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BACKGROUND Diffuse intrinsic pontine glioma represent approximately 10% to 20% of all pediatric central nervous system tumors. Classic brain stem symptoms are cranial nerve deficits, long tract signs, ataxia, alone or in combination. Focal radiotherapy has been the standard of care in patients with diffuse intrinsic pontine gliomas with minimum response. Here, we present an unusual case with excellent tumor regression with radiotherapy and good clinical outcome. CASE REPORT A 13-year-old girl presented with headache and imbalance during walking for the past 2-3 months, along with a deviation of the right eye in the last month. Brain magnetic resonance imaging (MRI) suggested a well-defined solid cystic altered-signal-intensity lesion involving the pons and medulla, causing its expansion up to the midbrain on the left side. The lesion was 4.6×3.7×3.6 cm. We applied the intensity-modulated radiotherapy technique (IMRT) using a 6-MV photon beam with the conventional dose fractionation of 54 Gy in 30 fractions (1.8 Gy/fraction). Three months later, MRI brain with spectroscopy and perfusion showed evidence of non-enhancing, altered-signal-intensity lesion in the pons and medulla, measuring 1.9×2.2×2.4 cm. CONCLUSIONS Early detection of symptoms of DIPG in a young patient along with effective radiological investigation with valid tumor board decision as definitive radiotherapy as a sole therapeutic treatment option and with robust radiotherapy planning resulted in an excellent response, with 80% reduction in gross tumor volume (GTV) as seen in pre-radiotherapy (RT) and post-RT MRI images.

Background and Aim: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and autonomic symptoms (SUNA) are trigeminal autonomic cephalalgias (TACs). The study explores the potential association between SUNCT/SUNA-like headaches and lateral pontine infarctions., Methods: Case series and systematic review., Results: We present three cases diagnosed with SUNCT following lateral pontine infarction on magnetic resonance imaging (MRI), along with a review of these cases and 10 others from the literature., Discussion and Conclusion: This review suggests a connection between SUNCT/SUNA-like symptoms and lateral pontine infarctions. The section also delves into the anatomy and pathophysiology of these symptoms, proposing a mechanism involving neural pathway remodelling in the lateral brainstem., (© 2024 European Pain Federation ‐ EFIC ®.)

Background: Central pain, characterized by neuropathic pain, can manifest due to injury to the superior spinothalamic tract. The brainstem includes sensory and motor pathways as well as nuclei of the cranial nerves, and therefore cancer metastasis in the region requires early intervention. Although stereotactic radiosurgery (SRS) is commonly employed for the treatment of brain metastasis, it poses risks of late complications like radiation necrosis (RN). RN exacerbates the progression of brain lesions within the irradiated area, and in the brainstem, it can damage multiple nerves, including the superior spinothalamic tract. Central neuropathic pain is often intractable and empirically managed with a combination of conventional drugs, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants. However, their efficacy is often limited, leading to a decline in performance status (PS) and quality of life (QOL)., Case Presentation: We present the case of a 53-year-old man diagnosed with stage IV lung cancer, referred to our palliative care team for managing severe central pain resulting from SRS-related RN in the pons. Despite administration of opioids, including oxycodone and hydromorphone, and adjuvant analgesics, the patient continued to require frequent use of immediate-release opioids. The addition of methadone alone proved successful in achieving optimal pain control., Conclusions: Provided that RN in the brainstem can lead to intractable neuropathic pain, it is advisable to avoid SRS for brainstem metastasis when possible. Add-on methadone should be considered as a viable pain management medication for patients experiencing unresolved central pain., (© 2024. The Author(s).)

Rationale: Myelin oligodendrocyte glycoprotein (MOG) antibody-related disease is a relatively recent entity in inflammatory demyelinating disease. Its clinical presentation varies in severity and the lack of specific imaging features makes it easy to misdiagnose. We now report the case of a MOG antibody-positive patient who presented with diplopia and dizziness, and whose brain magnetic resonance imaging (MRI) showed abnormal signals in the bilateral pontine brachium., Patient Concerns: A previously healthy 52-year-old woman presented with diplopia and dizziness, and was hospitalized 4 days after onset., Diagnoses: Brain MRI demonstrated abnormal hyperintense signals in the bilateral pontine brachium on T2-weighted fluid attenuated inversion recovery imaging. MRI enhancement showed abnormal enhancement foci in bilateral pontine brachium and pons. Cerebrospinal fluid examination showed Oligoclonal IgG bands were negative. The IgG index was normal, and serum aquaporin-4 antibody was negative, while serum MOG-Ab was positive (1:100). In conjunction with a positive serum MOG antibody and exclusion of other diseases, diagnosis of MOG antibody-related disease was made., Interventions: Intravenous methylprednisolone followed by oral corticosteroids., Outcomes: Symptoms resolved completely. At 4-month follow-up. Follow-up after 4 months showed disappearance of the abnormal signal in the left pontine brachium and diminution of abnormal high signal in the right compared to the previous one, and there was no recurrence 1 year after the onset of the disease., Lessons: If brain MRI indicating bilateral, multiple, and diffuse abnormal signals in the pontine brachium, and a discrepancy between the clinical symptoms and the imaging severity, a diagnosis of demyelinating disease should be considered highly probable. In such cases, anti-MOG antibody testing is essential for further defining the etiology. The clinical phenotype and imaging manifestations of MOG antibody-positive brainstem encephalitis may lack sufficient specificity to be readily identifiable. Timely diagnosis and early glucocorticoid therapy are beneficial in improving prognosis and preventing recurrence., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a discrete nosological entity characterized by punctate and curvilinear gadolinium enhancement "peppering" the pons and a strong response to steroids. MRI images typically show pontine and cerebellar punctate-enhancing lesions, which occasionally spread up to the juxtacortical areas and down to the spinal cord. Interestingly, the more distant the lesion is from the pons, the less intense they become. Herein, we describe an extremely rare case of CLIPPERS presenting with predominant spinal cord involvement; then, we searched in the literature the available cases with a similar presentation. Our case focuses attention on a rare MRI CLIPPERS presentation. Since CLIPPERS has a dramatic response to corticosteroid treatment, it is fundamental to promptly recognize its MRI pattern to start treatment as soon as possible., (© 2024. Fondazione Società Italiana di Neurologia.)

