Cerebellar Cognitive Affective Syndrome Research Articles

The Hungarian validation of the Cerebellar Cognitive-Affective Syndrome Scale

The Hungarian validation of the Cerebellar Cognitive-Affective Syndrome Scale

A combination of chlorzoxazone and folic acid improves recognition memory, anxiety and depression in SCA3-84Q mice.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is reported to be the most common type of autosomal dominant cerebellar ataxia (ADCA). SCA3 patients suffer from a progressive decline in motor coordination and other disease-associated symptoms. Moreover, recent studies have reported that SCA3 patients also exhibit symptoms of cerebellar cognitive affective syndrome (CCAS). We previously observed signs of CCAS in mouse model of SCA3. Particularly, SCA3-84Q mice suffer from anxiety, recognition memory decline, and also exhibit signs of low mood and aversion to activity. Here we studied the effect of long-term injections of SK channels activator chlorzoxazone (CHZ) together and separately with the folic acid (FA) on the cerebellar Purkinje cell (PC) firing and histology, and also on the motor and cognitive functions as well as mood alterations in SCA3-84Q hemizygous transgenic mice. We realized that both CHZ and CHZ-FA combination had similar positive effect on pure cerebellum impairments including PC firing precision, PC histology, and motor performance in SCA3-84Q mice. However, only the CHZ-FA combination, but not CHZ, had significantly ameliorated the signs of anxiety and depression, and also noticeably improved recognition memory in SCA3-84Q mice. Our results suggest that the combination therapy for both ataxia and non-motor symptoms is required for the complex treatment of ADCA.

Redefining cerebellar assessment: A comprehensive review of the cerebellum's cognitive and affective roles and the efficacy of CCAS scales.

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.

Proceedings of the first global meeting of the Posterior Fossa Society: state of the art in cerebellar mutism syndrome.

The Posterior Fossa Society, an international multidisciplinary group, hosted its first global meeting designed to share the current state of the evidence across the multidisciplinary elements of pediatric post-operative cerebellar mutism syndrome (pCMS). The agenda included keynote talks from world-leading speakers, compelling abstract presentations and engaging discussions led by members of the PFS special interest groups. This paper is a synopsis of the first global meeting, a 3-day program held in Liverpool, England, UK, in September 2022. Topics included nosology, patient and family experience, cerebellar modulation of cognition, and cerebellar cognitive affective syndrome. In addition, updates from large-scale studies were shared as well as abstracts across neuroradiology, neurosurgery, diagnosis/scoring, ataxia, and rehabilitation. Based on data-driven evidence and discussions, each special interest group created research priorities to target before the second global meeting, in the spring of 2024.

The Role of Verbal Fluency in the Cerebellar Cognitive Affective Syndrome Scale in Friedreich Ataxia.

Cerebellar pathology engenders the disturbance of movement that characterizes Friedreich ataxia (FRDA), yet the impact of cerebellar pathology on cognition in FRDA remains unclear. Numerous studies have unequivocally demonstrated the role of the cerebellar pathology in disturbed cognitive, language and affective regulation, referred to as Cerebellar Cognitive Affective Syndrome (CCAS), and quantified by the CCAS-Scale (CCAS-S). The presence of dysarthria in many individuals with ataxia, particularly FRDA, may confound results on some items of the CCAS-S resulting in false-positive scores. This study explored the relationship between performance on the CCAS-S and clinical metrics of disease severity in 57 adults with FRDA. In addition, this study explored the relationship between measures of intelligibility and naturalness of speech and scores on the CCAS-S in a subgroup of 39 individuals with FRDA. We demonstrated a significant relationship between clinical metrics and performance on the CCAS-S. In addition, we confirmed the items that returned the greatest rate of failure were based on Verbal Fluency Tasks, revealing a significant relationship between these items and measures of speech. Measures of speech explained over half of the variance in the CCAS-S score suggesting the role of dysarthria in the performance on the CCAS-S is not clear. Further work is required prior to adopting the CCAS-S as a cognitive screening tool for individuals with FRDA.

