Superior Cerebellar Peduncle Research Articles

Synthetic MR Imaging-Based WM Signal Suppression Identifies Neonatal Brainstem Pathways in Vivo.

Multidynamic multiecho sequence-based imaging enables investigators to reconstruct multiple MR imaging contrasts on the basis of a single scan. This study investigated the feasibility of synthetic MRI-based WM signal suppression (syWMSS), a synthetic inversion recovery approach in which a short TI suppresses myelin-related signals, for the identification of early myelinating brainstem pathways. Thirty-one cases of neonatal MR imaging, which included multidynamic multiecho data and conventionally acquired T1- and T2-weighted sequences, were analyzed. The multidynamic multiecho postprocessing software SyMRI was used to generate syWMSS data (TR/TE/TI = 3000/5/410 ms). Two raters discriminated early myelinating brainstem pathways (decussation of the superior cerebellar peduncle, medial lemniscus, central tegmental tract, and medial longitudinal fascicle [the latter 3 assessed at the level of the pons]) on syWMSS data and reference standard contrasts. On the basis of syWMSS data, the decussation of the superior cerebellar peduncle (31/31); left/right medial lemniscus (31/31; 30/31); left/right central tegmental tract (19/31; 20/31); and left/right medial longitudinal fascicle (30/31) were reliably identified by both raters. On the basis of T1-weighted contrasts, the decussation of the superior cerebellar peduncle (14/31); left/right medial lemniscus (22/31; 16/31); left/right central tegmental tract (1/31); and left/right medial longitudinal fascicle (9/31; 8/31) were reliably identified by both raters. On the basis of T2-weighted contrasts, the decussation of the superior cerebellar peduncle (28/31); left/right medial lemniscus (16/31; 12/31); left/right central tegmental tract (23/31; 18/31); and left/right medial longitudinal fascicle (15/31; 14/31) were reliably identified by both raters. syWMSS data provide a feasible imaging technique with which to study early myelinating brainstem pathways. MR imaging approaches that use myelin signal suppression contribute to a more sensitive assessment of myelination patterns at early stages of cerebral development.

Attention-deficit/hyperactivity disorder and white matter microstructure: the importance of dimensional analyses and sex differences.

Attention-deficit/hyperactive disorder (ADHD) has substantial heterogeneity in clinical presentation. A potentially important clue may be variation in brain microstructure. Using fractional anisotropy (FA), previous studies have produced equivocal results in relation to ADHD. This may be due to insufficient consideration of possible sex differences and ADHD's multi-componential nature. Using whole-brain analyses, we investigated the association between FA and both ADHD diagnosis and ADHD symptom domains in a well-characterized, ADHD (n = 234; 32% female youth) and non-ADHD (n = 177; 52% female youth), case-control cohort (ages 7-12). Sex-specific effects were tested. No ADHD group differences were found using categorical assessment of ADHD without consideration of moderators. However, dimensional analyses found total symptoms were associated with higher FA in the superior corona radiata. Further, inattention symptoms were associated with higher FA in the corpus callosum and ansa lenticularis, and lower FA in the superior longitudinal fasciculus, after control for overlap with hyperactivity-impulsivity. Hyperactivity-impulsivity symptoms were associated with higher FA in the superior longitudinal fasciculus, and lower FA in the superior cerebellar peduncles, after control for overlap with inattention. Meanwhile, both categorical and dimensional analyses revealed ADHD-by-sex interactions (voxel-wise p < 0.01). Girls with ADHD had higher FA, but boys with ADHD had lower FA (or no effect), compared to their same-sex peers, in the bilateral anterior corona radiata. Further, higher ADHD symptom severity was associated with higher FA in girls, but lower FA in boys, in the anterior and posterior corona radiata and cerebral peduncles. ADHD symptom domains appear to be differentially related to white matter microstructure, highlighting the multi-componential nature of the disorder. Further, sex differences will be crucial to consider in future studies characterizing ADHD-related differences in white matter microstructure.

Structural alterations of spinocerebellar ataxias type 3: from pre-symptomatic to symptomatic stage.

