Cerebellar Syndrome Research Articles

Characteristics of cerebellar cognitive affective syndrome in patients with acute cerebellar stroke and its impact on outcome

Purpose To evaluate the cerebellar cognitive affective syndrome scale (CCAS-S) in patients with acute cerebellar stroke (ACS) and examine its relationship with the discharge destination. Methods Patients with first-time ACS admitted to our hospital between April 2021 and April 2023 were included. The CCAS-S, Mini-Mental State Examination (MMSE), and Scale for the Assessment and Rating of Ataxia (SARA) were evaluated 1 week after stroke onset, and Functional Independence Measure (FIM)/Barthel Index (BI) at discharge, duration of hospitalization, and discharge destination were evaluated. The Mann–Whitney U test was used to compare CCAS-S and variables. Results Thirteen consecutive patients with ACS and age-matched comparison groups were included. The MMSE was within the normal range in all patients; however, patients with stroke had a lower total CCAS-S score (median 72, IQR 66–80) and a higher number of failed tests (median 4, IQR 3–5) than comparison. Significant deficits were observed in semantic fluency (p = 0.008), category switching (p = 0001), and similarity (p = 009). Definite CCAS were diagnosed 10 patients, respectively. Patients discharged home showed better SARA and FIM/BI but similar CCAS-S compared to those discharged to rehabilitation hospitals. Conclusion In patients with ACS, it is the impairment of motor function, not CCAS, that affects discharge destination.

RARE TUMORS OF POSTERIOR CRANIAL FOSSA IN ADULTS

Objectives Tumors arising in the posterior cranial fossa pertain to a special category of neoplasm in the manner that they can cause cerebellar syndrome, obstructive hydrocephalus, brainstem compression – cranial nerve dysfunction – and herniation. In the cerebellopontine angle, the most common tumors are acoustic neuromas followed by meningiomas. Among the petroclival tumors, the most common benign tumors are meningiomas and the most common malign tumors are chordomas and metastases. Among jugular foramen tumors, the common tumors are schwannomas, paragangliomas and meningiomas. We report our unit’s experience with the neurosurgical management of rare posterior cranial fossa tumors as compared to the main literature results, taking into consideration the clinical, radiological aspects and the outcome. Materials and Methods Retrospective analysis of a single unit cohort of patients diagnosed with rare posterior cranial fossa tumors, who underwent surgical treatment in the Neurosurgery I Department of the University Emergency Hospital Bucharest between 2017 and 2024. Relevant literature review was analyzed, as well as serial clinical examinations, imaging studies, and operative records were taken into consideration. Conclusions Depending on the location, size, and pathology of the posterior cranial fossa tumors, there are different treatment options, which include microsurgical resection, observation, stereotactic radiotherapy. These type of lesions still represent a challenge and require electing the most suitable approach whilst preserving the neurologic function of the patient.

NCMP-08. PRE-OPERATIVE AND INTRA-OPERATIVE RISK FACTORS OF POST-OPERATIVE CEREBELLAR MUTISM SYNDROME IN PEDIATRIC PATIENTS UNDERGOING POSTERIOR FOSSA TUMOR SURGERY: A SYSTEMATIC REVIEW

Abstract INTRODUCTION Post-operative cerebellar mutism syndrome (pCMS) is a complication of surgical removal of posterior fossa tumors. The neurological and linguistic symptoms of pCMS may resolve in approximately 6 months, however, the children are vulnerable to the burden of significant long-term residual deficits. The current literature lacks a review of intraoperative and preoperative risk factors of postoperative pCMS. The authors addressed this issue by conducting a systematic review of studies investigating these risk factors in pediatric patients with posterior fossa tumors. METHODS The authors extracted potential citations from Google Scholar, PubMed, Scopus, and Cochrane. The eligible studies included pediatric patients less than 18 years of age, who were diagnosed with posterior fossa tumors and developed CMS following the posterior fossa tumor surgery. RESULTS A total of 64 studies involving 6,420 patients were included in this systematic review. The preoperative risk factors delineated in this review are oncological, tumor location, tumor extension, structural invasion, radiological predictors, preoperative hydrocephalus, age, gender, and pre-operative language impairment. Of these factors, a substantial number of studies reported histopathological diagnosis of medulloblastoma, high-grade tumor histology, and midline location of posterior fossa tumor as significant risk factors of pCMS. The intraoperative risk factors significantly associated with pCMS included vermis incision, superior cerebellar peduncle involvement, medulloblastoma diagnosis, and gross total tumor resection. Only a few studies identified protective factors that reduced the risk of developing pCMS. CONCLUSION In this systematic review, we have pooled all the available studies with extractable data to identify the intraoperative and preoperative risk factors of postoperative pCMS in pediatric patients undergoing surgery for posterior fossa tumors. This data can be utilized by healthcare professionals including neurosurgeons in identifying factors that compound the risk of postoperative pCMS and factors that have opposite effects on postoperative outcomes.

