Hereditary chorea - what else to consider when the Huntington's disease genetics test is negative?

Chorea, cognitive, behavioural and psychiatric disturbance occur in varying combinations in Huntington's disease (HD). This is often easy to recognise particularly in the presence of an autosomal dominant history. Whilst HD may be the most common aetiology of such a presentation, several HD phenocopies should be considered if genetic testing for HD is negative. We searched PubMed and the Cochrane Database from January 1, 1946 up to January 1, 2016, combining the search terms: 'chorea', 'Huntington's disease', 'HDL' and 'phenocopies'. HD phenocopies frequently display additional movement disorders such as myoclonus, dystonia, parkinsonism and tics. Here, we discuss the phenotypes, and investigations of HD-like disorders where the combination of progressive chorea and cognitive impairment is obvious, but HD gene test result is negative. Conditions presenting with sudden onset chorea such as vascular, infectious and autoimmune causes are not the primary focus of our discussion, but we will make a passing reference to these as some of these conditions are potentially treatable. Hereditary forms of chorea are a heterogeneous group of conditions and this number is increasing. While most of these conditions are not curable, molecular genetic testing has enabled many of these disorders to be distinguished from HD. Getting a precise diagnosis may enable patients and their families to better understand the nature of their condition.

Relationship between [123 I]-FP-CIT SPECT and clinical progression in Parkinson's disease.

BACKGROUND: The demonstration of presynaptic dopaminergic deficiency on [123 I]-FP-CIT SPECT imaging is a useful ancillary tool in the diagnosis of Parkinson's disease (PD). Whilst there is evidence of a cross-sectional relationship between the degree of dopaminergic deficiency and severity of bradykinesia and rigidity, longitudinal studies are rare. Moreover, the relationship between motor subtypes and their dopaminergic deficient state is not well characterized. AIM: Our primary aim was to assess the correlations between dopaminergic deficiency on baseline [123 I]-FP-CIT SPECT imaging with the progression of motor severity in patients classified by motor subtype, and the development of motor complications. Our secondary aim was to assess the correlation between UPDRS-III subscores and the time to onset of motor complications. METHODS: 42 PD patients with abnormal baseline [123 I]-FP-CIT SPECT scans and at least 3 years of clinical follow-up were classified by motor subtype: akinetic-rigid, tremor-dominant or mixed. UPDRS-III scores at baseline and at 3-year follow-up, and time to onset of motor complications were recorded. RESULTS: [123 I]-FP-CIT uptake ratios were inversely correlated with UPDRS-III scores at 3 years only in akinetic-rigid patients (r=-.51, P=.04). Time to onset of motor complications was inversely correlated with UPDRS-III subscores for bradykinesia and rigidity at baseline (r=-.52, P=.02) and at 3 years (r=-.54, P=.01). CONCLUSION: The degree of dopaminergic deficiency on baseline [123 I]-FP-CIT SPECT inversely correlates with motor severity at 3-year follow-up in akinetic-rigid patients only. Furthermore, UPDRS-III subscores for bradykinesia and rigidity at baseline show an inverse correlation with time to onset of motor complications across all PD subtypes.

Baseline [(123) I]FP-CIT SPECT (DaTSCAN) severity correlates with medication use at 3 years in Parkinson's disease.

BACKGROUND: Presynaptic dopaminergic deficiency on dopamine transporter imaging supports a clinical diagnosis of Parkinson's disease and correlates with the severity of rigidity and bradykinesia. Baseline dopaminergic deficiency predicts clinical severity, but the relationship with subsequent medication use has not been reported. METHODS: A randomly selected cross section of 83 Parkinson's disease (PD) patients who had [(123) I] FP-CIT SPECT at the time of clinical diagnosis was identified. Dopaminergic deficiency was graded 1, 2 or 3 with increasing severity using visual assessment and by semiquantitative analysis of putamen and caudate uptake. Antiparkinson medication usage and clinical severity by Hoehn and Yahr were noted annually to 3 years. RESULTS: In 83 patients (66% male, median age 65.0 years, IQ 55.4-71.8), [(123) I]FP-CIT SPECT was grade 1 in 20 (24%), grade 2 in 53 (64%) and grade 3 in 10 patients (12%). Dopamine transporter uptake ratios were inversely associated with antiparkinson medication usage (r = -0.26, P = 0.0201) and Hoehn Yahr stage (r = -0.32, P = 0.0029) at 3 years from baseline, but there was considerable variation in drug usage in individual patients. At 3 years, patients with grade 1 scans at baseline received a median dose of 325 levodopa equivalent units (LEU) (interquartile range 175-433); grade 2 scan patients 400 LEU (interquartile range 300-635); and grade 3 scan patients 460 LEU (interquartile range 252-658). CONCLUSION: The degree of reduction in presynaptic dopaminergic uptake at baseline is associated with higher antiparkinson drug dosage at follow-up, but the wide variation means that the baseline FP-CIT SPECT does not reliably predict drug use in individual cases.

Duration of L-dopa and dopamine agonist monotherapy in Parkinson's disease.

The expected duration of initial antiparkinson monotherapy before the need for supplementation is not clearly defined for routine practice. The aim of this study was to define the length of L-dopa (L-3, 4-dihydrophenylalanine) and dopamine agonist monotherapy. The duration of monotherapy and discontinuation rates were investigated in a natural observational setting by plotting Kaplan-Meier survival curves. Out of 345 patients, 180 (52.2%) received L-dopa and 165 (47.8%) received a dopamine agonist as initial monotherapy. Half of the patients starting L-dopa received supplementary therapy with- in 3.6 years (95% confidence interval, 3.2-4.6), significantly longer than for dopamine agonist monotherapy (half required a second agent at 2.3 years [2.0-2.9]; P = 0.00017). Discontinuation of L-dopa therapy was 1%. Dopamine agonists were stopped (due to side-effects like impulse control disorders [6%], somnolence [4%] and light-headedness [3%]) in 20% over four years. The duration and tolerability of L-dopa and dopamine agonists as initial Parkinson's disease monotherapy are defined in this study; this may form part of the information exchange with patients.