Paraneoplastic Syndrome Case Presented As Nystagmus and Ataxia.

The incidence of paraneoplastic syndrome (PNS) is on the rise, attributed to the growing detection of antibody modalities in both the serum and cerebrospinal fluid (CSF). PNS can occur as different neurological symptoms. The revised guidelines streamline the diagnostic approach but identifying PNS still requires the detection of neurological manifestations concurrent with cancer, along with the presence of specific PNS autoantibodies.

Superficial Siderosis After Traumatic Brain Injury: A Case Report.

Superficial siderosis (SS) is a rare condition in which chronic accumulation of the blood in the subarachnoid space over time leads to the buildup of hemosiderin deposits, which in turn cause neurological dysfunction in those affected. While reversibility of the damage done by this condition is nearly impossible, early detection can allow for immediate surgical intervention and thus prevent further progression of ataxia, hearing loss, and other neurological deficits caused by SS. We present a case of a 53-year-old male who was successfully diagnosed with SS secondary to a chronic post-traumatic pseudomeningocele and underwent surgical repair with the resolution of his symptoms. We aim to encourage more extensive workups for common neurological dysfunctions such as tinnitus or vertigo in patients who have a history of traumatic brain injury or any significant motor vehicle accidents.

Effect of Regional Brain Activity Following Repeat Transcranial Magnetic Stimulation in SCA3: A Secondary Analysis of a Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

Effect of a Home-Base Core Stability Exercises in Hereditary Ataxia. A Randomized Controlled Trial. A Pilot Randomized Controlled Trial.

BACKGROUND: Core stability exercises (CSE) have been shown to be effective in improving trunk function in several neurological diseases, but the evidence is scarce on Hereditary Ataxias (HA). OBJECTIVE: To evaluate the effectiveness of a 5-week home-based CSE program in terms of ataxia severity, trunk function, balance confidence, gait speed, lower limb motor function, quality of life, health status and falls rate in HA individuals at short- and long-term. METHODS: This is an assessor-blind randomized controlled clinical trial parallel group 1:1. The individuals were divided in experimental group (EG) performed standard care in addition to CSE, and control group (CG) performed standard care alone. The CSE home-program was conducted 1-h/day, 5-day/week for 5-week. The assessment was performed at baseline, endpoint (5-week), and follow-up (10-week). The primary outcomes were ataxia severity assessed by the Scale for the Assessment and Rating of Ataxia and trunk function assessed by Spanish-version of Trunk Impairment Scale 2.0. The secondary outcomes were balance confidence assessed by Activities-specific Balance Confidence (ABC), gait speed by 4-meter walk test (4-MWT), the lower limb motor function by 30-s sit-to-stand, quality of life by EuroQol 5-dimension 5-level (EQ-5D-5L), health-status by EQ-5D and falls rate. RESULTS: Twenty-three HA individuals were recruited (51.8 ± 11.10 years). Statistically significant group-time interaction was shown in ABC (F:5.539; P = 0.007), EQ-5D-5L Total (F:4.836; P = 0.013), EQ 5D (F:7.207; P = 0.006). CONCLUSIONS: No statistical differences between groups for ataxia severity and trunk function were observed. However, were differences for balance confidence, gait speed, quality of life, and falls rate in HA individuals.

Case report: A novel mutation of glial fibrillary acidic protein gene causing juvenile-onset Alexander disease.

