Millard-Gubler Syndrome in a Patient with Pontine Infarction: A Case Report

Millard-Gubler Syndrome is a rare neurological condition caused by damage to the sixth and seventh cranial nerves, as well as the corticospinal tract in the brainstem. It is characterized by the presence of ipsilateral facial paralysis and contralateral hemiplegia. We report a 55-year-old male patient who presented with sudden onset of left-sided weakness. Imaging revealed a pontine infarct. The patient therefore, was diagnosed with Millard-Gubler Syndrome also known as Ventral Pontine Syndrome based on his symptoms and imaging findings. He was treated with Aspirin and Atorvastatin and was referred to neurology for further consultation and to physiotherapy for his weakness. This case report highlights the importance of prompt recognition and diagnosis of Millard-Gubler Syndrome in patients with pontine infarction. Early identification especially with the use of high-resolution MRI can facilitate appropriate management and treatment, ultimately improving patient outcomes.

Progressive multifocal exophytic pontine glioblastoma: a case report with literature review

Multifocal pontine glioblastoma exhibiting an exophytic growth pattern in the cerebello-pontine angle(CPA) is rare.We present a case of a 5-year-old girl with consecutive neurological imaging and other clinical findings indicating progressive multifocal exophytic pontine glioblastoma.Three lesions were reported,of which two were initially presented,and one was developed 2 months later.One lesion demonstrated a progressing exophytic extension in the cistern of the left side of the CPA.The other two lesions were located and confined within the pons.Initial magnetic resonance imaging and positron emission tomography-computed tomography indicated low-grade glioma or inflammatory disease.However,2 and 3 months later,subsequent magnetic resonance spectroscopy(MRS) displayed elevated choline and depressed N-acetyl aspartate peaks compared with the peaks on the initial MRS,indicating a high-grade glioma.Subtotal resection was performed for the CPA lesion.Histopathologic examination showed discrepant features of different parts of the CPA lesion.The patient received no further chemotherapy or radiotherapy and died 2 months after surgery.The multifocal and exophytic features of this case and the heterogeneous manifestations on neurological images were rare and confusing for both diagnosis and surgical decision-making.Our case report may contribute knowledge and helpful guidance for other medical doctors.

what drives progressive motor deficits in patients with acute pontine infarction?

Progressive motor deficits are relatively common in acute pontine infarction and frequently associated with increased functional disability. However, the factors that affect the progression of clinical motor weakness are largely unknown. Previous studies have suggested that pontine infarctions are caused mainly by basilar artery stenosis and penetrating artery disease. Recently, lower pons lesions in patients with acute pontine infarctions have been reported to be related to progressive motor deficits, and ensuing that damage to the corticospinal tracts may be respon- sible for the worsening of neurological symptoms. Here, we review studies on motor weakness progression in pontine infarction and discuss the mechanisms that may underlie the neurologic worsening.

Bilateral Hypertrophic Olivary Degeneration after Pontine Hemorrhage: A Case Report

BACKGROUND Hemorrhage lesions may lead to bilateral hypertrophic olivary degeneration(HOD)through interruption of the dentato-rubral-olivary pathway.The pathological features of HOD are unusual neuronal trans-synaptic degenerative changes.CASE SUMMARY A 56-year-old female was admitted to our hospital because her lower extremities and left upper ones were unable to move for 3 mo,and the swelling of her right lower extremities became worse 3 days ago.She had a hypertension history.Her characteristic clinical manifestations are palatal myoclonus and nystagmus.The patient’s magnetic resonance imaging(MRI)results showed that she had bilateral HOD after an acute pontine hemorrhage.She was given symptomatic and supportive treatment.The gabapentin,the memantine and the trihexyphenidyl were taken twice a day each.The rehabilitation and psychotherapy were implemented.After 3 months of treatment,her eye symptoms improved.CONCLUSION Bilateral HOD is a rare phenomenon after pontine hemorrhage.The key to diagnosis lies in the clinical manifestations and MRI results.

