Brainstem Structures Research Articles

Global and Regional Deep Learning Models for Multiple Sclerosis Stratification From MRI.

The combination of anatomical MRI and deep learning-based methods such as convolutional neural networks (CNNs) is a promising strategy to build predictive models of multiple sclerosis (MS) prognosis. However, studies assessing the effect of different input strategies on model's performance are lacking. To compare whole-brain input sampling strategies and regional/specific-tissue strategies, which focus on a priori known relevant areas for disability accrual, to stratify MS patients based on their disability level. Retrospective. Three hundred nineteen MS patients (382 brain MRI scans) with clinical assessment of disability level performed within the following 6 months (~70% training/~15% validation/~15% inference in-house dataset) and 440 MS patients from multiple centers (independent external validation cohort). Single vendor 1.5 T or 3.0 T. Magnetization-Prepared Rapid Gradient-Echo and Fluid-Attenuated Inversion Recovery sequences. A 7-fold patient cross validation strategy was used to train a 3D-CNN to classify patients into two groups, Expanded Disability Status Scale score (EDSS) ≥ 3.0 or EDSS < 3.0. Two strategies were investigated: 1) a global approach, taking the whole brain volume as input and 2) regional approaches using five different regions-of-interest: white matter, gray matter, subcortical gray matter, ventricles, and brainstem structures. The performance of the models was assessed in the in-house and the independent external cohorts. Balanced accuracy, sensitivity, specificity, area under receiver operating characteristic (ROC) curve (AUC). With the in-house dataset, the gray matter regional model showed the highest stratification accuracy (81%), followed by the global approach (79%). In the external dataset, without any further retraining, an accuracy of 72% was achieved for the white matter model and 71% for the global approach. The global approach offered the best trade-off between internal performance and external validation to stratify MS patients based on accumulated disability. 4 TECHNICAL EFFICACY: Stage 2.

A Phase II Trial of Intraoperative Radiotherapy after Surgical Resection of Brain Metastases: Feasibility and Efficacy NCT04847284

Intraoperative radiation therapy (IORT) is an alternative to local radiation therapy for brain metastases, reducing total treatment time, and improving patient comfort, but the most effective dose is unknown. The objective of this study is to evaluate the efficacy and safety of IORT in patients with surgical excision of brain metastases at a dose of 20 Gy. This trial is a single-institution, open-label, prospective, non-randomized study for intraoperative radiotherapy immediately after resection of brain metastases. Registered in January 2021, currently ongoing, planned to enroll 25 patients with IK ≥70, brain damage newly diagnosed by MRI, without dural contact and at least 1 cm to the optic nerve, chiasm and brainstem. In the baseline visit, the General Cognitive State will be carried out: Minimum Mental State Exams. Specific cognitive study: 1- Processing speed (SYmbol digit modalities test), 2- Executive function (TMT, back and forward digit span test, phonological and semantic verbal fluency test, Stroop color-word test), 3- Verbal memory (FCSRT). Quality of life will be monitored by completing the EORTC QL-C30 and BN20 questionnaires. Intraoperative radiation therapy will be performed with a 50 kV low energy X-ray portable linear accelerator using spherical applicators ranging from 1.5 to 4 cm kV to deliver 20 Gy to the surface. During IORT a maximum dose (DMax) of 8 Gy will be allowed to the optic nerve/chiasm and brainstem structures. MRI will be performed 72 hours after IORT. Neurocognitive Test and MRI after 6 weeks and every 3 months. The primary endpoint will be local progression free survival (PFS). Secondary endpoints will be overall survival, time to save cancer therapy, cognitive performance and quality of life, as well as IORT-related neurotoxicity complications will be evaluated according to the scale of the CTACAE version 4. The analysis of the median local progression free survival, overall survival will be analyzed using the Kaplan-Meier curve (long range test). All results will be considered statistically significant with a p value < 0.05. The statistical analysis will be carried out with statistical software. The trial is open and ongoing to recruitment; we have included 7 patients. The 85.7% were male, mean age was 61.4 years range (43-74). The 57.1% were lung cancer metastases. For now, no tumor recurrence or neurocognitive complications have been observed and then once you have the results ready, we will publish them. The limited current literature on the use of IORT in brain metastases appears to show efficacy and safety, but the most effective dose is unknown as well as whether it is as effective as other radiotherapy alternatives. Our study is ongoing and needs to be completed and evaluated with more follow-up in order to reach definitive conclusions.

