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Frontiers in Immunology 2024Cerebellar ataxia is an uncommon and atypical manifestation of anti--methyl-D-aspartate receptor (NMDAR) encephalitis, often accompanied by seizures, psychiatric...
Cerebellar ataxia is an uncommon and atypical manifestation of anti--methyl-D-aspartate receptor (NMDAR) encephalitis, often accompanied by seizures, psychiatric symptoms, and cognitive deficits. Previous cases of isolated brainstem-cerebellar symptoms in patients with anti-NMDAR encephalitis have not been documented. This report presents a case of anti-NMDAR encephalitis in which the patient exhibited cerebellar ataxia, nystagmus, diplopia, positive bilateral pathological signs, and hemiparesthesia with no other accompanying symptoms or signs. The presence of positive CSF anti-NMDAR antibodies further supports the diagnosis. Other autoantibodies were excluded through the use of cell-based assays. Immunotherapy was subsequently administered, leading to a gradual recovery of the patient.
Topics: Humans; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Brain Stem; Autoantibodies; Female; Cerebellar Ataxia; Cerebellum; Receptors, N-Methyl-D-Aspartate; Adult; Immunotherapy; Male; Magnetic Resonance Imaging
PubMed: 38799430
DOI: 10.3389/fimmu.2024.1388667 -
Human Brain Mapping Jun 2024Twin studies have found gross cerebellar volume to be highly heritable. However, whether fine-grained regional volumes within the cerebellum are similarly heritable is...
Twin studies have found gross cerebellar volume to be highly heritable. However, whether fine-grained regional volumes within the cerebellum are similarly heritable is still being determined. Anatomical MRI scans from two independent datasets (QTIM: Queensland Twin IMaging, N = 798, mean age 22.1 years; QTAB: Queensland Twin Adolescent Brain, N = 396, mean age 11.3 years) were combined with an optimised and automated cerebellum parcellation algorithm to segment and measure 28 cerebellar regions. We show that the heritability of regional volumetric measures varies widely across the cerebellum ( 47%-91%). Additionally, the good to excellent test-retest reliability for a subsample of QTIM participants suggests that non-genetic variance in cerebellar volumes is due primarily to unique environmental influences rather than measurement error. We also show a consistent pattern of strong associations between the volumes of homologous left and right hemisphere regions. Associations were predominantly driven by genetic effects shared between lobules, with only sparse contributions from environmental effects. These findings are consistent with similar studies of the cerebrum and provide a first approximation of the upper bound of heritability detectable by genome-wide association studies.
Topics: Humans; Cerebellum; Male; Adolescent; Female; Magnetic Resonance Imaging; Young Adult; Child; Adult; Organ Size; Twins, Monozygotic
PubMed: 38798116
DOI: 10.1002/hbm.26717 -
Hearing Research Aug 2024Although rats and mice are among the preferred animal models for investigating many characteristics of auditory function, they are rarely used to study an essential...
Although rats and mice are among the preferred animal models for investigating many characteristics of auditory function, they are rarely used to study an essential aspect of binaural hearing: the ability of animals to localize the sources of low-frequency sounds by detecting the interaural time difference (ITD), that is the difference in the time at which the sound arrives at each ear. In mammals, ITDs are mostly encoded in the medial superior olive (MSO), one of the main nuclei of the superior olivary complex (SOC). Because of their small heads and high frequency hearing range, rats and mice are often considered unable to use ITDs for sound localization. Moreover, their MSO is frequently viewed as too small or insignificant compared to that of mammals that use ITDs to localize sounds, including cats and gerbils. However, recent research has demonstrated remarkable similarities between most morphological and physiological features of mouse MSO neurons and those of MSO neurons of mammals that use ITDs. In this context, we have analyzed the structure and neural afferent and efferent connections of the rat MSO, which had never been studied by injecting neuroanatomical tracers into the nucleus. The rat MSO spans the SOC longitudinally. It is relatively small caudally, but grows rostrally into a well-developed column of stacked bipolar neurons. By placing small, precise injections of the bidirectional tracer biotinylated dextran amine (BDA) into the MSO, we show that this nucleus is innervated mainly by the most ventral and rostral spherical bushy cells of the anteroventral cochlear nucleus of both sides, and by the most ventrolateral principal neurons of the ipsilateral medial nucleus of the trapezoid body. The same experiments reveal that the MSO densely innervates the most dorsolateral region of the central nucleus of the inferior colliculus, the central region of the dorsal nucleus of the lateral lemniscus, and the most lateral region of the intermediate nucleus of the lateral lemniscus of its own side. Therefore, the MSO is selectively innervated by, and sends projections to, neurons that process low-frequency sounds. The structural and hodological features of the rat MSO are notably similar to those of the MSO of cats and gerbils. While these similarities raise the question of what functions other than ITD coding the MSO performs, they also suggest that the rat MSO is an appropriate model for future MSO-centered research.
