Neurocognition, cerebellar functions and psychiatric features in spinocerebellar ataxia type 34: a case series

The frequency and complications of respiratory viral infections (RVI) were studied in 50 ambulatory lung transplant patients during a single winter season, using viral antigens, viral cultures and PCR of nasal washes or bronchoalveolar lavages. Patients' survival, episodes of acute rejection and occurrence of bronchiolitis obliterans (BO) or BO syndrome (BOS) were monitored for 1 yr after the study. Overall, 32 (64%) patients had 49 symptomatic episodes. Documented infections included eight due to respiratory syncytial virus (RSV), one due to parainfluenza virus (PIV) and 10 due to influenza (FLU). Four of the FLU infections were serological rises without symptoms. Overall, 17 (34%) patients had documented viral infection; four patients had lower respiratory involvement and two (one RSV, one PIV) were hospitalised for aerosolised ribavirin treatment. After 1 yr there were three (6%) deaths unrelated to RVI. BO or BOS had occurred in one (6%) out of 17 patients with and three (12%) out of 33 without RVI. Respiratory viruses infected one-third of ambulatory lung transplant recipients in a single season. In conclusion, respiratory viral infection was not associated with subsequent graft dysfunction. Larger prospective studies are required to better define the acute and long-term morbidity of these infections.

To evaluate lesion location after pediatric cerebellar tumor resection in relation to the development of severe cognitive and affective disturbances, or cerebellar cognitive affective syndrome (CCAS). The postsurgical lesion location of 195 pediatric patients with cerebellar tumors was mapped onto a template brain. Individuals with CCAS were matched to 2 participants without CCAS by sex, age, and lesion volume. Lesion analyses included both a hypothesis-driven evaluation of the cerebellar outflow pathway (deep nuclei and superior cerebellar peduncles) and data-driven multivariate lesion symptom mapping. Lesion-associated networks were evaluated by comparing connectivity patterns between the lesion location of cases with and those without CCAS with resting-state functional connectivity MRI data from large normative adult and pediatric cohorts. CCAS was present in 48 of 195 participants (24.6%) and was strongly associated with cerebellar outflow tract lesions (p < 0.0001). Lesion symptom mapping also highlighted the cerebellar outflow pathway, with peak findings in the fastigial nuclei extending into the inferior vermis. Lesion network mapping revealed that the cerebellar region most associated with CCAS was functionally connected to the thalamic mediodorsal nucleus, among other sites, and that higher connectivity between lesion location and the mediodorsal nucleus predicts CCAS occurrence (p < 0.01). A secondary analysis of 27 participants with mutism revealed similar localization of lesions and lesion-associated networks. Lesions of the cerebellar outflow pathway and inferior vermis are associated with major cognitive and affective disturbances after pediatric cerebellar tumor resection, and disrupted communication between the cerebellum and the thalamic mediodorsal nucleus may be important.

Cerebellar pathology commonly shows important motor signs and less evident cognitive dysfunction. The 'cerebellar cognitive affective syndrome' is characterised by impairment on executive function, spatial cognition, language and behaviour. We report the case of a man with acute onset of transitory motor features and severe mental disorders. Cranial CT and brain MRI revealed extended cerebellar lesions. Neuropsychological assessment disclosed deficits of attention, executive function and memory. Auditory event-related potentials showed abnormal P300. These data suggest a pure "cerebellar cognitive affective syndrome"and strengthen the hypothesis of cerebellar cognitive function modulation.

