Kooperativer Bibliotheksverbund

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Format: 1 online resource (516 pages)

Edition: 1st ed.

ISBN: 0-323-99209-9

Series Statement: Issn Series

Note: Intro -- Inherited White Matter Disorders and Their Mimics -- Copyright -- Handbook of Clinical Neurology 3rd Series -- Foreword -- Preface -- Contributors -- Contents -- Section I: Introduction -- Chapter 1: Neuropathology of white matter disorders -- Classification of Leukodystrophies -- White Matter Composition and Associated Genetic Defects Resulting in Leukodystrophy -- Axons and neuronal cell bodies -- Myelin composition -- Oligodendrocytes -- Astrocytes -- Microglia -- Blood vessels -- Gene Defects Targeting Certain Organelles, Nucleic Acids, or Organic Acids -- Mitochondria -- Peroxisomes -- Lysosomes -- Defects in metabolism of nucleic acids -- Cellular vulnerability -- Regional vulnerability -- Leukodystrophies with additional PNS involvement -- Leukodystrophies with additional systemic manifestations -- Myelination impairment -- Neuropathology of Hypomyelinating Disorders -- Canavan disease -- POLR3-related leukodystrophy, aka Pol III deficiency or 4H (hypomyelination, hypodontia, hypogonadotropic hypogonadism) -- Hypomyelinating leukodystrophy due to mutations in genes encoding cytoplasmic or mitochondrial tRNA synthetizes -- Sjögren-Larsson syndrome -- Pelizaeus-Merzbacher disease (PMD) -- Neuropathology of disorders with white matter depletion of uncertain mechanism -- Neuropathology of demyelinating disorders -- Neuropathology of Vascular Diseases Causing Leukodystrophy -- Blood-brain barrier disruption -- Neuropathology of Leukodystrophies Associated With Cystic Degeneration and Gliosis -- References -- Chapter 2: Approaches to diagnosis for individuals with a suspected inherited white matter disorder -- Introduction -- MRI pattern recognition -- Newborn screening -- Standard of care diagnostic testing -- Next generation sequencing (NGS) -- NGS in the leukodystrophies. , The diagnostic algorithm for patients with a suspected genetic white matter disorder -- Persistently unsolved leukodystrophies and future directions in diagnosis -- Conclusion -- Acknowledgments -- Conflicts of Interest -- References -- Chapter 3: MRI pattern recognition in white matter disease -- Introduction -- General Approach -- Acquired Disorders -- Leukodystrophies -- Hypomyelinating leukodystrophies -- Leukodystrophies with demyelination -- Leukodystrophies with primary astrocyte involvement (astrocytopathies) -- Leukodystrophies with myelin vacuolization -- Leukodystrophies with primary axonal involvement (leuko-axonopathies) -- Leukodystrophies with primary microglia involvement (microgliopathies) -- Leukodystrophies with primary vascular pathology (leuko-vasculopathies) -- The Role of MR Spectroscopy -- The Spinal Cord in Leukodystrophies -- Pitfalls -- Conclusions -- The Future -- References -- Section II: Inherited disorders -- Chapter 4: Primary mitochondrial diseases -- Introduction -- Epidemiology -- Genetics -- Mitochondrial DNA -- Nuclear DNA -- Clinical Features -- Neurologic manifestations -- Nonneurologic manifestations -- Investigations -- Biochemical investigations in blood, urine, or cerebrospinal fluid -- Muscle pathology -- Respiratory chain enzyme analysis -- Molecular genetic testing -- Magnetic resonance imaging -- Magnetic resonance spectroscopy -- Cerebral White Matter Involvement -- Primary mitochondrial diseases caused by mitochondrial DNA mutations -- Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes -- Myoclonic epilepsy with ragged-red fibers -- Leber hereditary optic neuropathy -- Leigh syndrome -- Kearns-Sayre syndrome -- Primary mitochondrial diseases caused by nuclear DNA mutations -- Leigh syndrome -- Disorders of mitochondrial DNA maintenance -- POLG -- MPV17 -- TYMP. , Mitochondrial aminoacyl-tRNA synthetase disorders -- DARS2 -- EARS2 -- AARS 2 -- Management -- Genetic counseling -- Surveillance and pharmacologic treatments -- Conclusions -- References -- Chapter 5: Vanishing white matter -- History -- Clinical Manifestations -- Radiologic Manifestations -- Pathology -- Genetics -- Incidence and Prevalence -- Disease Models -- Physiologic Roles of eIF2B -- The role of eIF2B in translation initiation and protein synthesis -- Regulation of eIF2B activity -- Integrated stress response -- mRNA-specific translational control -- Pathophysiology of VWM -- Cellular mechanisms -- Molecular mechanisms underlying chronic neurologic decline -- Molecular mechanisms underlying (sub)acute episodic deterioration -- Biomarkers -- Treatment -- Molecular therapy -- Cell-based therapy -- Gene therapy -- Multimodal