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Diffuse demyelination of the cerebral white matter

MedGen UID:
870483
Concept ID:
C4024930
Anatomical Abnormality
HPO: HP:0007162

Definition

A diffuse loss of myelin from nerve fibers in the central nervous system. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDiffuse demyelination of the cerebral white matter

Conditions with this feature

Alexander disease
MedGen UID:
78724
Concept ID:
C0270726
Disease or Syndrome
Alexander disease, a progressive disorder of cerebral white matter caused by a heterozygous GFAP pathogenic variant, comprises a continuous clinical spectrum most recognizable in infants and children and a range of nonspecific neurologic manifestations in adults. This chapter discusses the spectrum of Alexander disease as four forms: neonatal, infantile, juvenile, and adult. The neonatal form begins in the first 30 days after birth with neurologic findings (e.g., hypotonia, hyperexcitability, myoclonus) and/or gastrointestinal manifestations (e.g., gastroesophageal reflux, vomiting, failure to thrive), followed by severe developmental delay and regression, seizures, megalencephaly, and typically death within two years. The infantile form is characterized by variable developmental issues: initially some have delayed or plateauing of acquisition of new skills, followed in some by a loss of gross and fine motor skills and language during in the first decade or in others a slow disease course that spans decades. Seizures, often triggered by illness, may be less frequent/severe than in the neonatal form. The juvenile form typically presents in childhood or adolescence with clinical and imaging features that overlap with the other forms. Manifestations in early childhood are milder than those in the infantile form (e.g., mild language delay may be the only developmental abnormality or, with language acquisition, hypophonia or nasal speech may alter the voice, often prior to appearance of other neurologic features). Vomiting and failure to thrive as well as scoliosis and autonomic dysfunction are common. The adult form is typically characterized by bulbar or pseudobulbar findings (palatal myoclonus, dysphagia, dysphonia, dysarthria or slurred speech), motor/gait abnormalities with pyramidal tract signs (spasticity, hyperreflexia, positive Babinski sign), or cerebellar abnormalities (ataxia, nystagmus, or dysmetria). Others may have hemiparesis or hemiplegia with a relapsing/remitting course or slowly progressive quadriparesis or quadriplegia. Other neurologic features can include sleep apnea, diplopia or disorders of extraocular motility, and autonomic dysfunction.
CARASIL syndrome
MedGen UID:
325051
Concept ID:
C1838577
Disease or Syndrome
HTRA1 disorder is a phenotypic spectrum in which some individuals have few to no symptoms and others manifest with the more severe CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy) phenotype. Those who have a heterozygous HTRA1 pathogenic variant may have mild neurologic findings (sometimes identified only on neuroimaging) or mild-to-moderate neurologic signs and symptoms of CARASIL. In this chapter, the term "classic CARASIL" refers to the more severe phenotype associated with biallelic pathogenic variants, and "HTRA1 cerebral small vessel disease" (HTRA1-CSVD) refers to the milder phenotype associated with a heterozygous HTRA1 pathogenic variant. Classic CARASIL is characterized by early-onset changes in the deep white matter of the brain observed on MRI, and associated neurologic findings. The most frequent initial symptom is gait disturbance from spasticity beginning between ages 20 and 40 years. Forty-four percent of affected individuals have stroke-like episodes before age 40 years. Mood changes (apathy and irritability), pseudobulbar palsy, and cognitive dysfunction begin between ages 20 and 50 years. The disease progresses slowly following the onset of neurologic symptoms. Scalp alopecia and acute mid- to lower-back pain (lumbago) before age 30 years are characteristic. The most frequent initial symptom in individuals with HTRA1-CSVD is slowly progressive gait disturbance after age 40 years, which may be followed by the development of mood changes and cognitive dysfunction. A majority of affected individuals have a stroke-like episode after age 40 years. Spondylosis and alopecia are seen in a minority of individuals with HTRA1-CSVD.