Alexander disease (AxD) is a rare inherited autosomal dominant (AD) disease with different clinical phenotypes according to the age of onset. It is caused by mutations in the glial fibrillary acid protein (GFAP) gene, which causes GFAP accumulation in astrocytes. A wide spectrum of mutations has been described. For some variants, genotype-phenotype correlations have been described, although variable expressivity has also been reported in late-onset cases among members of the same family. We present the case of a 19-year-old girl who developed gait ataxia and subtle involuntary movements, preceded by a history of enuresis and severe scoliosis. Her mother has been affected by ataxia since her childhood, which was then complicated by pyramidal signs and heavily worsened through the years. Beyond her mother, no other known relatives suffered from neurologic syndromes. The scenario was further complicated by a complex brain and spinal cord magnetic resonance imaging (MRI) pattern in both mother and daughter. However, the similar clinical phenotype made an inherited cause highly probable. Both AD and autosomal recessive (AR) ataxic syndromes were considered, lacking a part of the proband's pedigree, but no causative genetic alterations were found. Considering the strong suspicion for an inherited condition, we performed clinical exome sequencing (CES), which analyzes more than 4,500 genes associated with diseases. CES evidenced the new heterozygous missense variant c.260 T > A in exon 1 of the glial fibrillary acidic protein (GFAP) gene (NM_002055.4), which causes the valine to aspartate amino acid substitution at codon 87 (p. Val87Asp) in the GFAP. The same heterozygous variant was detected in her mother. This mutation has never been described before in the literature. This case should raise awareness for this rare and under-recognized disease in juvenile-adult cases.

Memantine suppresses the excitotoxicity but fails to rescue the ataxic phenotype in SCA1 model mice.

Spinocerebellar ataxia type 1 (SCA1) is a debilitating neurodegenerative disorder of the cerebellum and brainstem. Memantine has been proposed as a potential treatment for SCA1. It blocks N-methyl-D-aspartate (NMDA) receptors on neurons, reduces excitotoxicity and decreases neurodegeneration in Alzheimer models. However, in cerebellar neurodegenerative diseases, the potential value of memantine is still unclear. We investigated the effects of memantine on motor performance and synaptic transmission in the cerebellum in a mouse model where mutant ataxin 1 is specifically targeted to glia. Lentiviral vectors (LVV) were used to express mutant ataxin 1 selectively in Bergmann glia (BG). In mice transduced with the mutant ataxin 1, chronic treatment with memantine improved motor activity during initial tests, presumably due to preserved BG and Purkinje cell (PC) morphology and numbers. However, mice were unable to improve their rota rod scores during next days of training. Memantine also compromised improvement in the rota rod scores in control mice upon repetitive training. These effects may be due to the effects of memantine on plasticity (LTD suppression) and NMDA receptor modulation. Some effects of chronically administered memantine persisted even after its wash-out from brain slices. Chronic memantine reduced morphological signs of neurodegeneration in the cerebellum of SCA1 model mice. This resulted in an apparent initial reduction of ataxic phenotype, but memantine also affected cerebellar plasticity and ultimately compromised motor learning. We speculate that that clinical application of memantine in SCA1 might be hampered by its ability to suppress NMDA-dependent plasticity in cerebellar cortex.

Molecular Imaging in CANVAS: A Contribution for Differential Diagnosis?

BACKGROUND: Phenotypes of CANVAS are increasingly diversified, including bradykinesia and dysautonomia, so that its primary differential diagnoses are multiple system atrophy-cerebellar type (MSA-c), and spinocerebellar ataxia type 3 (SCA3). This case series aims to highlight key molecular imaging findings in CANVAS. CASES: We report a case series of six patients with CANVAS who underwent nuclear medicine examinations in our center and 13 patients from the literature. These include 18F-FDG brain positron emission tomography (PET), single photon emission computed tomography (SPECT) of dopamine transporter (DaT) activity, and 123I-MIBG cardiac scintigraphy of noradrenergic transmission. CONCLUSIONS: In CANVAS, 18F-FDG brain PET mainly shows cerebellar hypometabolism, with preserved brainstem and striatum metabolism, contrasting with SCA3 and MSA-c. Dopaminergic denervation on scintigraphy seems to be associated with clinical parkinsonism, ranging from normal to severely impaired DaT SPECT. Additionally, 123I-MIBG cardiac scintigraphy might show denervation in CANVAS, similar to SCA3, but not in most MSA-c patients.

De novo FRMD5 Missense Variants in Patients with Childhood-Onset Ataxia, Prominent Nystagmus, and Seizures.

