Cerebellar Peduncle Research Articles

β-carbolines that enhance GABAA receptor response expressed in oligodendrocytes promote remyelination in an in vivo rat model of focal demyelination.

Demyelination is typically followed by a remyelination process through mature oligodendrocytes (OLs) differentiated from precursor cells (OPCs) recruited into the lesioned areas, however, this event usually results in uncompleted myelination. Potentiation of the remyelination process is an important target for designing effective therapeutic strategies against white matter loss. Here, it was evaluated the remyelinating effect of different β-carbolines that present differential allosteric modulation on the GABAA receptor expressed in OLs. For this, we used a focalized demyelination model in the inferior cerebellar peduncle (i.c.p.) of rats (DRICP model), in which, demyelination by ethidium bromide (0.05%) stereotaxic injection was confirmed histologically by staining with Black-Gold II (BGII) and toluidine blue. In addition, a longitudinal analysis with diffusion-weighted magnetic resonance imaging (dMRI) was made by computing fractional anisotropy (FA), apparent diffusion coefficient (ADC) and diffusivity parameters to infer i.c.p. microstructural changes. First, dMRI analysis revealed FA decreases together with ADC and radial diffusivity (RD) increases after demyelination, which correlates with histological BGII observations. Then, we evaluated the effect produced by three allosteric GABAA receptor modulators, the N-butyl-β-carboline-3-carboxylate (β-CCB), ethyl 9H-pyrido [3,4-b]indole-3-carboxylate (β-CCE), and 4-ethyl-6,7-dimethoxy-9H-pyrido [3,4-b]indole-3-carboxylic acid methyl ester (DMCM). The results indicated that daily systemic β-CCB (1 mg/Kg) or β-CCE (1 mg/Kg) administration for 2 weeks, but not DMCM (0.35 mg/Kg), in lesioned animals increased FA and decreased ADC or RD, suggesting myelination improvement. This was supported by BGII staining analysis that showed a recovery of myelin content. Also, it was quantified by immunohistochemistry both NG2+ and CC1+ cellular population in the different experimental sceneries. Data indicated that either β-CCB or β-CCE, but not DMCM, produced an increase in the population of CC1+ cells in the lesioned area. Finally, it was also calculated the g-ratio of myelinated axons and observed a similar value in those lesioned animals treated with β-CCB or β-CCE compared to controls. Thus, using the DRICP model, it was observed that either β-CCB or β-CCE, positive modulators of the GABAA receptor in OLs, had a potent promyelinating effect.

Cognitive outcome and its neural correlates after cardiorespiratory arrest in childhood.

Hypoxia-ischaemia (HI) can result in structural brain abnormalities, which in turn can lead to behavioural deficits in various cognitive and motor domains, in both adult and paediatric populations. Cardiorespiratory arrest (CA) is a major cause of hypoxia-ischaemia in adults, but it is relatively rare in infants and children. While the effects of adult CA on brain and cognition have been widely studied, to date, there are no studies examining the neurodevelopmental outcome of children who suffered CA early in life. Here, we studied the long-term outcome of 28 children who suffered early CA (i.e., before age 16). They were compared to a group of control participants (n=28) matched for age, sex and socio-economic status. The patient group had impairments in the domains of memory, language and academic attainment (measured using standardised tests). Individual scores within the impaired range were most commonly found within the memory domain (79%), followed by academic attainment (50%), and language (36%). The patient group also had reduced whole brain grey matter volume, and reduced volume and fractional anisotropy of the white matter. In addition, lower performance on memory tests was correlated with bilaterally reduced volume of the hippocampi, thalami, and striatum, while lower attainment scores were correlated with bilateral reduction of fractional anisotropy in the superior cerebellar peduncle, the main output tract of the cerebellum. We conclude that patients who suffered early CA are at risk of developing specific cognitive deficits associated with structural brain abnormalities. RESEARCH HIGHLIGHTS: Our data shed light on the long-term outcome and associated neural mechanisms after paediatric hypoxia-ischaemia as a result of cardiorespiratory arrest. Patients had impaired scores on memory, language and academic attainment. Memory impairments were associated with smaller hippocampi, thalami, and striatum. Lower academic attainment correlated with reduced fractional anisotropy of the superior cerebellar peduncle.