A Phase II Study of Antineoplastons A10 and AS2-1 in Patients with Brainstem Gliomas. The Report on Non-Diffuse Intrinsic Pontine Glioma (Protocol BT-11)

Inoperable brainstem gliomas (BSG) are among the most difficult to treat malignancies. In the intent-to-treat (ITT) population of the BT-11 study for BSG, forty patients (median age 11.2 years old) were enrolled. Antineoplastons A10 and AS2-1 (ANP) were administered intravenously daily. The median daily dose of A10 was 8.70 g/kg/day and AS2-1 was 0.32 g/kg/day. Efficacy analyses were conducted in two subgroups: recurrent pediatric diffuse intrinsic pontine glioma (RPDIPG, N?= 17) and non-diffuse intrinsic pontine glioma (NDIPG, N?= 11). This paper reports the results of the study of the efficacy and safety of ANP in patients with NDIPG. The results in the RPDIPG group were reported before;complete response (CR) was 6%, partial response (PR) 23.5%, and stable disease (SD) 17.6%. One year overall survival (OS) was 29.4%, 2 years 11.8%, and 5, 10, and 15 years 6%. In the NDIPG group, there were 36% CR and 27.5% SD. OS at 1, 5, 10, and 15 years was 82%, 73%, 62%, and 50% correspondingly. There was only one serious adverse event (9%) reported in NDIPG represented by hypokalemia, Grade 4. The results suggest that ANP shows efficacy and an acceptable tolerability profile in patients with RPDIPG and NDIPG.

Spared integrity of corticospinal tract within a pontine infarct A diffusion tensor tractography study

Integrity of the corticospinal tract is mandatory for good recovery of impaired motor function in patients who have suffered a stroke.A 67-year-old left hemiparetic female showed an infarct in the right pons.Three months after onset,motor function of the affected extremities recovered rapidly to a nearly complete state.Diffusion tensor tractography of both hemispheres showed that the corticospinal tract originated from the primary sensori-motor cortex and descended through the known corticospinal tract pathway.The tract of the affected（right）hemisphere descended through an area within the pontine infarct.The diffusion tensor tractography results suggest that from the onset,the integrity of the corticospinal tract appears to have been spared within the pontine infarct.

Factors Determining the Outcome of Pontine Hemorrhage in the Absence of Surgical Intervention

Objectives and Importance: Although pontine hemorrhage is very often fatal, the clinical manifestations vary accord-ing to the location and extent of the hematoma. We investigated the prognostic factors of pontine hemorrhage by assessing clinical manifestation and CT findings in relation to outcome. Materials and Methods: The outcome and clinical features of 19 patients with pontine hemorrhage without surgical intervention were analyzed. The CT features of the hematoma were classified into four types: massive, tegmento-basilar, transverse oval, and small unilateral. The Glasgow Outcome Scale (GOS) was used to assess patient outcome (G, good recovery;MD, moderate disability;SD, severe disability, V, vegetative state, D, death) at discharge. Results: The outcome was MD in 7 cases, SD in 3, and D in 9. Eight of 9 patients with acute hydrocephalus died, whereas only one of 10 patients without hydrocephalus died (p 12, tetraparesis, or respiratory failure (p < 0.01, 0.05, 0.01, respectively). Four of 5 patients with CT evidence of massive hemorrhage died, and another patient became vegetative. The outcome in 6 patients with tegmento-basilar-type hematoma included D in 3, V in 2, and MD in 1, and that in 7 patients with transverse oval hematoma included D in 2, V in 1, SD in 1, and MD in 3. Five (65%) of the 8 patients with transverse oval or small unilateral hematomas were able to walk (MD) with or without assistance, whereas only 2 (18%) of 11 patients with tegmento-basilar-type and massive hematoma were ambulatory at discharge (p < 0.05). Conclu-sion: On the basis of CT classification, the functional prognosis of transverse oval pontine hemorrhage is as favorable as that of the small unilateral type.

