Bilateral effect of acupuncture on cerebrum and cerebellum in ischaemic stroke patients with hemiparesis: a randomised clinical and neuroimaging trial.

BACKGROUND: Acupuncture involving the limb region may be effective for stroke rehabilitation clinically, but the visualised and explanatory evidence is limited. Our objectives were to assess the specific effects of acupuncture for ischaemic stroke (IS) patients with hemiparesis and investigate its therapy-driven modification in functional connectivity. METHODS: IS patients were randomly assigned (2:1) to receive 10 sessions of hand-foot 12 needles acupuncture (HA, n=30) or non-acupoint (NA) acupuncture (n=16), enrolling gender-matched and age-matched healthy controls (HCs, n=34). The clinical outcomes were the improved Fugl-Meyer Assessment scores including upper and lower extremity (ΔFM, ΔFM-UE, ΔFM-LE). The neuroimaging outcome was voxel-mirrored homotopic connectivity (VMHC). Static and dynamic functional connectivity (sFC, DFC) analyses were used to study the neuroplasticity reorganisation. RESULTS: 46 ISs (mean(SD) age, 59.37 (11.36) years) and 34 HCs (mean(SD) age, 52.88 (9.69) years) were included in the per-protocol analysis of clinical and neuroimaging. In clinical, ΔFM scores were 5.00 in HA group and 2.50 in NA group, with a dual correlation between ΔFM and ΔVMHC (angular: r=0.696, p=0.000; cerebellum: r=-0.716, p=0.000) fitting the linear regression model (R2=0.828). In neuroimaging, ISs demonstrated decreased VMHC in bilateral postcentral gyrus and cerebellum (Gaussian random field, GRF corrected, voxel p<0.001, cluster p<0.05), which fitted the logistic regression model (AUC=0.8413, accuracy=0.7500). Following acupuncture, VMHC in bilateral superior frontal gyrus orbital part was increased with cerebro-cerebellar changes, involving higher sFC between ipsilesional superior frontal gyrus orbital part and the contralesional orbitofrontal cortex as well as cerebellum (GRF corrected, voxel p<0.001, cluster p<0.05). The coefficient of variation of VMHC was decreased in bilateral posterior cingulate gyrus (PPC) locally (GRF corrected, voxel p<0.001, cluster p<0.05), with integration states transforming into segregation states overall (p<0.05). There was no acupuncture-related adverse event. CONCLUSIONS: The randomised clinical and neuroimaging trial demonstrated acupuncture could promote the motor recovery and modified cerebro-cerebellar VMHC via bilateral static and dynamic reorganisations for IS patients with hemiparesis.

White and Gray Matter Changes are Associated With Neurocognitive Decline in HIV Infection.

OBJECTIVE: To investigate the relationship between neurocognitive deficits and structural changes on brain magnetic resonance imaging in people living with HIV (PLWH) with good virological control on combination antiretroviral therapy, compared with socioeconomically matched control participants recruited from the same communities. METHODS: Brain magnetic resonance imaging scans, and clinical and neuropsychological data were obtained from virologically controlled PLWH (viral load of <50 c/mL and at least 1 year of combination antiretroviral therapy) and socioeconomically matched control participants. Magnetic resonance imaging was carried out on 3 T scanner with 8-channel head coils and segmented using Classification using Derivative-based Features. Multiple regression analysis was performed to examine the association between brain volume and various clinical and neuropsychiatric parameters adjusting for age, race, and sex. To evaluate longitudinal changes in brain volumes, a random coefficient model was used to evaluate the changes over time (age) adjusting for sex and race. RESULTS: The cross-sectional study included 164 PLWH and 51 controls, and the longitudinal study included 68 PLWH and 20 controls with 2 or more visits (mean 2.2 years, range 0.8-5.1 years). Gray matter (GM) atrophy rate was significantly higher in PLWH compared with control participants, and importantly, the GM and global atrophy was associated with the various neuropsychological domain scores. Higher volume of white matter hyperintensities were associated with increased atherosclerotic cardiovascular disease risk score, and decreased executive functioning and memory domain scores in PLWH. INTERPRETATION: These findings suggest ongoing neurological damage even in virologically controlled participants, with significant implications for clinical management of PLWH. ANN NEUROL 2024;95:941-950.