Hungarian adaptation of the cerebellar cognitive affective/Schmahmann Syndrome Scale

Recent studies have reported that cerebellar lesions can cause cognitive, behavioral, and affective symptoms. This constellation is called the cerebellar cognitive affective syndrome (CCAS). A bedside instrument, the CCAS-Scale, has been developed to screen for this clinical presentation. The aim of this study is to adapt the CCAS-Scale to Hungarian according to international cross-cultural guidelines. In cooperation with the senior author of the original CCAS-Scale, we defined a five-step adaptation protocol (license number 6758-1/2021). Step 1: translation of the scale from English to Hungarian by two separate teams. Step 2: comparison of the two translated versions, synthesis (preliminary version). Step 3: back translation by an independent professional translator. Step 4: authorization, revision, and correction. Step 5: pre-testing the scale, measuring the test times. Following our protocol, we produced the CCAS-H and the instructions booklet. We pre-tested healthy (n = 10) and cerebellar stroke patients (n = 10) and finalized the scale. Although not significantly, but cerebellar patients reached lower raw scores compared with healthy subjects. Testing times differed significantly between the two groups. A meticulous validation protocol was outlined to assess the validity and reliability of the newly adapted test. CCAS-H is a quick and adequate scale to examine the cerebellar-cognitive affective syndrome, which will be available for Hungarian professionals. Our main challenge was to define the stimuli and cues with adequate psycholinguistic and psychometric properties. As a next step, we are gathering data for the validation with the help of six other Hungarian Neurology departments.

358 Quantifying Cognitive and Affective Dysfunction in Chiari Malformation Type I Patients With the Cerebellar Cognitive Affective Syndrome Scale and the Cerebellar Neuropsychiatric Rating Scale

INTRODUCTION: Cognitive and affective dysfunction in Chiari Malformation Type I (CM1) patients are well-documented, but often rely on extensive neuropsychological tests. METHODS: Symptomatic CM1 patients considering surgical decompression were assessed by a board-certified neuropsychologist using the 105-point CNRS (N = 87) and the 10-task CCAS (N = 23), as well as a full neuropsychological battery (N = 24: Wechsler Full Scale IQ, Digit Span, Coding; WRAML Finger Windows; DKEFS Trail Making; verbal list learning; Grooved Pegboard). Descriptive and correlative measures were computed. RESULTS: The study included 66 adults and 21 children. A neuropsychological battery revealed impairment in 29% of patients on 1 test, 12.8% on 2 tests, and 20.8% on 3 or more tests. The CCAS indicated 26% with "possible CCAS" (1 task), 27% with "probable CCAS" (2 tasks), and 18% with "definite CCAS" (3 or more tasks). The median CNRS composite score was 31.0 (IQR: 18.5, 49.0), with positive and negative symptom sub-scores of 18.0 (10.0, 26.5) and 14.0 (7.5, 23.5), respectively. Moderate correlation with the neuropsychological battery was found between impairment detected by CCAS (Spearman rank coefficient ρ = 0.67, p = 0.002) and CNRS (ρ = 0.56, p = 0.003). CONCLUSIONS: A high prevalence of cognitive and affective impairments in pre-operative CM1 patients was observed by all three testing batteries. In this first report of CNRS and CCAS usage in CM1 patients, increased CNRS and CCAS impairment correlated with impairment on standard neuropsychological testing. These tools show promise for future studies CM1, providing a more concise alternative to traditional testing for cognitive and affective dysfunction.

