, as well an option for treating dyskinesia.