Arterial spin labeling perfusion in acute Wernicke encephalopathy: a case series discussion.

Wernicke's encephalopathy (WE) is a life-threatening neurologic disorder resulting from thiamine (vitamin B1) deficiency that can be secondary to chronic alcohol abuse, gastrointestinal surgery, systemic infectious and non-infectious diseases, and chemotherapy. WE is classically characterized on MRI by reduced diffusion and T2 prolongation along the mammillothalamic tracts, periaqueductal gray and tectal plate. We present two patients with acute WE who had baseline arterial spin labeling (ASL) perfusion at the time of presentation, demonstrating increase in cerebral blood flow (CBF) within the classically involved brain regions and concurrent global cerebral cortical hypoperfusion. Both patients were successfully treated with intravenous thiamine infusion. Post-treatment MRI demonstrated improvement of reduced diffusion and normalization of CBF within the involved structures. Prior histopathological studies have documented prominent undulation and luminal dilatation of arteries and arterioles in acute WE lesions, likely explaining the increased perfusion shown by imaging. The root of this pathophysiologic process may trace back to thiamine's biochemical role in maintaining osmotic gradients and glucose metabolism, that if failed can lead to arterial hyper-perfusion. Our findings show that ASL-CBF can highlight the underlying pathophysiology in patients with acute WE by demonstrating increased CBF in involved central structures. This luxury perfusion may be a compensatory or protective mechanism by which increased metabolic demand is met in the acute setting and which, if treated timely, will show normalization of CBF on ASL imaging.

Case report: A novel biallelic FTO variant causing multisystem anomalies with severe epilepsy, widening the spectrum of FTO syndrome.

The fat mass and obesity-associated gene (FTO) codes for a DNA/RNA demethylase. Pathological variants in this gene are rare, with only three reports in the literature, all with mutations in the catalytic domain. We report the first biallelic human variant in fat mass and obesity-associated gene (c.287G>C, p.Arg96Pro/R96P) outside the catalytic site, causing numerous abnormalities across multiple organ systems, affecting respiratory, cardiovascular, and neurological function. Biochemical assays of cells with the patient's variant were performed to further quantify the effect of the variant on function. Loss-of-function resulting from the patient's R96P missense variant was demonstrated with in vitro biochemical characterization of demethylase activity, resulting in a 90% reduction in function of the fat mass and obesity-associated protein compared to wild-type. Our findings demonstrate a novel fat mass and obesity-associated gene non-catalytic site variant with a unique patient phenotype of bilateral multifocal epilepsy and multisystem congenital anomalies.

Recessive pathogenic variants in MCAT cause combined oxidative phosphorylation deficiency.

Malonyl-CoA-acyl carrier protein transacylase (MCAT) is an enzyme involved in mitochondrial fatty acid synthesis (mtFAS) and catalyzes the transfer of the malonyl moiety of malonyl-CoA to the mitochondrial acyl carrier protein (ACP). Previously, we showed that loss-of-function of mtFAS genes, including Mcat, is associated with severe loss of electron transport chain (ETC) complexes in mouse immortalized skeletal myoblasts (Nowinski et al., 2020). Here, we report a proband presenting with hypotonia, failure to thrive, nystagmus, and abnormal brain MRI findings. Using whole exome sequencing, we identified biallelic variants in MCAT. Protein levels for NDUFB8 and COXII, subunits of complex I and IV respectively, were markedly reduced in lymphoblasts and fibroblasts, as well as SDHB for complex II in fibroblasts. ETC enzyme activities were decreased in parallel. Re-expression of wild-type MCAT rescued the phenotype in patient fibroblasts. This is the first report of a patient with MCAT pathogenic variants and combined oxidative phosphorylation deficiency.

Novel Grading Scales for Static and Flexion-Extension Magnetic Resonance Imaging in Patients with Cervical Spondylotic Myelopathy.