Default mode network connectivity and social dysfunction in children with Attention Deficit/Hyperactivity Disorder

Objective: Attention Deficit/Hyperactivity Disorder (ADHD) negatively affects social functioning; however, its neurological underpinnings remain unclear. Altered Default Mode Network (DMN) connectivity may contribute to social dysfunction in ADHD. We investigated whether DMN's dynamic functional connectivity (dFC) alterations were associated with social dysfunction in individuals with ADHD. Methods: Resting-state fMRI was used to examine DMN subsystems (dorsal medial prefrontal cortex (dMPFC), medial temporal lobe (MTL)) and the midline core in 40 male ADHD patients (7-10 years) and 45 healthy controls (HCs). Connectivity correlations with symptoms and demographic data were assessed. Group-based analyses compared rsFC between groups with two-sample t-tests and post-hoc analyses. Results: Social dysfunction in ADHD patients was related to reduced DMN connectivity, specifically in the MTL subsystem and the midline core. ADHD patients showed decreased dFC between parahippocampal cortex (PHC) and left superior frontal gyrus, and between ventral medial prefrontal cortex (vMPFC) and right middle frontal gyrus compared to HCs (MTL subsystem). Additionally, decreased dFC between posterior cingulate cortex (PCC), anterior medial prefrontal cortex (aMPFC), and right angular gyrus (midline core) was observed in ADHD patients relative to HCs. No abnormal connectivity was found within the dMPFC. Conclusion: Preliminary findings suggest that DMN connectional abnormalities may contribute to social dysfunction in ADHD, providing insights into the disorder's neurobiology and pathophysiology. (AU)

On presentation of the human cerebral sulci from inside of the cerebrum.

The human cerebral cortex is highly convoluted forming patterns of gyri separated by sulci. The cerebral sulci and gyri are fundamental in cortical anatomy as well as neuroimage processing and analysis. Narrow and deep cerebral sulci are not fully discernible either on the cortical or white matter surface. To cope with this limitation, I propose a new sulci presentation method that employs the inner cortical surface for sulci examination from the inside of the cerebrum. The method has four steps, construct the cortical surface, segment and label the sulci, dissect (open) the cortical surface, and explore the fully exposed sulci from the inside. The inside sulcal maps are created for the left and right lateral, left and right medial, and basal hemispheric surfaces with the sulci parcellated by color and labeled. These three-dimensional sulcal maps presented here are probably the first of this kind created. The proposed method demonstrates the full course and depths of sulci, including narrow, deep, and/or convoluted sulci, which has an educational value and facilitates their quantification. In particular, it provides a straightforward identification of sulcal pits which are valuable markers in studying neurologic disorders. It enhances the visibility of sulci variations by exposing branches, segments, and inter-sulcal continuity. The inside view also clearly demonstrates the sulcal wall skewness along with its variability and enables its assessment. Lastly, this method exposes the sulcal 3-hinges introduced here.

Three-Dimensional Modeling and Extended Reality Simulations of the Cross-Sectional Anatomy of the Cerebrum, Cerebellum, and Brainstem.