A Machine Learning Model for Predicting Major Depressive Disorder Using Diffusion-Tensor Imaging Data

IntroductionMajor Depressive Disorder (MDD) stands as a prevalent psychiatric condition within the general population. Despite extensive research efforts, the identification of definitive diagnostic biomarkers for depressive disorders remains elusive. Currently, machine learning methods are gaining prominence in the diagnosis of medical illnesses.ObjectivesThis study aims to construct a machine learning-based prediction model for Major Depressive Disorder (MDD) by harnessing diffusion tensor imaging (DTI) data.MethodsThe DTI datasets comprising MDD (N=83) and Healthy Control (N=70) groups were procured from the cohort study of Anxiety and Depression conducted at the National Center for Mental Health in South Korea. A machine learning method using a decision tree algorithm was employed to select relevant brain regions and establish a robust diagnostic model. Features associated with white matter (WM) tracts were chosen through recursive feature elimination.Results Demographic characteristics, including age, sex, and handedness, displayed no significant differences between the MDD and Healthy Control groups. However, the total score of the Beck Depression Inventory was notably higher in individuals with MDD compared to Healthy Controls. A diagnostic model was crafted using the decision tree algorithms to distinguish between the two groups. The model demonstrated the following classification performance metrics: accuracy (65.6% ± 8.5), sensitivity (66.6% ± 12.5), and specificity (64.7% ± 13.6). Furthermore, through recursive feature elimination, specific neuroanatomical features tied to brain structures such as the inferior cerebellar peduncle, posterior thalamic radiation, cingulum (hippocampus), uncinate fasciculus, and tapetum were identified.ConclusionsDespite of limited performance of classification, a machine learning-based approach could provide insights into the development of a diagnostic model for MDD using neuroimaging data. Furthermore, these features, derived from DTI-derived data, may have implications for understanding the neural underpinnings of major depressive disorder.Disclosure of InterestNone Declared

Alterations of the cerebral microstructure in patients with noise-induced hearing loss: A diffusion tensor imaging study.

To explore the changes in the cerebral microstructure of patients with noise-induced hearing loss (NIHL) using diffusion tensor imaging (DTI). Overall, 122 patients with NIHL (mild [MP, n=79], relatively severe patients [including moderate and severe; RSP, n=32], and undetermined [lost to follow-up, n=11]) and 84 healthy controls (HCs) were enrolled. All clinical data, including age, education level, hearing threshold, occupation type, noise exposure time, and some scale scores (including the Mini-Mental State Examination [MMSE], tinnitus handicap inventory [THI], and Hamilton Anxiety Scale [HAMA]), were collected and analyzed. All participants underwent T1WI3DFSPGR and DTI, and tract-based spatial statistics and region of interest (ROI) analysis were used for assessment. The final sample included 71 MP, 28 RSP, and 75 HCs. The HAMA scores of the three groups were significantly different (p<.05). The noise exposure times, hearing thresholds, and HAMA scores of the MP and RSP were significantly different (p<.05). The noise exposure time was positively correlated with the hearing threshold and negatively correlated with the HAMA scores (p<.05), whereas the THI scores were positively correlated with the hearing threshold (p<.05). DTI analysis showed that all DTI parameters (fractional anisotropy [FA], axial diffusivity [AD], mean diffusivity [MD], and radial diffusivity [RD]) were significantly different in the left inferior longitudinal fasciculus (ILF) and left inferior fronto-occipital fasciculus (IFOF) for the three groups (p<.05). In addition, the FA values were significantly lower in the bilateral corticospinal tract (CST), right fronto-pontine tract (FPT), right forceps major, left superior longitudinal fasciculus (temporal part) (SLF), and left cingulum (hippocampus) (C-H) of the MP and RSP than in those of the HCs (p<.05); the AD values showed diverse changes in the bilateral CST, left IFOF, right anterior thalamic radiation, right external capsule (EC), right SLF, and right superior cerebellar peduncle (SCP) of the MP and RSP relative to those of the HC (p<.05). However, there were no significant differences among the bilateral auditory cortex ROIs of the three groups (p>.05). There was a significant negative correlation between the FA and HAMA scores for the left IFOF/ILF, right FPT, left SLF, and left C-H for the three groups (p<.05). There was a significant positive correlation between the AD and HAMA scores for the left IFOF/ILF and right EC of the three groups (p<.05). There were significantly positive correlations between the RD/MD and HAMA scores in the left IFOF/ILF of the three groups (p<.05). There was a significant negative correlation between the AD in the right SCP and noise exposure time of the MP and RSP groups (p<.05). The AD, MD, and RD in the left ROI were significantly positively correlated with hearing threshold in the MP and RSP groups (p<.05), whereas FA in the right ROI was significantly positively correlated with the HAMA scores for the three groups (p<.05). The changes in the white matter (WM) microstructure may be related to hearing loss caused by noise exposure, and the WM structural abnormalities in patients with NIHL were mainly located in the syndesmotic fibers of the temporooccipital region, which affected the auditory and language pathways. This confirmed that the auditory pathways have abnormal structural connectivity in patients with NIHL.