To investigate and characterize the structural alterations of the brain in SCA3, and their correlations with the scale for the assessment and rating of ataxia (SARA) and normal brain ATXN3 expression. We performed multimodal analyses in 52 SCA3 (15 pre-symptomatic) and healthy controls (HCs) (n = 35) to assess the abnormalities of gray and white matter (WM) of the cerebrum, brainstem, and cerebellum via FreeSurfer, SUIT, and TBSS, and their associations with disease severity. Twenty SCA3 patients (5 pre- and 15 symptomatic) were followed for at least a year. Besides, we uncovered the normal pattern of brain ATXN3 spatial distribution. Pre-symptomatic patients showed only WM damage, mainly in the cerebellar peduncles, compared to HCs. In the advanced stage, the WM damage followed a caudal-rostral pattern. Meanwhile, continuous nonlinear structure damage was characterized by brainstem volumetric reduction and relatively symmetric cerebellar and basal ganglia atrophy but spared the cerebral cortex, partially explained by the ATXN3 overexpression. The bilateral pallidum, brainstem, and cerebellar peduncles demonstrated a very large effect size. Besides, all these alterations were significantly correlated with SARA; the pons (r = -0.65) and superior cerebellar peduncle (r = -0.68) volume demonstrated a higher correlation than the cerebellum with SARA. The longitudinal study further uncovered progressive atrophy of pons in symptomatic SCA3. Significant WM damage starts before the ataxia onset. The bilateral pallidum, brainstem, and cerebellar peduncles are the most vulnerable targets. The volume of pons appears to be the most promising imaging biomarker for a longitudinal study. ClinicalTrial ID: ChiCTR2100045857 ( http://www.chictr.org.cn/edit.aspx?pid=55652&htm=4 ) KEY POINTS: • Pre- SCA3 showed WM damage mainly in cerebellar peduncles. Continuous brain damage was characterized by brainstem, widespread, and relatively symmetric cerebellar and basal ganglia atrophy. • Volumetric abnormalities were most evident in the bilateral pallidum, brainstem, and cerebellar peduncles in SCA3. • The volume of pons might identify the disease progression longitudinally.

Disruption of specificwhite matter tracts is associated with neurogenic lower urinary tract dysfunction in women with multiple sclerosis.

To identify specific white matter tracts (WMTs) whose disruption is associated with the severity of neurogenic lower urinary tract dysfunction (NLUTD) in two independent cohorts of women with multiple sclerosis(MS) and NLUTD. Cohort 1 consisted of twenty-eight women with MS and NLUTD. The validation cohort consisted of 10women with MS and NLUTD. Eleven healthy women served as controls. Participants of both MS cohorts had the same inclusion and exclusion criteria. Both MS cohorts and the healthy controls underwent the same clinical assessment and functional MRI(fMRI) protocol, except that the validation MS cohort underwent 7-Tesla fMRI scan. Fifteen WMTs (six coursing to relevant brainstem areas) involved in bladder control were a priori regions of interest (ROI). Spearman's correlation test was performed between each the Fractional Anisotropy (FA) and mean diffusivity (MD) of each WMT and the clinical parameters. Overall, we found a very high degree of overlap (100% of a priori ROI) in the tracts identified by our correlation analysis as having the greatest contribution to NLUTD symptoms in MS women. The right inferior cerebellar peduncle, left posterior limb of internal capsule, and left superior cerebellar peduncle displayed significant associations to the greatest number of clinical parameters. Our correlation analysis supports the role of specific WMT disruptions in the contribution of symptoms in women with MS and NLUTD, as confirmed in two independent MS cohorts.

Associations between myelin water imaging and measures of fall risk and functional mobility in multiple sclerosis.

