DOCSLIB.ORG

A Practical Approach to Diagnosing Adult Onset Leukodystrophies

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Practical Approach to Diagnosing Adult Onset Leukodystrophies Downloaded from jnnp.bmj.com on September 2, 2014 - Published by group.bmj.com Multiple sclerosis REVIEW A practical approach to diagnosing adult onset leukodystrophies Editor’s choice Scan to access more free content R M Ahmed,1 E Murphy,2 I Davagnanam,3 M Parton,4 J M Schott,1 C J Mummery,1 J D Rohrer,1 R H Lachmann,2 H Houlden,5 N C Fox,1 J Chataway6 ▸ Additional material is INTRODUCTION CASE STUDY published online only. To view The term leukodystrophy refers to a group of condi- A middle aged patient presented to an MS clinic please visit the journal online tions that are inherited and involve the progressive with a 2-year history of progressive gait and cogni- (http://dx.doi.org/10.1136/ 1 jnnp-2013-305888). destruction or loss of previously acquired myelin. tive difficulties. Two years earlier, the patient had The most commonly reported of these disorders noted dragging of the right leg, difficulty control- For numbered affiliations see end of article. have a metabolic origin and are associated with ling the leg and had had several falls. One year abnormalities on specialist biochemical testing. prior, clumsiness and weakness in the right hand Correspondence to Recently, a number of conditions caused by genes had been noted, as well as word finding difficulties, Dr J Chataway, Department of coding for proteins not directly involved in meta- slowness of thought, problems with episodic Neuroinflammation, Queen Square Multiple Sclerosis Centre, bolic pathways and for which the diagnosis relies memory and that their writing and spelling had National Hospital for Neurology directly on gene analysis have also been described. deteriorated. The patient had a past history of sciat- & Neurosurgery and University In clinical practice, distinguishing ‘classical’ inher- ica and long standing depression. The patient’s College London Institute of ited leukodystrophies from other causes of white mother had died at 65 years of age after a 5-year Neurology, Queen Square, matter disease, including vascular and inflammatory decline in gait and cognitive function, with MRI London WC1N 3BG, UK; [email protected] disorders, may not always be straightforward. brain showing generalised cerebral atrophy and Although individually rare, with no single condi- patchy signal change in the peri-ventricular white Received 19 September 2013 tion having a prevalence of >1 in 20 000, the matter. The mother had been given a diagnosis of Revised 4 November 2013 reported prevalence of adult onset leukodystrophies vascular dementia. There was no other family Accepted 19 November 2013 Published Online First is rising. This is likely to be related to the increased history of neurological or psychiatric illness. 19 December 2013 use of brain MRI and new genetic insights. On examination, the patient had broken smooth Collectively their incidence may rival that of mul- pursuit eye movements and hypometric saccades. tiple sclerosis (MS).2 Nonetheless, the rarity of The cranial nerves were intact. The upper limb each condition and the wide differential means that examination was normal. The lower limb examin- diagnosis can be challenging and most clinicians ation showed increased tone and power of 4/5 on will lack experience in the area. Currently, a signifi- the right, with a pyramidal pattern of weakness. cant proportion of individuals may remain without The reflexes were brisk throughout, with equivocal a precise diagnosis despite intensive investigations. plantar responses. The gait was apraxic. On cogni- Much has been written in the paediatric litera- tive testing she scored 22/30 on the Mini-Mental ture about leukodystrophies,3 but the adult neur- State Examination. On neuropsychometric testing, ologist, with a new case, is often left with an there was evidence for generalised cognitive decline extensive and detailed table of rare disorders to with marked impairments on tests sensitive to consider, without an obvious diagnostic pathway to frontal and parietal lobe functions. follow. In addition, leukodystrophies that classically MRI brain (see online supplementary figure S1) present in infancy or childhood may have a very showed extensive white matter change predomin- different or attenuated clinical presentation in antly affecting the frontal lobes with involvement adulthood, making diagnostic features less familiar. and