Dorsal Brainstem Research Articles

The involvement of proinflammatory cytokines in the pathogenesis of audiogenic epilepsy

Epilepsy is a heterogeneous disease, which determines the relevance of investigating the mechanisms of pathogenesis of its various types, including reflex epilepsy. Pharmacotherapy is common for the treatment of patients with epilepsy, however, despite the significant recent achievements, 20-30% of patients remain resistant to the ongoing treatment. The urgency of creating new antiepileptic drugs, in particular, immune ones is due not only to a significant proportion of pharmacoresistant cases, but also to the struggle for the quality of life of patients. The neuroinflammation system in animals with different genetically determined audiogenic epilepsy proneness was investigated. These genetic groups were Krushinsky–Molodkina rats (tonic seizures of maximum intensity in response to the action of sound) and “0” strain (control group, non-convulsive phenotype). The main proinflammatory cytokines levels in the dorsal striatum and brain stem in rats of these genetic groups were measured by multiplex immunofluorescence assay. Background levels of IL-1â, IL-6 and TNFá in the dorsal striatum of KM rats were significantly lower than in the control “0” strain rats, whereas in the brain stem in the “background” levels of these metabolites did not differ. Four hours after the sound exposure, the TNFá level in the dorsal striatum of KM rats was significantly lower than in “0” rats. In KM rats, after the sound exposure and subsequent tonic seizures, the levels of IL-1â and IL-6 in the dorsal striatum were significantly higher than in the background. The IL-2 content was not detected in the background in KM rats, whereas after audiogenic seizures its level was 14.01 pg/ml. In the brain stem of KM rats, the levels of IL-1â and TNFá after audiogenic seizures were significantly lower than in the background. In rats of the “0” strain, cytokine levels in the dorsal striatum after the sound exposure did not differ from those in the background, while IL-1ß levels in their brain stem were significantly lower than the background state. Particular modulating role of the studied proinflammatory cytokines in the pathogenesis of audiogenic epilepsy is assumed, as well as certain possibility of anti-inflammatory and immune drugs application in anticonvulsant and antiepileptic therapy.

ELIMS: Ensemble Learning-Based Spatial Segmentation of Mass Spectrometry Imaging to Explore Metabolic Heterogeneity.

Spatial segmentation is an essential processing method for image analysis aiming to identify the characteristic suborgans or microregions from mass spectrometry imaging (MSI) data, which is critical for understanding the spatial heterogeneity of biological information and function and the underlying molecular signatures. Due to the intrinsic characteristics of MSI data including spectral nonlinearity, high-dimensionality, and large data size, the common segmentation methods lack the capability for capturing the accurate microregions associated with biological functions. Here we proposed an ensemble learning-based spatial segmentation strategy, named eLIMS, that combines a randomized unified manifold approximation and projection (r-UMAP) dimensionality reduction module for extracting significant features and an ensemble pixel clustering module for aggregating the clustering maps from r-UMAP. Three MSI datasets are used to evaluate the performance of eLIMS, including mouse fetus, human adenocarcinoma, and mouse brain. Experimental results demonstrate that the proposed method has potential in partitioning the heterogeneous tissues into several subregions associated with anatomical structure, i.e., the suborgans of the brain region in mouse fetus data are identified as dorsal pallium, midbrain, and brainstem. Furthermore, it effectively discovers critical microregions related to physiological and pathological variations offering new insight into metabolic heterogeneity.

Revision Chiari surgery in adults: surgical evaluation algorithm and outcomes in a continuity-of-care practice.

