Possibilities of using computed tomography to treat mixed cervical dystonia with botulinum toxin type A

The paper describes a clinical case demonstrating the possibilities of using computed tomography (CT) in the diagnosis and treatment of botulinum toxin type A (BTA) treatment of mixed cervical dystonia (CD). The poor result of initial treatment is due to the fact that the abnormally active deep muscles of the neck were beyond the reach of injection. Routine clinical examination cannot identify a concurrence of the caput and collis types of CD in most cases, which occurred in our patient. Objective examination revealed displacement of the larynx to the left from the incisura thyroidea superior, which was characteristic of the left-sided rotational caput type of CD; however, CT detected mixed CD (a concurrence of torticollis and torticaput in the left). Cervical spine CT could visualize not only the superficial, but also deep dystonic muscles of the neck, specify a botulinum toxin therapy regimen, and estimate a difference in the volumes of the normal or dystonic inferior oblique muscle of the head with further intramuscular administration of botulinum toxin. The evaluation of the efficiency and safety of BTA therapy for this disease, as well as practical guidelines for the use of CT in the diagnosis and treatment of mixed CD are given

Клинико-эпидемиологические аспекты работы Казанского центра экстрапирамидной патологии

Pathology of extrapyramidal nervous system (EP) is one of the most complex sections of clinical neurology. Specificity of EP disorders accounts for the necessity of specialized assistance to patients with parkinsonism, tremor, dystonias, tics and other hyperkinesias. The article gives an account of a 4-year experience of Center for Extrapyramidal pathology work, as well as its problems and achievements. A total of 1 738 patients with different motor disorders (total of 4 301 consultations) were examined in the center for the whole period of its existence. Scientific research work is carried on as well. On the basis of the experience it was found out that neurologists. Сome across considerable difficulties in making diagnosis and choice of extrapyramidal diseases treatment. We are planning to expand the use of modern techniques in diagnosis and treatment (including botulotoxin injections, deep brain stimulation), identification of epidemiology of some extrapyramidal disorders in Kazan city.Патология экстрапирамидной нервной системы представляет собой один из наиболее сложных разделов клинической неврологии. Специфичность экстрапирамидных расстройств диктует необходимость создания специализированной помощи пациентам с паркинсонизмом, тремором, дистониями, тиками и другими гиперкинезами. В данной статье описан четырехлетний опыт работы Центра экстрапирамидной патологии (г. Казань), его проблемы и успехи. За время существования центра проведено 4 301 консультация 1 738 пациентам с различными двигательными расстройствами, ведется научно-просветительская работа. Опыт работы показал, что неврологи испытывают значительные сложности в диагностике и выборе методов лечения экстрапирамидных заболеваний. Планируется расширение использования современных методов диагностики и лечения (в том числе инъекций ботулотоксина, глубокой стимуляции мозга), установление эпидемиологии отдельных экстрапирамидных заболеваний в г. Казани

Levodopa-carbidopa intestinal gel in the treatment of patients with parkinson disease: Results of a 12-month open study

© 2017, Media Sphera. All rights reserved.Objective: To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs. Material and methods: A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of “off” periods, “on” periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient’s diaries) were assessed throughout the whole study. Results: The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of “off” periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of “on” periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of “on” periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study. Conclusion: LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction

Plasma catecholamine levels in the early stages of treatment-naïve Parkinson’s disease

Rationale: Parkinson's disease (PD) is a neurodegenerative disorder with predominant involvement of catecholamine-producing neurons of the central and peripheral nervous system. Taking into account the relative availability and low costs of plasma catecholamine measurements, it is worthwhile to study these parameters as biomarkers of the early stages of PD.Aim: To determinate whether plasma levels of dopamine (DA), norepinephrine (NE), L-3,4-dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC) in patients with early stages of PD are related with akinetic-rigid and tremor-dominant variants and to compare the results to healthy volunteers.Materials and methods: This was an observational cross-sectional cohort study performed from 2012 to 2015. The main study group included unselected outpatients who attended the Republican Consultative and Diagnostic Center of Movement Disorders and Botulinotherapy (Kazan, Russia) with newly diagnosed early PD (Hoehn and Yahr stages I and II, 1967), of various ages and both genders, who had not been given any specific antiparkinsonian treatment. The control group included healthy volunteers with no clinical signs of PD (they could have other chronic diseases of the non-extrapyramidal origin). Plasma catecholamine levels were measured by gas liquid chromatography.Results: One hundred and thirty (130) treatment-naïve patients with newly diagnosed PD (mean age 59.34 ± 8.42 years, male gender 45.38%) were enrolled into the main study group. The control group included 56 healthy volunteers matched for age and gender. The distribution of various PD forms and stages was as follows: PD tremor-dominant variant 56.9%, PD akinetic-rigid variant 43.1%; PD stage I 76.9%, PD stage II 23.1%. Irrespective of the variant and stage, the PD patients demonstrated decreased NE levels, compared to the controls (95% confidence intervals 124–216 and 248–428 pg/mL, respectively, р &lt; 0.026). DOPA plasma level was reduced only in the patients with akinetic-rigid PD variant (р = 0.017), while DOPAC level in the patients with PD stage II (р = 0.008). The average DA:NE:DOPA:DOPAC ratio was 1:32:105:64 in the control group, 1:62:238:88 in the patients with PD tremor-dominant variant (the difference is significant for NE and DOPA, р &lt; 0.05), and 1:29:96:32 in those with PD akinetic-rigid variant (p &gt; 0.05). In the healthy controls the changes in DOPA levels account for 84% of the DA and NE variability; no correlation between DOPAC and other catecholamines was found. On the contrary, in the PD patients regardless of the stage and the disease variant, DOPAC levels directly correlated with DA (p &lt; 0.04). The PD tremor-dominant variant patients demonstrated a direct correlation between plasma NE and DOPA levels (p &lt; 0.05).Conclusion: The results obtained on absolute and relative parameters catecholamine turnover in the patients with early PD stages support the hypothesis on different pathophysiology of the tremor-dominant and akinetic-rigid variants of PD