Compression of the bilateral corticospinal tracts by bilateral pontine hemorrhage A diffusion tensor tractography study

Bilateral spontaneous pontine hemorrhage is rare. In addition, bilateral corticospinal tract （CST） involvement in the pons may accompany serious motor sequelae. A 45-year-old right-handed woman was admitted for bilateral pontine hemorrhage. The patient presented with moderate quadriparesis at stroke onset and quickly recovered to the point of being able to extend the muscles of all four extremities against resistance, at 2 weeks from onset. At 4 weeks after stroke onset, she was able to perform all fine motor activities, as well as to walk with a normal gait. Diffusion tensor tractography results showed that the CSTs of both hemispheres originated from the primary sensorimotor cortex and descended through the corona radiata, the posterior limb of the internal capsule, midbrain, anterior pons, and the anterior medulla, along the known pathway of the CST. However, at midbrain and pons, the CSTs were compressed posterolaterally. The contralateral primary sensorimotor cortex, centered on the precentral knob, was activated during movement of either hand of the patient, as shown by functional MRI, which indicates the preservation of lateral CST. Findings from this study suggest that diffusion tensor tractography may be helpful in the elucidation of the CST status in patients with pontine hemorrhage.

Central pontine myelinolysis mimicking glioma in diabetes:A case report

BACKGROUND Central pontine myelinolysis(CPM)usually occurs during rapid correction of serum osmolality,typically with brainstem lesions presenting uniform signals following enhancement on magnetic resonance imaging(MRI).We report a case of CPM caused by diabetes,which was characterized by glioma-like imaging features and the patient responded well to corticosteroids.CASE SUMMARY A 49-year-old man with type 2 diabetes was admitted due to numbness and weakness for 6 mo with progressive aggravation for 2 wk.His complete blood count,serum electrolytes,renal and liver function parameters were within the normal range.MRI showed mass lesions in the brainstem,with unusually inhomogeneous signal intensity after contrast-enhanced scans.His symptoms worsened after hypoglycemic therapy.Due to his clinical history and examination results,CPM was considered the most likely diagnosis.Treatment with corticosteroids was administered with a methylprednisolone pulse in the acute phase followed by dose tapering.During the 8-mo follow-up period,his clinical symptoms and imaging features significantly improved.CONCLUSION Diabetes could rarely be accompanied by CPM,and patients who experience this neurological complication could benefit from corticosteroid treatment.Clinicians should recognize the special relationship between diabetes and CPM,and improve awareness of early identification and appropriate treatment.

Morphologic Relationship between the Pontine Micturition Center and the Sympathetic Center in the Spinal Cord of the Rat

To study whether the sympathetic nerves coordinate with the parasympathetic nerves during micturition in the rat. We used antegrade neural tracing with biotinylated dextran amine (BDA) injected into the pontine micturition center (PMC) to label the terminals in the L6-S1 cord. Preganglionic parasympathetic neurons (PPNs) in the L6-S1 segment were labelled by retrograde transport of Fluorogold (FG) from the major pelvic ganglion (MPG).We detected retrograde neurons in L6-S1 using retrograde transport of horseradish peroxidase (HRP) from the intermediolateral cell column (IML) of the L1-L2 segment where sympathetic preganglionic neurons (SPNs) are located. Immunohistochemical methods showed that PPNs were identified to be choline acetyltransferase-immunoreactive (ChAT-IR). HRP-labelled neurons were not ChAT-IR and located dorsal to PPNs. BDA-labelled terminals were located mainly in the bilateral IML of L6-S1, some of which had synaptic contact with the HRP-labelled neurons. In addition, there were some wheat germ agglutinin-horseradish peroxidase (WGA-HRP) labelled terminals in the ipsilateral IML of the L1-L2 segment after WGA-HRP was microinjected into SPN. We conclude that PMC may control the preganglionic neurons of sympathetic nerves through the interneurons located dorsal to PPNs.

