Insufficiency of plasmatic arginine/homoarginine during the initial postoperative phase among patients with tumors affecting the medulla oblongata heightens the likelihood of neurogenic pulmonary oedema following surgery.

BACKGROUND: This prospective clinical study aims to investigate the fluctuations of neurotransmitters in peripheral venous blood during the perioperative period and to identify independent predictors for postoperative neurogenic pulmonary oedema (NPE) in patients with medulla oblongata-involved tumours. MATERIALS AND METHODS: Peripheral venous blood samples of the enroled patients at seven perioperative time points, as well as their medical records and radiologic data were collected. High-performance liquid chromatography-tandem mass spectrometry was utilized to detect the concentrations of 39 neurotransmitters in these samples. The study applied univariate and multivariate generalized estimating equation (GEE) logistic regression analyses to explore independent predictors of postoperative NPE, and one-way repeated-measures ANOVA to compare the concentrations of the same neurotransmitter at different perioperative time points. RESULTS: The study included 36 patients with medulla oblongata-involved tumours from January to December 2019, and found that 13.9% of them experienced postoperative NPE. The absence of intraoperative use of sevoflurane ( P =0.008), decreased concentrations of arginine ( P =0.026) and homoarginine ( P =0.030), and prolonged postoperative tracheal extubation ( P <0.001) were identified as independent risk factors for postoperative NPE in medulla oblongata-involved tumour patients. Pairwise comparison analysis revealed that the perioperative decreases in arginine and homoarginine concentrations mainly occurred within the postoperative 8 h. CONCLUSION: This study demonstrates that NPE is not uncommon in patients with medulla oblongata-involved tumours. The absence of intraoperative use of sevoflurane, decreased concentrations of plasmatic arginine and homoarginine, and prolonged postoperative tracheal extubation are independent predictors of postoperative NPE. These two neurotransmitters' concentrations dropped mainly within the early postoperative hours and could serve as potential early warning indicators of postoperative NPE in clinical practice.

Substitution of Glu to Lys at Codon 332 on the GFAP Gene Alone Is Causative for Adult-onset Alexander Disease.

A 57-year-old man whose mother had been pathologically diagnosed with Alexander disease (ALXDRD), presented with cerebellar ataxia, pyramidal signs, and mild dysarthria. Brain magnetic resonance imaging revealed typical ALXDRD alterations, such as atrophy of the medulla oblongata (MO) and cervical spinal cord, a reduced sagittal diameter of the MO, and garland-like hyperintensity signals along the lateral ventricular walls. A genetic analysis of GFAP by Sanger sequencing revealed a single heterozygous mutation of Glu to Lys at codon 332 (c.994G>A) in the GFAP gene. Our results newly confirmed that p.E332K alone is the pathogenic causative mutation for adult-onset ALXDRD.

Formation of a Large Fusiform Aneurysm near a Medullary Infarction Caused by Dissection of the Posterior Inferior Cerebellar Artery.

Infarction of the posterior inferior cerebellar artery (PICA) can lead to ischemic stroke in the lateral medullary oblongata. PICA dissection can also elicit an ischemic event in this region, but its detection on radiological images is difficult because of the small diameter of the vessel. We report a case of Wallenberg syndrome due to PICA dissection in a 48-year-old man, which was difficult to diagnose on first admission. He reported sudden onset of sensory disturbance on the right side of his face, ataxic gait, and headache. Brain magnetic resonance imaging (MRI) revealed a fresh cerebral infarct in the right lateral medulla oblongata. Magnetic resonance angiography (MRA) performed at the time of his admission showed no cerebral vessel abnormalities. An MRI study 18 months after the event revealed a fusiform aneurysm on the lateral medullary segment of the PICA, which was extremely close to the cerebral infarct. We concluded that the infarct was due to PICA dissection because of the sudden onset of symptoms and because the infarcted territory of the occluded penetrating branch of the dissecting aneurysm was consistent with Wallenberg syndrome. The aneurysm was trapped and an occipital artery-PICA bypass was placed. At the latest follow-up, 1 year after the procedure, he had no neurological symptoms. Imaging findings at the time of his first admission indicated that the PICA was intact. However, 18 months later, MRI revealed enlargement of an aneurysm at the site of the dissection. A cerebral infarct with headache may indicate PICA dissection.

