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Purpose of Review: This review aims to rediscuss the leading theories concerning the role of basal ganglia and the thalamus in the genesis of aphasic symptoms in the absence of gross anatomical lesions in cortical language areas as assessed by conventional neuroimaging studies., Recent Findings: New concepts in language processing and modern neuroimaging techniques have enabled some progress in resolving the impasse between the current dominant theories: (a) direct and specific linguistic processing and (b) subcortical structures as processing relays in domain-general functions. Of particular interest are studies of connectivity based on functional magnetic resonance imaging (MRI) and tractography that highlight the impact of white matter pathway lesions on aphasia development and recovery. Connectivity studies have put into evidence the central role of the arcuate fasciculus (AF), inferior frontal occipital fasciculus (IFOF), and uncinate fasciculus (UF) in the genesis of aphasia. Regarding the thalamus, its involvement in lexical-semantic processing through modulation of the frontal cortex is becoming increasingly apparent., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To retrospectively explore the role of magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) in analyzing the corticospinal tract injury in acute cerebral anterior circulation infarction in the basal ganglia region and the correlation between DTI parameters and neurological function scores, patients with acute cerebral infarction and stroke had undergone plain MRI and DTI sequence scanning were enrolled. Diffusion tensor tractography was used to perform 3-dimensional reconstruction of bilateral corticospinal tracts (CST). The image data were processed to obtain fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values, and the correlation between the DTI parameters and neurological function scores of National Institutes of Health Stroke Scale (NIHSS) was evaluated. A total of thirty-two patients with acute ischemic cerebral infarction were retrospectively enrolled, including 19 males and 13 females with a mean age 63.22 ± 7.78 years. The CST score was 0 in 2 (6.25%) patients, 1 in 9 (28.13%), 2 in 9 (28.13%), 3 in 7 (21.88%), and 4 in 5 (15.63%). The FA value significantly (P = .01) decreased (0.52 ± 0.03 vs 0.62 ± 0.04) on the ischemic side compared with that on the normal side. A significant (P < .05) difference was detected in the number of nerve fibers (223.3 ± 110.0 vs 246.7 ± 104.4) rather than in the ADC values (0.86 ± 0.06 vs 0.84 ± 0.06) between the ischemic and healthy sides. The FA and ADC values were not significantly (P > .05) different according to the CST scores 0, 1, 2, 3, or 4 between the ischemic and healthy sides. There was a significant (P < .05) negative correlation between the FA value on the infarcted side and the NIHSS score. In conclusion, with the DTI technology, varying degrees of damage to the corticospinal tract at the infarcted side can be detected and important clinical information can be provided for the diagnosis and prognosis of acute cerebral infarction by evaluating the degree of corticospinal tract injury., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant inherited vascular disorder that can involve multiple organs, thus can be associated with so many clinical departments that proper screening and diagnosis of HHT are needed for providing better management of both patients and their family members., Case Presentation: We present a 58-year-old female patient with recurrent paradoxical brain embolism due to HHT. She received aspirin therapy and underwent pulmonary arteriovenous malformation embolization, recovering well and discharged 3 days postoperatively. Though ischemic stroke caused by HHT-induced vascular disorders has been reported, our patient presented with both recurrent paradoxical brain embolisms and radiologic findings of bilateral globus pallidus manganese deposition at the same time, a combination rarely reported. We also review the literature on the clinical features and management of HHT for prompt diagnosis of this genetic disease behind paradoxical embolism., Conclusions: When patients with ischemic stroke, especially recurrent ischemic stroke, have combined arteriovenous malformations (AVMs) in single or multiple organs, or clues for AVMs like manganese deposition in globus pallidus, genetic diseases such as HHT may be the reason for ischemic stroke and shouldn't be missed in the evaluation of embolic sources., (© 2024. The Author(s).)

Down syndrome (DS) is a genetic pathology characterized by various developmental defects. Unlike other clinical problems, intellectual disability is an invariant clinical trait of DS. Impairment of neurogenesis accompanied by brain hypotrophy is a typical neurodevelopmental phenotype of DS, suggesting that a reduction in the number of cells forming the brain may be a key determinant of intellectual disability. Previous evidence showed that fetuses with DS exhibit widespread hypocellularity in brain regions belonging to the temporal lobe memory systems, which may account for the typical explicit memory impairment that characterizes DS. In the current study, we have examined the basal ganglia, the insular cortex (INS), and the cingulate cortex (CCX) of fetuses with DS and age-matched controls (18-22 weeks of gestation), to establish whether cellularity defects involve regions that are not primarily involved in explicit memory. We found that fetuses with DS exhibit a notable hypocellularity in the putamen (-30%) and globus pallidus (-35%). In contrast, no cellularity differences were found in the INS and CCX, indicating that hypocellularity is not ubiquitous in the DS brain. The hypocellularity found in the basal ganglia, which are critically implicated in the control of movement, suggests that such alterations may contribute to the motor abnormalities of DS. The normal cytoarchitecture of the INS and CCX suggests that the alterations exhibited by people with DS in functions in which these regions are involved are not attributable to neuron paucity., (© 2024 Wiley Periodicals LLC.)

Background: Enlarged perivascular spaces (EPVSs) are commonly detected via magnetic resonance imaging. It is unclear whether EPVSs are associated with cognitive impairment within one month after an acute ischemic stroke (AIS) (i.e., early AIS with cognitive impairment (EAIS-CI)). This study explored the severity and location of EPVSs and their association with EAIS-CI severity and provides clinicians with early warning indicators before the onset of typical clinical symptoms in the Chinese population., Methods: The clinical data of 208 patients (176 AIS patients and 32 controls) were prospectively analyzed using the Montreal Cognitive Assessment Beijing version (MoCA-BJ) score as the primary group criterion and the Mini-Mental State Examination (MMSE) score as a supplementary criterion. When EPVS I as the main EPVS type detected by imaging, the basal ganglia (BG) is the area most severely affected. Statistical analysis was conducted on the relevant clinical data., Results: AIS patients were grouped based on MoCA-BJ scores. Age ( p < 0.01), education level ( p = 0.02), EPVS I as the main EPVS type ( p < 0.01), the number of right-sided BG-EPVSs ( p = 0.04), white matter hyperintensities (WMHs) (Fazekas scores: p = 0.02), brain atrophy (global cortical atrophy scores: p < 0.01, Koedam posterior atrophy visual scale scores: p = 0.01, medial temporal lobe atrophy scores: p < 0.01) and AIS lesion volume ( p = 0.01) were significantly greater in the EAIS-CI group than in the EAIS without cognitive impairment group. The cognitive domains of attention ( p = 0.04) and orientation ( p < 0.01) were more closely associated with EPVS I as the main EPVS type. However, multivariate regression analysis did not identify EPVS I as the main EPVS type as the main risk factor for EAIS-CI ( p = 0.098). Grouping by MMSE scores revealed that EPVS I as the main EPVS type was linked to low education level ( p < 0.01) and was significantly associated with EAIS in individuals with cognitive dementia ( p < 0.01)., Conclusions: As a result of multiple factors, EAIS-CI is significantly associated with a low education level, BG-EPVS, WMHs, and worsening brain atrophy severity. Imaging markers, such as the severity of BG-EPVS, can assist in the early diagnosis and assessment of EAIS-CI., Clinical Trial Registration: The study was registered with the China Clinical Trial Registry (https://www.chictr.org.cn/), registration number: ChiCTR2000038819., (© 2024 The Author(s). Published by IMR Press.)