Background: Diffuse intrinsic pontine gliomas are aggressive tumors that carry a poor prognosis with a 2-year survival rate of <10%. The imaging appearance is often pathognomonic, and surgical biopsy is not mandatory to initiate treatment in children. Studies of biopsy samples provide insight into the disease's molecular pathobiology and open prospects for targeted therapy. This study was conducted to determine the diagnostic yield and safety of stereotactic biopsies., Methods: This is a prospective observational study from a single tertiary health care center. All patients with clinical and radiological features diagnostic of diffuse intrinsic pontine gliomas (DIPGs) who underwent biopsy from July 2018 to June 2023 were included. Biopsies were performed using either stereotactic frame-based, frameless, or endoscopic techniques., Results: A total of 165 patients with DIPGs were evaluated in the study period. The option of biopsy with its associated risks and benefits was offered to all patients. A total of 76 biopsies were performed in 74 patients (40 children and 34 adults, including 2 repeat biopsies). The median age was 15 years. Diffuse midline gliomas, H3K27M altered, was the most common histopathological diagnosis (85% pediatric and 55.9% adults). The diagnostic efficacy of the procedure was 94.7%. The complication rate was 10.8%, with no permanent neurological deficits due to surgery. There was no procedure-related mortality., Conclusions: Establishing the safety of the procedure could be an important step toward popularizing the concept, which might offer a better understanding of the disease. Brainstem eloquence and a lack of direct benefit to patients are the primary obstacles to brainstem biopsy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: An 89-year-old man presented with progressive gait disturbance, diplopia, and ataxia. Initial brain MRI demonstrated T2/FLAIR hyperintense signal abnormality in the pons extending along the middle cerebellar peduncles into the cerebellum, with associated punctate, patchy, and linear enhancement on postcontrast imaging. Initially, this was attributed to brainstem encephalitis; however, sarcoidosis, histiocytosis, and paraneoplastic/autoimmune encephalitis remained on the differential. One month after initial MRI, 18 F-FDG brain PET/MRI was performed and showed marked pontine hypermetabolism corresponding to the signal abnormality and enhancement on structural imaging. Collectively, these findings are characteristic of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Wallerian degeneration (WD) of the middle cerebellar peduncles (MCPs) following pontine infarction is a rare secondary degenerative neurological condition. Due to its infrequency, there is limited research on its characteristics., Methods: This study aims to present three cases of WD of MCPs following pontine infarction and to analyze the prognosis, clinical manifestations, and neuroimaging features by amalgamating our cases with previously reported ones., Results: The cohort consisted of 25 cases, comprising 18 men and 7 women aged 29 to 77 years (mean age: 66.2 years). The majority of patients (94%) exhibit risk factors for cerebrovascular disease, with hypertension being the primary risk factor. Magnetic resonance imaging (MRI) can detect WD of MCPs within a range of 21 days to 12 months following pontine infarction. This degeneration is characterized by bilateral symmetric hyperintensities on T2/FLAIR-weighted images (WI) lesions in the MCPs. Moreover, restricted diffusion, with hyperintensity on diffusion-weighted imaging (DWI) and low apparent diffusion coefficient (ADC) signal intensity may be observed as early as 21 days after the infarction. Upon detection of WD, it was observed that 20 patients (80%) remained asymptomatic during subsequent clinic visits, while four (16%) experienced a worsening of pre-existing symptoms., Conclusions: These findings underscore the importance of neurologists enhancing their understanding of this condition by gaining fresh insights into the neuroimaging characteristics, clinical manifestations, and prognosis of individuals with WD of bilateral MCPs., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

This study aimed to investigate, for the first time, the potential role of the gigantocellular nucleus, a component of the reticular formation, in the pathogenetic mechanism of Sudden Infant Death Syndrome (SIDS), an event frequently ascribed to failure to arouse from sleep. This research was motivated by previous experimental studies demonstrating the gigantocellular nucleus involvement in regulating the sleep-wake cycle. We analyzed the brains of 48 infants who died suddenly within the first 7 months of life, including 28 SIDS cases and 20 controls. All brains underwent a thorough histological and immunohistochemical examination, focusing specifically on the gigantocellular nucleus. This examination aimed to characterize its developmental cytoarchitecture and tyrosine hydroxylase expression, with particular attention to potential associations with SIDS risk factors. In 68% of SIDS cases, but never in controls, we observed hypoplasia of the pontine portion of the gigantocellular nucleus. Alterations in the catecholaminergic system were present in 61% of SIDS cases but only in 10% of controls. A strong correlation was observed between these findings and maternal smoking in SIDS cases when compared with controls. In conclusion we believe that this study sheds new light on the pathogenetic processes underlying SIDS, particularly in cases associated with maternal smoking during pregnancy.