Professional guidelines

PubMed

Lehto J, Nylund M, Matilainen M, Sucksdorff M, Vuorimaa A, Rajander J, Wahlroos S, Hariri P, Airas L
Eur J Neurol 2023 Aug;30(8):2365-2375. Epub 2023 May 23 doi: 10.1111/ene.15834. PMID: 37154404
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J Infect 2009 May;58(5):321-8. Epub 2009 Apr 14 doi: 10.1016/j.jinf.2009.02.011. PMID: 19368974Free PMC Article

Recent clinical studies

Etiology

Tonduti D, Zambon AA, Ghezzi D, Lamantea E, Izzo R, Parazzini C, Baldoli C, van der Knaap MS, Fumagalli F
Neuropediatrics 2023 Jun;54(3):161-166. Epub 2023 Mar 3 doi: 10.1055/s-0043-1764214. PMID: 36868263
Carotenuto A, Cacciaguerra L, Pagani E, Preziosa P, Filippi M, Rocca MA
Brain 2022 Aug 27;145(8):2785-2795. doi: 10.1093/brain/awab454. PMID: 34919648
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Bells S, Lefebvre J, Longoni G, Narayanan S, Arnold DL, Yeh EA, Mabbott DJ
Glia 2019 Nov;67(11):2020-2037. Epub 2019 Jun 24 doi: 10.1002/glia.23661. PMID: 31233643
Kuhlmann T, Ludwin S, Prat A, Antel J, Brück W, Lassmann H
Acta Neuropathol 2017 Jan;133(1):13-24. Epub 2016 Dec 17 doi: 10.1007/s00401-016-1653-y. PMID: 27988845

Diagnosis

Tonduti D, Zambon AA, Ghezzi D, Lamantea E, Izzo R, Parazzini C, Baldoli C, van der Knaap MS, Fumagalli F
Neuropediatrics 2023 Jun;54(3):161-166. Epub 2023 Mar 3 doi: 10.1055/s-0043-1764214. PMID: 36868263
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Bells S, Lefebvre J, Longoni G, Narayanan S, Arnold DL, Yeh EA, Mabbott DJ
Glia 2019 Nov;67(11):2020-2037. Epub 2019 Jun 24 doi: 10.1002/glia.23661. PMID: 31233643
Hardy TA, Miller DH
Lancet Neurol 2014 Jul;13(7):740-6. doi: 10.1016/S1474-4422(14)70052-3. PMID: 24943346
Miller DH, Leary SM
Lancet Neurol 2007 Oct;6(10):903-12. doi: 10.1016/S1474-4422(07)70243-0. PMID: 17884680

Therapy

Dahlgren MK, Gonenc A, Sagar KA, Smith RT, Lambros AM, El-Abboud C, Gruber SA
Cannabis Cannabinoid Res 2022 Dec;7(6):827-839. Epub 2022 Nov 11 doi: 10.1089/can.2022.0097. PMID: 36367574Free PMC Article
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Curr Opin Neurol 2018 Jun;31(3):244-248. doi: 10.1097/WCO.0000000000000562. PMID: 29629942
Pitteri M, Magliozzi R, Bajrami A, Camera V, Calabrese M
Expert Opin Pharmacother 2018 Mar;19(4):387-395. Epub 2018 Feb 3 doi: 10.1080/14656566.2018.1434143. PMID: 29397790
Simon JH
Handb Clin Neurol 2014;122:405-25. doi: 10.1016/B978-0-444-52001-2.00017-0. PMID: 24507528
Walker RW, Rosenblum MK
Neurology 1992 Oct;42(10):2005-10. doi: 10.1212/wnl.42.10.2005. PMID: 1407584