Cerebellar cognitive-affective syndrome (CCAS) results from cerebellar degeneration, but its prevalence in spinocerebellar ataxias (SCAs) remains underexplored. This study assessed CCAS prevalence, severity, and progression across different SCAs. We included polyglutamine (PolyQ) SCA expansion carriers (ATXN1/SCA1, ATXN2/SCA2, ATXN3/SCA3, and ATXN7/SCA7), patients with FGF14/SCA27B and SPG7, and controls. Cognitive function was assessed with the CCAS scale and ataxia severity with the Scale for the Assessment and Rating of Ataxia (SARA) and Composite Cerebellar Functional Severity (CCFS) score. We correlated CCAS score with ataxia severity, brain MRI, and plasma neurofilament light chain (NfL) levels. Subtest comparisons among genotypes were adjusted for age, education, and SARA score. In PolyQ SCA carriers, we explored CCAS progression. We included 371 participants: 66 with SCA1, 28 with SCA2, 158 with SCA3, 24 with SCA7, 35 with SPG7, 17 with SCA27B, and 43 controls. Those with SCA27B and SPG7 were older (69.5 ± 9.5 and 57.8 ± 10.6 years) with lower education (11.4 ± 4.2 and 12.7 ± 3.6 years) than those with PolyQ SCAs (from 40.3 ± 14.0 for SCA7 group to 45.9 ± 11.2 years in SCA3 group, p < 0.0001; education ranging from 14.4 ± 3.1 for SCA2 group to 15.4 ± 2.8 years for SCA7 group, p < 0.0001). Among ataxic patients, definite CCAS was detected in 88% of patients with SCA27B and 71% of SPG7 carriers, followed by SCA2 (67%), SCA7 (67%), SCA1 (50%), and SCA3 (41%) groups. Among preataxic PolyQ SCA carriers, CCAS was present in 11% (10/89), similar to controls (11.6%, p = 1). However, phonemic fluency showed an early impairment in preataxic SCA1 carriers (11.8 ± 4.5 vs 14.6 ± 3.8, p = 0.04). In PolyQ SCA carriers, the CCAS total raw score correlated with SARA score (r = -0.54, p < 0.0001), CCFS score (r = -0.45; p < 0.0001), and plasma NfL levels (r = -0.26, p = 0.002). CCAS scores correlated with cerebellar volume in those with SCA2 (r = 0.64, p < 0.001). Patients with SPG7 showed significantly poorer performance in executive function, short-term memory, and abstract reasoning compared with those with SCA3 and SCA7. In PolyQ SCA carriers, improvements were observed during the first 3 years after inclusion (+2.0 ± 0.7 points, p = 0.002; +2.6 ± 0.8 points, p = 0.0007; +2.7 ± 0.8, p = 0.001, respectively). By year 4, the increase was not significant (+0.73 ± 1.16 points, p = 0.52). We observed early cognitive impairment in PolyQ SCA carriers, correlating with clinical measures, NfL levels, and cerebellum volume. Improvement over 3 years likely reflects a practice effect, potentially limiting the scale's longitudinal utility.

Emerging research expands our understanding of the cerebellum beyond motor control to include cognitive, emotional, and autonomic functions. This review examines the cerebellum's complex role, spotlighting Schmahmann's syndrome, or cerebellar cognitive affective syndrome (CCAS), which impairs executive functions, language, and spatial processing. It emphasizes advancements in diagnosing CCAS and the imperative of developing superior diagnostic tools for managing cerebellar pathologies effectively. A comprehensive literature search was performed using databases such as PubMed, OVID Embase, and OVID Medline. Using the keywords "cerebellar cognitive, affective syndrome" and "Schmahmann syndrome," the search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines for systemic review, in which the selection process narrowed down an initial set of 54 articles to 12, focusing on the impact of the CCAS scale on diagnosing and understanding Schmahmann's syndrome. The review's analysis confirms the cerebellum's roles in motor and cognitive functions and underscores the CCAS scale as a significant advancement in detecting cerebellar deficits, surpassing traditional assessments such as the mini-mental state examination and Montreal cognitive assessment. This review emphasizes the importance of understanding the cerebellum's involvement in cognition and emotion and the crucial role of the CCAS scale for identifying cerebellar impairments. It calls for better diagnostic tools to assess CCAS accurately and suggests enhancing the CCAS Scale to reflect cultural and educational diversity. This will improve the diagnosis and treatment of cerebellar disorders, promoting a comprehensive neurological perspective on the cerebellum's functions.