BACKGROUND: FRMD5 variants were recently identified in patients with developmental delay, ataxia, and eye movement abnormalities. OBJECTIVES: We describe 2 patients presenting with childhood-onset ataxia, nystagmus, and seizures carrying pathogenic de novo FRMD5 variants. Weighted gene co-expression network analysis (WGCNA) was performed to gain insights into the function of FRMD5 in the brain. METHODS: Trio-based whole-exome sequencing was performed in both patients, and CoExp web tool was used to conduct WGCNA. RESULTS: Both patients presented with developmental delay, childhood-onset ataxia, nystagmus, and seizures. Previously unreported findings were diffuse choreoathetosis and dystonia of the hands (patient 1) and areas of abnormal magnetic resonance imaging signal in the white matter (patient 2). WGCNA showed that FRMD5 belongs to gene networks involved in neurodevelopment and oligodendrocyte function. CONCLUSIONS: We expanded the phenotype of FRMD5-related disease and shed light on its role in brain function and development. We recommend including FRMD5 in the genetic workup of childhood-onset ataxia and nystagmus. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PGT-M for spinocerebellar ataxia type 1: development of a STR panel and a report of two clinical cases.

PURPOSE: To present the developed preimplantation genetic testing (PGT) for spinocerebellar ataxia type 1 (SCA1) and the outcomes of IVF with PGT. METHODS: PGT was performed for two unrelated couples from the Republic of Sakha (Yakutia) with the risk of SCA1 in one spouse. We have developed a system for PGT of a monogenic disease (PGT-M) for SCA1, which includes the analysis of a panel of 11 polymorphic STR markers linked to the ATXN1 gene and a pathogenic variant of the ATXN1 gene using nested PCR and fragment analysis. IVF/ICSI programs were performed according to standard protocols. Multiple displacement amplification (MDA) was used for whole genome amplification (WGA) and array comparative genomic hybridization (aCGH) for aneuploidy testing (PGT-A). RESULTS: Eight STRs were informative for the first couple and ten for the second. Similarity of the haplotypes carrying pathogenic variants of the ATXN1 gene was noted. In the first case, during IVF/ICSI-PGT, three embryos reached the blastocyst stage and were biopsied. One embryo was diagnosed as normal by maternal STR haplotype and the ATXN1 allele. PGT-A revealed euploidy. The embryo transfer resulted in a singleton pregnancy, and a healthy boy was born. Postnatal diagnosis confirmed normal ATXN1. In the second case, two blastocysts were biopsied. Both were diagnosed as normal by PGT-M, but PGT-A revealed aneuploidy. CONCLUSION: Birth of a healthy child after PGT for SCA1 was the first case of successful preimplantation prevention of SCA1 for the Yakut couple and the first case of successful PGT for SCA1 in Russia.

Assessing Long-Term Neurologic Outcomes in SAMD9L-Related Ataxia-Pancytopenia Syndrome.

BACKGROUND: Most published reports on SAMD9L-related ataxia-pancytopenia syndrome (ATXPC) have emphasized the hematologic findings. Fewer details are known about the progression of neurologic manifestations and methods for monitoring them. CASES: We present six individuals from two families transmitting a heterozygous variant in SAMD9L, exhibiting clinical variations in their hematologic and neurologic findings. Serial motor function testing was used to monitor motor proficiency over a 2 to 3 year period in the proband and his father from Family 1. CONCLUSIONS: Our case series focuses on the neurologic progression in patients with heterozygous variants in SAMD9L. Patients with ATXPC should be followed to evaluate a wide range of neurologic manifestations. Serial motor function testing using a standardized method is helpful to track changes in balance and coordination in children and adults with ATXPC and could aid in a future extended natural history study.

Closure of the neuro-central synchondrosis and other physes in foal cervical spines.

