Isolated ipsilateral ptosis associated with ventral midbrain infarction: a case report and literature review.

Documented cases of ipsilateral ptosis caused by midbrain infarction remain rare. Herein, we present a patient with isolated ipsilateral ptosis that was initially considered to be a consequence of myasthenia gravis but was subsequently attributed to ventral midbrain infarction. We also discuss the possible underlying mechanisms; ipsilateral ptosis in our patient was attributed to selective damage of the levator palpebral muscle branch of the oculomotor nerve. The patient was started on aspirin (200 mg once daily) and atorvastatin (40 mg once daily). Improvement in ptosis occurred from day 5 of admission, and the patient was subsequently discharged. Ptosis disappeared 1 month after onset. This report describes an extremely rare case of ventral midbrain infarction presenting with isolated ipsilateral ptosis. Careful examination, including magnetic resonance imaging, is essential in such patients, especially in those with multiple cerebrovascular risk factors.

Assessing midbrain neuromelanin and its relationship to reward learning in anorexia nervosa: Stage 1 of a registered report.

INTRODUCTION: Anorexia nervosa (AN) is a debilitating and potentially chronic eating disorder, characterized by low hedonic drive toward food, which has been linked with perturbations in both reward processing and dopaminergic activity. Neuromelanin-sensitive magnetic resonance imaging (MRI) is an emerging method to index midbrain neuromelanin-a by-product of dopaminergic synthesis. The assessment of midbrain neuromelanin, and its association with AN psychopathology and reward-related processes, may provide critical insights into reward circuit function in AN. METHODS: This study will incorporate neuromelanin-sensitive MRI into an existing study of appetitive conditioning in those with AN. Specifically, those with acute and underweight AN (N = 30), those with weight-restored AN (N = 30), and age-matched healthy controls (N = 30) will undergo clinical assessment of current and previous psychopathology, in addition to structural neuromelanin-sensitive MRI, diffusion MRI, and functional MRI (fMRI) during appetitive conditioning. CONCLUSION: This study will be among the first to interrogate midbrain neuromelanin in AN-a disorder characterized by altered dopaminergic activity. Results will help establish whether abnormalities in the midbrain synthesis of dopamine are evident in those with AN and are associated with symptomatic behavior and reduced ability to experience pleasure and reward.

Pure downgaze palsy from isolated infarction of the left paramedian thalamic-mesencephalon junction.

A 65-years-old female was hospitalized 24 h after experiencing the sudden onset of subjective reduction in visual acuity and hypersomnia. On admission to the neurological ward, she presented isolated downgaze palsy. A Magnetic Resonance Imaging of the brain disclosed a discrete, ovalar hyperintensity involving the left paramedian thalamic-mesencephalon junction. The lesion was consistent with infarction. Isolated downgaze palsy has been described in thrombosis of Artery of Percheron leading to infarction of bilateral paramedian thalami along with structures from the mesencephalic-diencephalic junction such as the Medial Longitudinal Fasciculus (riMLF). While neurons from the riMLF controlling upward vertical saccades project to either ipsilateral and contralateral oculomotor nuclear complexes, those involved in regulating downgaze descend ipsilaterally in the brain stem. Isolated downgaze palsy has an extreme localizer value to the diencephalic-mesencephalon junction and can arise from a unilateral lesion.

Wasp sting-induced bilateral thalamic and midbrain infarction.

A male patient in his early 40s presented to the emergency department with an acute onset of respiratory distress and facial oedema, indicative of anaphylaxis. These symptoms emerged 2 hours subsequent to a wasp sting on the left side of his face. Despite initial stabilisation, the patient's state deteriorated into somnolence and disorientation. Notably, he denied any history of seizures, sensory or motor deficits, or bowel/bladder complications. Physical examination unveiled no focal neurological deficits. Routine laboratory tests and drug screening yielded no significant findings. Subsequent brain MRI with angiography exposed bilateral thalami diffusion restriction, strongly implying an acute infarction within the artery of Percheron territory, an atypical vascular variant. The sequence of events, alongside the absence of other conclusive aetiologies, indicated a wasp sting-induced thalamic infarction driven by vasogenic and thrombogenic effects of inflammatory substances.

Serum uric acid is associated with midbrain enlarged perivascular spaces: Results from Multi-modality Medical imaging sTudy bAsed on KaiLuan Study (META-KLS).