Objectives To study different components of social cognition and quality of life in patients with early multiple sclerosis and low Expanded Disability Status Scale and to test the influence of cognitive performance, fatigue and neuropsychiatric symptoms on social cognition performance. Methods Thirty-four patients with relapsing-remitting MS, with ≤2 years of disease duration and scores ≤2 on the EDSS and 30 healthy controls underwent neuropsychological assessment with the Brief Repeatable Neuropsychological Test Battery. Components of social cognition, such as emotion recognition, theory of mind, empathy, and emotional reactivity, were assessed with the Reading the Mind in the Eyes test, the Faux Pas task, the International Affective Imagery System, and the Empathy Quotient. Anxiety, depression, fatigue and quality of life were measured. Results Patients showed significant differences in verbal memory, executive functions and social cognition, especially emotion recognition and ToM. Regarding emotional reactivity, patients showed a positive bias in the interpretation of the valence of neutral images. Conclusions Patients with early MS showed impairments in several components of social cognition independent of cognitive performance, neuropsychiatric symptoms and fatigue. Social cognition deficits may be present in MS even in the early stages.

Background The long-term effects of Cerebellar Cognitive Affective Syndrome (CCAS) after cerebellar stroke on daily life remain unclear. Life space, evaluated using Life Space Assessment (LSA), reflects mobility, social participation, and independence, providing real-world insight into CCAS. Case Description We report the case of a 68-year-old Japanese woman with normal premorbid cognition and independence who underwent emergent craniotomy for a right cerebellar hemorrhage involving lobules VII – VIII and the dentate nucleus. Initially, the patient exhibited severe ataxia (Scale for the Assessment and Rating of Ataxia (SARA) 22.5), inability to walk (Functional Ambulation Category (FAC) 0), and cognitive deficits (Mini Mental State Examination (MMSE) 23; CCAS-Scale 50) with anosognosia and reduced speech coherence. After 2 months, motor function improved (SARA 7, FAC 4), allowing discharge, though executive and attentional deficits persisted despite MMSE improving to 27. Three years later, motor recovery was nearly complete (SARA 2.5, FAC 5) with preserved independence in activities of daily living. However, neuropsychological impairment remained (Trail Making Test-B 330 s; CCAS-Scale 75, categorized definite CCAS). LSA decreased from 92 prehemorrhage to 39, indicating marked restriction beyond the neighborhood. Conclusions This case highlights that CCAS can impose long-term life-space limitation despite excellent motor recovery.

P-MD008. Differential effects of thyrotropin releasing hormone on motor performance and motor adaptation in patients with spinocerebellar degeneration

BackgroundAccumulating evidence demonstrated that the cerebellum contributes to a wide range of sensorimotor and cognitive functions. However, the relationship between cerebellar function and cognitive abilities in normal aging populations remains unclear.MethodsThe present cross-sectional study tested cerebellar-related cognitive changes across middle to late adulthood using the Cerebellar Cognitive Affective Syndrome (CCAS) scale and a perceptual serial reaction time (SRT) task. Participants were divided into three groups: early-middle-aged adults (N = 18, 30–45 years), late-middle-aged adults (N = 19, 46–57 years), and older adults (N = 18, 60–78 years).ResultsAlthough all participants were identified as cognitively healthy by the Mini-Mental State Examination (MMSE), older adults showed significant impairments in the CCAS scale, especially in semantic and phonemic fluency, category switching, digit span backward as well as cube drawing/copy. In the perceptual SRT task, older adults responded slower than their counterparts, reflecting age-related impairments in sensorimotor integration efficiency. However, there were no age-related group differences in learning new procedural knowledge. Importantly, participants with poorer CCAS performance demonstrated slower response speed and lower accuracy in the perceptual SRT task.DiscussionThe current results indicate a dissociation between general cognitive scores screened by MMSE and cerebellar-specific cognitive impairments. Furthermore, as the cerebellum plays a critical role in both sensorimotor and cognitive domains, the current study highlight the importance of incorporating screening tools which are sensitive to cerebellar functions in aging research.