Facial paralysis presents as unilateral mouth drooping and lagophthalmos. The main causes of peripheral facial paralysis are Bell's palsy and Ramsay-Hunt syndrome. However, rarely occurring pontine infarctions of the facial nucleus also manifest a lower motor neuron pattern of facial paralysis. We report a case of a man in his 50s who presented to the emergency department with unilateral peripheral facial paralysis. The initial diffusion-weighted images were unremarkable, and the patient was managed as per guidelines for hypertensive encephalopathy or Bell's palsy. On the 3rd day after admission, he was diagnosed with left pontine infarction and suspected infarction of the left anterior inferior cerebellar artery. We propose that in similar cases, re-examination of imaging results should be considered, as diffusion-weighted imaging is characteristically prone to generate false-negative results in patients with early onset or posterior circulation infarction., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The term Pontocerebellar Hypoplasia (PCH) was initially used to designate a heterogeneous group of fetal-onset genetic neurodegenerative disorders. As a descriptive term, PCH refers to pons and cerebellum of reduced volume. In addition to the classic PCH types described in OMIM, many other disorders can result in a similar imaging appearance. This study aims to review imaging, clinical and genetic features and underlying etiologies of a cohort of children with PCH on imaging. We systematically reviewed brain images and clinical charts of 38 patients with radiologic evidence of PCH. Our cohort included 21 males and 17 females, with ages ranging between 8 days to 15 years. All individuals had pons and cerebellar vermis hypoplasia, and 63% had cerebellar hemisphere hypoplasia. Supratentorial anomalies were found in 71%. An underlying etiology was identified in 68% and included chromosomal (21%), monogenic (34%) and acquired (13%) causes. Only one patient had pathogenic variants in an OMIM listed PCH gene. Outcomes were poor regardless of etiology, though no one had regression. Approximately one third of patients deceased at a median age of 8 months. All individuals had global developmental delay, 50% were non-verbal, 64% were non-ambulatory and 45% required gastrostomy feeding. This cohort demonstrates that radiologic PCH has heterogenous etiologies and the "classic" OMIM-listed PCH genes underlie only a minority of cases. Broad genetic testing, including chromosomal microarray and exome or multigene panels, is recommended in individuals with PCH-like imaging appearance. Our results strongly suggest that the term PCH should be used to designate radiologic findings, and not to imply neurogenerative disorders., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Behcet's disease; it is a vascular-inflammatory chronic recurrent disease that can affect many systems in the body. Millard Gubler syndrome is one of the brainstem syndromes that occurs due to lesions involving the ventral part of the caudal pons. We wanted to present a case of Millard Gubler syndrome, which developed due to Behçet's syndrome lesion in the pons ventral region in a patient who presented with limitation of outward gaze on the left, inability to close the left eye completely, inability to completely wrinkle the left side of the forehead, and loss of contralateral muscle strength. Keywords: Behcet's syndrome, parenchymal, abducens, facial, lesion.

Objectives: The presence of dysphagia in stroke is associated with mortality and morbidity. The aim of this retrospective study is to present the relationship between dysphagia and the demographic characteristics of the patient, and the type and localisation of brain lesion in the acute period in stroke patients with dysphagia., Materials and Methods: The data of 284 patients who had stroke-related dysphagia, had a disease duration 1-3 months, had no history of swallowing dysfunction before the event, and had their brain MRI/CT reports in the hospital were included., Results: The rate of tube-dependent oral areas was higher in the lesions located in the pons and the medulla than in the lesions located in the MCA cortex, the basal ganglia, and the cerebellum ( p  ˂ 0.001, p  = 0.032 and p  = 0.011, respectively) and the percentage of those fed with NG + TPN + PEG was statistically significantly higher ( p  = 0.002, p  = 0.032 and p  = 0.011, respectively). History of pneumonia was found to be statistically significantly higher in the lesions located in the pons and the medulla than in the lesions located in the MCA cortex, ACA cortex, PCA cortex, the basal ganglia, periventricular white matter, the thalamus, the cerebellum, and the midbrain ( p  ˂ 0.001, p  = 0.005, p  = 0.023, p  ˂ 0.001, p  = 0.023, p  = 0.001, p  = 0.011 and p  = 0.023, respectively)., Conclusion: In conclusion, although lesion localisation in the acute period in patients with dysphagia varied in terms of clinical swallowing evaluation findings, weight loss, pneumonia history, the rate of tube-dependent intake, were shown to be higher in patients who had lesions in the pons and the medulla, which is a finding that should be considered in the clinical follow-up of acute stroke patients with lesions in the pons and the medulla.

