Cerebellar ataxias: an update Manto, Mario; Gandini, Jordi; Feil, Katharina ...
Current opinion in neurology,
02/2020, Letnik:
33, Številka:
1
Journal Article
Recenzirano
Providing an update on the pathophysiology, cause, diagnosis and treatment of cerebellar ataxias. This is a group of sporadic or inherited disorders with heterogeneous clinical presentation and ...notorious impact on activities of daily life in many cases. Patients may exhibit a pure cerebellar phenotype or various combinations of cerebellar deficits and extracerebellar deficits affecting the central/peripheral nervous system. Relevant animal models have paved the way for rationale therapies of numerous disorders affecting the cerebellum.
Clinically, the cerebellar syndrome is now divided into a cerebellar motor syndrome, vestibulocerebellar syndrome and cerebellar cognitive affective syndrome with a novel clinical scale. This subdivision on three cornerstones is supported by anatomical findings and neuroimaging. It is now established that the basal ganglia and cerebellum, two major subcortical nodes, are linked by disynaptic pathways ensuring bidirectional communication. Inherited ataxias include autosomal recessive cerebellar ataxias (ARCAs), autosomal dominant spinocerebellar ataxias and episodic ataxias and X-linked ataxias. In addition to the Movement Disorders Society genetic classification of ARCAs, the classification of ARCAs by the Society for Research on the Cerebellum and Ataxias represents major progress for this complex subgroup of cerebellar ataxias. The advent of next-generation sequencing has broadened the spectrum of cerebellar ataxias.
Cerebellar ataxias require a multidisciplinary approach for diagnosis and management. The demonstration of anatomical relationships between the cerebellum and basal ganglia impacts on the understanding of the cerebello-basal ganglia-thalamo-cortical system. Novel therapies targeting deleterious pathways, such as therapies acting on RNA, are under development.
To explain physical activity behavior, social-cognitive theories were most commonly used in the past. Besides conscious processes, the approach of dual processes additionally incorporates ...non-conscious regulatory processes into physical activity behavior theories. Habits are one of various non-conscious variables that can influence behavior and thus play an important role in terms of behavior change. The aim of this review was to examine the relationship between habit strength and physical activity behavior in longitudinal studies.
According to the PRISMA guidelines, a systematic search was conducted in three databases. Only peer-reviewed articles using a longitudinal study design were included. Both, habit and physical activity were measured at least once, and habit was related to physical activity behavior. Study quality was evaluated by assessment tools of the NHLBI.
Of 3.382 identified publications between 2016 and 2019, fifteen studies with different study designs were included. Most studies supported that positive correlations between habit and physical activity exist. Some positive direct and indirect effects of habit on physical activity were detected and only a minority of studies showed the influence of physical activity on habit strength. Studies differentiating between instigation and execution habit found positive correlations and revealed instigation habit as a stronger predictor of physical activity. The quality of studies was rated as reasonable using assessment tools of the NHLBI.
This review revealed a bidirectional relationship between habit and physical activity. Whether habit predicts physical activity or vice versa is still unclear. The observation of habit influencing physical activity may be most appropriate in studies fostering physical activity maintenance while the influence of physical activity on habit may be reasonable in experimental studies with physical activity as intervention content to form a habit. Future investigations should differentiate between habit formation and physical activity maintenance studies depending on the research objective. Long-term study designs addressing the complexity of habitual behavior would be beneficial for establishing cue-behavior associations for the formation of habits. Furthermore, studies should differentiate between instigation and execution habit in order to investigate the influence of both variables on physical activity behavior independently.
The present study contains an affect-based intervention intended to support exercise trainers in positively influencing their course participants’ affective responses to their exercise courses. We ...argue that positive affective responses are associated with habit formation, thereby being a promising approach for avoiding high drop-out rates in exercise courses. First, the present study aimed to investigate whether the intervention for exercise trainers could increase (a) affective attitudes, and (b) exercise instigation habit strength, and influence the development of (c) weekly measured affective responses and (d) automaticity among adult participants of exercise courses. Second, it examined the relationship between the development of affective responses and exercise instigation habit strength. Ten exercise trainers of weekly sports and exercise courses at a German university received either an affect-based intervention or a control intervention. 132 of their course participants answered the Self-Report Habit Index (SRHI; the automaticity sub-scale SRBAI was also analyzed) for exercise instigation habit strength and items to measure affective attitude in the initial and final assessment. Moreover, they were assessed for a duration of 10 weeks during which, each time after attending the course, they reported their affective response to exercise as well as their automaticity in arriving at the decision to exercise. In the repeated measures ANOVA, there was a significant main effect of time for exercise instigation habit strength. Overall, habit strength was higher in the final than in the initial assessment. However, there were no significant differences between the two conditions in all study variables. In the latent growth curve model, the trajectory of the latent growth curve of valence was a significant predictor of the final exercise instigation habit strength. While the applied affect-based intervention was not successful in enhancing positive affective responses to exercise, the results indicate that positive affective responses may contribute to strengthening exercise instigation habits. Future studies should examine the effectiveness of interventions in long-term study designs.