therapy -- Management -- Counseling -- Conclusion -- Acknowledgments -- References -- Chapter 6: Childhood-inherited white matter disorders with calcification -- Introduction -- Detection of calcification on neuroimaging -- Differential Diagnosis -- Type 1 Interferonopathies -- Aicardi-Goutières Syndrome -- Clinical features -- Clinical course -- Other clinical features -- Diagnosis -- Neuroimaging (Fig. 6.1) -- Other investigations -- Cerebrospinal fluid studies -- Interferon and interferon signature -- Molecular genetics -- TREX1 (AGS 1) -- RNASEH2A, B & -- C. (AGS2,3,4) -- SAMHD1 (AGS5) -- ADAR1 (AGS 6) -- IFIH1 (AGS7) -- LSM11, RNU7 (AGS 8 & -- 9) -- Pathology -- Pathogenesis -- Management -- Treatment -- Coats Plus (CP) and Leukoencephalopathy With Calcifications and Cysts (LCC) -- Coats Plus Disease -- Neuroimaging (Fig.6.3) (Linnankivi et al., 2006 -- Briggs et al., 2008 -- Livingston et al., 2012, 2014a) -- Pathology -- Molecular genetics -- Management of CP. , Leukoencephalopathy With Calcifications and Cysts (LCC) (Labrune Syndrome) -- Neuroimaging (Fig.6.3) (Livingston et al., 2014a, 2014c) -- Pathology -- Molecular genetics -- Management -- Cystic Leukoencephalopathy Without Macrocephaly (RNASET2 Mutation) -- Other Disorders Featuring Leukoencephalopathy and Calcification -- References -- Chapter 7: White matter disorders with cerebral calcification in adulthood -- Introduction -- Physiologic Cerebral Calcification -- Pathologic Cerebral Calcification -- Metabolic Causes of Leukodystrophies With Cerebral Calcification -- Leukoencephalopathies With Predominant Basal Ganglia Calcification -- Primary familial brain calcification -- Mitochondrial disorders -- Krabbe disease -- Other inherited conditions presenting with CC -- Leukoencephalopathies With Calcification and Cysts -- Coats Plus Disease and leukoencephalopathy with calcification and cysts -- Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia -- Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy -- Vascular Leukoencephalopathies Associated With Cranial Calcification -- COL4A1-related disorders -- Retinal vasculopathy with cerebral leukoencephalopathy -- Familial cerebral amyloid angiopathy -- Cerebral Calcification in Diseases Involving the Immune System -- Other Causes of Brain Calcification in Adults -- Vascular causes of cerebral calcifications -- Neurocutaneous syndromes -- Brain neoplasms -- Diagnostic Approaches -- Clinical and laboratory investigations -- Neuroimaging Evaluation -- Imaging modalities of choice -- Calcification patterns and localization -- Genetic Testing -- Management of Patients With Leukoencephalopathies and Calcifications -- Symptomatic treatment -- Underlying cause-specific approaches -- Genetic counseling -- Multidisciplinary care -- Conclusion -- References. , Chapter 8: Adrenoleukodystrophy -- Introduction -- Diagnosing adrenoleukodystrophy -- Clinical Features of Adrenoleukodystrophy -- Adrenal failure in ALD -- Testicular failure in ALD -- The leukodystrophy of ALD -- The spinal cord disease and peripheral neuropathy of ALD -- Treatment of ALD -- Prognosis of ALD -- Conclusions -- References -- Chapter 9: Peroxisomal leukodystrophy -- The Discovery of Peroxisomes -- Cell Biology and Biochemistry -- Clinical Features and Diagnosis of Specific Peroxisomal Disorders Associated with MRI Abnormalities -- Clinical features -- General principles of diagnosis for peroxisomal disorders -- Peroxisomal metabolic disorders and leukodystrophy -- X-linked adrenoleukodystrophy (ALD) -- Zellweger spectrum disorders (ZSD) -- D-bifunctional protein deficiency (DBP) and peroxisomal acyl-CoA oxidase 1 deficiency (ACOX1) -- Alpha-Methylacyl-CoA Racemase (AMACR) deficiency -- Other peroxisomal disorders -- Conclusion -- References -- Chapter 10: Lysosomal storage diseases -- Introduction -- Demyelinating Leukodystrophies -- Krabbe disease -- Clinical features -- Laboratory investigations -- Neuroimaging -- Metachromatic leukodystrophy -- Clinical features -- Laboratory investigations -- Neuroimaging -- Hypomyelinating Leukodystrophies -- Free sialic acid storage disorders -- Clinical features -- Laboratory investigations -- Neuroimaging -- Fucosidosis -- Clinical features -- Laboratory investigations -- Neuroimaging -- Mucolipidosis type IV -- Clinical features -- Laboratory investigations -- Neuroimaging -- Lysosomal Leukoencephalopathies -- GM1 gangliosidosis -- Clinical features -- Laboratory investigations -- Neuroimaging -- GM2 gangliosidosis -- Clinical features -- Laboratory investigations -- Neuroimaging -- Neuronal ceroid lipofuscinosis -- Clinical features -- Laboratory investigations -- Neuroimaging. , Mucopolysaccharidoses.