Myelin water fraction (MWF) deficits as measured by myelin water imaging (MWI) have been related to worse motor function in persons with multiple sclerosis (PwMS). However, it is unknown if measures from MWI metrics in motor areas relate to fall risk measures in PwMS. The objective of this study was to examine the relationship between MWI measures in motor areas to performance on clinical measures of fall risk and disability in PwMS. Sixteen individuals with relapsing-remitting MS participated (1 male, 15 female; age 47.1 years [12.3]; Expanded Disability Status Scale 4.0 [range 0-6.5]) and completed measures of walking and fall risk (Timed 25 Foot Walk [T25FW] and Timed Up and Go). MWF and the geometric mean of the intra-/extracellular water T2 (geomT2IEW ) values reflecting myelin content and contribution of large-diameter axons/density, respectively, were assessed in three motor-related regions. The geomT2IEW of the corticospinal tract (r=-.599; p=.018) and superior cerebellar peduncles (r=-.613; p=.015) demonstrated significant inverse relationships with T25FW, suggesting that decreased geomT2IEW was related to slower walking. Though not significant, MWF in the corticospinal tract and superior cerebellar peduncles also demonstrated fair relationships with the T25FW, suggesting that worse performance on the T25FW was associated with lower MWF values. MWI of key motor regions was associated with walking performance in PwMS. Further MWI studies are needed to identify relationships between pathology and clinical function in PwMS to guide targeted rehabilitation therapies aimed at preventing falls.

Multimodal magnetic resonance imaging of youth sport-related concussion reveals acute changes in the cerebellum, basal ganglia, and corpus callosum that resolve with recovery.

Magnetic resonance imaging (MRI) can provide a number of measurements relevant to sport-related concussion (SRC) symptoms; however, most studies to date have used a single MRI modality and whole-brain exploratory analyses in attempts to localize concussion injury. This has resulted in highly variable findings across studies due to wide ranging symptomology, severity and nature of injury within studies. A multimodal MRI, symptom-guided region-of-interest (ROI) approach is likely to yield more consistent results. The functions of the cerebellum and basal ganglia transcend many common concussion symptoms, and thus these regions, plus the white matter tracts that connect or project from them, constitute plausible ROIs for MRI analysis. We performed diffusion tensor imaging (DTI), resting-state functional MRI, quantitative susceptibility mapping (QSM), and cerebral blood flow (CBF) imaging using arterial spin labeling (ASL), in youth aged 12-18 years following SRC, with a focus on the cerebellum, basal ganglia and white matter tracts. Compared to controls similar in age, sex and sport (N = 20), recent SRC youth (N = 29; MRI at 8 ± 3 days post injury) exhibited increased susceptibility in the cerebellum (p = 0.032), decreased functional connectivity between the caudate and each of the pallidum (p = 0.035) and thalamus (p = 0.021), and decreased diffusivity in the mid-posterior corpus callosum (p < 0.038); no changes were observed in recovered asymptomatic youth (N = 16; 41 ± 16 days post injury). For recent symptomatic-only SRC youth (N = 24), symptom severity was associated with increased susceptibility in the superior cerebellar peduncles (p = 0.011) and reduced activity in the cerebellum (p = 0.013). Fewer days between injury and MRI were associated with reduced cerebellar-parietal functional connectivity (p < 0.014), reduced activity of the pallidum (p = 0.002), increased CBF in the caudate (p = 0.005), and reduced diffusivity in the central corpus callosum (p < 0.05). Youth SRC is associated with acute cerebellar inflammation accompanied by reduced cerebellar activity and cerebellar-parietal connectivity, as well as structural changes of the middle regions of the corpus callosum accompanied by functional changes of the caudate, all of which resolve with recovery. Early MRI post-injury is important to establish objective MRI-based indicators for concussion diagnosis, recovery assessment and prediction of outcome.

Clinicopathological features of progressive supranuclear palsy with asymmetrical atrophy of the superior cerebellar peduncle.

Progressive supranuclear palsy (PSP) can be diagnosed despite the presence of asymmetrical parkinsonism depending on the clinical diagnostic criteria. Some studies have reported that atrophy of the superior cerebellar peduncle (SCP) is more frequent in PSP than in Parkinson's disease. There have also been reports of PSP cases with an asymmetrically atrophic SCP. Therefore, we analyzed 48 specimens from consecutive autopsy cases that were neuropathologically diagnosed as PSP to investigate the laterality of brain lesions, including the SCP. We measured the width of the SCP and evaluated the laterality of atrophy. We semi-quantitatively evaluated neuronal loss, atrophy/myelin pallor, and tau pathology in three steps. Asymmetrical atrophy of the SCP was present in seven (14.6%) of 48 cases. The atrophic side of the SCP corresponded to the dominant side of the tau pathology in the cerebellar dentate nucleus. It was opposite to the dominant side of the myelin pallor and tau pathology in the red nucleus and of the tau pathology in the central tegmental tract and inferior olivary nucleus, coinciding with the neurologically systematic anatomy of the Guillain-Mollaret triangle. Neurodegeneration of PSP can progress asymmetrically from one side to the initially intact side in PSP with an initial predominance of Richardson's syndrome, progressive gait freezing, ocular motor dysfunction, parkinsonism, or corticobasal syndrome. To our knowledge, no previous study has reported asymmetrical PSP neuropathology; this is the first study to report the presence of PSP cases with asymmetrical SCP atrophy and systematically asymmetrical degeneration of the Guillain-Mollaret triangle.