Objective: In the authors' microsurgical experience, the trans-middle cerebellar peduncle (MCP) approach to the lateral and central pons has been the most common approach to brainstem cavernous malformations (BSCMs). This approach through a well-tolerated safe entry zone (SEZ) allows a wide vertical or posterior trajectory, reaching pontine lesions extending into the midbrain, medulla, and pontine tegmentum. Better understanding of the relationships among lesion location, surgical trajectory, and long-term clinical outcomes could determine areas of safe passage., Methods: A single-surgeon cohort study of all primary trans-MCP BSCM resections was conducted from July 1, 2017, to June 30, 2021. Preoperative and postoperative MR images were independently reviewed by 3 investigators blinded to the intervention, using a standardized rubric to define BSCM regions of interest (ROIs) involved with a lesion or microsurgical tract. Statistical testing, including the chi-square test with the Bonferroni correction, logistic regression, and structural equation modeling, was performed to analyze relationships between ROIs and clinical outcomes., Results: Thirty-one patients underwent primary trans-MCP BSCM resection during the study period. The median age was 50 years (IQR 24-49 years); 19 (61%) patients were female, and 12 (39%) were male. Seven (23%) patients had familial cavernous malformation syndromes. The median follow-up was 9 months (range 6-37 months). At the last follow-up, composite neurological outcomes were favorable: 22 (71%) patients had 0 (n = 12, 39%) or 1 (n = 10, 32%) major persistent deficit, 5 patients (16%) had 2 deficits, 2 (7%) had 3 deficits, and 1 patient each (3%) had 4 or 6 deficits. Unfavorable composite outcomes were significantly associated with lesions (OR 7.14, p = 0.04) or surgical tracts (OR 12.18, p < 0.001) extending from the superior cerebellar peduncle (SCP) into the contralateral medial midbrain. The ipsilateral dorsal pons was the most frequently implicated ROI involving a surgical tract and the development of new postoperative deficits. This region involved the rhomboid pontine territory and transgression of the pontine tegmentum (OR 7.53, p < 0.001). Structural equation modeling supported medial midbrain and pontine tegmentum transgression as the primary drivers of morbidity., Conclusions: Trans-MCP resection is a safe and effective treatment for BSCMs, including lesions with marked superior or inferior ipsilateral extension. Two trajectories are associated with increased neurological risk: first, a superomedial trajectory to lesions extending into the midbrain that transgresses the SCP, its decussation, or both; and second, a posteromedial trajectory to lesions extending into the pontine tegmentum. The corticospinal tract, SCP, and pontine tegmentum form an invisible triangle within the pontine white matter tolerant of transgression. When the surgeon works within this triangle, most deep pontine BSCMs, including large lesions, those with contralateral or posterior extension, and others extending into the midbrain and medulla, can be resected safely with the trans-MCP approach.

Introduction: Diffuse midline glioma (DMG) of the pons occurs in pediatric patients and carries a dismal prognosis. Biopsy is not necessary for diagnosis but provides information, particularly H3K27M status, with prognostic implications. Additionally, biopsy information may open therapeutic options such as clinical trials that require mutation status. Therefore, we sought to assess the safety of surgical biopsy in DMG patients as well as its potential impact on clinical course., Methods: Retrospective analysis of patients who were radiographically and clinically diagnosed with pontine DMG in the last 5 years was performed. We assessed demographic, clinical, radiographic, surgical, and follow-up data., Results: 25 patients were included; 18 (72%) underwent biopsy while 7 (28%) declined. 12 biopsies (67%) were performed with robotic arm and 5 (27%) with frameless stereotaxy. Three biopsied patients (17%) experienced new post-operative neurologic deficits (1 facial palsy, 1 VI nerve palsy and 1 ataxia) that all resolved at 2-week follow-up. All biopsies yielded diagnostic tissue. Fourteen patients (78%) had H3K27M mutation. Median OS for H3K27M patients was 10 months compared to 11 months in the wild-type patients (p = 0.30, log-rank test). Median OS for patients enrolled in clinical trials was 12 months compared to 8 months for non-trial patients (p = 0.076)., Conclusion: In our series, stereotactic pontine DMG biopsies did not carry any permanent deficit or complication and yielded diagnostic tissue in all patients. Similar post-operative course was observed in both robot-assisted and frameless stereotactic approaches. There was no significant difference in survival based on mutation status or clinical trial enrollment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: We report a patient with extraordinary pontine infarction-induced contralateral central facial palsy and weakened limb strength., Case Report: This is a 66-year-old man with left arm movement difficulty for 10 days and worsening over the last 1 day. His left nasolabial fold flattening and left arm strength and sensory were decreased. He could not complete the finger-nose test well with his right hand. Magnetic resonance and magnetic resonance angiography tests confirmed his right pontine acute infarction but without large vessel stenosis or occlusion., Conclusion: "Uncrossed paralysis" patients may present with contralateral face and body weakness with pontine infarcts, if the infarct occurs above the level of the facial nucleus head, and may be simmilar with the higher level pontine lesions or cerebrum semisphere infarction, which need particular attention during clinical practice., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Diffuse intrinsic pontine glioma (DIPG) is a primary brainstem tumor of childhood that carries a dismal prognosis, with median survival of less than 1 year. Because of the brain stem location and pattern of growth within the pons, Dr. Harvey Cushing, the father of modern neurosurgery, urged surgical abandonment. Such a dismal prognosis remained unchanged for decades, coupled with a lack of understanding of tumor biology and an unchanging therapeutic panorama. Beyond palliative external beam radiation therapy, no therapeutic approach has been widely accepted. In the last one to two decades, however, increased tissue availability, an improving understanding of biology, genetics, and epigenetics have led to the development of novel therapeutic targets. In parallel with this biological revolution, new methods intended to enhance drug delivery into the brain stem are contributing to a surge of exciting experimental therapeutic strategies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pontine gliomas represent difficult to treat entity due to the location and heterogeneous biology varying from indolent low-grade gliomas to aggressive diffuse intrinsic pontine glioma (DIPG). Making the correct tumor diagnosis in the pontine location is thus critical. Here, we report a case study of a 14-month-old patient initially diagnosed as histone H3 wild-type DIPG. Due to the low age of the patient, the MRI appearance of DIPG, and anaplastic astrocytoma histology, intensive chemotherapy based on the HIT-SKK protocol with vinblastine maintenance chemotherapy was administered. Rapid clinical improvement and radiological regression of the tumor were observed with nearly complete remission with durable effect and excellent clinical condition more than 6.5 years after diagnosis. Based on this unexpected therapeutic outcome, genome-wide DNA methylation array was employed and the sample was classified into the methylation class "Low-grade glioma, MYB(L1) altered." Additionally, RT-PCR revealed the presence of MYB::QKI fusion. Taken together, the histopathological classification, molecular-genetic and epigenetic features, clinical behavior, and pontine location have led us to reclassify the tumor as a pontine MYB-altered glioma. Our case demonstrates that more intensive chemotherapy can achieve long-term clinical effect in the treatment of MYB-altered pontine gliomas compared to previously used LGG-based regimens or radiotherapy. It also emphasizes the importance of a biopsy and a thorough molecular investigation of pontine lesions., (© 2023. The Author(s).)