Objective
To uncover possible impairments of walking and dynamic postural stability in patients with primary orthostatic tremor (OT).
Methods
Spatiotemporal gait characteristics were quantified in 18 ...patients with primary OT (mean age 70.5 ± 5.9 years, 10 females) and 18 age-matched healthy controls. One-third of patients reported disease-related fall events. Walking performance was assessed on a pressure-sensitive carpet under seven conditions: walking at preferred, slow, and maximal speed, with head reclination or eyes closed, and while performing a cognitive or motor dual-task paradigm.
Results
Patients exhibited a significant gait impairment characterized by a broadened base of support (
p
= 0.018) with increased spatiotemporal gait variability (
p
= 0.010). Walking speed was moderately reduced (
p
= 0.026) with shortened stride length (
p
= 0.001) and increased periods of double support (
p
= 0.001). Gait dysfunction became more pronounced during slow walking (
p
< 0.001); this was not present during fast walking. Walking with eyes closed aggravated gait disability as did walking during cognitive dual task (
p
< 0.001).
Conclusion
OT is associated with a specific gait disorder with a staggering wide-based walking pattern indicative of a sensory and/or a cerebellar ataxic gait. The aggravation of gait instability during visual withdrawal and the normalization of walking with faster speeds further suggest a proprioceptive or vestibulo-cerebellar deficit as the primary source of gait disturbance in OT. In addition, the gait decline during cognitive dual task may imply cognitive processing deficits. In the end, OT is presumably a complex network disorder resulting in a specific spino-cerebello-frontocortical gait disorder that goes beyond mere tremor networks.
Background and aims:
Intravenous thrombolysis (IVT) is standard of care for disabling acute ischemic stroke (AIS) within a time window of ⩽ 4.5 h. Some AIS patients cannot be treated with IVT due to ...limiting contraindications, including heparin usage in an anticoagulating dose within the past 24 h or an elevated activated prothrombin time (aPTT) > 15 s. Protamine is a potent antidote to unfractionated heparin.
Objectives:
The objective of this study was to investigate the safety and efficacy of IVT in AIS patients after antagonization of unfractionated heparin with protamine.
Methods:
Patients from our stroke center (between January 2015 and September 2021) treated with IVT after heparin antagonization with protamine were analyzed. National Institutes of Health Stroke Scale (NIHSS) was used for stroke severity and modified Rankin Scale (mRS) for outcome assessment. Substantial neurological improvement was defined as the difference between admission and discharge NIHSS of ⩾8 or discharge NIHSS of ⩽1. Good outcome at follow-up after 3 months was defined as mRS 0–2. Safety data were obtained for mortality, symptomatic intracerebral hemorrhage (sICH), and for adverse events due to protamine. Second, a systematic review was performed searching PubMed and Scopus for studies and case reviews presenting AIS patients treated with IVT after heparin antagonization with protamine. The search was limited from January 1, 2011 to September 29, 2021. Furthermore, we conducted a propensity score matching comparing protamine-treated patients to a control IVT group without protamine (ratio 2:1, match tolerance 0.2).
Results:
A total of 16 patients, 5 treated in our hospital and 11 from literature, 65.2 ± 13.1 years, 37.5% female, median premorbid mRS (pmRS) 1 (IQR 1, 4) treated with IVT after heparin antagonization using protamine were included and compared to 31 IVT patients 76.2 ± 10.9 years, 45% female, median pmRS 1 (IQR 0, 2). Substantial neurological improvement was evident in 68.8% of protamine-treated patients versus 38.7% of control patients (p = 0.028). Good clinical outcome at follow-up was observed in 56.3% versus 58.1% of patients (p = 0.576). No adverse events due to protamine were reported, one patient suffered sICH after secondary endovascular thrombectomy of large vessel occlusion. Mortality was 6.3% versus 22.6% (p = 0.236).