RÜLFS CRAMP AND OTHER PAROXYSMAL DYSKINESIA

Paroxysmal dyskinesia comprise a significant and fascinating part of movement disorders, which represent a diagnostic challenge for neurologists working on the borderlands of psychiatry and epilepsy. The current classification based on the relation of attacks to a movement is supported by the response to treatment and genetic difference. We reviewed clinical characteristics and the main advances in genetics of these unique, usually hereditary diseases. Clinical diagnosis remains the key to the treatment choice. Psychogenic causes are common in sporadic cases, but paroxysmal dyskinesia secondary to systemic or primary neurological disorders should not be missed and warrant careful investigation

Levodopa-carbidopa intestinal gel in the treatment of patients with parkinson disease: Results of a 12-month open study

© 2017, Media Sphera. All rights reserved.Objective: To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs. Material and methods: A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of “off” periods, “on” periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient’s diaries) were assessed throughout the whole study. Results: The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of “off” periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of “on” periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of “on” periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study. Conclusion: LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction

Levodopa-carbidopa intestinal gel in the treatment of patients with parkinson disease: Results of a 12-month open study

© 2017, Media Sphera. All rights reserved.Objective: To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs. Material and methods: A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of “off” periods, “on” periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient’s diaries) were assessed throughout the whole study. Results: The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of “off” periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of “on” periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of “on” periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study. Conclusion: LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction

Safety and efficacy of pridopidine in patients with Huntington's disease (PRIDE-HD): a phase 2, randomised, placebo-controlled, multicentre, dose-ranging study

Background: Previous trials have shown that pridopidine might reduce motor impairment in patients with Huntington's disease. The aim of this study was to ascertain whether higher doses of pridopidine than previously tested reduce motor symptoms in a dose-dependent manner while maintaining acceptable safety and tolerability. Methods: PRIDE-HD was a randomised, placebo-controlled, phase 2, dose-ranging study in adults (aged ≥21 years) with Huntington's disease at outpatient clinics in 53 sites across 12 countries (Australia, Austria, Canada, Denmark, France, Germany, Italy, Poland, Russia, the Netherlands, the UK, and the USA). Eligible patients had clinical onset after age 18 years, 36 or more cytosine-adenine-guanine repeats in the huntingtin gene, motor symptoms (Unified Huntington's Disease Rating Scale total motor score [UHDRS-TMS] ≥25 points), and reduced independence (UHDRS independence score ≤90%). Patients were randomly assigned (1:1:1:1:1) with centralised interactive-response technology to receive one of four doses of pridopidine (45, 67·5, 90, or 112·5 mg) or placebo orally twice a day for 52 weeks. Randomisation was stratified within centres by neuroleptic drug use. The primary efficacy endpoint was change in the UHDRS-TMS from baseline to 26 weeks, which was assessed in all randomised patients who received at least one dose of study drug and had at least one post-baseline efficacy assessment (full analysis set). Participants and investigators were masked to treatment assignment. This trial is registered with EudraCT (2013-001888-23) and ClinicalTrials.gov (NCT02006472). Findings: Between Feb 13, 2014, and July 5, 2016, 408 patients were enrolled and randomly assigned to receive placebo (n=82) or pridopidine 45 mg (n=81), 67·5 mg (n=82), 90 mg (n=81), or 112·5 mg (n=82) twice daily for 26 weeks. The full analysis set included 397 patients (81 in the placebo group, 75 in the 45 mg group, 79 in the 67·5 mg group, 81 in the 90 mg group, and 81 in the 112·5 mg group). Pridopidine did not significantly change the UHDRS-TMS at 26 weeks compared with placebo at any dose. The most frequent adverse events across all groups were diarrhoea, vomiting, nasopharyngitis, falls, headache, insomnia, and anxiety. The most common treatment-related adverse events were insomnia, diarrhoea, nausea, and dizziness. Serious adverse events occurred in the pridopidine groups only and were most frequently falls (n=5), suicide attempt (n=4), suicidal ideation (n=3), head injury (n=3), and aspiration pneumonia (n=3). No new safety or tolerability concerns emerged in this study. One death in the pridopidine 112·5 mg group due to aspiration pneumonia was considered to be possibly related to the study drug. Interpretation: Pridopidine did not improve the UHDRS-TMS at week 26 compared with placebo and, thus, the results of secondary or tertiary analyses in previous trials were not replicated. A potentially strong placebo effect needs to be ruled out in future studies. Funding: Teva Pharmaceutical Industries

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (&gt;59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30\u201350 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of 6435 or a UHDRS motor score of 645 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P &lt;.001). Overall motor and cognitive performance (P &lt;.001) were worse, however only disease motor progression was slower (coefficient, 120.58; SE 0.16; P &lt;.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P &lt;.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P &lt;.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients