Training dual tasks together or apart in Parkinson's disease: Results from the DUALITY trial.

BACKGROUND AND OBJECTIVES: Many controversies surround the usefulness of dual-task training in Parkinson's disease (PD). This study (1) compared the efficacy of two different dual-task training programs for improving dual-task gait and (2) assessed the possible fall risk of such training. METHODS: Patients (N = 121) with a diagnosis of PD (aged 65.93 [±9.22] years, Hoehn and Yahr stage II-III on-medication) were randomized to (1) a consecutive group in which gait and cognitive tasks were trained separately or (2) an integrated group in which gait and cognitive tasks were trained simultaneously. Both interventions involved 6 weeks of at-home physiotherapist-led training. Two baseline tests were performed as a 6-week control period before training. Posttests were performed immediately after training and at 12-week follow-up. Dual-task gait was assessed during trained and untrained secondary tasks to assess consolidation of learning. Fall risk was determined by a weekly telephone call for 24 weeks. RESULTS: No significant time by group interactions were found, suggesting that both training modes had a similar effect on dual-task gait. Immediately after training, and not after the control period, significant improvements (P < .001) in dual-task gait velocity were found in all trained and untrained dual tasks. Improvements ranged between 7.75% and 13.44% when compared with baseline values and were retained at 12-week follow-up. No significant change in fall risk occurred in both study arms (P = .84). CONCLUSIONS: Consecutive and integrated dual-task training led to similar and sustained improvements in dual-task gait velocity without increasing fall risk. These novel findings support adoption of dual-task training in clinical practice. © 2017 International Parkinson and Movement Disorder Society.

A case of mental nerve paresthesia due to dynamic compression of alveolar inferior nerve along an elongated styloid process.

Spontaneous paresthesia of the mental nerve is considered an ominous clinical sign. Mental nerve paresthesia has also been referred to as numb chin syndrome. Several potentially different factors have been investigated for their role in interfering with the inferior alveolar nerve (IAN) and causing mental nerve neuropathy. In the present case, the patient had an elongated calcified styloid process that we hypothesized had caused IAN irritation during mandibular movement. This eventually resulted in progressive loss of sensation in the mental nerve region. To our knowledge, this dynamic irritation, with complete recovery after resection of the styloid process, has not been previously reported.

Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations.

Early-onset Parkinson's disease (EOPD) has been associated with recessive mutations in parkin (PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large deletions or duplications. Although many different rearrangements have been found in parkin before, the exact breakpoints involving these rearrangements are rarely mapped. In the present study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13 patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests were developed as a rapid and low cost tool to confirm MLPA results and to test family members or patients with similar parkin deletions/duplications. Besides several different deletions, an exon 3 deletion, an exon 4 deletion and an exon 7 duplication were found in multiple families. Haplotype analysis in four families showed that a common haplotype of 1.2 Mb could be distinguished for the exon 7 duplication and a common haplotype of 6.3 Mb for the deletion of exon 4. These findings suggest common founder effects for distinct large rearrangements in parkin.

Vascular chorea in adults and children.

Chorea may occur as part of the symptomatology of acute stroke; it occasionally also may be delayed or progressive. Patients with vascular-related chorea typically present with an acute or subacute onset of chorea of one side of the body (hemichorea), contralateral to the lesion. Cerebrovascular disease is the most common cause of sporadic chorea. Lesions are most frequently found in the thalamus and lentiform nucleus, and less often in subthalamic nucleus. The differential diagnosis of choreic syndromes relies not so much on differences in the phenomenology of the hyperkinesia but the age at onset, mode of onset, time course, family history, drug use, distribution of chorea in the body, and presence of accompanying neurological findings. Magnetic resonance imaging is preferred to demonstrate the presence of strategic small lesions in regions that are difficult to image with computed tomography, such as the globus pallidus, thalamus, and subthalamic nucleus. Although the prognosis of hemichorea can be benign, the long-term prognosis is not specifically determined by the hemichorea but by the long-term prognosis of stroke patients. Symptomatic treatment with antichoreic drugs may be necessary in the acute phase. Surgery is rarely indicated to treat vascular chorea.

The role of imaging in the diagnosis of vascular parkinsonism.

Parkinsonism is a syndrome that features bradykinesia (slowness of the initiation of voluntary movement) and at least 1 of the following conditions: rest tremor, muscular rigidity, or postural instability. Criteria for the clinical diagnosis of vascular parkinsonism (VP) have been proposed, which are derived from a postmortem examination study. Computed tomography and magnetic resonance imaging can support this clinical diagnosis with positive imaging findings. Dopamine transporter single-photon emission computed tomography may also be of help to distinguish VP from Parkinson disease and other parkinsonisms.