Conclusion:
IVT after heparin antagonization with protamine seems to be safe and, prospectively, may extend the number of AIS patients who can benefit from reperfusion treatment using IVT. Further prospective registry trials would be helpful to further investigate the clinical applicability of heparin antagonization.
Background
Endovascular treatment (ET) in orally anticoagulated (OAC) patients has not been evaluated in randomized clinical trials and data regarding this issue are sparse.
Methods
We analyzed data ...from the German Stroke Registry-Endovascular Treatment (GSR-ET; NCT03356392, date of registration: 22 Nov 2017). The primary outcomes were successful reperfusion defined as modified thrombolysis in cerebral infarction (mTICI 2b-3), good outcome at 3 months (modified Rankin scale mRS 0–2 or back to baseline), and intracranial hemorrhage (ICH) on follow-up imaging at 24 h analyzed by unadjusted univariate and adjusted binary logistic regression analysis. Additionally, we analyzed mortality at 3 months with adjusted binary logistic regression analysis.
Results
Out of 6173 patients, there were 1306 (21.2%) OAC patients, 479 (7.8%) with vitamin K antagonists (VKA) and 827 (13.4%) with non-vitamin K antagonist oral anticoagulation (NOAC). The control group consisted of 4867 (78.8%) non-OAC patients. ET efficacy with the rates of mTICI 2b-3 was similar among the three groups (85.6%, 85.3% vs 84.3%,
p
= 0.93 and 1). On day 90, good outcome was less frequent in OAC patients (27.8%, 27.9% vs 39.5%,
p
< 0.005 and < 0.005). OAC status was not associated with ICH at 24 h (NOAC: odd’s ratio OR 0.89, 95% confidence interval CI 0.67–1.20; VKA: OR 1.04, CI 0.75–1.46).
Binary logistic regression analysis revealed no influence of OAC status on good outcome at 3 months (NOAC: OR 1.25, CI 0.99–1.59; VKA: OR 1.18, CI 0.89–1.56) and mortality at 3 months (NOAC: OR 1.03, CI 0.81–1.30; VKA: OR 1.04, CI 0.78–1.1.37).
Conclusions
ET can be performed safely and successfully in LVO stroke patients treated with OAC.
Clinical trial registration-URL
http://www.clinicaltrials.gov
. Unique identifier: NCT03356392.
Future-oriented emotions could influence our decisions in everyday life and help understand why some individuals are physically active whilst others are not. Current literature distinguishes between ...two future-oriented emotion constructs: anticipatory and anticipated emotions. While anticipatory emotions are currently experienced emotions about a future event, anticipated emotions refer to the emotions that a person is expected to experience when confronted with a future event. The main aims of the present study were (1) to identify and describe (a) categories of anticipatory emotions experienced before exercise, and (b) categories of anticipated emotions expected to be experienced during and after exercise, and (2) to develop a theoretical model of anticipated emotion categories. Sixteen participants (
M
age
= 26.03,
SD
= 6.66) were recruited for semi-structured interviews, and their statements were analyzed using principles of the Grounded Theory. In total, 13 different anticipatory and anticipated emotion categories were identified, such as enjoyment, anxiety, pride, self-anger, and relief. Anticipatory emotions seem to reflect the current affective valence of exercising and may be influenced by daily factors. With regards to anticipated emotions, the results show that regular exercisers anticipated also negative emotions such as anxiety, disappointment, and self-anger, and non-regular exercisers also anticipated positive emotions such as enjoyment, pride, and satisfaction. Therefore, future research should not only focus on the valence of future-oriented emotions, but should investigate the possible impact of specific anticipated emotions on exercise behavior. In addition, a theoretical model of anticipated emotion categories in exercise behavior derived from the interviews. The model outlines different categories of anticipated emotions based on appraisal processes. In conclusion, we assume that this developmental process of anticipated emotions may be embedded in a broader, cyclical process within the context of exercising.