Background: CHANTER (Cerebellar Hippocampal and Basal Nuclei Transient Edema with Restricted diffusion) is a recently described syndrome occurring in the context of drug abuse. While clinical findings are rather unspecific (disorientation, unresponsiveness), MR imaging (MRI) discloses a characteristic pattern (restricted diffusion in the basal ganglia and hippocampi, cerebellar oedema and haemorrhage), allowing for timely diagnosis before complications such as cerebellar swelling and herniation do occur. Here we report a case of CHANTER primarily based on imaging findings, as there was no evidence of drug abuse on admission., Case Presentation: A 62-year-old Patient was admitted to our hospital after being unresponsive at home. Prehospital intubation was performed, which limited neurological assessment. Under these circumstances no obvious symptoms could be determined, i.e. pupils were isocoric and responsive, and there were no signs of seizures. While the initial CT scan was unremarkable, the subsequent MRI scan showed a distinct imaging pattern: moderately enhancing areas in the basal ganglia and hippocampi with diffusion restriction, accompanied by cerebellar haemorrhage and oedema (Figs. 1 and 2). A comprehensive clinical and laboratory work-up was performed, including drug screening, spinal tap, Holter ECG, echocardiography and EEG. The only conspicuous anamnestic finding was a chronic pain syndrome whose medication had been supplemented with opioids two months previously. The opioid medication was discontinued, which led to a rapid improvement in the patient's clinical condition without any further measures. The patient was able to leave the intensive care unit and was discharged 10 days after admission without persistent neurological deficits., Conclusion: Familiarity with typical MRI patterns of toxic encephalopathy in patients from high-risk groups, such as drug abusers, is crucial in emergency neuroradiology. In the presence of typical MRI findings, CHANTER syndrome should be included in the differential diagnosis, even if there is no history of drug abuse, to avoid delay in diagnosis and treatment., (© 2024. The Author(s).)

Background: Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA., Methods: We first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs., Results: Compared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083)., Conclusion: PSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: Pathologic perivascular spaces (PVS), the fluid-filled compartments surrounding brain vasculature, may underlie cognitive decline in Parkinson's disease (PD). However, whether this impacts specific cognitive domains has not been investigated., Objectives: This study examined the relationship of PVS volume at baseline with domain-specific and global cognitive change over 2 years in PD individuals., Methods: A total of 39 individuals with PD underwent 3T T1w magnetic resonance imaging to determine PVS volume fraction (PVS volume normalized to total regional volume) within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, and superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of cognitive domains and global cognitive function at baseline and after 2 years., Results: Higher basal ganglia PVS at baseline was associated with greater decline in attention, executive function, and global cognition scores., Conclusions: While previous reports have associated elevated PVS volume in the basal ganglia with decline in global cognition in PD, our findings show such decline may affect the attention and executive function domains., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Background: Cerebral small vessel disease (CSVD) causes cognitive decline and perivascular space enlargement is one of the image markers for CSVD., Purpose: To search for clinical significance in the time-course augmentation of perivascular space in basal ganglia (BG-PVS) for cognitive decline., Material and Methods: This study population included 179 participants from a community-based cohort, aged 70 years at baseline. They had undergone magnetic resonance imaging (MRI) studies two or three times between 2000 and 2008. Based on the severity of BG-PVS or white matter hyperintensity lesions (WMHL) in 2000, the participants were divided into low-grade or high-grade groups, respectively. In addition, their time-course augmentation was evaluated, and we created a categorical BG-PVS WMHL change score based on their augmentation (1 = neither, 2 = BG-PVS augmentation only, 3 = WMHL augmentation only, 4 = both). Cognitive function was assessed based on the Mini-Mental State Examination (MMSE); the change was defined as the difference between scores in 2000 and 2008. We used simple or multiple regression analysis for MMSE score change according to MRI findings and clinical characteristics that were probably related to cognitive decline., Results: In univariate analysis, MMSE score change was negatively associated with BG-PVS high grade at baseline and BG-PVS WMHL change score 4; this remained significant in multivariate analysis. In the final model based on the Akaike Information Criterion, BG-PVS WMHL change score 4 was associated with a 3.3-point decline in subsequent MMSE score., Conclusions: This study suggested that augmentation in both BG-PVS and WMHL was associated with subsequent cognitive decline., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Previous studies have demonstrated associations between enlarged perivascular spaces (EPVS) and dementias such as Alzheimer's disease. However, an association between EPVS and dementia with Lewy bodies (DLB) has not yet been clarified. We performed a cross-sectional analysis of our prospective study cohort of 109 participants (16 with DLB). We assessed cognitive function, pulse wave velocity (PWV), and brain magnetic resonance imaging features. The relationships between EPVS and DLB were evaluated using multivariable logistic regression analyses. Compared with the non-dementia group, the DLB group was more likely to have EPVS in the basal ganglia. Compared with participants without EPVS, those with EPVS were older and had cognitive impairment and high PWV. In multivariable analyses, EPVS in the basal ganglia was independently associated with DLB. High PWV was also independently associated with EPVS in both the basal ganglia and centrum semiovale. High PWV may cause cerebrovascular pulsatility, leading to accelerated EPVS in DLB participants., (© 2024. The Author(s).)