BACKGROUND: Flexion-extension magnetic resonance imaging (MRI) has potential to identify cervical pathology not detectable on conventional static MRI. Our study evaluated standard quantitative and novel subjective grading scales for assessing the severity of cervical spondylotic myelopathy in dynamic sagittal MRI as well as in static axial and sagittal images. METHODS: Forty-five patients underwent both conventional and flexion-extension MRI prior to anterior cervical discectomy and fusion from C4 through C7. In addition to measuring Cobb angles and cervical canal diameter, grading scales were developed for assessment of vertebral body translation, loss of disc height, change in disc contour, deformation of cord contour, and cord edema. Data were collected at all levels from C2-C3 through C7-T1. Variations in measurements between cervical levels and from flexion through neutral to extension were assessed using Mann-Whitney, Kruskal-Wallis, and two-way ANOVA tests. RESULTS: Cervical canal diameter, vertebral translation, and posterior disc opening changed significantly from flexion to neutral to extension positions (P < 0.01). When comparing operative versus nonoperative cervical levels, significant differences were found when measuring sagittal cervical canal dimensions, vertebral translation, and posterior disc opening (P < 0.01). Degenerative loss of disc height, disc dehydration, deformation of ventral cord contour, and cord edema were all significantly increased at operative levels versus nonoperative levels (P < 0.01). CONCLUSIONS: Flexion-extension MRI demonstrated significant changes not available from conventional MRI. Subjective scales for assessing degenerative changes were significantly more severe at levels with operative cervical spondylotic myelopathy. The utility of these scales for planning surgical intervention at specific and adjacent levels is currently under investigation.

Giant chondrosarcoma of the falx in an adolescent: A case report.

BACKGROUND: Intracranial chondrosarcomas are slowly growing malignant cartilaginous tumors that are especially rare in adolescents. CASE DESCRIPTION: A 19-year-old woman with no medical history presented with symptoms of intermittent facial twitching and progressive generalized weakness for 6 months. The patient's physical examination was unremarkable. Imaging revealed a large bifrontal mass arising from the falx cerebri, with significant compression of both cerebral hemispheres and downward displacement of the corpus callosum. The patient underwent a bifrontal craniotomy for gross total resection of tumor. Neuropathologic examination revealed a bland cartilaginous lesion most consistent with low-grade chondrosarcoma. Her postoperative course was uneventful, and she was discharged to home on postoperative day 3. CONCLUSION: This is an unusual case of an extra-axial, non-skull base, low-grade chondrosarcoma presenting as facial spasm in an adolescent patient.

Chordoid glioma: a rare old foe but a new pathological and radiological presentation.

Chordoid glioma (CG) is a rare WHO Grade II neoplasm of the anterior third ventricle. We report two cases of CG with new presentation in terms of histopathology and location: a case of CG with osseous metaplasia evident on imaging, and another CG, unusually located in the posterior portion of the third ventricle.

Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor.

De novo, heterozygous, loss-of-function variants were identified in Pou domain, class 4, transcription factor 1 (POU4F1) via whole-exome sequencing in four independent probands presenting with ataxia, intention tremor, and hypotonia. POU4F1 is expressed in the developing nervous system, and mice homozygous for null alleles of Pou4f1 exhibit uncoordinated movements with newborns being unable to successfully right themselves to feed. Head magnetic resonance imaging of the four probands was reviewed and multiple abnormalities were noted, including significant cerebellar vermian atrophy and hypertrophic olivary degeneration in one proband. Transcriptional activation of the POU4F1 p.Gln306Arg protein was noted to be decreased when compared with wild type. These findings suggest that heterozygous, loss-of-function variants in POU4F1 are causative of a novel ataxia syndrome.

Body Mass Index Correlates with Skin to Spinal Canal Distance: A Large Retrospective Single-Center Study.

BACKGROUND AND PURPOSE: Despite increasing demand for fluoroscopy-guided lumbar puncture (FG-LP), there is limited quantitative and epidemiological data on patients undergoing this procedure. Additionally, data are scarce on the correlation of iliac crest landmarks to the actual anatomical lumbar level (intercristal line). The aim of this study is to determine if (1) body mass index (BMI) correlates with skin to spinal canal distance (SCD) and (2) the iliac crest landmark correlates with the presumed anatomical landmark on cross-sectional imaging. METHODS: In this retrospective, single-center IRB-approved study, we assessed 495 patients who underwent FG-LP and had lumbar computed tomography/magnetic resonance imaging within 6 months of presentation. SCD was measured on the sagittal view at the L3-L4, L4-L5, and L5-S1 intervertebral levels. RESULTS: In our cohort of 495 adults (mean age ± standard deviation [SD], 53.2 ± 16.4 years), there was a statistically significant linear correlation between BMI and SCD at each intervertebral level. Mean ± SD (R2 ) SCD at L3-4, L4-5, and L5-S1 was 6.7 ± 1.6 cm (.5486), 7.4 ± 1.9 cm (.5894), and 7.8 ± 1.9 cm (.5968), respectively. The intercristal line aligned with L3-L4, L4-L5, and L5-S1 in 2.1%, 72.4%, and 6.2% of patients, respectively. CONCLUSIONS: There was direct, positive linear correlation between BMI and SCD at clinically relevant lumbar disc levels. Furthermore, there is considerable anatomical variance in the intervertebral space that aligns with the superior aspect of the iliac crest.