Cerebellar Transcranial Direct Current Stimulation in the Cerebellar Cognitive Affective Syndrome: A Randomized, Double-Blind, Sham-Controlled Trial.

The cerebellar cognitive affective syndrome (CCAS) encompasses cognitive and affective symptoms in patients with cerebellar disorders, for which no proven treatment is available. Our primary objective was to study the effect of cerebellar anodal transcranial direct current stimulation (tDCS) on cognitive performance in CCAS patients. Secondary effects on ataxia severity, mood, and quality of life were explored. We performed a randomized, double-blind, sham-controlled trial. Thirty-five patients with CCAS were included and received 10 sessions of 20 minutes sham (n = 17) or real (n = 18) tDCS, with a current of 2 mA. Cognitive performance was assessed using executive function subtests of the computerized Test of Attentional Performance (TAP), with the composite as primary endpoint. Secondary outcomes were ataxia severity, mood, and quality of life. Outcomes were evaluated 1, 3, 6, and 12 months post-intervention. Cerebellar tDCS was well tolerated and no serious adverse events related to the intervention occurred. No significant tDCS effect was found on cognitive performance. Improvement on the TAP was observed in the sham group 1 month post-treatment (estimate = -0.248, 95% CI, -0.49 to -0.01), but not clinically relevant. A positive tDCS effect was observed for ataxia severity 1 month post-treatment (estimate = -0.985, 95% CI, -1.94 to -0.03). Ten sessions of 20 minutes cerebellar anodal tDCS did not prove efficacious for CCAS-related cognitive impairment, but a significant positive effect of tDCS was found for ataxia severity, aligning with previous findings indicative of tDCS as a therapeutic neuromodulation tool in cerebellar disorders. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

P50 Systemic lupus erythematous presenting as Kikuchi-Fujimoto disease complicated with haemophagocytic lymphohistiocytosis: a case report and review of the literature