Abstract TP84: Characteristics of Cerebellar Cognitive Affective Syndrome in Patients With Acute Cerebellar Stroke and Its Impact on Outcome

Background: Recently, cerebellar cognitive affective syndrome-scale (CCAS-S) was developed to assess CCAS in which cognitive impairment is caused by cerebellar lesions. However, very few studies have been conducted regarding CCAS in patients with stroke, and its impact on outcomes is unclear. This study aimed to evaluate CCAS in patients with acute cerebellar stroke and examine its association with outcome. Methods: Patients who experienced acute cerebellar stroke for the first time and were admitted to Steel Memorial Yawata Hospital, Japan within seven days of stroke onset between April 2021 and April 2023 were included in this observational study. CCAS-S, Mini-Mental State Examination (MMSE), and Scale for Assessment and Rating of Ataxia (SARA) scores were measured one week after stroke onset, and Functional Independence measure (FIM)/ Barthel Index (BI) at discharge, physical function, activities of daily living, length of hospital stay, and outcome (discharge destination) were evaluated. The Mann-Whitney U test was used to compare CCAS-S scores and other variables between patients with acute cerebellar stroke and healthy controls. Additionally, we compared these variables between patients discharged home and those discharged to a rehabilitation hospital. A significance level of less than 5%. Results: Thirteen consecutive patients with acute cerebellar stroke (9 women) and age-and sex-matched healthy controls (7 women) were included. The MMSE score was within the normal range in all patients; however, patients with stroke had a lower total CCAS-S score (median 72, interquartile range [IQR] 66-80) and a higher number of failed tests (median 4, IQR 3-5) than healthy controls. Significant deficits were observed in semantic fluency (p=0.008), category switching (p=0001), and similarity (p=009). Possible, probable, and definite CCAS were diagnosed in 2, 1, and 10 patients, respectively. Patients discharged home showed better SARA and FIM/BI scores but similar CCAS-S scores compared to those discharged to rehabilitation hospitals. Conclusion: CCAS along with impaired executive and language functions is frequently observed in patients with acute cerebellar stroke; however, impaired motor function, and not CCAS, influenced the outcome.

Cognitive, Emotional, and Other Non-motor Symptoms of Spinocerebellar Ataxias.

Spinocerebellar ataxias (SCAs) are autosomal dominant degenerative syndromes that present with ataxia and brain stem abnormalities. This review describes the cognitive and behavioral symptoms of SCAs in the context of recent knowledge of the role of the cerebellum in higher intellectual function. Recent studies suggest that patients with spinocerebellar ataxia can display cognitive deficits even early in the disease. These have been given the term cerebellar cognitive affective syndrome (CCAS). CCAS can be tracked using newly developed rating scales. In addition, patients with spinocerebellar ataxia also display impulsive and compulsive behavior, depression, anxiety, fatigue, and sleep disturbances. This review stresses the importance of recognizing non-motor symptoms in SCAs. There is a pressing need for novel therapeutic interventions to address these symptoms given their deleterious impact on patients' quality of life.

Cerebellar-Induced Aphasia After Stroke: Evidence for the "Linguistic Cerebellum".

The cerebellum is traditionally known to subserve motor functions. However, for several decades, the concept of the "cerebellar cognitive affective syndrome" has evolved. Studies in healthy participants and patients have confirmed the cerebellar role in language. The exact involvement of the cerebellum regarding cerebellar aphasia remains uncertain. We included 43 cerebellar stroke patients who were tested at 3 months post-onset with the Boston Naming Test (BNT), the Token Test (TT), and the Diagnostic Instrument for Mild Aphasia (DIMA). Lesion side (left/right) and volume (cm3) were investigated. Patients significantly deviated on the following: BNT (p<0.001), TT (p<0.05), DIMA subtests: sentences repetition (p=0.001), semantic odd-picture-out (p<0.05), sentence completion (p<0.05) without an effect of lesion location (left/right) or volume (cm3) (p>0.05). Our clinical study confirms a non-lateralized cerebellar aphasia post-stroke, characterized by impairments in word retrieval, phonology, semantics, and syntax resembling cerebral-induced aphasia. The integral cerebellum appears to interact with eloquent cortico-subcortical language areas.

Frontotemporal disorders: the expansive panoply of syndromes and spectrum of etiologies.