Cerebellar Cognitive Affective Syndrome in Dandy-Walker Variant Disorder

IntroductionAutism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social cognition and repetitive behaviors with onset in early infancy. Deficits in emotion recognition, social perception, and communication have been identified as core symptoms of ASD.Comorbid disorders are frequent, namely psychiatric illness, epilepsy, sleep disruption, and hyperactivity.Immune profile changes during early life may contribute to pathogenesis of ASD. Other risk factors include advanced parental age, fetal environment, fertility treatments, medications, and nutritional and toxic factors.Several brain regions are involved in the pathophysiology of ASD but the cerebellum is the structure most consistently found altered. An increased risk of ASD is associated with cerebellar damage.ObjectivesTo highlight the importance of understanding the key processes of cerebellar development and how altered cerebellar function leads to social and cognitive impairments, and consequently ASD.MethodsNon-systematic review of the literature using Pubmed database. Papers were selected according to their relevance.ResultsFrom imaging studies, we can understand that cerebellum is not just about motor function. Different tasks like adding working memory, emotional and social processing, and language seem to be part of core functions of the cerebellar circuit.Adults with lesions in the cerebellum can develop cerebellar cognitive affective syndrome (CCAS), with core symptoms of impaired executive function, difficulties in spatial cognition, blunted affect, or inappropriate behavior. Some children who have tumor resection surgery for medulloblastomas also exhibit symptoms of CCAS, and some experience posterior fossa syndrome (PFS).The linguistic, cognitive, and behavioral deficits in CCAS and PFS may contribute to explaining how cerebellar alterations are related to ASD, which is a neurodevelopmental disorder characterized by an earlier onset and broader spectrum of these symptoms.ConclusionsThe literature has suggested an important role for cerebellar dysfunction in etiology of ASD, under certain premises: (a) cerebellar expansion temporarily coincides with onset of ASD; (b) cerebellum is prone to lesions during this period; (3) cerebellar lesions contribute to dysfunctional social and language abilities.Disturbances in cerebellar development lead to alterations in higher cognitive functions, due to changes in Purkinje cells. These dysfunctional neurons, once integrated into a brain circuit that controls complex tasks, lead to these functions becoming aberrant.It is therefore fair to say that cerebellum is important for development of the so-called “cognitive and social brain” since it is itself part of this network. So, the cerebellum certainly plays a relevant role in pathophysiology of ASD.Disclosure of InterestNone Declared

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant cerebellar ataxia, characterized by epilepsy, ataxic symptoms, and cognitive impairments linked to Cerebellar Cognitive Affective Syndrome (CCAS). The Cerebellar Cognitive Affective Syndrome Scale (CCAS-S) has been developed to identify CCAS across various cerebellar pathologies. To determine whether patients with SCA10 exhibit CCAS using the CCAS-S, and to compare its effectiveness with the Montreal Cognitive Assessment (MoCA). A secondary objective was to evaluate the effect of demographic and clinical data on CCAS-S performance. Fifteen patients with SCA10 and fifteen matched controls underwent assessments using the CCAS-S, the MoCA, the Scale for the Assessment and Rating of Ataxia (SARA), and the Center for Epidemiologic Studies Depression Scale (CES-D). Diagnostic accuracy was analyzed using ROC curve analysis, comparing total and subcategory scores between groups. Demographic and clinical data were examined for relations with CCAS-S scores. The CCAS-S effectively distinguished cognitive impairments in SCA10 patients, showing satisfactory sensitivity and specificity (AUC of 0.83). Although no significant differences were found in the AUCs between CCAS-S and MoCA (p = 0.45), the CCAS-S demonstrated a significantly larger effect size in the comparison between patients and control group (d = 2.33). Cognitive performance was poorer in patients than in controls (p = < 0.001), with depressive symptoms and age having a significant impact on CCAS-S outcomes. Patients with the SCA10 mutation exhibit CCAS. Besides the significant cognitive impairment, also detected by MoCA, the CCAS-S score was significantly affected by indicators of depressive mood and age, highlighting the importance of considering these variables during outcome analyses.