thinning of the corpus callosum. In this review, taking a clinical case as a starting point, we address: ▸ the most commonly presenting leukodystrophies in adults What is the differential diagnosis and which ▸ their clinical presentations initial investigations should be performed? ▸ MRI patterns for specific leukodystrophies With this symptom complex and widespread white ▸ how to investigate leukodystrophies in an adult matter change on MRI, there are a number of ▸ current and future treatment possibilities. acquired conditions that need to be excluded before Table 1 summarises the most frequent of the an inherited leukodystrophy is considered. These inherited leukodystrophies that have been reported include inflammatory, autoimmune, infectious, neo- to present in adulthood (age of onset of plastic, metabolic, drug and toxic causes. Suggested >16 years). This list is not exhaustive and almost initial (Round 1) investigations are outlined in To cite: Ahmed RM, — Murphy E, Davagnanam I, certainly underestimates the true numbers with online supplementary table S1. A very rapid onset et al. J Neurol Neurosurg more widespread access to genetic testing it is likely and progression over months is much more likely Psychiatry 2014;85: that the list of potential diagnoses and actual preva- to be acquired than genetic, though cerebral adre- – 770 781. lences will continue to increase. noleukodystrophy (ALD) can present abruptly. 770 Ahmed RM, et al. J Neurol Neurosurg Psychiatry 2014;85:770–781. doi:10.1136/jnnp-2013-305888 Ahmed RM, Table 1 Leukodystrophies presenting in adulthood Disorder Age of onset Prevalence of adult disease Ethnic predilection Inheritance Useful investigation(s) Gene(s) et al X linked adrenoleukodystrophy Childhood to adulthood Up to 40/million, adult cerebral ALD X linked. Female Very long chain fatty acid levels ABCD1 . – J Neurol Neurosurg Psychiatry adrenomyeloneuropathy (ALD/ accounts for 5% of cases; 15% 20% of carriers can develop AMN)45 heterozygote women are symptomatic AMN/spastic paraparesis Cerebral autosomal dominant Migraine: mean 30 years 10–40/million AD and sporadic Electron microscopy of skin biopsy NOTCH3 arteriopathy with subcortical infarcts (range 6–48 years). and leukoencephalopathy Ischaemic events: mean Downloaded from (CADASIL)67* 50 years (range 20– 70 years) Globoid cell leukodystrophy (Krabbe Up to 60 years 10/million, 10% adult onset AR Galactocerebrosidase (GALC) enzyme activity GALC; disease)89 (leukocytes/fibroblasts) PSAP 2014; Metachromatic leukodystrophy Up to 70 years 2/million, 20% adult onset AR Arylsulfatase A (ARSA) enzyme activity ARSA; (MLD)10 (leukocytes/fibroblasts)† PSAP 85 jnnp.bmj.com :770 Cerebrotendinous xanthomatosis Juvenile to adulthood 2/million AR Sterol profile. Urine bile alcohols CYP27A1 (CTX)811 – 781. doi:10.1136/jnnp-2013-305888– 771 Mitochondrial disorders12 14* Childhood and adulthood Total prevalence 100–165/million, Maternal, AD, AR Lactate (blood/CSF). Mitochondrial respiratory Various —any age prevalence of leukoencephalopathy in chain enzyme activity adults is not known, paediatric literature suggests it is common onSeptember2,2014-Publishedby Hereditary diffuse Mean 40 years (range 15– 52 cases described in literature, AD and sporadic Characteristic brain biopsy findings (now CSFR1 leukoencephalopathy with 78 years) incidence increasing with recent superseded by molecular genetic testing) neuroaxonal spheroids (HDLS)15 discovery of CSF1R gene Adult polyglucosan body disease 40–60 years 47 cases Ashkenazi Jewish AR Sural nerve biopsy. Glycogen brancher enzyme GBE1 (APBD)16 (GBE) activity (fibroblasts) Alexander disease17 12–62 years 36 cases AD and sporadic Characteristic brain biopsy findings (now GFAP superseded by molecular genetic testing) Adult onset autosomal dominant 30–50 years Unknown: at least 27 cases reported in AD LMNB1 leukodystrophy (ADLD)18 19 literature Vanishing white matter disease Mean 30 years (range 16– 177 cases in total, 25 with onset AR eIF2B 1–5 (VWM)20 62 years) >16 years Cerebral autosomal recessive 20–50 years Unknown, thought to be rare, 50 cases Most reported cases in Japan AR On brain pathology, CARASIL is characterised by HTRA1 arteriopathy with subcortical infarcts described thus far and China intense arteriolosclerosis without the deposition and leukoencephalopathy of granular osmiophilic materials in small arteries group.bmj.com (CARASIL)21* and arterioles that is seen in CADASIL Hexosaminidase A (HEX A) deficiency 20–40 years Small case series 64% Jewish origin AR β-HEX A enzymatic activity (leukocytes) HEXA (GM2 gangliosidosis, adult onset Tay–Sachs disease)22 Megalencephalic 6 months–50 years 11 cases aged >20 years Asian-Indian, Turkish AR MLC1; leukoencephalopathy with subcortical HEPACAM cysts (MLC)23 Multiple sclerosis MTHFR deficiency24 Any age Limited case reports AR Plasma amino acid profile MTHFR α-Mannosidosis25 Adolescence, but severe Limited case reports AR Urine oligosaccharides. Vacuolated lymphocytes. MAN2B1 ataxia 30–40 years α-Mannosidase enzyme activity (leukocytes) Mucolipidosis type IV826 Usually infant childhood, 1 Late onset reported due to attenuated Ashkenazi Jewish AR MCOLN1 case onset 16 years14