Sub-millimeter variation in human locus coeruleus is associated with dimensional measures of psychopathology: An in vivo ultra-high field 7-Tesla MRI study.

The locus coeruleus (LC) has a long-established role in the attentional and arousal response to threat, and in the emergence of pathological anxiety in pre-clinical models. However, human evidence of links between LC function and pathological anxiety has been restricted by limitations in discerning LC with current neuroimaging techniques. We combined ultra-high field 7-Tesla and 0.4 × 0.4 × 0.5 mm quantitative MR imaging with a computational LC localization and segmentation algorithm to delineate the LC in 29 human subjects including subjects with and without an anxiety or stress-related disorder. Our automated, data-driven LC segmentation algorithm provided LC delineations that corresponded well with postmortem anatomic definitions of the LC. There was variation of LC size in healthy subjects (125.7 +/- 59.3 mm3), which recapitulates histological reports. Patients with an anxiety or stress-related disorder had larger LC compared to controls (Cohen's d = 1.08, p = 0.024). Larger LC was additionally associated with poorer attentional and inhibitory control and higher anxious arousal (FDR-corrected p's<0.025), trans-diagnostically across the full sample. This study combined high-resolution and quantitative MR with a mixture of supervised and unsupervised computational techniques to provide robust, sub-millimeter measurements of the LC in vivo, which were additionally related to common psychopathology. This work has wide-reaching applications for a range of neurological and psychiatric disorders characterized by expected LC dysfunction.

Characterization of Bilateral Parietal Thinning.

BACKGROUND: Bilateral parietal thinning (BPT) of the calvarium is uncommon but can lead to significant morbidity, including pain or communication through the thinned bone. This study aimed to define and characterize a novel grading system for BPT. METHODS: Coronal CT scans of patients with BPT were retrospectively analyzed and anatomic measurements were taken including (1) thinning ratio, defined as calvarial thickness at the thinnest point divided by the average thickness of the surrounding bone and (2) width of the defect. In addition, patient demographics and comorbidities were collected. RESULTS: Forty-three patients were identified with BPT, with an average age of 73 ±â€Š16 years and 74% were female. The authors' novel grading scheme based on depth of calvarium involvement was found to be significantly correlated to thinning ratio (P < 0.001) and width (P < 0.001). When controlling for comorbidities, increasing age (P = 0.044) was the only significant independent risk factor associated with thinning ratio. With respect to defect size, when controlling for comorbidities, both hypertension (P = 0.025) and increasing age (P = 0.024) were found to be significant independent risk factors related to increasing defect size. Twenty patients (47%) had multiple CT scans (range 5 month-5 year interval). In this group, patients had an average of 0.66 ±â€Š0.11 mm decrease in parietal thickness per each year of increasing age, showing progressive parietal thinning with time. CONCLUSION: This study proposes a novel quantitatively-characterized grading scheme for BPT. The authors' results indicate that when controlling for comorbidities, BPT thinning is associated with increasing age, while defect width is associated with increasing age and hypertension. This grading scheme can help to diagnose, classify, and monitor patients with parietal bone thinning.

Diagnosis and Supportive Management of Fucosidosis: A Case Report.

Fucosidosis is a lysosomal storage disease, resulting from a deficiency of the enzyme alpha-L-fucosidase. We present the case of an affected female with numerous manifestations, clinically and radiographically. In fucosidosis, advanced interventions are not always necessary to have rewarding outcomes. In fact, early diagnosis and management of the symptoms with a multi-systemic supportive care approach can improve the quality of life and may also prolong the life of those patients diagnosed with fucosidosis.

The Distal Spine: Normal Embryogenesis and Derangements Leading to Malformation.

The spine and spinal cord are composed of multiple segments initiated by different embryologic mechanisms and advanced under different systems of control. In humans, the upper central nervous system is formed by primary neurulation, the lower by secondary neurulation, and the intervening segment by junctional neurulation. This article focuses on the distal spine and spinal cord to address their embryogenesis and the molecular derangements that lead to some distal spinal malformations.

Systemic Changes Affecting the Morphology of Calvarial Bone.

