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BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

Substantial evidence highlights the role of the cerebellum in the pathophysiology of tremor in essential tremor (ET), although its potential involvement in altered movement execution in this condition remains unclear. This study aims to explore potential correlations between the cerebellum and basal ganglia functional connectivity and voluntary movement execution abnormalities in ET, objectively assessed with kinematic techniques. A total of 20 patients diagnosed with ET and 18 healthy subjects were enrolled in this study. Tremor and repetitive finger tapping were recorded using an optoelectronic kinematic system. All participants underwent comprehensive 3T-MRI examinations, including 3D-T1 and blood-oxygen-level dependent (BOLD) sequences during resting state. Morphometric analysis was conducted on the 3D-T1 images, while a seed-based analysis was performed to investigate the resting-state functional connectivity (rsFC) of dorsal and ventral portions of the dentate nucleus and the external and internal segments of the globus pallidus. Finally, potential correlations between rsFC alterations in patients and clinical as well as kinematic scores were assessed. Finger tapping movements were slower in ET than in healthy subjects. Compared to healthy subjects, patients with ET exhibited altered FC of both dentate and globus pallidus with cerebellar, basal ganglia, and cortical areas. Interestingly, both dentate and pallidal FC exhibited positive correlations with movement velocity in patients, differently from that we observed in healthy subjects, indicating the higher the FC, the faster the finger tapping. The findings of this study indicate the possible role of both cerebellum and basal ganglia in the pathophysiology of altered voluntary movement execution in patients with ET. [ABSTRACT FROM AUTHOR]

Background: Febrile seizures are a common form of convulsions in childhood, with poorly known cellular mechanisms. The objective of this pioneering study was to provide qualitative and quantitative ultrastructural research on the large neuronal perikarya in the cerebellar dentate nucleus (DN), using an experimental model of hyperthermia-induced seizures (HSs), comparable to febrile seizures in children. Methods: The study used young male Wistar rats, divided into experimental and control groups. The HSs were evoked by a hyperthermic water bath at 45 °C for 4 min for four consecutive days. Specimens (1 mm3) collected from the DN were routinely processed for transmission electron microscopy studies. Results: The ultrastructure of the large neurons in the DN affected by hyperthermic stress showed variously pronounced lesions in the perikarya, including total cell disintegration. The most pronounced neuronal lesions exhibited specific morphological signs of aponecrosis, i.e., dark cell degeneration ('dark neurons'). In close vicinity to the 'dark neurons', the aponecrotic bodies were found. The findings of this qualitative ultrastructural study correspond with the results of the morphometric analysis of the neuronal perikarya. Conclusions: Our results may constitute interesting comparative material for similar submicroscopic observations on large DN neurons in HS morphogenesis and, in the future, may help to find potential treatment targets to prevent febrile seizures or reduce recurrent seizures in children. [ABSTRACT FROM AUTHOR]

This document is a compilation of references to various scientific articles and studies related to the cerebellum and its role in various neurological conditions and cognitive processes. The articles cover topics such as the development of the cerebellum, its involvement in autism spectrum disorder and dementia, and the impact of cerebellar dysfunction on cognitive function. The references provide a starting point for library patrons conducting research on these specific topics and offer a diverse range of perspectives on the subject matter. [Extracted from the article]

Objective: Vestibular function is controlled by interactions between various neuropathways that have different effects on balance and are connected to various brain areas. However, few studies have investigated the relation between changes in VN connectivity and aging using neuroimaging. We investigated neural connectivities in the vestibular nucleus (VN) and ventralis intermedius (VIM) nucleus of the thalamus in young and old healthy adults by diffusion tensor imaging. Methods: This study recruited twenty-three normal healthy adults with no history of a neurological or musculoskeletal disease, that is, eleven old healthy adults (6 males, 5 females; mean age 63.36 ± 4.25 years) and 12 young healthy adults (7 males, 5 females; mean age 28.42 ± 4.40 years). Connectivity was defined as the incidence of connection between the VN, VIM, and target brain regions. Incidence of connection was counted from VN and VIM to each brain region. The subjective visual vertical (SVV) and the Berg balance scale (BBS) were used to assess vestibular function and balance. Results: The VN showed high connectivity with brainstem (dentate nucleus, medial longitudinal fasciculus, and VIM), but relatively low connectivity with cerebral cortex (parieto-insular vestibular cortex (PIVC) and primary somatosensory cortex) at a threshold of 30 streamlines. In particular, VN connectivity with PIVC was significantly lower in elderly adults (> 60 years old) than in young adults (20–40 years old) (p < 0.05). VIM showed high to mid connectivity with brainstems and cerebral cortexes at a threshold of 30, but no significant difference was observed between young and old adults (p > 0.05). SVV and BBS showed no significant differences between young and old adults (p > 0.05). Conclusion: We investigated incidences of neural connectivities of VN and VIM in young and old healthy adults. Our results provide basic data that might be clinically useful following injury of vestibular-related areas. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 30-year-old man with slowly progressive gait disturbances and imbalance since childhood. The patient also developed slurred speech and had high levels of blood cholesterol. Clinical examination revealed a wide-based gait, areflexia, and decreased vibration sense in the lower limbs, but no oculomotor apraxia. Brain MRI showed cerebellar atrophy and dentate nuclei abnormalities. Genetic testing identified a compound heterozygous mutation in the APTX gene, which is associated with ataxia with oculomotor apraxia type 1 (AOA1). The patient's phenotype was milder than typical AOA1 cases, possibly due to the specific genotype. The study highlights the importance of considering AOA1 as a diagnosis even without oculomotor apraxia, especially when suggestive brain MRI findings are present. [Extracted from the article]