BACKGROUND: The neuro-central synchondrosis (NCS) is a physis responsible for the growth of the dorsal third of the vertebral body and neural arches. When the NCS of pigs is tethered to model scoliosis, stenosis also ensues. It is necessary to describe the NCS for future evaluation of its potential role in equine spinal cord compression and ataxia (wobbler syndrome). OBJECTIVES: To describe the NCS, including when it and other physes closed in computed tomographic (CT) scans of the cervical spine of foals, due to its potential role in vertebral stenosis. STUDY DESIGN: Post-mortem cohort study. METHODS: The cervical spine of 35 cases, comprising both sexes and miscellaneous breeds from 153 gestational days to 438 days old, was examined with CT and physes scored from 6: fully open to 0: fully closed. The dorsal physis, physis of the dens and mid-NCS were scored separately, whereas the cranial and caudal NCS portions were scored together with the respective cranial and caudal vertebral body physes. RESULTS: The NCS was a pair of thin physes located in a predominantly dorsal plane between the vertebral body and neural arches. The mid-NCS was closed in C1 from 115 days of age, and in C2-C7 from 38 days of age. The dorsal physis closed later than the NCS in C1, and earlier than the NCS in C2-C7. The dens physis was closed from 227 days of age. The cranial and caudal physes were closing, but not closed from different ages in the different vertebrae of the oldest cases. MAIN LIMITATIONS: Hospital population. CONCLUSIONS: The NCS was a thin physis that contributed mainly to height-wise growth, but also width- and length-wise growth of the vertebral body and neural arches. The mid-NCS was closed in all cervical vertebrae from 115 days of age. The NCS warrants further investigation in the pathogenesis of vertebral stenosis.

HISTORIAL: La sincondrosis neuro­central (NCS) es la fisis responsable del crecimiento del tercio dorsal del cuerpo vertebral y de los arcos neurales. Cuando la NCS en cerdos se asocia a un modelo de escoliosis, también se produce estenosis. Es necesario describir la NCS para la futura evaluación de su rol potencial en la comprensión de la medula espinal equina y ataxia (síndrome de Wobbler). OBJETIVOS: Describir la NCS incluyendo cuando ella y otras fisis se cierran, por tomografía computarizada (CT) de la columna cervical de potrillos, debido a su rol potencial en la estenosis vertebral. DISEÑO DEL ESTUDIO: Estudio de cohorte post­mortem. MÉTODOS: La columna cervical de 35 casos, incluyendo ambos sexos y diferentes razas, desde 153 días gestacionales hasta 438 días de edad, fueron examinadas por CT y las fisis fueron dadas un puntaje de, 6: completamente abiertas a, 0: completamente cerradas. La fisis dorsal, la fisis del hueso odontoides y NCS media fueron evaluadas en forma separada, mientras las porciones de NCS craneal y caudal fueron evaluadas juntas con las respectiva fisis del cuerpo vertebral craneal y caudal. RESULTADOS: La NCS es un par de fisis delgadas localizadas predominantemente en el plano dorsal entre el cuerpo vertebral y los arcos vertebrales. La NCS media estaba cerrada en C1 desde los días 115 de edad, y en C2­C7 a partir de los 38 días de edad. La fisis dorsal se cerró más tarde que la NCS en C1, y antes que la NCS en C2­C7. La fisis del hueso odontoides estaba cerradas a partir de los 227 días de edad. Las fisis craneal y caudal estaban cerrándose, pero no estaban cerradas a distintas edades en las diferentes vertebras en los casos mayores de edad. LIMITACIONES PRINCIPALES: Población de hospital CONCLUSIONES: La NCS es una fisis delgada que contribuye principalmente al crecimiento en altura, pero también en ancho y largo del cuerpo vertebral y arcos vertebrales. La NCS media estaba cerrada en todas las vértebras cervicales a partir de los 115 días de edad. La NCS merece ser investigada más en la patogénesis de la estenosis vertebral. Palabras Clave: ataxia, tomografía computarizada, caballo, osteocondrosis, estenosis, crecimiento vertebral.