Plastic surgeons are frequently consulted to evaluate concerns about a patient's skull. Imaging studies often reveal abnormalities in bone morphology, from increased porosity to sclerotic changes. While focal findings imply a benign or malignant neoplasm, the etiology of more diffuse findings can be more varied, making the correct diagnosis challenging. The present review summarizes the differential diagnosis of osseous lesions of the calvarium that affect the bone and contribute to changes seen on imaging studies.

Demystifying the "Triple Point: " Technical Nuances of the Fronto-Orbital Advancement.

Removal of the fronto-orbital bandeau is one of the most critical components for procedures designed to correct anomalies of the craniofacial skeleton and remodel the anterior calvarial vault. It is also used to improve exposure of the anterior cranial fossa. It is arguably one of the more difficult portions of some craniofacial procedures. While the technique for fronto-orbito-sphenoid osteotomy has been frequently described, it has only been minimally detailed. Separation of bone in this region remains challenging due to the bone thickness, adjacent vital structures, and limited direct visibility. The present paper describes the anatomy of this particular region, which the authors have termed the "triple point", to facilitate successful osteotomy and avoid potential injury.

Reproducibility of myelin content-based human habenula segmentation at 3 Tesla.

In vivo morphological study of the human habenula, a pair of small epithalamic nuclei adjacent to the dorsomedial thalamus, has recently gained significant interest for its role in reward and aversion processing. However, segmenting the habenula from in vivo magnetic resonance imaging (MRI) is challenging due to the habenula's small size and low anatomical contrast. Although manual and semi-automated habenula segmentation methods have been reported, the test-retest reproducibility of the segmented habenula volume and the consistency of the boundaries of habenula segmentation have not been investigated. In this study, we evaluated the intra- and inter-site reproducibility of in vivo human habenula segmentation from 3T MRI (0.7-0.8 mm isotropic resolution) using our previously proposed semi-automated myelin contrast-based method and its fully-automated version, as well as a previously published manual geometry-based method. The habenula segmentation using our semi-automated method showed consistent boundary definition (high Dice coefficient, low mean distance, and moderate Hausdorff distance) and reproducible volume measurement (low coefficient of variation). Furthermore, the habenula boundary in our semi-automated segmentation from 3T MRI agreed well with that in the manual segmentation from 7T MRI (0.5 mm isotropic resolution) of the same subjects. Overall, our proposed semi-automated habenula segmentation showed reliable and reproducible habenula localization, while its fully-automated version offers an efficient way for large sample analysis.

Multimodality Treatment of Posterior Inferior Cerebellar Artery Aneurysms.

OBJECTIVE: Posterior inferior cerebellar artery (PICA) aneurysms are heterogeneous, uncommon lesions that can be treated in many fashions. Many previous series have focused on a specific aneurysm subset or treatment paradigm. The aim of this study was to present a comprehensive approach for all PICA aneurysms and analyze outcomes by PICA location. METHODS: All PICA aneurysms treated from 2012 until present were reviewed retrospectively and classified by location. Angiographic and clinical outcome were assessed. RESULTS: We identified 30 patients (average age 56 years, female 76.7%, subarachnoid hemorrhage 83.3%) with 30 aneurysms (saccular 50.0%) who underwent 36 treatments. Locations included the vertebral artery-PICA junction: 8; anterior medullary (AM): 7; lateral medullary: 3; tonsillomedullary: 1; telovelotonsillar: 5; and cortical: 6. Treatments included clipping: 6; trapping: 2; coiling: 13; balloon-assisted coiling: 1; stent-assisted coiling: 1; flow diversion: 1; and endovascular parent vessel occlusion: 6. There were 3 procedural complications. Recurrence and retreatment rates were 23.3% and 20.0%, respectively. Retreatments included coiling: 1; clipping: 4; and bypass: 1. Seven patients had an associated cerebellar arteriovenous malformation, of whom 5 have undergone resection. Good clinical outcome was achieved in 43.3% at discharge and 84.6% at follow-up (average 10.7 months). Aneurysms distal to the AM segment were more likely to occur in older patients (P = 0.007), with cerebellar arteriovenous malformations (P = 0.031), and to be treated with parent vessel occlusion (P = 0.001). Recurrences were more common for AM segment aneurysms (P = 0.016). Poor outcome was associated with poor SAH grade (P = 0.010), not aneurysm morphology (P = 0.356), location (P = 0.867), or treatment type (P = 0.365). CONCLUSIONS: Our 5-year modern experience highlights the diversity of PICA aneurysms and the need for multimodality paradigms to treat them successfully. The AM segment has the greatest rate of recurrence. Aggressive management is warranted given that the majority of patients can have a good neurologic outcome.