Brainstem and subcortical regions volume loss in patients with degenerative cervical myelopathy and its association with spinal cord compression severity

BackgroundIn recent years, structural and functional reorganization of the brain and changes in brainstem structural connectivity have been shown in patients with degenerative cervical myelopathy (DCM). We hypothesized that volume loss in the basal ganglia, thalami, and brainstem structures exists and is associated with spinal cord compression severity in patients with DCM. MethodsForty-seven patients with DCM and 25 patients with cervical radiculopathy were evaluated using cervical spinal cord and brain magnetic resonance imaging (MRI). Brainstem structures, basal ganglia, and thalami volumes were evaluated with FreeSurfer and compared between groups with correction for individual intracranial volume, as well as patient age and sex. Additionally, spinal cord MRI data were analysed with the Spinal Cord Toolbox, and cross-sectional area (CSA) and fractional anisotropy (FA) values were calculated. Correlations between MR-morphometry data and spinal cord structural changes, as well as disease duration, were also evaluated in patients with DCM. ResultsA statistically significant reduction in the volume of the whole brainstem was revealed in the DCM group compared to the radiculopathy group (p < 0.01, FDR-corrected). Additionally, reductions in medulla oblongata, pons and midbrain volumes were found in patients with DCM (p < 0.01, p < 0.01 and p < 0.05, respectively, FDR-corrected). Additionally, a trend in the loss of volume of the left putamen was found (p = 0.087, FDR-corrected). Furthermore, medulla oblongata volume was correlated with spinal cord compression severity (R = 0.54, adjusted p < 0.001) and white matter damage (R = 0.46, adjusted p < 0.05) in patients with DCM. Negative correlations between the duration of the disease and the severity of spinal cord compression (R = −0.42, adjusted p < 0.05) and white matter damage (R = −0.49, adjusted p < 0.05) were also revealed, as well as a trend toward a negative association between the duration of the disease and the volume of the medulla oblongata (R = −0.35; adjusted p < 0.1). ConclusionsWe revealed a reduction in the volume of brainstem structures in patients with DCM compared to patients with radiculopathy. Moreover, we found that these changes are associated with cord compression severity.

Clinical and neurophysiological correlations in patients with acute non-traumatic hemispheric hematomas

The aim of the study was to identify the relationship between clinical and neurophysiological parameters in patients with non-traumatic supratentorial hematomas. We examined 90 patients in acute period of parenchymal hemorrhagic stroke; the Glasgow Coma Scale (at first day) and the NIHSS (at 1st, 3rd, and 14th days) were used for the assessment of clinical dynamics. Two groups of patients were identified by means of cluster analysis. Cluster 1 included the patients with lower number of correlations between neurophysiologic parameters; cluster 2 included the patients with higher level of conjugacy in the mechanisms of nervous regulation. The clinical and neurophysiological correlations that differed between the groups of the patients were found. The role of EEG slow-wave activity and its association with the severity of neurological symptoms in the group of the patients with regress of neurological deficit were described. The role of desynchronizing influences in minimizing the severity of neurological deficit in patients with unfavorable course of disease was established. In conclusion, we emphasize the heterogeneity of the groups of the patients with parenchymal hemorrhagic stroke due to their clinical course; the role of synchronizing and desynchronizing influences of the brainstem structures according to EEG data in the assessment of the course of acute period of hemorrhagic stroke is highlighted.

Magnetic susceptibility changes in the brainstem reflect REM sleep without atonia severity in isolated REM sleep behavior disorder