Abstract Introduction Kikuchi-Fujimoto disease (KFD) or histiocytic necrotising lymphadenitis is a rare, self-limiting inflammatory condition that can be associated with autoimmune connective tissue disorders (CTD) especially systemic lupus erythematosus (SLE). The aetiopathogenesis remains unclear but it is thought to be triggered by an infection in individuals with autoimmune predisposition leading to T-cells mediated apoptosis and inflammatory cascade. This condition most commonly affects children and young adults of Asian descent with a slight female preponderance although it can affect any age and ethnic groups. Cervical lymphadenopathy and fever are the salient manifestations, and it can be fatal if complicated with haemophagocytic lymphohistiocytosis (HLH). Case description A 16 year old girl presented with a 2-month history of persistent fever, progressive bilateral cervical lymphadenopathy, generalised maculopapular rash, angioedema-like facial swelling, oral ulcers and B symptoms. Laboratory investigations revealed pancytopaenia, profound acute phase response and abnormalities consistent with HLH with an HScore of 200 points. A thorough infectious workup was unrevealing apart from serological evidence of past Epstein-Barr virus (EBV) infection. ANA, anti-Sm, anti-RNP and anti-B2GP1 IgG were positive. An ultrasound of her neck showed bilateral multilevel cervical lymphadenopathy and the excision biopsy of her lymph node confirmed features of histiocytic necrotising lymphadenitis and ruled out lymphoma. Notably, there were scattered EBV-positive blasts and the special staining for mycobacteria was negative. A CT scan has also demonstrated bilateral axillary and abdominal lymphadenopathy with no hepatosplenomegaly. There was thrombosis in her right internal jugular vein with no intracranial or cardiac extension of the thrombus. The patient was admitted to ITU for close monitoring due to concerns about possible airway compromise but she did not require any respiratory support. She received intravenous (IV) methylprednisolone pulses for three consecutive days, mycophenolate mofetil, hydroxychloroquine and treatment dose of enoxaparin with good response and did not require IV immunoglobulins (IVIG) and/or interleukin-1 receptor antagonists. However, she subsequently developed an abscess in her neck which was complicated by Staphylococcus aureus bacteraemia and underwent an emergency incision and drainage of the abscess. She recovered well with IV antibiotics and was followed up in the CTD clinic with continuous psychological support from the rheumatology clinical nurse specialists. Discussion KFD most commonly presents with acute to subacute tender cervical lymphadenopathy and fevers which can be associated with other systemic features such as arthralgia, various cutaneous manifestations with great histologic heterogeneity, and neurological manifestations including aseptic meningitis, meningoencephalitis, acute cerebellar syndrome and optic neuritis. Generalised lymphadenopathy has been reported in 22% of cases but hepato- and/or splenomegaly is uncommon (3-5% of cases). Various infectious agents including the EBV have been implicated as the potential trigger of this condition but the evidence remains inconclusive. Our patient’s lymph node biopsy has demonstrated EBV-positive blasts with serological evidence of past EBV infection but a causal relationship between these findings and KFD cannot be established with certainty. It remains a diagnostic challenge to differentiate KFD from the other more sinister pathologies such as lymphoma, various infectious lymphadenitis and autoimmune conditions such as sarcoidosis and Kawasaki disease. Therefore, early excisional biopsy of the affected lymph nodes is essential for establishing the correct diagnosis and may obviate the need for inappropriate treatments. Both KFD and SLE share a complex clinicopathological relationship as SLE may precede, occur concurrently as in this case or develop later following the diagnosis of KFD. Moreover, lupus lymphadenitis can mimic KFD clinically and these two entities can only be distinguished histologically by the demonstration of haematoxylin bodies in lupus lymphadenitis. Our patient developed thrombosis in her right internal jugular vein which was thought to be secondary to the compressive effect from her cervical lymphadenopathy rather than due the antiphospholipid syndrome as her repeat antiphospholipid screen was negative. Key learning points • Clinicians should be aware of this rare clinical entity to make an early diagnosis and avoid unnecessary investigations. Differentiating KFD from the other sinister conditions such as lymphoma remains a diagnostic challenge therefore an early excisional biopsy of the affected lymph nodes would avoid delayed diagnosis and obviate the need for potentially risky treatments. Patients with KFD should be carefully screened and monitored for SLE as it can precede, occur in conjunction with or follow the diagnosis of SLE. Most cases of KFD resolve within 1-6 months although recurrence has been reported in 3-4% and the mortality rate is estimated to be 2.1%. It is crucial to follow up these patients given the increased risk of recurrence which can continue for many years. Despite having a good response to treatments, our patient suffered from significant alopecia and post-inflammatory hyperpigmentation in her skin which has had a great impact on her self-esteem and mental well-being. We would like to highlight in this case the biopsychosocial ramifications of this condition and demonstrate the importance of a multidisciplinary approach in the management of young people with CTD.

Paraneoplastic Neurologic Syndromes Associated With Merkel Cell Carcinoma.