In progressive supranuclear palsy (PSP), subcortical tau and cortical perfusion can be assessed using the tracer [18F]PI-2620. We investigated if subcortical tau (globus pallidus internus, dentate nucleus) and frontal/limbic perfusion correlate in a cohort of 32 PSP patients. Tau in subcortical regions showed significant negative correlation with perfusion in limbic cortex. Perfusion in frontal regions was negatively associated with tau in both subcortical regions, but the significance threshold was only passed for the dentate nucleus. A reason could be a diaschisis-like phenomenon; that is, subcortical tau could lead to reduced connectivity to frontal regions and, thereby, to decreased perfusion. Plain Language Summary: In a study of 32 patients with progressive supranuclear palsy (PSP), we used a molecular imaging tracer called [18F]PI-2620 to measure two things: the presence of a protein called tau in deep brain areas (specifically, the globus pallidus internus and dentate nucleus) and the function of the brain's cortex by assessing blood flow (perfusion). We found that higher amounts of tau in these deep brain areas were associated with reduced blood flow in the limbic cortex, which is involved in emotion regulation. Also, the frontal areas of the brain showed reduced blood flow related to tau in these deep brain regions. However, this connection was statistically significant only for the dentate nucleus. This study suggests that the buildup of tau protein in deeper brain areas can disrupt function in parts of the brain's cortex, highlighting the damaging role of tau in PSP. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Our case report highlights that Prompt recognition of cerebellar mutism syndrome (CMS) is critical in clinical practice, as it is often misdiagnosed as just being reduction in the level of consciousness, particularly in pediatrics trauma patients. Cerebellar mutism syndrome is defined as transient mutism following posterior fossa surgery, hemorrhage or traumatic insults involving the cerebellum. Cerebellar mutism syndrome (CMS) is now recognized as a form of cerebellar cognitive affective syndrome (CCAS/Schmahmann syndrome). CMS following head injury is exceedingly rare with very few cases reported. Five years old boy with normal developmental milestones and no significant medical history, sustained closed head injury following road traffic accident, the clinical scenario in addition to the radiological findings led to the diagnosis of cerebellar mutism syndrome. CMS is defined as of neurologic and cognitive disorders, mainly speech disorder. Patient non‐motor signs recovered in a period of few weeks from the mutism syndrome with remaining mild motor deficit. CMS is a set of neurologic and cognitive disorders, the most distinct of which is speech disorder (usually reversible), what is unique about this case is the selective site of the contusion at the region of the dentate nucleus and superior cerebellar peduncle. Such cases offer a better understanding to the function of the cerebellum and its role in cognition. Additionally, the knowledge of this aspect of cerebellar function helps in better predicting the clinical course of such lesions which in turn helps in communication and explanation to patient's families. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is characterized by disconnected cerebral networks. Recent studies have shown that functional connectivity between the cerebellar dorsal dentate nucleus (dDN) and cerebrum is correlated with psychotic symptoms, and processing speed in SZ patients. Dynamic effective connectivity (dEC) is a reliable indicator of brain functional status. However, the dEC between the dDN and cerebrum in patients with SZ remains largely unknown. Resting-state functional MRI data, symptom severity, and cognitive performance were collected from 74 SZ patients and 53 healthy controls (HC). Granger causality analysis and sliding time window methods were used to calculate dDN-based dEC maps for all subjects, and k-means clustering was performed to obtain several dEC states. Finally, between-group differences in dynamic effective connectivity variability (dECV) and clinical correlations were obtained using two-sample t -tests and correlation analysis. We detected four dEC states from the cerebrum to the right dDN (IN states) and three dEC states from the right dDN to the cerebrum (OUT states), with SZ group having fewer transitions in the OUT states. SZ group had increased dECV from the right dDN to the right middle frontal gyrus (MFG) and left lingual gyrus (LG). Correlations were found between the dECV from the right dDN to the right MFG and symptom severity and between the dECV from the right dDN to the left LG and working memory performance. This study reveals a dynamic causal relationship between cerebellar dDN and the cerebrum in SZ and provides new evidence for the involvement of cerebellar neural circuits in neurocognitive functions in SZ. [ABSTRACT FROM AUTHOR]

Cerebellar mutism syndrome (CMS) is a frequent complication of surgical intervention on posterior fossa in children. It has been only occasionally reported in adults and its features have not been fully characterized. In children and in young adults, medulloblastoma is the main reason for neurosurgery. A single case of postsurgical CMS is presented in an adult patient with a cerebellar hemorrhage and a systematic review of the published individual cases of CMS in adults was done. Literature review of individual cases found 30 patients, 18/30 (60%) males, from 20 to 71 years at diagnosis. All but one case was post-surgical, but in one of the post-surgical cases iatrogenic basilar artery occlusion was proposed as cause for CMS. The causes were: primary tumors of the posterior fossa in 16/22 (72.7%) metastasis in 3/30 (10%), ischemia in 3/30 (10%) cerebellar hemorrhage in 3/30 (10%), and benign lesions in 2/30 (6.7%) patients. 8/30 patients (26.7%) were reported as having persistent or incomplete resolution of CMS within 12 months. CMS is a rare occurrence in adults and spontaneous cerebellar hemorrhage has been reported in 3/30 (10%) adult patients. The generally accepted hypothesis is that CMS results from bilateral damage to the dentate nucleus or the dentate-rubro-thalamic tract, leading to cerebro–cerebellar diaschisis. Several causes might contribute in adults. The prognosis of CMS is slightly worse in adults than in children, but two thirds of cases show a complete resolution within 6 months. [ABSTRACT FROM AUTHOR]

Abstract Background Magnetic resonance spectroscopy (MRS) studies have indicated that the imbalance between gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels was the potential cause of migraine development. However, the changes in the GABA and Glx levels in patients with New daily persistent headache (NDPH) remain unclear. This study aimed to investigate the changes in GABA and Glx levels in the periaqueductal gray (PAG) and dentate nucleus (DN) in patients with NDPH using the MEGA-PRESS sequence. Methods Twenty-one NDPH patients and 22 age- and sex-matched healthy controls (HCs) were included and underwent a 3.0T MRI examination, using the MEGA-PRESS sequence to analyze GABA and Glx levels of PAG and DN. The correlations between these neurotransmitter levels and clinical characteristics were also analyzed. Results There were no significant differences in the GABA+/Water, GABA+/Cr, Glx/Water, and Glx/Cr levels in both PAG and DN between the two groups (all p > 0.05). Moderate-severe NDPH patients had lower levels of Glx/Water (p = 0.034) and Glx/Cr (p = 0.012) in DN than minimal-mild NDPH patients. In patients with NDPH, higher Glx/Water levels in the PAG (r=-0.471, p = 0.031, n = 21) and DN (r=-0.501, p = 0.021, n = 21) and higher Glx/Cr levels in DN (r=-0.483, p = 0.026, n = 21) were found to be correlated with lower Visual Analogue Scale scores. Additionally, a positive correlation was observed between the GABA+/Cr levels in the DN and the Generalized Anxiety Disorder-7 scores (r = 0.519, p = 0.039, n = 16). Conclusions The results of this study indicated that the GABA and Glx levels in the PAG and DN may not be the primary contributor to the development of NDPH. The correlations between certain clinical scales and the neurotransmitter levels may be derived from the NDPH related symptoms.

