Corrigendum: Newborn screening for X-linked adrenoleukodystrophy in Italy: diagnostic algorithm and disease monitoring.

[This corrects the article DOI: 10.3389/fneur.2022.1072256.].

A biallelic variant in COX18 cause isolated Complex IV deficiency associated with neonatal encephalo-cardio-myopathy and axonal sensory neuropathy.

Pathogenic variants impacting upon assembly of mitochondrial respiratory chain Complex IV (Cytochrome c Oxidase or COX) predominantly result in early onset mitochondrial disorders often leading to CNS, skeletal and cardiac muscle manifestations. The aim of this study is to describe a molecular defect in the COX assembly factor gene COX18 as the likely cause of a neonatal form of mitochondrial encephalo-cardio-myopathy and axonal sensory neuropathy. The proband is a 19-months old female displaying hypertrophic cardiomyopathy at birth and myopathy with axonal sensory neuropathy and failure to thrive developing in the first months of life. Serum lactate was consistently increased. Whole exome sequencing allowed the prioritization of the unreported homozygous substitution NM_001297732.2:c.667 G > C p.(Asp223His) in COX18. Patient's muscle biopsy revealed severe and diffuse COX deficiency and striking mitochondrial abnormalities. Biochemical and enzymatic studies in patient's myoblasts and in HEK293 cells after COX18 silencing showed a severe impairment of both COX activity and assembly. The biochemical defect was partially rescued by delivery of wild-type COX18 cDNA into patient's myoblasts. Our study identifies a novel defect of COX assembly and expands the number of nuclear genes involved in a mitochondrial disorder due to isolated COX deficiency.

Vertebral Augmentation: Is It Time to Get Past the Pain? A Consensus Statement from the Sardinia Spine and Stroke Congress.

Vertebral augmentation has been used to treat painful vertebral compression fractures and metastatic lesions in millions of patients around the world. An international group of subject matter experts have considered the evidence, including but not limited to mortality. These considerations led them to ask whether it is appropriate to allow the subjective measure of pain to so dominate the clinical decision of whether to proceed with augmentation. The discussions that ensued are related below.

Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring.

Introduction: X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder caused by variants in the ABCD1 gene. The main phenotypes observed in men with X-ALD are primary adrenal insufficiency, adrenomyeloneuropathy, and cerebral ALD (cALD). Cerebral ALD consists of a demyelinating progressive cerebral white matter (WM) disease associated with rapid clinical decline and is fatal if left untreated. Hematopoietic stem cell transplantation is the standard treatment for cALD as it stabilizes WM degeneration when performed early in the disease. For this reason, early diagnosis is crucial, and several countries have already implemented their newborn screening programs (NBS) with the assessment of C26:0-lysophosphatidylcholine (C26:0-LPC) values as screening for X-ALD. Methods: In June 2021, an Italian group in Lombardy launched a pilot study for the implementation of X-ALD in the Italian NBS program. A three-tiered approach was adopted, and it involved quantifying the values of C26:0-LPC and other metabolites in dried blood spots with FIA-MS/MS first, followed by the more specific ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technique and, finally, the genetic confirmation via focused NGS. Discussion: Genetically confirmed patients are set to undergo a follow-up protocol and are periodically evaluated to promptly start a specific treatment if and when the first signs of brain damage appear, as suggested by international guidelines. A specific disease monitoring protocol has been created based on literature data and personal direct experience. Conclusion: The primary aim of this study was to develop a model able to improve the early diagnosis and subsequent follow-up and timely treatment of X-ALD. Ethics: The study was approved by the local ethics committee. The research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Efficacy of an ethyl alcohol gel in symptomatic disc herniation.