Deep Learning-based Approach for Brainstem and Ventricular MR Planimetry: Application in Patients with Progressive Supranuclear Palsy.

Purpose To develop a fast and fully automated deep learning (DL)-based method for the MRI planimetric segmentation and measurement of the brainstem and ventricular structures most affected in patients with progressive supranuclear palsy (PSP). Materials and Methods In this retrospective study, T1-weighted MR images in healthy controls (n = 84) were used to train DL models for segmenting the midbrain, pons, middle cerebellar peduncle (MCP), superior cerebellar peduncle (SCP), third ventricle, and frontal horns (FHs). Internal, external, and clinical test datasets (n = 305) were used to assess segmentation model reliability. DL masks from test datasets were used to automatically extract midbrain and pons areas and the width of MCP, SCP, third ventricle, and FHs. Automated measurements were compared with those manually performed by an expert radiologist. Finally, these measures were combined to calculate the midbrain to pons area ratio, MR parkinsonism index (MRPI), and MRPI 2.0, which were used to differentiate patients with PSP (n = 71) from those with Parkinson disease (PD) (n = 129). Results Dice coefficients above 0.85 were found for all brain regions when comparing manual and DL-based segmentations. A strong correlation was observed between automated and manual measurements (Spearman ρ > 0.80, P < .001). DL-based measurements showed excellent performance in differentiating patients with PSP from those with PD, with an area under the receiver operating characteristic curve above 0.92. Conclusion The automated approach successfully segmented and measured the brainstem and ventricular structures. DL-based models may represent a useful approach to support the diagnosis of PSP and potentially other conditions associated with brainstem and ventricular alterations. Keywords: MR Imaging, Brain/Brain Stem, Segmentation, Quantification, Diagnosis, Convolutional Neural Network Supplemental material is available for this article. © RSNA, 2024 See also the commentary by Mohajer in this issue.

Neuroimaging Findings in US Government Personnel and Their Family Members Involved in Anomalous Health Incidents

US government personnel stationed internationally have reported anomalous health incidents (AHIs), with some individuals experiencing persistent debilitating symptoms. To assess the potential presence of magnetic resonance imaging (MRI)-detectable brain lesions in participants with AHIs, with respect to a well-matched control group. This exploratory study was conducted at the National Institutes of Health (NIH) Clinical Center and the NIH MRI Research Facility between June 2018 and November 2022. Eighty-one participants with AHIs and 48 age- and sex-matched control participants, 29 of whom had similar employment as the AHI group, were assessed with clinical, volumetric, and functional MRI. A high-quality diffusion MRI scan and a second volumetric scan were also acquired during a different session. The structural MRI acquisition protocol was optimized to achieve high reproducibility. Forty-nine participants with AHIs had at least 1 additional imaging session approximately 6 to 12 months from the first visit. AHIs. Group-level quantitative metrics obtained from multiple modalities: (1) volumetric measurement, voxel-wise and region of interest (ROI)-wise; (2) diffusion MRI-derived metrics, voxel-wise and ROI-wise; and (3) ROI-wise within-network resting-state functional connectivity using functional MRI. Exploratory data analyses used both standard, nonparametric tests and bayesian multilevel modeling. Among the 81 participants with AHIs, the mean (SD) age was 42 (9) years and 49% were female; among the 48 control participants, the mean (SD) age was 43 (11) years and 42% were female. Imaging scans were performed as early as 14 days after experiencing AHIs with a median delay period of 80 (IQR, 36-544) days. After adjustment for multiple comparisons, no significant differences between participants with AHIs and control participants were found for any MRI modality. At an unadjusted threshold (P < .05), compared with control participants, participants with AHIs had lower intranetwork connectivity in the salience networks, a larger corpus callosum, and diffusion MRI differences in the corpus callosum, superior longitudinal fasciculus, cingulum, inferior cerebellar peduncle, and amygdala. The structural MRI measurements were highly reproducible (median coefficient of variation <1% across all global volumetric ROIs and <1.5% for all white matter ROIs for diffusion metrics). Even individuals with large differences from control participants exhibited stable longitudinal results (typically, <±1% across visits), suggesting the absence of evolving lesions. The relationships between the imaging and clinical variables were weak (median Spearman ρ = 0.10). The study did not replicate the results of a previously published investigation of AHIs. In this exploratory neuroimaging study, there were no significant differences in imaging measures of brain structure or function between individuals reporting AHIs and matched control participants after adjustment for multiple comparisons.

Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy.