Patients with a prior surgical history for Chiari malformation (CM) as a child or an adult who presents with a recurrence or persistence of symptoms pose a challenging clinical scenario. The authors analyzed preoperative presentations, surgical histories, and outcomes of adult CM revision cases to create an algorithm for the assessment of revision surgery in adult CM patients and contrast this with the care of pediatric CM patients within the context of an integrated continuity-of-care CM practice seeing pediatric and adult patients. The authors retrospectively reviewed the records of patients with CM0, -1, and -1.5 who were 21 years of age or older, had a prior history of CM surgery as either children or adults, and underwent revision surgery as adults at the authors' institution from December 2009 to February 2020. The cohort was divided into three groups depending on the type of revision surgery performed: posterior fossa decompression with or without duraplasty (PFD/D group), occipitocervical fusion without ventral decompression (OCF group), and ventral decompression in the form of endoscopic endonasal odontoidectomy (VD group). A total of 50 adult revision cases were divided into 30 PFD/D cases, 13 OCF cases, and 7 VD cases. Forty cases had previously undergone one CM surgery, and 10 had undergone two. Preoperatively, the PFD/D group had significantly fewer cases of diagnosed craniocervical instability (CCI), Ehlers-Danlos syndrome, and dysautonomia than the OCF and VD groups. A retroflexed odontoid was significantly more common in the VD group than in the PFD/D and OCF groups. Postoperatively, rates of improvement were 60.0% with PFD/D, 84.6% with OCF, and 85.7% with VD, but differences in these rates were not statistically significant. In this challenging group of CM patients, possible etiologies warranting additional surgery included residual dorsal compression, persistent syrinx, CCI, and ventral brainstem compression from a significant retroflexed odontoid. Outcomes after revision were often favorable, but careful evaluation, patient selection, and communication with patients are needed in deciding to reoperate. The suggested algorithm can aid decision-making.

The usefulness of combined analysis using CIScore and VSRAD parameters for differentiating between dementia with Lewy body and Alzheimer’s disease

PurposeThe Cingulate Island score (CIScore) is useful index for differentiating between dementia with Lewy body (DLB) and Alzheimer’s disease (AD) using regional cerebral blood flow (rCBF) SPECT. The Z score standing for medial temporal lobe (MTL) atrophy and the ratio of Z score between dorsal brain stem (DBS) to MTL are useful indices for differentiating between DLB and AD using MRI with VSRAD. The current study investigated the diagnostic ability by the combined use of rCBF SPECT and MRI in the differentiation between AD and DLB.Materials and methodsIn cases with 42 AD and 28 DLB undertaken Tc-99m-ECD SPECT and MRI, we analyzed differential diagnostic ability between AD and DLB among following conditions by single or combined settings. Namely, they were (1) the CIScore as a parameter of rCBF SPECT (DLB ≦ 0.25), (2) Z score value of MTL atrophy (DLB ≦ 2.05), (3) the ratio of Z score of DBS to medial temporal gray matter as a parameter of brain atrophy using VSRAD (DLB ≧ 0.38). Also, we analyzed them both including and omitting the elderly (over 75 years old).ResultsThe accuracy of differential diagnosis in this condition was 74% for (1), 69% for (2), and 67% for (3). The accuracy by combination condition was 84% for (1) and (2), 81% for (1) and (3), and 67% for (2) and (3), respectively. The combination method by CIScore and the Z score of MTL showed the best accuracy. When we confined condition to ages younger than 75 years, the accuracy improved to 94% in the combination method.ConclusionThe combined use of CIScore and Z score of MTL was suggested to be useful in the differential diagnosis between DLB and AD particularly in younger than 75 years old.

Altered Serotonin 1B Receptor Binding After Escitalopram for Depression Is Correlated With Treatment Effect.

Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively. The effect of SSRI treatment on 5-HT1B receptor binding in patients with MDD has not been examined previously. This positron emission tomography (PET) study aimed to quantify brain 5-HT1B receptor binding changes in vivo after SSRI treatment for MDD in relation to treatment effect. Eight unmedicated patients with moderate to severe MDD underwent PET with the 5-HT1B receptor radioligand [11C]AZ10419369 before and after 3 to 4 weeks of treatment with the SSRI escitalopram 10mg daily. Depression severity was assessed at time of PET and after 6 to 7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale. We observed a significant reduction in [11C]AZ10419369 binding in a dorsal brainstem (DBS) region containing the median and dorsal raphe nuclei after escitalopram treatment (P = .036). Change in DBS [11C]AZ10419369 binding correlated with Montgomery-Åsberg Depression Rating Scale reduction after 3-4 (r = 0.78, P = .021) and 6-7 (r = 0.94, P < .001) weeks' treatment. Our findings align with the previously reported reduction of 5-HT1B receptor binding in the raphe nuclei after SSRI administration and support future studies testing change in DBS 5-HT1B receptor binding as an SSRI treatment response marker.

Reduction in Constitutively Activated Auditory Brainstem Microglia in Aging and Alzheimer's Disease.

