Cerebellar Deficits Research Articles

MNGA-08 SKULL BASE TUMOR RESECTION IN LOW-RESOURCE SETTINGS: A REVIEW OF THREE CASES AT THE KENYATTA NATIONAL HOSPITAL

Abstract Skull-based tumors are challenging to treat surgically due to their proximity to vital structures and the risk of complications. In low-resource settings, the availability of advanced neurosurgical equipment and expertise is limited, which may affect the outcomes of these patients. We report the outcomes of three patients with skull base tumors who underwent surgery at the Kenyatta National Hospital, Kenya. We retrospectively reviewed the medical records and followed up with three patients who underwent surgery for skull base tumors between October and November 2023. We collected data on their demographic characteristics, clinical presentation, imaging findings, surgical procedures, histopathological diagnosis, and postoperative course. The three patients were male, aged 42, 40, and 36 years. The common presentation was with headache, but dizziness and other cerebellar deficits were common. Imaging revealed defined lesions in the posterior fossa, involving the cerebellum and brainstem. The differential diagnosis included hemangioblastoma and meningioma. The surgical approach with anatomically-specified craniotomy with resection of the tumor and decompression. The postoperative course was uneventful for the first and third patients, who showed improvement in their neurological symptoms and signs. The second patient had repeat surgery. Skull base tumor surgery in a low-resource setting can achieve favorable outcomes with careful patient selection, meticulous surgical technique, and multidisciplinary care. However, the challenges of limited resources and high complication rates remain. Further studies are needed to evaluate the long-term outcomes and quality of life of these patients.

Spliceosomal GTPase Eftud2 deficiency-triggered ferroptosis leads to Purkinje cell degeneration

Spliceosomal GTPase elongation factor Tu GTP binding domain containing 2 (EFTUD2) is a causative gene for mandibulofacial dysostosis with microcephaly (MFDM) syndrome comprising cerebellar hypoplasia and motor dysfunction. How EFTUD2 deficiency contributes to these symptoms remains elusive. Here, we demonstrate that specific ablation of Eftud2 in cerebellar Purkinje cells (PCs) in mice results in severe ferroptosis, PC degeneration, dyskinesia, and cerebellar atrophy, which recapitulates phenotypes observed in patients with MFDM. Mechanistically, Eftud2 promotes Scd1 and Gch1 expression, upregulates monounsaturated fatty acid phospholipids, and enhances antioxidant activity, thereby suppressing PC ferroptosis. Importantly, we identified transcription factor Atf4 as a downstream target to regulate anti-ferroptosis effects in PCs in a p53-independent manner. Inhibiting ferroptosis efficiently rescued cerebellar deficits in Eftud2 cKO mice. Our data reveal an important role of Eftud2 in maintaining PC survival, showing that pharmacologically or genetically inhibiting ferroptosis may be a promising therapeutic strategy for EFTUD2 deficiency-induced disorders.

Environmental enrichment reduces restricted repetitive behavior by altering gray matter microstructure.

Restricted, repetitive behaviors are common symptoms in neurodevelopmental disorders including autism spectrum disorder. Despite being associated with poor developmental outcomes, repetitive behaviors remain poorly understood and have limited treatment options. Environmental enrichment attenuates the development of repetitive behaviors, but the exact mechanisms remain obscure. Using the C58 mouse model of repetitive behavior, we performed diffusion tensor imaging to examine microstructural alterations associated with the development of repetitive behavior and its attenuation by environmental enrichment. The C57BL/6 mouse strain, which displays little or no repetitive behavior, was used as a control group. We observed widespread differences in diffusion metrics between C58 mice and C57BL/6 mice. In juvenile C58 mice, repetitive motor behavior displayed strong negative correlations with fractional anisotropy in multiple gray matter regions, whereas in young adult C58 mice, high repetitive motor behavior was most strongly associated with lower fractional anisotropy and higher radial diffusivity in the striatum. Environmental enrichment increased fractional anisotropy and axial diffusivity throughout gray matter regions in the brains of juvenile C58 mice and overlapped predominantly with cerebellar and sensory regions associated with repetitive behavior. Our results suggest environmental enrichment reduces repetitive behavior development by altering gray matter microstructure in the cerebellum, medial entorhinal cortex, and sensory processing regions in juvenile C58 mice. Under standard laboratory conditions, early pathology in these regions appears to contribute to later striatal and white matter dysfunction in adult C58 mice. Future studies should examine the role these regions play in the development of repetitive behavior and the relationship between sensory processing and cerebellar deficits and repetitive behavior.