Leukodystrophies are rare genetic white matter disorders that have been regarded as mainly occurring in childhood. This perception has been altered in recent years, as a growing number of leukodystrophies have been described as having an onset in adulthood. Still, many adult patients presenting with white matter changes remain without a specific molecular diagnosis. We describe a novel adult onset leukodystrophy in 16 patients from eight families carrying one of four different stop-gain or frameshift dominant variants in the CST3 gene. Clinical and radiological features differ markedly from the previously described Icelandic cerebral amyloid angiopathy found in patients carrying p.Leu68Asn substitution in CST3. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid to older adult ages. In addition, in some cases acute onset clinical deterioration led to a prolonged episode with reduced consciousness and even early death. Radiologically, pathognomonic changes are found at typical predilection sites involving the deep cerebral white matter sparing a periventricular and directly subcortical rim, the middle blade of corpus callosum, posterior limb of the internal capsule, middle cerebellar peduncles, cerebral peduncles and specifically the globus pallidus. Histopathologic characterization in two autopsy cases did not reveal angiopathy, but instead micro- to macrocystic degeneration of the white matter. Astrocytes were activated at early stages and later displayed severe degeneration and loss. In addition, despite the loss of myelin, elevated numbers of partly apoptotic oligodendrocytes were observed. A structural comparison of the variants in CST3 suggests that specific truncations of cystatin C result in an abnormal function, possibly by rendering the protein more prone to aggregation. Future studies are required to confirm the assumed effect on the protein and to determine pathophysiologic downstream events at the cellular level.

Structural connectivity at term equivalent age and language in preterm children at 2 years corrected.

We previously reported interhemispheric structural hyperconnectivity bypassing the corpus callosum in children born extremely preterm (<28 weeks) versus term children. This increased connectivity was positively associated with language performance at 4-6 years of age in our prior work. In the present study, we aim to investigate whether this extracallosal connectivity develops in extremely preterm infants at term equivalent age by leveraging a prospective cohort study of 350 very and extremely preterm infants followed longitudinally in the Cincinnati Infant Neurodevelopment Early Prediction Study. For this secondary analysis, we included only children born extremely preterm and without significant brain injury (n = 95). We use higher-order diffusion modelling to assess the degree to which extracallosal pathways are present in extremely preterm infants and predictive of later language scores at 22-26 months corrected age. We compare results obtained from two higher-order diffusion models: generalized q-sampling imaging and constrained spherical deconvolution. Advanced MRI was obtained at term equivalent age (39-44 weeks post-menstrual age). For structural connectometry analysis, we assessed the level of correlation between white matter connectivity at the whole-brain level at term equivalent age and language scores at 2 years corrected age, controlling for post-menstrual age, sex, brain abnormality score and social risk. For our constrained spherical deconvolution analyses, we performed connectivity-based fixel enhancement, using probabilistic tractography to inform statistical testing of the hypothesis that fibre metrics at term equivalent age relate to language scores at 2 years corrected age after adjusting for covariates. Ninety-five infants were extremely preterm with no significant brain injury. Of these, 53 had complete neurodevelopmental and imaging data sets that passed quality control. In the connectometry analyses adjusted for covariates and multiple comparisons (P < 0.05), the following tracks were inversely correlated with language: bilateral cerebellar white matter and middle cerebellar peduncles, bilateral corticospinal tracks, posterior commissure and the posterior inferior fronto-occipital fasciculus. No tracks from the constrained spherical deconvolution/connectivity-based fixel enhancement analyses remained significant after correction for multiple comparisons. Our findings provide critical information about the ontogeny of structural brain networks supporting language in extremely preterm children. Greater connectivity in more posterior tracks that include the cerebellum and connections to the regions of the temporal lobes at term equivalent age appears to be disadvantageous for language development.

Neglected tracts of the brainstem: transverse peduncular tract of Gudden and taenia pontis.

The anatomy and function of the brainstem have fascinated scientists for centuries; however, the brainstem remains one of the least studied regions of the human brain. As the authors delved into studying this structure, they observed a growing tendency to forget or neglect previously identified structures. The aim of this study was to describe two such structures: the transverse peduncular tract, also known as the Gudden tract, and the taenia pontis. The authors analyzed the potential effects of neglecting these structures during brainstem surgery and the implications for clinical practice. After removal of the arachnoid and vascular structures, 20 human brainstem specimens were frozen and stored at -16°C for 2 weeks, according to the method described by Klingler. The specimens were then thawed and dissected with microsurgical techniques. The results of microsurgical fiber dissection at each step were photographed. This study revealed two previously neglected or forgotten structures within the brainstem. The first is the transverse peduncular tract of Gudden, which arises from the brachium of the superior colliculus. This tract follows an arcuate course along the lateral and ventral surfaces of the midbrain, perpendicular to the cerebral peduncle, and terminates in the nuclei of the transverse peduncular tract within the interpeduncular fossa. The second structure is the taenia pontis, which originates contralaterally in the interpeduncular fossa. It becomes visible at the level of the pontomesencephalic sulcus and extends to the base of the lateral mesencephalic sulcus, where it divides into several thin bundles. Along the interpeduncular sulcus, between the superior and middle cerebellar peduncles, it reaches the parabrachial recess and enters the cerebellum. Recently, with increasing understanding and expertise in brainstem research, surgical approaches to this area have become more common, emphasizing the importance of a detailed knowledge of the brainstem. The two structures mentioned in this paper are described in history books and were widely studied in the 19th century but have not been mentioned in modern literature. The authors propose that a deeper understanding of these structures may prove valuable in neurosurgical practice and help reduce patient comorbidity.