Alzheimer's disease (AD) pathology is considered to begin in the brainstem, and cerebral microglia are known to play a critical role in AD pathogenesis, yet little is known about brainstem microglia in AD. Translocator protein (TSPO) PET, sensitive to activated microglia, shows high signal in dorsal brainstem in humans, but the precise location and clinical correlates of this signal are unknown. To define age and AD associations of brainstem TSPO PET signal in humans. We applied new probabilistic maps of brainstem nuclei to quantify PET-measured TSPO expression over the whole brain including brainstem in 71 subjects (43 controls scanned using 11C-PK11195; 20 controls and 8 AD subjects scanned using 11C-PBR28). We focused on inferior colliculi (IC) because of visually-obvious high signal in this region, and potential relevance to auditory dysfunction in AD. We also assessed bilateral cortex. TSPO expression was normally high in IC and other brainstem regions. IC TSPO was decreased with aging (p = 0.001) and in AD subjects versus controls (p = 0.004). In cortex, TSPO expression was increased with aging (p = 0.030) and AD (p = 0.033). Decreased IC TSPO expression with aging and AD-an opposite pattern than in cortex-highlights underappreciated regional heterogeneity in microglia phenotype, and implicates IC in a biological explanation for strong links between hearing loss and AD. Unlike in cerebrum, where TSPO expression is considered pathological, activated microglia in IC and other brainstem nuclei may play a beneficial, homeostatic role. Additional study of brainstem microglia in aging and AD is needed.

Parkinsonism-dystonia-2: Case-series study from Saudi Arabia.

Parkinsonism-dystonia-2 PKDYS2 is an autosomal-recessive disorder, caused by pathogenic biallelic variants in SLC18A2 which encodes the vesicular monoamine transporter (VMAT2) protein. PKDYS2 is a treatable neurotransmitter disease, and the rate of diagnosis of this disorder has increased significantly with the advance of genomic technologies. Our report highlights a novel pathologic variant in one case and a novel finding on MRI Brain, consisting of a normal symmetrical signal intensity in the dorsal brainstem and pons, and it substantiates the significance of genetic testing in the evaluation of children with developmental delays, which influences clinical decisions to enhance patient outcomes.

Brain connectivity changes to fast versus slow dopamine increases

The rewarding effects of stimulant drugs such as methylphenidate (MP) depend crucially on how fast they raise dopamine in the brain. Yet how the rate of drug-induced dopamine increases impacts brain network communication remains unresolved. We manipulated route of MP administration to generate fast versus slow dopamine increases. We hypothesized that fast versus slow dopamine increases would result in a differential pattern of global brain connectivity (GBC) in association with regional levels of dopamine D1 receptors, which are critical for drug reward. Twenty healthy adults received MP intravenously (0.5 mg/kg; fast dopamine increases) and orally (60 mg; slow dopamine increases) during simultaneous [11C]raclopride PET-fMRI scans (double-blind, placebo-controlled). We tested how GBC was temporally associated with slow and fast dopamine increases on a minute-to-minute basis. Connectivity patterns were strikingly different for slow versus fast dopamine increases, and whole-brain spatial patterns were negatively correlated with one another (rho = −0.54, pspin < 0.001). GBC showed “fast>slow” associations in dorsal prefrontal cortex, insula, posterior thalamus and brainstem, caudate and precuneus; and “slow>fast” associations in ventral striatum, orbitofrontal cortex, and frontopolar cortex (pFDR < 0.05). “Fast>slow” GBC patterns showed significant spatial correspondence with D1 receptor availability (estimated via normative maps of [11C]SCH23390 binding; rho = 0.22, pspin < 0.05). Further, hippocampal GBC to fast dopamine increases was significantly negatively correlated with self-reported ‘high’ ratings to intravenous MP across individuals (r(19) = −0.68, pbonferroni = 0.015). Different routes of MP administration produce divergent patterns of brain connectivity. Fast dopamine increases are uniquely associated with connectivity patterns that have relevance for the subjective experience of drug reward.

Coronavirus disease 2019-associated persistent cough and Chiari malformation type I resulting in acute respiratory failure: illustrative case.