Although previous studies have suggested that subtype B HIV-1 proviruses in the brain are associated with physiological changes and immune activation accompanied with microgliosis and astrogliosis, and indicated that both HIV-1 subtype variation and geographical location might influence the neuropathogenicity of HIV-1 in the brain. The natural course of neuropathogenesis of the most widespread subtype C HIV-1 has not been adequately investigated, especially for people living with HIV (PLWH) in sub-Saharan Africa. To characterize the natural neuropathology of subtype C HIV-1, postmortem frontal lobe and basal ganglia tissues were collected from nine ART-naïve individuals who died of late-stage AIDS with subtype C HIV-1 infection, and eight uninfected deceased individuals as controls. Histological staining was performed on all brain tissues to assess brain pathologies. Immunohistochemistry (IHC) against CD4, p24, Iba-1, GFAP, and CD8 in all brain tissues was conducted to evaluate potential viral production and immune activation. Histological results showed mild perivascular cuffs of lymphocytes only in a minority of the infected individuals. Viral capsid p24 protein was only detected in circulating immune cells of one infected individual, suggesting a lack of productive HIV-1 infection of the brain even at the late-stage of AIDS. Notably, similar levels of Iba-1 or GFAP between HIV + and HIV- brain tissues indicated a lack of microgliosis and astrogliosis, respectively. Similar levels of CD8 + cytotoxic T lymphocyte (CTL) infiltration between HIV + and HIV- brain tissues indicated CTL were not likely to be involved within subtype C HIV-1 infected participants of this cohort. Results from this subtype C HIV-1 study suggest that there is a lack of productive infection and limited neuropathogenesis by subtype C HIV-1 even at late-stage disease, which is in contrast to what was reported for subtype B HIV-1 by other investigators., (© 2024. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Recent research indicates that some brain structures show alterations in conditions such as Autism Spectrum Disorder (ASD). Among them, are the basal ganglia that are involved in motor, cognitive and behavioral neural circuits., Objective: Review the literature that describes possible volumetric alterations in the basal ganglia of individuals with ASD and the impacts that these changes have on the severity of the condition., Methodology: This systematic review was registered in the design and reported according to the PRISMA Items and registered in PROSPERO (CRD42023394787). The study analyzed data from published clinical, case-contemplate, and cohort trials. The following databases were consulted: PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials, using the Medical Subject Titles (MeSH) "Autism Spectrum Disorder" and "Basal Ganglia". The last search was carried out on February 28, 2023., Results: Thirty-five eligible articles were collected, analyzed, and grouped according to the levels of alterations., Conclusion: The present study showed important volumetric alterations in the basal ganglia in ASD. However, the examined studies have methodological weaknesses that do not allow generalization and correlation with ASD manifestations., (© 2024 International Society for Developmental Neuroscience.)