BACKGROUND: Serum uric acid (SUA) is a major cause of cardiovascular and cerebrovascular diseases. Whether and to what extent the excess risk of enlarged perivascular spaces (EPVS) conferred by SUA is unknown. The study was conducted to investigate the association between SUA and EPVS in different brain regions. METHODS: Data are from Multi-modality medical imaging study based on Kailuan study (META-KLS) in this cross-sectional study. Participants were divided into five groups based on SUA levels, and EPVS in basal ganglia (BG), centrum semiovale (CSO) and midbrain (MB) was systematically assessed and divided into Low and High group. Odds ratio (OR) and 95% confidence intervals (95% CIs) for high EPVS outcomes were estimated using multivariable logistic regression analysis. Restricted cubic spline (RCS) was used to further investigate dose-response relationship. RESULTS: A total of 1014 participants aged 25-83 years from 11 centers were enrolled in the study. In the multivariable-adjusted model, SUA, as an independent risk factor, correlated positively with high degree of MB-EPVS (OR, 1.002; 95% CI, 1.000 to 1.004; p = 0.023) in general population. In addition, RCS further demonstrated the linear association between SUA and MB-EPVS (p = 0.072). No association was found between SUA and BG-EPVS or CSO-EPVS. CONCLUSION: SUA was an independent risk factor of MB-EPVS. High SUA levels were more predictive of increased risk occurrence of high degree of MB-EPVS, supporting a linear association between SUA and MB-EPVS and further indicating that SUA may play an important role in cerebral small vessel disease. TRIAL REGISTRATION: The KaiLuan Study and META-KLS were registered online (ChiCTR2000029767 on chictr.org.cn and NCT05453877 on Clinicaltrials.gov, respectively).

Delayed levodopa-responsive parkinsonism following acute midbrain injury.

Acute midbrain injury may cause both hyperkinetic movement disorders and parkinsonism. The temporal interval between the insult and the emergence of hyperkinetic disorders can last years. A delayed appearance of parkinsonism, on the other hand, was rarely described. We present three cases of male patients (50-, 58- and 28-year-old) who developed levodopa-responsive parkinsonism 20, 8 and two years, respectively, after acute brain insult involving the midbrain. Insults included subcortical intracerebral hemorrhage dissecting into the midbrain, embolic basilar occlusion and trauma. A fluorodopa scan, performed in two cases, revealed reduced striatal uptake. All individuals improved on low doses of levodopa and developed motor fluctuations shortly after levodopa was introduced. We conclude that delayed, levodopa-responsive parkinsonism following midbrain injury should be recognized in the relevant clinical setup. Possible mechanisms include age-related loss of dopaminergic neurons superimposed on acute injury and secondary neurodegeneration.

Midbrain lesion-induced disconjugate gaze: a unifying circuit mechanism of ocular alignment?

BACKGROUND: Disconjugate eye movements are essential for depth perception in frontal-eyed species, but their underlying neural substrates are largely unknown. Lesions in the midbrain can cause disconjugate eye movements. While vertically disconjugate eye movements have been linked to defective visuo-vestibular integration, the pathophysiology and neuroanatomy of horizontally disconjugate eye movements remains elusive. METHODS: A patient with a solitary focal midbrain lesion was examined using detailed clinical ocular motor assessments, binocular videooculography and diffusion-weighted MRI, which was co-registered to a high-resolution cytoarchitectonic MR-atlas. RESULTS: The patient exhibited both vertically and horizontally disconjugate eye alignment and nystagmus. Binocular videooculography showed a strong correlation of vertical and horizontal oscillations during fixation but not in darkness. Oscillation intensities and waveforms were modulated by fixation, illumination, and gaze position, suggesting shared visual- and vestibular-related mechanisms. The lesion was mapped to a functionally ill-defined area of the dorsal midbrain, adjacent to the posterior commissure and sparing nuclei with known roles in vertical gaze control. CONCLUSION: A circumscribed region in the dorsal midbrain appears to be a key node for disconjugate eye movements in both vertical and horizontal planes. Lesioning this area produces a unique ocular motor syndrome mirroring hallmarks of developmental strabismus and nystagmus. Further circuit-level studies could offer pivotal insights into shared pathomechanisms of acquired and developmental disorders affecting eye alignment.

Effects of umbilical vein flow on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study.