Chiari malformation type I (CM-I) is the herniation of cerebellar tonsils through the foramen magnum, potentially resulting in the obstruction of cerebrospinal fluid flow and brainstem compression. Sleep-disordered breathing (SDB) is common in patients with CM-I, and symptomatic exacerbations have been described after Valsalva-inducing stressors. Acute decompensation in the setting of coronavirus disease 2019 (COVID-19) has not been described. After violent coughing episodes associated with COVID-19 infection, a 44-year-old female developed several months of Valsalva-induced occipital headaches, episodic bulbar symptoms, and worsening SDB, which led to acute respiratory failure requiring mechanical ventilation. Imaging demonstrated 12 mm of cerebellar tonsillar descent below the foramen magnum, dorsal brainstem compression, and syringobulbia within the dorsal medulla. She underwent posterior fossa and intradural decompression with near-complete resolution of her symptoms 6 months postoperatively. Although CM-I can remain asymptomatic, Valsalva-inducing stressors, including COVID-19 infection, can initiate or acutely exacerbate symptoms, placing patients at risk for CM-I-associated brainstem dysfunction and, in rare cases, acute respiratory failure. Worsening Valsalva maneuvers can contribute to further cerebellar tonsil impaction, brainstem compression, syringomyelia/syringobulbia, and worsening CM-I intradural pathology. Ventilator support and timely decompressive surgery are paramount, as brainstem compression can reduce central respiratory drive, placing patients at risk for coma, neurological deficits, and/or death.

10159-STMO-7 INTRAOPERATIVE MRI SURGERY FOR POSTERIOR FOSSA LESIONS

Abstract Background: Intraoperative MRI (iMRI) is an important modality in brain tumor surgery to identify residual tumors, however, it is problematic due to patient positional limitations. In this study, we investigated the usefulness of iMRI for posterior fossa lesions. Materials and Methods: Of 320 cases of brain tumors removed using iMRI from June 2016 to April 2023, 24 cases of posterior fossa lesions were included. Tumor type, approach method, imaging availability, tumor removal rate, and complications were examined retrospectively. Results: Tumor types included 8 gliomas, 5 epidermoid cysts, 4 meningiomas, 3 metastatic brain tumors, 1 schwannoma, and 3 others. Eleven patients underwent midline suboccipital approach in the supine position, 8 patients underwent lateral suboccipital approach, 2 patients underwent occipital transtentorial approach, and 2 patients underwent anterior transpetrosal approach in the supine position. transpetrosal approach in 2 cases and subtemporal approach in 1 case. iMRI showed residual lesion in 14 of 24 patients. More than half of the gliomas and epidermoid cysts had intraoperative residual disease, whereas only one meningioma did. Total resection was achieved except for one case of intentional residual schwannoma and two cases of glioma. Discussion: iMRI requires the upper body to fit within a gantry, and it is difficult to image in the park bench position. However, various approaches is possible by using a supine-lateral or semi-prone position. In the concorde position, where the fourth ventricle and upper cerebellum are approached, it is useful to insert a mat in the anterior thoracic and raise the upper body. For tumors in the dorsal brainstem and upper cerebellum, the occipital transtentorial approach was used. iMRI is effective in the removal of all tumors, including gliomas in intramedullary tumors and epidermoid cysts in extramedullary tumors. Conclusion: iMRI can be used in posterior cranial fossa lesions.

CSIG-01. DEFINING THE INVOLVEMENT OF THE PERIVASCULAR NICHE IN BRAIN TUMOR METASTASES

Abstract Medulloblastomas (MB) are the most prevalent malignant pediatric brain tumors, originating in either the cerebellum or the dorsal brainstem. They are classified into four distinct subgroups (WNT, SHH, Group 3, and Group 4), characterized by unique gene expression profiles, metastatic patterns, and recurrence rates. Metastatic progression of MB is frequently associated with poor prognosis, affecting approximately 30% of patients at diagnosis. Despite considerable research on primary tumors, there are currently no approved specific treatments for MB leptomeningeal metastases. Thus, gaining further insights into metastatic MB and developing targeted therapies are imperative. The leptomeningeal niche, where metastatic MB tumor cells reside, comprises a complex network of blood vessels supported by perivascular cells, including pericytes, smooth muscle cells, and fibroblasts. However, the specific adhesion molecules and signaling pathways within the leptomeningeal niche that contribute to tumor cell colonization remain elusive. In this study, we hypothesize that the perivascular niche plays a critical role in the colonization and survival of metastatic cells within the leptomeninges. To investigate this, we employed an innovative sLP-mCherry niche labeling system in conjunction with single-cell RNA sequencing to spatially identify and examine the perivascular cells neighboring metastatic MB tumor cells. Through our analysis, we identified upregulated genes associated with cholesterol export in tumor-associated perivascular cells, suggesting their potential involvement in supporting metastatic cell colonization. To further explore this mechanism, we utilized CRISPR and lentiviral overexpression constructs to modulate cholesterol uptake in MB cell lines, observing subsequent changes in metastatic burden. In summary, our study elucidates the importance of the perivascular niche in metastatic medulloblastomas and provides novel insights into the molecular mechanisms that drive tumor cell colonization within the leptomeninges. These investigations into the lipid transport mechanism in the vascular microenvironment opens doors for the development of innovative treatments targeting MB metastases.