Causal relationship between multiparameter brain MRI phenotypes and age: evidence from Mendelian randomization.

To explore the causal relationship between age and brain health (cortical atrophy, white matter integrity, white matter hyperintensities and cerebral microbleeds in various brain regions) related multiparameter imaging features using two-sample Mendelian randomization. Age was determined as chronological age of the subject. Cortical volume, white matter micro-integrity, white matter hyperintensity volume and cerebral microbleeds of each brain region were included as phenotypes for brain health. Age and imaging of brain health related genetic data were analysed to determine the causal relationship using inverse-variance weighted model, validated by heterogeneity and horizontal pleiotropy variables. Age is causally related to increased volumes of white matter hyperintensities (β = 0.151). For white matter micro-integrity, fibres of the inferior cerebellar peduncle (axial diffusivity β = -0.128, orientation dispersion index β = 0.173), cerebral peduncle (axial diffusivity β = -0.136), superior fronto-occipital fasciculus (isotropic volume fraction β = 0.163) and fibres within the limbic system were causally deteriorated. We also detected decreased cortical thickness of multiple frontal and temporal regions (P < 0.05). Microbleeds were not related with aging (P > 0.05). Aging is a threat of brain health, leading to cortical atrophy mainly in the frontal lobes, as well as the white matter degeneration especially abnormal hyperintensity and deteriorated white matter integrity around the hippocampus.

Histologic tau lesions and magnetic resonance imaging biomarkers differ across two progressive supranuclear palsy variants.

Progressive supranuclear palsy is a neurodegenerative disease characterized by the deposition of four-repeat tau in neuronal and glial lesions in the brainstem, cerebellar, subcortical and cortical brain regions. There are varying clinical presentations of progressive supranuclear palsy with different neuroimaging signatures, presumed to be due to different topographical distributions and burden of tau. The classic Richardson syndrome presentation is considered a subcortical variant, whilst progressive supranuclear palsy with predominant speech and language impairment is considered a cortical variant, although the pathological underpinnings of these variants are unclear. In this case-control study, we aimed to determine whether patterns of regional tau pathology differed between these variants and whether tau burden correlated with neuroimaging. Thirty-three neuropathologically confirmed progressive supranuclear palsy patients with either the Richardson syndrome (n = 17) or speech/language (n = 16) variant and ante-mortem magnetic resonance imaging were included. Tau lesion burden was semi-quantitatively graded in cerebellar, brainstem, subcortical and cortical regions and combined to form neuronal and glial tau scores. Regional magnetic resonance imaging volumes were converted to Z-scores using 33 age- and sex-matched controls. Diffusion tensor imaging metrics, including fractional anisotropy and mean diffusivity, were calculated. Tau burden and neuroimaging metrics were compared between groups and correlated using linear regression models. Neuronal and glial tau burden were higher in motor and superior frontal cortices in the speech/language variant. In the subcortical and brainstem regions, only the glial tau burden differed, with a higher burden in globus pallidus, subthalamic nucleus, substantia nigra and red nucleus in Richardson's syndrome. No differences were observed in the cerebellar dentate and striatum. Greater volume loss was observed in the motor cortex in the speech/language variant and in the subthalamic nucleus, red nucleus and midbrain in Richardson's syndrome. Fractional anisotropy was lower in the midbrain and superior cerebellar peduncle in Richardson's syndrome. Mean diffusivity was greater in the superior frontal cortex in the speech/language variant and midbrain in Richardson's syndrome. Neuronal tau burden showed associations with volume loss, lower fractional anisotropy and higher mean diffusivity in the superior frontal cortex, although these findings did not survive correction for multiple comparisons. Results suggest that a shift in the distribution of tau, particularly neuronal tau, within the progressive supranuclear palsy network of regions is driving different clinical presentations in progressive supranuclear palsy. The possibility of different disease epicentres in these clinical variants has potential implications for the use of imaging biomarkers in progressive supranuclear palsy.