REM sleep without atonia (RWA) is the hallmark of isolated REM sleep behavior disorder (iRBD) and is caused by neurodegeneration of brainstem structures. Previously, quantitative susceptibility mapping (QSM) was shown to detect microstructural tissue changes in neurodegenerative diseases. The goal of the study was to compare brainstem magnetic susceptibility (MS) in iRBD and controls using the voxel-based QSM approach and to examine the association between brainstem MS and severity of RWA in iRBD. Sixty iRBD patients and 41 healthy controls were included in the study. Phasic, tonic, mixed RWA and SINBAR score was quantified. QSM maps were reconstructed with QSMbox software from a multi-gradient-echo sequence acquired at 3T MRI system and normalized using a custom T1 template. Voxel-based analysis with age and gender as covariates was performed using a two-sample t-test model for between-group comparison and using a linear regression model for association with the RWA parameters. Statistical maps were generated using threshold free cluster enhancement with p-value p < 0.05, corrected for family wise error. Compared to controls, the iRBD group had higher MS in bilateral substantia nigra (SN), red nucleus and the ventral tegmental area. MS positively correlated with iRBD duration in the right pedunculotegmental nucleus and white matter of caudal mesencephalic and pontine tegmentum and with phasic RWA in bilateral SN. QSM was able to detect MS abnormalities in several brainstem structures in iRBD. Association of MS levels in the brainstem with the intensity of RWA suggests that increased iron content in SN is related to RWA severity.

Longitudinal imaging in Kleefstra syndrome—Brief report and literature review

AbstractBackgroundKleefstra syndrome (KS) is a rare genetic condition affecting the euchromatic histone methyltransferase 1 (EHMT1) gene, typically presenting with developmental delay, generalized hypotonia, distinctive facial dysmorphisms, and neuropsychiatric anomalies.MethodsWe collected longitudinal magnetic resonance imaging (MRI) data of a child with KS and cerebrospinal fluid (CSF) dissection over 16 years and reviewed the literature focusing on articles reporting MRI findings in KS based on a PubMed search.ResultsAn 18‐year‐old female with KS presented with developmental delay at age 18 months and seizures at age 10 years. At age 23 months, MRI showed ventriculomegaly. Follow‐up MRI nine years later showed CSF dissection from the right lateral ventricle, which progressed similarly in the contralateral side 3 years later and stabilized over time. To date, only 20 articles report MRI findings from 49 patients with KS. The brain imaging findings range from normal (about 25%) to various abnormalities, including ventriculomegaly, white matter signal abnormalities, and dysmorphic corpus callosum and brainstem structures. CSF dissection was not found in any cases with white matter or other abnormalities.ConclusionsCSF dissection may be a rare neuroimaging finding of KS. Its etiology is unclear, but we speculate that epigenetic mutations could indirectly affect the development and integrity of ependymal cell lining along the ventricles. Alternatively, the long‐standing hydrocephalus may have caused the development of pseudodiverticula and subsequent CSF dissection.

Brain MRI detects early-stage alterations and disease progression in Friedreich ataxia.

Friedreich ataxia is a progressive neurodegenerative disorder characterized by cerebellar and spinal atrophy. However, studies to elucidate the longitudinal progression of the pathology in the brain are somewhat inconsistent and limited, especially for early-stage Friedreich ataxia. Using a multimodal neuroimaging protocol, combined with advanced analysis methods, we sought to identify macrostructural and microstructural alterations in the brain of patients with early-stage Friedreich ataxia to better understand its distribution patterns and progression. We enrolled 28 patients with Friedreich ataxia and 20 age- and gender-matched controls. Longitudinal clinical and imaging data were collected in the patients at baseline, 12, 24 and 36 months. Macrostructural differences were observed in patients with Friedreich ataxia, compared to controls, including lower volume of the cerebellar white matter (but not cerebellar grey matter), superior cerebellar peduncle, thalamus and brainstem structures, and higher volume of the fourth ventricle. Diffusion tensor imaging and fixel-based analysis metrics also showed microstructural differences in several brain regions, especially in the cerebellum and corticospinal tract. Over time, many of these macrostructural and microstructural alterations progressed, especially cerebellar grey and white matter volumes, and microstructure of the superior cerebellar peduncle, posterior limb of the internal capsule and superior corona radiata. In addition, linear regressions showed significant associations between many of those imaging metrics and clinical scales. This study provides evidence of early-stage macrostructural and microstructural alterations and of progression over time in the brain in Friedreich ataxia. Moreover, it allows to non-invasively map such brain alterations over a longer period (3 years) than any previous study, and identifies several brain regions with significant involvement in the disease progression besides the cerebellum. We show that fixel-based analysis of diffusion MRI data is particularly sensitive to longitudinal change in the cerebellar peduncles, as well as motor and sensory white matter tracts. In combination with other morphometric measures, they may therefore provide sensitive imaging biomarkers of disease progression for clinical trials.