Load more

Recommended publications
  • Adult Onset) an Information Sheet for the Person Who Has Been Diagnosed with a Leukodystrophy, Their Family, and Friends
    Leukodystrophy (Adult Onset) An information sheet for the person who has been diagnosed with a leukodystrophy, their family, and friends. ‘Leukodystrophy’ and the related term ‘leukoencephalopathy’ The person may notice they trip more easily, particularly on refer to a group of conditions that affect the myelin, or white uneven ground or steps. matter, of the brain and spinal cord. Other symptoms that people with adult-onset Leukodystrophies are neurological, degenerative disorders, leukodystrophy may experience include: sensitivity to and most are genetic. This means that a person’s condition extremes of temperature, such as difficulty tolerating hot is caused by a change to one of the genes that are involved summer weather; pain or abnormal sensation, particularly in in the development of myelin, leading to deterioration in the legs; shaking or tremors; loss of vision and/or hearing; many of the body’s neurological functions. The pattern headaches, and difficulty with coordination. of symptoms varies from one type of leukodystrophy to People with leukodystrophy often experience long delays another, and there may even be some variation between before receiving a correct diagnosis. This is partly because different people with the same condition, however all are the symptoms can be quite vague and associated with described as progressive. This means that although there many different disorders. Leukodystrophies are rare, and may be periods of stability, the condition doesn’t go into it is routine medical practice to rule out more common and ‘remission’ as may be seen in some other neurological treatable causes before testing for rarer conditions. There conditions, and over time the condition worsens.
    [Show full text]
  • Child Neurology: Hereditary Spastic Paraplegia in Children S.T
    RESIDENT & FELLOW SECTION Child Neurology: Section Editor Hereditary spastic paraplegia in children Mitchell S.V. Elkind, MD, MS S.T. de Bot, MD Because the medical literature on hereditary spastic clinical feature is progressive lower limb spasticity B.P.C. van de paraplegia (HSP) is dominated by descriptions of secondary to pyramidal tract dysfunction. HSP is Warrenburg, MD, adult case series, there is less emphasis on the genetic classified as pure if neurologic signs are limited to the PhD evaluation in suspected pediatric cases of HSP. The lower limbs (although urinary urgency and mild im- H.P.H. Kremer, differential diagnosis of progressive spastic paraplegia pairment of vibration perception in the distal lower MD, PhD strongly depends on the age at onset, as well as the ac- extremities may occur). In contrast, complicated M.A.A.P. Willemsen, companying clinical features, possible abnormalities on forms of HSP display additional neurologic and MRI abnormalities such as ataxia, more significant periph- MD, PhD MRI, and family history. In order to develop a rational eral neuropathy, mental retardation, or a thin corpus diagnostic strategy for pediatric HSP cases, we per- callosum. HSP may be inherited as an autosomal formed a literature search focusing on presenting signs Address correspondence and dominant, autosomal recessive, or X-linked disease. reprint requests to Dr. S.T. de and symptoms, age at onset, and genotype. We present Over 40 loci and nearly 20 genes have already been Bot, Radboud University a case of a young boy with a REEP1 (SPG31) mutation. Nijmegen Medical Centre, identified.1 Autosomal dominant transmission is ob- Department of Neurology, PO served in 70% to 80% of all cases and typically re- Box 9101, 6500 HB, Nijmegen, CASE REPORT A 4-year-old boy presented with 2 the Netherlands progressive walking difficulties from the time he sults in pure HSP.