Background: Magnetic resonance spectroscopy (MRS) studies have indicated that the imbalance between gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels was the potential cause of migraine development. However, the changes in the GABA and Glx levels in patients with New daily persistent headache (NDPH) remain unclear. This study aimed to investigate the changes in GABA and Glx levels in the periaqueductal gray (PAG) and dentate nucleus (DN) in patients with NDPH using the MEGA-PRESS sequence. Methods: Twenty-one NDPH patients and 22 age- and sex-matched healthy controls (HCs) were included and underwent a 3.0T MRI examination, using the MEGA-PRESS sequence to analyze GABA and Glx levels of PAG and DN. The correlations between these neurotransmitter levels and clinical characteristics were also analyzed. Results: There were no significant differences in the GABA+/Water, GABA+/Cr, Glx/Water, and Glx/Cr levels in both PAG and DN between the two groups (all p > 0.05). Moderate-severe NDPH patients had lower levels of Glx/Water (p = 0.034) and Glx/Cr (p = 0.012) in DN than minimal-mild NDPH patients. In patients with NDPH, higher Glx/Water levels in the PAG (r=-0.471, p = 0.031, n = 21) and DN (r=-0.501, p = 0.021, n = 21) and higher Glx/Cr levels in DN (r=-0.483, p = 0.026, n = 21) were found to be correlated with lower Visual Analogue Scale scores. Additionally, a positive correlation was observed between the GABA+/Cr levels in the DN and the Generalized Anxiety Disorder-7 scores (r = 0.519, p = 0.039, n = 16). Conclusions: The results of this study indicated that the GABA and Glx levels in the PAG and DN may not be the primary contributor to the development of NDPH. The correlations between certain clinical scales and the neurotransmitter levels may be derived from the NDPH related symptoms. [ABSTRACT FROM AUTHOR]

Primary familial brain calcification (PFBC) is a genetic neurological disorder characterized by symmetric brain calcifications that manifest with variable neurological symptoms. This study aimed to explore the genetic basis of PFBC and elucidate the underlying pathophysiological mechanisms. Six patients from four pedigrees with brain calcification were enrolled. Whole-exome sequencing identified two novel homozygous variants, c.488G > T (p.W163L) and c.2135G > A (p.W712*), within the myogenesis regulating glycosidase (MYORG) gene. Cerebellar ataxia (n = 5) and pyramidal signs (n = 4) were predominant symptoms, with significant clinical heterogeneity noted even within the same family. An autopsy of one patient revealed extensive brainstem calcifications, sparing the cerebral cortex, and marked by calcifications predominantly in capillaries and arterioles. The pathological study suggested morphological alterations characterized by shortened foot processes within astrocytes in regions with pronounced calcification and decreased immunoreactivity of AQP4. The morphology of astrocytes in regions without calcification remains preserved. Neuronal loss and gliosis were observed in the basal ganglia, thalamus, brainstem, cerebellum, and dentate nucleus. Notably, olivary hypertrophy, a previously undescribed feature in MYORG-PFBC, was discovered. Neuroimaging showed reduced blood flow in the cerebellum, highlighting the extent of cerebellar involvement. Among perivascular cells constituting the blood-brain barrier (BBB) and neurovascular unit, MYORG is most highly expressed in astrocytes. Astrocytes are integral components of the BBB, and their dysfunction can precipitate BBB disruption, potentially leading to brain calcification and subsequent neuronal loss. This study presents two novel homozygous variants in the MYORG gene and highlights the pivotal role of astrocytes in the development of brain calcifications, providing insights into the pathophysiological mechanisms underlying PFBC associated with MYORG variants. [ABSTRACT FROM AUTHOR]

This study reported a case of MELAS syndrome presenting as the initial imaging characteristics of Fahr's syndrome with "near" sudden unexpected death in epilepsy (SUDEP) and lateralized periodic discharges (LPD). The patient, a young boy, experienced loss of consciousness 2 days prior, which was followed by two limb and facial convulsions. He was later found in cardiac arrest during hospitalization, but regained consciousness gradually after receiving cardiopulmonary resuscitation and tracheal intubation. The patient exhibited short stature, intellectual disability, poor sports abilities, and academic performance since childhood, but had no family history. Emergency head computed tomography (CT) revealed high density calcification in bilateral caudate nucleus, lentiform nucleus, thalamus, and dentate nucleus with evidence of an acute process. The patient was transferred to the neurology department where he continued to recover consciousness, though he experienced dysarthria, left limb hemiplegia, and hemiparesthesia. Changes in head magnetic resonance imaging (MRI) findings were noted at admission, 1 month later, and 6 months later. LPD were observed in his video electroencephalogram. The CT urography indicated a narrow left ureteropelvic junction with left hydronephrosis, which was suggestive of ureteropelvic junction obstruction. Ultimately, a diagnosis of near-SUDEP was suspected in this patient, indicating a rare case of MELAS syndrome with near-SUDEP and LPD. The gene tests results revealed the presence of the mitochondrial DNA A3243G mutation, leading to the final diagnosis of MELAS syndrome. This case expands the clinical disease spectrum of the MELAS syndrome. [ABSTRACT FROM AUTHOR]

Background: Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed. Methods: In this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis. Results: The clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76. Conclusions: The newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD. [ABSTRACT FROM AUTHOR]

While ipsilesional cortical electroencephalography has been associated with poststroke recovery mechanisms and outcomes, the role of the cerebellum and its interaction with the ipsilesional cortex is still largely unknown. We have previously shown that poststroke motor control relies on increased corticocerebellar coherence (CCC) in the low beta band to maintain motor task accuracy and to compensate for decreased excitability of the ipsilesional cortex. We now extend our work to investigate corticocerebellar network changes associated with chronic stimulation of the dentato-thalamo-cortical pathway aimed at promoting poststroke motor rehabilitation. We investigated the excitability of the ipsilesional cortex, the dentate (DN), and their interaction as a function of treatment outcome measures. Relative to baseline, 10 human participants (two women) at the end of 4-8 months of DN deep brain stimulation (DBS) showed (1) significantly improved motor control indexed by computerized motor tasks; (2) significant increase in ipsilesional premotor cortex event-related desynchronization that correlated with improvements in motor function; and (3) significant decrease in CCC, including causal interactions between the DN and ipsilesional cortex, which also correlated with motor function improvements. Furthermore, we show that the functional state of the DN in the poststroke state and its connectivity with the ipsilesional cortex were predictive of motor outcomes associated with DN-DBS. The findings suggest that as participants recovered, the ipsilesional cortex became more involved in motor control, with less demand on the cerebellum to support task planning and execution. Our data provide unique mechanistic insights into the functional state of corticocerebellar-cortical network after stroke and its modulation by DN-DBS. [ABSTRACT FROM AUTHOR]

Objective: The dentato‐thalamo‐cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach. Methods: MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross‐sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison. Results: Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted. Interpretation: Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping. Aims: We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS. Methods: Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38–98 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC/D) and microglia/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology. Results: Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death. Conclusion: Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesized that severe tau burden in brain regions involved in direct or indirect pathways of the basal ganglia correlate with more severe striatal dopamine deficiency in four-repeat (4R) tauopathies. Therefore, we correlated [18F]PI-2620 tau-positron-emission-tomography (PET) imaging with [123I]-Ioflupane single-photon-emission-computed tomography (SPECT) for dopamine transporter (DaT) availability. Methods: Thirty-eight patients with clinically diagnosed 4R-tauopathies (21 male; 69.0 ± 8.5 years) and 15 patients with clinically diagnosed α-synucleinopathies (8 male; 66.1 ± 10.3 years) who underwent [18F]PI-2620 tau-PET and DaT-SPECT imaging with a time gap of 3 ± 5 months were evaluated. Regional Tau-PET signals and DaT availability as well as their principal components were correlated in patients with 4R-tauopathies and α-synucleinopathies. Both biomarkers and the residuals of their association were correlated with clinical severity scores in 4R-tauopathies. Results: In patients with 4R-tauopathies, [18F]PI-2620 binding in basal ganglia and midbrain regions was negatively associated with striatal DaT availability (i.e. globus pallidus internus and putamen (β = − 0.464, p = 0.006, Durbin-Watson statistics = 1.824) in a multiple regression model. Contrarily, [18F]PI-2620 binding in the dentate nucleus showed no significant regression factor with DaT availability in the striatum (β = 0.078, p = 0.662, Durbin-Watson statistics = 1.686). Patients with α-synucleinopathies did not indicate any regional associations between [18F]PI-2620-binding and DaT availability. Higher DaT-SPECT binding relative to tau burden was associated with better clinical performance (β = − 0.522, p = 0.011, Durbin-Watson statistics = 2.663) in patients with 4R-tauopathies. Conclusion: Tau burden in brain regions involved in dopaminergic pathways is associated with aggravated dopaminergic dysfunction in patients with clinically diagnosed primary tauopathies. The ability to sustain dopamine transmission despite tau accumulation may preserve motor function. [ABSTRACT FROM AUTHOR]