The latest tremor classification suggested to stratify patients with Essential Tremor (ET) into pure (pET) and plus (ET-plus) forms. Cognitive dysfunction in ET might reflect the Cerebellar Cognitive Affective Syndrome (CCAS), but there is no evidence in ET-plus. We aimed to evaluate the CCAS in ET-plus, further attempting to explore possible motor-cognitive associations.Thirty-nine patients with ET-plus and 19 matched healthy controls (HC) performed the CCAS-scale (CCAS-S). Patients were also assessed using the Tremor Research Group Essential Tremor Rating Scale and the Scale for the Assessment and Rating of Ataxia. Moreover, data about their soft signs were recorded. The obtained data were further compared to a published series of pET. Patients with ET-plus had worse CCAS-S performances than HC, with 69.4% of the former having a definite CCAS. Cognitive performances did not correlate with any of the clinical data, but with the presence of slowing. While the rate of definitive CCAS was similar between pET and ET-plus, they demonstrated different cognitive profiles. Poorer CCAS-S performance had a detrimental impact on activity of daily living beyond tremor severity. Our results demonstrate a pervasive cognitive impairment in ET-plus, possibly sustained by a cerebellar dysfunction. However, the association of cognitive deficits with the presence of slowing and the qualitative differences between ET-plus and pET might suggest a more widespread pathology with the involvement of extra-cerebellar brain areas, indicating that they reflect two different entities.

The cerebellum is no longer considered a purely motor control device, and convincing evidence has demonstrated its relationship to cognitive and emotional neural circuits. The aims of the present study were to establish the core cognitive features in our patient population and to determine the presence of Cerebellar Cognitive Affective Syndrome (CCAS) in this group. We recruited 38 patients with spinocerebellar ataxia type 3 (SCA3) or Machado–Joseph disease (MJD)-SCA3/MJD and 31 controls. Data on disease status were recorded (disease duration, age, age at onset, ataxia severity, and CAG repeat length). The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. The neuropsychological assessment consisted of the Mini-Mental State Examination, Clock Drawing Test, Wechsler Adult Intelligence Scale, Rey–Osterrieth Complex Figure, Wisconsin Card Sorting Test, Stroop Color–Word Test, Trail-Making Test, Verbal Paired Associates, and verbal fluency tests. All subjects were also submitted to the Hamilton Anxiety Scale and Beck Depression Inventory. After controlling for multiple comparisons, spatial span, picture completion, symbol search, Stroop Color–Word Test, phonemic verbal fluency, and Trail-Making Tests A and B were significantly more impaired in patients with SCA3/MJD than in controls. Executive and visuospatial functions are impaired in patients with SCA3/MJD, consistent with the symptoms reported in the CCAS. We speculate on a possible role in visual cortical processing degeneration and executive dysfunction in our patients as a model to explain their main cognitive deficit.

Accumulating evidence points toward an association between older age and performance decrements in social cognition (SC). We explored age-related variations in four components of SC: emotion recognition, theory of mind, social judgment, and blame attributions. A total of 120 adults divided into three stages (18–34 years, 35–59 years, 60–85 years) completed a battery of SC. Between and within age-group differences in SC were investigated. Path analyses were used to identify relationships among the components. Emotion recognition and theory of mind showed differences beginning either in midlife, or after. Blame attributions and social judgment did not show a significant difference. However, social judgment varied significantly within groups. Path models revealed a relationship between emotion recognition and theory of mind. Findings highlight age-related differences in some components and a link between two components. Strategies promoting social functioning in aging might help to maintain or improve these abilities over time.