Frontotemporal lobe disorders (FTD) are amongst the most common brain neurodegenerative disorders. Their relatively covert, frequently subtle presentations and diverse etiologies, pose major challenges in diagnosis and treatments. Recent studies have yielded insights that the etiology in the majority are due to environmental and sporadic causes, rather than genetic in origin. To retrospectively examine the cognitive and behavioral impairments in the veteran population to garner the range of differing syndrome presentations and etiological subcategories with a specific focus on frontotemporal lobe disorders. The design is a retrospective, observational registry, case series with the collection of epidemiological, clinical, cognitive, laboratory and radiological data on people with cognitive and behavioral disorders. Inclusion criteria for entry were veterans evaluated exclusively at Orlando VA Healthcare System, neurology section, receiving a diagnosis of FTD by standard criteria, during the observation period dated from July 2016 to March 2021. Frontotemporal disorders (FTD) were delineated into five clinical 5 subtypes. Demographic, cardiovascular risk factors, cognitive, behavioral neurological, neuroimaging data and presumed etiological categories, were collected for those with a diagnosis of frontotemporal disorder. Of the 200 patients with FTD, further cognitive, behavioral neurological evaluation with standardized, metric testing was possible in 105 patients. Analysis of the etiological groups revealed significantly different younger age of the traumatic brain injury (TBI) and Gulf War Illness (GWI) veterans who also had higher Montreal Cognitive Assessment (MOCA) scores. The TBI group also had significantly more abnormalities of hypometabolism, noted on the PET brain scans. Behavioral neurological testing was notable for the findings that once a frontotemporal disorder had been diagnosed, the four different etiological groups consistently had abnormal FRSBE scores for the 3 principal frontal presentations of (i) abulia/apathy, (ii) disinhibition, and (iii) executive dysfunction as well as abnormal Frontal Behavioral Inventory (FBI) scores with no significant difference amongst the etiological groups. The most common sub-syndromes associated with frontotemporal syndromes were the Geschwind-Gastaut syndrome (GGS), Klüver-Bucy syndrome (KBS), involuntary emotional expression disorder (IEED), cerebellar cognitive affective syndrome (CCA), traumatic encephalopathy syndrome (TES) and prosopagnosia. Comparisons with the three principal frontal lobe syndrome clusters (abulia, disinhibition, executive dysfunction) revealed a significant association with abnormal disinhibition FRSBE T-scores with the GGS. The regression analysis supported the potential contribution of disinhibition behavior that related to this complex, relatively common behavioral syndrome in this series. The less common subsyndromes in particular, were notable, as they constituted the initial overriding, presenting symptoms and syndromes characterized into 16 separate conditions. By deconstructing FTD into the multiple sub-syndromes and differing etiologies, this study may provide foundational insights, enabling a more targeted precision medicine approach for future studies, both in treating the sub-syndromes as well as the underlying etiological process.

Multi‐Modal Structural Covariance Patterns Predictive of Dementia Ratings and Geriatric Depression Severity

AbstractBackgroundMore than 6 million Americans suffer from Alzheimer’s disease (AD), the most common age‐associated, neurodegenerative dementia, characterized by progressive cognitive decline and the sporadic emergence of neuropsychiatric symptoms (NPS). We applied linked independent component analysis (LICA), a unsupervised learning approach for data fusion, to identify multi‐modal gray matter patterns of covariation that were predictive of dementia ratings and depression symptoms to understand the brain circuitry underlying both.MethodPublicly available data from 277 participants (177 healthy controls, 61 mild cognitive impairment, and 39 AD (aged 58 – 93) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset were used to conduct secondary analyses.T1‐weighted MR images were used to compute spatial maps of cortical thickness (CT) and pial surface area (PSA) using Freesurfer and grey matter (GM) density maps using FSLVBM. CT, PSA and GM maps for each modality were concatenated across participants into 4D data files that were analyzed using FSL Linked ICA to estimate 25 multi‐modal spatial components and subject loadings quantifying the strength of each component pattern per participant. Random forest regression with 5‐fold cross validation was used to predict CDR and GDS from the resulting subject loadings (with age, sex and site).ResultTwo LICA components (Fig 1) had highest feature importance in predicting CDR (R2 = 0.41). The same two patterns (Fig1) plus two additional patterns (Fig 2) were most important in predicting GDS (R2 = 0.08).ConclusionGreater CDR was predicted by larger (Fig 1A) decreased GM and CT of widespread temporal lobe regions and (Fig 1B) of reduced GM of entorhinal cortex/mesial temporal lobe with nodes of the default mode network, implicated in disease progression. Greater GDS was also predicted by these two patterns as well as a pattern (Fig 2A) reflecting decreased GM in nucleus accumbens, amygdala and a cerebellar‐thalomocortical (CTC) circuit strongly implicated in cerebellar cognitive affective syndrome (CCAS) and another (Fig 2B) comprised of CT decreases in cortex and temporal regions and GM decreases in frontoparietal regions resembling areas of the frontopariatal functional connectivity network. These multi‐modal brain‐behavior mappings could be translated to better understand dementia and neuropsychiatric symptoms of AD.