The Role of Physical Medicine and Rehabilitation in the Management of Multiple Sclerosis: A Review of the Literature

The progression of multiple sclerosis, whether treated or not, can sooner or later lead to the onset of disability that is not limited to locomotor disorders alone, despite therapeutic advances. Generated by years of relapses, followed by the insidious but continuous onset of motor, sensory, cerebellar, sensory or cognitive deficits, the consequences are physical, psychological and even socio-economic, and include functional rehabilitation, the efficacy of which now seems to be well established. Various types of treatment are available, involving a wide range of healthcare professionals (physiotherapists, occupational therapists, nurses, psychomotor therapists, orthoprosthetists, speech therapists, etc.), coordinated by a doctor specializing in physical medicine and rehabilitation. Programs are usually multidisciplinary, including rehabilitation techniques, functional exercises and even exercise training

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.

Potential Prodromal Digital Postural Sway Markers for Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Detected via Dual-Tasking and Sensory Manipulation.

FXTAS is a neurodegenerative disorder occurring in some Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene premutation carriers (PMCs) and is characterized by cerebellar ataxia, tremor, and cognitive deficits that negatively impact balance and gait and increase fall risk. Dual-tasking (DT) cognitive-motor paradigms and challenging balance conditions may have the capacity to reveal markers of FXTAS onset. Our objectives were to determine the impact of dual-tasking and sensory and stance manipulation on balance in FXTAS and potentially detect subtle postural sway deficits in FMR1 PMCs who are asymptomatic for signs of FXTAS on clinical exam. Participants with FXTAS, PMCs without FXTAS, and controls underwent balance testing using an inertial sensor system. Stance, vision, surface stability, and cognitive demand were manipulated in 30 s trials. FXTAS participants had significantly greater total sway area, jerk, and RMS sway than controls under almost all balance conditions but were most impaired in those requiring vestibular control. PMCs without FXTAS had significantly greater RMS sway compared with controls in the feet apart, firm, single task conditions both with eyes open and closed (EC) and the feet together, firm, EC, DT condition. Postural sway deficits in the RMS postural sway variability domain in asymptomatic PMCs might represent prodromal signs of FXTAS. This information may be useful in providing sensitive biomarkers of FXTAS onset and as quantitative balance measures in future interventional trials and longitudinal natural history studies.

Bilateral vestibulopathy as the initial presentation of CANVAS

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a slowly progressing autosomal recessive ataxic disorder linked to an abnormal biallelic intronic (most commonly) AAGGG repeat expansion in the replication factor complex subunit 1 (RFC1). While the clinical diagnosis is relatively straightforward when the three components of the disorder are present, it becomes challenging when only one of the triad (cerebellar ataxia, neuropathy or vestibular areflexia) manifests. Isolated cases of Bilateral Vestibulopathy (BVP) or vestibular areflexia that later developed the other components of CANVAS have not been documented. We report four cases of patients with chronic imbalance and BVP that, after several years, developed cerebellar and neuropathic deficits with positive genetic testing for RFC1. Our report supports the concept that CANVAS should be considered in every patient with BVP of unknown etiology, even without the presence of the other triad components. This is especially important given that about 50% of cases in many BVP series are diagnosed as idiopathic, some of which may be undiagnosed CANVAS.

Evaluation of risk factors for postoperative neurologic intensive care admission after brain tumor craniotomy: A single-center longitudinal study.