Quadriplegia, Dysphagia and Ataxia Manifested in a Child With COVID-19 Related Acute Necrotizing Encephalopathy: A Case Report.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, presents primarily with respiratory symptoms. However, children with COVID-19 are usually asymptomatic or mild acute symptoms and also neurological manifestations have also been observed. We report the case of a 7-year-old girl who presented with high fever and altered mental status, leading to a diagnosis of COVID-19 and acute necrotizing encephalopathy (ANE). The patient received intensive medical care in the intensive care unit and subsequently underwent rehabilitation programs due to neurological functional sequelae. Neurological complications in COVID-19, including ANE, may result from potential viral nerve involvement, cytokine storms, and the blood-brain barrier disruption. Early rehabilitation plays a pivotal role in managing COVID-19-related neurological complications and enhancing patients' functional outcomes. Further research is essential to gain a better understanding of the mechanisms and treatment strategies for neurological manifestations in pediatric COVID-19 patients, particularly those with multisystem inflammatory syndrome in child.

Genetic aspects of ataxias in a cohort of Turkish patients.

INTRODUCTION: Ataxia is one of the clinical findings of the movement disorder disease group. Although there are many underlying etiological reasons, genetic etiology has an increasing significance thanks to the recently developing technology. The aim of this study is to present the variants detected in WES analysis excluding non-genetic causes, in patients with ataxia. METHODS: Thirty-six patients who were referred to us with findings of ataxia and diagnosed through WES or other molecular genetic analysis methods were included in our study. At the same time, information such as the onset time of the complaints, consanguinity status between parents, and the presence of relatives with similar symptoms were evaluated. If available, the patient's biochemical and radiological test results were presented. RESULTS: Thirty-six patients were diagnosed through WES or CES. The rate of detected autosomal recessive inheritance disease was 80.5%, while that of autosomal dominant inheritance disease was 19.5%. Abnormal cerebellum was detected on brain MRI images in 26 patients, while polyneuropathy was detected on EMG in eleven of them. While the majority of the patients were compatible with similar cases reported in the literature, five patients had different/additional features (variants in MCM3AP, AGTPBP1, GDAP2, and SH3TC2 genes). CONCLUSIONS: The diagnosis of ataxia patients with unknown etiology is made possible thanks to these clues. Consideration of a genetic approach is recommended in patients with ataxia of unknown etiology.

Ultra-high-field 7-Tesla magnetic resonance imaging in fragile X tremor/ataxia syndrome (FXTAS).

Fragile X tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder characterized by premutation expansion of fragile X mental retardation 1 (FMR1) gene. It is a common single-gene cause of tremor, ataxia, and cognitive decline in adults. FXTAS affects the central, peripheral and autonomic nervous systems, leading to a range of neurological symptoms from dementia to dysautonomia. A characteristic imaging feature of FXTAS is symmetric T2 hyperintensity in the deep white matter of the cerebellar hemispheres and middle cerebral peduncle. However, recent studies have reported additional findings on diffusion weighted images (DWI), such as a symmetric high-intensity band-like signal at the cerebral corticomedullary junction. These findings, along with the characteristic cerebellar signal alterations, overlap with imaging findings seen in adult-onset neuronal intranuclear inclusion disease (NIID). Importantly, recent pathology studies have shown that both FXTAS and NIID can manifest intranuclear inclusion bodies, posing a diagnostic challenge and potential for misdiagnosis. We describe a 58-year-old man with FXTAS who received an erroneous diagnosis based on imaging and histopathology results. We emphasize the potential pitfalls in distinguishing NIID from FXTAS and stress the importance of genetic analysis in all cases with suspected NIID and FXTAS for confirmation. Additionally, we present the 7T MRI brain findings of FXTAS.

[Gastrointestinal disorders in hyperkinetic movement disorders and ataxia]. / Gastrointestinale Störungen bei hyperkinetischen Bewegungsstörungen und Ataxien.

Disorders of the gastrointestinal tract in patients suffering from hypokinetic movement disorders, and in particular Parkinson's disease, have increasingly been the subject of more intensive neuromedical research. So far, few data are available for patients with hyperkinetic movement disorders and ataxias. This review article summarizes the currently available and relevant publications on this topic. The particular focus is on essential tremor, restless legs syndrome, Huntington's disease and the group of hereditary ataxias. Further intensive research will be necessary in the future to collect detailed information also for these disease symptoms about specific disturbance patterns, in order to understand the underlying pathological pathways and to derive specific treatment approaches.