BACKGROUND: Understanding the anatomy of the human cerebrum, cerebellum, and brainstem and their 3-dimensional (3D) relationships is critical for neurosurgery. Although 3D photogrammetric models of cadaver brains and 2-dimensional images of postmortem brain slices are available, neurosurgeons lack free access to 3D models of cross-sectional anatomy of the cerebrum, cerebellum, and brainstem that can be simulated in both augmented reality (AR) and virtual reality (VR). OBJECTIVE: To create 3D models and AR/VR simulations from 2-dimensional images of cross-sectionally dissected cadaveric specimens of the cerebrum, cerebellum, and brainstem. METHODS: The Klingler method was used to prepare 3 cadaveric specimens for dissection in the axial, sagittal, and coronal planes. A series of 3D models and AR/VR simulations were then created using 360° photogrammetry. RESULTS: High-resolution 3D models of cross-sectional anatomy of the cerebrum, cerebellum, and brainstem were obtained and used in creating AR/VR simulations. Eleven axial, 9 sagittal, and 7 coronal 3D models were created. The sections were planned to show important deep anatomic structures. These models can be freely rotated, projected onto any surface, viewed from all angles, and examined at various magnifications. CONCLUSION: To our knowledge, this detailed study is the first to combine up-to-date technologies (photogrammetry, AR, and VR) for high-resolution 3D visualization of the cross-sectional anatomy of the entire human cerebrum, cerebellum, and brainstem. The resulting 3D images are freely available for use by medical professionals and students for better comprehension of the 3D relationship of the deep and superficial brain anatomy.

Discrepancy between clinical presentation and cerebral imaging requires further diagnostic effort.

No abstract available.

Altered Effective Connectivity Among the Cerebellum and Cerebrum in Patients with Major Depressive Disorder Using Multisite Resting-State fMRI.

Major depressive disorder (MDD) is a serious and widespread psychiatric disorder. Previous studies mainly focused on cerebrum functional connectivity, and the sample size was relatively small. However, functional connectivity is undirected. And, there is increasing evidence that the cerebellum is also involved in emotion and cognitive processing and makes outstanding contributions to the symptomology and pathology of depression. Therefore, we used a large sample size of resting-state functional magnetic resonance imaging (rs-fMRI) data to investigate the altered effective connectivity (EC) among the cerebellum and other cerebral cortex in patients with MDD. Here, from the perspective of data-driven analysis, we used two different atlases to divide the whole brain into different regions and analyzed the alterations of EC and EC networks in the MDD group compared with healthy controls group (HCs). The results showed that compared with HCs, there were significantly altered EC in the cerebellum-neocortex and cerebellum-basal ganglia circuits in MDD patients, which implied that the cerebellum may be a potential biomarker of depressive disorders. And, the alterations of EC brain networks in MDD patients may provide new insights into the pathophysiological mechanisms of depression.

What lies underneath: Precise classification of brain states using time-dependent topological structure of dynamics

The self-organising global dynamics underlying brain states emerge from complex recursive nonlinear interactions between interconnected brain regions. Until now, most efforts of capturing the causal mechanistic generating principles have supposed underlying stationarity, being unable to describe the non-stationarity of brain dynamics, i.e. time-dependent changes. Here, we present a novel framework able to characterise brain states with high specificity, precisely by modelling the time-dependent dynamics. Through describing a topological structure associated to the brain state at each moment in time (its attractor or 'information structure'), we are able to classify different brain states by using the statistics across time of these structures hitherto hidden in the neuroimaging dynamics. Proving the strong potential of this framework, we were able to classify resting-state BOLD fMRI signals from two classes of post-comatose patients (minimally conscious state and unresponsive wakefulness syndrome) compared with healthy controls with very high precision

Resonancia magnética cerebral sin anestesia en niños menores de 3 meses / Brain MRI without anesthesia in children less than 3 months old