PURPOSE: To evaluate the clinical outcome of DiscoGel® chemonucleolysis for symptomatic disc herniation in patients who fail conservative treatment. MATERIAL AND METHODS: Consecutive patients with symptomatic disc herniation confirmed on MRI who failed conservative management for at least 6 months were included. Visual analogue scale (VAS), Oswestry Disability Index (ODI) scores, and analgesic use were recorded at baseline, and 12 months after treatment. Multidetector CT (MDCT) was performed at baseline, and 12 months after treatment to assess for DiscoGel® extravasation and alteration in treated disc volume. In a unique long-term subgroup analysis of 31 patients, telephonic follow-up was performed utilizing VAS and ODI parameters 7 years after the procedure. RESULTS: A total of 87 disc herniations were treated in 71 patients; majority (54%) were treated at L4/5 and L5/S1. VAS score of 8 before treatment was reduced to 3 at 12 months after treatment (p = 0.0001); ODI score of 51 before treatment was reduced to 15 at 12 months after treatment (p = 0.0001). Analgesic use of 70.4% was reduced to 29.6% after treatment. There were no symptomatic procedural complications; MDCT revealed 1 asymptomatic peri-neural DiscoGel® extravasation. In the 31 subjects that underwent telephonic follow-up the VAS and ODI parameters maintained their values without statistically significant differences when compared with the 12-month follow-up. CONCLUSION: Patients with symptomatic disc herniation who failed conservative treatment and were treated with DiscoGel® chemonucleolysis achieved significant gains in pain relief and reduced disability without symptomatic complication. DiscoGel® chemonucleolysis is a feasible, minimally invasive technique for treatment of symptomatic disc herniation.

Neuroimaging of the Postoperative Spine.

Operative treatments of the spine are becoming increasingly more common for the availability of a wide range of surgical and minimally invasive procedures. MR imaging allows for excellent evaluation of both normal and abnormal findings in the postoperative spine. This article provides the basic tools to evaluate complications after different operative procedures and offers an overview on the main topics a radiologist may encounter during his or her professional carrier.

MRI helps depict clinically undetectable risk factors in advanced stage retinoblastomas.

This study compared high-resolution MRI with histology in advanced stage retinoblastomas in which ophthalmoscopy and ultrasonography did not give an exhaustive depiction of the tumour and/or its extension. MRI of orbits and head in 28 retinoblastoma patients (28 eyes) treated with primary enucleation were evaluated. Iris neoangiogenesis, infiltrations of optic nerve, choroid, anterior segment and sclera suspected at MR and histology were compared. Abnormal anterior segment enhancement (AASE) was also correlated with histologically proven infiltrations. Brain images were also evaluated. Significant values were obtained for: prelaminar optic nerve (ON) sensitivity (0.88), positive predictive value (PPV) (0.75) and negative predictive value (NPV) (0.71); post-laminar ON sensitivity (0.50), specificity (0.83), PPV (0.50) and NPV (0.83); overall choroid sensitivity (0.82), and massive choroid NPV (0.69); scleral specificity (1), and NPV (1). AASE correlated with iris neoangiogenesis in 14 out of 19 eyes, and showed significant values for: overall ON PPV (0.65), prelaminar ON sensitivity (0.65), and PPV (0.61), post-laminar ON NPV (0.64); overall choroid sensitivity (0.77), PPV (0.59) and NPV (0.73); scleral NPV (0.83); anterior segment sensitivity (1), and NPV (1). Odds ratios (OR) and accuracy were significant in scleral and prelaminar optic nerve infiltration. Brain examination was unremarkable in all cases. High-resolution MRI may add important findings to clinical evaluation of advanced stage retinoblastomas.

Methadone-induced toxic leukoencephalopathy: diagnosis and follow-up by magnetic resonance imaging including diffusion-weighted imaging and apparent diffusion coefficient maps.

BACKGROUND AND PURPOSE: Effects of methadone misuse have been rarely described. The purpose of this case report is to increase the knowledge of methadone-related leukoencephalopathy. METHODS: We report the long-term follow-up by brain magnetic resonance imaging including isotropic diffusion-weighted imaging and mean apparent diffusion coefficient values of a 49-year-old patient who attempted suicide by intravenous methadone. RESULTS AND CONCLUSIONS: Lesion pattern included subtle cerebellar involvement, mainly reversible extensive bilateral and symmetric brain involvement, cystic degeneration in the periventricular regions, sparing of corpus callosum and subcortical U-fibers, development of diffuse brain atrophy, and clear-cut clinical improvement.

Spindle cell lipoma of the orbit: a case report of an unusual orbital pathology.

Spindle cell lipoma is a rare and distinct variant of soft tissue tumour characterised by spindle cells in which the fat content may be scarce or absent. Most spindle cell lipomas arise as a subcutaneous mass of the neck, shoulders or back. Rarely, they can also be found in unusual sites, such as the oral cavity, larynx, bronchus, breast, and extremities. Localisation of spindle cell lipoma in the orbit has been described in a few cases. We report here on a case of an orbital mass surgically excised in an adult male and discuss the differential diagnosis with other soft tissue tumours with a lipomatous component, such as lipomatous haemangiopericytoma, a rare variant of haemangiopericytoma.