Objective: To investigate morphological predictors of neurological deterioration (ND) in patients with acute isolated pontine infarct., Methods: Acute isolated pontine infarct patients within 7 days after onset of stroke symptoms were included retrospectively and classified into ND and non-ND groups. Morphological phenotypes (paramedian pontine infarct [PPI], atypical PPI, small deep infarct, and other types), topographical location, and lesion size were evaluated on axial diffusion-weighted imaging., Results: There were 210 eligible patients, of whom 62 patients had ND (29.5%). The proportion of PPI was significantly higher in ND than that in non-ND (62.9% vs 39.6%). ND occurred more frequently in PPI patients than non-PPI patients (39.8% vs 20.5%). PPI located more frequently in lower pontine (20.4% vs 8.0%) and less in upper pontine (17.3% vs 30.4%, P = 0.028), and had larger ventro-dorsal length (13.8 ± 3.8 vs 9.9 ± 3.1) and width (8.3 ± 2.3 vs 6.2 ± 1.8) than non-PPI patients. The morphological phenotype of PPI was an independent risk factor for ND (OR 4.81, 95%CI 1.54-15.07, P = 0.007) in patients with isolated pontine infarct. The ventro-dorsal length of pontine infarct lesion was associated with ND (OR 1.18, 95%CI 1.01, 1.37, P = 0.034) in PPI patients., Conclusions: The morphological phenotype of PPI was a potential predictor for ND in patients with acute isolated pontine infarct. The ventro-dorsal length of pontine infarct lesion was possibly associated with ND in PPI patients., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

Objectives: Standardised uptake value ratio (SUVR) is usually obtained by dividing the SUV of the region of interest (ROI) by that of the cerebellar cortex. Cerebellar cortex is not a valid reference in cases where amyloid β deposition or lesions are present. Only few studies have evaluated the use of other regions as references. We compared the validity of the pons and corpus callosum as reference regions for the quantitative evaluation of brain positron emission tomography (PET) using 11 C-PiB compared to the cerebellar cortex., Methods: We retrospectively evaluated data from 86 subjects with or without Alzheimer's disease (AD). All subjects underwent magnetic resonance imaging, PET imaging, and cognitive function testing. For the quantitative analysis, three-dimensional ROIs were automatically placed, and SUV and SUVR were obtained. We compared these values between AD and healthy control (HC) groups., Results: SUVR data obtained using the pons and corpus callosum as reference regions strongly correlated with that using the cerebellar cortex. The sensitivity and specificity were high when either the pons or corpus callosum was used as the reference region. However, the SUV values of the corpus callosum were different between AD and HC (p < 0.01)., Conclusions: Our data suggest that the pons and corpus callosum might be valid reference regions., (© 2023. The Author(s).)

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is still a rare autoimmune disease in the world. In recent years, there are more and more reports about the clinical manifestations of CLIPPERS, but the specific etiology and pathogenesis are not clear. In this paper, by collating the literature reported in recent years, in the reported effective treatment cases, we found the current hypothesis about the pathogenesis of CLIPPERS. Three pathogenesis hypotheses: organ-specific autoimmunity; virus infection affects autoimmunity; and helper T lymphocyte 17 mediates autoimmunity. Although it is hypothetical, it is expected to further clarify the pathogenesis, evolution characteristics, and treatment of CLIPPERS, so as to provide a reference for further understanding of the disease. In the future, more observations and studies are needed to further verify the feasibility of the hypothesis. This article expands on atypical clinical manifestations and summarizes treatment options. Hope to provide a reference for clinical diagnosis and treatment of CLIPPERS., Competing Interests: The authors have no funding and conflicts of interest to disclose.All data generated or analyzed during this study are included in this published article [and its supplementary information files]., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Spastic paretic hemifacial contracture (SPHC) is a rare clinical phenomenon characterized by facial weakness and simultaneous well-sustained contraction of the unilateral half of the face, mimicking a paresis of the normal contralateral side on casual inspection. We present three cases with such phenomenon and have postulated the underlying mechanisms. One patient had intrinsic brainstem glioma, and the others were operated for extra-axial lesions compressing the pons. The former presented with SPHC, whereas the latter two gradually developed this phenomenon following postoperative facial paresis. This condition is possibly due to denervation hyper-excitability of the facial supranuclear pathway or an aberrant regeneration secondary to nerve injury leading to functional facial-nerve nuclear reorganization. SPHC occurrence is not limited to intra-axial lesions but can also be seen after partial injury to the facial nerve beyond its exit from the brainstem., Competing Interests: None