Safety of entacapone and apomorphine coadministration in levodopa-treated Parkinson's disease patients: pharmacokinetic and pharmacodynamic results of a multicenter, double-blind, placebo-controlled, cross-over study.

We investigated whether administration of the catechol-O-methyl transferase (COMT) inhibitor entacapone, at doses of 200 mg and 400 mg, alters the pharmacokinetics of apomorphine in Parkinson's disease patients experiencing severe motor fluctuations. In addition, the pharmacodynamics and safety of entacapone and apomorphine coadministration in these patients were examined. The study followed a three-sequence, three-period, crossover design. Patients were randomly assigned to one of three sequences that included single oral doses of entacapone 200 mg, entacapone 400 mg, and placebo in a predefined order. On 3 separate test days, study treatment was administered before apomorphine. The study evaluations (pharmacokinetics, tapping test, and dyskinesia evaluation [Abnormal Involuntary Movements Scale - AIMS]) were performed on these days. Furthermore, Unified Parkinson Disease Rating Scale (UPDRS) scores were evaluated at baseline and study end. Pharmacokinetic parameters for apomorphine (C(max), AUC, t(max), t(1/2)) were unchanged by the administration of entacapone, and changes in both the tapping test and AIMS score were similar with all treatments (entacapone 200 mg, entacapone 400 mg, and placebo). There was no significant difference in mean total UPDRS scores between baseline and study end. The administration of entacapone did not change the pharmacokinetic or pharmacodynamic effects of apomorphine in these patients or prolong the clinical effect of apomorphine. Thus, apomorphine may be safely administered to patients receiving therapy with levodopa and entacapone, providing a useful addition to treatment for patients with advanced Parkinson's disease.

Clinicopathological investigation of vascular parkinsonism, including clinical criteria for diagnosis.

Vascular parkinsonism (VP) is difficult to diagnose with any degree of clinical certainty. We investigated the importance of macroscopic cerebral infarcts and pathological findings associated with microscopic "small vessel disease" (SVD) in the aetiology of VP. The severity of microscopic SVD pathology (perivascular pallor, gliosis, hyaline thickening, and enlargement of perivascular spaces) and the presence of macroscopically visible infarcts were assessed in 17 patients with parkinsonism and no pathological evidence of either Parkinson's disease or any histopathological condition known to be associated with a parkinsonian syndrome, and compared with age-matched controls. Microscopic SVD pathology was significantly more severe in the parkinsonian brains. Most patients presented with bilateral bradykinesia and rigidity together with a gait disorder characterised predominantly by a shuffling gait. Four patients presented acutely with hemiparesis and then progressed to develop a parkinsonian syndrome. They could be distinguished from the remaining VP patients by the presence at autopsy of macroscopically visible lacunar infarcts in regions where contralateral thalamocortical drive might be reduced. The clinical features at presentation varied according to the speed of onset and the underlying vascular pathological state. New clinical criteria for a diagnosis of VP are proposed based on the clinicopathological findings of this study.

[123I]beta-CIT SPECT distinguishes vascular parkinsonism from Parkinson's disease.

We investigated whether [(123)I]-beta-CIT and single-photon emission computed tomography (SPECT) imaging distinguishes patients with clinically suspected vascular parkinsonism (VP) from patients with idiopathic Parkinson's disease (PD). [(123)I]beta-CIT SPECT is a sensitive marker of dopaminergic degeneration, and the degree of striatal binding reduction in PD correlates with disease severity. Thirteen patients who fulfilled rigid clinical criteria for VP (mean +/- S.D.: age, 76.5 +/- 5.3 years; disease duration, 3.6 +/- 2.8 years), 20 PD patients (age, 66.2 +/- 9.5 years; disease duration, 4.3 +/- 2.7 years), and 30 healthy persons (age, 44.6 +/- 19.2 years) underwent [(123)I]beta-CIT SPECT imaging. Age-corrected striatal beta-CIT binding was reduced on average by 40.8% in PD but was near normal in the VP group (mean reduction, 1.2%). This difference was statistically significant (Z = 4.68; P < 0.001). The left-right asymmetry of striatal beta-CIT binding was significantly increased in the PD group compared with normal controls and the VP group (F(2) = 17.4, P <0.001). Moreover, putamen-caudate nucleus ratios were significantly reduced in PD compared with both VP patients and healthy controls (F(2) = 65.5, P < 0.001). Whole striatal beta-CIT binding was more than one standard deviation above the mean PD values in all but one of the individual VP patients. Our findings suggest that the presynaptic dopaminergic deficits seen in PD are absent in most patients with VP. [(123)I]beta-CIT SPECT imaging may be useful to help distinguish between PD and VP patients during life.