Full cervical cord tractography: A new method for clinical use.

Despite recent improvements in diffusion-weighted imaging, spinal cord tractography is not used in routine clinical practice because of difficulties in reconstructing tractograms, with a pertinent tri-dimensional-rendering, in a long post-processing time. We propose a new full tractography approach to the cervical spinal cord without extensive manual filtering or multiple regions of interest seeding that could help neurosurgeons manage various spinal cord disorders. Four healthy volunteers and two patients with either cervical intramedullary tumors or spinal cord injuries were included. Diffusion-weighted images of the cervical spinal cord were acquired using a Philips 3 Tesla machine, 32 diffusion directions, 1,000 s/mm2 b-value, 2 × 2 × 2 mm voxel size, reduced field-of-view (ZOOM), with two opposing phase-encoding directions. Distortion corrections were then achieved using the FSL software package, and tracking of the full cervical spinal cord was performed using the DSI Studio software (quantitative anisotropy-based deterministic algorithm). A unique region of avoidance was used to exclude everything that is not of the nervous system. Fiber tracking parameters used adaptative fractional anisotropy from 0.015 to 0.045, fiber length from 10 to 1,000 mm, and angular threshold of 90°. In all participants, a full cervical cord tractography was performed from the medulla to the C7 spine level. On a ventral view, the junction between the medulla and spinal cord was identified with its pyramidal bulging, and by an invagination corresponding to the median ventral sulcus. On a dorsal view, the fourth ventricle—superior, middle, and inferior cerebellar peduncles—was seen, as well as its floor and the obex; and gracile and cuneate tracts were recognized on each side of the dorsal median sulcus. In the case of the intramedullary tumor or spinal cord injury, the spinal tracts were seen to be displaced, and this helped to adjust the neurosurgical strategy. This new full tractography approach simplifies the tractography pipeline and provides a reliable 3D-rendering of the spinal cord that could help to adjust the neurosurgical strategy.

Toward More Accessible Fully Automated 3D Volumetric MRI Decision Trees for the Differential Diagnosis of Multiple System Atrophy, Related Disorders, and Age-Matched Healthy Subjects.

Differentiating multiple system atrophy (MSA) from related neurodegenerative movement disorders (NMD) is challenging. MRI is widely available and automated decision-tree analysis is simple, transparent, and resistant to overfitting. Using a retrospective cohort of heterogeneous clinical MRIs broadly sourced from a tertiary hospital system, we aimed to develop readily translatable and fully automated volumetric diagnostic decision-trees to facilitate early and accurate differential diagnosis of NMDs. 3DT1 MRI from 171 NMD patients (72 MSA, 49 PSP, 50 PD) and 171 matched healthy subjects were automatically segmented using Freesurfer6.0 with brainstem module. Decision trees employing substructure volumes and a novel volumetric pons-to-midbrain ratio (3D-PMR) were produced and tenfold cross-validation performed. The optimal tree separating NMD from healthy subjects selected cerebellar white matter, thalamus, putamen, striatum, and midbrain volumes as nodes. Its sensitivity was 84%, specificity 94%, accuracy 84%, and kappa 0.69 in cross-validation. The optimal tree restricted to NMD patients selected 3D-PMR, thalamus, superior cerebellar peduncle (SCP), midbrain, pons, and putamen as nodes. It yielded sensitivities/specificities of 94/84% for MSA, 72/96% for PSP, and 73/92% PD, with 79% accuracy and 0.62 kappa. There was correct classification of 16/17 MSA, 5/8 PSP, 6/8 PD autopsy-confirmed patients, and 6/8 MRIs that preceded motor symptom onset. Fully automated decision trees utilizing volumetric MRI data distinguished NMD patients from healthy subjects and MSA from other NMDs with promising accuracy, including autopsy-confirmed and pre-symptomatic subsets. Our open-source methodology is well-suited for widespread clinical translation. Assessment in even more heterogeneous retrospective and prospective cohorts is indicated.