Topics: Animals; Superior Olivary Complex; Auditory Pathways; Sound Localization; Axons; Rats; Male; Dextrans; Biotin; Acoustic Stimulation; Efferent Pathways; Olivary Nucleus; Female; Neuroanatomical Tract-Tracing Techniques; Rats, Wistar
PubMed: 38797037
DOI: 10.1016/j.heares.2024.109036 -
Nature Communications May 2024About half of the neurons in the parabrachial nucleus (PB) that are activated by CO are located in the external lateral (el) subnucleus, express calcitonin gene-related...
About half of the neurons in the parabrachial nucleus (PB) that are activated by CO are located in the external lateral (el) subnucleus, express calcitonin gene-related peptide (CGRP), and cause forebrain arousal. We report here, in male mice, that most of the remaining CO-responsive neurons in the adjacent central lateral (PBcl) and Kölliker-Fuse (KF) PB subnuclei express the transcription factor FoxP2 and many of these neurons project to respiratory sites in the medulla. PBcl neurons show increased intracellular calcium during wakefulness and REM sleep and in response to elevated CO during NREM sleep. Photo-activation of the PBcl neurons increases respiration, whereas either photo-inhibition of PBcl or genetic deletion of PB/KF neurons reduces the respiratory response to CO stimulation without preventing awakening. Thus, augmenting the PBcl/KF response to CO in patients with sleep apnea in combination with inhibition of the PBel neurons may avoid hypoventilation and minimize EEG arousals.
Topics: Animals; Hypercapnia; Neurons; Male; Parabrachial Nucleus; Forkhead Transcription Factors; Mice; Carbon Dioxide; Wakefulness; Respiration; Mice, Inbred C57BL; Calcitonin Gene-Related Peptide; Sleep, REM; Repressor Proteins
PubMed: 38796568
DOI: 10.1038/s41467-024-48773-5 -
Cellular and Molecular Life Sciences :... May 2024Vanishing white matter (VWM) is a leukodystrophy caused by biallelic pathogenic variants in eukaryotic translation initiation factor 2B. To date, it remains unclear...
Vanishing white matter (VWM) is a leukodystrophy caused by biallelic pathogenic variants in eukaryotic translation initiation factor 2B. To date, it remains unclear which factors contribute to VWM pathogenesis. Here, we investigated the basis of VWM pathogenesis using the 2b5 mouse model. We first mapped the temporal proteome in the cerebellum, corpus callosum, cortex, and brainstem of 2b5 and wild-type (WT) mice. Protein changes observed in 2b5 mice were then cross-referenced with published proteomic datasets from VWM patient brain tissue to define alterations relevant to the human disease. By comparing 2b5 mice with their region- and age-matched WT counterparts, we showed that the proteome in the cerebellum and cortex of 2b5 mice was already dysregulated prior to pathology development, whereas proteome changes in the corpus callosum only occurred after pathology onset. Remarkably, protein changes in the brainstem were transient, indicating that a compensatory mechanism might occur in this region. Importantly, 2b5 mouse brain proteome changes reflect features well-known in VWM. Comparison of the 2b5 mouse and VWM patient brain proteomes revealed shared changes. These could represent changes that contribute to the disease or even drive its progression in patients. Taken together, we show that the 2b5 mouse brain proteome is affected in a region- and time-dependent manner. We found that the 2b5 mouse model partly replicates the human disease at the protein level, providing a resource to study aspects of VWM pathogenesis by highlighting alterations from early to late disease stages, and those that possibly drive disease progression.