Although manifesting contrasting phenotypes, Parkinson's disease and dystonia, the two most common movement disorders, can originate from similar pathophysiology. Previously, we demonstrated that lesioning (silencing) of a discrete dorsal region in the globus pallidus (rodent equivalent to globus pallidus externa) in rats and produced parkinsonism, while lesioning a nearby ventral hotspot-induced dystonia. Presently, we injected fluorescent-tagged multi-synaptic tracers into these pallidal hotspots (n = 36 Long Evans rats) and permitted 4 days for the viruses to travel along restricted connecting pathways and reach the motor cortex before sacrificing the animals. Viral injections in the Parkinson's hotspot fluorescent labeled a circumscribed region in the secondary motor cortex, while injections in the dystonia hotspot labeled within the primary motor cortex. Custom probability mapping and N200 staining affirmed the segregation of the cortical territories for Parkinsonism and dystonia to the secondary and primary motor cortices. Intracortical microstimulation localized territories specifically to their respective rostral and caudal microexcitable zones. Parkinsonian features are thus explained by pathological signaling within a secondary motor subcircuit normally responsible for initiation and scaling of movement, while dystonia is explained by abnormal (and excessive) basal ganglia signaling directed at primary motor corticospinal transmission., (© 2024 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Neurofeedback (NF) techniques support individuals to self-regulate specific features of brain activity, which has been shown to impact behavior and potentially ameliorate clinical symptoms. Electrophysiological NF (epNF) may be particularly impactful for patients with Parkinson's disease (PD), as evidence mounts to suggest a central role of pathological neural oscillations underlying symptoms in PD. Exaggerated beta oscillations (12-30 Hz) in the basal ganglia-cortical network are linked to motor symptoms (e.g., bradykinesia, rigidity), and beta is reduced by successful therapy with dopaminergic medication and Deep Brain Stimulation (DBS). PD patients also experience non-motor symptoms related to sleep, mood, motivation, and cognitive control. Although less is known about the mechanisms of non-motor symptoms in PD and how to successfully treat them, low frequency neural oscillations (1-12 Hz) in the basal ganglia-cortical network are particularly implicated in non-motor symptoms. Here, we review how cortical and subcortical epNF could be used to target motor and non-motor specific oscillations, and potentially serve as an adjunct therapy that enables PD patients to endogenously control their own pathological neural activities. Recent studies have demonstrated that epNF protocols can successfully support volitional control of cortical and subcortical beta rhythms. Importantly, this endogenous control of beta has been linked to changes in motor behavior. epNF for PD, as a casual intervention on neural signals, has the potential to increase understanding of the neurophysiology of movement, mood, and cognition and to identify new therapeutic approaches for motor and non-motor symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: We aimed to determine the frequency of cerebellar injury using delayed magnetic resonance imaging (MRI) in children with cerebral palsy, diagnosed with term hypoxic-ischemic injury (HII), and to characterize this for the different MRI patterns of HII., Methods: We retrospectively reviewed delayed MRI scans in children with cerebral palsy, of whom 1175 had term HII. The pattern of HII was classified into basal ganglia-thalamus (BGT) pattern, watershed (WS) pattern, combined BGT/WS, and multicystic HII. Cerebellar location (hemisphere versus vermis) and the MRI characteristics were documented overall and for each of the different patterns of HII, as well as the association with thalamic injury., Results: Cerebellar injury was found in 252 of 1175 (21.4%) (median age 6 years [interquartile range: 3 to 9 years]). Of these, 49% (124 of 252) were associated with a BGT pattern, 13% (32 of 252) with a WS pattern, 28% (72 of 252) with a combined BGT/WS pattern, and 10% (24 of 252) with a multicystic pattern. The vermis was abnormal in 83% (209 of 252), and the hemispheres were abnormal in 34% (86 of 252) (with 17% [43 of 252] showing both vermis and hemispheric abnormality)., Conclusions: Over a fifth of patients with cerebral palsy due to HII had a cerebellar abnormality on delayed MRI, most commonly involving the vermis (83%), and as part of a BGT pattern of injury in just under half of these likely reflecting the association of cerebellar vermis injury with profound insults., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Dementia is common in Parkinson's disease (PD), but there is wide variation in its timing. A critical gap in PD research is the lack of quantifiable markers of progression, and methods to identify early stages of dementia. Atrophy-based magnetic resonance imaging (MRI) has limited sensitivity in detecting or tracking changes relating to PD dementia, but quantitative susceptibility mapping (QSM), sensitive to brain tissue iron, shows potential for these purposes., Objective: The objective of the paper is to study, for the first time, the longitudinal relationship between cognition and QSM in PD in detail., Methods: We present a longitudinal study of clinical severity in PD using QSM, including 59 PD patients (without dementia at study onset), and 22 controls over 3 years., Results: In PD, increased baseline susceptibility in the right temporal cortex, nucleus basalis of Meynert, and putamen was associated with greater cognitive severity after 3 years; and increased baseline susceptibility in basal ganglia, substantia nigra, red nucleus, insular cortex, and dentate nucleus was associated with greater motor severity after 3 years. Increased follow-up susceptibility in these regions was associated with increased follow-up cognitive and motor severity, with further involvement of hippocampus relating to cognitive severity. However, there were no consistent increases in susceptibility over 3 years., Conclusions: Our study suggests that QSM may predict changes in cognitive severity many months prior to overt cognitive involvement in PD. However, we did not find robust longitudinal changes in QSM over the course of the study. Additional tissue metrics may be required together with QSM for it to monitor progression in clinical practice and therapeutic trials. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Alcohol use disorder (AUD) is characterized by cycles of abuse, withdrawal, and relapse. Neuroadaptations in the basal ganglia are observed in AUD; specifically in the putamen, globus pallidus (GP), and ventral pallidum (VP). These regions are associated with habit formation, drug-seeking behaviors, and reward processing. While previous studies have shown the crucial role of glial cells in drug seeking, it remains unknown whether glial cells in the basal ganglia are altered in AUD. Glial cells in the putamen, GP, and VP were examined in human post-mortem tissue of AUD and alcohol remission cases. Immunohistochemistry was performed to analyze cell count, staining intensity, and morphology of microglia and astrocytes, using markers Iba-1 and GFAP. Morphological analysis revealed a significant decrease in microglia cell size and process retraction, indicating activation or a dystrophic microglia phenotype in individuals with AUD compared to controls. Microglia staining intensity was also higher in the GP and VP in AUD cases, whereas microglia staining intensity and cell size in remission cases were not different to control cases. In contrast, no astrocyte changes were observed in examined brain regions for both AUD and remission cases compared to controls. These results suggest alcohol exposure alters microglia, potentially contributing to dysfunctions in the basal ganglia that maintain addiction, and abstinence from alcohol may reverse microglia changes and associated dysfunctions. Overall, this study further characterizes AUD neuropathology and implicates microglia in the putamen, GP, and VP as a potential target for therapy., (© 2024 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background and Purpose: Cerebral infarction in the basal ganglia may cause secondary and delayed neuronal degeneration in the substantia nigra (SN). However, the clinical significance of SN degeneration remains poorly understood., Methods: This retrospective observational study included patients with acute ischemic stroke in the basal ganglia on initial diffusion-weighted imaging who underwent follow-up diffusion-weighted imaging between 4 and 30 days after symptom onset. SN degeneration was defined as a hyperintensity lesion in the SN observed on diffusion-weighted imaging. We compared functional outcomes at 3 months between patients with and without SN degeneration. A poor outcome was defined as a score of 3-6 (functional dependence or death) on the modified Rankin Scale., Results: Of 350 patients with basal ganglia infarction (median age = 74.0 years, 53.7% male), 125 (35.7%) had SN degeneration. The proportion of functional dependence or death was 79.2% (99/125 patients) in patients with SN degeneration, which was significantly higher than that in those without SN degeneration (56.4%, 127/225 patients, p < 0.001). SN degeneration was more frequent in patients with functional dependence or death (99/226 patients, 43.8%) than in those with functional independence (26/124 patients, 21.0%, p < 0.001). Multivariable logistic regression analysis showed a significant association between SN degeneration and functional dependence or death (odds ratio = 2.91, 95% confidence interval = 1.17-7.21, p = 0.021)., Conclusions: The study showed that patients with degeneration of SN were associated with functional dependence or death at 3 months, suggesting that secondary degeneration is a predictor of poor stroke outcomes and a potential therapeutic target., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Aminoacylase-1 deficiency (ACY1D) is an autosomal recessive rare inborn error of metabolism, which is caused by disease-causing variants in the ACY1. This disorder is characterized by increased urinary excretion of specific N-acetyl amino acids. Affected individuals demonstrate heterogeneous clinical manifestations which are primarily neurologic problems. In neuroimaging, corpus callosum hypoplasia, cerebellar vermis atrophy, and delayed myelination of cerebral white matter have been reported., Aims: Finding disease-causing variant and expanding imaging findings in a patient with persistent basal ganglia involvement., Methods: Whole-exome sequencing was performed in order to identify disease-causing variants in an affected 5-year-old male patient who presented with neurologic regression superimposed on neurodevelopmental delay following a febrile illness. He had inability to walk, cognitive impairment, speech delay, febrile-induced seizures, truncal hypotonia, moderate to severe generalized dystonia, and recurrent metabolic decompensation., Results: All metabolic tests were normal except for a moderate metabolic acidosis following febrile illnesses. The results of serial brain magnetic resonance imaging (MRI) at ages 1 and 4.5 years revealed persistent bilateral and symmetric abnormal signals in basal ganglia mainly caudate and globus pallidus nuclei with progression over time in addition to a mild supratentorial atrophy. A homozygous missense variant [NM&#95;000666.3: c.1057C>T; p.(Arg353Cys)] was identified in the ACY1, consistent with aminoacylase-1 deficiency. Variant confirmation in patient and segregation analysis in his family were performed using Sanger sequencing., Conclusions: Our findings expanded the phenotype spectrum of ACY1-related neurodegeneration by demonstrating persistent basal ganglia involvement and moderate to severe generalized dystonia., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Objective: The aim of this study was to clarify the roles of the cerebellum and basal ganglia for temporal integration., Methods: We studied 39 patients with spinocerebellar degeneration (SCD), comprising spinocerebellar atrophy 6 (SCA6), SCA31, Machado-Joseph disease (MJD, also called SCA3), and multiple system atrophy (MSA). Thirteen normal subjects participated as controls. Participants were instructed to tap on a button in synchrony with isochronous tones. We analyzed the inter-tap interval (ITI), synchronizing tapping error (STE), negative asynchrony, and proportion of delayed tapping as indicators of tapping performance., Results: The ITI coefficient of variation was increased only in MSA patients. The standard variation of STE was larger in SCD patients than in normal subjects, especially for MSA. Negative asynchrony, which is a tendency to tap the button before the tones, was prominent in SCA6 and MSA patients, with possible basal ganglia involvement. SCA31 patients exhibited normal to supranormal performance in terms of the variability of STE, which was surprising., Conclusions: Cerebellar patients generally showed greater STE variability, except for SCA31. The pace of tapping was affected in patients with possible basal ganglia pathology., Significance: Our results suggest that interaction between the cerebellum and the basal ganglia is essential for temporal processing. The cerebellum and basal ganglia and their interaction regulate synchronized tapping, resulting in distinct tapping pattern abnormalities among different SCD subtypes., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Research has linked enlarged perivascular spaces (EPVS) to cerebral venous reflux (CVR) in patients with hypertensive intracerebral hemorrhage, but it is unclear whether this association exists in recent small subcortical infarct (RSSI) patients., Objective: This study aimed to investigate the correlation between EPVS and CVR in patients with RSSI., Method: This study included 297 patients, selected from patients with RSSI in the lenticulostriate artery admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University. CVR was assessed by time-of-flight magnetic resonance angiography (TOF-MRA). The relationship between EPVS and CVR was studied using multiple logistic regression analysis., Results: This study included patients with an average age of 59.84±12.27 years, including 201 males (67.7%). CVR was observed in 40 (13.5%) patients. Compared to the group without CVR, the proportions of male patients and patients with a history of smoking and drinking were higher in the CVR group. The proportions of high-grade EPVS in the centrum semiovale region [23 cases (57.5%) vs. 108 cases (42.0%), p =0.067] and the basal ganglia region [30 cases (75.0%) vs. 133 cases (51.8%), p =0.006] were higher in the CVR group. After multiple logistic regression analysis, high-grade EPVS in the basal ganglia region was still associated with CVR (OR, 2.68; 95% CI, 1.22-5.87; p =0.014)., Conclusion: In the population with RSSI, EPVS in basal ganglia is significantly associated with CVR, suggesting a close relationship between venous dysfunction and the formation of EPVS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: To investigate the characteristics of the putative meningeal lymphatics located at the posterior wall of the sigmoid sinus (PML-PSS) in human subjects imaged before and after intravenous administration (IV) of a gadolinium-based contrast agent (GBCA). The appearance of the PML-PSS and the enhancement of the perivascular space of the basal ganglia (PVS-BG) were analyzed for an association with gender, age, and clearance of the GBCA from the cerebrospinal fluid (CSF)., Methods: Forty-two patients with suspected endolymphatic hydrops were included. Heavily T2-weighted 3D-fluid attenuated inversion recovery (hT2w-3D-FLAIR) and 3D-real inversion recovery (IR) images were obtained at pre-administration, immediately post-administration, and at 4 and 24 hours after IV-GBCA. The appearance of the PML-PSS and the presence of enhancement in the PVS-BG were analyzed for a relationship with age, gender, contrast enhancement of the CSF at 4 hours after IV-GBCA, and the washout ratio of the GBCA in the CSF from 4 to 24 hours after IV-GBCA., Results: The PML-PSS and PVS-BG were seen in 23 of 42 and 21 of 42 cases, respectively, at 4 hours after IV-GBCA. In all PML-PSS positive cases, hT2w-3D-FLAIR signal enhancement was highest at 4 hours after IV-GBCA. A multivariate analysis between gender, age, CSF signal elevation at 4 hours, and washout ratio indicated that only the washout ratio was independently associated with the enhancement of the PML-PSS or PVS-BG. The odds ratios (95% CIs; P value) were 4.09 × 10 -5 (2.39 × 10 -8 - 0.07; 0.0078) for the PML-PSS and 1.7 × 10 -4 (1.66 × 10 -7 - 0.174; 0.014) for the PVS-BG., Conclusion: The PML-PSS had the highest signal enhancement at 4 hours after IV-GBCA. When the PML-PSS was seen, there was also often enhancement of the PVS-BG at 4 hours after IV-GBCA. Both observed enhancements were associated with delayed GBCA excretion from the CSF.