White matter alterations in pediatric brainstem glioma: An national brain tumor registry of China study.

BackgroundPrevious studies have identified alterations in structural connectivity of patients with glioma. However, white matter (WM) integrity measured by diffusion kurtosis imaging (DKI) in pediatric patients with brainstem glioma (BSG) was lack of study. Here, the alterations in WM of patients with BSG were assessed through DKI analyses.Materials and methodsThis study involved 100 patients with BSG from the National Brain Tumor Registry of China (NBTRC) and 50 age- and sex-matched healthy controls from social recruitment. WM tracts were segmented and reconstructed using U-Net and probabilistic bundle-specific tracking. Next, automatic fiber quantitative (AFQ) analyses of WM tracts were performed using tractometry module embedded in TractSeg.ResultsWM quantitative analysis identified alterations in DKI-derived values in patients with BSG compared with healthy controls. WM abnormalities were detected in the projection fibers involved in the brainstem, including corticospinal tract (CST), superior cerebellar peduncle (SCP), middle cerebellar peduncle (MCP) and inferior cerebellar peduncle (ICP). Significant WM alterations were also identified in commissural fibers and association fibers, which were away from tumor location. Statistical analyses indicated the severity of WM abnormality was statistically correlated with the preoperative Karnofsky Performance Scale (KPS) and symptom duration of patients respectively.ConclusionThe results of this study indicated the widely distributed WM alterations in patients with BSG. DKI-derived quantitative assessment may provide additional information and insight into comprehensively understanding the neuropathological mechanisms of brainstem glioma.

The Molar Tooth Sign of Brain Mri: A Case Report of Joubert Syndrome

Joubert syndrome is a rare genetic disorder of autosomal recessive inheritance characterized by congenital malformation of the brainstem and agenesis or hypoplasia of the cerebellar vermis resulting in respiratory disorders, nystagmus, hypotonia, ataxia and delayed motor development. Magnetic resonance imaging allows the diagnosis to be made by demonstrating the "molar tooth sign". We report the observation of an infant aged 1 year 4 months, from a 2nd degree consanguineous marriage, hospitalized for seizures. On examination, she presented with hypotonia. She had abnormal eye movements such as nystagmus. The cerebral magnetic resonance image revealed hypoplasia of the cerebellar vermis and enlargement of the superior cerebellar peduncles with a "molar tooth" aspect in favor of a Joubert syndrome. The evolution was marked by the installation of a delay in psychomotor development.

Examining The Effects Of Mild Traumatic Brain Injury On Brainstem Integrity

Concussion-related brainstem injuries have received little attention in research, yet concussion-related symptoms, e.g. headache and postural instability, share a common neurological origin within the brainstem. As advanced neuroimaging techniques evolve, so do opportunities to better examine the underlying damage in the brainstem and its related white matter (WM) circuitry following an mTBI. PURPOSE: To examine the brainstem integrity in mTBI patients using advanced neuroimaging techniques. METHODS: T1-weighted and diffiusion-weighted MRI scans were performed on 13 mTBI participants within 14 days of their injuries and 3 individuals without history of brain injury. Diffusion images were acquired using a multishell high-definition fiber tracking sequence. The data were reconstructed using generalized q-sampling imaging, then a deterministic fiber tracking algorithm was applied to generate WM tract profiles indicating the quantitative anisotropy (QA) for the bilateral frontal, parietal, and occipital corticopontine tracts (CPT), the corticospinal tracts (CST), the corticoreticular tracts (CRT), and the middle cerebellar peduncle (MCP). Volumes of the midbrain, pons, medulla oblongata, and superior cerebellar peduncle were determined using Freesurfer v6. A two-sample t-test was used to determine between-group differences in the segmented brainstem structures. One-dimensional statistical parametric mapping was performed to compare WM tracts, and Hedge’s g was calculated to determine between-group effect size.RESULTS: QA values for the first 5% (caudal end) of the left CPT-F was significantly lower in the mTBI group (p = .021). Large effect sizes were found when comparing mTBI to control groups for overall tract QA for the right CPT-O and CPT-F, left and right CPT-P, CST, CRT, and MCP (g > 0.8), with the largest effect for the left CPT-F tract (g = 1.64). There were no significant differences between groups in the segmented brainstem volumes. CONCLUSION: Lower QA values in the caudal portion of the CPT-F indicate that WM near the brainstem may be susceptible to mTBI-related change despite a lack of effect on brainstem volume. Further research should investigate the brainstem after mTBI. Supported by NIH Grant R21 12973518