    [Show full text]
  • Hereditary Spastic Paraparesis: a Review of New Developments
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.69.2.150 on 1 August 2000. Downloaded from 150 J Neurol Neurosurg Psychiatry 2000;69:150–160 REVIEW Hereditary spastic paraparesis: a review of new developments CJ McDermott, K White, K Bushby, PJ Shaw Hereditary spastic paraparesis (HSP) or the reditary spastic paraparesis will no doubt Strümpell-Lorrain syndrome is the name given provide a more useful and relevant classifi- to a heterogeneous group of inherited disorders cation. in which the main clinical feature is progressive lower limb spasticity. Before the advent of Epidemiology molecular genetic studies into these disorders, The prevalence of HSP varies in diVerent several classifications had been proposed, studies. Such variation is probably due to a based on the mode of inheritance, the age of combination of diVering diagnostic criteria, onset of symptoms, and the presence or other- variable epidemiological methodology, and wise of additional clinical features. Families geographical factors. Some studies in which with autosomal dominant, autosomal recessive, similar criteria and methods were employed and X-linked inheritance have been described. found the prevalance of HSP/100 000 to be 2.7 in Molise Italy, 4.3 in Valle d’Aosta Italy, and 10–12 Historical aspects 2.0 in Portugal. These studies employed the In 1880 Strümpell published what is consid- diagnostic criteria suggested by Harding and ered to be the first clear description of HSP.He utilised all health institutions and various reported a family in which two brothers were health care professionals in ascertaining cases aVected by spastic paraplegia. The father was from the specific region.
    [Show full text]
  • Autosomal Dominant Leukodystrophy with Autonomic Symptoms
    List of Papers This thesis is based on the following papers, which are referred to in the text by their Roman numerals. I MR imaging characteristics and neuropathology of the spin- al cord in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. Sundblom J, Melberg A, Kalimo H, Smits A, Raininko R. AJNR Am J Neuroradiol. 2009 Feb;30(2):328-35. II Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms. Schuster J, Sundblom J, Thuresson AC, Hassin-Baer S, Klopstock T, Dichgans M, Cohen OS, Raininko R, Melberg A, Dahl N. Neurogenetics. 2011 Feb;12(1):65-72. III Bedside diagnosis of rippling muscle disease in CAV3 p.A46T mutation carriers. Sundblom J, Stålberg E, Osterdahl M, Rücker F, Montelius M, Kalimo H, Nennesmo I, Islander G, Smits A, Dahl N, Melberg A. Muscle Nerve. 2010 Jun;41(6):751-7. IV A family with discordance between Malignant hyperthermia susceptibility and Rippling muscle disease. Sundblom J, Mel- berg A, Rücker F, Smits A, Islander G. Manuscript submitted to Journal of Anesthesia. Reprints were made with permission from the respective publishers. Contents Introduction..................................................................................................11 Background and history............................................................................... 13 Early studies of hereditary disease...........................................................13 Darwin and Mendel................................................................................
    [Show full text]
  • Hereditary Spastic Paraplegias
    Hereditary Spastic Paraplegias Authors: Doctors Enza Maria Valente1 and Marco Seri2 Creation date: January 2003 Update: April 2004 Scientific Editor: Doctor Franco Taroni 1Neurogenetics Istituto CSS Mendel, Viale Regina Margherita 261, 00198 Roma, Italy. e.valente@css- mendel.it 2Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, Università degli studi di Bologna, Laboratorio di Genetica Medica, Policlinico S.Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy.mailto:[email protected] Abstract Keywords Disease name and synonyms Definition Classification Differential diagnosis Prevalence Clinical description Management including treatment Diagnostic methods Etiology Genetic counseling Antenatal diagnosis References Abstract Hereditary spastic paraplegias (HSP) comprise a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and hyperreflexia of the lower limbs. Clinically, HSPs can be divided into two main groups: pure and complex forms. Pure HSPs are characterized by slowly progressive lower extremity spasticity and weakness, often associated with hypertonic urinary disturbances, mild reduction of lower extremity vibration sense, and, occasionally, of joint position sensation. Complex HSP forms are characterized by the presence of additional neurological or non-neurological features. Pure HSP is estimated to affect 9.6 individuals in 100.000. HSP may be inherited as an autosomal dominant, autosomal recessive or X-linked recessive trait, and multiple recessive and dominant forms exist. The majority of reported families (70-80%) displays autosomal dominant inheritance, while the remaining cases follow a recessive mode of transmission. To date, 24 different loci responsible for pure and complex HSP have been mapped. Despite the large and increasing number of HSP loci mapped, only 9 autosomal and 2 X-linked genes have been so far identified, and a clear genetic basis for most forms of HSP remains to be elucidated.