Language: English

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ISSN: 1526-632X

Content: Objective To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of replication factor complex subunit 1 (RFC1) repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). - Methods Multimodal RFC1 repeat screening (PCR, Southern blot, whole-exome/genome sequencing-based approaches) combined with cross-sectional and longitudinal deep phenotyping in (1) cross-European cohort A (70 families) with ≥2 features of CANVAS or ataxia with chronic cough (ACC) and (2) Turkish cohort B (105 families) with unselected late-onset ataxia. - Results Prevalence of RFC1 disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1 disease was also identified in Western and Eastern Asian individuals and even by whole-exome sequencing. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (〉90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea or dystonia (11%). Ataxia progression was ≈1.3 Scale for the Assessment and Rating of Ataxia points per year (32 cross-sectional, 17 longitudinal assessments, follow-up ≤9 years [mean 3.1 years]) but also included early falls, variable nonlinear phases of MSA-C-like progression (SARA points 2.5-5.5 per year), and premature death. Treatment trials require 330 (1-year trial) and 132 (2-year trial) patients in total to detect 50% reduced progression. - Conclusions RFC1 disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our natural history data help to inform future RFC1 treatment trials. - Classification of Evidence This study provides Class II evidence that RFC1 repeat expansions are associated with CANVAS and ACC.

In: Neurology, Philadelphia, Pa. : Wolters Kluwer, 1951, 96(2021), 9, Artikel-ID e1369-e1382, 1526-632X

In: volume:96

In: year:2021

In: number:9

In: elocationid:e1369-e1382

Language: English

DOI: 10.1212/WNL.0000000000011528

URL: Volltext  (lizenzpflichtig)

URL: Volltext  (lizenzpflichtig)

Author information: Traschütz, Andreas 1985-

Author information: Rujescu, Dan

Author information: Hartmann, Annette M. 1965-