Case report: Cystic vestibular schwannoma

Background: Cerebellopontine angle tumors are a severe condition because of their life-threatening and functional loss potential, explained by the narrowness of the posterior fossa. The vestibular schwannoma, or acoustic neuroma, is a benign, well-circumscribed extraaxial tumor that arises from Schwann cells of the vestibulocochlear cranial nerve. The tumor is usually mainly solid, but can sometimes develop small cystic areas, due to degenerative modifications, causing microcyst formation. The coalescent of small cysts leading to forming a larger one, and responsible of a predominant cystic contingent, is rare, which makes interesting the case we are about to present. Case report: We are about to report the case of a 64-year-old male patient, with no particular medical history, which clinical interview has noted only tinnitus as a present symptom. He had experienced one year ago several disequilibrium and dizziness episodes, who have subsequently stopped over time, without any particular treatment. He also felt a little loss of hearing, especially in the left ear, but thought it was probably age related. No clinical abnormality including the facial nerve palsy was found. The MRI showed a stage 4 (Koos classification) left cystic vestibular schwannoma. This lesion was compressing the left vertebral and basilar arteries, the brain stream, the left cerebellar hemisphere, the left middle cerebellar peduncle, and the fourth ventricle, causing a triventricular hydrocephalus. After reviewing all potential therapeutic options, the patient declined surgery and decided to postpone the treatment. Conclusion: MRI is definitely the best way to explore the posterior fossa, especially the cerebellopontine angle, and helps us differentiate between all numerous tumors than can develop in this space.

Impaired cognitive flexibility and disrupted cognitive cerebellum in degenerative cerebellar ataxias.

There is a clinically unmet need for a neuropsychological tool that reflects the pathophysiology of cognitive dysfunction in cerebellar degeneration. We investigated cognitive flexibility in degenerative cerebellar ataxia patients and aim to identify the pathophysiological correlates of cognitive dysfunction in relation to cerebellar cognitive circuits. We prospectively enrolled degenerative cerebellar ataxia patients with age-matched healthy controls who underwent 3 T 3D and resting-state functional MRI. All 56 participants were evaluated with the Scale for Assessment and Rating of Ataxia and neuropsychological tests including the Wisconsin Card Sorting Test, Trail Making Test, Montreal Cognitive Assessment and Mini-Mental State Examination. From MRI scans, we analysed the correlation of whole-brain volume and cortico-cerebellar functional connectivity with the Wisconsin Card Sorting Test performances. A total of 52 participants (29 ataxia patients and 23 healthy controls) were enrolled in this study. The Wisconsin Card Sorting Test scores (total error percentage, perseverative error percentage, non-perseverative error percentage and categories completed), Trail Making Test A and Montreal Cognitive Assessment were significantly impaired in ataxia patients (P < 0.05) compared to age-matched healthy controls. The Wisconsin Card Sorting Test error scores showed a significant correlation with the ataxia score (P < 0.05) controlling for age and sex. In volumetric analysis, the cerebellar right crus I, II, VIIb and VIII atrophy correlated with non-perseverative error percentage in the ataxia group. In functional connectivity analysis, the connectivity between crus I, II and VIIb of the cerebellum and bilateral superior parietal and superior temporal gyrus was significantly altered in ataxia patients. The functional connectivity between left crus II and VIIb of the cerebellum and dorsolateral prefrontal and superior frontal/parietal cortices showed a positive correlation with perseverative error percentage. The connectivity between left crus VIIb and pontine nucleus/middle cerebellar peduncle showed a significant negative correlation with non-perseverative error percentage in the ataxia group. The impaired cognitive flexibility represented by the Wisconsin Card Sorting Test was significantly impaired in degenerative cerebellar ataxia patients and correlated with disease severity. The Wisconsin Card Sorting Test performance reflects hypoactivity of the cognitive cerebellum and disrupted cortico-cerebellar connectivity in non-demented patients with degenerative cerebellar ataxia.

Cerebellar symptoms after dengue fever with bright middle cerebellar peduncle sign

Dengue fever is a seasonal epidemic that effects population all across Pakistan every monsoon season and leads to thousands of cases every year. Dengue fever can be associated with neurological complications both during the acute stage and after recovery. These include encephalitis and hemorrhagic complications as well as late immune-related conditions such as Guillain-Barre syndrome and acute disseminated encephalomyelitis. Here we present case of a patient who developed new onset cerebellar symptoms two weeks after recovery from dengue fever, with a middle cerebellar peduncle sign on MRI Brain.