Perioperative variable parameters can be significant risk factors for postoperative intensive care unit (ICU) admission after elective craniotomy for intracranial neoplasm, as assessed by various scoring systems such as Cranio Score. This observational study evaluates the relationship between these factors and early postoperative neurological complications necessitating ICU admission. In total, 119 patients, aged 18 years and above, of either sex, American Society of Anesthesiologists (ASA) grades I-III, scheduled for elective craniotomy and tumor excision were included. The primary objective was to evaluate the relationship between perioperative risk factors and the incidence of early postoperative complications as a means of validation of the Cranio Score. The secondary outcomes studied were 30-day postoperative morbidity/mortality and the association with patient-related risk factors. Forty-five of 119 patients (37.82%) required postoperative ICU care with the mean duration of ICU stay being 1.92 ± 4.91 days. Tumor location (frontal/infratemporal region), preoperative deglutition disorder, Glasgow Coma Scale (GCS) less than 15, motor deficit, cerebellar deficit, midline shift >3 mm, mass effect, tumor size, use of blood products, lateral position, inotropic support, elevated systolic/mean arterial pressures, and duration of anesthesia/surgery were associated with a higher incidence of ICU care. Maximum (P = 0.035, AOR = 1.130) and minimum systolic arterial pressures (P = 0.022, Adjusted Odds Ratio (AOR) = 0.861) were the only independent risk factors. Cranio Score was found to be an accurate predictor of complications at a cut-off point of >10.52%. The preoperative motor deficit was the only independent risk factor associated with 30-day morbidity (AOR = 4.66). Perioperative hemodynamic effects are an independent predictor of postoperative ICU requirement. Further Cranio Score is shown to be a good scoring system for postoperative complications.

Disentangling Cerebellar and Parietal Contributions to Gait and Body Schema: A Repetitive Transcranial Magnetic Stimulation Study

The overlap between motor and cognitive signs resulting from posterior parietal cortex (PPC) and cerebellar lesions can mask their relative contribution in the sensorimotor integration process. This study aimed to identify distinguishing motor and cognitive features to disentangle PPC and cerebellar involvement in two sensorimotor-related functions: gait and body schema representation. Thirty healthy volunteers were enrolled and randomly assigned to PPC or cerebellar stimulation. Sham stimulation and 1 Hz-repetitive-Transcranial-Magnetic-Stimulation were delivered over P3 or cerebellum before a balance and a walking distance estimation task. Each trial was repeated with eyes open (EO) and closed (EC). Eight inertial measurement units recorded spatiotemporal and kinematic variables of gait. Instability increased in both groups after real stimulation: PPC inhibition resulted in increased instability in EC conditions, as evidenced by increased ellipse area and range of movement in medio-lateral and anterior–posterior (ROMap) directions. Cerebellar inhibition affected both EC (increased ROMap) and EO stability (greater displacement of the center of mass). Inhibitory stimulation (EC vs. EO) affected also gait spatiotemporal variability, with a high variability of ankle and knee angles plus different patterns in the two groups (cerebellar vs parietal). Lastly, PPC group overestimates distances after real stimulation (EC condition) compared to the cerebellar group. Stability, gait variability, and distance estimation parameters may be useful clinical parameters to disentangle cerebellar and PPC sensorimotor integration deficits. Clinical differential diagnosis efficiency can benefit from this methodological approach.

Cerebellar white and gray matter abnormalities in temporal lobe epilepsy: a voxel-based morphometry study.

Previous structural neuroimaging studies linked cerebellar deficits to temporal lobe epilepsy (TLE). The functions of various cerebellar regions are increasingly being valued, and their changes in TLE patients warrant further in-depth investigation. In this study, we used the Spatially Unbiased Infratentorial (SUIT) toolbox with a new template to evaluate the cerebellar structural abnormalities in patients with TLE, and further explored the relationship between the changes of different cerebellar regions and cognition. Thirty-two patients with TLE were compared with 39 healthy controls (HC) matched according to age, gender, handedness, and education level. All participants underwent a high-resolution T1-weighted MRI scan on a 3.0 Tesla scanner. We used a voxel-based morphometry (VBM) approach utilizing the SUIT toolbox to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with TLE. Compared with HC, TLE patients showed a significant reduction in the volume of gray matter in the Left lobule VI and white matter in the Right Crus II. In the TLE patient group, we conducted partial correlation analysis between the volumes of different cerebellar regions and cognitive rating scale scores, such as MMSE and MoCA. The volume of the Left lobule VI (GM) exhibited a positive correlation with the MMSE score, but no significant correlation was found with the MoCA score. On the other hand, there was no significant correlation observed between the volume of the Right Crus II (WM) and the two cognitive scale scores mentioned above. Furthermore, it was observed that the MMSE was more effective than the MoCA in identifying epilepsy patients with cognitive impairment. This study supported previous research indicating that temporal lobe epilepsy (TLE) is linked to structural changes in the cerebellum, specifically affecting the volume of both gray and white matter. These findings offer valuable insights into the neurobiology of TLE and hold potential to inform the development of enhanced diagnostic methods and more effective treatment approaches.