Cognitive-affective manifestations since premanifest phases of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease

BackgroundCognitive deficits were related to Spinocerebellar Ataxia type 3/Machado-Joseph Disease (SCA3/MJD), but the Cerebellar Cognitive Affective Syndrome (CCAS) needs further investigation in this disorder. We aimed to characterize cognitive-affective deficits in manifest and premanifest SCA3/MJD carriers. MethodsSubjects at 50% risk, manifest carriers and unrelated controls were evaluated in-person or in virtual settings with CCAS Scale (CCAS-S), Stroop Color-Word Test (SCWT), Trail-Making Test (TMT), and Reading the Mind in the Eyes Test (RMET). Scale for Assessment and Rating of Ataxia (SARA) >2.5 or Friedreich Ataxia Rating Scale/Activities of Daily Living (FARS-adl) >4 divided carriers into manifest and premanifest. Time after onset or time left to gait ataxia onset (TimeToAfterOnset) were estimated. Differences between groups and correlations with TimeToAfterOnset, SARA and FARS-adl were checked. ResultsAfter random selection to balance groups, 23 manifest and 35 premanifest carriers, and 58 controls were included. CCAS-S, semantic fluency, phonemic fluency, category switching, affect, SCWT, and RMET showed significant differences between manifest carriers and controls; premanifest carriers mostly displayed intermediate values between controls and manifest carriers. These variables correlated with TimeToAfterOnset and SARA scores of the carriers. Correlations with SARA were stronger in the pre-ataxic group. CCAS-S had the strongest correlations with time and SARA. DiscussionCognitive-affective deficits in SCA3/MJD involve executive function, language, affect, and social cognition, which seem to be altered prior to the ataxia onset, and correlate with markers of motor progression. CCAS-S was the most promising biomarker and should be evaluated in longitudinal studies.

The CODECS study: COgnitive DEficits in Cerebellar Stroke

Part of the extra-pyramidal system, the cerebellum is more and more recognized by its non-motor functions known as the cerebellar cognitive affective syndrome. Several studies have identified disturbances specifically in executive and attentional functions after focal cerebellar lesions. However, most studies were performed in small and heterogeneous patient groups. Furthermore, there is a substantial variation in the methodology of assessment. Here, we present the results of a large and homogeneous cohort of patients with isolated uniform cerebellar lesions. After three months post-stroke all patients underwent structural neuroimaging to confirm an isolated lesion and were given neuropsychological testing. The results show that cerebellar lesions relate to mild but long-term cognitive impairment in a broad spectrum of neurocognitive functions compared to normative values. These findings confirm involvement of the cerebellum in cognitive processing and supports the theory of ‘dysmetria of thought’ based upon uniform cerebellar processing in multiple cognitive domains. This study highlights the following results: 1-Cognitive impairments after isolated cerebellar stroke is confirmed in several cognitive domains. 2-Semantic and phonemic fluency are most affected in cerebellar stroke patients. 3-Verbal deficits show an age-independent long term effect post-stroke and should be studied further in depth. 4-Cognitive disorders after cerebellar stroke are more prominent in women than men.

The Cerebellum's Role in Affective Disorders: The Onset of Its Social Dimension.