Radiological correlates of pseudobulbar affect: Corticobulbar and cerebellar components in primary lateral sclerosis.

INTRODUCTION: Pseudobulbar affect (PBA) is a distressing symptom of a multitude of neurological conditions affecting patients with a rage of neuroinflammatory, neurovascular and neurodegenerative conditions. It manifests in disproportionate emotional responses to minimal or no contextual stimulus. It has considerable quality of life implications and treatment can be challenging. METHODS: A prospective multimodal neuroimaging study was conducted to explore the neuroanatomical underpinnings of PBA in patients with primary lateral sclerosis (PLS). All participants underwent whole genome sequencing and screening for C9orf72 hexanucleotide repeat expansions, a comprehensive neurological assessment, neuropsychological screening (ECAS, HADS, FrSBe) and PBA was evaluated by the emotional lability questionnaire. Structural, diffusivity and functional MRI data were systematically evaluated in whole-brain (WB) data-driven and region of interest (ROI) hypothesis-driven analyses. In ROI analyses, functional and structural corticobulbar connectivity and cerebello-medullary connectivity alterations were evaluated separately. RESULTS: Our data-driven whole-brain analyses revealed associations between PBA and white matter degeneration in descending corticobulbar as well as in commissural tracts. In our hypothesis-driven analyses, PBA was associated with increased right corticobulbar tract RD (p = 0.006) and decreased FA (p = 0.026). The left-hemispheric corticobulbar tract, as well as functional connectivity, showed similar tendencies. While uncorrected p-maps revealed both voxelwise and ROI trends for associations between PBA and cerebellar measures, these did not reach significance to unequivocally support the "cerebellar hypothesis". CONCLUSIONS: Our data confirm associations between cortex-brainstem disconnection and the clinical severity of PBA. While our findings may be disease-specific, they are consistent with the classical cortico-medullary model of pseudobulbar affect.

Dynamic changes of the direction and angle of radiographic ocular lateral deviation in patients with lateropulsion after stroke onset.

OBJECTIVE: To examine if radiographic ocular lateral deviation (rOLD) could be provoked in stroke patients with mild-to-moderate lateropulsion according to vertical perception. METHODS: In this single-center, retrospective study, acute stroke patients with mild-to-moderate lateropulsion assessed by the Scale for Contraversive Pushing were enrolled. Computed tomography or magnetic resonance imaging was performed on all patients on admission and then according to their conditions. The direction and angle of rOLD were compared among three groups according to the responsible lesion: lateral medullary (LM), pontine (P), and hemispheric (H). RESULTS: Sixty-six patients (male, 47; average age, 67 years) were enrolled and divided into the LM (n = 37), P (n = 8), and H (n = 21) groups. All patients had body tilt. Patients in the LM group showed body tilt to the ipsilesional side during hospitalization, while those in the P and H groups tilted to the contralesional side. All patients had rOLD at the final assessment at an average of 13 days after onset; patients in the P and H groups showed contralateral rOLD, while those in the LM group showed ipsilateral rOLD if they did not have cerebellar or pontine lesions. Significant decreases in the angle and changes in direction of rOLD according to lesion site were observed during hospitalization. CONCLUSION: Serial changes in rOLD findings after stroke onset are different according to the responsible lesion. The direction of rOLD in most patients is in accordance with vertical perception after the acute stage of stroke.

The locus coeruleus input to the rostral ventromedial medulla mediates stress-induced colorectal visceral pain.