Simulation of the occipital transtentorial approach incorporating visualization of the cerebellar tentorium using three-dimensional computed tomography angiography and gadolinium-enhanced T1-weighted magnetic resonance imaging: technical note

The occipital transtentorial approach (OTA) is one of the useful approaches to the lesions of the pineal region, dorsal brainstem, and supracerebellar region. However, a wide operative field is sometimes difficult to obtain due to the tentorial sinus and bridging veins. This study evaluated the usefulness of preoperative simulation of OTA, specifically including the cerebellar tentorium in 9 patients. All patients underwent computed tomography angiography and venography and gadolinium-enhanced three-dimensional T1-weighted magnetic resonance images (Gd-3D-T1WI). The images were fused, and the cerebellar tentorium, vessels, and tumor were manually extracted from Gd-3D-T1WI to obtain the simulation images. Visualization of the cerebellar tentorium could discriminate between bridging veins from the occipital lobe and cerebellum, and recognize the site of bridging to the tentorial sinus and variants which may interfere with the tentorial incision. Simulation of the tentorial incision was also possible based on the relationships between the tumor, tentorial sinus, bridging vein, and cerebellar tentorium. The simulation suggested that safe tentorial incision was difficult in two sides because of the crossed tentorial sinus draining the left basal vein and draining veins from the glioblastoma. The OTA was performed in eight cases, and no difficulty was experienced in the tentorial incision in all cases. The simulation findings of the bridging vein and tentorial sinus were consistent with the intraoperative findings. Preoperative simulation including the cerebellar tentorium is useful for determining the optimum and safe side and required extent of the tentorial incision necessary for tumor resection with the OTA.

Prospective analysis of video head impulse tests in patients with acute posterior circulation stroke.

Video head impulse tests (vHITs), assessing the vestibulo-ocular reflex (VOR), may be helpful in the differential diagnosis of acute dizziness. We aimed to investigate vHITs in patients with acute posterior circulation stroke (PCS) to examine whether these findings could exhibit significant abnormalities based on lesion locations, and to evaluate diagnostic value of vHIT in differentiating dizziness between PCS and vestibular neuritis (VN). We prospectively recruited consecutive 80 patients with acute PCS and analyzed vHIT findings according to the presence of dorsal brainstem stroke (DBS). We also compared vHIT findings between PCS patients with dizziness and a previously studied VN group (n = 29). Receiver operating characteristic (ROC) analysis was performed to assess the performance of VOR gain and its asymmetry in distinguishing dizziness between PCS and VN. Patients with PCS underwent vHIT within a median of 2 days from stroke onset. Mean horizontal VOR gain was 0.97, and there was no significant difference between PCS patients with DBS (n = 15) and without (n = 65). None exhibited pathologic overt corrective saccades. When comparing the PCS group with dizziness (n = 40) to the VN group (n = 29), patients with VN demonstrated significantly lower mean VOR gains in the ipsilesional horizontal canals (1.00 vs. 0.57, p < 0.001). VOR gain and their asymmetry effectively differentiated dizziness in the PCS from VN groups, with an area under the ROC curve of 0.86 (95% CI 0.74-0.98) and 0.91 (95% CI 0.83-0.99, p < 0.001), respectively. Significantly abnormal vHIT results were rare in patients with acute PCS, even in the presence of DBS. Moreover, vHIT effectively differentiated dizziness between PCS and VN, highlighting its potential for aiding differential diagnosis of acute dizziness.

