Executive cognitive deficits in primary dystonia.

Primary dystonia is a disorder of movement for which no consistent pathophysiology has been identified; in the absence of evidence to the contrary, it is assumed to be cognitively benign. We have studied a clinically heterogeneous group of 14 patients with primary dystonia on a battery of neuropsychological tests. Despite well-preserved speed of information processing, language, spatial, memory and general intellectual skills relative to normal controls, we have identified a constellation of attentional-executive cognitive deficits on the Cambridge Neuropsychological Test Automated Battery (CANTAB). Specifically, patients demonstrated significant difficulties negotiating the extra-dimensional set-shifting phase of the IED task. The implications of these findings for the pathophysiology of primary dystonia are discussed. This is, to the best of our knowledge, the first report of a significant cognitive deficit in patients with primary dystonia.     

Review of clinical and haematological response to low-dose cytosine arabinoside in acute myeloid leukaemia

15 patients with acute myeloid leukaemia (AML) were treated with low-dose cytosine arabinoside (LD ARA-C). 2 patients had complete remissions, which lasted for 8 and 3 months, and 5 patients had a partial remission. 46% of the patients thus responded to LD ARA-C. This included 1 responding patient who had not previously responded to therapy with 6-mercaptopurine, thioguanine, or vinblastine. The 2 patients with complete remission did not show LD ARA-C-induced hypoplasia of bone marrow, although 1 had hypoplastic AML before therapy. Leukaemic cells from 1 patient showed in vivo maturation from M1 to M3 after LD ARA-C treatment. The present results, together with the published data, indicate that: a. LD ARA-C treatment, although it may have some toxic effects, is an effective treatment for some patients with AML, especially those with hypoplastic AML; b. Response to LD ARA-C can be obtained after one or several courses of treatment; c. LD ARA-C-induced remissions are sometimes obtained even in patients who fail in more conventional treatments; d. LD ARA-C-induced remissions can be achieved without bone marrow hypoplasia, and induction of hypoplasia by itself does not always result in complete remission; e. LD ARA-C can induce in vivo maturation of leukaemic cells. It is suggested that induction of remission in AML patients by LD ARA-C may result from either differentiation of leukaemic blast cells, cytotoxicity to leukaemic blasts, or both mechanisms acting together.     

Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson''s disease

To assess the effect of levodopa on distinct freezing of gait (FOG) subtypes in patients with 'off' FOG. Nineteen patients (12 men, mean age 62.0 +/- 8.4 years) with Parkinson's disease and clinically significant FOG during 'off' states were videotaped whilst walking 130 m during 'off' and 'on' states. Three independent observers characterized the type, duration, and clinical manifestations and quantified FOG by analyzing the videotapes. Their combined mean scores were used for statistical analysis. The intra-class correlation coefficient assessed inter-observer reliability. Wilcoxon and Friedman tests evaluated differences in mean frequencies of FOG characteristics. During 'off' states, FOG was elicited by turns (63%), starts (23%), walking through narrow spaces (12%) and reaching destinations (9%). These respective values were only 14, 4, 2 and 1% during 'on' states (P < 0.011). Moving forward with very small steps and leg trembling in place were the most common manifestations of FOG; total akinesia was rare. Most FOG episodes took <10 s and tended to be shorter during 'on' states. Levodopa significantly decreased FOG frequency (P < 0.0001) and the number of episodes with akinesia (P < 0.001). Distinction amongst FOG subtypes enables evaluation of distinctive therapeutic response. Levodopa helps in reducing the frequency and duration of 'off'-related FOG.     

Rotigotine transdermal patch in early Parkinson's disease: a randomized, double-blind, controlled study versus placebo and ropinirole.

Rotigotine is a new, non-ergot dopamine agonist formulated in a transdermal delivery system. The present study was to investigate the efficacy and safety of the rotigotine transdermal patch in the treatment of early Parkinson's disease. Patients (n = 561) were randomized to rotigotine, ropinirole, or placebo. The titration period was up to 13 weeks, and there was a minimum dose-maintenance period of 24 weeks for ropinirole and 33 weeks for rotigotine. The primary endpoint was the proportion of patients with a minimum of 20% decrease in the combined Unified Parkinson's Disease Rating Scale Part II and Part III scores. The responder rate in the rotigotine group was significantly higher than in the placebo group (52% vs. 30%, P < 0.0001). Transdermal rotigotine at doses < or =8 mg/24 h did not show noninferiority to ropinirole at doses < or =24 mg/day. In a post-hoc subgroup analysis, rotigotine < or =8 mg/24 hours had a similar efficacy to ropinirole at doses < or =12 mg/day. The rotigotine transdermal patch was well tolerated. The most common adverse events were application-site reactions, nausea, and somnolence. Application-site reactions were predominantly mild or moderate in intensity. In conclusion, the rotigotine transdermal patch represents an effective and safe option for the treatment of patients with early Parkinson's disease.     

Freezing of gait affects quality of life of peoples with Parkinson's disease beyond its relationships with mobility and gait.

The aim of this study was to examine the association between freezing of gait (FOG) and quality of life (QoL) in patients with Parkinson's disease (PD). PD patients (n = 118) completed the PDQ-39 (QoL) and FOG-Q questionnaires. Disease severity was assessed by the Hoehn and Yahr (H&Y) staging and the Unified Parkinson's Disease Rating Scale (UPDRS). The relations between those parameters were assessed using regression models. 66 men and 52 women (mean age 65.8 +/- 10.2 years, UPDRS total score 48.4 +/- 17.1, disease duration 8.5 +/- 5.8 years, H&Y stage 2.7 +/- 0.8) participated. FOG severity had a significant effect on QoL (P < 0.0015), accounting for disease severity assessed by UPDRS. Specifically, FOG severity was correlated with all the dimensions of the PDQ-39 except for stigma and social support, as follows: with mobility, bodily discomfort, activity of daily living (ADL) (P < 0.005 in all), with emotional, communication, and cognition (P < 0.05 in all). FOG severity (FOG-Q) was also found to affect a modified PDQ total score, without the mobility aspect (P = 0.0081). FOG should be viewed as a highly important symptom with regard to QoL of PD patients beyond its effect on gait and mobility. On the basis of the present results, special attention should be given to FOG in the treatment of patients with PD.     

Long-term remission of idiopathic cervical dystonia after treatment with botulinum toxin

Botulinum toxin type A (BTX-A) treatment for cervical dystonia is traditionally considered a purely symptomatic treatment. BTX-A blocks acetyl choline exocytosis for 3-6 months and most patients require reinjection after this period. We report on 6 patients (mean age 41.6 years, range 18-69) with idiopathic cervical dystonia who were treated with BTX-A injections and became asymptomatic for 2-4 years. Four patients showed remission after the first BTX-A treatment, 1 patient after the second set of injections and 1 after the third session. Amelioration of neck dystonia was observed within 1-4 weeks after the last BTX-A treatment and all 6 patients are symptom-free, off antidystonic medications for over 2 years. The possibility that BTX-A treatment may increase the chances of development of clinical remission in patients with idiopathic cervical dystonia is discussed.     

Changes in the EEG spectral power during dual-task walking with aging and Parkinson’s disease: initial findings using Event-Related Spectral Perturbation analysis

Journal of Neurology - The ability to maintain adequate motor-cognitive performance under increasing task demands depends on the regulation and coordination of neural resources. Studies have shown...