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Hereditary and Metabolic Diseases of the Central Nervous System in Adults
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Other features useful in diagnosis include: Movement disorders (selected disorders presented in Table 10.8). Many genetic disorders display wide phenotypic variability, where different patients with the same disease may have different combinations of hyper- and hypokinetic movement symptoms. Therefore, the pattern of presentation, associated clinical features, and brain MRI findings can be very helpful in the initial diagnostic evaluation.Prominent white matter involvement (leukodystrophies) (selected disorders presented in Table 10.9). Disorders affecting white matter may be separated into leukodystrophies and leukoencephalopathies, or more recently, any genetic disorder with primary CNS white matter involvement may be considered a leukodystrophy. These can be classified based on the most affected cell type(s) (Table 10.9).7 Disorders of myelination can further be classified based on hypomyelination, demyelination, or myelin vacuolization. The pattern of involvement on MRI can help distinguish leukodystrophies.8The presence of eye findings (Table 10.10).
Adrenoleukodystrophy
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Neuroimaging by computed tomography (CT) or magnetic resonance imaging (MRI) [42–44] reveals evidence of leukodystrophy in the cerebral white matter (Figures 62.4–62.6). Temporal and parieto-occipital involvement are seen most frequently, but there may be widespread involvement, including the cerebellar white matter and the corticospinal tracts. Some patients have had cerebral atrophy. There are widespread symmetric, confluent, low-density lesions on CT or T1-weighted MRI or increased density on T2 in the periventricular white matter of the parieto-occipital areas that enhance anteriorly in the CT on infusion of contrast material. Repeated scans over time show a caudal–rostral progression of the demyelination. The enhancement with contrast reflects breakdown of the blood–brain barrier, and this is seen also on brain scintiscan, which shows increased uptake in the involved areas. In some patients, the lesions found on imaging the white matter have been the first clue to the diagnosis. In a few patients, atypical unilateral lesions have, along with (in one patient) symptomatology of unilateral headache, visual loss, weakness, and hyperreflexia, led to a diagnosis of brain tumor [45]. Biopsy revealed leukodystrophy, and that suggested the diagnosis. In asymptomatic patients at a mean age of 6.7 years, MRIs were normal and psychologic testing revealed normal cognitive function [46]. In 56 adult patients with white matter abnormalities, 42 had corticospinal disease, and 50 percent of these had progression of lesions over three to five years, but disease progression was slower than in affected children [47].
Genetic diseases mimicking multiple sclerosis
Published in Postgraduate Medicine, 2021
Chueh Lin Hsu, Piotr Iwanowski, Chueh Hsuan Hsu, Wojciech Kozubski
Metachromatic leukodystrophy (MLD) is caused by a mutation in the ARSA gene encoding arylsulfatase A, with subsequent buildup of sulfatides in both central and peripheral nervous systems. Sulfatides are most abundant and make up 4% of the sphingolipids of myelin. With a normal amount, they function to maintain myelin [140]. However, the accumulation of excess sulfatides results in demyelination, possibility due to the triggering of apoptosis [141]. MLD is classified into three subtypes based on the age of onset: late-infantile type, juvenile type, and adult type. Late- infantile and juvenile types are characterized by their rapidly progressive disease courses and are distinguished by the first signs of disorder with psychomotor regression and behavior abnormalities, respectively [142]. Genetic testing for mutational ARSA gene and PSAP gene is one of the reliable methods to diagnose MLD. However, a diagnosis should not be confirmed only based on the detection of mutations due to the incompleted identification of all the MLD associated mutations [143].
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies
Published in Expert Review of Neurotherapeutics, 2020
Mahmoud Reza Ashrafi, Man Amanat, Masoud Garshasbi, Reyhaneh Kameli, Yalda Nilipour, Morteza Heidari, Zahra Rezaei, Ali Reza Tavasoli
“Leukoencephalopathy” is a term used to describe all diseases with exclusive or predominant CNS white matter abnormalities and can be divided into inherited and acquired forms. Over 100 inherited leukoencephalopathies were described (Supplemental Table 1). These conditions can be split into leukodystrophies and genetic leukoencephalopathies [10]. As leukodystrophies primarily affect CNS white matter; genetic leukoencephalopathies are systemic disorders with white matter involvement as their secondary findings. Since both groups have genetic etiology in nature, the differences can be attributed to the cell metabolic dysfunctions and the cardinal clinical symptoms of affected individuals due to a specified genetic defect [11,12]. Determining the type of heritable disorders with white matter involvement (especially the recent described ones) can sometimes be challenging based on their broad features and our limited knowledge about their pathophysiologic mechanisms. Furthermore, new categorizations are essential due to the overwhelming increase in number of inherited leukoencephalopathies. In fact, the current classification is fading away and “leukodystrophy” is used instead of “genetic leukoencephalopathy” in most recent studies [4].
An overview of the pharmacotherapeutics for dystonia: advances over the past decade
Published in Expert Opinion on Pharmacotherapy, 2022
O. Abu-hadid, J. Jimenez-Shahed
Robust research that associates impairments in the noradrenergic system with dystonia is absent. Nevertheless, clonidine has been shown to be helpful in the management of secondary dystonia as well as dystonic storms, specifically in the pediatric population. A case report shows that using clonidine via the subcutaneous or transdermal route was helpful in providing comfort for a patient with end-stage leukodystrophy who was in a pre-status dystonicus state [103]. A retrospective case series observed 24 children and young people with dystonia who received clonidine as an add-on therapy [104]. The study shows some improvement in the gross motor function classification scale, but no statistical analysis was done [104].