Structural neuroimaging and neuropsychological correlates of a single case of focal central pontine myelinolysis: Intact memory function with decreased intellectual and motor functions

We report on the case of middle-aged right-handed woman with central pontine myelinolysis (CPM) revealed by high resolution structural T2-weighted FLAIR MRI imaging. There was a general flattening of Wechsler Adult Intelligence Scale—Fourth Edition subtest scores which were 1 standard deviation below expected values. In contrast Wechsler Memory Scale—Fourth Edition visual and auditory memory scores remained within the normal range. Verbal working memory appeared mildly impaired while nonverbal working memory was not. Scores on the Advanced Clinical Solution’s Social Perception battery were all in the normal range as were academic skills measured by the Wide Range Achievement Test—Fourth Edition. Performance was impaired on the Delis-Kaplan Executive Function System’s counterpart of the Trail-Making Test: Part B. Similarly, on the Draw-A-Person Test there was a discrepancy in that our patient’s standard score was 76 compared to her estimated premorbid FSIQ in the average range. She also displayed bilateral motor coordination slowing on the Finger Tapping task collectively suggesting damage to pontine motor tracts. The Minnesota Multiphasic Personality Inventory—Second Edition—Restructured Form profile was consistent with a diagnosis of severe anxiety and depression perhaps due to damage to serotoninergic neural tracts originating within the central pons. Finally, the patient displayed severe sleep disturbances and other signs of reticular activating formation injury. CPM may constitute a unique means of studying reversible subcortical lesions in the central pons in otherwise healthy subjects with benign illness. To our knowledge this is among the first patients with CPM without the usual risk factors for the disorder and who was otherwise healthy. Knowledge of the etiology and neuropsychology of such patients might aid in understanding the interaction of the fronto-ponto-cerebellar tracts in executive functions and motor programming.

Hypertensive brain stem encephalopathy with pontine hemorrhage: A case report

Hypertensive brain stem encephalopathy(HBE) is a rare, under diagnosed subtype of hypertensive encephalopathy(HE) which is usually reversible, but with a potentially fatal outcome if hypertension is not managed promptly. To the best of our knowledge, only one case of HE with brain stem hemorrhage has been reported. We report a case of HBE with pontine hemorrhage in a 36-year-old male patient. The patient developed severe arterial hypertension associated with initial computed tomography showing the left basilar part of pons hemorrhage, fluid-attenuated inversion-recovery showing hyperintense signals in the pons and bilateral periventricular, anterior part of bilateral centrum ovale. The characteristic clinical findings were walking difficulty, right leg weakness, and mild headache with nausea which corresponded to the lesions of MR imagings. The lesions improved gradually with improvements in hypertension, which suggested that edema could be the principal cause of the unusual hyperintensity on magnetic resonance images.

Computed Tomography-Guided Virtual Stereotactic Puncture and Catheter Drainage for a Brainstem Pontine Hemorrhage: A Case Report

Background: Patients with severe hypertensive brainstem hemorrhages have poor prognoses if they only receive conservative medical management. In contrast, aggressive operative interventions may decrease the morbidity and mortality in such patients. These operative treatments include craniotomy for evacuation of the hematoma, stereotactic positioning, and neuronavigational-guided hemorrhage puncture and drainage. Here, we report a novel and relatively simple procedure to achieve satisfactory outcomes in a patient with a brainstem pontine hemorrhage. Case Presentation: A 53-year-old man who was diagnosed with brainstem pontine hemorrhage. On hospital day 6, he underwent CT-guided, virtual stereotactic puncture and catheter drainage of this brainstem pontine hemorrhage. Medical treatments were continued after this procedure. On postoperative day 16 (hospital day 22), the patient was discharged from the hospital, awake and able to answer questions appropriately. Muscle strengths were grades V and IV for the left and right extremities, respectively. The patient was continued with active rehabilitation and achieved a Barthel index of 85 points at one month after the percutaneous drainage procedure. Conclusion: CT-guided, virtual stereotactic percutaneous transcranial puncture and catheter drainage for brainstem pontine hemorrhages has obvious potential advantages and offers a possible alternative to achieve the best outcomes with minimal operative trauma compared to open microcraniotomy.