OBJECTIVES: To investigate midbrain growth, including corpus callusum (CC) and cerebellar vermis (CV) and cortical development in late fetal growth restricted (FGR) subclassified according to the umbilical vein blood flow (UVBF) values. METHODS: This was a prospective study on singleton fetuses late FGR with abnormal placental cerebral ratio (PCR). FGR fetuses were further subdivided into normal (≥fifth centile) and abnormal (

Colocalization of Increased Midbrain Signals in Neuroinflammation and Tau PET Imaging Suggests the Diagnosis of Progressive Supranuclear Palsy.

ABSTRACT: Clinical overlap with multiple other neurological diseases makes the diagnosis of autoimmune encephalitis challenging; consequently, a broad range of neurological diseases are misdiagnosed as autoimmune encephalitis. A 58-year-old man presented with abnormal behavior, irritability for 3 years, oculomotor disturbance, unsteady walking, and dysphagia and was suspected as having anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis as the anti-DPPX antibody was positive in the serum. However, the therapeutic effect of immunotherapy was unsatisfactory. Subsequently, colocalization of increased midbrain signals was observed in neuroinflammation PET using [ 18 F]DPA-714 and in tau PET using [ 18 F]florzolotau, suggesting the diagnosis of progressive supranuclear palsy.

Transcallosal-Transchoroidal Fissure Approach for Midbrain and Thalamic Cavernous Malformations: 2-Dimensional Operative Video.

INDICATIONS CORRIDOR AND LIMITS OF EXPOSURE: Cavernous malformations of the third ventricle arise from the medial thalamus and/or periaqueductal midbrain. Microsurgical resection is indicated when the lifetime risk of hemorrhage outweighs the surgical risks. ANATOMIC ESSENTIALS NEED FOR PREOPERATIVE PLANNING AND ASSESSMENT: superior sagittal sinus, callosomarginal and pericallosal arteries, corpus callosum, foramen of Monro, choroidal fissure, fornix, thalamostriate veins, internal cerebral veins (ICVs), velum interpositum, and thalamus. ESSENTIAL STEPS OF THE PROCEDURE: The patient consents to the procedure. With the patient supine, the head is turned 90° and laterally flexed 45°. A bifrontal craniotomy positioned two-thirds anterior and one-third posterior to the coronal suture is performed. The interhemispheric fissure is opened, and a 2-cm corpus callosotomy is performed. Choroid plexus cauterization exposes the choroidal fissure. Sharp division of the taenia fornicea opens the velum interpositum, where the thalamostriate vein can be followed around the venous angle to the ICV. The anterior septal vein may be divided to communicate between the foramen of Monro and choroidal fissure. Dissection between the ICVs opens the velum interpositum into the third ventricle. PITFALLS/AVOIDANCE OF COMPLICATIONS: Frontal or deep vein occlusion causes venous infarction, and dissection on the nondominant hemisphere is preferred. Other complications include arterial infarction, fornix injury from choroidal fissure dissection or forniceal retraction, and thalamic or midbrain injury during lesion resection. VARIANTS AND INDICATIONS FOR THEIR USE: The contralateral choroidal fissure is used for low-lying medial thalamic and midbrain lesions. The ipsilateral choroidal fissure is used for high-lying or large lesions extending laterally. Transchoroidal approaches are not needed for superior (transcallosal only) or anterior (contralateral transcallosal-contralateral transforaminal) thalamic lesions. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.

A novel radiological classification of midbrain pilocytic astrocytomas and its implication for surgical management: a single-institution experience of 57 cases.