Progressive generalized tonic-clonic seizures in a transgenic mouse model of adult-onset epilepsy: Implications for morphological changes in cortico-limbic and brainstem structures

Video/cortical electroencephalography (EEG) is monitored to assess progressive severity of generalized tonic clonic seizures (GTCSs) in a transgenic mouse model of adult-onset epilepsy with increased death risk. The mice overexpress the brain derived neurotrophic factor (BDNF) in the forebrain under the calcium/calmodulin dependent protein kinase 2a (termed TgBDNF) and develop GTCSs in response to tail suspension/cage agitation stimulation at 3–4 months of age. With successive GTCSs (a total of 16 across 10 weeks of assessment), seizures became more severe as evidenced by increased duration of postictal generalized EEG suppression (PGES) associated with loss of posture/consciousness. Mice also developed spike wave discharges with behavioral arrest during the seizure recovery that increased in duration as a function of number of GTCSs. Overall seizure duration (from preictal spike to offset of PGES) and ictal spectral power (full spectra) were also increased. Half of the TgBDNF mice expired following a long period of PGES at the last recorded GTCS. Seizure-evoked general arousal impairment was associated with a striking decrease in total number of gigantocellular neurons of the brainstem nucleus pontis oralis along with increase in volumes of the anterior cingulate cortex and dorsal dentate gyrus in severely convulsive TgBDNF mice compared to litter-matched WT controls and non-convulsive TgBDNF mice. The latter effect was accompanied with an increase in total number of hippocampal granule neurons. These results provide structure-function associations in an animal model of adult-onset GTCSs that progressively increase in severity with clinical relevance for sudden unexpected death following generalized seizures.

Tongue acupuncture for the treatment of post-stroke dysphagia: a meta-analysis of randomized controlled trials.

Post-stroke dysphagia is the most common neurological impairment after stroke. The swallowing process is controlled by a network made up of the cerebral cortex, subcortical area, and brainstem structure. The disruption of the swallowing network after stroke leads to dysphagia. The affected swallowing muscles after stroke mainly include the laryngeal muscles (suprahyoid muscle and thyrohyoid muscle) and infrahyoid muscle. These muscles experience kinematic effects and muscle strength weakens, resulting in reduced movement in the swallowing process. Acupuncture can change the excitability of cerebral cortical nerve cells, promote the recovery of neurological function, and enhance neuromuscular excitability, ultimately improving the control of swallowing-related nerves and muscles and promoting swallowing functional recovery. In this meta-analysis, we systematically evaluate the clinical efficacy of acupuncture in the treatment of post-stroke dysphagia. Randomized controlled trials of tongue acupuncture therapy for post-stroke dysphagia were searched and selected from seven electronic databases (PubMed, CBM, Cochrane, Embase, CNKI, VPCS, and Wan fang). The Cochrane Collaboration tool was used to conduct methodological quality assessment. Rev. Man 5.4 software was utilized to perform data analysis. A total of 15 studies with 1,094 patients were included. Meta-analysis Showed that WST score WST score (MD = -0.56, 95% CI (-1.23, 0.12), Z = 1.62, p < 0.00001), SSA score (MD = -1.65, 95% CI (-2.02, -1.28), Z = 8.77, p < 0.00001). These results suggested that the treatment group (tongue acupuncture or tongue acupuncture combined with other therapies) was superior to the control group in reducing WST scores and SSA scores. The clinical efficacy of the tongue acupuncture group was better compared with the control group (MD = 3.83, 95% CI (2.61, 5.62), Z = 6.88, p < 0.00001). The meta-analysis showed that the total effective rate of patients with dysphagia after stroke in the treatment group (acupuncture, tongue acupuncture, and acupuncture combined with other therapy) was higher than that in the control group. These results indicated that acupuncture, tongue acupuncture, and acupuncture combined with other therapy can improve post-stroke dysphagia.

Surgical outcomes in large vestibular schwannomas: should cerebellopontine edema be considered in the grading systems?