Sudden unilateral hearing loss and recurrent positional vertigo following delayed cerebellar perfusion deficit and infarction

Sudden unilateral hearing loss and recurrent positional vertigo following delayed cerebellar perfusion deficit and infarction

Cerebellar, Not Nigrostriatal Degeneration Impairs Dexterity in Multiple System Atrophy.

Multiple system atrophy (MSA) clinically manifests with either predominant nigrostriatal or cerebellopontine degeneration. This corresponds to two different phenotypes, one with predominant Parkinson's symptoms (MSA-P [multiple system atrophy-parkinsonian subtype]) and one with predominant cerebellar deficits (MSA-C [multiple system atrophy-cerebellar subtype]). Both nigrostriatal and cerebellar degeneration can lead to impaired dexterity, which is a frequent cause of disability in MSA. The aim was to disentangle the contribution of nigrostriatal and cerebellar degeneration to impaired dexterity in both subtypes of MSA. We thus investigated nigrostriatal and cerebellopontine integrity using diffusion microstructure imaging in 47 patients with MSA-P and 17 patients with MSA-C compared to 31 healthy controls (HC). Dexterity was assessed using the 9-Hole Peg Board (9HPB) performance. Nigrostriatal degeneration, represented by the loss of cells and neurites, leading to a larger free-fluid compartment, was present in MSA-P and MSA-C when compared to HCs. Whereas no intergroup differences were observed between the MSAs in the substantia nigra, MSA-P showed more pronounced putaminal degeneration than MSA-C. In contrast, a cerebellopontine axonal degeneration was observed in MSA-P and MSA-C, with stronger effects in MSA-C. Interestingly, the degeneration of cerebellopontine fibers is associated with impaired dexterity in both subtypes, whereas no association was observed with nigrostriatal degeneration. Cerebellar dysfunction contributes to impaired dexterity not only in MSA-C but also in MSA-P and may be a promising biomarker for disease staging. In contrast, no significant association was observed with nigrostriatal dysfunction. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Innovative multidimensional gait evaluation using IMU in multiple sclerosis: introducing the semiogram.

Quantifying gait using inertial measurement units has gained increasing interest in recent years. Highly degraded gaits, especially in neurological impaired patients, challenge gait detection algorithms and require specific segmentation and analysis tools. Thus, the outcomes of these devices must be rigorously tested for both robustness and relevancy in order to recommend their routine use. In this study, we propose a multidimensional score to quantify and visualize gait, which can be used in neurological routine follow-up. We assessed the reliability and clinical coherence of this method in a group of severely disabled patients with progressive multiple sclerosis (pMS), who display highly degraded gait patterns, as well as in an age-matched healthy subjects (HS) group. Twenty-two participants with pMS and nineteen HS were included in this 18-month longitudinal follow-up study. During the follow-up period, all participants completed a 10-meter walk test with a U-turn and back, twice at M0, M6, M12, and M18. Average speed and seven clinical criteria (sturdiness, springiness, steadiness, stability, smoothness, synchronization, and symmetry) were evaluated using 17 gait parameters selected from the literature. The variation of these parameters from HS values was combined to generate a multidimensional visual tool, referred to as a semiogram. For both cohorts, all criteria showed moderate to very high test-retest reliability for intra-session measurements. Inter-session quantification was also moderate to highly reliable for all criteria except smoothness, which was not reliable for HS participants. All partial scores, except for the stability score, differed between the two populations. All partial scores were correlated with an objective but not subjective quantification of gait severity in the pMS population. A deficit in the pyramidal tract was associated with altered scores in all criteria, whereas deficits in cerebellar, sensitive, bulbar, and cognitive deficits were associated with decreased scores in only a subset of gait criteria. The proposed multidimensional gait quantification represents an innovative approach to monitoring gait disorders. It provides a reliable and informative biomarker for assessing the severity of gait impairments in individuals with pMS. Additionally, it holds the potential for discriminating between various underlying causes of gait alterations in pMS.

Verbal Working Memory-Balance program training alters the left fusiform gyrus resting-state functional connectivity: A randomized clinical trial study on children with dyslexia.

