Iatrogenic cerebral radiation necrosis.

Cerebral radiation necrosis is the most serious late reaction to high doses of ionising radiation to the brain, and its treatment is generally unsatisfactory. We present a patient who developed cerebral radiation necrosis after protracted fluoroscopy during repeated embolisations of an extracranial arteriovenous malformation. Treatment with bevacizumab (a humanised murine monoclonal antibody against vascular endothelial growth factor) was followed by neurological and radiological improvements.

Functional characterization of the first missense variant in CEP78, a founder allele associated with cone-rod dystrophy, hearing loss, and reduced male fertility.

Inactivating variants in the centrosomal CEP78 gene have been found in cone-rod dystrophy with hearing loss (CRDHL), a particular phenotype distinct from Usher syndrome. Here, we identified and functionally characterized the first CEP78 missense variant c.449T>C, p.(Leu150Ser) in three CRDHL families. The variant was found in a biallelic state in two Belgian families and in a compound heterozygous state-in trans with c.1462-1G>T-in a third German family. Haplotype reconstruction showed a founder effect. Homology modeling revealed a detrimental effect of p.(Leu150Ser) on protein stability, which was corroborated in patients' fibroblasts. Elongated primary cilia without clear ultrastructural abnormalities in sperm or nasal brushes suggest impaired cilia assembly. Two affected males from different families displayed sperm abnormalities causing infertility. One of these is a heterozygous carrier of a complex allele in SPAG17, a ciliary gene previously associated with autosomal recessive male infertility. Taken together, our data indicate that a missense founder allele in CEP78 underlies the same sensorineural CRDHL phenotype previously associated with inactivating variants. Interestingly, the CEP78 phenotype has been possibly expanded with male infertility. Finally, CEP78 loss-of-function variants may have an underestimated role in misdiagnosed Usher syndrome, with or without sperm abnormalities.

Quantifying the Financial Savings of Motion Correction in Brain MRI: A Model-Based Estimate of the Costs Arising From Patient Head Motion and Potential Savings From Implementation of Motion Correction.

BACKGROUND: Patient head motion is a major concern in clinical brain MRI, as it reduces the diagnostic image quality and may increase examination time and cost. PURPOSE: To investigate the prevalence of MR images with significant motion artifacts on a given clinical scanner and to estimate the potential financial cost savings of applying motion correction to clinical brain MRI examinations. STUDY TYPE: Retrospective. SUBJECTS: In all, 173 patients undergoing a PET/MRI dementia protocol and 55 pediatric patients undergoing a PET/MRI brain tumor protocol. The total scan time of the two protocols were 17 and 40 minutes, respectively. FIELD STRENGTH/SEQUENCES: 3 T, Siemens mMR Biograph, MPRAGE, DWI, T1 and T2 -weighted FLAIR, T2 -weighted 2D-FLASH, T2 -weighted TSE. ASSESSMENT: A retrospective review of image sequences from a given clinical MRI scanner was conducted to investigate the prevalence of motion-corrupted images. The review was performed by three radiologists with different levels of experience using a three-step semiquantitative scale to classify the quality of the images. A total of 1013 sequences distributed on 228 MRI examinations were reviewed. The potential cost savings of motion correction were estimated by a cost estimation for our country with assumptions. STATISTICAL TEST: The cost estimation was conducted with a 20% lower and upper bound on the model assumptions to include the uncertainty of the assumptions. RESULTS: 7.9% of the sequences had motion artifacts that decreased the interpretability, while 2.0% of the sequences had motion artifacts causing the images to be nondiagnostic. The estimated annual cost to the clinic/hospital due to patient head motion per scanner was $45,066 without pediatric examinations and $364,242 with pediatric examinations. DATA CONCLUSION: The prevalence of a motion-corrupted image was found in 2.0% of the reviewed sequences. Based on the model, repayment periods are presented as a function of the price for applying motion correction and its performance. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 6 J. Magn. Reson. Imaging 2020;52:731-738.

Postprandial gut hormone responses and glucose metabolism in cholecystectomized patients.

Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat-rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum bile acids were measured. We found similar basal glucose concentrations in the two groups, whereas cholecystectomized subjects had elevated postprandial glucose excursions. Cholecystectomized subjects had reduced postprandial concentrations of duodenal bile acids, but preserved postprandial plasma GLP-1 responses, compared with control subjects. Also, cholecystectomized patients exhibited augmented fasting glucagon. Basal plasma CCK concentrations were lower and peak concentrations were higher in cholecystectomized patients. The concentrations of GIP, GLP-2, and gastrin were similar in the two groups. In conclusion, cholecystectomized subjects had preserved postprandial GLP-1 responses in spite of decreased duodenal bile delivery, suggesting that gallbladder emptying is not a prerequisite for GLP-1 release. Cholecystectomized patients demonstrated a slight deterioration of postprandial glycemic control, probably because of metabolic changes unrelated to incretin secretion.

CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels.

CEP78 is a centrosomal protein implicated in ciliogenesis and ciliary length control, and mutations in the CEP78 gene cause retinal cone-rod dystrophy associated with hearing loss. However, the mechanism by which CEP78 affects cilia formation is unknown. Based on a recently discovered disease-causing CEP78 p.L150S mutation, we identified the disease-relevant interactome of CEP78. We confirmed that CEP78 interacts with the EDD1-DYRK2-DDB1VPRBP E3 ubiquitin ligase complex, which is involved in CP110 ubiquitination and degradation, and identified a novel interaction between CEP78 and CEP350 that is weakened by the CEP78L150S mutation. We show that CEP350 promotes centrosomal recruitment and stability of CEP78, which in turn leads to centrosomal recruitment of EDD1. Consistently, cells lacking CEP78 display significantly increased cellular and centrosomal levels of CP110, and depletion of CP110 in CEP78-deficient cells restored ciliation frequency to normal. We propose that CEP78 functions downstream of CEP350 to promote ciliogenesis by negatively regulating CP110 levels via an EDD1-dependent mechanism.

Central and peripheral nervous system complications of COVID-19: a prospective tertiary center cohort with 3-month follow-up.

OBJECTIVE: To systematically describe central (CNS) and peripheral (PNS) nervous system complications in hospitalized COVID-19 patients. METHODS: We conducted a prospective, consecutive, observational study of adult patients from a tertiary referral center with confirmed COVID-19. All patients were screened daily for neurological and neuropsychiatric symptoms during admission and discharge. Three-month follow-up data were collected using electronic health records. We classified complications as caused by SARS-CoV-2 neurotropism, immune-mediated or critical illness-related. RESULTS: From April to September 2020, we enrolled 61 consecutively admitted COVID-19 patients, 35 (57%) of whom required intensive care (ICU) management for respiratory failure. Forty-one CNS/PNS complications were identified in 28 of 61 (45.9%) patients and were more frequent in ICU compared to non-ICU patients. The most common CNS complication was encephalopathy (n = 19, 31.1%), which was severe in 13 patients (GCS ≤ 12), including 8 with akinetic mutism. Length of ICU admission was independently associated with encephalopathy (OR = 1.22). Other CNS complications included ischemic stroke, a biopsy-proven acute necrotizing encephalitis, and transverse myelitis. The most common PNS complication was critical illness polyneuromyopathy (13.1%), with prolonged ICU stay as independent predictor (OR = 1.14). Treatment-related PNS complications included meralgia paresthetica. Of 41 complications in total, 3 were para/post-infectious, 34 were secondary to critical illness or other causes, and 4 remained unresolved. Cerebrospinal fluid was negative for SARS-CoV-2 RNA in all 5 patients investigated. CONCLUSION: CNS and PNS complications were common in hospitalized COVID-19 patients, particularly in the ICU, and often attributable to critical illness. When COVID-19 was the primary cause for neurological disease, no signs of viral neurotropism were detected, but laboratory changes suggested autoimmune-mediated mechanisms.

After stroke, apraxia of eyelid opening is associated with high mortality and right hemispheric infarction.

INTRODUCTION: Apraxia of eyelid opening (AEO) refers to impaired voluntary eyelid elevation of supranuclear origin. AEO is well-described in neurodegenerative disorders, but its frequency in stroke is unknown. METHODS: To investigate the frequency of AEO after stroke, we enrolled patients with an anterior circulation occlusion admitted for endovascular thrombectomy (EVT). Exclusion criteria were posterior circulation stroke, impaired consciousness and ophthalmological disorders. Forty-eight hours after EVT, patients were screened for AEO, conjugated gaze palsies and cortical ptosis. Neurological deficits were classified using the National Institute of Health Stroke Scale (NIHSS). A blinded neuroradiologist analyzed CT brain 24 h after EVT using the Alberta Stroke Program Early CT Score. RESULTS: Ninety-eight EVT patients were included in 9 months. Six patients had AEO (6%), 37 conjugated gaze palsy (38%) and 16% cortical ptosis (16%). AEO was associated with higher median NIHSS compared to no eye symptoms (18.5 vs. 3; p < 0.001) and gaze palsy or cortical ptosis (18.5 vs. 7; p = 0.003). The median modified Rankin Scale (mRS) after 3 months was 2 in patients without AEO, but 6 in patients with AEO (mRS in AEO patients nr. 1-6: 3, 4, 6, 6, 6, and 6; p = 0.015; no longer significant after adjustment for stroke severity), including 4 deaths (66%) in AEO patients. All patients with AEO had right hemisphere stroke (6/6 vs. 43/98 in total, p = 0.006). CONCLUSION: AEO was observed in 6% of EVT patients who showed poor survival and outcome. AEO occurred exclusively in right hemispheric infarctions, suggesting that supranuclear eyelid control is under the influence of the right cerebral hemisphere.