Upper cerebellar glucose hypermetabolism in patients with temporal lobe epilepsy and interictal psychosis.

Psychosis is an important comorbidity in epilepsy, but its pathophysiology is still unknown. The imaging modality 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG PET) is widely used to measure brain glucose metabolism, and we speculated that 18 F-FDG PET may detect characteristic alteration patterns in individuals with temporal lobe epilepsy (TLE) and psychosis. We enrolled 13 patients with TLE and interictal psychosis (TLE-P) and 21 patients with TLE without psychosis (TLE-N). All underwent interictal 18 F-FDG-PET scanning. Statistical Parametric Mapping (SPM)12 software was used for the normalization process, and we performed a voxel-wise comparison of the TLE-P and TLE-N groups. Cerebral hypometabolic areas were observed in the ipsilateral temporal pole to hippocampus in both patient groups. In the TLE-P group, the voxel-wise comparison revealed significantly increased 18 F-FDG signals in the upper cerebellum, superior cerebellar peduncle, and midbrain. There were no significant between-group metabolic differences around the focus or other cerebral areas. Our results demonstrated significant hypermetabolism around the upper cerebellum in patients with TLE and interictal psychosis compared to patients with TLE without psychosis. These findings may reflect the involvement of the cerebellum in the underlying neurobiology of interictal psychosis and could contribute to a better understanding of this disorder.

Microsurgical Anatomy of the Cerebellar Interpeduncular Entry Zones

The cerebellar interpeduncular region, particularly the middle cerebellar peduncle (MCP) and interpeduncular sulcus (IPS) are significant surgical relevance areas due to the high prevalence of vascular and tumoral pathologies, such as cavernomas, arteriovenous malformations, and gliomas. We defined safer access areas of the MCP and the IPS, according to the surface anatomy, involved vessels, and fiber tracts of the cerebellar interpeduncular region. Fifteen formalin-fixed and silicone-injected cadaveric heads and 23 human brainstems with attached cerebellums prepared with the Klingler's technique were bilaterally dissected to study the vascular and intrinsic anatomy. Surface anatomy: The mean length of the IPS was 12.73mm (standard deviation [SD],2.15mm), and the average measured angle formed by the IPS and the lateral mesencephalic sulcus was 144.53°. The mean distance from the uppermost point of the IPS to cranial nerve IV was 2.63mm (SD, 2.84mm). Vascular anatomy: The perforating branches of the superior cerebellar peduncle, IPS, and MCP originated predominantly from the caudal trunk of the superior cerebellar artery. The inferior third of the superior cerebellar peduncle and IPS was the third most pierced by perforating arteries, and for the MCP, was its superior third. Crossing vessels: The branches of the pontotrigeminal vein and the caudal trunk of the superior cerebellar artery crossed the IPS mostly. The superior third of the IPS was the most crossed by arteries and veins. The middle thirds of the IPS and MCP as entry zones might be safer than their superior and inferior thirds due to fewer perforating branches, arterial trunks, and veins crossing the sulcus as fewer eloquent tracts.

Morphometric magnetic resonance imaging cortico-subcortical features in Parkinson's disease with mild cognitive impairment.