    [Show full text]
  • Blueprint Genetics Leukodystrophy and Leukoencephalopathy Panel
    Leukodystrophy and Leukoencephalopathy Panel Test code: NE2001 Is a 118 gene panel that includes assessment of non-coding variants. In addition, it also includes the maternally inherited mitochondrial genome. Is ideal for patients with a clinical suspicion of leukodystrophy or leukoencephalopathy. The genes on this panel are included on the Comprehensive Epilepsy Panel. About Leukodystrophy and Leukoencephalopathy Leukodystrophies are heritable myelin disorders affecting the white matter of the central nervous system with or without peripheral nervous system myelin involvement. Leukodystrophies with an identified genetic cause may be inherited in an autosomal dominant, an autosomal recessive or an X-linked recessive manner. Genetic leukoencephalopathy is heritable and results in white matter abnormalities but does not necessarily meet the strict criteria of a leukodystrophy (PubMed: 25649058). The mainstay of diagnosis of leukodystrophy and leukoencephalopathy is neuroimaging. However, the exact diagnosis is difficult as phenotypes are variable and distinct clinical presentation can be present within the same family. Genetic testing is leading to an expansion of the phenotypic spectrum of the leukodystrophies/encephalopathies. These findings underscore the critical importance of genetic testing for establishing a clinical and pathological diagnosis. Availability 4 weeks Gene Set Description Genes in the Leukodystrophy and Leukoencephalopathy Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ABCD1*
    [Show full text]
  • Acute Disseminated Encephalomyelitis: Treatment Guidelines
    [Downloaded free from http://www.annalsofian.org on Monday, February 06, 2012, IP: 115.113.56.227] || Click here to download free Android application for this journal S60 Acute disseminated encephalomyelitis: Treatment guidelines Alexander M., J. M. K. Murthy1 Department of Neurological Sciences, Christian Medical College, Vellore, 1The Institute of Neurological Sciences, CARE Hospital, Hyderabad, India For correspondence: Dr. Alexander Mathew, Professor of Neurology, Department of Neurological Sciences, Christian Medical College, Vellore, Tamil Nadu, India Annals of Indian Academy of Neurology 2011;14:60-4 Introduction of intracranial space occupying lesion, with tumefactive demyelinating lesions.[ 13-17] Acute disseminated encephalomyelitis (ADEM) is a monophasic, postinfectious or postvaccineal acute infl ammatory Certain clinical presentations may be specifi c with certain demyelinating disorder of central nervous system (CNS).[1,2] The infections: cerebellar ataxia for varicella infection, myelitis pathophysiology involves transient autoimmune response for mumps, myeloradiculopathy for Semple antirabies vaccination, and explosive onset with seizures and mild directed at myelin or other self-antigens, possibly by molecular [18,19] mimicry or by nonspecifi c activation of autoreactive T-cell pyramidal dysfunction for rubella. Acute hemorrhagic clones.[3] Histologically, ADEM is characterized by perivenous leukoencephalitis and acute necrotizing hemorrhagic leukoencephalitis of Weston Hurst represent the hyperacute, demyelination and infi ltration of vessel wall and perivascular [20] spaces by lymphocytes, plasma cells, and monocytes.[4] fulminant form of postinfectious demyelination. Diagnosis The annual incidence of ADEM is reported to be 0.4–0.8 per 100,000 and the disease more commonly affects children Cerebrospinal fl uid (CSF) is abnormal in about two-thirds and young adults, probably related to the high frequency of of patients and shows a moderate pleocytosis with raised exanthematous and other infections and vaccination in this age proteins.