There are currently eight groups of drugs for the pharmacotherapy of vertigo, nystagmus, and cerebellar disorders: antiemetics; anti‐inflammatories, antimenieres, and antimigraineous medications; ...antidepressants, anticonvulsants, aminopyridines, and acetyl‐dl‐leucine (“the eight A's”). In acute unilateral vestibulopathy, corticosteroids improve the recovery of peripheral vestibular function, but there is not sufficient current evidence for a general recommendation. There is also insufficient evidence that 48 or 144 mg/day betahistine has an effect in Ménière's disease. Therefore, higher dosages are currently recommended; in animal studies, it was shown that betahistine increases cochlear blood flow. In vestibular paroxysmia, oxcarbazepine was effective (one yet not randomized controlled trial (RCT)). Aminopyridines are recommended for the treatment of downbeat nystagmus (two RCTs) and episodic ataxia type 2 (EA2, one RCT). There are so far no RCTs on vestibular migraine, so currently no treatment can be recommended. Acetyl‐dl‐leucine improves cerebellar ataxia (three observational studies); it also accelerates central compensation in an animal model of acute unilateral lesion, but RCTs were negative. There are ongoing RCTs on vestibular paroxysmia with carbamazepine (VESPA), acute unilateral vestibulopathy with betahistine (BETAVEST), vestibular migraine with metoprolol (PROVEMIG), benign paroxysmal positional vertigo with vitamin D (VitD@BPPV), EA2 with 4‐aminopyridine versus acetazolamide (EAT‐2‐TREAT), and cerebellar ataxias with acetyl‐dl‐leucine (ALCAT).
Zusammenfassung
Bei Personen mit einer Geschlechtsinkongruenz besteht eine Diskrepanz zwischen dem bei Geburt zugewiesenen Geschlecht und der empfundenen Geschlechtsidentität. Mit Einsetzen der ...Pubertät erleben viele trans Personen eine deutliche Verminderung der Lebensqualität. Studien belegen, dass eine Geschlechtsinkongruenz häufig mit erheblichen negativen Auswirkungen auf die psychische Gesundheit assoziiert ist. Eine geschlechtsangleichende Hormontherapie (GAHT) kann zu einer Linderung der psychischen Symptome führen und die Lebensqualität steigern. Eine GAHT sollte nach den Bedürfnissen der einzelnen Person geplant werden, eine ausführliche Aufklärung über Möglichkeiten und Grenzen der GAHT ist empfehlenswert. Aufgrund der weitreichenden Auswirkungen einer geschlechtsangleichenden Therapie auf die Fertilität sollte bereits vor Beginn einer GAHT eine Aufklärung und Beratung hinsichtlich der Möglichkeiten der Fertilitätsprotektion für einen späteren Kinderwunsch erfolgen.
Within the past 10 years, immune mechanisms associated with acute ischemic stroke (AIS) have been brought into focus, but data on B cell activation and intrathecal Ig production is still scarce. In ...this study, we determined the prevalence of an elevated IgG index, positive oligoclonal bands (OCBs) and chemokine C-X-C motif ligand 13 (CXCL13) levels in the cerebrospinal fluid (CSF) as markers of intrathecal IgG synthesis and B cell activation in patients with AIS.
In a retrospective study we analyzed the cerebrospinal fluid (CSF) from 212 patients with AIS from December 2013 to May 2018 assessing intrathecal Ig synthesis, OCBs and CXCL13 concentrations.
Overall, 5.7% (12/212) of AIS patients showed an intrathecal IgG synthesis, 0.5% (1/212) with isolated elevated IgG index, 5.2% (7/136) isolated positive OCBs and 2.9% (4/136) both elevated IgG index and positive OCBs. CXCL13 levels were elevated in 3.6% (3/83) of the patients. Approximately one third of these patients had simultaneously chronic inflammatory CNS disease (multiple sclerosis, neuromyelitis optica spectrum disorder, neurosarcoidosis). There was no significant association between CSF findings and stroke characteristics including vascular territory, localization, volume, etiology, acute treatment, or blood-brain barrier dysfunction. Intrathecal IgG synthesis was more common in patients with prior stroke. Longitudinal CSF analysis did not reveal any newly-occurring, but instead mostly persistent or even disappearing intrathecal IgG synthesis after AIS.
We found no evidence of a relevant B cell recruitment and intrathecal IgG synthesis in patients with AIS. In fact, the occurrence of intrathecal IgG synthesis was associated with concurrent chronic inflammatory CNS disease or previous stroke. Consequently, in patients with first-ever AIS and intrathecal IgG synthesis, physicians should search for concomitant inflammatory CNS disease.
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