Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan’s unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p < 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p < 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = −0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = −0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = −0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate (z = −0.02, p < 0.001) and frontal white matter Glx (z = −0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies

Look in the Back (Video)

A 59-year old man with Graves disease developed increasing proptosis and diplopia. Attributing these abnormalities to worsening of the Graves disease, an ophthalmologist treated him with high-dose oral and intravenous corticosteroids. When improvement did not occur, he underwent orbital x-irradiation (unknown dose). He developed new bilateral hearing loss, bilateral lower extremity weakness, and urinary retention eliciting catheter placement. Visual acuity declined, so he was referred to our institution for urgent orbital decompression. When we first encountered him, he was confused and drowsy. Best-corrected visual acuity was 20/80 in the right eye and 20/200 in the left eye. There was no afferent pupillary defect. External examination revealed marked proptosis. Extraocular motility was reduced in all directions. There was marked superficial punctate keratopathy bilaterally. Ophthalmoscopy through dilated pupils revealed multifocal white/yellow subretinal lesions without vitreous cells in both eyes. He had bilateral sensorineural hearing loss and bilateral lower extremity weakness with diminished lower extremity deep tendon reflexes. Orbital CT revealed bilaterally enlarged extraocular muscles with fullness at the orbital apex but no clear compression of the optic nerves. Brain MRI revealed diffuse intracranial leptomeningeal enhancement and enhancement of both auditory canals. Additionally, there was; restricted diffusion in the left fornix and right putamen. Spine MRI revealed enhancement of the cauda equina roots. Lumbar puncture showed a normal opening pressure with a white blood cell count of 578 (78% lymphocytes), a protein of 348 mg/dL, and negative cytology. The leading diagnosis was non-Hodgkin lymphoma (NHL). The putaminal and fornix abnormalities, believed to be; consistent with ischemic stroke, led to more detailed review of the brain MRI, which disclosed vessel wall enhancement of the right internal carotid artery. A procedure was performed

Look in the Back (Slides)

A 59-year old man with Graves disease developed increasing proptosis and diplopia. Attributing these abnormalities to worsening of the Graves disease, an ophthalmologist treated him with high-dose oral and intravenous corticosteroids. When improvement did not occur, he underwent orbital x-irradiation (unknown dose). He developed new bilateral hearing loss, bilateral lower extremity weakness, and urinary retention eliciting catheter placement. Visual acuity declined, so he was referred to our institution for urgent orbital decompression. When we first encountered him, he was confused and drowsy. Best-corrected visual acuity was 20/80 in the right eye and 20/200 in the left eye. There was no afferent pupillary defect. External examination revealed marked proptosis. Extraocular motility was reduced in all directions. There was marked superficial punctate keratopathy bilaterally. Ophthalmoscopy through dilated pupils revealed multifocal white/yellow subretinal lesions without vitreous cells in both eyes. He had bilateral sensorineural hearing loss and bilateral lower extremity weakness with diminished lower extremity deep tendon reflexes. Orbital CT revealed bilaterally enlarged extraocular muscles with fullness at the orbital apex but no clear compression of the optic nerves. Brain MRI revealed diffuse intracranial leptomeningeal enhancement and enhancement of both auditory canals. Additionally, there was; restricted diffusion in the left fornix and right putamen. Spine MRI revealed enhancement of the cauda equina roots. Lumbar puncture showed a normal opening pressure with a white blood cell count of 578 (78% lymphocytes), a protein of 348 mg/dL, and negative cytology. The leading diagnosis was non-Hodgkin lymphoma (NHL). The putaminal and fornix abnormalities, believed to be; consistent with ischemic stroke, led to more detailed review of the brain MRI, which disclosed vessel wall enhancement of the right internal carotid artery. A procedure was performed

Frontal sinus fibrous dysplasia with atypical radiological features: A case report and review of the literature

Objectives: To present a case of frontal sinus fibrous dysplasia with atypical radiological features and to perform a literature review. Case report: A 63 year old gentleman presented to clinic with a one year history of right eye proptosis. CT and MRI were performed and identified a mass filling the frontal sinus and eroding the orbital wall. The patient had a combined endoscopic and open approach to the right frontal sinus with the final diagnosis being fibrous dysplasia. Study design: Case report and literature review. Methods: Systematic literature review was conducted with the review focusing on the radiological features of fibrous dysplasia in the head and neck. Results: Fibrous dysplasia can present in a variety of ways in the head and neck. There are certain features in its radiological appearance that can aid in early identification of the disease, thereby leading to the development of better management plans. In CT scan, the ground glass appearance is the most persistent presentation. While in MRI, the degree of mineralization of the lesion dictates its signal intensity. Keywords: Fibrous dysplasia, Frontal sinus, Orbital erosion, Proptosi

Intracranial paragangliomas versus schwannomas: Role of dynamic susceptibility contrast perfusion and diffusion MRI