OBJECTIVE: Surgery for midbrain pilocytic astrocytoma (PA) remains a formidable challenge. To facilitate decision-making and achieve a better outcome in the management of patients with midbrain PA, the authors have proposed a novel radiological classification of midbrain PAs with long-term follow-up. METHODS: Fifty-seven midbrain PA patients who underwent surgery at Beijing Tiantan Hospital, Capital Medical University, from January 2008 to June 2021, were reviewed. Based on tumor location and the topological anatomical change identified on MRI, midbrain PAs were categorized into four types: crural (12/57, 21.1%), tegmental (25/57, 43.9%), aqueductal (5/57, 8.8%), and tectal (15/57, 26.3%) PAs. The relevant clinical, radiological, and pathological data; surgical procedures and results; and long-term outcomes were collected and analyzed. RESULTS: The 1-, 3-, and 5-year survival rates reached 98%, 96%, and 96%, respectively, with gross-total resection achieved in 66.7% of cases, followed by near-total resection in 17.5% cases. The clinical and radiological features, selection of surgical approaches, and long-term postoperative deficits were distinct among each type. Crural PAs were associated with younger age (median 9 years, IQR 5.0-12.8 years); the largest tumor volume (median 31.9 cm3, IQR 17.2-42.6 cm3); the lowest preoperative Karnofsky Performance Scale (KPS) score (median 65, IQR 50-70); the most frequent preoperative motor deficit (91.7%); a mixed solid-cystic component (75%); occupation of the crural cistern; elevation and rotation of the thalamus (medial and/or lateral); displacement of the anterior third ventricle, uncus, and anterior commissure; the most diverse surgical approaches; more frequent use of multimodality image-guided surgery (58.3%); and the most remarkable improvement in KPS score at long-term follow-up. Tegmental PAs were associated with adolescents and young adults (median age 21 years, IQR 8-33 years); tumor volume (median 13.9 cm3, IQR 9.5-20.5 cm3); a good preoperative KPS score (median 80, IQR 70-80); a mixed solid-cystic component (72%); occupation of the ambient cistern and cerebellomesencephalic fissure; a close relationship with the dorsal pons, superior cerebellar peduncle, and posterior inferior third ventricle; and a higher probability of permanent postoperative sensory deficits (40%). Aqueductal and tectal PAs were associated with small tumor volume (median 9.14 cm3, IQR 5.1-17.4 cm3 and median 11.84 cm3, IQR 5.7-18.3 cm3, respectively), a higher percentage of hydrocephalus (80% and 86.7%, respectively), and a straightforward selection of limited surgical approaches. CONCLUSIONS: A novel and comprehensive radiological classification of midbrain PAs was established, which will serve as a valuable tool in patient management and promote uniform communication and comparison across different studies and publications.

Sub-Chronic Ketamine Administration Increases Dopamine Synthesis Capacity in the Mouse Midbrain: a Preclinical In Vivo PET Study.

PURPOSE: There is robust evidence that people with schizophrenia show elevated dopamine (DA) synthesis capacity in the striatum. This finding comes from positron emission tomography (PET) studies using radiolabelled l-3,4-dihydroxyphenylalanine (18F-DOPA). DA synthesis capacity also appears to be elevated in the midbrain of people with schizophrenia compared to healthy controls. We therefore aimed to optimise a method to quantify 18F-DOPA uptake in the midbrain of mice, and to utilise this method to quantify DA synthesis capacity in the midbrain of the sub-chronic ketamine model of schizophrenia-relevant hyperdopaminergia. PROCEDURES: Adult male C57Bl6 mice were treated daily with either ketamine (30 mg/kg, i.p.) or vehicle (saline) for 5 days. On day 7, animals were administered 18F-DOPA (i.p.) and scanned in an Inveon PET/CT scanner. Data from the saline-treated group were used to optimise an atlas-based template to position the midbrain region of interest and to determine the analysis parameters which resulted in the greatest intra-group consistency. These parameters were then used to compare midbrain DA synthesis capacity (KiMod) between ketamine- and saline-treated animals. RESULTS: Using an atlas-based template to position the 3.7 mm3 midbrain ROI with a T*-Tend window of 15-140 min to estimate KiMod resulted in the lowest intra-group variability and moderate test-retest agreement. Using these parameters, we found that KiMod was elevated in the midbrain of ketamine-treated animals in comparison to saline-treated animals (t(22) = 2.19, p = 0.048). A positive correlation between DA synthesis capacity in the striatum and the midbrain was also evident in the saline-treated animals (r2 = 0.59, p = 0.005) but was absent in ketamine-treated animals (r2 = 0.004, p = 0.83). CONCLUSIONS: Using this optimised method for quantifying 18F-DOPA uptake in the midbrain, we found that elevated striatal DA synthesis capacity in the sub-chronic ketamine model extends to the midbrain. Interestingly, the dysconnectivity between the midbrain and striatum seen in this model is also evident in the clinical population. This model may therefore be ideal for assessing novel compounds which are designed to modulate pre-synaptic DA synthesis capacity.

Midbrain atrophy in pathologically diagnosed Lewy body disease and clinically diagnosed Parkinson's disease.