Topics: Animals; Proteomics; Mice; Humans; Proteome; Leukoencephalopathies; Disease Models, Animal; White Matter; Corpus Callosum; Eukaryotic Initiation Factor-2B; Brain; Mice, Inbred C57BL; Cerebellum
PubMed: 38789799
DOI: 10.1007/s00018-024-05258-4 -
Experimental Neurology Aug 2024Cerebral Palsy (CP) is the main motor disorder in childhood resulting from damage to the developing brain. Treatment perspectives are required to reverse the primary...
Neonatal resveratrol treatment in cerebral palsy model recovers neurodevelopment impairments by restoring the skeletal muscle morphology and decreases microglial activation in the cerebellum.
Cerebral Palsy (CP) is the main motor disorder in childhood resulting from damage to the developing brain. Treatment perspectives are required to reverse the primary damage caused by the early insult and consequently to recover motor skills. Resveratrol has been shown to act as neuroprotection with benefits to skeletal muscle. This study aimed to investigate the effects of neonatal resveratrol treatment on neurodevelopment, skeletal muscle morphology, and cerebellar damage in CP model. Wistar rat pups were allocated to four experimental groups (n = 15/group) according CP model and treatment: Control+Saline (CS), Control+Resveratrol (CR), CP + Saline (CPS), and CP + Resveratrol (CPR). CP model associated anoxia and sensorimotor restriction. CP group showed delay in the disappearance of the palmar grasp reflex (p < 0.0001) and delay in the appearance of reflexes of negative geotaxis (p = 0.01), and free-fall righting (p < 0.0001), reduced locomotor activity and motor coordination (p < 0.05) than CS group. These motor skills impairments were associated with a reduction in muscle weight (p < 0.001) and area and perimeter of soleus end extensor digitorum longus muscle fibers (p < 0.0001), changes in muscle fibers typing pattern (p < 0.05), and the cerebellum showed signs of neuroinflammation due to elevated density and percentage of activated microglia in the CPS group compared to CS group (p < 0.05). CP animals treated with resveratrol showed anticipation of the appearance of negative geotaxis and free-fall righting reflexes (p < 0.01), increased locomotor activity (p < 0.05), recovery muscle fiber types pattern (p < 0.05), and reversal of the increase in density and the percentage of activated microglia in the cerebellum (p < 0.01). Thus, we conclude that neonatal treatment with resveratrol can contribute to the recovery of the delay neurodevelopment resulting from experimental CP due to its action in restoring the skeletal muscle morphology and reducing neuroinflammation from cerebellum.
Topics: Resveratrol; Animals; Rats, Wistar; Cerebellum; Rats; Animals, Newborn; Microglia; Cerebral Palsy; Muscle, Skeletal; Disease Models, Animal; Stilbenes; Male; Recovery of Function; Female
PubMed: 38789024
DOI: 10.1016/j.expneurol.2024.114835 -
Medicine May 2024Subacute combined degeneration of the spinal cord is a degenerative disease of the central and peripheral nervous systems caused by vitamin B12 deficiency, mainly...
RATIONALE
Subacute combined degeneration of the spinal cord is a degenerative disease of the central and peripheral nervous systems caused by vitamin B12 deficiency, mainly involving the spinal cord posterior, lateral, and peripheral nerves, but rarely involving the cerebellum.
PATIENT CONCERNS
A 41-year-old woman presented with a 2-year history of walking unsteadily. Her hematologic examination revealed megaloblastic anemia and vitamin B12 deficiency. Electromyography showed multiple peripheral nerve damage (sensory fibers and motor fibers were involved). Imaging examination showed long T2 signal in the cervical, thoracic and lumbar spinal cord and cerebellum. Gastroscopy revealed autoimmune gastritis.
DIAGNOSES
Subacute combined degeneration of the spinal cord.
INTERVENTIONS
By supplementing with vitamin B12.
OUTCOMES
The patient's symptoms of limb weakness, diet, and consciousness were improved, and the muscle strength of both lower limbs recovered to grade IV.
LESSONS
The symptomatic people should seek medical treatment in time to avoid further deterioration of the disease. When esophagogastroduodenoscopy is performed as part of routine physical examination in asymptomatic people, it should be checked for the presence of autoimmune gastritis. Early diagnosis can prevent irreversible neuropathy.