Distant recurrence in the cerebellar dentate nucleus through the dentato-rubro-thalamo-cortical pathway in supratentorial glioma cases

BackgroundDistant 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.MethodsA 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.ResultsOf 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.ConclusionDistant 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 WP161: Characterizing the Underlying Microangiopathy of Deep Cerebellar Intracerebral Hemorrhage

Introduction: Superficial (gray matter, vermis) cerebellar intracerebral hemorrhage (cICH) is associated with strictly lobar supratentorial cerebral microbleeds—a strong marker for cerebral amyloid angiopathy. However, for deep (white matter, deep nuclei, cerebellar peduncle) cICH, it is unclear whether hypertensive cerebral small vessel disease (HTN-cSVD) is the underlying microangiopathy. Hypothesis: We hypothesized that left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, and non-hemorrhagic imaging markers of HTN-cSVD such as peri-basal ganglia (BG) white matter hyperintensity (WMH) pattern, deep lacunes, and severe BG enlarged perivascular spaces (EPVS) would be associated with deep vs. superficial cICH. Methods: Brain MRI scans from a prospective database of consecutive non-traumatic ICH patients admitted to a single referral center (2003 to 2019) were analyzed for the presence of cerebral microbleeds (CMBs) and non-hemorrhagic neuroimaging markers. The presence of clinical risk factors, LVH, and neuroimaging markers were compared between patients with deep and superficial cICH in univariate and multivariable models. Results: Of 1,791 patients with spontaneous ICH, 129 (7%) were found to have cICH (mean age 73±12 years, 46% female). Of these, 83 (64%) patients had deep cICH and 46 (36%) patients had superficial cICH. Hypertension (94% vs. 67%, p &lt; 0.01) and LVH (60% vs. 28%, p &lt; 0.01) were more common among patients with deep vs. superficial cICH. Among those who received a brain MRI (74%), the frequency of peri-BG WMH pattern (24% vs. 5%, p = 0.02), deep lacunes (59% vs. 14%, p &lt; 0.01), severe BG EPVS (27% vs. 3%, p &lt; 0.01), deep CMBs (51% vs. 16%, p &lt; 0.01), and mixed location CMBs (37% vs. 11%, p &lt; 0.01) was greater among patients with deep cICH compared to superficial cICH. When these variables were entered into a multivariable regression model, LVH (OR 3.10, 95% CI [1.07-8.97], p = 0.04) and deep lacunes (OR 4.38, 95% CI [1.25-15.31], p = 0.02) remained significantly associated with deep cICH. Conclusions: Because supratentorial HTN-cSVD imaging markers are common in deep cICH, and deep lacunes and LVH are independently associated with deep cICH, it is likely that HTN-cSVD is the underlying microangiopathy of deep cICH.

Unusual PSMA uptake in seronegative paraneoplastic brainstem encephalitis: A case report

Paraneoplastic encephalitis, especially seronegative, is a heterogeneous group of disorders with varied symptoms at presentation. We present the case of a 63-year-old male who presented with motor weakness and altered sensorium. Magnetic resonance imaging of the brain showed altered signal intensity in the midbrain, pons, anterior part of the medulla, and bilateral middle cerebellar peduncle. T2 hyperintensity was also seen in the bilateral basal ganglia and internal capsule region. 18 fluoro-deoxyglucose positron emission tomography/computed tomography (18 FDG PET/CT) showed increased FDG uptake in the brain stem, left thalamus, and periventricular location. 68Ga-prostate-specific membrane antigen (PSMA) PET/CT done in view of elevated serum Prostate-specific antigen levels show a focal PSMA-avid lesion in the prostate gland and increased PSMA uptake in the brain stem, which is an atypical site of PSMA uptake. Our study highlights the importance of paraneoplastic syndromes with varied clinical presentation and low specificity to antibodies. These spectra of diseases are fatal but treatable and therefore should be evaluated diligently to reduce morbidity

Correlation between postoperative microstructural changes in cerebral white matter and early postoperative cognitive function in patients undergoing meningioma resection