To define the clinical and immunologic profile of patients with paraneoplastic neurologic syndromes (PNSs) associated with Merkel cell carcinoma (MCC). Retrospective analysis was conducted on patients with suspected MCC-related PNS assessed at the French Reference Center, and cases were identified by a systematic review of the literature (MEDLINE, Embase) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 17 patients were identified in our center and 30 in the systematic review, resulting in an overall cohort of 47 patients. The median age was 65 years (range 41-90), and 30 of 46 (65%) were men. Lambert-Eaton myasthenic syndrome (LEMS) (14/47, 29%), rapidly progressive cerebellar syndrome (11/47, 23%), and encephalomyelitis (EM) (8/47, 17%) were the most common associated clinical phenotypes. The most frequently associated neural antibodies (Abs) were voltage-gated calcium channel (VGCC)-Abs (14/45, 31%), followed by Hu-Abs (8/45, 17%) and neurofilament (NF)-Abs (8/45, 17%). Patients with NF-Abs only exhibited CNS disorders (8/8, 100%) and often had antibodies against >1 NF subunit (6/8, 75%). At onset, 26 of 43 patients (60%) had no identifiable primary skin tumor but had lymph node metastasis; these patients were more frequently men (21/26, 80%, vs 7/17, 41%; p = 0.007), had more frequently VGCC-Abs (12/26, 46%, vs 2/17, 11%, p = 0.02) predominantly among those with LEMS, and presented reduced mortality than patients with a known primary tumor (5/25, 20%, vs 8/15, 53%; p = 0.02). MCC-related PNSs present as a heterogeneous clinical spectrum including central and/or peripheral nervous system disorders such as LEMS, RCPS, and EM, mainly associated with VGCC-Abs, NF-Abs, and Hu-Abs. NF-Abs were only seen among patients with CNS disorders. At onset, the absence of a primary skin tumor but presence of lymph node metastasis is frequently observed, and this particular clinical presentation is linked to reduced mortality, highlighting distinctive clinical and immunologic features of MCC-related PNS.

Seminoma Resulting in Rapidly Progressive Cerebellar Syndrome with Associated Dual Positive Kelch-like Protein 11 (KLHL11) and Leucine Zipper 4 (LUZP4)–immunoglobulin G (IgG) Antibodies

Seminoma Resulting in Rapidly Progressive Cerebellar Syndrome with Associated Dual Positive Kelch-like Protein 11 (KLHL11) and Leucine Zipper 4 (LUZP4)–immunoglobulin G (IgG) Antibodies

Current Overview of Spinocerebellar Ataxia Type 7 in Mexican Population: Challenges in Specialized Care for a Rare Disease.

Spinocerebellar ataxia type 7 (SCA7) is a rare genetic disease characterized by progressive cerebellar syndrome and macular degeneration. In a previous study, we clinically and genetically characterized a group of Mexican patients, which represented one of the largest cohorts of SCA7 patients worldwide and demonstrated that all patients had a unique genetic origin. Our laboratory developed a program for the diagnosis, medical care, and long-term follow-up of these patients living in Veracruz State, and in this report, we present an update to this research, covering 2013 to 2024. So far, we identified 172 SCA7 carriers, with a few cases outside Veracruz, and our data support that the length of the CAG repeat tract mainly determines disease severity and life expectancy, and accordingly, we define three different phenotypes, early-onset (EO), classical-onset (CO), and late-onset (LO), with EO patients showing the lowest life expectancy. Furthermore, we found that parental transmission of mutant alleles leads to increased CAG repeat instability, compared to maternal ones. Interestingly, a haplotype analysis revealed that patients outside Veracruz may have different genetic origins. In conclusion, longitudinal observations of SCA7 patients provide insight into the natural history of SCA7 and help to design strategies for diagnosis, genetic counseling, physical rehabilitation, and therapeutic alternatives.

Age-Related Features of Clinical and Neurological Characteristics and Pathogenetic Therapy in Patients with Multiple Sclerosis

INTRODUCTION: Multiple sclerosis (MS) is a neurological demyelinating disease of the central nervous system manifested by pronounced heterogeneous symptoms. Peculiarities of the onset, progression rate, and severity of syndromes are different in different age groups. An increase in the frequency of exacerbations, high degree of disability of patients in different age groups evidence insufficient effectiveness of the conducted pathogenetic therapy. Due to a wide choice of multiple sclerosis disease modifying drugs (MSDMDs), it is important to study the clinical and neurological characteristics of patients with MS in different age groups with the aim of further developing an individual approach to treatment. AIM: To study clinical and neurological features and effectiveness of pathogenetic therapy of MS in patients of different age groups. MATERIALS AND METHODS: A prospective analysis of the data of neurological examination and results of magnetic resonance imaging of 100 patients of different age groups with relapsing-remitting MS, who received outpatient treatment in Kursk Regional Multidisciplinary Clinical Hospital, was conducted in the period of stable remission. RESULTS: The leading syndromes in patients with relapsing-remitting course of MS were cerebellar (78%) and pyramidal (70%) syndromes, besides, dysfunction of the cranial nerves (71%) was also observed. A quantitative parameter of explicitness of pelvic disorder syndrome predominated in middle-aged and elderly patients compared to young ones (p 0.001). Cognitive disorders were more often (14%) recorded in middle-aged and elderly patients (p 0.001). The use of glatiramer acetate permitted to reduce the degree of disability in young subjects (p 0.05); in patients of the middle age group, the most effective was a timely transition from interferon beta to ocrelizumab (p 0.05). The use of first-line MSDMDs (interferon-beta) in elderly patients demonstrated low effectiveness (p 0.05). CONCLUSION: In middle-aged and elderly patients with equal timing of MS onset, the neurological deficit is more expressed than in young ones. First-line pathogenetic therapy, in particular, glatiramer acetate, is more effective in young patients, while patients of middle age are recommended an early transition to second-line MSDMDs.

