Treatable inherited rare movement disorders.

There are many rare movement disorders, and new ones are described every year. Because they are not well recognized, they often go undiagnosed for long periods of time. However, early diagnosis is becoming increasingly important. Rapid advances in our understanding of the biological mechanisms responsible for many rare disorders have enabled the development of specific treatments for some of them. Well-known historical examples include Wilson disease and dopa-responsive dystonia, for which specific and highly effective treatments have life-altering effects. In recent years, similarly specific and effective treatments have been developed for more than 30 rare inherited movement disorders. These treatments include specific medications, dietary changes, avoidance or management of certain triggers, enzyme replacement therapy, and others. This list of treatable rare movement disorders is likely to grow during the next few years because a number of additional promising treatments are actively being developed or evaluated in clinical trials. © 2017 International Parkinson and Movement Disorder Society.

Diagnostic cutoff points for ¹²³I-MIBG myocardial scintigraphy in a Caucasian population with Parkinson's disease.

PURPOSE: Molecular imaging with (123)I-metaiodobenzylguanidine (MIBG) has been used in Parkinson's disease (PD), but there is no consensual index to discriminate between normal and PD patients in the Caucasian population. The purpose of this study was to determine diagnostic cutoff points in the quantification of MIBG cardiac uptake in our population of PD patients. We have also calculated the reproducibility over a range of interpretation expertise. METHODS: The study included 14 PD patients and 14 normal age- and sex-matched controls. Heart to mediastinum ratios (H/M) were calculated at 15 min (H/M15m) and 4 h (H/M4h) post-injection by three observers with different interpretation expertise, one of whom drew the regions of interest at three different times. The intraobserver and interobserver reliability was calculated (interclass correlation coefficient and coefficient of variability). Diagnosis was estimated by maximizing the Youden index for H/M and washout ratios. Discrimination ability was assessed by the area under the curve (AUC). Sensitivity and specificity were reported, using our thresholds. RESULTS: The parameter with the best diagnostic accuracy was the H/M4h ratio, with a major AUC (0.976 area under the receiver-operating characteristic curve). The threshold was 1.43 with a 95% confidence interval of 1.37-1.50. Using this threshold, the sensitivity and specificity were 93 and 100%. The interobserver and intraobserver variabilities measuring this ratio were 3.2 and 3.1%, respectively. CONCLUSION: The diagnostic cutoff point for (123)I-MIBG myocardial scintigraphy in a Caucasian population with PD was 1.43 for the H/M4h index, with a good sensitivity and specificity. The technique is easy to use, with a good reproducibility over a range of interpretation expertise.

123I-MIBG cardiac uptake and smell identification in parkinsonian patients with LRRK2 mutations.

Reduced uptake of (123)I- metaiodobenzylguanidine (MIBG) on cardiac gammagraphy and impaired odor identification are markers of neurodegenerative diseases with Lewy bodies (LB) as a pathological hallmark, such as idiopathic Parkinson's disease (IPD). LRRK2 patients present with a clinical syndrome indistinguishable from IPD, but LB have not been found in some cases. Patients with such mutations could behave differently than patients with IPD with respect to MIBG cardiac uptake and olfaction. We studied 14 LRRK2 patients, 14 IPD patients matched by age, gender, disease duration and severity, and 13 age and gender matched control subjects. Olfaction was analyzed through the University of Pennsylvania Smell Identification Test (UPSIT). MIBG cardiac uptake was evaluated through the H/M ratio. The late H/M was 1.44 ± 0.31 for LRRK2 patients, 1.19 ± 0.15 for PD patients, and 1.67 ± 0.16 for control subjects. LRRK2 patients presented lower but not statistically significant MIBG cardiac uptake than controls (p = 0.08) and significant higher uptake than PD patients (p = 0.04). UPSIT mean scores were 21.5 ± 7.3 for LRRK2 patients, 18.7 ± 6.2 for IPD patients and 29.7 ± 5.7 for control subjects. UPSIT score was lower in both LRRK2 and PD than in controls. In LRRK2 patients a positive correlation was found between myocardial MIBG uptake and UPSIT scores, (R = 0.801, p < 0.001). In LRRK2 patients, MIBG cardiac uptake was less impaired than in PD; a positive correlation between MIBG cardiac uptake and UPSIT scores was observed. As MIBG cardiac reduced uptake and impaired odor identification are markers of LB pathology, this findings may represent neuropathological heterogeneity among LRRK2 patients.