Large (> 3cm) vestibular schwannomas pose complexity in surgical management because of narrow working corridors and proximity to the cranial nerves, brainstem, and inner ear structures. With current vestibular schwannoma classifications limited in information regarding cerebellopontine edema, our retrospective series examined this radiographic feature relative to clinical outcomes and its possible role in preoperative scoring. Of 230 patients who underwent surgical resection of vestibular schwannoma (2014-2020), we identified 107 patients with Koos grades 3 or 4 tumors for radiographic assessment of edema in the middle cerebellar peduncle (MCP), brainstem, or both. Radiographic images were graded and patients grouped into Koos grades 3 or 4 or our proposed grade 5 with edema. Tumor volumes, radiographic features, clinical presentations, and clinical outcomes were evaluated. The 107 patients included 22 patients with grade 3 tumors, 39 with grade 4, and 46 with grade 5. No statistical differences were noted among groups for demographic data or complication rates. Unlike grades 3 and 4 patients, grade 5 patients presented with worse hearing (p < 0.001), larger tumors (p < 0.001), lower rates of gross total resection (GTR), longer hospital stays, and higher rates of balance dysfunction. With edema detected in 43% of this cohort, special considerations are warranted for grade 5 vestibular schwannomas given the preoperative findings of worse hearing, lower GTR rates, longer hospital stays, and 96% who pursued postoperative balance therapy. We propose that grade 5 with edema offers a more nuanced interpretation of a radiographic feature that holds relevance to treatment selection and patient outcomes.

The Role of The Rostral Ventromedial Medulla in Stress Responses.

The rostral ventromedial medulla (RVM) is a brainstem structure critical for the descending pain modulation system involved in both pain facilitation and inhibition through its projection to the spinal cord. Since the RVM is well connected with pain- and stress-engaged brain structures, such as the anterior cingulate cortex, nucleus accumbens, and amygdala, its involvement in stress responses has become a matter of great interest. While chronic stress has been proposed as a trigger of pain chronification and related psychiatric comorbidities due to maladaptive stress responses, acute stress triggers analgesia and other adaptative responses. Here we reviewed and highlighted the critical role of the RVM in stress responses, mainly in acute stress-induced analgesia (SIA) and chronic stress-induced hyperalgesia (SIH), providing insights into pain chronification processes and comorbidity between chronic pain and psychiatric disorders.

Locus coeruleus ablation in mice: protocol optimization, stereology and behavioral impact.

The Locus Coeruleus (LC) is in the brainstem and supplies key brain structures with noradrenaline, including the forebrain and hippocampus. The LC impacts specific behaviors such as anxiety, fear, and motivation, as well as physiological phenomena that impact brain functions in general, including sleep, blood flow regulation, and capillary permeability. Nevertheless, the short- and long-term consequences of LC dysfunction remain unclear. The LC is among the brain structures first affected in patients suffering from neurodegenerative diseases such as Parkinson's disease and Alzheimer's Disease, hinting that LC dysfunction may play a central role in disease development and progression. Animal models with modified or disrupted LC function are essential to further our understanding of LC function in the normal brain, the consequences of LC dysfunction, and its putative roles in disease development. For this, well-characterized animal models of LC dysfunction are needed. Here, we establish the optimal dose of selective neurotoxin N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP-4) for LC ablation. Using histology and stereology, we compare LC volume and neuron number in LC ablated (LCA) mice and controls to assess the efficacy of LC ablation with different numbers of DSP-4 injections. All LCA groups show a consistent decrease in LC cell count and LC volume. We then proceed to characterize the behavior of LCA mice using a light-dark box test, Barnes maze test, and non-invasive sleep-wakefulness monitoring. Behaviorally, LCA mice differ subtly from control mice, with LCA mice generally being more curious and less anxious compared to controls consistent with known LC function and projections. We note an interesting contrast in that control mice have varying LC size and neuron count but consistent behavior whereas LCA mice (as expected) have consistently sized LC but erratic behavior. Our study provides a thorough characterization of an LC ablation model, firmly consolidating it as a valid model system for the study of LC dysfunction.