An assessment of the effects of neurokinin1 receptor antagonism against nausea and vomiting: Relative efficacy, sites of action and lessons for future drug development.

A broad-spectrum anti-vomiting effect of neurokinin1 receptor antagonists (NK1 RA), shown in pre-clinical animal studies, has been supported by a more limited range of clinical studies in different indications. However, this review suggests that compared with vomiting, the self-reported sensation of nausea is less affected or possibly unaffected (depending on the stimulus) by NK1 receptor antagonism, a common finding for anti-emetics. The stimulus-independent effects of NK1 RAs against vomiting are explicable by actions within the central pattern generator (ventral brainstem) and the nucleus tractus solitarius (NTS; dorsal brainstem), with additional effects on vagal afferent activity for certain stimuli (e.g., highly emetogenic chemotherapy). The central pattern generator and NTS neurones are multifunctional so the notable lack of obvious effects of NK1 RAs on other reflexes mediated by the same neurones suggests that their anti-vomiting action is dependent on the activation state of the pathway leading to vomiting. Nausea requires activation of cerebral pathways by projection of information from the NTS. Although NK1 receptors are present in cerebral nuclei implicated in nausea, and imaging studies show very high receptor occupancy at clinically used doses, the variable or limited ability of NK1 RAs to inhibit nausea emphasizes: (i) our inadequate understanding of the mechanisms of nausea; and (ii) that classification of a drug as an anti-emetic may give a false impression of efficacy against nausea vs. vomiting. We discuss the potential mechanisms for the differential efficacy of NK1 RA and the implications for future development of drugs that can effectively treat nausea, an area of unmet clinical need.

Telovelar/Transcerebellomedullary Fissure Approach: Giant Distal Posterior Inferior Cerebellar Artery Aneurysm, Epidermoid Cyst, and Brainstem Cavernoma: 2-Dimensional Operative Video.

The telovelar or transcerebellomedullary fissure approach can provide wide exposure of the cerebellomedullary fissure and fourth ventricle by separating the natural plane between the medulla and cerebellum.1-5. The cerebellar tonsil is attached to the adjacent cerebellum only by the tonsillar peduncle at its superolateral edge.2 The posterior inferior cerebellar artery (PICA) runs in the cerebellomedullary fissure, usually making its caudal and cranial loops.6,7. After widely opening the foramen magnum, the tonsil is gently elevated by shearing the tela choroidea up to the lateral recess from the taenia, where the vein of the inferior cerebellar peduncle courses.8,9. The developed occipital sinus, posterior condylar vein, and anomalies of the vertebral artery and PICA origin can obstruct the exposure. Detailed neuromonitoring is essential for accomplishing the procedure safely.10,11. This exposure can be extended to the lower cerebellopontine angle and can also be applied to the dorsal brainstem surgery.2,12 The patients consented to the procedure and to the publication of their images.Image Credits: Department of Neurosurgery, Tokyo Medical University logo used by permission. Image at 0:10, 1:02, 2:46, 6:22, and 7:10 from Matsushima and Kohno,1 used by permission from Medical View Co., Ltd.Right image at 0:14 and also upper image at 0:46, image at 1:26, and for left and lower right images at 1:54 from Matsushima et al,2 by permission from Journal of Neurosurgery Publishing Group (JNSPG). Left image at 0:14, from Matsushima et al,4 used by permission from the Congress of Neurological Surgeons. Lower image at 0:46 reprinted from Matsushima et al,9 by permission from Elsevier. Left image at 1:06 from Matsushima et al,8 used by permission from the Congress of Neurological Surgeons.Image at top right at 1:54 from Lister et al,6 used by permission from the Congress of Neurological Surgeons. Image in center at 6:56 from Matsushima et al,11 used by permission from Springer Nature. Image at right at 6:56 from Matsushima et al,10 used by permission from JNSPG. Images at 9:48, by year: 1982 article screenshot and figure from Matsushima et al,4 by permission from the Congress of Neurological Surgeons; 1992: article title screenshot from Matsushima et al,3 by permission from the Congress of Neurological Surgeons; 1996: used with permission of McGraw-Hill Health Professions Division, from Microsurgical Anatomy of the Fourth Ventrical, Matshushiam T and Rhoton AL Jr, in Neurosurgery, eds Wilkins and Rengachary, vol 1, 1996, permission conveyed through Copyright Clearance Center, Inc.; 2000: article title screenshot from Mussi et al,5 reused with permission from JNSPG; 2001: article title screenshot from Matsushima, Transcerebellomedullary fissure approach with special reference to methods of dissecting the fissure, J Neurosurg, vol 91, 2001, p. 257-264, by permission from JNSPG; 2021: article title screenshot from Matsushima et al,12 by permission from Springer Nature. Images at 11:05 from Inoue T et al, "Surgical approach to the mesencephalic vascular malformation" [in Japanese], Surg Cereb Stroke, vol 26, 1998, p 288-289, by permission from the Japanese Society on Surgery for Cerebral Stroke. Cadaveric image at 11:56 from Matsushima T et al, "Exposure of the wide interior of the fourth ventricle without splitting the vermis: importance of cutting procedures for the tela choroidea" Neurosurg Rev, vol 35, 2012, p 563-571, used with permission from Springer Nature.