Sufficient activation of the left fusiform gyrus is important in reading ability acquisition due to its role in reading and naming, working memory (WM), and balance tasks. Recently, a newly-designed training program, Verbal Working Memory-Balance (VWM-B), has been evaluated on children with dyslexia, and its positive effects were shown on reading ability, WM capacity, and postural control. In the present study, we aimed to estimate the functional connectivity alterations of the left fusiform gyrus following training by the VWM-B. Before and after 15 sessions of training, the fMRI and other tools data were collected on a sample of children with dyslexia, who were allocated into two control and experiment groups. Data analyses showed the increased functional connectivity of the left fusiform gyrus between the left anterior temporal fusiform cortex, left and right Crus II regions of the cerebellum, and the left middle frontal gyrus. Moreover, VWM-B training significantly improved the reading and naming ability, WM capacity, and postural control of participants in the experiment group in comparison to the control. The current study findings emphasize the critical role of the left fusiform gyrus in reading ability. Moreover, it provides evidence to support the existence of cerebellar deficits in dyslexia.

Ablation of Projection Glutamatergic Neurons in the Lateral Cerebellar Nuclei Alters Motor Coordination in Vglut2-Cre+ Mice.

Cerebellar nuclei (CN) constitute the sole cerebellar output to the rest of the central nervous system and play a central role in cerebellar circuits. Accumulating evidence from both human genetics and animal studies point to a crucial role for CN connectivity in neurological diseases, including several types of ataxia. However, because of the compact and restricted topography and close functional connection between the CN and the cerebellar cortex, identifying cerebellar deficits exclusively linked to CN is challenging. In this study, we have experimentally ablated large projection glutamatergic neurons of the lateral CN and evaluated the impact of this selective manipulation on motor coordination in mice. To this end, through stereotaxic surgery, we injected the lateral CN of Vglut2-Cre+ mice with an adeno-associated virus (AAV) encoding a Cre-dependent diphtheria toxin receptor (DTR), followed by an intraperitoneal injection of diphtheria toxin (DT) to ablate the glutamatergic neurons of the lateral nucleus. Double immunostaining of cerebellar sections with anti-SMI32 and -GFP antibodies revealed GFP expression and provided evidence of SMI32+ neuron degeneration at the site of AAV injection in the lateral nucleus of Vglut2-Cre+ mice. No changes were observed in Vglut2-Cre negative mice. Analysis of motor coordination by rotarod test indicated that the latency to fall was significantly different before and after AAV/DT injection in the Vglut2-Cre+ group. Elapsed time and number of steps in the beam walking test were significantly higher in AAV/DT injected Vglut2-Cre+ AAV/DT mice compared to controls. We demonstrate for the first time that partial degeneration of glutamatergic neurons in the lateral CN is sufficient to induce an ataxic phenotype.

Graded regional cerebellar volume deficits in adolescents and adults with Fetal Alcohol Effect (FAE) and Fetal Alcohol Syndrome (FAS)

Graded regional cerebellar volume deficits in adolescents and adults with Fetal Alcohol Effect (FAE) and Fetal Alcohol Syndrome (FAS)

Alteration in mitochondrial dynamics promotes the proinflammatory response of microglia and is involved in cerebellar dysfunction of young and aged mice following LPS exposure

Cerebellar dysfunction is implicated in impaired motor coordination and balance, thus disturbing the dynamics of sensorimotor integration. Neuroinflammation and aging could be prominent contributors to cerebellar aberration. Additionally, changes in mitochondrial dynamics may precede microglia activation in several chronic neurodegenerative diseases; however, the underlying mechanism remains largely unknown. Here using LPS (1 mg/kg i.p. for four consecutive days) stimulation in both young (3 months old) and aged (12 months old) mice, followed by molecular analysis on the 21st day, we have explored the correlation between aging and mitochondrial dynamic alteration in the backdrop of chronic neuroinflammation. Following LPS stimulation, we observed microglia activation and subsequent elevation in proinflammatory cytokines (M1; TNF-α, IFN-γ) with NLRP3 activation and a concomitant reduction in the expression of anti-inflammatory markers (M2; YM1, TGF-β1) in the cerebellar tissue of aged mice compared with the young LPS and aged controls. Remarkably, senescence (p21, p27, p53) and epigenetic (HDAC2) markers were found upregulated in the cerebellum tissue of the aged LPS group, suggesting their crucial role in LPS-induced cerebellar deficit. Further, we demonstrated alteration in the antagonistic forces of mitochondrial fusion and fission with increased expression of the mitochondrial fission-related gene [FIS1] and decreased fusion-related genes [MFN1 and MFN2]. We noted increased mtDNA copy number, microglia activation, and inflammatory response of IL1-β and IFN-γ post-chronic neuroinflammation in aged LPS group. Our results suggest that the crosstalk between mitochondrial dynamics and altered microglial activation paradigm in chronic neuroinflammatory conditions may be the key to understanding the cerebellar molecular mechanism.