Proton pump inhibitor-induced hypomagnesemia, a rare cause of reversible delirium: A case report with literature review.

Hypomagnesemia is associated with multiple electrolyte disturbances such as hypokalemia, hypocalcemia and hypoparathyroidism. Proton pump inhibitors (PPIs) are widely used in gastrointestinal disorders and are generally considered safe by clinicians. However, it is unusual side effect of hypomagnesemia is potentially under-recognized. Delirium is usually thought to be a clue of cerebrovascular disease, and the association between delirium and hypomagnesemia is unexpected. We describe a patient used PPI with hypomagnesemia showed normal parathyroid hormone (PTH) despite hypocalcemia and reversible delirium. To enhance clinicians' vigilance, we performed a literature review on cerebellar syndromes due to hypomagnesemia. A 74-year-old woman was admitted to our hospital with intermittent nausea, vomiting, hand tremors, and delirium. Laboratory analysis showed hypokalemia, hypomagnesemia, and normal parathyroid hormone despite hypocalcemia, physical examination showed horizontal nystagmus and the brain MRI was negative. Surprising, detailed medical history revealed that the etiology was the usage of omeprazole. Omeprazole was discontinued and oral supplementation with magnesium, calcium, and potassium was administered. Delirium quickly disappeared and the serum potassium, magnesium, and calcium levels gradually normalized; at discharge, nystagmus gradually disappeared, and plasma electrolyte levels were stable at follow-up. Hypomagnesemia is associated with a variety of neurological symptoms up to life-threatening conditions if left untreated; as Mg is not present in routine electrolyte panels, hypoparathyroidism, hypokalemia, and delirium may be a clue, and physicians must be alert to consider PPI as a potential cause of unexplained hypomagnesemia, and timely treatment to avoid sequelae.

B-076 Detection of KLHL11 Autoantibodies Using a New Cell-based Indirect Immunofluorescence Assay

Abstract Background Autoantibodies against kelch-like protein 11 (KLHL11) were first described in 2019 as markers of paraneoplastic encephalitis. Early diagnosis and treatment are imperative to improve prognosis and outcome of affected patients. Rat brain immunohistochemistry was reported to be not useful in routine screening for KLHL11 antibodies. This study evaluates the performance of a new recombinant cell-based assay for the standardized detection of KLHL11-specific IgG and reports the characteristics of the examined patients. Methods Serum (n=9), CSF (n=5) and/or plasmapheresis (n=1) samples from 10 patients with clinical presentations compatible with anti-KLHL11 encephalitis as well as sera from 100 healthy blood donors were analyzed using a prototype indirect immunofluorescence assay (IFA; EUROIMMUN) based on recombinant HEK293 cells expressing human KLHL11. Results KLHL11 autoantibodies were detected at high titers in all samples (serum >1:1,000; CSF >1:320; plasma >1:100,000) from all (10/10) patients but in none (0/100) of the blood donors, indicating 100% sensitivity and specificity. Anti-KLHL11-positive patients had a median age of 52 years (range 27-71) and 80% were male. The most common reported clinical presentations were cerebellar syndrome (ataxia), brainstem diencephalic encephalitis, rhombencephalitis and limbic encephalitis. Testicular or ovarian tumors were found in 87.5% (7/8) of the cases with available results from malignancy screening. Conclusions The new cell-based IFA enables the sensitive and specific detection of KLHL11 autoantibodies, thus supporting the diagnosis of patients with predominantly paraneoplastic brainstem cerebellar syndrome. Future studies will evaluate assay performance in larger patient cohorts to address the reported association of KLHL11 autoimmunity with a wider spectrum of syndromes and tumors.