Radiological Profile of Patients with Wilson’s Disease Attending Tertiary Care Neurology Centre (P13-11.009)

<h3>Objective:</h3> To assess the radiological profile of patients with Wilson’s disease attending a tertiary care neurology center. <h3>Background:</h3> Wilson’s disease (WD) is an autosomal recessive disorder with varied manifestations, resulting from the deposition of copper in organs such as the brain, liver and cornea. This study was aimed at assessing the radiological profile of patients with WD. <h3>Design/Methods:</h3> This study was conducted at the Neurology department of a tertiary care centre. Patients with diagnosed WD (modified Leipzig score 3 or more) underwent 3 Tesla MRI brain with T1W, T2W, FLAIR, diffusion weighted and susceptibility weighted (SWI) sequences. <h3>Results:</h3> Between June 2021 and September 2022, twenty patients (15 males) of WD had brain MRI. Median age of cohort was 21 years (IQR 16–23). The mean duration of the illness was 5 years (range: 2–17) and 90% (18/20) were receiving chelation therapy at the time of imaging. The most common neurological manifestation was dystonia, seen in all the patients. Tremor was seen in 35% (7/20) and ataxia in 30% (6/20) of patients. The most common radiological finding was the hyperintensity of brainstem structures in T2W and FLAIR sequences, seen in 18/20 (90%) patients, followed by basal ganglia (BG) involvement. Putamen (17/20, 85%) was the most common BG structure involved, followed by the caudate nucleus (14/20, 70%). Thalamic involvement was seen in 12/20 (60%) of cases. SWI revealed blooming, most commonly in substantia nigra (12/20, 60%), followed by the globus pallidus (11/20, 55%), and caudate nucleus (7/20, 35%). Cerebellar and cerebral atrophy were seen in 14/20 (70%) and 9/20 (45%) patients, respectively. <h3>Conclusions:</h3> Brainstem involvement was seen most common radiological finding in our cohort, followed by the basal ganglia (putamen) involvement. Findings from our study need to be validated in larger studies and correlated with clinical features, stage of the disease and treatment status. <b>Disclosure:</b> Ms. Aliyar has nothing to disclose. Dr. Radhakrishnan has received research support from Indian Council of Medical Research, New Delhi, India. Dr. Radhakrishnan has received research support from World Federation of Neurology . Ajay Garg has nothing to disclose. Dr. Srivastava has nothing to disclose. Roopa Rajan has received research support from DBT. Roopa Rajan has received research support from DST-SERB. The institution of Roopa Rajan has received research support from Michael J Fox Foundaton. Awadh K. Pandit has nothing to disclose. Dr. Das has nothing to disclose. Dr. Agarwal has nothing to disclose.

Direct localization and delineation of human pedunculopontine nucleus based on a self-supervised magnetic resonance image super-resolution method.

The pedunculopontine nucleus (PPN) is a small brainstem structure and has attracted attention as a potentially effective deep brain stimulation (DBS) target for the treatment of Parkinson's disease (PD). However, the in vivo location of PPN remains poorly described and barely visible on conventional structural magnetic resonance (MR) images due to a lack of high spatial resolution and tissue contrast. This study aims to delineate the PPN on a high-resolution (HR) atlas and investigate the visibility of the PPN in individual quantitative susceptibility mapping (QSM) images. We combine a recently constructed Montreal Neurological Institute (MNI) space unbiased QSM atlas (MuSus-100), with an implicit representation-based self-supervised image super-resolution (SR) technique to achieve an atlas with improved spatial resolution. Then guided by a myelin staining histology human brain atlas, we localize and delineate PPN on the atlas with improved resolution. Furthermore, we examine the feasibility of directly identifying the approximate PPN location on the 3.0-T individual QSM MR images. The proposed SR network produces atlas images with four times the higher spatial resolution (from 1 to 0.25 mm isotropic) without a training dataset. The SR process also reduces artifacts and keeps superb image contrast for further delineating small deep brain nuclei, such as PPN. Using the myelin staining histological atlas as guidance, we first identify and annotate the location of PPN on the T1-weighted (T1w)-QSM hybrid MR atlas with improved resolution in the MNI space. Then, we relocate and validate that the optimal targeting site for PPN-DBS is at the middle-to-caudal part of PPN on our atlas. Furthermore, we confirm that the PPN region can be identified in a set of individual QSM images of 10 patients with PD and 10 healthy young adults. The contrast ratios of the PPN to its adjacent structure, namely the medial lemniscus, on images of different modalities indicate that QSM substantially improves the visibility of the PPN both in the atlas and individual images. Our findings indicate that the proposed SR network is an efficient tool for small-size brain nucleus identification. HR QSM is promising for improving the visibility of the PPN. The PPN can be directly identified on the individual QSM images acquired at the 3.0-T MR scanners, facilitating a direct targeting of PPN for DBS surgery.