Major Depressive Disorder (MDD) and Bipolar Disorder (BD) are the most frequent mental disorders whose indeterminate etiopathogenesis spurs to explore new aetiologic scenarios. In light of the neuropsychiatric symptoms characterizing Cerebellar Cognitive Affective Syndrome (CCAS), the objective of this narrative review is to analyze the involvement of the cerebellum (Cbm) in the onset of these conditions. It aims at detecting the repercussions of the Cbm activities on mood disorders based on its functional subdivision in vestibulocerebellum (vCbm), pontocerebellum (pCbm) and spinocerebellum (sCbm). Despite the Cbm having been, for decades, associated with somato-motor functions, the described intercellular pathways, without forgiving the molecular impairment and the alteration in the volumetric relationships, make the Cbm a new important therapeutic target for MDD and BD. Given that numerous studies have showed its activation during mnestic activities and socio-emotional events, this review highlights in the Cbm, in which the altered external space perception (vCbm) is strictly linked to the cognitive-limbic Cbm (pCbm and sCbm), a crucial role in the MDD and BD pathogenesis. Finally, by the analysis of the cerebellar activity, this study aims at underlying not only the Cbm involvement in affective disorders, but also its role in social relationship building.

Memory decline, anxiety and depression in the mouse model of spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant hereditary disorder, caused by an expansion of polyglutamine in the ataxin-3 protein. SCA3 symptoms include progressive motor decline caused by an atrophy of the cerebellum and brainstem. However, it was recently reported that SCA3 patients also suffer from the cerebellar cognitive affective syndrome. The majority of SCA3 patients exhibit cognitive decline and approximately half of them suffer from depression and anxiety. The necessity to find a combined therapy for both motor and cognitive deficits in a SCA3 mouse model is required for the development of SCA3 treatment. Here, we demonstrated that the SCA3-84Q transgenic mice exhibited anxiety over the novel brightly illuminated environment in the open field, novelty suppressed feeding, and light-dark place preference tests. Moreover, SCA3-84Q mice also suffered from a decline in recognition memory during the novel object recognition test. SCA3-84Q mice also demonstrated floating behavior during the Morris water maze that can be interpreted as a sign of low mood and aversion to activity, i.e. depressive-like state. SCA3-84Q mice also spent more time immobile during the forced swimming and tail suspension tests which is also evidence for depressive-like behavior. Therefore, the SCA3-84Q mouse model may be used as a model system to test the possible treatments for both ataxia and non-motor symptoms including depression, anxiety, and memory loss.

Postoperative pediatric cerebellar mutism syndrome: A literature review

Introduction: Postoperative pediatric cerebellar mutism syndrome (POPCMS) is a significant complication observed after posterior fossa surgery for tumors, particularly in pediatric neurosurgery. This paper presents a literature review on the physiopathology, diagnosis, treatment, and long-term outcomes of POPCMS.&#x0D; Methods: A systematic review following PRISMA guidelines, searching for articles published in PubMed, Web of Science, and Lilacs in the last ten years. Inclusion criteria involved studies on human subjects under 18 years of age, focusing on the pathophysiology, diagnosis, treatment, and outcome of POPCMS.&#x0D; Results: The review identified 34 studies on POPCMS for final inclusion. Preoperative risk factors commonly associated with cerebellar mutism included midline tumor location, diagnosis of medulloblastoma, younger age at diagnosis, preoperative language impairment, brainstem infiltration, and tumor histology. The SHH subgroup was found to reduce the risk of CMS. Diagnostic criteria for POPCMS included language impairment, emotional lability, hypotonia, oropharyngeal dysfunction, dysphagia, cerebellar motor syndrome, cerebellar cognitive affective syndrome, and brainstem dysfunction. Treatment approaches varied, with medications showing potential benefits. Rehabilitation options for speech and language deficits were limited. Cognitive remediation programs showed promise in improving academic achievement and attention. A significant proportion of patients experienced clinical improvement. &#x0D; Conclusion: POPCMS remains a challenging complication following posterior fossa surgery. Further research is needed to develop standardized diagnostic criteria, effective treatments, and rehabilitation strategies to improve long-term outcomes for patients with POPCMS.