Objective: To analyze the correlation between microstructure changes in cerebral white matter before and after surgery and early postoperative cognitive function in patients undergoing meningioma resection. Methods: A total of 17 patients who underwent their first meningioma resection at Xuanwu Hospital of Capital Medical University from April 2022 to April 2023 were prospectively included as observation group, with 5 males and 12 females, aged (56.4±7.3) years. Another 15 age- and education-matched patients with cerebral benign tumor were recruited as control group during the same period, with 5 males and 10 females, aged (55.2±8.0) years. Neuropsychological tests (NST), mainly including auditory verbal learning test of Huashan version (AVLT-H), the Montreal cognitive assessment-basic (MoCA-B), clock drawing task-30 (CDT-30), shape trails test-B (STT-B) and animal fluence test (AFT), were conducted at 1 day before surgery, 1 day and within 3-4 days after surgery in the observation group. Simultaneously, magnetic resonance imaging (MRI) scans were performed to collect diffusion tensor imaging (DTI) images at 1 day before surgery and within 3-4 days after surgery. The same NST were conducted at 1 day, 3 days and 6 days after admission in the control group to adjust for learning effects from repeated tests. The microstructure changes of the whole brain white matter were evaluated at the group level by using tract-based spatial statistics (TBSS) technology, including changes of fractional anisotropy (FA), mean diffusion (MD), axial diffusion (AD), and radial diffusion (RD). Then, correlation was performed between DTI indicators with statistically significant and cognitive function. Results: After adjusting for the learning effects, the AVLT-H (R), MoCA-B, and CDT-30 scores decreased, and the evaluation time of STT-B prolonged after surgery in patients with meningioma. And their perioperative decreased values were -0.78 (95%CI:-3.28--0.28) points, -2.22 (95%CI:-4.22--0.72) points, -2.74 (95%CI:-5.29--0.19) points, and 61.49 (95%CI: 5.71-117.27) seconds, respectively, with statistically significant differences (all P<0.05). Group level analysis of TBSS based on DTI images showed decreased FA mainly in the right superior cerebellar peduncle, left posterior limb of internal capsule and genu of corpus callosum, and increased RD mainly in the left anterior corona radiata in patients undergoing meningioma resection, with statistically significant differences (all PFWE<0.05). Linear correlation showed that the perioperative decreased values of FA in genu of corpus callosum and right superior cerebellar peduncle were positively correlated with the perioperative decreased values of AVLT-H (L) after adjusting for learning effects (r=0.72, 0.52, all PFWE<0.05). Conclusions: Patients undergoing meningioma resection are at risk of postoperative cognitive decline. Perioperative decreased values of FA in genu of corpus callosum and right superior cerebellar peduncle based on DTI images are positively correlated with the perioperative decreased values of AVLT-H (L) after adjusting for learning effects.

Hot cross bun in pediatric age multi-system atrophy an unusual presentation

A 10-year-old female was brought to emergency department with complaint fever, cold, and cough for 5 days followed by weakness of upper limb weakness more than Lower limb associated with inability to walk/stand, brought to emergency with altered sensorium. Nervous system: Confused and altered, tone is normal, power: 3/3 in upper limbs 2/2 in lower limbs and reflexes in bilateral knee brisk, bilateral plantar-extensor; On general examination revealed hypomimia, dysarthria and bilateral bradykinesia along with ataxic gait and pyramidal signs. Blood investigation were normal and diagnosis made by neuroimaging s/o: Bilaterally symmetrical abnormal signal in both postero-medial thalami, bilateral insular cortices, pons and bilateral middle cerebellar peduncles. It is extending into pons involving transverse pontocerebellar tracts and median pontine raphe nuclei giving 'Hot cross bun sign' (HCBS). During course of treatment child had autonomic disturbances. Child was treated with supportive medication and methyl-presdnisolone followed by oral steroid. Child had responded to treatment given and child has been discharged with no neurological deficit on oral medications. We concluded autonomic dysfunction in any patient presenting with acute onset of weakness with short duration must evaluate for MSA and institute appropriate treatment.

Deep neurological phenotyping in oculo-dento-digital syndrome.

Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant congenital malformation syndrome characterized by high penetrance and great phenotypic heterogeneity. Neurological manifestations are thought to occur in about one third of cases, but systematic studies are not available. We performed deep neurological phenotyping of 10 patients in one ODDD pedigree. Retrospective case series. We analyzed in depth the neurological phenotype of a three-generation family segregating the heterozygous c.416T > C, p.(Ile139Thr) in GJA1. Clinical and neuroradiological features were retrospectively evaluated. Brain MRI and visual evoked potentials were performed in 8 and 6 cases, respectively. Central nervous system manifestations occurred in 5 patients, the most common being isolated ataxia either in isolation or combined with spasticity. Furthermore, sphincteric disturbances (neurogenic bladder and fecal incontinence) were recognized as the first manifestation in most of the patients. Subclinical electrophysiological alteration of the optic pathway occurred in all the examined patients. Neuroimaging was significant for supratentorial hypomyelination pattern and hyperintense superior cerebellar peduncle in all examined patients. The neurological involvement in ODDD carriers is often missed but peculiar clinical and radiological patterns can be recognized. Deep neurological phenotyping is needed to help untangle ODDD syndrome complexity and find genotype-phenotype correlations.