Parkinson's disease (PD) patients with cognitive impairment undergo progressive atrophy of several cortical and subcortical areas. The aim was to study the magnetic resonance imaging (MRI) morphometric features of PD patients with mild cognitive impairment (MCI). Patients from the Parkinson's Disease Cognitive Impairment Study (PACOS) cohort with an available structural volumetric brain MRI and morphometric measurements of the midbrain and pons areas, middle cerebellar peduncle, superior cerebellar peduncle width and midbrain anteroposterior diameter (A-Pdiam) were included. MCI was diagnosed according to the Movement Disorder Society level II criteria. Additionally, cortical thickness analysis was performed and correlated with morphometric brainstem measurements. Morphometric measurements were available for 168 subjects, of whom 67 (39.9%) were diagnosed with PD-MCI. The mean age (± standard deviation) of the sample was 64.2 ± 9.8. Amongst patients, 84 (50%) were men with a disease duration of 5.2 ± 5.4 years and a Unified Parkinson's Disease Rating Scale-Motor Examination score of 32.1 ± 12.9. In the univariate and multivariate analysis, after adjusting for age, sex, years of schooling and disease duration, MCI was associated with midbrain area (odds ratio 0.98; 95% confidence interval 0.96-0.99; p=0.048) and A-Pdiam (odds ratio 0.63; 95% confidence interval 0.46-0.86; p=0.005). Furthermore, 121 PD patients underwent cortical thickness analysis, which showed the presence of cortical thinning in lateral orbitofrontal regions of patients with PD-MCI. No correlation was found between cortical thickness and brainstem morphometric measurements. A mild midbrain atrophy and the presence of frontal cortical thickness reduction might be considered a structural MRI feature of PD patients with MCI.

Nothnagel Syndrome.

The internist Hermann Nothnagel (1841-1905) took a special interest in the cerebellum. In an early experimental study on rabbits conducted in 1876, he demonstrated the involvement of the vermis in the pathophysiology of motor ataxia. Between 1879 and 1889, he reported four cases of tectal tumors that clinically manifested with bilateral ophthalmoplegia and unilateral gait ataxia, culminating in the Cerebellar Classic highlighted here. Nothnagel attributed this clinical syndrome to lesions of the colliculi ("quadrigeminal bodies") and compression of the nuclei of the third cranial nerves, but also left open the possibility of the involvement of neighboring structures, such as the cerebellar vermis. Today, the ataxic component of Nothnagel syndrome is explained by a dorsal midbrain abnormality of either neoplastic or vascular origin, involving the superior cerebellar peduncles, besides the oculomotor nerves.

Posterior fossa syndrome in a population of children and young adults with medulloblastoma: a retrospective, multicenter Italian study on incidence and pathophysiology in a histologically homogeneous and consecutive series of 136 patients.

Posterior fossa syndrome (PFS) is a set of debilitating complications that can occur after surgery for posterior fossa tumors. This study aimed to assess the preoperative radiological and surgical risk factors for the onset of PFS in a histologically homogeneous population of children with medulloblastoma and compare it to a similar population of young adults. Included patients underwent posterior fossa surgery for medulloblastoma at 11 Italian neurosurgical wards (2003-2019) and were referred to Fondazione IRCCS Istituto Nazionale dei Tumori in Milan (INT) for postoperative treatments. We collected patients' pre- and post-operative clinical, surgical and radiological data from the INT charts. To compare the distribution of variables, we used the Mann-Whitney and Fisher tests for continuous and categorical variables, respectively. 136 patients (109 children and 27 young adults) were included in the study. Among children, 29 (27%) developed PFS, and all of them had tumors at midline site with invasion of the fourth ventricle. Radiological evidence of involvement of the right superior (39% versus 12%; p = 0.011) or middle cerebellar peduncles (52% versus 18%; p = 0.002) seemed more common in children who developed PFS. Young adults showed an expected lower incidence of PFS (4 out of 27; 15%), that may be due to anatomical, physiological and oncological elements. This study confirmed some factors known to be associated with PFS onset and shed light on other debated issues. Our findings enhance an already hypothesized role of cerebellar language lateralization. The analysis of a population of young adults may shed more light on the often-neglected existence of PFS in non-pediatric patients.

The Role of Stereotactic Frame-Based Biopsy for Brainstem Tumors in the Era of Molecular-Based Diagnosis and Treatment Decisions.