Background: Enlarged perivascular spaces (EPVS) of the brain may be involved in dementia, such as Alzheimer's disease and cerebral small vessel disease (CSVD). Hypertension has been reported to be a risk factor for dementia and CSVD, but the association between blood pressure (BP) and perivascular spaces is still unclear. The aim of this study was to determine the association between BP and EPVS volumes and to examine the interactions of relevant factors., Methods: A total of 9296 community-dwelling subjects aged ≥65 years participated in a brain magnetic resonance imaging and health status screening examination. Perivascular volume was measured using a software package based on deep learning that was developed in-house. The associations between BP and EPVS volumes were examined by analysis of covariance and multiple regression analysis., Results: Mean EPVS volumes increased significantly with rising systolic and diastolic BP levels ( P for trend = .003, P for trend<.001, respectively). In addition, mean EPVS volumes increased significantly for every 1-mmHg-increment in systolic and diastolic BPs (both P values <.001). These significant associations were still observed in the sensitivity analysis after excluding subjects with dementia., Conclusions: The present data suggest that higher systolic and diastolic BP levels are associated with greater EPVS volumes in cognitively normal older people., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Toshiharu Ninomiya received funds from the Japan Agency for Medical Research and Development and Suntory Holdings Limited (Osaka, Japan). The other authors assert that they have no competing interests.

Excessive neural synchronization of neural populations in the beta (β) frequency range (12-35 Hz) is intimately related to the symptoms of hypokinesia in Parkinson's disease (PD). Studies have shown that delayed feedback stimulation strategies can interrupt excessive neural synchronization and effectively alleviate symptoms associated with PD dyskinesia. Work on optimizing delayed feedback algorithms continues to progress, yet it remains challenging to further improve the inhibitory effect with reduced energy expenditure. Therefore, we first established a neural mass model of the cortex-basal ganglia-thalamus-pedunculopontine nucleus (CBGTh-PPN) closed-loop system, which can reflect the internal properties of cortical and basal ganglia neurons and their intrinsic connections with thalamic and pedunculopontine nucleus neurons. Second, the inhibitory effects of three delayed feedback schemes based on the external globus pallidum (GPe) on β oscillations were investigated separately and compared with those based on the subthalamic nucleus (STN) only. Our results show that all four delayed feedback schemes achieve effective suppression of pathological β oscillations when using the linear delayed feedback algorithm. The comparison revealed that the three GPe-based delayed feedback stimulation strategies were able to have a greater range of oscillation suppression with reduced energy consumption, thus improving control performance effectively, suggesting that they may be more effective for the relief of Parkinson's motor symptoms in practical applications., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Anatomical taxonomy is a practical tool that has successfully guided clinical decision-making for patients with brain arteriovenous malformations and brainstem cavernous malformations (CMs). Deep CMs are similarly complex lesions that are difficult to access and highly variable in size, shape, and position. The authors propose a novel taxonomy for deep CMs in the basal ganglia based on clinical presentation (syndromes) and anatomical location., Methods: The taxonomy system was developed and applied to an extensive 2-surgeon experience over 19 years (2001-2019). Lesions involving the basal ganglia were identified and subtyped on the basis of the predominant superficial presentation identified on preoperative MRI. Three subtypes of basal ganglia CMs were defined: caudate (31, 57%), putaminal (16, 30%), and pallidal (7, 13%). Neurological outcomes were assessed using the modified Rankin Scale (mRS). Postoperative mRS scores ≤ 2 were defined as a favorable outcome, and scores > 2 were defined as a poor outcome. Clinical and surgical characteristics and neurological outcomes were compared among subtypes., Results: Fifty-four basal ganglia lesions were identified in 54 patients. Each basal ganglia CM subtype was associated with a recognizable constellation of neurological symptoms. The most common symptoms at presentation were severe or worsening headaches (25, 43%), mild hemiparesis (13, 24%), seizures (7, 13%), and dysmetria or ataxia (6, 11%). Patients with caudate CMs were the most likely to present with headaches and constitutional symptoms. Patients with putaminal CMs were the most likely to present with hemibody sensory deficits and dysmetria or ataxia. Patients with pallidal CMs were the most likely to present with mild hemiparesis and visual field deficits. A single surgical approach was preferred (> 80% of cases) for each basal ganglia subtype: caudate (contralateral transcallosal-transventricular, 28/31, 90%), putaminal (transsylvian-anterior transinsular, 13/16, 81%), and pallidal (transsylvian supracarotid-infrafrontal, 7/7, 100%). Most patients with follow-up had stable or improved mRS scores postoperatively (94%, 44/47); mRS scores of > 2 at final follow-up did not differ among the 3 basal ganglia subtypes., Conclusions: The study confirms the authors' hypothesis that this taxonomy for basal ganglia CMs meaningfully guides the selection of surgical approach and resection strategy. Furthermore, the proposed taxonomy can increase the diagnostic acumen at the patient bedside, help identify optimal surgical approaches, enhance the consistency of clinical communications and publications, and improve patient outcomes.

