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- Petzold, Axel, et al.
(författare)
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Diagnosis and classification of optic neuritis
- 2022
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Ingår i: Lancet Neurology. - : ELSEVIER SCIENCE INC. - 1474-4422 .- 1474-4465. ; 21:12, s. 1120-1134
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Forskningsöversikt (refereegranskat)abstract
- There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.
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| 2. |
- Sedghi, Maryam, et al.
(författare)
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Motor neuron diseases caused by a novel VRK1 variant - A genotype/phenotype study
- 2019
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Ingår i: Annals of Clinical and Translational Neurology. - : John Wiley & Sons. - 2328-9503. ; 6:11, s. 2197-2204
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Tidskriftsartikel (refereegranskat)abstract
- Background Motor neuron disorders involving upper and lower neurons are a genetically and clinically heterogenous group of rare neuromuscular disorders with overlap among spinal muscular atrophies (SMAs) and amyotrophic lateral sclerosis (ALS). Classical SMA caused by recessive mutations in SMN1 is one of the most common genetic causes of mortality in infants. It is characterized by degeneration of anterior horn cells in the spinal cord, leading to progressive muscle weakness and atrophy. Non-SMN1-related spinal muscular atrophies are caused by variants in a number of genes, including VRK1, encoding the vaccinia-related kinase 1 (VRK1). VRK1 variants have been segregated with motor neuron diseases including SMA phenotypes or hereditary complex motor and sensory axonal neuropathy (HMSN), with or without pontocerebellar hypoplasia or microcephaly. Results Here, we report an association of a novel homozygous splice variant in VRK1 (c.1159 + 1G>A) with childhood-onset SMA or juvenile lower motor disease with brisk tendon reflexes without pontocerebellar hypoplasia and normal intellectual ability in a family with five affected individuals. We show that the VRK1 splice variant in patients causes decreased splicing efficiency and a mRNA frameshift that escapes the nonsense-mediated decay machinery and results in a premature termination codon. Conclusions Our findings unveil the impact of the variant on the VRK1 transcript and further support the implication of VRK1 in the pathogenesis of lower motor neuron diseases.
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