OBJECTIVE: Midbrain atrophy is considered specific to progressive supranuclear palsy (PSP) compared with Parkinson's disease (PD). We aimed to determine how often midbrain atrophy is observed in pathologically diagnosed Lewy body disease (LBD) and clinically diagnosed PD and the robustness of midbrain atrophy assessed by the One-Line Method previously developed for the diagnosis of PSP. METHODS: We studied two separate cohorts with MRI: the first pathologically diagnosed cohort consisted of patients with LBD (n = 13), PSP (n = 6), multiple system atrophy (MSA, n = 7), and corticobasal degeneration (CBD, n = 2); the second cohort consisted of patients with PD (n = 122). Midbrain length was measured using the One-Line Method and FreeSurfer estimated volumes of the subcortical nuclei. RESULTS: The area under the curve of midbrain length differentiating PSP from LBD, MSA, and CBD in a pathologically diagnosed cohort was 0.91. Midbrain length with cut-off values of 10.5 mm and 9.5 mm had a sensitivity of 100% and 67% and a specificity of 68% and 96%, respectively. In the first cohort, 7.7% and 23.0% of patients with LBD showed midbrain lengths <9.5 mm and 10.5 mm, respectively, and in the second cohort, 4.9% and 19.7% showed midbrain lengths <9.5 mm and 10.5 mm, respectively. INTERPRETATION: Midbrain length measured using the One-Line Method is helpful in the diagnosis of PSP. Some cases of pathologically diagnosed LBD and clinically diagnosed PD present with midbrain atrophy.

Detailed Assessment of 18F-THK5351 Distribution Pattern in the Midbrain: Comparison With Progressive Supranuclear Palsy and Corticobasal Syndrome.

BACKGROUND: 18F-THK5351 PET is used to image ongoing astrogliosis by estimating monoamine oxidase B levels. 18F-THK5351 preferentially accumulates around the substantia nigra (SN) and periaqueductal gray (PG) in the midbrain under healthy conditions and exhibits a "trimodal pattern." In progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), the midbrain 18F-THK5351 uptake can be increased by astrogliosis, collapsing the "trimodal pattern." We aimed to elucidate cases in which the "trimodal pattern" collapses in PSP and CBS. PATIENTS AND METHODS: Participants in the PSP (n = 11), CBS (n = 17), Alzheimer disease (n = 11), and healthy control (n = 8) groups underwent 18F-THK5351 PET. Volumes of interest (VOIs) were placed on the SN, PG, and their midpoints. The midbrain uptake ratio (MUR) was calculated to assess the trimodal pattern as follows: MUR = (VOI value on the midpoint)/(VOI value on the SN and PG). Approximately, the trimodal pattern can be identified at MUR <1 but not at MUR >1. RESULTS: Compared with the healthy control group, MUR significantly increased in the PSP (P < 0.01) and CBS (P < 0.01) groups, but was unchanged in the Alzheimer disease group (P = 0.10). In the PSP group, all patients, including 2 with mild symptoms and a short disease duration, showed MUR >1. In the CBS group, MUR varied widely. CONCLUSIONS: In PSP, the trimodal pattern can collapse even in the early phase when symptoms are mild. In CBS, the trimodal pattern may or may not collapse depending on the underlying pathology.

Anisocoria without extraocular muscle impairment due to moderate traumatic brain injury with midbrain contusion: a case report.

BACKGROUND: New-onset anisocoria is an important clinical clue to life-threatening intracranial injury. Anisocoria alone without impairment of extraocular muscles is a rare presentation of moderate traumatic brain injury (TBI). CASE PRESENTATION: A 79-year-old woman was transported to hospital soon after falling off a bicycle. Glasgow Coma Scale score on arrival was 11 (E3V3M5). On examination at admission, she was found to be drowsy. Bruising was seen around the right eye and pupil diameters differed (right, 4.5 mm; left, 3.0 mm; both reactive to light). Computed tomography of the head revealed hemorrhagic contusion in the left temporal lobe and left pretectal area of the midbrain, right clavicular fracture, and pulmonary contusion with fractures of the 3rd and 4th ribs. Magnetic resonance imaging confirmed hemorrhagic contusion of the midbrain. The patient achieved full recovery of motor and mental functions with conservative treatment and was discharged on hospital day 17. CONCLUSION: We encountered a case of anisocoria without major extraocular muscle impairment due to moderate TBI with midbrain contusion.