Background: Perinatal hypoxic ischemic injury (HII) has a higher prevalence in the developing world. One of the primary concepts for suggesting that an imaging pattern reflects a global insult to the brain is when the injury is noted to be bilateral and symmetric in distribution. In the context of HII in term neonates, this is either bilateral symmetric ( a ) peripheral/watershed (WS) injury or ( b ) bilateral symmetric basal-ganglia-thalamus (BGT) pattern, often with the peri-Rolandic and hippocampal injury. Unilateral, asymmetric, or unequal distribution of injury may therefore be misdiagnosed as perinatal arterial ischemic stroke., Objectives: We aimed to determine the prevalence of unequal cerebral injury in HII, identify patterns, and determine their relationship with existing classification of HII., Materials and Methods: Review of brain magnetic resonance imaging from a database of children with HII. Reports with any unequal pattern of injury were included and further classified as a unilateral, bilateral asymmetric, or symmetric but unequal degree pattern of HII., Results: A total of 1213 MRI scans in patients with a diagnosis of HII revealed 156 (13%) with unequal involvement of the hemispheres: unilateral in 2 of 1213 (0.2%) (involvement only in the WS), asymmetric in 48 of 1213 (4%) (WS in 6 [0.5%], BGT in 4 [0.3%], and combined BGT and WS in 38 [3.1%]), and bilateral symmetric but unequal degree in 106 of 1213 (8.7%) (WS in 20 [1.6%], BGT in 17 [1.4%], and combined BGT and WS in 69 [5.7%])., Conclusions: The majority of children with cerebral palsy due to HII demonstrate a characteristic bilateral symmetric pattern of injury. In our study, 13% demonstrated an unequal pattern. Differentiation from perinatal arterial ischemic stroke, which is mostly unilateral and distributed typically in the middle cerebral artery territory, should be possible and recognition of the typical BGT or WS magnetic resonance imaging patterns should add confidence to the diagnosis, in such scenarios., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Inherited and Acquired Choreas: Paolo Claudio M. de Gusmao, Jeff L. Waugh Seminars in Pediatric Neurology Volume 25, April 2018, Pages 42-53 Chorea is a symptom of a broad array of genetic, structural, and metabolic disorders. While chorea can result from systemic illness and damage to diverse brain structures, injury to the basal ganglia, especially the putamen or globus pallidus, appears to be a uniting features of these diverse neuropathologies. The timing of onset, rate of progression, and the associated neurological or systemic symptoms can often narrow the differential diagnosis to a few disorders. Recognizing the correct etiology for childhood chorea is critical, as numerous disorders in this category are potentially curable, or are remediable, with early treatment., Competing Interests: Declaration of Competing Interest All listed authors have confirmed that they have no disclosures, no financial relationships with parties that could potentially profit or benefit from this work, and no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There is growing interest in the use of natural products for the treatment of Parkinson's disease (PD). Mucuna pruriens has been used in the treatment of humans with PD. The goal of this study was to determine if daily oral treatment with an extract of Mucuna pruriens, starting after the MPTP-induced loss of nigrostriatal dopamine in male mice, would result in recovery/restoration of motor function, tyrosine hydroxylase (TH) protein expression in the nigrostriatal pathway, or glutamate biomarkers in both the striatum and motor cortex. Following MPTP administration, resulting in an 80 % loss of striatal TH, treatment with Mucuna pruriens failed to rescue either striatal TH or the dopamine transporter back to the control levels, but there was restoration of gait/motor function. There was an MPTP-induced loss of TH-labeled neurons in the substantia nigra pars compacta and in the number of striatal dendritic spines, both of which failed to be recovered following treatment with Mucuna pruriens. This Mucuna pruriens-induced locomotor recovery following MPTP was associated with restoration of two striatal glutamate transporter proteins, GLAST (EAAT1) and EAAC1 (EAAT3), and the vesicular glutamate transporter 2 (Vglut2) within the motor cortex. Post-MPTP treatment with Mucuna pruriens, results in locomotor improvement that is associated with recovery of striatal and motor cortex glutamate transporters but is independent of nigrostriatal TH restoration., Competing Interests: Declaration of competing interest None., (Published by Elsevier Inc.)

Background: Parkinson's disease (PD) rest tremor emerges from pathological activity in the basal ganglia and cerebello-thalamo-cortical circuits. A well-known clinical feature is the waxing and waning of PD tremor amplitude, but the mechanisms that drive this variability are unclear. Previous work has shown that arousal amplifies PD tremor by increasing between-network connectivity. Furthermore, brain states in PD are biased toward integration rather than segregation, a pattern that is also associated with increased arousal., Objective: The aim was to test the hypothesis that fluctuations in integrative brain states and/or arousal drive spontaneous fluctuations in PD rest tremor., Methods: We compared the temporal relationship between cerebral integration, the ascending arousal system, and tremor, both during cognitive load and in the resting state. In 40 tremor-dominant PD patients, we performed functional magnetic resonance imaging using concurrent tremor recordings and proxy measures of the ascending arousal system (pupil diameter, heart rate). We calculated whole-brain dynamic functional connectivity and used graph theory to determine a scan-by-scan measure of cerebral integration, which we related to the onset of tremor episodes., Results: Fluctuations in cerebral integration were time locked to spontaneous changes in tremor amplitude: cerebral integration increased 13 seconds before tremor onset and predicted the amplitude of subsequent increases in tremor amplitude. During but not before tremor episodes, pupil diameter and heart rate increased and correlated with tremor amplitude., Conclusions: Integrative brain states are an important cerebral environment in which tremor-related activity emerges, which is then amplified by the ascending arousal system. New treatments focused on attenuating enhanced cerebral integration in PD may reduce tremor. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: T1-hyperintensity of the basal ganglia (BG) due to manganese deposition is a known radiologic finding in patients with hereditary hemorrhagic telangiectasia (HHT), but risk factors and associated clinical manifestations are unclear. This study conducted a quantitative analysis of the association of T1-hyperintensity in HHT patients with specific risk factors, signs, and symptoms., Methods: Patients seen at our center between 2005 and 2020 with a definitive diagnosis of HHT who had an available non-contrast T1-weighted brain MRI were included. Hyperintensity was evaluated using oval regions of interest measurements. The BG: thalamus intensity ratio was used to quantitatively evaluate T1-hyperintensity. Patient laboratory values and clinical findings were collected from electronic medical records. Hyperintensity was analyzed for its association with laboratory values, and clinical findings. Variables were analyzed through regression analysis., Results: A total of 239 patients were included in this study. On 1.5 T scanners, values that were significant on multivariable regression analysis were age (p < .001), hepatic AVMs (p < .001), iron deficiency anemia (p = .0021), and cirrhosis (p = .016). On 3 T scanners, values that were significant on multivariable analysis were hepatic AVMs (p = .0024) and cirrhosis (p = .0056). On 3 T scanners, hyperintensity was significantly associated with tremor (OR = 1.17, p = .033), restless leg syndrome (OR = 1.22, p = .0086), and memory problems (OR = 1.17, p = .046)., Conclusions: BG hyperintensity due to manganese deposition is significantly associated with hepatic risk factors on 1.5 T and 3 T scanners and iron deficiency anemia on 1.5 T scanners. On 3 T scanners, T1-hyperintensity is associated with neuropsychiatric signs and symptoms, such as tremor, restless leg syndrome, and memory problems., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This paper presents a male, immunocompetent case aged 62-year-old with cryptococcal granuloma in the basal ganglia. No cryptococcal infection occurred in other areas. The diagnosis was made by biopsy. Cryptococcal granuloma was tough and unsuitable for sterotactic biopsy. The patient died of postoperative bleeding and we suggest avoiding stereotactic biopsy of lesions suspected of being cryptococcal granulomas.