Lymphomatoid granulomatosis with the central nervous system involvement as the main manifestation: a case report

BackgroundLymphomatoid granulomatosis (LyG) is a rare extralymphatic lymphoproliferative disease characterized by lymphocytic invasion into vascular walls and damage to blood vessels. The lungs are affected in 90% of LyG cases, followed by the skin, central nervous system (CNS), kidneys and liver.Case presentationHere we report a case of a young woman with LyG, with CNS involvement as the initial clinical manifestation. Computer tomography (CT) scans showed multiple nodular, patchy and flocculent high-density shadows in both lungs without mediastinal lymph node enlargement. Magnetic resonance imaging (MRI) scans showed multiple abnormal signal intensities in the right cerebellar hemisphere, frontal, parietal and temporal lobes, and dorsal brainstem, which became patchy and annular after enhancement. The post-operative pathological analysis of lesion samples confirmed the diagnosis of grade II LyG.ConclusionsLyG should be concerned in young adults showing multiple radiological brain and lung lesions. Resection and postoperative medication of steroid hormones and IFN-α may be effective in the treatment of LyG.

Comparison Between the Supracerebellar Infratentorial and Precuneal Interhemispheric, Transtentorial Approaches to the Cerebellomesencephalic Fissure: An Anatomoradiological Study and Illustrative Cases.

The dorsal brainstem and cerebellomesencephalic fissure are challenging surgical targets. To afford a preferentially craniocaudal trajectory to this region, the precuneal interhemispheric transtentorial approach (PCIT) has been proposed. To didactically describe and compare exposures and anatomic indications of the supracerebellar infratentorial approach (SCIT) and PCIT to the cerebellomesencephalic fissure. Nine formalin-fixed, latex-injected cadaveric head specimens were used to perform a midline SCIT and bilateral PCITs and measure the distance of each approach. Twenty-four formalin-fixed specimens were used to measure the distance from the most posterior cortical bridging vein entering the superior sagittal sinus to the calcarine sulcus and the torcula. Fifty-one magnetic resonance images were reviewed to calculate the angle of each approach. Three illustrative surgical cases were described. Mean distances from the brain or cerebellar surface to the operative target of the PCIT and SCIT were 7.1 cm (range: 5-7.7 cm) and 5.5 cm (range: 3.8-6.2 cm), respectively. The SCIT provided direct access to structures of the quadrigeminal cistern bilaterally. The PCIT provided access from the ipsilateral inferior colliculus to the ipsilateral infratrochlear zone. The PCIT's benefit was the direct access it provided to the cerebellomesencephalic fissure because of its superior to inferior trajectory. The PCIT is indicated for unilateral lesions of the cerebellomesencephalic fissure and dorsal brainstem that harbor a craniocaudal long axis and do not have a superior extension beyond the superior colliculi. The SCIT is beneficial for lesions that extend bilaterally, have an anteroposterior long axis, or involve the Galenic complex.

