Phenotypic characterization of paroxysmal dyskinesia in Maltese dogs
Dakir PolidoroLuc Van HamPatrick SantensIne CornelisMarios CharalambousBart J. G. BroeckxS.F.M. Bhatti
17
Citation
36
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract Background Paroxysmal dyskinesias (PDs) are a group of central nervous system diseases characterized by episodes of abnormal involuntary hyperkinetic movement without altered consciousness that increasingly have been recognized in dogs. Objectives To present the phenotypical characterization, treatment, and outcome of a PD observed in Maltese dogs. Animals Client‐owned Maltese dogs (n = 19) with presumed diagnosis of PD. Methods Data were collected retrospectively from medical records (2014‐2019), and supporting information was added prospectively by using a questionnaire directed to the owners of the affected dogs. Results The episodes were characterized mainly by sudden dystonia of ≥1 limbs and generalized body tremors with preserved consciousness. The mean age of clinical onset was 5.4 years. Episode frequency varied widely both among and within individuals. Median episode duration was 4.5 minutes. Most episodes were stress‐ or exercise‐induced. Acetazolamide was administered to 6 dogs, and 4 dogs experienced a decrease in episode frequency. In 7 dogs that received a gluten‐free diet, 6 dogs became episode‐free. In 4 dogs, the episodes stopped spontaneously and in 2 dogs no medication or specific diet was given and the episodes continued at the same frequency. Conclusions and Clinical Importance Given the breed predisposition and regional distribution of the disease, additional research should focus on elucidating the underlying genetic cause doing so might advance both our understanding of the pathophysiology and treatment of this disease, not only in dogs, but also in humans. Regardless of the treatment protocol selected, prognosis appears fair to good.Keywords:
Medical record
Movement Disorders
Cite
Citations (0)
Paroxysmal dyskinesia
Cite
Citations (17)
Early onset of dystonia in a limb is highly suggestive of a hereditary form of dystonia, with DYT1 dystonia being the most common form. DYT1 dystonia is always caused by the same GAG deletion in the DYT1 gene, making genetic testing easy and inexpensive. Genetic testing of the Tor1A gene should be considered in any patient with isolated dystonia beginning before the age of 26 years, or in a patient with later onset isolated dystonia of a limb and a positive family history. Although DYT1 dystonia follows an autosomal dominant inheritance pattern, penetrance (likelihood of developing the disease in a mutation carrier) is markedly reduced and the clinical spectrum is very broad, ranging from mild writer’s cramp to severe generalized dystonia (variable expressivity). Disease manifestations and the clinical course cannot be predicted in an individual mutation carrier/patient; however, an early age at onset is associated with a higher tendency of the dystonia to generalize, whereas dystonia rarely manifests in mutation carriers beyond the age of 26 years. The clinical presentation, genetic diagnosis, and treatment of early-onset dystonia is outlined in this chapter.
Penetrance
Cite
Citations (0)
Dystonia is the debilitating movement disorder of central nervous system, often inherited, appearing as involuntary movements that occur due to deficiency or excess of neurotransmitters. The penetrance of dystonia is 30%, which means, that inherited dystonia is manifested only in 30% of mutating gene carriers, while the rest suffer from latent forms, so called forms frustes of this disorder. Until now only few mutations responsible for dystonia, had been unveiled, but we expect to exist up to 100 such mutations. Unless we uncover all mutations responsible for dystonia, we require reliable test for diagnosing latent forms of dystonia; and this necessity explains the importance of present study. The purpose of this research was to elaborate discrimination of dystonia on the basis of biogenic amines exchange peculiarities. The study presents the observational case control study. The control group was randomly composed of those patients, who were checked for neuroglial tumors. We checked catecholamines and serotonin metabolites in plasma and urine of 12 dystonia patients main group by means of chromatography method and compared the results obtained from these two groups by means of the decision tree method, discriminant analysis, and factor analysis. We revealed increased serotonin turnover in dystonia, and on the base of those increased metabolites in plasma, such as 5-hydroxytryptophane and 5-hydroxiindolacetic acid, by means of advanced statistical methods we eleborated sensitive and specific test for diagnosis of dystonia. We recommend introducing into clinical practice of diagnostic tests for dystonia on the base of analysis of diagnosing level in plasma of 5-hydroxytryptophane and 5-hydroxiindolacetic acid by means of discriminant analysis and classification tree method due to high sensitivity and high specifity of those methods.