Contraversive Ocular Tilt Reaction, Body Lateropulsion and Gaze-Evoked Nystagmus After Inferior Cerebellar Peduncle and Dentate Nucleus Stroke

Contraversive Ocular Tilt Reaction, Body Lateropulsion and Gaze-Evoked Nystagmus After Inferior Cerebellar Peduncle and Dentate Nucleus Stroke

Evidence of abnormal scalar timing property in alexithymia.

Evidence suggests that incidental modulation of affective states affects the ability to keep track of time. Alexithymia represents an ideal condition to further address the emotion-time processing link, as it refers to a trait characterized by a deficit of affective processing. 31 healthy participants completed an online version of the TAS-20 scale, which measures alexithymia, and a time reproduction task of visual stimuli related to positive (i.e., happiness) and negative (i.e., anger) facial expressions. Results documented a positive correlation between TAS-20 score and the variability in reproducing sub-second durations of the anger expression stimuli We also found an overestimation of sub-second durations of non-affective expressions in borderline/alexithymic participants. Finally, in line with the literature, we confirmed the overall tendency to overestimate the duration of anger expression stimuli. These findings, which can be interpreted in terms of abnormal scalar timing property in alexithymia, expand previous investigations linking this personality trait with abnormal processing of negative emotions. The evidence that alexithymia predicts the reproduction variability of sub-second durations of negative affective stimuli corroborates previous neuroimaging studies documenting cerebellar deficits in these individuals.

Hypothyroidism induces motor deficit via altered cerebellar HB-EGF/EGFR and autophagy.

Thyroid hormones (TH) are vital for brain functions, while TH deficiency, i.e. hypothyroidism, induces neurological impairment in children and adults. Cerebellar neuronal apoptosis and motor deficits are crucial events in hypothyroidism; however, the underlying mechanism is less-known. Using a methimazole-treated hypothyroidism rat model, we investigated cerebellar autophagy, growth factor, and apoptotic mechanisms that participate in motor functions. We first identified that methimazole up-regulated cerebellar autophagy, marked by enhanced LC3B-II, Beclin-1, ATG7, ATG5-12, p-AMPKα/AMPKα, and p62 degradation as well as reduced p-AKT/AKT, p-mTOR/mTOR, and p-ULK1/ULK1 in developing and young adult rats. We probed upstream effectors of this abnormal autophagy and detected a methimazole-induced reduction in cerebellar phospho-epidermal growth factor receptor (p-EGFR)/EGFR and heparin-binding EGF-like growth factor (HB-EGF). Here, while a thyroxine-induced TH replenishment alleviated autophagy process and restored HB-EGF/EGFR, HB-EGF treatment regulated AKT-mTOR and autophagy signaling in the cerebellum. Moreover, neurons of the rat cerebellum demonstrated this reduced HB-EGF-dependent increased autophagy in hypothyroidism. We further checked whether the above events were related to cerebellar neuronal apoptosis and motor functions. We detected that comparable to thyroxine, treatment with HB-EGF or autophagy inhibitor, 3-MA, reduced methimazole-induced decrease in Nissl staining and increase in c-Caspase-3 and TUNEL-+ve apoptotic count of cerebellar neurons. Additionally, 3-MA, HB-EGF, and thyroxine attenuated the methimazole-induced diminution in riding time on rota-rod and grip strength for the motor performance of rats. Overall, our study enlightens HB-EGF/EGFR-dependent autophagy mechanism as a key to cerebellar neuronal loss and functional impairments in developmental hypothyroidism, which may be inhibited by HB-EGF and 3-MA treatments, like thyroxine.