Two more families supporting the existence of monogenic spinocerebellar ataxia 48.

The reduced penetrance of TBP intermediate alleles and the recently proposed possible digenic TBP/STUB1 inheritance raised questions on the possible mechanism involved opening a debate on the existence of SCA48 as a monogenic disorder. We here report clinical and genetic results of two apparently unrelated patients carrying the same STUB1 variant(c.244G > T;p.Asp82Tyr) with normal TBP alleles and a clinical picture fully resembling SCA48, including cerebellar ataxia, dysarthria and mild cognitive impairment. This report provides supportive evidence that this specific ataxia can also occur as a monogenic disease, considering classical TBP allelic ranges.

The Neem Limonoid Nimbolide Modulates Key Components of the DNA Damage Response Signalling in Cellular and Animal Models of Oral Squamous Cell Carcinoma

BACKGROUND: Deregulated DNA damage response (DDR) network is implicated in cancer progression and therapy resistance. OBJECTIVE: The present study was designed to investigate whether nimbolide, an anticancer neem limonoid, targets key components of the DDR signalling pathway in cellular and animal models of oral squamous cell carcinoma (OSCC). METHODS: OSCC cells (SCC-4 and SCC-9), 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinoma model, chemoresistant OSCC patient-derived xenograft (PDX) model established in athymic nude mice, and tissue sections from patients with oral premalignant/malignant disease were used for the study. Key molecules that orchestrate the DDR, including the MRN complex, ATM, DNA-PKcs, H2AX, and p53, were analysed by qRT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry. Cell proliferation and apoptosis indices were evaluated. RESULTS: Nimbolide significantly reduced 8-oxodG levels, expression of MRN, ATMS1891, and γ-H2AX, with an increase in p-p53S15 in OSCC cells as well as in the HBP model. Nimbolide potentiated the effect of KU-55933 in ATM inhibition. In the PDX model, nimbolide suppressed tumor formation, stimulated DDR and apoptosis, inhibited cell proliferation, and enhanced sensitivity to cisplatin. Analysis of p-ATM expression revealed a significant increase during the sequential progression of hamster and human OSCC. CONCLUSIONS: This study provides compelling evidence that nimbolide functions as a DDR inhibitor in cellular and hamster OSCC models and as a DDR activator in the PDX model primarily by targeting ATM. Small molecules like nimbolide that modulate DDR are of immense benefit in cancer therapy. The study has also unveiled p-ATM as a promising biomarker of tumour progression in human OSCCs.

Purkinje cell dysfunction causes disrupted sleep in ataxic mice.

Purkinje cell dysfunction disrupts movement and causes disorders such as ataxia. Recent evidence suggests that Purkinje cell dysfunction may also alter sleep regulation. Here, we used an ataxic mouse model generated by silencing Purkinje cell neurotransmission (L7Cre;Vgatfx/fx) to better understand how cerebellar dysfunction impacts sleep physiology. We focused our analysis on sleep architecture and electrocorticography (ECoG) patterns based on their relevance to extracting physiological measurements during sleep. We found that circadian activity is unaltered in the mutant mice, although their sleep parameters and ECoG patterns are modified. The L7Cre;Vgatfx/fx mutant mice have decreased wakefulness and rapid eye movement (REM) sleep, while non-rapid eye movement (NREM) sleep is increased. The mutants have an extended latency to REM sleep, which is also observed in human ataxia patients. Spectral analysis of ECoG signals revealed alterations in the power distribution across different frequency bands defining sleep. Therefore, Purkinje cell dysfunction may influence wakefulness and equilibrium of distinct sleep stages in ataxia. Our findings posit a connection between cerebellar dysfunction and disrupted sleep and underscore the importance of examining cerebellar circuit function in sleep disorders.