    [Show full text]
  • Childhood Neurological Conditions and Disorders
    Childhood neurological conditions and disorders Please note: We do include rare conditions. If your one is not in the list below we will still consider your survey responses. Epilepsies Autosomal dominant epilepsy with auditory features (ADEAF) Autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) Benign epilepsy with centrotemporal spikes (BECTS) Benign familial infantile epilepsy Benign familial neonatal epilepsy (BFNE) Benign infantile epilepsy Benign neonatal seizures (BNS) Childhood absence epilepsy (CAE) Cyclin Dependent Kinase-Like 5 (CDKL5) Deficiency Disorder Dravet syndrome Early myoclonic encephalopathy (EME) Epilepsy of infancy with migrating focal seizures Epilepsy with generalized tonic–clonic seizures alone Epilepsy with myoclonic absences Epilepsy with myoclonic atonic (previously astatic) seizures Epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS) Familial focal epilepsy with variable foci (childhood to adult) Febrile seizures (FS) Febrile seizures plus (FS+) (can start in infancy) Gelastic seizures with hypothalamic hamartoma Hemiconvulsion–hemiplegia–epilepsy Juvenile absence epilepsy (JAE) Juvenile myoclonic epilepsy (JME) Landau-Kleffner syndrome (LKS) Late onset childhood occipital epilepsy (Gastaut type) Lennox-Gastaut syndrome Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE with HS) Myoclonic epilepsy in infancy (MEI) Ohtahara syndrome Panayiotopoulos syndrome Photosensitive absence epilepsies including Jeavons syndrome, Sunflower syndrome Progressive myoclonus epilepsies
    [Show full text]
  • Late Onset Globoid Cell Leukodystrophy Patient's Late Onset (At Age 14
    980 Matters arising can not only show "some abnormality that 6 Mas JL, Henin D, Bousser MG, Chain F, Hauw 1 Hinse P, Thie A, L. Dissection of Lachenmayer J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.55.10.980-b on 1 October 1992. Downloaded from encourages angiographic examination" but JJ. Dissecting aneurysm ofthe vertebral artery the extracranial vertebral artery: report of and cervical manipulation: a case report with four cases and review of the literature. Jf can also diagnose dissections involving the autopsy. Neurology 1989;39:512-5. Neurol Neurosurg Psychiatry 199 1;54:863-9. pretransverse, C6-C5 and C5-C4 intertrans- 7 D'Anglejan-Chatillon J, Ribeiro V, Mas JL, Youl 2 Mokri B, Houser OW, Sandok BA, Piepgras verse segments of the VA.5 The diagnosis is BD, Bousser MG. Migraine-A risk factor for DG. Spontaneous dissections of the vertebral dissections of cervical arteries. Headache arteries. Neurology 1988;38:880-5. based on the association of a localised 1989;29:560-1. 3 Mas JL, Bousser MG, Hasboun D, Laplane D. increase in arterial diameter with haemody- Extracranial vertebral artery dissections: a namic signs of stenosis or occlusion and/or review of 13 cases. Stroke 1987;18:1037-47. decreased pulsatility and intravascular echoes Hinse and Thie reply: 4 Mokri B. Traumatic and spontaneous extrac- ranial internal carotid artery dissections. J at the same level. Furthermore, ultrasonic We thank Dr Mas and colleagues for their Neurol 1990;237:356-61. examination is an excellent tool for the follow interest in our recent paper,' and we appre- 5 Touboul PJ, Mas JL, Bousser MG, Laplane D.