Plaques of Nonstenotic Basilar Arteries with Isolated Pontine Infarction on Three-dimensional High Isotropic Resolution Magnetic Resonance Imaging

Background： There are few studies for evaluating plaque characteristics of nonstenotic basilar arteries （BA）. Our aim was to determine entire BA plaques with a three-dimensional volumetric isotropic turbo spin-echo acquisition （VISTA） and investigate the differences between the patients with and without isolated pontine infarction （IPI）. Methods： Twenty-four consecutive symptomatic patients with nonstenotic BA on time of flight magnetic resonance angiography （TOF MRA） were enrolled from China-Japan Friendship Hospital between January 2014 and December 2014. BA was classified as ＂normal＂ or ＂irregular＂ based on TOF MRA, and ＂normal wall＂, ＂slight wall-thickening＂, and ＂plaque＂ based on three-dimensional VISTA images. Outcomes from MRA and VISTA were compared. Patients were categorized as IPI and non-lPl groups based on the diffusion-weighted imaging. Clinical and plaque characteristics were compared between the two groups. Results： A total of 1024 image slices including 311 （30.37%） plaque slices, 427 （41.70%） slight wall-thickening slices, and 286 （27.93%） normal wall slices for the entire BA from 23 patients were finally included for analysis. VISTA images detected plaques in all the 9 （100%） irregular MRA patients and 7 of 14 （50%） normal MRA patients. IPl was found in 11 （47.83%） patients. Compared to non-IPI group, the IPI group had a higher percentage of plaque slices （P = 0.001 ） and lower percentage of normal wall slices （P = 0.014） than non-IPl group. Conclusions： Three-dimensional V1STA images enable detection of BA plaques not visualized by MRA. BA plaques could be found in both the IPl and non-IPl group. However, IPI group showed plaques more extensively in BA than the non-IPI group.

Clinical and Radiological Features of Wallerian Degeneration of the Middle Cerebellar Peduncles Secondary to Pontine Infarction

Background： Wallerian degeneration （WD） of bilateral middle cerebellar its characteristics have not yet been clarified because of the low incidence peduncles （MCPs） can occur following pontine infarction, but Thus, the present study discussed the clinical and radiological features to improve the awareness of this disease. Methods： Clinical and radiological information from consecutive individuals diagnosed with WD of bilateral MCPs following pontine infarction in three hospitals over the past 4 years between October 2012 and October 2016 were retrospectively investigated and compared with a control group （patients with pontine infarction had no secondary WD）. Results： This study involved 30 patients with WD of MCPs, with a detection rate of only 4.9%. The primary infarctions （χ2 -24.791, P = 0.001, vs. control group） were located in the paramedian pons in 21 cases （70.0%）, and ventrolateral pons in nine cases （30.0%）. WD of the MCPs was detected 8-24 weeks after pons infarction using conventional magnetic resonance imaging （M RI）; all secondary WDs were asymptomatic and detected incidentally. All WD lesions exhibited bilateral, symmetrical, and boundary blurring on MRI. The signal features were hypointense on Tl-weighted imaging, hyperintense on T2-weighted imaging and fluid-attenuated inversion recovery, and slightly hyperintense or isointense on diffusion-weighted imaging and apparent diffusion coefficient maps. Secondary brainstem atrophy was found in six （20.0%） cases. A Modified Rankin Scale score 0-2 was found in 10 （33.3%） cases and score 〉2 in 20 （66.7%） cases at 90 days after discharge, and the short-term prognosis was worse than that in control group （χ2 =12.814, P - 0.001 ）. Conclusions： Despite the rarity of bilateral and symmetrical lesions of MCPs, secondary WD should be highly suspected if these lesions occur within 6 months after pontine infarction, particularly parainedian ports. Conventional MRI appears to be a relatively sensitive method for detecting WD of MCPs, which might affect the short-term prognosis.

Diffuse intrinsic pontine glioma:current insights and future directions

Diffuse intrinsic pontine glioma(DIPG)is a lethal pediatric brain tumor and the leading cause of brain tumor–related death in children.As several clinical trials over the past few decades have led to no significant improvements in outcome,the current standard of care remains fractionated focal radiation.Due to the recent increase in stereotactic biopsies,tumor tissue availabilities have enabled our advancement of the genomic and molecular characterization of this lethal cancer.Several groups have identified key histone gene mutations,genetic drivers,and methylation changes in DIPG,providing us with new insights into DIPG tumorigenesis.Subsequently,there has been increased development of in vitro and in vivo models of DIPG which have the capacity to unveil novel therapies and strategies for drug delivery.This review outlines the clinical characteristics,genetic landscape,models,and current treatments and hopes to shed light on novel therapeutic avenues and challenges that remain.