Monocular torsional eye oscillations are a rare form of disconjugate nystagmus and the underlying pathophysiology is not well understood. Here, we present and discuss a case with disabling torsional oscillopsia in one eye only. The patient exhibited (i) spontaneous pendular torsional nystagmus of the left eye and (ii) rhythmic involuntary movements of the soft palate and uvula, consistent with the syndrome of oculopalatal tremor with monocular nystagmus. Brain MRI revealed an infarct of the left dentate nucleus in the cerebellum and, more caudally, a secondary hypertrophic degeneration of the right inferior olivary nucleus. To account for the presence of torsional nystagmus on the eye contralateral to the side of inferior olivary hypertrophy and ipsilateral to the lesioned dentate nucleus, we discuss the hypothesis of a (inferior olivary nucleus-mediated) malfunctioning adaptation of the anterior canal vestibulo-ocular reflex. [ABSTRACT FROM AUTHOR]

Objective: Despite being one of the most prevalent neurological diseases, the pathophysiology of essential tremor (ET) is not fully understood. Neuropathological studies have identified numerous degenerative changes in the cerebellum of ET patients, however. These data align with considerable clinical and neurophysiological data linking ET to the cerebellum. While neuroimaging studies have variably shown mild atrophy in the cerebellum, marked atrophy is not a clear feature of the cerebellum in ET and a search for a more suitable neuroimaging signature of neurodegeneration is in order. Postmortem studies in ET have examined different neuropathological alterations in the cerebellum, but as of yet have not focused on measures of generalized synaptic markers. This pilot study focuses on synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in practically all synapses in the brain, as a measure of synaptic density in postmortem ET cases. Methods: The current study utilized autoradiography with the SV2A radioligand [18F]SDM-16 to assess synaptic density in the cerebellar cortex and dentate nucleus in three ET cases and three age-matched controls. Results: Using [18F]SDM-16, SV2A was 53% and 46% lower in the cerebellar cortex and dentate nucleus, respectively, in ET cases compared to age-matched controls. Conclusion: In this pilot study, using in vitro SV2A autoradiography, we have observed significantly lower synaptic density in the cerebellar cortex and dentate nucleus of ET cases. Future research could expand on our sample size and focus on in vivo imaging in ET to explore whether SV2A imaging could serve as a much-needed disease biomarker. [ABSTRACT FROM AUTHOR]

This article presents a case study of a former professional football player who developed chronic traumatic encephalopathy (CTE) later in life. The study provides detailed information about the patient's symptoms, cognitive decline, and functional impairments, as well as findings from neuroimaging and neuropathological examinations. The article emphasizes the need for further research to better understand CTE and its associated pathologies. It also suggests that FDG-PET imaging may be a useful diagnostic tool for early-stage CTE and highlights the potential link between traumatic brain injury and other brain pathologies. [Extracted from the article]

A 65‐year‐old woman developed metronidazole‐induced encephalopathy (MIE) with prolonged severe total aphasia during treatment for a liver abscess. Brain magnetic resonance imaging revealed restricted diffusion in the left cerebral white matter and splenium of the corpus callosum, along with transient cortical lesions but no typical dentate nucleus involvement. Despite discontinuing metronidazole, aphasia persisted for over a month, leading to her death. Although the white matter lesions persisted, the cortical lesions diminished after 2 weeks. This case highlights that MIE can involve the cerebral cortex, similar to Wernicke's encephalopathy. [ABSTRACT FROM AUTHOR]

Introduction: Metronidazole-induced encephalopathy is an uncommon but potentially severe complication of metronidazole treatment. Although the exact pathophysiology remains elusive, proposed hypotheses include RNA binding, neurotoxicity from free radicals, and modulation of neurotransmitter receptors. Most cases demonstrate improvement upon discontinuation of metronidazole, highlighting the importance of early recognition. Magnetic resonance imaging plays a critical role in diagnosing metronidazole-induced encephalopathy, with characteristic imaging findings frequently observed in the dentate nuclei and corpus callosum. Case summary: A 63-year-old man treated with metronidazole for lumbar spondylodiscitis developed neurological symptoms consistent with metronidazole-induced encephalopathy. Images: Magnetic resonance imaging revealed characteristic bilateral hyperintense lesions in the cerebellar dentate nuclei, corpus callosum, and brainstem. Prompt recognition and discontinuation of metronidazole led to symptom resolution. Conclusion: This case underscores the importance of clinicians and radiologists being aware of this condition and emphasizes the pivotal role of magnetic resonance imagining in establishing the diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. Methods Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. Discussion Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. Trial registration ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

Purpose: The dentate nucleus (DN) is the largest, most lateral, and phylogenetically most recent of the deep cerebellar nuclei. Its pivotal role encompasses the planning, initiation, and modification of voluntary movement but also spans non-motor functions like executive functioning, visuospatial processing, and linguistic abilities. This review aims to offer a comprehensive description of the DN, detailing its embryology, anatomy, physiology, and clinical relevance, alongside an analysis of dentatotomy. Methods and results: We delve into the history, embryology, anatomy, vascular supply, imaging characteristics, and clinical significance of the DN. Furthermore, we thoroughly review the dentatotomy, emphasizing its role in treating spasticity. Conclusions: Understanding the intricacies of the anatomy, physiology, vasculature, and projections of the DN has taken on increased importance in current neurosurgical practice. Advances in technology have unveiled previously unknown functions of the deep cerebellar nuclei, predominantly related to non-motor domains. Such discoveries are revitalizing older techniques, like dentatotomy, and applying them to newer, more localized targets. [ABSTRACT FROM AUTHOR]