Introducción: El uso de anestesia general en niños pequeños conlleva riesgos, a corto y largo plazo. El objetivo de este estudio fue evaluar la eficacia de la técnica de resonancia magnética (RM) cerebral sin anestesia mediante fijación con colchón en niños menores de 3 meses. Pacientes y métodos: Estudio prospectivo de casos y controles realizado en el año 2019. Los casos fueron pacientes menores de 3 meses con indicación de RM craneal, estables y sin soporte ventilatorio; las resonancias se realizaron usando la técnica de dar de comer y dormir y un colchón inmovilizador. Los controles fueron pacientes de la misma edad y sexo, inestables clínicamente, derivados para realizar RM craneal con anestesia general. Tres radiólogos pediátricos evaluaron el éxito de la RM (si respondía a la pregunta clínica), si era necesario repetirla y calificaron la presencia de artefactos de movimiento en una escala del 1 al 4. Resultados: 47 casos fueron incluidos en este estudio (28 niños, 19 niñas; media: 31 días de vida), de los cuales (89%) 42 RM fueron llevadas a cabo de manera exitosa. Los estudios realizados de manera ambulatoria se asociaron a mayor posibilidad de fallo de la técnica que los realizados a ingresados (valor de p 0,02). El 60% de las RM de los casos realizados tuvieron calidad óptima y el 30%, subóptima (artefacto de movimiento en una o dos secuencias). No se detectaron problemas de seguridad con esta técnica. La media de duración de los estudios fue de 16,6 minutos (rango 6-30 minutos). El 100% de las RM de los controles bajo anestesia general se llevaron a cabo con éxito, con una calidad óptima en el 89% y subóptima en el 11% restante. En el primer año de experiencia con esta técnica, de 47 RM realizadas, se evitó el uso de anestesia general a 42 recién nacidos. Conclusión: La técnica de dar de comer y dormir y fijación con colchón neumático para realizar RM sin anestesia puede realizarse de forma eficaz y segura en niños menores de 3 meses.(AU)

Introduction: The use of general anesthesia in infants involves both short-term and long-term risks. The aim of this study is to evaluate the efficacy of brain MRI without anesthesia in infants younger than 3-month-old immobilized with a pillow. Patients and methods: This prospective case-control study was done in 2019. Cases were stable patients less than 3 months old who did not require ventilatory support for whom brain MRI was indicated. Patients were fed so they would fall asleep and placed in the scanner with an immobilizing pillow. Controls were clinically unstable patients matched for age and sex referred for brain MRI under general anesthesia. Three pediatric radiologists evaluated the success of the MRI study (whether it answered the clinical question), recorded whether it was necessary to repeat the study, and rated the presence of motion artifacts on a scale ranging from 1 to 4. Results: A total of 47 cases were included (28 boys and 19 girls; mean age, 31 days). Of these, 42 (89%) MRI studies were considered successful. The proportion of successful MRI studies was lower in outpatients than in inpatients (p=0.02). The quality of MRI in cases was considered optimal in 60% and suboptimal (motion artifacts in one or two sequences) in 30%. No safety issues related with the technique were detected. The mean duration of the studies was 16.6minutes (range, 6-30minutes). All of the MRI studies in controls were considered successful; quality was considered optimal in 89% and suboptimal in 11%. In the first year in which we used this technique, we avoided the use of general anesthesia in 47 MRI studies in 42 newborns. Conclusion: Brain MRI using the feed and sleep technique in infants younger than 3-month-old immobilized with a pillow can be done safely and efficaciously without general anesthesia.(AU)

Tomografía computarizada cerebral solicitada desde Urgencias: la realidad / Brain CT requests from emergency department: reality

Objetivos: Evaluar los motivos más frecuentes por los que se solicitan estudios de imagen craneales desde el Servicio de Urgencias y calcular la prevalencia de la patología aguda urgente en este grupo de población. Material y métodos: Se recogieron las tomografías computarizadas (TC) cerebrales solicitadas por el Servicio de Urgencias en los meses de octubre y noviembre de 2018. Se recogieron los siguientes datos: edad, sexo, motivo de solicitud del estudio, hallazgos encontrados en la prueba de imagen, administración de medios de contraste y motivo, y en caso de que el paciente tuviera estudios de imagen craneales previos, reseñar la existencia de cambios. Se utilizó el programa SPSS para hacer el análisis estadístico. Resultados: Se realizaron 507 TC de cerebro urgentes, 41,4% en hombres y 58,6% en mujeres, con una edad media de 65,4±20 años. El motivo de solicitud más frecuente fue el traumatismo craneal (40,5%), y de ellos únicamente el 15,6% presentó patología intracraneal postraumática aguda. El segundo motivo fue sintomatología neurológica focal (16%), de los cuales el 16% presentó infarto isquémico reciente o hemorragia aguda. En cuanto a los hallazgos, el 43,2% de los estudios fueron informados como normales. El hallazgo más frecuentemente encontrado fue lesiones isquémicas de pequeño vaso, en un 20%. En un 3,9% de todos los pacientes se encontraron lesiones ocupantes de espacio, incluyendo lesiones tanto benignas como malignas. Conclusiones: La mayoría de los estudios cerebrales solicitados desde urgencias no muestran patología que modifique el manejo del paciente. La sobreutilización de la TC cerebral urgente sobrecarga los servicios de radiología y somete a la población a radiación innecesaria.(AU)