Mutations in tubulin alpha 4a (TUBB4A) result in a spectrum of leukodystrophies, including Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC), resulting from a recurring mutation p.Asp249Asn (TUBB4A D249N ). H-ABC presents with dystonia, motor and cognitive impairment and pathological features of hypomyelination and loss of cerebellar and striatal neurons. We have generated three induced pluripotent stem cell (iPSC) lines from fibroblast and peripheral blood mononuclear cells (PBMCs) of individuals with TUBB4A D249N mutation. The iPSCs were assessed to confirm a normal karyotype, pluripotency, and trilineage differentiation potential. The iPSCs will allow for disease modeling, understanding mechanisms and testing of therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Perivascular spaces (PVS) and their enlargement (EPVS) have been gaining interest as EPVS can be visualized non-invasively by magnetic resonance imaging (MRI) when viewing T-2-weighted images. EPVS are most commonly observed in the regions of the basal ganglia and the centrum semiovale; however, they have also been identified in the frontal cortex and hippocampal regions. EPVS are known to be increased in aging and hypertension, and are considered to be a biomarker of cerebral small vessel disease (SVD). Interest in EPVS has been significantly increased because these PVS are now considered to be an essential conduit necessary for the glymphatic pathway to provide the necessary efflux of metabolic waste. Metabolic waste includes misfolded proteins of amyloid beta and tau that are known to accumulate in late-onset Alzheimer's disease (LOAD) within the interstitial fluid that is delivered to the subarachnoid space and eventually the cerebral spinal fluid (CSF). The CSF acts as a sink for accumulating neurotoxicities and allows clinical screening to potentially detect if LOAD may be developing early on in its clinical progression via spinal fluid examination. EPVS are thought to occur by obstruction of the PVS that associates with excessive neuroinflammation, oxidative stress, and vascular stiffening that impairs flow due to a dampening of the arterial and arteriolar pulsatility that aids in the convective flow of the metabolic debris within the glymphatic effluxing system. Additionally, increased EPVS has also been associated with Parkinson's disease and non-age-related multiple sclerosis (MS).

The caudolenticular (or transcapsular) gray bridges (CLGBs) connect the caudate nucleus (CN) and putamen across the internal capsule. The CLGBs function as the main efferent terminus from premotor and supplementary motor area cortex to the basal ganglia (BG). We conjectured if inherent variations in numbers and sizes of CLGBs could contribute to abnormal cortical-subcortical connectivity in Parkinson's disease (PD), a neurodegenerative disorder featuring a hindrance of BG processing. However, there are no literature accounts of normative anatomy and morphometry of CLGBs. We therefore retrospectively analyzed axial and coronal 3T fast spoiled gradient-echo magnetic resonance images (MRIs) of 34 healthy individuals for bilateral CLGBs symmetry, their numbers, dimensions of thickest and longest bridge, and axial surface areas of CN head and putamen. We calculated Evans' index (EI) to account for any brain atrophy. We statistically tested associations between sex or age and measured dependent variables, and linear correlations between all measured variables (significance at p < 0.05). Study subjects were F:M = 23:11 with mean age 49.9 years. All EI's were normal (<0.3). All but three CLGBs were bilaterally symmetrical with a mean 7.4 CLGBs per side. Mean CLGBs thickness and lengths were 1.0 and 4.6 mm, respectively; CN head and putamen areas were 205 and 382.0 mm 2 , respectively. Females had thicker CLGBs (p = 0.02) but we found no significant interactions between sex or age and measured dependent variables, and no correlations between CN head or putamen areas and CLGBs dimensions. These normative MRI dimensions of the CLGBs will help guide future studies on the possible role of CLGBs morphometry in PD predisposition., (© 2023 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