    [Show full text]
  • Leukodystrophies by Raphael Schiffmann MD (Dr
    Leukodystrophies By Raphael Schiffmann MD (Dr. Schiffmann, Director of the Institute of Metabolic Disease at Baylor Research Institute, received research grants from Amicus Therapeutics, Protalix Biotherapeutics, and Shire.) Originally released January 17, 2013; last updated November 25, 2016; expires November 25, 2019 Introduction Overview Leukodystrophies are a heterogeneous group of genetic disorders affecting the white matter of the central nervous system and sometimes with peripheral nervous system involvement. There are over 30 different leukodystrophies, with an overall population incidence of 1 in 7663 live births. They are now most commonly grouped based on the initial pattern of central nervous system white matter abnormalities on neuroimaging. All leukodystrophies have MRI hyperintense white matter on T2-weighted images, whereas T1 signal may be variable. Mildly hypo-, iso-, or hyperintense T1 signal relative to the cortex suggests a hypomyelinating pattern. A significantly hypointense T1 signal is more often associated with demyelination or other pathologies. Recognition of the abnormal MRI pattern in leukodystrophies greatly facilitates its diagnosis. Early diagnosis is important for genetic counseling and appropriate therapy where available. Key points • Leukodystrophies are classically defined as progressive genetic disorders that predominantly affect the white matter of the brain. • The pattern of abnormalities on brain MRI, and sometimes brain CT, is the most useful diagnostic tool. • Radial diffusivity on brain diffusion weighted imaging correlates with motor handicap. • X-linked adrenoleukodystrophy is the most common leukodystrophy and has effective therapy if applied early in the disease course. • Lentiviral hemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy shows promise. Historical note and terminology The first leukodystrophies were identified early last century.
    [Show full text]
  • Late-Onset Leukodystrophy Mimicking Hereditary Spastic Paraplegia Without Diffuse Leukodystrophy on Neuroimaging
    Neuropsychiatric Disease and Treatment Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Late-Onset Leukodystrophy Mimicking Hereditary Spastic Paraplegia without Diffuse Leukodystrophy on Neuroimaging Tongxia Zhang1,2 Purpose: Leukodystrophies are frequently regarded as childhood disorders, but they can Chuanzhu Yan1,3 occur at any age, and the clinical and imaging patterns of the adult-onset form are usually Yiming Liu1 different from the better-known childhood variants. Several reports have shown that various Lili Cao1 late-onset leukodystrophies, such as X-linked adrenoleukodystrophy and Krabbe disease, Kunqian Ji1 may present as spastic paraplegia with the absence of the characteristic white matter lesions on neuroimaging; this can be easily misdiagnosed as hereditary spastic paraplegia. The Duoling Li1 objective of this study was to investigate the frequency of late-onset leukodystrophies in Lingyi Chi2,4,5 1 patients with spastic paraplegia. Yuying Zhao Patients and Methods: We performed genetic analysis using a custom-designed gene 1Research Institute of Neuromuscular and panel for leukodystrophies in 112 hereditary spastic paraplegia-like patients. Neurodegenerative Diseases and Results: We identified pathogenic mutations in 13 out of 112 patients, including five patients Department of Neurology, Qilu Hospital, Shandong University, Jinan, People’s Republic with adrenomyeloneuropathy, three with Krabbe disease, three with Alexander disease, and of China; 2School of Basic Medical
    [Show full text]
  • Migraine and Stroke
    Open Access Review Stroke Vasc Neurol: first published as 10.1136/svn-2017-000077 on 29 May 2017. Downloaded from Migraine and stroke Yonghua Zhang,1 Aasheeta Parikh,1 Shuo Qian2 To cite: Zhang Y, Parikh A, ABSTRACT association between ischaemic stroke and Qian S. Migraine and stroke. Migraines are generally considered a relatively benign migraine with aura, especially in younger Stroke and Vascular Neurology neurological condition. However, research has shown an (age ≤45 years) women, is already estab- 2017;2: e000077. doi:10.1136/ association between migraines and stroke, and especially 5–8 svn-2017-000077 lished and well accepted, but there is still between migraine with aura and ischaemic stroke. Patients uncertainty with respect to its mechanisms, can also suffer from migrainous infarction, a subset correlation between stroke and migraine of ischaemic stroke that often occurs in the posterior Received 7 February 2017 without aura, management, prophylaxis Revised 6 April 2017 circulation of younger women. The exact pathogenesis Accepted 9 April 2017 of migrainous infarct is not known, but it is theorised in clinical practice and so on. However, that the duration and local neuronal energy level from these two conditions are known to have in cortical spreading depression may be a key factor. Other common the following: (1) pathogenesis, factors contributing to migrainous infarct may include (2) risk factors and (3) clinical and imaging vascular, inflammatory, endothelial structure, patent manifestation. foramen ovale, gender, oral contraceptive pill use and In this review, we will discuss epidemi- smoking. Vasoconstrictors such as the triptan and ergot ology, possible mechanisms, advanced class are commonly used to treat migraines and may also genetic findings and clinical management play a role.
    [Show full text]