Objectives: To evaluate the most common reasons for requesting brain CT studies from the emergency department and to calculate the prevalence of urgent acute pathology on this population group. Material and methods: We reviewed brain CT studies requested from the emergency department during October and November 2018. We recorded the following variables: age, sex, reason for requesting the study, CT findings, use of contrast agents and reasons for using them, and, in patients who had undergone previous head CT studies, whether the findings had changed. SPSS was used for statistical analyses. Results: A total of 507 urgent brain CT studies were done (41.4% in men, 58.6% in women; mean age, 65.4±20 years). The most common reason for requesting the study was head trauma (40.5%); only 15.6% of these studies showed acute posttraumatic intracranial lesions. The second most common reason was focal neurologic symptoms (16%); only 16% of these studies showed recent ischemic infarcts or acute bleeding. No pathological findings were reported in 43.2% of the studies. The most common abnormal finding was small vessel disease (20%). Space-occupying lesions (both benign and malignant) were found in 3.9% of all patients. Conclusions: Most brain CT studies requested from the emergency department showed no findings that would modify the management of the patient. Overuse of urgent brain CT increases the radiology department's workload and exposes patients to radiation unnecessarily.(AU)

Cambios estructurales cerebrales en la epilepsia mioclónica juvenil farmacorresistente / Structural changes to the brain in drug-resistant juvenile myoclonic epilepsy

Introducción: El objetivo de la investigación es determinar los cambios en las estructuras cerebrales, tanto corticales como subcorticales, de pacientes con epilepsia mioclónica juvenil (EMJ) farmacorresistente, para aportar al conocimiento de las características del síndrome farmacorresistente y brindar posibles respuestas e hipótesis para nuevos estudios y tratamientos más adecuados. Sujetos y métodos: Estudio observacional de casos y controles. Se define un tamaño de muestra a conveniencia de cuatro casos y 16 controles sanos para garantizar la viabilidad del proyecto (relación 4:1). Los datos recolectados para los pacientes con EMJ farmacorresistentes provienen de un equipo de resonancia magnética de 1,5 T. Para determinar las áreas corticales y subcorticales, tanto en la EMJ farmacorresistente como en los controles sanos, se usó el software FreeSurfer. Resultados: Se incluyó a un total de 20 participantes en el estudio, de los cuales cuatro (20%) corresponden a EMJ farmacorresistentes y 16 (80 %) a controles sanos. La localización de los clústeres con diferencias estadísticamente significativas en el grosor cortical se encuentra en el giro precentral, el giro temporal superior, el giro temporal transverso, el giro temporal medial y el giro supramarginal, con predominancia en el hemisferio izquierdo. Conclusiones: Se evidencian cambios estructurales cerebrales en pacientes con EMJ farmacorresistente, cambios que pueden pasar desapercibidos por las técnicas convencionales en el procesamiento de las imágenes de resonancia magnética.(AU)