Unlike physiological stress, which carries survival value, pathological stress is widespread in modern society and acts as a main risk factor for visceral pain. As the main stress-responsive nucleus in the brain, the locus coeruleus (LC) has been previously shown to drive pain alleviation through direct descending projections to the spinal cord, but whether and how the LC mediates pathological stress-induced visceral pain remains unclear. Here, we identified a direct circuit projection from LC noradrenergic neurons to the rostral ventromedial medulla (RVM), an integral relay of the central descending pain modulation system. Furthermore, the chemogenetic activation of the LC-RVM circuit was found to significantly induce colorectal visceral hyperalgesia and anxiety-related psychiatric disorders in naïve mice. In a dextran sulfate sodium (DSS)-induced visceral pain model, the mice also presented colorectal visceral hypersensitivity and anxiety-related psychiatric disorders, which were associated with increased activity of the LC-RVM circuit; LC-RVM circuit inhibition markedly alleviated these symptoms. Furthermore, the chronic restraint stress (CRS) model precipitates anxiety-related psychiatric disorders and induces colorectal visceral hyperalgesia, which is referred to as pathological stress-induced hyperalgesia, and inhibiting the LC-RVM circuit attenuates the severity of colorectal visceral pain. Overall, the present study clearly demonstrated that the LC-RVM circuit could be critical for the comorbidity of colorectal visceral pain and stress-related psychiatric disorders. Both visceral inflammation and psychological stress can activate LC noradrenergic neurons, which promote the severity of colorectal visceral hyperalgesia through this LC-RVM circuit.

Bilateral medial medullary infarction with intravenous thrombolytic therapy: A case report.

RATIONALE: Bilateral medial medullary infarction is a rare stroke subtype. To investigate its clinical manifestations, etiology, imaging features and thrombolytic effect, We here in reported a patient with acute ischemic stroke in the bilateral medial medullary and reviewed the related literatures. PATIENTS CONCERN: A 64-year-old female was taken to our hospital after 4.5 hours of dizziness in the morning, followed by somnolence and limb weakness. She gradually worsened into a rapidly progressive tetraparesis and slurred speech. DIAGNOSES: Diffusion weighted imaging exhibited a "heart appearance" sign in bilateral medial medulla oblongata, and high-resolution magnetic resonance imaging suggested the left vertebral artery-4 thromboembolism. INTERVENTIONS: Timely intravenous thrombolysis was performed. OUTCOME: After intravenous thrombolysis, the patient's symptoms did not worsen in a short time. Although the symptoms were aggravated in the later stage, they were alleviated after active treatment. LESSONS: Diffusion weighted imaging can assist in the early diagnosis of bilateral medial medullary infarction, which will help in the decision to proceed with intravenous thrombolysis therapy. High-resolution magnetic resonance imaging should be improved as soon as possible, which can provide basis for the next intravascular interventional therapy.

Motor and somatosensory degenerative myelopathy responsive to pantothenic acid in piglets.

This report describes 2 events of degenerative myelopathy in 4- to 27-day-old piglets, with mortality rates reaching 40%. Sows were fed rations containing low levels of pantothenic acid. Piglets presented with severe depression, weakness, ataxia, and paresis, which were more pronounced in the pelvic limbs. No significant gross lesions were observed. Histologically, there were degeneration and necrosis of neurons in the spinal cord, primarily in the thoracic nucleus in the thoracic and lumbar segments, and motor neurons in nucleus IX of the ventral horn in the cervical and lumbar intumescence. Minimal-to-moderate axonal and myelin degeneration was observed in the dorsal funiculus of the spinal cord and in the dorsal and ventral nerve roots. Immunohistochemistry demonstrated depletion of acetylcholine neurotransmitters in motor neurons and accumulation of neurofilaments in the perikaryon of neurons in the thoracic nucleus and motor neurons. Ultrastructurally, the thoracic nucleus neurons and motor neurons showed dissolution of Nissl granulation. The topographical distribution of the lesions indicates damage to the second-order neurons of the spinocerebellar tract, first-order axon cuneocerebellar tract, and dorsal column-medial lemniscus pathway as the cause of the conscious and unconscious proprioceptive deficit, and damage to the alpha motor neuron as the cause of the motor deficit. Clinical signs reversed and no new cases occurred after pantothenic acid levels were corrected in the ration, and piglets received parenteral administration of pantothenic acid. This study highlights the important and practical use of detailed neuropathological analysis to refine differential diagnosis.