Periaqueductal gray matter echogenicity as a marker of migraine chronification: a case control study

BackgroundMigraine is one of the most prevalent and disabling medical diseases in the world. The periaqueductal gray matter and the red nucleus play an important role in its pathogenesis. Our aim was to evaluate the echogenicity of the periaqueductal gray matter and the red nucleus in patients with migraine, by means of transcranial ultrasound.MethodsIn this cross-sectional study, a group of patients with migraine (according to the International Classification of Headache Disorders) and a group of control subjects with comparable age-and-sex distribution were prospectively included. We evaluated the area and echogenicity of the periaqueductal gray matter and the red nucleus by means of transcranial ultrasound, both bedside and posteriorly analyzed with the medical image viewer Horos.ResultsWe included 115 subjects: 65 patients with migraine (39 of them with chronic migraine and 26 with episodic migraine), and 50 controls. Median disease duration in patients with chronic migraine was 29 (IQR: 19; 40) years, with a median of 18 (IQR: 14; 27) days of migraine per month. The area of the periaqueductal gray matter was larger in patients with chronic migraine compared to episodic migraine and controls (0.15[95%CI 0.12;0.22]cm2; 0.11[95%CI 0.10;0.14]cm2 and 0.12[95%CI 0.09;0.15]cm2, respectively; p = 0.043). Chronic migraine patients showed an intensity of the periaqueductal gray matter echogenicity lower than controls (90.57[95%CI 70.87;117.26] vs 109.56[95%CI 83.30;122.64]; p = 0.035). The coefficient of variation of periaqueductal gray matter echogenicity was the highest in chronic migraine patients (p = 0.009). No differences were observed regarding the area or intensity of red nucleus echogenicity among groups.ConclusionPatients with chronic migraine showed a larger area of echogenicity of periaqueductal gray matter, a lower intensity of its echogenicity and a higher heterogenicity within this brainstem structure compared to patients with episodic migraine and controls. The echogenicity of the periaqueductal gray matter should be further investigated as a biomarker of migraine chronification.

Dizziness: efficient approach to treatment and prevention

The article deals with the diagnosis of dizziness as one of the most common reasons for contacting the primary care system. The term “vertigo” refers to the illusory sensation of the rotational movement of objects around the patient or the patient himself. Traditionally, the clinic distinguishes “systemic” and “non-systemic” dizziness. However, the use of these two terms “systemic” (rotational) and “non-systemic” (presyncope, imbalance caused by a violation of the neural mechanisms for maintaining balance and balance of the body and postural phobic) dizziness can make it difficult to diagnose the etiological factor due to the ambiguity of the term “non-systemic”. The most severe and painful for the patient is rotational dizziness. Most often, dizziness is caused by pathological changes in the peripheral part of the vestibular system: vestibular neuronitis, benign paroxysmal positional vertigo, Meniere’s disease. Treatment of patients with dizziness involves etiopathogenetic and symptomatic therapy. Important, from a practical point of view, is the relief of rotational dizziness itself, regardless of its etiology. A number of studies have shown the possibility of using the combined drug cinnarizine 20 mg + dimenhydrinate 40 mg in the treatment of peripheral and central vertigo. The effectiveness of therapy for dizziness with the use of a combined drug is due to the fact that one component (cinnarizine) acts mainly on peripheral structures (labyrinth), and the second (dimenhydrinate) – on central (vestibular nuclei and related centers of the brain stem) structures, providing a good vestibulolytic effect . The drug has minimal undesirable effects, which makes it possible to use it in patients of different age groups. In the article, the authors consider the effectiveness of a fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg for the treatment and prevention of rotational verti go (vertigo) of various etiologies with the analysis of clinical cases.

Spatial-dependent suppressive aftereffect produced by a sound in the rat's inferior colliculus is partially dependent on local inhibition.