Introduction: The aim of this research is to determine the changes in brain structures, both cortical and subcortical, in patients with drug-resistant juvenile myoclonic epilepsy (JME), in order to contribute to the understanding of the characteristics of the drug-resistant syndrome and to offer possible answers and hypotheses for further studies and more adequate treatments. Subjects and methods: Observational case-control study. A convenience sample size of four cases and 16 healthy controls was defined to ensure the feasibility of the project (ratio of 4:1). The data collected for patients with drug-resistant JME came from 1.5T MRI equipment. FreeSurfer software was used to determine cortical and subcortical areas in both drug-resistant JME patients and healthy controls. Results: A total of 20 participants were included in the study, of whom four (20%) were drug-resistant JME patients and 16% (80%) were healthy controls. The clusters with statistically significant differences in cortical thickness are located in the precentral gyrus, superior temporal gyrus, transverse temporal gyrus, medial temporal gyrus and supramarginal gyrus, predominantly in the left hemisphere. Conclusions: Structural brain changes are observed in patients with drug-resistant JME that may go undetected by the conventional processing techniques used in magnetic resonance imaging.(AU)

Functional mapping and cooperation between the cerebellum and cerebrum during word reading.

Multiple areas in the cerebellum have been reported to be engaged in reading. However, how these regions cooperate with the reading-related areas in the cerebrum remains unclear. Here, brain images of fifty-two adults were acquired via functional magnetic resonance imaging. By comparing the cerebellar activation across three localization tasks targeting orthographic, phonological, and semantic processing, we first identified three different reading-related areas in the cerebellum, biased toward orthography, phonology, and semantics, respectively. Then, functional connectivity (FC) analyses demonstrated that the mean FC between functionally corresponding areas across the cerebrum and cerebellum was greater than that between noncorresponding areas during silent word reading. FC patterns of functionally corresponding areas could significantly predict reading speed, with the FC driven from orthographic and semantic areas contributing the most. Effective FC analyses further showed that orthographic and semantic areas in the cerebellum had selective and direct connectivity to areas in the cerebrum with similar functional specificity. These results suggest that reading-related areas vary in their functions to reading, and cooperation between areas with corresponding functions was greater than that between noncorresponding areas. These findings emphasize the importance of functional cooperation between the cerebrum and cerebellum during reading from a new perspective.

Negative bias effects during audiovisual emotional processing in major depression disorder.

Aberrant affective neural processing and negative emotional bias are trait-marks of major depression disorders (MDDs). However, most research on biased emotional perception in depression has only focused on unimodal experimental stimuli, the neural basis of potentially biased emotional processing of multimodal inputs remains unclear. Here, we addressed this issue by implementing an audiovisual emotional task during functional MRI scanning sessions with 37 patients with MDD and 37 gender-, age- and education-matched healthy controls. Participants were asked to distinguish laughing and crying sounds while being exposed to faces with different emotional valences as background. We combined general linear model and psychophysiological interaction analyses to identify abnormal local functional activity and integrative processes during audiovisual emotional processing in MDD patients. At the local neural level, MDD patients showed increased bias activity in the ventromedial prefrontal cortex (vmPFC) while listening to negative auditory stimuli and concurrently processing visual facial expressions, along with decreased dorsolateral prefrontal cortex (dlPFC) activity in both the positive and negative visual facial conditions. At the network level, MDD exhibited significantly decreased connectivity in areas involved in automatic emotional processes and voluntary control systems during perception of negative stimuli, including the vmPFC, dlPFC, insula, as well as the subcortical regions of posterior cingulate cortex and striatum. These findings support a multimodal emotion dysregulation hypothesis for MDD by demonstrating that negative bias effects may be facilitated by the excessive ventral bottom-up negative emotional influences along with incapability in dorsal prefrontal top-down control system.

Massive cerebral air embolism following percutaneous transhepatic biliary drainage: A case report.