Optical imaging of neurons related to fictive swallowing using GCaMP6f in an arterially perfused rat preparation

ObjectiveIt is difficult to comprehensively study the activity patterns and distribution of neurons in the brainstem that control the act of swallowing, as they are located deep in the brain. In this study, we aimed to evaluate the usefulness of calcium imaging using GCaMP6f in arterially perfused preparations to study the activity of swallowing-related neurons in the brainstem. MethodsArterially perfused rat preparations were prepared 3–4 weeks after the injection of a neuron-specific virus expressing GCaMP6f. Fictive swallowing was induced by repetitive electrical stimulation of the superior laryngeal nerve (SLN). Simultaneously, the activity of GCaMP6f-expressing neurons in the dorsal brainstem, between 0.1 and 4.8 mm rostral to the obex, was assessed by changes in the intracellular calcium concentration using confocal laser microscopy. ResultsNeurons responding to stimulation of the SLN included swallowing-related neurons (48%), which showed an increase in fluorescence intensity at the time of swallowing bursts in the cervical vagus nerve, and stimulation-related neurons (52%), which showed an increase in fluorescence intensity through stimulation, regardless of the swallowing bursts. Despite a broad search area, swallowing-related neurons were localized exclusively in and around the solitary nucleus. In contrast, most stimulation-related neurons were located in the brainstem reticular formation, which is more rostral than the solitary nucleus. ConclusionsCalcium imaging using GCaMP in arterially perfused rat preparations is useful for an efficient search of the activity pattern and distribution of neurons located in a wide area of the brainstem.

Associations Between Cognition and Serotonin 1B Receptor Availability in Healthy Volunteers: A [11C]AZ10419369 Positron Emission Tomography Study.

The serotonin system has been implicated in several psychiatric disorders. All major psychiatric disorders are associated with cognitive impairment, but treatment improving cognitive deficits is lacking, partly due to limited understanding of the neurobiology of cognitive functioning. Several markers for the serotonin system have been associated with cognitive functions. Our research group previously has reported a positive correlation between serotonin (5-HT1B) receptor availability in the dorsal brainstem and visuospatial memory in a pilot study of healthy individuals. Here, we aim to replicate our previous finding in a larger group of healthy volunteers as well as to investigate putative associations between 5-HT1B receptor availability and other cognitive domains. Forty-three healthy individuals were examined with positron emission tomography using the 5-HT1B receptor radioligand [11C]AZ10419369 and a visuospatial memory test to replicate our previous finding as well as tests of verbal fluency, cognitive flexibility, reaction time, and planning ability to explore other domains potentially associated with the serotonin system. Replication analysis revealed no statistically significant association between 5-HT1B receptor availability in the dorsal brainstem and visuospatial memory performance. Exploratory analyses showed age-adjusted correlations between 5-HT1B receptor availability in whole brain gray matter and specific brain regions, and number of commission errors, reaction time, and planning ability. Higher 5-HT1B receptor availability was associated with more false-positive responses and faster reaction time but lower performance in planning and problem-solving. These results corroborate previous research supporting an important role of the serotonin system in impulsive behavior and planning ability.

Anatomical Aspects and Clinical Application of a Unilateral Uvulotonsillar Approach via a Minimally Invasive Open-Door Suboccipital Craniotomy to Remove Lesions of the Fourth Ventricle and Dorsal Brainstem

Today, a median suboccipital craniotomy with access to the cavity of the fourth ventricle through the foramen of Magendie is widely used to remove neoplasms of the fourth ventricle and brainstem. However, according to modern literature, the median approach to the posterior cranial fossa is associated with a high risk of CSF leakage and pseudomeningocele. We propose a modified unilateral uvulotonsillar approach via a median suboccipital open-door craniotomy, which can potentially reduce the incidence of CSF leakage and preserve the ligamentous apparatus of the craniovertebral junction. Herein, we describe the implementation of this approach on cadaveric material and provide a clinical case. The material used for the study was 3 cadavers and 1 clinical case. Step-by-step dissection imitating the described approach was carried out. During the dissection, surgical landmarks were identified at the macro- and microstages, which should be considered when performing the proposed approach. A detailed description of the technique for performing open-door craniotomy, the features of the incision in the dura mater, unilateral dissection of the uvulotonsillar fissure, and the structures of the cavity of the fourth ventricle that could be visualized through this approach were described. This approach allows preservation of the normal anatomy of the craniovertebral junction and stable fixation of the bone flap. Unilateral dissection of the uvulotonsillar fissure provides adequate visualization of almost all parts of the rhomboid fossa, and the convenience of suturing the minimal arcuate incision in the dura mater potentially reduces the risk of CSF leakage.