Mixed Germ Cell Tumor with a Yolk Sac Tumor Component in the Medulla Oblongata of a 50-year-old Patient: A Case Report and Literature Review.

Yolk sac tumor (YST) is a rare primary brain tumor that occurs almost exclusively in patients under 30 years old. Intracranial germ cell tumors are most frequently located in the pineal and suprasellar region. Medulla oblongata YSTs are particularly rare. Extragonadal YSTs may be difficult to diagnose because of their characteristics, such as the rarity and variety of growth patterns. Furthermore, they are known to have a very poor prognosis. We herein report a case of YST of the medulla oblongata in a 50-year-old woman. She was followed up for 18 months without any tumor recurrence.

Vertebral artery dissection induced lateral medullary syndrome characterized with severe bradycardia: a case report and review of the literature.

BACKGROUND: Lateral medullary syndrome is the most common type of brainstem infarction. Lateral medullary syndrome results in damage to the corresponding cranial nerve nuclei and the nucleus tractus solitarius, with vertigo, ipsilateral ataxia, crossed sensory disturbances, Horner's sign, bulbar palsy, and other underlying symptoms or signs. However, cases with cardiac arrhythmia and other autonomic dysfunctions as the primary manifestations are less common. Clinically, sudden death occasionally occurs in patients with lateral medullary syndrome, which may be associated with severe cardiac arrhythmia. These patients may suffer in life-threatening arrhythmia and even cardiac arrest, and vital signs should be closely monitored to prevent sudden death. In younger patients, vertebral artery dissection is the most common cause. CASE DESCRIPTION: Here, we present a case of lateral medullary syndrome caused by vertebral artery dissection with severe bradycardia. The patient was a 49-year-old man who was admitted with "sudden onset of numbness in the left limbs and right side of the face for 1 hour". Electrocardiogram (ECG) monitoring showed a repeated heart rate decrease to as low as 23 beats/min, followed by a gradual increase in heart rate to 35-55 beats/min after 2-3 seconds. Head magnetic resonance imaging (MRI) examination revealed right dorsolateral cerebral infarction of the medulla oblongata. Digital subtraction angiography (DSA) revealed a right vertebral artery dissecting aneurysm. We performed an emergency placement of a temporary pacemaker, followed by conservative treatment with platelet aggregation inhibitors, vascular softening agents and improved collateral circulation. Elective spring coil embolization of the vertebral artery dissecting aneurysm and stent implantation were performed. At outpatient follow-up, the patient had a good prognosis. CONCLUSIONS: Clinical management of patients with lateral medullary syndrome should be prioritized, with close cardiac monitoring at the early stages of observation and pacemaker placement and tracheal intubation as required to prevent adverse events.

Pathological Appearance of a Case of Preclinical Multiple System Atrophy: A Comparison With Advanced Cases.

We aimed to investigate the frequency of multiple system atrophy (MSA) in a large number of forensic autopsies and characterize the pathological appearance of preclinical MSA. We investigated a series of 1930 brains from forensic autopsies. In addition to performing immunohistochemistry for phosphorylated α-synuclein, the levels of 3 autonomic nervous system markers (catecholaminergic, serotonergic, and cholinergic) were used to assess the peripheral nerve (heart and superior cervical ganglion) and medulla oblongata. The results were compared to those of healthy control and Parkinson disease (PD) cases. Four cases (0.21%) were identified as having MSA. Cases 1-3 were symptomatic, and Case 4 was incipient; that is, although no neuronal loss was evident, the cerebellar dentate nucleus exhibited marked grumose degeneration. Immunohistochemistry revealed a marked reduction in autonomic nervous system marker levels expressed in the medulla; this reduction was more prominent in the 3 symptomatic MSA cases than in the PD case. The opposite occurred for the peripheral nerve. Case 4 exhibited mild cholinergic nerve reduction. Two cases showed possible significant pathological changes in the heart. Grumose degeneration, few oligodendroglial cytoplasmic inclusions without neuronal loss, and less reduction of autonomic nervous tissue were more prominent in the preclinical case than in symptomatic cases.