Acute Cerebellitis Following COVID-19: Alarming Clinical Presentation Challenged by Normal Paraclinical Findings.

We report the case of an acute cerebellitis following COVID-19 in 32-year-old man who presented with a life-threatening critical cerebellar syndrome contrasting with normal paraclinical findings. Despite this fulminant critical presentation, the patient fully recovered in 37days after early treatment with high-dose steroids and intravenous immunoglobulins. This case highlights the need for clinicians to be aware of acute cerebellitis following COVID-19, despite normal laboratory, imaging and electroencephalography findings and the importance to start appropriate treatment as soon as possible.

CACNA1G Causes Dominantly Inherited Myoclonus-Ataxia with Intellectual Disability: A Case Report.

Spinocerebellar ataxias (SCAs) are characterized by substantial phenotypic variability. Among them, SCA42 is a rare non-expansion entity presenting with slowly progressive cerebellar syndrome but whose clinical spectrum may be also wider. A 53-year-old male presented with progressive myoclonus-ataxia and intellectual disability. Genetic screening revealed a novel c.3835G > A (p. Asp1279Asn) variant in the CACNA1G gene. SCA42 is a rare non-expansion SCA caused by mutations in CACNA1G on chromosome 17q21, encoding the Ca(V)3.1, a low-threshold voltage-gated T-type calcium channel. The novel variant we identified is potentially involved in channel activity. This case expands the knowledge regarding CACNA1G-associated phenotype and highlights the importance of genetic screening in myoclonus-ataxia disorders.

Predicting cerebellar mutism syndrome in children using lesion map combined with clinical features.

This study aimed to develop a predictive model for cerebellar mutism syndrome (CMS) in pediatric patients with posterior fossa tumors, integrating lesion-symptom mapping (LSM) data with clinical factors, and to assess the model's performance. A cohort of pediatric patients diagnosed with posterior fossa tumors and undergoing surgery at Beijing Children's Hospital from July 2013 to December 2023 was analyzed. Clinical variables gender, age at surgery, tumor characteristics, hydrocephalus, surgical route and pathology were collected. LSM was used to link tumor locations with CMS outcomes. Lasso regression and logistic regression were employed for feature selection and model construction, respectively. Model performance was assessed using area under the curve (AUC) and accuracy metrics. The study included 197 patients in total, with CMS rates consistent across training, validation, and prospective groups. Significant associations were found between CMS and gender, tumor type, hydrocephalus, paraventricular edema, surgical route, and pathology. A predictive model combining voxel location data from LSM with clinical factors achieved high predictive performance (C-index: training 0.956, validation 0.933, prospective 0.892). Gender, pathology, and voxel location were identified as key predictors for CMS. The study established an effective predictive model for CMS in pediatric posterior fossa tumor patients, leveraging LSM data and clinical factors. The model's accuracy and robustness suggest its potential utility in clinical practice for early CMS risk assessment and intervention planning.

Cerebellar cognitive affective syndrome and vertebrobasilar ischemia. From cerebello-cerebral diaschisis to "dysmetria of thought"