The primary aim of this study is to report long-term outcomes associated with deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) performed at our institution. We further aimed to elicit the factors associated with loss of efficacy and to discuss the need for exploring and establishing reliable rescue targets. To study long-term outcomes, we performed a retrospective chart review and extracted tremor scores of 43 patients who underwent VIM DBS lead implantation for essential tremor at our center. We further evaluated factors that could influence outcomes over time, including demographics, body mass index, duration of follow-up, degree of parenchymal atrophy indexed by the global cortical atrophy scale, and third ventricular width. In this cohort, tremor scores on the latest follow-up (median 52.7 months) were noted to be worse than initial postoperative scores in 56% of DBS leads. Furthermore, 14% of leads were associated with clinically significant loss of benefit. Factors including the length of time since the lead implantation, age at the time of surgery, sex, body mass index, preoperative atrophy, and third ventricular width were not predictive of long-term outcomes. Our study identified a substantial subgroup of VIM-DBS patient who experienced a gradual decline in treatment efficacy over time. We propose that this phenomenon can be attributed primarily to habituation and disease progression. Furthermore, we discuss the need to establish reliable and effective rescue targets for this subpopulation of patients, with ventral-oralis complex and dentate nucleus emerging as potential candidates. [ABSTRACT FROM AUTHOR]

Background: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by the John Cunningham virus. Various brain regions are affected by PML. Therefore, patients with PML show various neurological symptoms. However, tremors are rare neurological symptoms of PML. Case Presentation: A 49‐year‐old man developed intermittent slow tremor in the left hand, bilateral dysesthesia and gait disturbance. Brain magnetic resonance imaging showed hyperintense lesions in the right parietofrontal lobe, right thalamus, left middle cerebellar peduncle, left dentate nucleus, pons and medulla oblongata on fluid‐attenuated inversion recovery images. The patient was positive for HIV antibodies. In addition, HIV‐1 RNA was increased. Quantitative real‐time polymerase chain reaction identified John Cunningham virus DNA in the cerebrospinal fluid; HIV‐associated PML was diagnosed. Surface electromyography showed 3‐Hz grouped discharges in the left flexor carpi ulnaris and extensor carpi radialis, which were consistent with Holmes tremor (HT). Although we administered antiretroviral therapy and mirtazapine, the neurological and radiological findings progressively worsened, and the patient died on day 90. Including the present case, there have been 10 reported cases of PML with HT. Conclusions: Although tremors are rarely observed in PML, HT might be a common tremor phenotype in patients with PML. If the neurologist observes HT in patients with multiple brain lesions, PML should be considered. [ABSTRACT FROM AUTHOR]

Objectives: Iron deposition and mitochondrial dysfunction are closely associated with the genesis and progression of Parkinson's disease (PD). This study aims to extract susceptibility and oxygen extraction fraction (OEF) values of deep grey matter (DGM) to explore spatiotemporal progression patterns of brain iron-oxygen metabolism in PD. Methods: Ninety-five PD patients and forty healthy controls (HCs) were included. Quantitative susceptibility mapping (QSM) and OEF maps were computed from MRI multi-echo gradient echo data. Analysis of covariance (ANCOVA) was used to compare mean susceptibility and OEF values in DGM between early-stage PD (ESP), advanced-stage PD (ASP) patients and HCs. Then Granger causality analysis on the pseudo-time-series of MRI data was applied to assess the causal effect of early altered nuclei on iron content and oxygen extraction in other DGM nuclei. Results: The susceptibility values in substantia nigra (SN), red nucleus, and globus pallidus (GP) significantly increased in PD patients compared with HCs, while the iron content in GP did not elevate obviously until the late stage. The mean OEF values for the caudate nucleus, putamen, and dentate nucleus were higher in ESP patients than in ASP patients or/and HCs. We also found that iron accumulation progressively expands from the midbrain to the striatum. These alterations were correlated with clinical features and improved AUC for early PD diagnosis to 0.824. Conclusions: Abnormal cerebral iron deposition and tissue oxygen utilization in PD measured by QSM and OEF maps could reflect pathological alterations in neurodegenerative processes and provide valuable indicators for disease identification and management. Clinical relevance statement: Noninvasive assessment of cerebral iron-oxygen metabolism may serve as clinical evidence of pathological changes in PD and improve the validity of diagnosis and disease monitoring. Key Points: • Quantitative susceptibility mapping and oxygen extraction fraction maps indicated the cerebral pathology of abnormal iron accumulation and oxygen metabolism in Parkinson's disease. • Iron deposition is mainly in the midbrain, while altered oxygen metabolism is concentrated in the striatum and cerebellum. • The susceptibility and oxygen extraction fraction values in subcortical nuclei were associated with clinical severity. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxias (SCAs) are heterogeneous autosomal dominant progressive ataxic disorders. SCA25 has been linked to PNPT1 pathogenic variants. Although pediatric onset is not unusual, to date only one patient with onset in the first years of life has been reported. This study presents an additional case, wherein symptoms emerged during the toddler phase, accompanied by the identification of a novel PNPT1 variant. The child was seen at 3 years because of frequent falls. Neurological examination revealed cerebellar signs and psychomotor delay. Brain MRI showed cerebellar atrophy (CA), cerebellar cortex, and dentate nuclei hyperintensities. Metabolic and genetic testing was inconclusive. At follow-up (age 6), the child had clinically and radiologically worsened; electroneurography (ENG) revealed axonal sensory neuropathy. Screening of genes associated with ataxias and mitochondrial disease identified a novel, heterozygous variant in PNPT1, which was probably pathogenic. This variant was also detected in the proband's mother and maternal grandmother, both asymptomatic, which aligns with the previously documented incomplete penetrance of heterozygous PNPT1 variants. Our study confirms that SCA25 can have onset in early childhood and characterizes natural history in pediatric cases: progressive cerebellar ataxia with sensory neuropathy, which manifests during the course of the disease. We report for the first time cerebellar gray matter hyperintensities, suggesting that SCA25 should be included in the differential diagnosis of cerebellar ataxias associated with such brain imaging features. In summary, SCA25 should be considered in the diagnostic workup of early onset pediatric progressive ataxias. Additionally, we confirm an incomplete penetrance and highly variable expressivity of PNPT1 -associated SCA25. [ABSTRACT FROM AUTHOR]

GNB1 encephalopathy is a rare genetic disease caused by pathogenic variants in the G Protein Subunit Beta 1 (GNB1) gene, with only around 68 cases documented worldwide. Although most cases had been caused by de novo germline mutations, in this case, the pathogenic variant was inherited from patient's mother, indicating an autosomal dominant inheritance pattern. The patient presented at 25 years of age with mild developmental delay and cognitive impairment, prominent generalized dystonia, and horizontal nystagmus which are all characterizing symptoms of GNB1 encephalopathy. Electroencephalography (EEG) showed no epileptiform patterns, and magnetic resonance imaging (MRI) revealed hypointensities in globus pallidus and dentate nucleus areas. The main theory for GNB1 encephalopathy pathogenesis is neuronal hyperexcitability caused by impaired ion channel regulation. Due to low specificity of symptoms, diagnosis relies on genetic testing. As there are no standardized GNB1 encephalopathy treatment guidelines, evaluation of different treatment options is based on anecdotal cases. Reviewing different treatment options, deep brain stimulation and intrathecal baclofen pump, as well as some other medications still in preclinical trials, seem to be the most promising. [ABSTRACT FROM AUTHOR]