Background and PurposeDifferentiating paragangliomas from schwannomas and distinguishing sporadic from neurofibromatosis type 2 (NF 2)-related schwannomas is challenging but clinically important. This study aimed to assess the utility of dynamic susceptibility contrast perfusion MRI (DSC-MRI) and diffusion-weighted imaging (DWI) in discriminating infratentorial extra-axial schwannomas from paragangliomas and NF2-related schwannomas.MethodsThis retrospective study included 41 patients diagnosed with paragangliomas, sporadic schwannomas, and NF2-related schwannomas in the infratentorial extra-axial space between April 2013 and August 2021. All cases had pretreatment DSC-MRI and DWI. Normalized mean apparent diffusion coefficient (nADCmean), normalized relative cerebral blood volume (nrCBV), and normalized relative cerebral blood flow (nrCBF) were compared between paragangliomas and schwannomas and between sporadic and NF2-related schwannomas as appropriate.ResultsnrCBV and nrCBF were significantly higher in paragangliomas than in sporadic/NF2-related schwannomas (nrCBV: median 11.5 vs. 1.14/3.74; p < .001 and .004, nrCBF: median 7.43 vs. 1.13/2.85; p < .001 and .007, respectively), while nADCmean were not. The corresponding diagnostic performances were area under the curves (AUCs) of .99/.92 and 1.0/.90 with cutoffs of 2.56/4.22 and 1.94/3.36, respectively. nADCmean were lower, and nrCBV and nrCBF were higher in NF2-related than in sporadic schwannomas (nADCmean: median 1.23 vs. 1.58, nrCBV: median 3.74 vs. 1.14, nrCBF: median 2.85 vs. 1.13; all p < .001), and the corresponding diagnostic performances were AUCs of .93, .91, and .95 with cutoffs of 1.37, 2.63, and 2.48, respectively.ConclusionsDSC-MRI and DWI both can aid in differentiating paragangliomas from schwannomas and sporadic from NF2-related schwannomas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/174950/1/jon13002_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/174950/2/jon13002.pd

Neuroimaging correlates of apathy and depression in Alzheimer’s disease

A consecutive series of 79 patients with probable Alzheimer’s disease were assessed with a structured psychiatric evaluation, and diagnoses of apathy and depression were made using standardized criteria. Three-dimensional MRI scans were obtained from all patients, and images were segmented into gray matter, white matter, and CSF. White matter hyperintensities were edited on segmented images, and lobar assignments (frontal, temporal, parietal, and occipital) were made based on Talairach coordinates. Patients with apathy showed a significantly larger volume of frontal white matter hyperintensities than patients without apathy. Patients with depression had a significantly larger volume of right parietal white matter hyperintensities than patients without depression. However, neither apathy nor depression was significantly associated with lobar gray or white matter atrophy. Frontal and right parietal white matter hyperintensities are the strongest brain structural correlates of apathy and depression in Alzheimer’s disease

Neurofibromatosis type 2 versus sporadic vestibular schwannoma: The utility of MR diffusion and dynamic contrast-enhanced imaging

Background and PurposeThe goal of this study was to assess the utility of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to distinguish sporadic vestibular schwannomas (VSs) from those related to neurofibromatosis type 2 (NF2).MethodsWe retrospectively reviewed 265 patients pathologically diagnosed with VSs between January 2015 and October 2020 in a single institution. There were 28 patients (male: 19, female: 9; age 11-67 years) including 23 sporadic and five NF2-related VSs, who had pretreatment DWI and DCE-MRI. Normalized mean apparent diffusion coefficient (nADCmean) and DCE-MRI parameters along with tumor characteristics were compared between sporadic and NF2-related VSs as appropriate. The diagnostic performances were calculated based on the receiver operating characteristic curve analysis for the values that showed significant differences. To identify significant modalities, multivariate logistic regression analysis was performed using nADCmean and the combination of statistically significant DCE-MRI parameters.ResultsNADCmean, fractional volume of extracellular space (Ve), and forward volume transfer constant (Ktrans) were significantly different between sporadic and NF2-related VSs (nADCmean: median 1.62 vs. 1.16, P�=�.002; Ve: median 0.40 vs. 0.66, P�=�.007; Ktrans: median 0.17 vs. 0.33, P�=�.007), whereas fractional plasma volume (Vp), reverse�reflux rate�constant (Kep), and tumor characteristics were not. The diagnostic performances of nADCmean, Ve, and Ktrans were 0.93, 0.90, and 0.90 area under the curves with cutoffs of 1.46, 0.51, and 0.29, respectively. nADCmean and the combination of Ve and Ktrans were both chosen as significant differentiators by multivariate logistic regression analysis (P�=�.027).ConclusionsDWI and DCE-MRI are both promising modalities to distinguish sporadic and NF2-related VSs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172857/1/jon12966.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172857/2/jon12966_am.pd