Influence of Strategic Cortical Infarctions on Pupillary Function.

Objective: Cortical activity, including cognitive and emotional processes, may influence pupillary function. The exact pathways and the site of cortical pupillary innervation remain elusive, however. We investigated the effects of select cortical strokes, i.e. ischemic infarcts affecting the insular cortex and prefrontal eye field, on pupillary function. Methods: Seventy-four patients with acute ischemic stroke, consecutively admitted to our institution from March to July 2018, were assessed 24 h after endovascular recanalization therapy (i.e., day 2 after the stroke), using automated pupillometry. Stroke location and volume and clinical severity (estimated by the Alberta Stroke Program Early CT Score and National Institute of Health Stroke Scale) were recorded. We excluded patients with posterior circulation stroke, intracranial pathology other than ischemic stroke, midline shift on computed tomography exceeding 5 millimeters or a history of eye disease. Pupillometry data from 25 neurologically normal patients with acute myocardial infarction were acquired for control. Results: Fifty stroke patients after thrombectomy were included for analysis. Twenty-five patients (50%) had insular cortex or prefrontal eye field involvement (group 1, strategic infarcts); 25 patients had infarcts located in other cerebral areas (group 2, other infarcts). The pupillary light reflex, as measured by constriction velocity and maximal/minimal pupillary diameters, was within physiological limits in all patients, including controls. However, while pupillary size and constriction velocities were correlated in all subjects, the correlation of size and dilatation velocity was absent in right-hemispheric infarcts (left hemisphere infarcts, group 1 (r 2 = 0.15, p = 0.04), group 2 (r 2 = 0.41, p = 0.0007); right hemisphere infarcts, group 1 (r 2 = 0.008, p = 0.69); group 2 (r 2 = 0.12, p = 0.08); controls (r 2 = 0.29, p ≤ 0.0001). Conclusions: Cortical infarcts of the prefrontal eye field or insula do not impair the pupillary light reflex in humans. However, subtle changes may occur when the pupils dilate back to baseline, probably due to autonomic dysfunction. Replication is needed to explore the possible influence of hemispheric lateralization. We suggest that endovascular therapy for acute ischemic stroke may serve as a clinical research model for the study of acquired cortical lesions in humans.

Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited.

BACKGROUND: Invasive infection with Streptococcus pneumoniae (pneumococci) causes significant morbidity and mortality. Case series and experimental data have shown that the capsular serotype is involved in the pathogenesis and a determinant of disease outcome. METHODS: Retrospective review of 464 cases of invasive disease among adults diagnosed between 1990 and 2001. Multivariate Cox proportional hazard analysis. RESULTS: After adjustment for other markers of disease severity, we found that infection with serotype 3 was associated with an increased relative risk (RR) of death of 2.54 (95% confidence interval (CI): 1.22-5.27), whereas infection with serotype 1 was associated with a decreased risk of death (RR 0.23 (95% CI, 0.06-0.97)). Additionally, older age, relative leucopenia and relative hypothermia were independent predictors of mortality. CONCLUSION: Our study shows that capsular serotypes independently influenced the outcome from invasive pneumococcal disease. The limitations of the current polysaccharide pneumococcal vaccine warrant the development of alternative vaccines. We suggest that the virulence of pneumococcal serotypes should be considered in the design of novel vaccines.

[Petrous apex cephalocele is a rare disease]. / Petrous apex cephalocele er en sjælden lidelse.

Petrous apex cephalocele (PAC) is a rare lesion, which represents a herniation from the posteriolateral portion of Meckel's cave into the petrous apex. The pathologic explanation is still unknown. We report a patient with clinical symptoms of facial pain, hearing loss and cerebrospinal fluid otorrhea. A computertomography and a magnetic resonance scan revealed that the symptoms were caused by PAC. The patient was later successfully operated by means of middle fossa approach.