Stereotactic frame-based brain tumor biopsy (SFB) is a potent diagnostic tool considering its minimal invasiveness, though its diagnostic power and safety for brainstem lesions remain to be discussed. Here, we aimed to examine the usefulness of SFB for brainstem tumors. Twenty-two patients with brainstem tumors underwent 23 SFBs at our institution during 2002–2021. We retrospectively analyzed patient characteristics, tumor pathology, surgical procedures, and outcomes, including surgery-related complications and the diagnostic value. Seven (32%) tumors were located from the midbrain to the pons, eleven (50%) in the pons only, and four (18%) from the pons to the medulla oblongata. The target lesions were in the middle cerebellar peduncles in sixteen procedures (70%), the cerebellum in four (17%), the inferior cerebellar peduncles in two (9%), and the superior cerebellar peduncles in one (4%). A definitive diagnosis was made in 21 patients (95%) at the first SFB. The diagnoses were glioma in seventeen (77%) cases, primary central nervous system lymphoma in four (18%), and a metastatic brain tumor in one (5%). The postoperative complications (cranial nerve palsy in three [13%] cases, ataxia in one [4%]) were all transient. SFB for brainstem tumors yields a high diagnostic rate with a low risk of morbidity.

Connections of the Dentate Nucleus with the Amygdala: Experimental Rat and Human 3-Tesla Tractography Study.

Background: The role of the cerebellum in motor function is well recognized. However, its role in higher nervous system activities such as cognition, emotion, endocrine, and autonomic activities is less known. The present study aims to show direct dento-amygdala projections using a biotinylated dextran amine (BDA) tracer in rats and 3-tesla (T) high-resolution diffusion tensor imaging (DTI)-based tractography in humans. Materials and Methods: The BDA tracer was pressure injected into the dentate nucleus of the cerebellum of Wistar albino rats. Labeled cells and axons were documented. High-resolution 3-T tractography data were obtained from the Human Connectome Project database. Dento-amygdala tracts were analyzed using diffusion spectrum imaging (DSI) Studio software. Results: The experimental study showed bilateral projections between the dentate nucleus and the central and basal nuclei and ipsilateral projections between lateral nuclei of the amygdala. The fibers from the dentate nucleus reached the amygdala through the superior cerebellar peduncle (SCP), and the contralateral fibers crossed in the decussation of SCP at the midbrain. The dento-amygdala results of the experimental study corresponded with the 3-T tractography findings on humans. Additionally, DTI findings showed that most of the dentate fibers passed through the hypothalamus before reaching the amygdala, and the amygdalae of the two sides are connected through the anterior commissure. Discussion: The 3-T DTI data of adult humans showed both direct dento-amygdala and indirect dento-hypothalamo-amygdala projections. Thus, this may indicate cerebellar contribution in modulation of emotional and autonomic functions. Furthermore, this can explain the emotional and cognitive deficits that occur in patients with cerebellar or SCP damage. Impact statement The present study showed direct dento-amygdala connections in the rat brain and human brain, which may provide evidence for cerebellar contribution in modulation of emotional and autonomic functions.

Human Brain Lipidomics: Investigation of Formalin Fixed Brains.

Human brain lipidomics have elucidated structural lipids and lipid signal transduction pathways in neurologic diseases. Such studies have traditionally sourced tissue exclusively from brain bank biorepositories, however, limited inventories signal that these facilities may not be able to keep pace with this growing research domain. Formalin fixed, whole body donors willed to academic institutions offer a potential supplemental tissue source, the lipid profiles of which have yet to be described. To determine the potential of these subjects in lipid analysis, the lipid levels of fresh and fixed frontal cortical gray matter of human donors were compared using high resolution electrospray ionization mass spectrometry. Results revealed commensurate levels of specific triacylglycerols, diacylglycerols, hexosyl ceramides, and hydroxy hexosyl ceramides. Baseline levels of these lipid families in human fixed tissue were identified via a broader survey study covering six brain regions: cerebellar gray matter, superior cerebellar peduncle, gray and subcortical white matter of the precentral gyrus, periventricular white matter, and internal capsule. Whole body donors may therefore serve as supplemental tissue sources for lipid analysis in a variety of clinical contexts, including Parkinson’s disease, Alzheimer’s disease, Lewy body dementia, multiple sclerosis, and Gaucher’s disease.