Objectives: In spinal cord injury (SCI), the primary mechanical injury is followed by secondary sequelae that develop over the subsequent months and manifests in biochemical, functional, and microstructural alterations, at the site of direct injury but also in the spinal cord tissue above and below the actual lesion site. Noninvasive magnetic resonance spectroscopy (MRS) can be used to assess biochemical modulation occurring in the secondary injury phase, in addition to and supporting conventional MRI, and might help predict and improve patient outcome. In this article, we aimed to examine the metabolic levels in the pons of subacute SCI by means of in vivo proton MRS at 3 T and explore the association to clinical scores., Materials and Methods: In this prospective study, between November 2015 and February 2018, single-voxel short-echo MRS data were acquired in healthy controls and in SCI subjects in the pons once during rehabilitation. Besides the single-point MRS examination, in addition, in participants with SCI, the clinical status (ie, motor, light touch, and pinprick scores) was assessed twice: (1) around the MRS session (approximately 10 weeks postinjury) and (2) before discharge (at approximately 9 months postinjury). The group differences were assessed with Kruskal-Wallis test, the post hoc comparison was assessed with Wilcoxon rank sum test, and the clinical correlations were conducted with Spearman rank correlation test. Bayes factor calculations completed the statistical part providing relevant evidence values., Results: Twenty healthy controls (median age, 50 years; interquartile range, 41-55 years; 18 men) and 18 subjects with traumatic SCI (median age, 50 years; interquartile range, 32-58 years; 16 men) are included. Group comparison showed an increase of total N -acetylaspartate and combined glutamate and glutamine levels in complete SCI and a reduction of total creatine in incomplete paraplegic SCI. The proton MRS-based glutathione levels at baseline correlate to the motor score improvement during rehabilitation in incomplete subacute SCI., Conclusions: This exploratory study showed an association of the metabolite concentration of glutathione in the pons assessed at approximately 10 weeks after injury with the improvements of the motor score during the rehabilitation. Pontine glutathione levels in subjects with traumatic subacute incomplete SCI acquired remote from the injury site correlate to clinical score and might therefore be beneficial in the rehabilitation assessments., Competing Interests: Conflicts of interest and sources of funding: This study was funded by the Swiss Paraplegic Foundation (Research Program Radiology), Swiss National Science Foundation (grant number 143715), Hartmann-Müller-Stiftung (grant number 2047), and ERC Starting Grant (SYNAPLAST MR, grant number 679927)., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory disorder of the central nervous system, characterized by symptoms referable to the brainstem and cerebellum such as, diplopia, gait ataxia and cerebellar dysarthria. The features and outcomes of CLIPPERS remains uncertain. we conducted this comprehensive systematic review to summarize all the existing studies that described CLIPPERS in the literature and to provide a quantitative assessment on the clinical characteristics, management, and outcomes of this rare syndrome., Methods: A comprehensive search of PubMed and Web of Science databases was conducted from inception until January 15, 2022, was conducted. We only included the cases that clearly reported probable or definite diagnosis of CLIPPERS based on Taieb et al.'s criteria. The quality of the included studies was assessed using the JBI Critical Appraisal Tool. Descriptive statistics were performed to analyze the studies. Data were expressed as mean and standard deviation (SD) for continuous variables and proportions for categorical variables., Results: We identified 100 case reports and series including a total of 140 patients with CLIPPERS (mean age: 46±18 years and males were 60%). The average follow-up duration was 32.27±57.8 months. Ataxia was the most common presenting symptom. Sixteen percent of the cases were associated with malignancy, mostly hematologic malignancies. The overall relapse rate was 59.2%, and the duration of steroid therapy was considerably shorter in the relapsed cases than in the non-relapsed (mean 6.19±7.9 vs. 10.14±12.1 days, respectively, P = 0.04). The overall mortality rate was 10%, but mortality in patients with malignancy was 30% and it was 12% in patients with relapses. In the case of steroid dosing (less than 20 mg/d versus greater than 20 mg/d) there was no significant modification in the risk of relapse., Conclusion: CLIPPERS is a rare clinical syndrome that affects mainly middle-aged males. Diagnosis of CLIPPERS is often challenging, and delays in diagnosis and treatment can lead to unfavorable outcomes. Therefore, neurologists should maintain a high index of suspicion for CLIPPERS in any patient presenting with symptoms and signs referrable to the brainstem. These patients should be screened for associated malignancies, especially hematological malignancies. The cases associated with malignancy tend to have worse outcomes. The relapse rate is relatively high. The relapse rate may be associated with worse mortality. Based on our findings, we recommend that CLIPPERS be treated with high-dose steroid therapy for at least ten days during the acute phase with a very slow taper. Prospective studies with a larger sample size are needed to validate our findings and guide the clinical care of these patients., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Vertical pendular nystagmus (PN) rarely occurs with acute pontine lesions. To hypothesize a pathophysiology for acute vertical PN, we analyzed the clinical characteristics and quantitative eye-movement recordings of one new case with acute vertical PN and an additional 11 patients from the literature. Most patients had extensive pontine lesions causing either the locked-in syndrome or unresponsiveness, but two conscious patients had focal lesions restricted to the paramedian caudal pontine tegmentum. All patients presented a complete or partial horizontal gaze palsy, and about half showed ocular bobbing before or during the appearance of vertical PN. The vertical oscillations were conjugate at a frequency of 1-5 Hz, and the amplitudes were variable, ranging from 0.2° to 40°. The peak velocities were asymmetric in some patients, faster with downward movements. About half of the patients developed palatal tremor several weeks or months after presenting with acute vertical PN. Based on the location of the lesions and results of eye-movement recordings, we suggest two possible mechanisms for acute vertical PN; oscillations originating in the inferior olives due to disruption of the central tegmental tract or low-velocity saccadic oscillations caused by omnipause neuron damage., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Primary Sjögren's syndrome (pSS) is an autoimmune inflammatory disease characterized by dryness of the eyes, mouth and other mucous membranes. Patients with pSS can also present with extraglandular manifestations, such as pulmonary, kidney and nervous system involvement. Central nervous system (CNS) manifestations have rarely been described in pSS., Case Presentation: A 33-year-old man was admitted with a one-month history of dizziness, speech disturbance, and walking instability. His brain enhanced magnetic resonance imaging (MRI) showed symmetrical, enhanced "salt-and-pepper-like" speckled lesions in the brainstem, basal ganglia, and subcortical regions, and his diagnosis was considered possible chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Further examination revealed that anti-SSA antibody was positive, and the Schirmer test and labial salivary gland histopathology were abnormal, which supported the diagnosis of pSS., Conclusion: pSS is a chronic systemic autoimmune disease that involves neurological complications. This case suggests that CNS lesions of pSS can present with clinical and MRI findings similar to those of CLIPPERS., (© 2022. The Author(s).)