Cerebellum, along with it' s role in coordinating motor functions, exercises a significant regulatory influence in fields of cognitive and affective functions. Therefore, studying the effect of cerebrovascular atherosclerotic pathology on mood and cognition should not be limited to stenotic dysfunctions of carotid arteries, but also extend its methodological framework to the consideration of the integrity of vertebrobasilar system (VBS), cerebellar perfusion and posterior cerebral circulation in general, as it has not been yet sufficiently addressed whether VBS insufficiency is associated with deterioration of patients' mental and emotional status and quality of life (QoL). Vertebrobasilar circulatory dysfunction has been pointed out, since decades, as a cause of progressive memory impairment and dementia, due to multiple infarcts in cerebral areas which are topographically critical for mental and emotional functions. Indicative of the pathophysiological and anatomic-functional association of VBS with these neuro-psychiatric domains are cerebellar cognitive-affective syndrome (CCAS) and crossed cerebello-cerebral diaschisis (CCCD). Mental and psychiatric components of CCAS, along with ataxic motor disability, constitute the conceptual hypothesis of "dysmetry of thought", while diagnostic significance of mental dysfunctions and psychopathological manifestations, in terms of symptoms preceding motor impairments that ascribe cerebellar malfunction in the epicenter of their pathophysiology, such as cerebellar ataxias, in which, early recognition of CCAS may facilitate therapeutic interventions aimed at improving QoL, reveal that cerebellar pathology, either of degenerative etiology or vascular substrate on the ground of vertebrobasilar insufficiency (VBI) or other surgical conditions of the posterior fossa, is associated with deterioration of patients' QoL which is related to significant impairments in their cognitive functions with (co)manifested emotional disorders. Studies in animal models also support these conclusions. Since VBI is responsible for a wide range of psychiatric and neurological symptoms, new findings concurred with current indications advocating that, without consideration of VBS disorders, it is impossible to clarify the connection of cerebral perfusion dysfunctions to neurocognitive deficits. The inclusion of cerebellar perfusion disorders in scientific research and clinical approaches to cognitive and affective disorders that may occur in patients with cerebrovascular lesions constitutes a paradigm of best clinical practices implementation and interdisciplinary convergence of neurosciences and vascular medicine.

Thorough perioperative and anesthetic considerations for cerebellar syndrome induced by posterior fossa tumors

Posterior fossa tumors are relatively rare pathologies, predominantly observed in pediatric populations. Nevertheless, there have been documented cases in adults, where these tumors are often associated with a higher prevalence of vascular lesions compared to those found in children. Given the inherent high mortality risk associated with this condition, meticulous anesthetic management is paramount. A comprehensive evaluation of patient-specific factors, including existing comorbidities, hemodynamic stability, and neurological status, is essential. Moreover, perioperative considerations such as patient positioning, the choice of anesthetic technique, and the duration of the surgical procedure must be carefully planned to optimize outcomes. This article presents a case review of a young adult patient with no significant medical history who was diagnosed with a posterior fossa tumor. The discussion encompasses the anatomical considerations of this pathology, critical preoperative assessments, anesthetic strategies tailored to this surgical context, and an analysis of the patient’s postoperative course.

Decoding Multiple Antibody Positivity: Lessons from Paraneoplastic Sensory Ataxia.

Paraneoplastic neurologic syndromes are cancer-associated, immune-mediated neurologic manifestations that may involve any part of the nervous system. They usually present with characteristic neurologic features and should be considered in high-risk phenotypes such as limbic encephalitis, encephalomyelitis, rapidly progressive cerebellar syndrome, opsoclonus-myoclonus, sensory neuronopathy, enteric neuropathy, and Lambert-Eaton myasthenic syndrome. The diagnosis is made by antibody positivity in the serum or cerebrospinal fluid, in the presence of an appropriate clinical phenotype. Findings on antibody testing by immunoblot should always be verified by immunofluorescence. We report a rare case of sensory neuronopathy with triple paraneoplastic antibody positivity (anti-Hu, anti-collapsing response-mediator protein 5, and anti-amphiphysin) on immunoblot but only anti-Hu positivity on immunofluorescence. The presence of lower facial dyskinesias should raise the possibility of an immune-mediated neurologic syndrome in the appropriate clinical context.

Association of Neurofibromatosis Type 1 and Multiple Sclerosis: A Case Report

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder, while multiple sclerosis (MS) is a prevalent chronic inflammatory demyelinating disease of the central nervous system. The coexistence of these two conditions is rare. Thus, patients with NF1 may exhibit signal abnormalities on brain imaging, referred to as focal areas of signal intensity (FASI), which can mimic lesions seen in MS and complicate the differential diagnosis. We present the case of a female patient suffering from progressive paraparesis, accompanied by urinary disorders and coordination disorders of the upper limbs. Neurological examination revealed a pyramidal syndrome and a cerebellar syndrome, with an Expanded Disability Status Scale (EDSS) score of 7.5. Additionally, the skin examination showed multiple café-au-lait spots larger than 15 mm and numerous diffuse neurofibromas. Brain magnetic resonance imaging showed white matter lesions typical of MS, and isoelectrofocalization of cerebrospinal fluid proteins revealed positive oligoclonal bands. The diagnosis was primary progressive multiple sclerosis associated with neurofibromatosis type 1. The aim of this case report is to document the association of these two conditions and discuss the challenges in differential diagnosis and treatment, as early diagnosis of MS is crucial to prevent further disability in patients with NF1.