Brain and spinal cord lesions in 28 inbred strains of aging mice.

Brain and spinal cord histopathology findings in male and female 20-month-old mice in a large-scale aging study of 28 inbred Jackson Laboratory mouse strains from 7 genetic families are described. Brain sections from selected strains at 12 and 24 months of age or older were also reviewed. Common lesions include axonal dystrophy in the gracile and/or cuneate nucleus in the sensory tract of the dorsal medulla and in the spinal cord in all strains. Hirano-like bodies were seen in 24/28 strains, and mineralization was observed in the thalamus of 9/28 strains. Less common lesions were also seen in the cerebellum, cerebral cortex, and other brain areas. No brain or spinal cord tumors were found. Evidence of an impairment of the ubiquitin-proteasome system (UPS) and/or suspected autophagy was manifested as medullary axonal dystrophy with intra-axonal granular eosinophilic bodies and LC3B immunohistochemistry in most strains. RIIIS/J, the most severely affected strain, showed moderate axonal dystrophy at 12 months, which progressed to severe lesions at 20 months. Comparative pathology in various species is discussed.

The stroke mechanism, clinical presentation, and radiological feature of bilateral medial medullary infarction.

BACKGROUND: Bilateral medial medullary infarction (BMMI) is a rare type of posterior circulation stroke. The aim of this study is to characterize its stroke mechanisms, clinical manifestations, neuroradiological features, and prognosis. METHODS: From January 2015 to June 2021, a retrospective review of 15 patients diagnosed with BMMI was conducted. The clinical and neuroradiological features were summarized by our experienced neurologists. RESULTS: Fifteen patients (12 male, 3 female), ranging in age from 48 to 72 years, satisfied the inclusion criteria. The common clinical presentations included motor weakness (100%), deep sensory disturbance (93.3%), vertigo/dizziness (80%), dysarthria (93.3%), and dysphagia (66.7%). Vertically, infarct lesions in the rostral medulla were observed in all included patients. Horizontally, "heart appearance," "Y appearance," and "fan appearance" infarcts occurred in 9 cases (60%), 5 cases (33.3%), and 1 (6.7%) case, respectively. Patients (53.3%) had severe stenosis or occlusion in unilateral vertebral artery (VA), and 33.3% had normal findings in the vertebrobasilar artery. Patients (93.3%) achieved poor prognosis. CONCLUSION: BMMI is more frequently located in the rostral medulla and comprises three forms of infarction. The two main stroke etiologies of BMMI are large-artery atherosclerosis (LAA) and small vessel disease (SVD). BMMI is always associated with bad clinical outcome.

Bilateral medial medullary stroke: A rare stroke syndrome masquerading as myasthenia crisis in a young diabetic lady.

Bilateral medial medullary stroke is a rare stroke syndrome. The clinical presentation of bilateral medial medullary stroke is heterogenous and often overlaps with other non-stroke neurology emergencies such as Guillain-Barrésyndrome, myasthenic crisis and acute vestibular syndrome, leading to misdiagnosis. We wish to present a case of a young lady with type 1 diabetes mellitus, who had presented with subacute neuromuscular weakness which was erroneously treated as myasthenic crisis. Her case was subsequently diagnosed as bilateral medial medullary stroke, following evolving clinical signs and magnetic resonance imaging (MRI) findings of a heart-shaped abnormality at the rostral medulla. This rare stroke syndrome represented a diagnostic challenge which necessitated a strong clinical suspicion and an urgent MRI scan of the brain for prompt diagnosis to enable appropriate treatment initiation.

Chronological Progression and Management of Syringobulbia Caused by Spinal Hemangioblastoma: A Case Series and Review of the Literature.