Background: Disseminated diffuse midline glioma (DMG) is a devastating diagnosis. Molecular subtyping has increased our understanding of this tumor., Case: Here, we report the case of an 8-year-old girl who presented with symptoms of brainstem dysfunction and was found to have disseminated DMG with lesions in the pons, thalamus and bilateral temporal lobes. Molecular subtyping of the temporal lobe tumor tissue was consistent with H3 K27me3 loss and EZHIP overexpression, falling under the newly designated "H3 K27-altered" AQ5WHO subtype of DMG. Pathology from biopsy of the orbital lesion showed poorly differentiated rhabdoid-like disseminated tumor cells. The patient went on to develop lesions in the peritoneum, infratemporal fossa, and along the lumbosacral nerve roots., Conclusion: This unique case illustrates the aggressive behavior of H3 K27-altered tumors and their potential to metastasize., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Morphological differences that can lead the trigeminal nerve to neurovascular conflict and a new solitary pontine lesion are associated with the pathogenesis of trigeminal neuralgia (TN). In this case-control study, we aimed to contribute to the current discussions about the pathogenesis of TN by investigating the anatomical structures that may have an effect on the morphometric parameters of the trigeminal nerve., Methods: This study included 25 patients with TN followed up for pain in the Department of Algology, Faculty of Medicine, and 25 age- and gender-matched controls. We performed morphometric measurements including the length and volume of the trigeminal nerve, cerebellopontine cistern, pons, and posterior fossa in the MRIs of these individuals. Comparative analyses were performed for the mean of the affected and unaffected sides of the TN patients and the right, left, and both sides of the control group., Results: In patients with TN, on the affected side, length and volume of the trigeminal nerve and cerebellopontine cistern volume were found smaller than controls (p < 0.05). Pons volume was higher in patients with TN compared to controls (p < 0.05). The length of the affected nerve was significantly related to prepontine cistern length and cerebellopontine cistern volume (p < 0.05)., Discussion: The cerebellopontine cistern volume has a significant impact on the morphometric characteristics of the trigeminal nerve. Especially, whether the increase in the volume of pons causes a decrease in the volume of cerebellopontine cistern should be clarified with further research.

Competing Interests: Competing interests: None declared.

Background: Pontine infarctions are often associated with extrapontine infarcts. We aimed to elucidate differences in clinical characteristics, mechanisms, and functional outcomes between isolated pontine infarction (IPI) and pontine plus infarction (PPI)., Methods: We studied patients with acute pontine infarction between January 2019 and August 2021 and divided them into IPI and PPI according to diffusion-weighted magnetic resonance image. Vertical locations were classified into rostral, middle, and caudal, and horizontal locations were categorized as basal/tegmental and unilateral/bilateral. Factors associated with poor 90-day outcome (modified Rankin scale 3-6) were analyzed., Results: Among 241 patients, 170 (70.5%) had IPI and 71 (29.5%) had PPI. The most frequently observed extrapontine areas were cerebellar (59.1%), followed by posterior cerebral artery territory (45.1%). Mental status changes, sensory changes, and ataxia were more common, and motor dysfunction was less common in PPI patients. The PPI patients more often had rostral (P < 0.001), bilateral lesions (P < 0.001), and moderate/severe vascular stenosis and atrial fibrillation; therefore, large artery disease (LAD) and cardioembolism were more common stroke mechanisms (P < 0.001). In IPI patients, high initial National Institutes of Health Stroke Scale (NIHSS) (adjusted Odds ratio (OR) = 1.38; P = 0.001) and old age (aOR = 1.05; P = 0.049) were associated with poor functional outcome, whereas moderate/severe stenosis (Reference: no stenosis, aOR = 7.17; P = 0.014) and high initial NIHSS (aOR = 1.39; P = 0.006) were related to unfavorable outcomes in PPI patients., Conclusions: PPI patients more often had extensive pontine lesions, LAD and cardioembolism, and their outcome was more often influenced by underlying severe vascular diseases. These differences need to be considered in the prevention and therapeutic strategies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The morphological changes in the pons and cerebellum of neonates experiencing profound asphyxia in the early period of life remain to be clarified., Purpose: To assess the changes in the size of the pons and cerebellum during the first two weeks of life in term neonates with pontine and cerebellar injury caused by hypoxic-ischemic encephalopathy in comparison with a control group., Material and Methods: Two groups were investigated: a group with pontine/cerebellar injury (PCI) (n = 10) demonstrated by magnetic resonance imaging (MRI) diffusion-weighted imaging; and a control group without PCI - focal-multifocal white matter injury and a normal pattern (n = 24). The anteroposterior diameter (APD) and height of the pons and cerebellar vermis, and the transverse width of the cerebellum were measured twice in the first and second weeks of life. Differences between the groups were analyzed statistically using paired and unpaired Student's t-test at a significance level of P  < 0.05., Results: In the PCI group, the pontine APD and cerebellar vermian height were significantly decreased in the second week. An increase of pons and cerebellar size was evident during the first two weeks of life in the control groups., Conclusion: Infants with PCI and profound asphyxia show rapid decreases in pontine APD and cerebellar vermian height within the first two weeks of life.