Introduction: Iron accumulation in the brain has been linked to diabetes, but its role in subcortical structures involved in motor and cognitive functions remains unclear. Quantitative susceptibility mapping (QSM) allows the non-invasive quantification of iron deposition in the brain. This systematic review and metaanalysis examined magnetic susceptibility measured by QSM in the subcortical nuclei of patients with type 2 diabetes mellitus (T2DM) compared with controls. Methods: PubMed, Scopus, and Web of Science databases were systematically searched [following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines] for studies reporting QSM values in the deep gray matter (DGM) regions of patients with T2DM and controls. Pooled standardized mean differences (SMDs) for susceptibility were calculated using fixed-effects meta-analysis models, and heterogeneity was assessed using I2. Sensitivity analyses were conducted, and publication bias was evaluated using Begg's and Egger's tests. Results: Six studies including 192 patients with T2DM and 245 controls were included. This study found a significant increase in iron deposition in the subcortical nuclei of patients with T2DM compared to the control group. The study found moderate increases in the putamen (SMD = 0.53, 95% CI 0.33 to 0.72, p = 0.00) and dentate nucleus (SMD = 0.56, 95% CI 0.27 to 0.85, p = 0.00) but weak associations between increased iron levels in the caudate nucleus (SMD = 0.32, 95% CI 0.13 to 0.52, p = 0.00) and red nucleus (SMD = 0.22, 95% CI 0.00 0.44, p = 0.05). No statistical significance was found for iron deposition alterations in the globus pallidus (SMD = 0.19; 95% CI -0.01 to 0.38; p = 0.06) and substantia nigra (SMD = 0.12, 95% CI -0.10, 0.34, p = 0.29). Sensitivity analysis showed that the findings remained unaffected by individual studies, and consistent increases were observed in multiple subcortical areas. Discussion: QSM revealed an increase in iron in the DGM/subcortical nuclei in T2DM patients versus controls, particularly in the motor and cognitive nuclei, including the putamen, dentate nucleus, caudate nucleus, and red nucleus. Thus, QSM may serve as a potential biomarker for iron accumulation in T2DM patients. However, further research is needed to validate these findings. [ABSTRACT FROM AUTHOR]

To explore the use of quantitative susceptibility mapping (QSM) in assessing changes in brain iron deposits and their association with cognitive function in patients with minimal hepatic encephalopathy (MHE). The study cohort comprised 27 cases with hepatitis B-associated cirrhosis with MHE (MHE group), 25 with hepatitis B-associated cirrhosis without MHE (NMHE group), and 25 healthy controls (HC group). Iron deposits in the bilateral frontal white matter, caudate nucleus (CN), putamen, globus pallidus, thalamus, red nucleus, substantia nigra (SN), hippocampus, and dentate nucleus were measured by QSM. The associations between iron deposition with the time taken to complete number connection tests A (NCT-A) and the score on digital–symbol test (DST) were analysed. Susceptibility values differed significantly in the bilateral CN, left thalamus, right SN, and left hippocampus in the MHE group compared with the other groups and were positively associated with the times taken to complete the NCT-A in the bilateral CN, left thalamus, and right SN and negatively associated with DST scores in the bilateral CN, left TH, and left HP. Reduced cognitive function in MHE patients was significantly associated with abnormally increased iron deposition in certain brain areas. The quantification of brain iron deposition by QSM may thus be an objective and accurate means of evaluating MHE. • MHE patients showed abnormal brain iron deposition. • Regional brain iron deposition was correlated with cognitive impairment. • Confirmed the feasibility of QSM assessment of cognitive function in MHE patients. [ABSTRACT FROM AUTHOR]

Purpose Metabolic abnormalities in hepatic encephalopathy (HE) cause brain edema or demyelinating disease, resulting in symmetric regional cerebral edema (SRCE) on MRI. This study aimed to investigate the usefulness of the clustering analysis of SRCE in predicting the development of brain failure. Materials and Methods MR findings and clinical data of 98 consecutive patients with HE were retrospectively analyzed. The correlation between the 12 regions of SRCE was calculated using the phi (φ) coefficient, and the pattern was classified using hierarchical clustering using the φ2 distance measure and Ward's method. The classified patterns of SRCE were correlated with clinical parameters such as the model for end-stage liver disease (MELD) score and HE grade. Results Significant associations were found between 22 pairs of regions of interest, including the red nucleus and corpus callosum (φ = 0.81, p < 0.001), crus cerebri and red nucleus (φ = 0.72, p < 0.001), and red nucleus and dentate nucleus (φ = 0.66, p < 0.001). After hierarchical clustering, 24 cases were classified into Group I, 35 into Group II, and 39 into Group III. Group III had a higher MELD score (p = 0.04) and HE grade (p = 0.002) than Group I. Conclusion Our study demonstrates that the SRCE patterns can be useful in predicting hepatic preservation and the occurrence of cerebral failure in HE. [ABSTRACT FROM AUTHOR]

Background: Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway. Methods: A total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed. Results: Of the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway. Conclusion: Distant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF. [ABSTRACT FROM AUTHOR]

The cerebellum has been implicated in the regulation of social behavior. Its influence is thought to arise from communication, via the thalamus, to forebrain regions integral in the expression of social interactions, including the anterior cingulate cortex (ACC). However, the signals encoded or the nature of the communication between the cerebellum and these brain regions is poorly understood. Here, we describe an approach that overcomes technical challenges in exploring the coordination of distant brain regions at high temporal and spatial resolution during social behavior. We developed the E-Scope, an electrophysiology-integrated miniature microscope, to synchronously measure extracellular electrical activity in the cerebellum along with calcium imaging of the ACC. This single coaxial cable device combined these data streams to provide a powerful tool to monitor the activity of distant brain regions in freely behaving animals. During social behavior, we recorded the spike timing of multiple single units in cerebellar right Crus I (RCrus I) Purkinje cells (PCs) or dentate nucleus (DN) neurons while synchronously imaging calcium transients in contralateral ACC neurons. We found that during social interactions a significant subpopulation of cerebellar PCs were robustly inhibited, while most modulated neurons in the DN were activated, and their activity was correlated with positively modulated ACC neurons. These distinctions largely disappeared when only non-social epochs were analyzed suggesting that cerebellar-cortical interactions were behaviorally specific. Our work provides new insights into the complexity of cerebellar activation and co-modulation of the ACC during social behavior and a valuable open-source tool for simultaneous, multimodal recordings in freely behaving mice. [ABSTRACT FROM AUTHOR]