Natural history of non-polyglutamine CACNA1A disease in Austria.

Non-polyglutamine CACNA1A variants underlie an extremely variable phenotypic spectrum encompassing developmental delay, hemiplegic migraine, epilepsy, psychiatric symptoms, episodic and chronic cerebellar signs. We provide our experience with the long-term follow-up of CACNA1A patients and their response to interval therapy. Patients with genetically confirmed non-polyglutamine CACNA1A disease were prospectively followed at the Center for Rare Movement Disorders of the Medical University of Innsbruck from 2004 to 2024. We recruited 41 subjects with non-polyglutamine CACNA1A disease, of which 38 (93%) familial cases. The mean age at the first examination was 35 ± 22years. Disease onset was in the childhood/adolescence in 31/41 patients (76%). Developmental delay and episodic symptoms were the first disease manifestation in 9/41 (22%) and 32/41 (78%) patients respectively. Chronic neurological signs encompassed a cerebellar syndrome in 35/41 (85%), which showed almost no progression during the observation period, as well as cognitive deficits in 9/20 (45%, MOCA test score < 26), psychiatric and behavioral symptoms in 11/41(27%). Seizures occurred in two patients concomitant to severe hemiplegic migraine. At the last visit, 27/41 patients (66%) required an interval prophylaxis (including acetazolamide, flunarizine, 4-aminopyridine, topiramate), which was efficacious in reducing the frequency and severity of episodic symptoms in all cases. In one patient in his 70ies with progressively therapy resistant hemiplegic migraine, treatment with the anti-CGRP antibody galcanezumab successfully reduced the frequency of migraine days from 4 to 1/month. Non-polyglutamine CACNA1A disease show an evolving age-dependent presentation. Interval prophylaxis is effective in reducing the burden of episodic symptoms.

A novel neurodevelopmental-neurodegenerative syndrome that cosegregates with a homozygous SPAG9/JIP4 stop-codon deletion

This report outlines the clinical features of a complex neurological phenotype shared by three siblings from a consanguineous family, characterized by intellectual disabilities, speech developmental delay, gait disturbance, cerebellar syndrome signs, cataracts, and dysmorphic features (square and coarse facial features, thick lips, deep palate, small and spaced teeth, low-set ears, strabismus, eyelid ptosis, and blond hair). Seizures and brain atrophy were later evident. In the cosegregation analysis, five family members and 12 family controls were studied by whole-exome and Sanger sequencing. The structural and functional effects of the protein were explored to define the mutated variant's potential deleterious impairment. Neurological and neuropsychological follow-ups and brain magnetic resonance imaging (MRI) were performed. We identified a single frameshift homozygous nucleotide deletion in the SPAG9/JIP4 gene (NM_001130528.3): c.2742del (p. Tyr914Ter), causing a premature stop codon and truncating the protein and originating a possible loss of function. The variant cosegregated in affected individuals as an autosomal recessive trait. The in silico protein functional analyses indicate a potential loss of 66 phosphorylation and 29 posttranslational modification sites. Additionally, a mutated protein structure model shows a significant modification of the folding that very likely will compromise functional interactions. SPAG9/JIP4 is a dynein-dynactin motor adapter for retrograde axonal transport, regulating the constitutive movement of neurotrophic factor signaling and autophagy-lysosomal products. Under stress conditions, it can potentiate this transport by the p38 mitogen-activated protein kinases (p38MAPK) signaling cascade. Both functions could be associated with the disease mechanism, altering the axon's development and growth, neuronal specification, dendrite formation, synaptogenesis, neuronal pruning, recycling neurotransmitters and finally, neuronal homeostasis—promising common mechanisms to be used with investigational molecules for neurodevelopmental diseases and neurodegeneration.