In a natural acoustic environment, a preceding sound can suppress the perception of a succeeding sound which can lead to auditory phenomena such as forward masking and the precedence effect. The degree of suppression is dependent on the relationship between the sounds in sound quality, timing, and location. Correlates of such phenomena exist in sound-elicited activities of neurons in hearing-related brain structures. The present study recorded responses to pairs of leading-trailing sounds from ensembles of neurons in the rat's inferior colliculus. Results indicated that a leading sound produced a suppressive aftereffect on the response to a trailing sound when the two sounds were colocalized at the ear contralateral to the site of recording (i.e., the ear that drives excitatory inputs to the inferior colliculus). The degree of suppression was reduced when the time gap between the two sounds was increased or when the leading sound was relocated to an azimuth at or close to the ipsilateral ear. Local blockage of the type-A γ-aminobutyric acid receptor partially reduced the suppressive aftereffect when a leading sound was at the contralateral ear but not at the ipsilateral ear. Local blockage of the glycine receptor partially reduced the suppressive aftereffect regardless of the location of the leading sound. Results suggest that a sound-elicited suppressive aftereffect in the inferior colliculus is partly dependent on local interaction between excitatory and inhibitory inputs which likely involves those from brainstem structures such as the superior paraolivary nucleus. These results are important for understanding neural mechanisms underlying hearing in a multiple-sound environment.

Sex differences in brainstem structure volumes in patients with schizophrenia

Patients with schizophrenia (SZ) display moderate reductions in brainstem volumes, including the midbrain, pons, superior cerebellar peduncle, and medulla oblongata. Here, we investigated alterations in brainstem volumes between SZ patients and healthy controls (HCs) stratified by sex. T1-weighted MRI brain scans were processed with FreeSurfer v6.0 in 156 SZ patients (61 males/95 females) and 205 HCs (133/72). Of the brainstem structures, pons volumes were significantly reduced, particularly in male SZ patients. The decreased pons volumes were correlated with lower levels of education but not duration of illness in male patients. These findings suggest that the reduction in pons volume in male patients might be occurred before or around the onset of the disorder.

Spectrum of Autoimmune Diseases—Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS)—Clinical Case

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a rare inflammatory disease of an undetermined aetiology. The condition is characterised by a range of clinical manifestations generally associated with damage to brainstem structures, the cerebellum, with characteristic magnetic resonance imaging (MRI) findings. The main feature is a good clinical and radiological response to glucocorticosteroid (GCS)-based immunosuppressive treatment. The diagnosis of CLIPPERS is difficult and requires extensive differential diagnosis. A specific biomarker in serum or cerebrospinal fluid (CSF) for this disorder is currently unknown. The pathogenesis of CLIPPERS remains poorly understood and its nosological position has not yet been established. Whether CLIPPERS represents an independent, genuine new disorder or a syndrome in the course of diseases with heterogeneous aetiology and/or their precursor stages remains debatable and incompletely clarified. We present a case report of a patient who was diagnosed with CLIPPERS syndrome on the basis of her clinical and radiological features and by performing an extensive differential diagnosis. The patient has been under neurological follow-up for five years.

Emotional Lability as a Symptom of Extra-axial Posterior Fossa Tumors: a Case-Control Review of Neuroanatomy and Patient-Reported Quality of Life.

Introduction Emotional lability (EL), the uncontrollable and unmotivated expression of emotion, is a rare and distressing symptom of brainstem compression. In published case reports, EL from an extra-axial posterior fossa tumor was alleviated by tumor resection. The primary aim herein was to radiographically establish the degree of compression from mass lesions onto brainstem structures. Secondarily, we compared changes in patient-reported quality of life (QOL) pre- and postoperatively. Methods A retrospective review of posterior fossa tumors treated between 2002 and 2018 at Vancouver General Hospital revealed 11 patients with confirmed EL. Each case was matched to three controls. A lateral brainstem compression scale characterized mass effect at the level of the medulla, pons, and midbrain in preoperative axial T2-weighted fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) scans. Compression and clinical variables were compared between patient groups. Short Form-36 version 1 health surveys were retrospectively obtained from patient charts to compare pre- versus postoperative changes in survey scores between EL and control patients. Results EL symptoms ceased postoperatively for all EL patients. EL tumors exert greater compression onto the pons ( p = 0.03) and EL patients more commonly have cerebellar findings preoperatively ( p = 0.003). Patients with EL-causing tumors experienced greater improvement postoperatively in "Health Change" ( p = 0.05), which was maintained over time. Conclusion Findings suggest that compression onto the pons inhibits control over involuntary, stereotyped expression of emotion. This adds to evidence that EL may be attributed to cerebellum deafferentation from cortical and limbic structures through the basis pontis, leading to impaired modulation of emotional response. QOL results augment benefits of offering patients EL-alleviating tumor resection surgery.