Topics: Humans; Female; Adult; Subacute Combined Degeneration; Vitamin B 12 Deficiency; Gastritis; Vitamin B 12; Cerebellum; Magnetic Resonance Imaging
PubMed: 38788012
DOI: 10.1097/MD.0000000000037605 -
No Shinkei Geka. Neurological Surgery May 2024The basilar artery(BA)is formed by the fusion of two longitudinal arteries, and incomplete development may lead to BA fenestration. The BA provides many short... (Review)
Review
The basilar artery(BA)is formed by the fusion of two longitudinal arteries, and incomplete development may lead to BA fenestration. The BA provides many short perforating arteries and long lateral pontine arteries to the brain stem. The anterior inferior cerebellar artery(AICA)usually branches from the proximal third of the BA and primarily perfuses the ventral, inferior and lateral aspect of the cerebellum and inner ear organ. However, there are many variations to the AICA that depend on the degree of posterior inferior cerebellar artery development. The superior cerebellar artery(SCA)branches into not only to the rostral, ventral aspect of the cerebellar hemisphere, but also to the deeper cerebellar nucleus and brain stem. Duplications within this vessel are frequently identified, but it is not missing.
Topics: Humans; Basilar Artery; Cerebellum
PubMed: 38783494
DOI: 10.11477/mf.1436204944 -
No Shinkei Geka. Neurological Surgery May 2024The angioarchitecture of the hindbrain is homologous to that of the spinal cord, and its vascular system can be analyzed at the longitudinal and axial structures. During... (Review)
Review
[Anatomical Variations to the Vertebral Artery and Posterior Inferior Cerebellar Artery are Associated with the Partial Persistence of Primitive Lateral Basirovertebral Anastomosis].
The angioarchitecture of the hindbrain is homologous to that of the spinal cord, and its vascular system can be analyzed at the longitudinal and axial structures. During embryonic development, there are two main longitudinal arteries: the longitudinal neural artery and the primitive lateral basilovertebral anastomosis. Commonly observed variations are formed by the fenestration and duplication of either the vertebrobasilar artery, or cerebellar artery, which can be observed when the primitive lateral basilovertebral anastomosis partially persists. Understanding the pattern and development of blood supply to the hindbrain provides useful information of various anomalies in the vertebrobasilar junction and cerebellar arteries.
Topics: Humans; Vertebral Artery; Cerebellum; Male; Female
PubMed: 38783493
DOI: 10.11477/mf.1436204943 -
Scientific Reports May 2024Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral...
Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral prefrontal cortex (LDLPFC). However, the therapeutic effectiveness of rTMS at this site remains inconclusive and increasingly, studies are focusing on cerebellar rTMS. Recently, prolonged intermittent theta-burst stimulation (iTBS) has emerged as a rapid-acting form of rTMS with promising clinical benefits. This study explored the cognitive and neurophysiological effects of prolonged iTBS administered to the LDLPFC and cerebellum in a healthy cohort. 50 healthy participants took part in a cross-over study and received prolonged (1800 pulses) iTBS targeting the LDLPFC, cerebellar vermis, and sham iTBS. Mixed effects repeated measures models examined cognitive and event-related potentials (ERPs) from 2-back (P300, N200) and Stroop (N200, N450) tasks after stimulation. Exploratory non-parametric cluster-based permutation tests compared ERPs between conditions. There were no significant differences between conditions for behavioural and ERP outcomes on the 2-back and Stroop tasks. Exploratory cluster-based permutation tests of ERPs did not identify any significant differences between conditions. We did not find evidence that a single session of prolonged iTBS administered to either the LDLPFC or cerebellum could cause any cognitive or ERP changes compared to sham in a healthy sample.
Topics: Humans; Male; Transcranial Magnetic Stimulation; Female; Adult; Cerebellum; Executive Function; Prefrontal Cortex; Evoked Potentials; Young Adult; Healthy Volunteers; Cross-Over Studies; Theta Rhythm; Cognition; Dorsolateral Prefrontal Cortex
PubMed: 38782921
DOI: 10.1038/s41598-024-61404-9