RATIONALE: Cerebral air embolism from portal venous gas rarely occurs due to invasive procedures (e.g., endoscopic procedures, liver biopsy, or percutaneous transhepatic biliary drainage) that disrupt the gastrointestinal or hepatobiliary structures. Here, we report a rare case of fatal cerebral air embolism following a series of percutaneous transhepatic biliary drainage tube insertions. PATIENT CONCERNS: A 50-year-old woman with a history of cholecystectomy, liver wedge resection, and hepaticojejunostomy for gallbladder cancer presented with altered mental status 1 week after percutaneous transhepatic biliary drainage tube placement. DIAGNOSES: Extensive cerebral air embolism and acute cerebral infarction. INTERVENTIONS: Brain computed tomography and magnetic resonance imaging, hyperbaric oxygen therapy, medical therapy. OUTCOMES: Despite the use of hyperbaric oxygen therapy and medical treatment including vasopressors, the patient eventually died due to massive systemic air embolism. LESSONS: To date, there have been no reports of cerebral air embolism due to percutaneous transhepatic biliary drainage with pronounced radiologic images. We reviewed previously reported fatal cases associated with endoscopic hepatobiliary procedures and assessed the possible mechanisms and potential causes of air embolism.

Analysis of Changes in Microcirculation Parameters of Symmetrical Areas of the Human Head under Conditions of Hypoxic Influences.

The reactions of microcirculation parameters of symmetrical areas of the human head to hypoxic loads were studied. The study was conducted in 10 healthy male volunteers aged 18-19 years. Short-term hypoxia was modeled using a ReOxy Cardio normobaric device (S. A. Aimediq). Synchronous measurements of microcirculation parameters in symmetrical temporal regions of the head at the basal state and immediately after short-term hypoxic exposure were carried out by the method of laser Doppler flowmetry. We evaluated statistical characteristics of perfusion of both sides, as well as regression characteristics of the relationship between changes in the microcirculation parameters and the initial values of these parameters. It was shown that the reaction of the microcirculation parameters in symmetrical regions of the head to hypoxia depends on the initial microcirculation parameters in ipsi- and contralateral sides. 3D graphs were constructed and regression equations describing these relationships were formulated. A new method of geometric sensing is proposed, which allows predicting the direction of reactions to hypoxic effects. The obtained data illustrate the specificity of regulation of microcirculation of paired organs determined by the presence of functional asymmetry. A new method of geometric zoning is proposed, which allows solving the problems of personalized assessments of the state of the microcirculation system in patients.

Genotype-associated cerebellar profiles in ALS: focal cerebellar pathology and cerebro-cerebellar connectivity alterations.

OBJECTIVE: Cerebellar disease burden and cerebro-cerebellar connectivity alterations are poorly characterised in amyotrophic lateral sclerosis (ALS) despite the likely contribution of cerebellar pathology to the clinical heterogeneity of the condition. METHODS: A prospective imaging study has been undertaken with 271 participants to systematically evaluate cerebellar grey and white matter alterations, cerebellar peduncle integrity and cerebro-cerebellar connectivity in ALS. Participants were stratified into four groups: (1) patients testing positive for GGGGCC repeat expansions in C9orf72, (2) patients carrying an intermediate-length repeat expansion in ATXN2, (3) patients without established ALS-associated mutations and (4) healthy controls. Additionally, the cerebellar profile of a single patient with ALS who had an ATXN2 allele length of 62 was evaluated. Cortical thickness, grey matter and white matter volumes were calculated in each cerebellar lobule complemented by morphometric analyses to characterise genotype-associated atrophy patterns. A Bayesian segmentation algorithm was used for superior cerebellar peduncle volumetry. White matter diffusivity parameters were appraised both within the cerebellum and in the cerebellar peduncles. Cerebro-cerebellar connectivity was assessed using deterministic tractography. RESULTS: Cerebellar pathology was confined to lobules I-V of the anterior lobe in patients with sporadic ALS in contrast to the considerable posterior lobe and vermis disease burden identified in C9orf72 mutation carriers. Patients with intermediate ATXN2 expansions did not exhibit significant cerebellar pathology. CONCLUSIONS: Focal rather than global cerebellar degeneration characterises ALS. Pathognomonic ALS symptoms which are typically attributed to other anatomical regions, such as dysarthria, dysphagia, pseudobulbar affect, eye movement abnormalities and cognitive deficits, may be modulated, exacerbated or partially driven by cerebellar changes in ALS.