DIPG (diffuse intrinsic pontine glioma) is a deadly cancerous tumor of the brainstem that spreads across the pons. The tumor's infiltrative nature, as well as the tumor's critical pathway and nuclei compression, contributes to the tumor's extremely poor prognosis and limited existing therapeutic options. A previous study revealed that in 40 patients with brainstem glioma, 13 (33%) patients had leptomeningeal spreading. In this paper, we reported a 7-year-old female patient who presented with a history of decreased consciousness and weakness of the right limb. Her magnetic resonance imaging (MRI) revealed a pontine mass. She was given 35 fractions of 54 Gy whole-brain radiotherapy. The post-radiotherapy MRI evaluation showed multiple nodules in periventricular region, and was suggestive of leptomeningeal and subependymal seeding of the pontine glioma in the lateral ventricles. This case report elucidated the leptomeningeal seeding in a pediatric patient with diffuse intrinsic pontine glioma., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: There are scarce data regarding pontine arteries anatomy, which is the basis for ischemic lesions following their occlusion. The aim of this study was to examine pontine vasculature and its relationships with the radiologic and neurologic features of pontine infarctions., Materials and Methods: Branches of eight basilar arteries and their twigs, including the larger intrapontine branches, were microdissected following an injection of a 10% mixture of India ink and gelatin. Two additional brain stems were prepared for microscopic examination after being stained with luxol fast blue and cresyl violet. Finally, 30 patients with pontine infarctions underwent magnetic resonance imaging (MRI) in order to determine the position and size of the infarctions., Results: The perforating arteries, which averaged 5.8 in number and 0.39 mm in diameter, gave rise to paramedian and anteromedial branches, and also to anterolateral twigs (62.5%). The longer leptomeningeal and cerebellar arteries occasionally gave off perforating and anterolateral twigs, and either the lateral or posterior branches. Occlusion of some of these vessels resulted in the paramedian (30%), anterolateral (26.7%), lateral (20%), and combined infarctions (23.3%), which were most often isolated and unilateral, and rarely bilateral (10%). They were located in the lower pons (23.3%), middle (10%) or rostral (26.7%), or in two or three portions (40%). Each type of infarction usually produced characteristic neurologic signs. The clinical significance of the anatomic findings was discussed., Conclusions: There was a good correlation between the intrapontine vascular territories, the position, size and shape of the infarctions, and the type of neurologic manifestations., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Central pontine myelinolysis is most commonly associated with rapid correction of hyponatremia and has historically been associated with alcoholism. In this case report, 2 deaths with gross findings of central pontine lesions led to the possibility that CPM may have been a potential mechanism of death. Subsequent analysis revealed that these lesions were incidental findings. This case report discusses the importance of appropriate microscopic and immunohistochemical analysis of suspected CPM cases., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: Imaging biomarkers derived from different brainstem structures are suggested to differentiate among parkinsonian disorders, but clinical implementation requires normative data. The main objective was to establish high-quality, sex-specific data for relevant brainstem structures derived from MR imaging in healthy subjects from the general population in their sixth and seventh decades of life., Materials and Methods: 3D T1WI acquired on the same 1.5T scanner of 996 individuals (527 women) between 50 and 66 years of age from a prospective population study was used. The area of the midbrain and pons and the widths of the middle cerebellar peduncles and superior cerebellar peduncles were measured, from which the midbrain-to-pons ratio and Magnetic Resonance Parkinsonism Index [MRPI = (Pons Area / Midbrain Area) × (Middle Cerebellar Peduncles / Superior Cerebellar Peduncles)] were calculated. Sex differences in brainstem measures and correlations to age, height, weight, and body mass index were investigated., Results: Inter- and intrareliability for measuring the different brainstem structures showed good-to-excellent reliability (intraclass correlation coefficient = 0.785-0.988). There were significant sex differences for the pons area, width of the middle cerebellar peduncles and superior cerebellar peduncles, midbrain-to-pons ratio, and MRPI (all, P  <  .001; Cohen D = 0.44-0.98), but not for the midbrain area ( P  = .985). There were significant very weak-to-weak correlations between several of the brainstem measures and age, height, weight, and body mass index in both sexes. However, no systematic difference in distribution caused by these variables was found, and because age had the highest and most consistent correlations, age-/sex-specific percentiles for the brainstem measures were created., Conclusions: We present high-quality, sex-specific data and age-/sex-specific percentiles for the mentioned brainstem measures. These normative data can be implemented in the neuroradiologic work-up of patients with suspected brainstem atrophy to avoid the risk of misdiagnosis., (© 2022 by American Journal of Neuroradiology.)

Millard-Gubler syndrome (MGS) is a ventral pontine syndrome due to an ipsilateral involvement of abducens and facial nerve with a contralateral hemiparesis or hemiplegia. Although classically described as a vascular brainstem syndrome, various other aetiologies such as infection or demyelination may lead to MGS. In this case, a young female presented with MGS, which was attributed to a strategically located infective granuloma of the brainstem. In countries, where tuberculosis is still considered an endemic, central nervous system involvement due to tuberculosis may have protean manifestations., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)