Cervical dystonia
Penetrance
Cite
Citations (0)
Dyskinesias are abnormal involuntary movements that patients with mid-stage and advanced Parkinson's disease (PD) may suffer from. These troublesome motor impairments are reduced by adjusting the dose or frequency of medication levodopa. However, to make a successful adjustment, the treating physician needs information about the severity rating of dyskinesia as patients experience in their natural living environment. In this work, we used movement data collected from the upper and lower extremities of PD patients along with a deep model based on Long Short-Term Memory to estimate the severity of dyskinesia. We trained and validated our model on a dataset of 14 PD subjects with dyskinesia. The subjects performed a variety of daily living activities while their dyskinesia severity was rated by a neurologist. The estimated dyskinesia severity ratings from our developed model highly correlated with the neurologist-rated dyskinesia scores (r=0.86 (p<0.001) and 1.77 MAE (6%)) indicating the potential of the developed the approach in providing the information required for effective medication adjustments for dyskinesia management.
Movement Disorders
Cite
Citations (7)
Objective: To clinically characterize the temporal relationship between dyskinesia and the antiparkinsonian response when dyskinesia first emerges during long-term levodopa therapy and to determine if it is consistent with the hypothesized mechanism by which dyskinesia develops. Methods: Dyskinesia and the antiparkinsonian response to levodopa during 2-hour levodopa infusions were monitored at intervals through the first 4 years of long-term levodopa therapy in 20 subjects with idiopathic Parkinson disease (PD) and previously untreated with levodopa. The onset and offset of the antiparkinsonian response and dyskinesia were compared when dyskinesia first appeared during the 4 years. The findings were compared to 20 subjects with PD on long-term levodopa with dyskinesia and motor fluctuations. Results: The onset and offset of the antiparkinsonian response and dyskinesia generally coincided when dyskinesia first appeared during the 4 years and did not suggest any temporal dissociation of the 2 responses. Further, the latency to the onsets of dyskinesia and the antiparkinsonian response tended to shorten during long-term levodopa therapy, suggesting that both responses were sensitized by long-term levodopa. Conclusions: The similar onsets and offsets of the antiparkinsonian response and dyskinesia when dyskinesia first appears are not consistent with the postulated progressive decrease in threshold for dyskinesia during long-term levodopa therapy. Other mechanisms for the development of dyskinesia need to be considered.
Paroxysmal dyskinesia
Cite
Citations (50)
Cite
Citations (0)
In clinical trials for patients with Parkinson's disease (PD) with motor fluctuations, efficacy is generally ascribed to an intervention if motor function is significantly improved or if "off" time is significantly reduced. However, we have argued that patients might not be improved if off time is reduced only to the extent that unwanted dyskinesia is increased. Therefore, a home diary should include an assessment of dyskinesia to provide an accurate reflection of clinical status over a period of time. We undertook two studies to develop a home diary to assess functional status in patients with PD with motor fluctuations and dyskinesia. In both studies, patients concurrently completed a test and a reference diary. In Study I, we evaluated the impact of different severities of dyskinesia on patient-defined functional status. There were 1,149 evaluable half-hour time periods from 24 patients; 94.3% of off time was considered "bad" time and 90.2% of "on" time without dyskinesia, 72.6% of on time with mild dyskinesia, 43.0% of on time with moderate dyskinesia, and 15.2% of on time with severe dyskinesia was considered "good" time. In Study II, we evaluated a new home diary designed to separate dyskinesia that had a negative impact on patient-defined functional status from dyskinesia that did not. There were 816 evaluable time periods from 17 patients; 84.9% of off time and 89.9% of on time with troublesome dyskinesia was considered bad time while 85.5% of on time without dyskinesia and 93.8% of on time with nontroublesome dyskinesia was considered good time. With this diary (Diary II), the effect of an intervention can be expressed as the change in off time and the change in on time with troublesome dyskinesia (bad time). The sum can be used as an outcome variable and compared to baseline or across groups. In evaluating the efficacy of an intervention, assessment of change in off time and change in on time with troublesome dyskinesia provides a more accurate reflection of clinical response than change in off time alone.
Paroxysmal dyskinesia
Cite
Citations (271)
Paroxysmal dyskinesia
Movement Disorders
Neuropathology
Cite
Citations (169)