BACKGROUND: Syringomyelia often accompanies spinal hemangioblastoma (SHB). It often shows progression to the medulla oblongata, dubbed as "syringobulbia", which presents critical symptoms such as dysphagia and respiratory compromise. Appropriate management of chronological syringomyelia progression toward syringobulbia is not set in stone. This study aims to unravel the clinical and chronological behavior of syringobulbia and its management. METHODS: A single-institution case series study of 5 patients operated for SHB with syringobulbia was conducted. Serial preoperative magnetic resonance imaging scans were analyzed in further details, especially focusing on the chronological progression of syringomyelia. A literature review was performed to describe clinical/imaging characteristics. RESULTS: Chronological imaging analyses revealed that despite the relatively steady progression of syringomyelia over years, it accelerated when developing syringobulbia. Intramedullary signal change ("presyringomyelia") was observed in the area where syringomyelia subsequently occurred. Literature review yielded another 15 cases of SHB with syringobulbia, totaling 20 cases. Bulbar dysfunction was seen in 4 cases (20%). Gross total resection was performed in all cases except 1, which underwent just syringotomy. Rapid postoperative symptom improvement was observed in all cases, as well as immediate imaging resolution of syringomyelia. CONCLUSIONS: The symptoms associated with syringobulbia often become life-threatening. Notably, its resolution may be near-synchronous to surgical resection of the spinal lesion. The speed of progression of syringomyelia is usually steady, but it may accelerate when extending to syringobulbia. Regular imaging follow-up is thus highly recommended to determine the best timing of intervention when presyringomyelia and syringomyelia are ascending toward the medulla oblongata.

Midlateral medullary infarction presenting with isolated thermoanaesthesia: a case report.

BACKGROUND: A small lateral medullary lesion could produce isolated impairment of temperature sensation without concomitant impaired pain sensation. However, only one such case has ever been reported, and there are no reports on subjective symptoms and detailed somatosensory testing. CASE PRESENTATION: Herein, we report the case of a 53-year-old female patient presenting with impaired temperature sensation on the left half of her body, from the neck down, following a small infarction of the right midlateral medulla. The chronological changes in the patient's introspection regarding impairment of thermoception and the results of detailed somatosensory tests, including thermal sense, are shown in this report. CONCLUSIONS: Thorough somatosensory tests, personal descriptions of symptoms, and electrophysiological quantification of similar cases are needed to improve our understanding of the neurological separation of the sensations of pain and temperature at the medullary level.

Clinical characteristics of patients with lateral medullary infarction who had fatal respiratory failure.

INTRODUCTION: Respiratory failure is a fatal complication of lateral medullary infarction (LMI). However, the clinical characteristics associated with respiratory failure in patients with LMI have not been fully elucidated. We aimed to evaluate the clinical characteristics associated with respiratory failure in patients with LMI. METHODS: Among the 6365 consecutive patients who were admitted to our institute within 7 days of onset of acute ischemic stroke between January 2007 and December 2019, we identified those with acute LMI as verified by magnetic resonance imaging. We evaluated the associations between clinical characteristics and fatal respiratory failure that occurred within 10 days of stroke onset. RESULTS: Of 102 patients with acute LMI, eight had fatal respiratory failure within 10 days of stroke onset. Patients with fatal respiratory failure had a higher premorbid modified Rankin Scale score than did those without (3 vs. 0, p < 0.001), as well as a higher frequency of pulmonary disease (37.5% vs. 2.1%, p = 0.003). Severe dysphagia (100% vs. 30.9%, p < 0.001), dysarthria (100% vs. 56.4%, p = 0.020), ipsilateral hemiparesis (50.0% vs. 5.3%, p = 0.002), and urinary retention (50.0% vs. 2.1%, p < 0.001) were also significantly more common in patients with fatal respiratory failure than in those without. There were no significant differences in infarct locations between patients with fatal respiratory failure and those without. CONCLUSIONS: Assessment of pre-stroke history and monitoring of neurological symptoms that occur during the first 10 days post-stroke onset would be useful for predicting the risk of respiratory failure in patients with acute LMI.