In neurodegenerative diseases, the characterization of the prodromal phase is essential for the future application of disease-modifying therapies. X-linked dystonia-parkinsonism is a hereditary neurodegenerative movement disorder characterized by severe adult-onset dystonia accompanied by parkinsonism. Distinct striatal and pallidal atrophy is present already in early disease stages indicating a long-lasting presymptomatic degenerative process. To gain insight into the prodromal phase of X-linked dystonia-parkinsonism, structural and iron-sensitive magnetic resonance imaging (MRI) was performed in 10 non-manifesting carriers and 24 healthy controls in a double-blind fashion. Seventeen patients with X-linked dystonia-parkinsonism were recruited to replicate previous findings of basal ganglia pathology and iron accumulation. Age at onset was estimated in non-manifesting carriers and patients using the repeat length of the hexanucleotide expansion and 3 single-nucleotide polymorphisms associated with age at onset. Voxel-based morphometry and subcortical volumetry showed striatal and pallidal atrophy in non-manifesting carriers (~10%) and patients (~40%). Substantia nigra volume was similarly reduced in patients (~40%). Caudate volume correlated with time to estimated onset in non-manifesting carriers. Susceptibility-weighted imaging confirmed iron deposition in the anteromedial putamen in patients. Non-manifesting carriers also showed small clusters of iron accumulation in the same area after lowering the statistical threshold. In conclusion, basal ganglia atrophy and iron accumulation precede the clinical onset of X-linked dystonia-parkinsonism and can be detected years before the estimated disease manifestation. It thereby highlights the potential of multimodal imaging to identify clinically unaffected mutation carriers with incipient neurodegeneration and to monitor disease progression independent of clinical measures. Longitudinal studies are needed to further elucidate the onset and progression rate of neurodegeneration in prodromal X-linked dystonia-parkinsonism. ANN NEUROL 2023;93:999-1011., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Purpose: We aimed to investigate the association between perivascular space (PVS) visible on MRI and brain atrophy or morphological change using quantitative indexes., Method: This population-based cohort study included 216 older participants. The PVS in basal ganglia (BG-PVS) and cerebral white matter (WM-PVS) was evaluated using a four-point visual rating scale. We segmented brain parenchyma and CSF, and calculated the CSF/intracranial volume ratio, which represents atrophic change. WM lesions were classified using the Fazekas scale. We introduced a new category "idiopathic normal pressure hydrocephalus (iNPH)-like conformation", which was based on two quantitative indexes: Evans index and callosal angle. The association between PVS grade and demographic or morphological factors was evaluated., Results: A stepwise increase in the CSF/intracranial volume ratio with BG-PVS grade progression and a stepwise decrease with WM-PVS grade progression were observed. A higher CSF/intracranial volume ratio was significantly related to a higher BG-PVS grade in a univariate analysis, but this significance disappeared in a multivariate analysis. The iNPH-like group was significantly related to a lower WM-PVS grade in a univariate analysis, and this significance remained in a multivariate analysis., Conclusions: The association between BG-PVS enlargement and atrophic changes was verified. On the contrary, WM-PVS showed a different trend, and a lower WM-PVS grade was associated with an iNPH-like conformation. This result implies that the less-visible WM-PVS on imaging as well as BG-PVS enlargement would reflect abnormal brain change., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Parkinson's disease is a progressive neurodegenerative disorder caused by the degeneration of dopaminergic neurons. This leads to the pathogenesis of multiple basal ganglia-thalamomotor loops and diverse neurotransmission alterations. Dopamine replacement therapy, and on top of that, levodopa and l-3,4-dihydroxyphenylalanine (L-DOPA), is the gold standard treatment, while it develops numerous complications. Levodopa-induced dyskinesia (LID) is well-known as the most prominent side effect. Several studies have been devoted to tackling this problem. Studies showed that metabotropic glutamate receptor 5 (mGluR5) antagonists and 5-hydroxytryptamine receptor 1B (5HT1B) agonists significantly reduced LID when considering the glutamatergic overactivity and compensatory mechanisms of serotonergic neurons after L-DOPA therapy. Moreover, it is documented that these receptors act through an adaptor protein called P11 (S100A10). This protein has been thought to play a crucial role in LID due to its interactions with numerous ion channels and receptors. Lately, experiments have shown successful evidence of the effects of P11 blockade on alleviating LID greater than 5HT1B and mGluR5 manipulations. In contrast, there is a trace of ambiguity in the exact mechanism of action. P11 has shown the potential to be a promising target to diminish LID and prolong L-DOPA therapy in parkinsonian patients owing to further studies and experiments., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To explore the clinical characteristics and genetic etiology of a patient with adolescent-onset hypomyelinated leukodystrophy with atrophy of basal ganglia and cerebellum (H-ABC)., Methods: A patient who was diagnosed with H-ABC in March 2018 at the First Affiliated Hospital of Nanjing Medical University was selected as the study subject. Clinical data was collected. Peripheral venous blood samples of the patient and his parents were collected. The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing., Results: The patient, a 31-year-old male, had manifested with developmental retardation, cognitive decline and abnormal gait. WES revealed that he has harbored a heterozygous c.286G>A variant of the TUBB4A gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Analysis with SIFT online software indicated the amino acid encoded by this variant is highly conserved among various species. This variant has been recorded by the Human Gene Mutation Database (HGMD) with a low population frequency. The 3D structure constructed by PyMOL software showed that the variant has a harmful effect on the structure and function of the protein. According to the guidelines formulated by the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic., Conclusion: The c.286G>A (p.Gly96Arg) variant of the TUBB4A gene probably underlay the hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum in this patient. Above finding has enriched the spectrum of TUBB4A gene variants and enabled early definitive diagnosis of this disorder.

Background Mounting evidence suggests that perivascular spaces (PVSs) visible at MRI reflect the function of the glymphatic system. Understanding PVS burden in neonates may guide research on early glymphatic-related pathologic abnormalities. Purpose To perform a visual and volumetric evaluation of PVSs that are visible at MRI in neonates and to evaluate potential associations with maturation, sex, and preterm birth. Materials and Methods In this retrospective study, T2-weighted brain MRI scans in neonates from the Developing Human Connectome Project were used for visual grading (grades 0-4) of PVSs in the basal ganglia (BG) and white matter (WM) and for volumetric analysis of BG PVSs. The BG PVS fraction was obtained by dividing the BG PVS volume by the deep gray matter volume. The association between postmenstrual age at MRI and BG PVS burden was evaluated using linear regression. PVS burden was compared according to sex and preterm birth using the Mann-Whitney test. Results A total of 244 neonates were evaluated (median gestational age at birth, 39 weeks; IQR, 6 weeks; 145 male neonates; 59%), including 88 preterm neonates (median gestational age at birth, 33 weeks; IQR, 6 weeks; 53 male neonates; 60%) and 156 term neonates (median gestational age at birth, 40 weeks; IQR, 2 weeks; 92 male neonates; 59%). For BG PVSs, all neonates showed either grade 0 (90 of 244; 37%) or grade 1 (154 of 244; 63%), and for WM PVSs, most neonates showed grade 0 (227 of 244; 93%). The BG PVS fraction demonstrated a negative relationship with postmenstrual age at MRI ( r = -0.008; P < .001). No evidence of differences was found between the sexes for BG PVS volume ( P = .07) or BG PVS fraction ( P = .28). The BG PVS volume was smaller in preterm neonates than in term neonates (median, 45.3 mm 3 [IQR, 15.2 mm 3 ] vs 49.9 mm 3 [IQR, 21.3 mm 3 ], respectively; P = .04). Conclusion The fraction of perivascular spaces (PVSs) in the basal ganglia (BG) was lower with higher postmenstrual age at MRI. Preterm birth affected the volume of PVSs in the BG, but sex did not. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Huisman in this issue.

A 3-year-old spayed female domestic short-haired cat presented with a head turning to the left, circling to the right, seizures, and opisthotonos for approximately one month. Neurological examination revealed a deficit in the postural reaction of the left limbs and visual abnormalities. Forensic computed tomography revealed a hyperattenuating round mass of 1.3 cm diameter with a hypoattenuating center in the right hemisphere. Histopathology showed multifocal granuloma lesions with the major mass mostly affecting the right basal ganglia. Cryptococcus neoformans variety grubii molecular type VNI/ST31 was isolated from the cryptococcal granulomas. This report highlights the epidemiological distribution and differential diagnosis of a feline central nervous system cryptococcosis caused by C. neoformans that occurred in an Asian country.