Prognosis

Carotenuto A, Cacciaguerra L, Pagani E, Preziosa P, Filippi M, Rocca MA
Brain 2022 Aug 27;145(8):2785-2795. doi: 10.1093/brain/awab454. PMID: 34919648
Shahriari M, Sotirchos ES, Newsome SD, Yousem DM
AJR Am J Roentgenol 2021 Apr;216(4):1031-1039. Epub 2021 Feb 17 doi: 10.2214/AJR.20.24061. PMID: 32755221
Razek AAKA, Elsebaie NA
J Comput Assist Tomogr 2020 Mar/Apr;44(2):248-254. doi: 10.1097/RCT.0000000000000997. PMID: 32195804
Bells S, Lefebvre J, Longoni G, Narayanan S, Arnold DL, Yeh EA, Mabbott DJ
Glia 2019 Nov;67(11):2020-2037. Epub 2019 Jun 24 doi: 10.1002/glia.23661. PMID: 31233643
Lassmann H
Front Immunol 2018;9:3116. Epub 2019 Jan 10 doi: 10.3389/fimmu.2018.03116. PMID: 30687321Free PMC Article

Clinical prediction guides

Li H, Jacob MA, Cai M, Duering M, Chamberland M, Norris DG, Kessels RPC, de Leeuw FE, Marques JP, Tuladhar AM
Brain 2023 Nov 2;146(11):4659-4673. doi: 10.1093/brain/awad220. PMID: 37366338Free PMC Article
Benzoni C, Moscatelli M, Farina L, Magri S, Ciano C, Scaioli V, Alverà S, Cammarata G, Bianchi-Marzoli S, Castellani M, Zito FM, Marotta G, Piacentini S, Villacara A, Mantegazza R, Gellera C, Durães J, Gouveia A, Matos A, do Carmo Macário M, Pareyson D, Taroni F, Di Bella D, Salsano E
J Neurol 2023 Sep;270(9):4219-4234. Epub 2023 May 12 doi: 10.1007/s00415-023-11762-7. PMID: 37171481
Tonduti D, Zambon AA, Ghezzi D, Lamantea E, Izzo R, Parazzini C, Baldoli C, van der Knaap MS, Fumagalli F
Neuropediatrics 2023 Jun;54(3):161-166. Epub 2023 Mar 3 doi: 10.1055/s-0043-1764214. PMID: 36868263
Cairns J, Vavasour IM, Traboulsee A, Carruthers R, Kolind SH, Li DKB, Moore GRW, Laule C
J Neuroimaging 2022 Jan;32(1):5-16. Epub 2021 Nov 9 doi: 10.1111/jon.12945. PMID: 34752664
Bells S, Lefebvre J, Longoni G, Narayanan S, Arnold DL, Yeh EA, Mabbott DJ
Glia 2019 Nov;67(11):2020-2037. Epub 2019 Jun 24 doi: 10.1002/glia.23661. PMID: 31233643

Recent systematic reviews

Seyedmirzaei H, Nabizadeh F, Aarabi MH, Pini L
J Magn Reson Imaging 2023 Oct;58(4):1011-1029. Epub 2023 Apr 12 doi: 10.1002/jmri.28727. PMID: 37042392
Lindsey HM, Hodges CB, Greer KM, Wilde EA, Merkley TL
Neuropsychol Rev 2023 Mar;33(1):42-121. Epub 2021 Mar 15 doi: 10.1007/s11065-021-09485-5. PMID: 33721207
Aronica R, Enrico P, Squarcina L, Brambilla P, Delvecchio G
Neurosci Biobehav Rev 2022 Dec;143:104922. Epub 2022 Oct 19 doi: 10.1016/j.neubiorev.2022.104922. PMID: 36272579
Adams SJ, Kirk A, Auer RN
J Clin Neurosci 2018 Feb;48:42-49. Epub 2017 Nov 6 doi: 10.1016/j.jocn.2017.10.060. PMID: 29122458
Prosperini L, Piattella MC, Giannì C, Pantano P
Neural Plast 2015;2015:481574. Epub 2015 May 6 doi: 10.1155/2015/481574. PMID: 26064692Free PMC Article

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