Cognitive impairment in essential tremor assessed by the cerebellar cognitive affective syndrome scale.

Essential tremor (ET) is a movement disorder characterized by cerebellar neurodegenerative changes. ET is also associated with non-motor symptoms including cognitive impairment. The neuropsychologic profile of a patient with ET could relate to cerebellar cognitive affective syndrome (CCAS). This study aimed to assess the prevalence of cognitive impairment in patients with ET and identify whether the cognitive impairment in ET corresponds to a CCAS. Cognitive functions were evaluated with the CCAS-Scale (CCAS-S) in 20 patients with ET and 20 controls matched for age, sex, and level of education. The results of the CCAS-S were compared between patients and controls. The underlying determinant of CCAS inpatients with ET was identified through the correlation between the results of the CCAS-S and age at onset of symptoms, disease duration, and the Essential Tremor Rating Assessment Scale (TETRAS). On a group level, ET patients performed significantly worse than matched controls. In total, 13 individuals with ET had a definite CCAS (CCAS-S failed items ≥ 3). ASO and TETRAS scores significantly correlated with CCAS-S performances in ET patients. CCAS is highly prevalent in patients with ET which supports the cerebellar pathophysiology of associated cognitive impairment and supports a more systematic use of the CCAS-S to cognitively assessed patients with ET.

A chlorzoxazone–folic acid combination improves cognitive affective decline in SCA2-58Q mice

Spinocerebellar ataxia type 2 (SCA2) is a polyglutamine disorder caused by a pathological expansion of CAG repeats in ATXN2 gene. SCA2 is accompanied by cerebellar degeneration and progressive motor decline. Cerebellar Purkinje cells (PCs) seem to be primarily affected in this disorder. The majority of the ataxia research is focused on the motor decline observed in ataxic patients and animal models of the disease. However, recent evidence from patients and ataxic mice suggests that SCA2 can also share the symptoms of the cerebellar cognitive affective syndrome. We previously reported that SCA2-58Q PC-specific transgenic mice exhibit anxiolytic behavior, decline in spatial memory, and a depressive-like state. Here we studied the effect of the activation of the small conductance calcium-activated potassium channels (SK channels) by chlorzoxazone (CHZ) combined with the folic acid (FA) on the PC firing and also motor, cognitive and affective symptoms in SCA2-58Q mice. We realized that CHZ-FA combination improved motor and cognitive decline as well as ameliorated mood alterations in SCA2-58Q mice without affecting the firing rate of their cerebellar PCs. Our results support the idea of the combination therapy for both ataxia and non-motor symptoms in ataxic mice without affecting the firing frequency of PCs.

Arnold-Chiari Malformation-I Borderline Personality Disorder

Introduction: Arnold-Chiari Malformation I (AM-I) is a congenital anomaly that manifests with cerebellar dysfunction. There is a displacement of cerebellar tonsils into the foramen magnum. Several mood disorders, personality disorders, and intellectual disabilities are associated with AM-I. Borderline personality disorder (BPD) is characterized by symptoms of mood lability, impulsivity, extreme efforts of abandonment, splitting and dysfunctional relationships. Case Description: The patient is an early aged adult with a past medical history of AM-I, hypothyroidism, Wolff-Parkinson-White syndrome, and diabetes mellitus type II. The patient was admitted to the hospital after ingesting foreign bodies. He/she presented with mood lability, sad mood, anhedonia, insomnia, panic attacks, ruminative worries, feelings of emptiness, and recurrent suicidal gestures and threats. The patient was eventually diagnosed with borderline personality disorder. This case suggests a possible connection between AM-I and BPD. Discussion: Emerging from contemporary research involving the cerebellum, it is important to acknowledge that the current definition of control of fine motor and balance is inadequate. Symptoms associated with AM-I and BPD may be better explained by Cerebellar Cognitive Affective Syndrome (CCAS), a condition that ties the cerebellum with the higher cognitive functioning in the brain.