Extensive evidence supports the claim that the serum neurofilament light chain (sNfL) can be used as a biomarker to monitor disease severity in patients with spinocerebellar ataxia type 3 (SCA3). However, little is known about the associations between sNfL levels and neurochemical alterations in SCA3 patients. In this study, we performed a cross-sectional study to analyze the association between sNfL and brain metabolic changes in SCA3 patients. The severity of ataxia was assessed by using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). The sNfL levels and brain metabolic changes, represented by N-acetyl aspartate (NAA)/creatine (Cr) and choline complex (Cho)/Cr ratios, were measured by a single-molecule array and proton magnetic resonance spectroscopy, respectively. In this cohort, we observed consistently elevated sNfL levels and reduced brain metabolites in the cerebellar hemispheres, dentate nucleus, and cerebellar vermis. However, this correlation was further validated in the cerebellar cortex after analysis using pairwise comparisons and a Bonferroni correction. Taken together, our results further confirmed that sNfL levels were increased in SCA3 patients and were negatively correlated with metabolic changes in the cerebellar cortex. Our data also support the idea that sNfL levels are a promising potential complementary biomarker for patients with SCA3. [ABSTRACT FROM AUTHOR]

Vigabatrin is an anti-epileptic drug that inhibits the enzyme γ-aminobutyric acid (GABA)-transaminase. The anticonvulsant effect of vigabatrin involves increasing GABA levels and attenuating glutamate–glutamine cycling. Vigabatrin indications include infantile spasms and refractory focal seizures. Despite having a significant role in paediatric epileptology, vigabatrin has adverse effects, such as retinal toxicity, in up to 30% of patients after 1 year of use and brain abnormalities on magnetic resonance imaging (MRI). The percentage of patients with brain abnormalities on MRI varies between 22–32% of children using vigabatrin to treat infantile spasms. Risk factors for presenting these imaging abnormalities are cryptogenic infantile spasms, age <12 months old, high dosage, and possible concomitant hormonal therapy. Clinically, these abnormalities are usually asymptomatic. Histopathological analysis reveals white matter vacuolation and intramyelinic oedema. The typical findings of vigabatrin-associated brain abnormalities on MRI are bilateral and have a symmetrical hyperintense signal on T2-weighted imaging, with diffusion restriction, that often compromise the globi pallidi, thalami, subthalamic nuclei, cerebral peduncles, midbrain, dorsal brainstem, including the medial longitudinal fasciculi, and dentate nuclei of the cerebellum. In this article, the authors intend to review the clinical manifestations, histopathological features, imaging aspects, and differential diagnosis of vigabatrin-associated brain abnormalities on MRI. • Vigabatrin use can be associated with brain abnormalities on MRI. • 22–32% of paediatric patients using vigabatrin are affected. • Brain MRI shows bilateral and symmetrical restricted diffusion in deep central structures. • Globi pallidi, thalami, subthalamic nuclei, brainstem and dentate nuclei can be affected. • These alterations usually resolve in follow-up studies. [ABSTRACT FROM AUTHOR]

Heart, dentate nucleus, and dorsal root ganglia (DRG) are targets of tissue damage in Friedreich ataxia (FA). This report summarizes the histology and histopathology of iron in the main tissues affected by FA. None of the affected anatomical sites reveals an elevation of total iron levels. In the myocardium, a small percentage of fibers shows iron-reactive granular inclusions. The accumulation of larger iron aggregates and fiber invasion cause necrosis and damage to the contractile apparatus. In the dentate nucleus, the principal FA-caused tissue injury is neuronal atrophy and grumose reaction. X-ray fluorescence mapping of iron in the dentate nucleus in FA shows retention of the metal in the center of the collapsed structure. Immunohistochemistry of ferritin, a surrogate marker of tissue iron, confirms strong expression in oligodendrocytes of the efferent white matter of the dentate nucleus and abundance of ferritin-positive microglia in the atrophic gray matter. Iron dysmetabolism in DRG is complex and consists of prominent expression of ferritin in hyperplastic satellite cells and residual nodules, also a loss of the iron export protein ferroportin from the cytoplasm of the remaining DRG nerve cells. [ABSTRACT FROM AUTHOR]

The olivo-cerebellar circuit is thought to play a crucial role in the pathophysiology of essential tremor (ET). Whether olivo-cerebellar circuit dysfunction is also present at rest, in the absence of clinical tremor and linked voluntary movement, remains unclear. Assessing this network in detail with fMRI is challenging, considering the brainstem is close to major arteries and pulsatile cerebrospinal fluid–filled spaces obscuring signals of interest. Here, we used methods tailored to the analysis of infratentorial structures. We hypothesize that the olivo-cerebellar circuit shows altered intra-network connectivity at rest and decreased functional coupling with other parts of the motor network in ET. In 17 ET patients and 19 healthy controls, we investigated using resting state fMRI intracerebellar functional and effective connectivity on a dedicated cerebellar atlas. With independent component analysis, we investigated data-driven cerebellar motor network activations during rest. Finally, whole-brain connectivity of cerebellar motor structures was investigated using identified components. In ET, olivo-cerebellar pathways show decreased functional connectivity compared with healthy controls. Effective connectivity analysis showed an increased inhibitory influence of the dentate nucleus towards the inferior olive. Cerebellar independent component analyses showed motor resting state networks are less strongly connected to the cerebral cortex compared to controls. Our results indicate the olivo-cerebellar circuit to be affected at rest. Also, the cerebellum is "disconnected" from the rest of the motor network. Aberrant activity, generated within the olivo-cerebellar circuit could, during action, spread towards other parts of the motor circuit and potentially underlie the characteristic tremor of this patient group. [ABSTRACT FROM AUTHOR]

The longstanding idea that the cerebral cortex is the main neural correlate of human cognition can be elaborated by comparative analyses along the vertebrate phylogenetic tree that support the view that the cerebello-cerebral system is suited to support non-motor functions more generally. In humans, diverse accounts have illustrated cerebellar involvement in cognitive functions. Although the neocortex, and its transmodal association cortices such as the prefrontal cortex, have become disproportionately large over primate evolution specifically, human neocortical volume does not appear to be exceptional relative to the variability within primates. Rather, several lines of evidence indicate that the exceptional volumetric increase of the lateral cerebellum in conjunction with its connectivity with the cerebral cortical system may be linked to non-motor functions and mental operation in primates. This idea is supported by diverging cerebello-cerebral adaptations that potentially coevolve with cognitive abilities across other vertebrates such as dolphins, parrots, and elephants. Modular adaptations upon the vertebrate cerebello-cerebral system may thus help better understand the neuroevolutionary trajectory of the primate brain and its relation to cognition in humans. Lateral cerebellar lobules crura I-II and their reciprocal connections to the cerebral cortical association areas appear to have substantially expanded in great apes, and humans. This, along with the notable increase in the ventral portions of the dentate nucleus and a shift to increased relative prefrontal-cerebellar connectivity, suggests that modular cerebellar adaptations support cognitive functions in humans. In sum, we show how comparative neuroscience provides new avenues to broaden our understanding of cerebellar and cerebello-cerebral functions in the context of cognition. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this study was to clarify the dentato‐rubro‐thalamic (DRT) pathway in action tremor in comparison to normal controls (NC) and disease controls (i.e., rest tremor) by using multi‐modality magnetic resonance imaging (MRI). Methods: This study included 40 essential tremor (ET) patients, 57 Parkinson's disease (PD) patients (29 with rest tremor, 28 without rest tremor), and 41 NC. We used multi‐modality MRI to comprehensively assess major nuclei and fiber tracts of the DRT pathway, which included decussating DRT tract (d‐DRTT) and non‐decussating DRT tract (nd‐DRTT), and compared the differences in DRT pathway components between action and rest tremor. Results: Bilateral dentate nucleus (DN) in the ET group had excessive iron deposition compared with the NC group. Compared with the NC group, significantly decreased mean diffusivity and radial diffusivity were observed in the left nd‐DRTT in the ET group, which were negatively correlated with tremor severity. No significant difference in each component of the DRT pathway was observed between the PD subgroup or the PD and NC. Conclusion: Aberrant changes in the DRT pathway may be specific to action tremor and were indicating that action tremor may be related to pathological overactivation of the DRT pathway. [ABSTRACT FROM AUTHOR]