Diffuse Intrinsic Pontine Gliomas Exhibit Cell Biological and Molecular Signatures of Fetal Hindbrain-Derived Neural Progenitor Cells

Diffuse intrinsic pontine glioma(DIPG) is the main cause of brain tumor-related death among children.Until now, there is still a lack of effective therapy with prolonged overall survival for this disease. A typical strategy for preclinical cancer research is to find out the molecular differences between tumor tissue and para-tumor normal tissue, in order to identify potential therapeutic targets. Unfortunately, it is impossible to obtain normal tissue for DIPG because of the vital functions of the pons.Here we report the human fetal hindbrain-derived neural progenitor cells(pontine progenitor cells, PPCs) as normal control cells for DIPG. The PPCs not only harbored similar cell biological and molecular signatures as DIPG glioma stem cells, but also had the potential to be immortalized by the DIPG-specific mutation H3 K27 M in vitro. These findings provide researchers with a candidate normal control and a potential medicine carrier for preclinical research on DIPG.

Research progress in the efficacy of deep brain stimulation with different targets in Parkinson's disease

Parkinson's disease(PD)is a chronic progressive neurodegenerative disease.Deep brain stimulation(DBS)is an effective treatment for patients with advanced PD.There are many DBS targets for PD,including subthalamic nucleus(STN),globus pallidus(GPi),meso-ventral thalamic nucleus(VIM),pontine peduncle nucleus(PPN),posterior subthalamic region(PSA)and zonation of undetermined zone(ZI).This paper summarizes the efficacy of each target in the treatment of PD with DBS,not only makes a systematic analysis and comparison of motor symptoms,but also makes a detailed description of the efficacy of non-motor symptoms,so as to provide a personalized treatment basis for PD patients to select appropriate target targets in DBS.

Exploratory therapy for brainstem gliomas

Brainstem gliomas comprise both slow-growing and highly aggressive tumors,the latter carrying a dismal prognosis of approximately 10 months in children.Given their common locations along the brainstem,they are often not amenable to surgical resection.There are currently a host of exploratory therapies under investigation ranging from immunotherapy,small molecular inhibitors,epigenetic-modifying agents,and radiation protocols to combat these difficult-to-treat tumors.Recent discoveries highlighting the role of H3 histone mutations in diffuse midline glioma oncogenesis have yielded a variety of new targetable antigens and aberrant signaling pathways.Although many of these studies have shown promise in terms of inhibiting tumor growth and disease progression,results to date have been modest in their ability to translate into meaningful clinical benefit.This review will serve as an updated report on the current state of literature concerning pre-clinical and clinical therapies being investigated for brainstem glioma.In addition,this review will serve as a guide for clinicians as we review the evolving nomenclature of brainstem gliomas,commonly presenting symptoms,diagnostic tools,and standard therapies.

Pontin在结肠癌中的表达及其意义

目的通过检测Pontin在结肠癌组织、腺瘤组织和切缘黏膜组织中的表达,分析三者表达与结肠癌不同临床病理特征的关系,探讨其对预后的判断意义。方法收集86例结肠腺癌(腺癌组)、60例结肠腺瘤(腺瘤组)和60例结肠癌旁正常组织(切缘黏膜组),应用免疫组化SP法检测3组中Pontin蛋白的表达。结果 Pontin在腺癌组、腺瘤组、切缘黏膜组中阳性率分别为66.3%、31.7%和15%,Pontin表达的阳性率依次降低且差异极显著(P<0.01)。结肠腺癌组中Pontin的高表达与分化差、有淋巴结转移、Ⅲ+Ⅳ期、肿瘤直径>3 cm、浸润深度达浆膜及以外Ki-67高表达相关(P<0.01);与性别、年龄、炎细胞浸润、部位无关(P>0.05)。Pontin高表达患者的预后差(P<0.01)。结论 Pontin的高表达可能促进结肠癌的进展,检测Pontin蛋白的表达有助于判断结肠癌预后。