Fahr's syndrome affects fewer than 1 in 100,000 people. It is an inherited neurological disorder, which is distinguished by atypical calcium deposition in the movement-controlling areas of brain, that is thalamus, dentate nucleus, basal ganglia, cerebellum, cerebral cortex, hippocampus and subcortical white matter. The majority of patients often experience extrapyramidal symptoms, cerebellar signs, speech difficulty, dementia and neuropsychiatric manifestations. This disease's molecular genetics have not been thoroughly investigated. Typically, young to middle-aged adults are affected though basal ganglia calcification in hypoparathyroidism is quite uncommon. Laboratory results and radiographic brain imaging helps in reaching the diagnosis. The treatment is mainly symptomatic. We present a case of Fahr's syndrome associated with hypoparathyroidism. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the differences in accuracy (trueness and precision) of five different optical impression systems.Materials and Methods: The accuracy of the following optical impression systems was tested: (1) CEREC Bluecam (BL; Dentsply Sirona), (2) CEREC Omnicam (OM, Dentsply Sirona); (3) PlanScan (PL; Planmeca); (4) True Definition Scanner (TD; 3M ESPE); and (5) Trios 3 (TR; 3Shape). A standard plastic study model represented a patient with a fully dentate maxilla (ANA-4 V CER, frasaco). Three clinical situations were simulated: Patient 1 (P1): fully dentate; Patient 2 (P2): anterior partial edentulism (two missing incisors); and Patient 3 (P3): posterior partial edentulism (P3) (missing premolar and molar). The models were scanned with a reference scanner (IScan D104i, Imetric), and the digitalized models were used as reference for all comparisons. Then, optical impressions were made for the three clinical scenarios (n = 10 per group).Results: In situation P1, the TD group provided the highest trueness (180.2 ± 46.3μm). In situation P2, the highest trueness was found in the TD (97.9 ± 27.6 μm) and TR (105 ± 9.5μm) groups, and in situation P3, TR had the highest trueness (P < .05) with a median RMS value of 76.2 ± 5.6 μm. In terms of precision, TR provided the highest precision (P < .05) in all three clinical situations, with RMS values 76.7 ± 26 μm for P1, 46.8 ± 14.1 μm for P2, and 39.7 ± 9.1 μm for P3.Conclusion: Two optical impression systems (TR and TD) were superior to the other tested systems in most of the measurements. However, none of the tested systems was clearly superior with respect to both trueness and precision. [ABSTRACT FROM AUTHOR]

We aimed to systematically characterize the magnetic resonance imaging (MRI) findings in vigabatrin-related neurotoxicity in children and determine the reversibility of lesions based on follow-up images. We evaluated children with a history of refractory seizures who had a brain MRI while on vigabatrin therapy. We included available brain MRI studies before vigabatrin therapy initiation, during vigabatrin treatment, and after vigabatrin was discontinued. A pediatric neuroradiologist systematically assessed images on T2/fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging /apparent diffusion coefficient sequences to identify hyperintense lesions and/or restricted diffusion. The frequency of abnormal signal at each location was determined, as well as the reversibility of these after vigabatrin discontinuation. MRIs of 43 patients were reviewed: 13 before vigabatrin initiation, 18 during treatment, and 12 after vigabatrin discontinuation. In the MRIs acquired during vigabatrin treatment, most lesions on T2/FLAIR occurred in the globus pallidi, thalami, and midbrain. Correspondingly, the most common locations for restricted diffusion were the globus pallidi, thalami, and subthalamic nuclei. On MRI after vigabatrin discontinuation, complete resolution of lesions on T2/FLAIR in all patients was seen in the midbrain, dentate nuclei, subthalamic nuclei, and hypothalami. Complete resolution of restricted diffusion was observed in the globus pallidi, midbrain, dentate nuclei, hippocampi, anterior commissure, and hypothalami. Globus pallidi and thalami are the most commonly affected structures in vigabatrin-related toxicity, and most vigabatrin-related neuroimaging findings are reversible. [ABSTRACT FROM AUTHOR]

Objective: Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is a rare neurodegenerative disease for which there is no specific treatment. Very few cases have been treated with single-target deep brain stimulation (DBS), and the results were not satisfactory. We applied multi-target DBS to an SCA3/MJD patient and performed positron emission computed tomography (PET) before and after DBS to explore the short-term clinical therapeutic effect. Materials andmethods: A 26-year-old right-hand-dominant female with a family history of SCA3/MJD suffered from cerebellar ataxia and dystonia. Genetic testing indicated an expanded CAGtrinucleotide repeat in the ATXN3 gene and a diagnosis of SCA3/MJD. Conservative treatment had no obvious effect; therefore, leads were implanted in the bilateral dentate nucleus (DN) and the globus pallidus internus (GPi) and connected to an external stimulation device. The treatment effect was evaluated in a double-blind, randomized protocol in five phases (over a total of 15 days): no stimulation, GPi, DN, or sham stimulation, and combined GPi and DN stimulation. 18F-fluoro-2-deoxy-d-glucose and dopamine transporter PET, Scale for the Assessment and Rating of Ataxia, Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM), Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), and SF-36 quality of life scores were compared before and after DBS. Results: The Total Scale for the Assessment and Rating of Ataxia scores improved by ~42% (from 24 to 14). The BFMDRS movement scores improved by ~30% (from 40.5 to 28.5). The BFMDRS disability scores improved by ~12.5% (from 16 to 14). Daily living activities were not noticeably improved. Compared with the findings in pre-DBS imaging, 18F-fluoro-2-deoxy-d-glucose uptake increased in the cerebellum, while according to dopamine transporter imaging, there were no significant differences in the bilateral caudate nucleus and putamen. Conclusion: Multi-target acute stimulation (DN DBS and GPi DBS) in SCA3/MJD can mildly improve cerebellar ataxia and dystonia and increase cerebellar metabolism. [ABSTRACT FROM AUTHOR]