TY  - CHAP
M1  - Book, Section
TI  - Multiple Sclerosis
A1  - Bove, Riley
A1  - De Jager, Philip L.
A2  - Murray, Michael F.
A2  - Babyatsky, Mark W.
A2  - Giovanni, Monica A.
A2  - Alkuraya, Fowzan S.
A2  - Stewart, Douglas R.
PY  - 2014
T2  - Clinical Genomics: Practical Applications in Adult Patient Care
AB  - Disease  summary:Multiple  sclerosis  (MS)  is  a  genetically  complex  disorder,  involving  many  susceptibility  loci  that  probably  interact  with  environmental  factors  to  trigger  the  disease.MS  is  a  chronic,  inflammatory  demyelinating  disorder  of  the  central  nervous  system  (CNS)  typically  characterized  by  demyelinating  lesions  disseminated  “in  time  and  space,”  meaning  that  different  parts  of  the  CNS  are  involved  and  that  a  patient  has  had  at  least  two  inflammatory  events  3  months  apart.Demyelinating  lesions  can  occur  in  the  brain,  spinal  cord,  and  optic  nerves.Clinical  presentation  includes  focal  sensory  or  motor  impairment,  optic  neuritis,  transverse  myelitis,  loss  of  bowel  or  bladder  function,  gait  instability,  fatigue,  depression,  cognitive  impairment.  Vertigo,  Uhthoff  phenomenon,  and  Lhermitte  sign  are  common.Disease  course  is  divided  into  three  categories:  relapsing  remitting  MS  (RRMS,  85%  of  first  presentations),  secondary  progressive  MS  (SPMS,  many  RRMS  patients  go  on  to  exhibit  a  gradual  functional  and  decline  reminiscent  of  neurodegenerative  diseases),  and  primary  progressive  MS  (PPMS,  patients  who  never  had  a  clinical  relapse).More  rare  forms  include  neuromyelitis  optica  (NMO),  Marburg  variant,  Schilder  disease,  Baló  concentric  sclerosis,  and  tumefactive  MS.Differential  diagnosis:Can  be  organized  by  site  of  CNS  involvement  and  includes:Cerebrum  and  brain  stem:  acute  demyelinating  encephalomyelitis  (ADEM),  lymphoma,  infection  (Lyme  disease,  HIV,  progressive  multifocal  leukoencephalopathy  [PML],  syphilis),  small  vessel  disease  (leukoaraiosis),  CADASIL,  vasculitis,  rheumatologic  diseases  (systemic  lupus  erythematosus  [SLE]),  rheumatoid  arthritis  (RA),  Sjögren  syndrome),  antiphospholipid  antibody  syndrome  (APLAS),  spinocerebellar  ataxia,  and  leukodystrophyOptic  neuritis:  NMO,  sarcoidosis,  retinal  artery  occlusion,  retinal  detachment,  acute  glaucomaSpinal  cord:  sarcoidosis,  spinal  stenosis,  syrinx,  epidural  abscess,  spinal  arteriovenous  malformation  (AVM),  infectious  myelitis  (HIV,  HTLV-1,  Mycoplasma),  nutritional  (B12,  copper  or  zinc)  deficiencies,  toxicity,  hereditary  spastic  paraparesis,  adrenomyeloneuropathyMonogenic  forms:No  single  gene  cause  of  MS  is  known  to  exist.Family  history:The  lifetime  risk  of  developing  MS  for  a  sibling  or  a  child  of  an  MS  patient  is  2%  to  3%,  which  is  about  30  times  greater  than  the  risk  to  the  general  population.Twin  studies:Monozygotic  twins  have  a  30%  concordance  rate  for  clinical  disease;  in  one  study,  concordance  was  50%  if  magnetic  resonance  imaging  (MRI)  is  performed  and  clinically  silent  MS-like  lesions  are  considered  as  evidence  of  the  disease.Environmental  factors:In  terms  of  MS  susceptibility,  good  epidemiologic  data  support  the  role  of  (1)  the  Epstein-Barr  virus  (EBV)  (particularly  in  its  clinical  manifestation  as  infectious  mononucleosis),  (2)  low  vitamin  D  levels,  and  (3)  smoking.  More  preliminary  evidence  supports  the  role  of  elevated  adolescent  body  mass  index  (BMI)  and  living  in  Northern  latitude  during  childhood,  which  may  be  related  to  vitamin  D.  There  is  some  evidence  for  a  gene-environment  interaction.  For  example,  individuals  who  have  both  the  HLA  DRB1*1501  allele  and  high  levels  of  antibodies  directed  against  the  EBV  protein  EBNA-1  (two  known  risk  factors),  have  a  ninefold  increase  in  risk  over  individuals  that  have  neither  risk  factor.Genome-wide  associations:About  49  well-validated  susceptibility  loci  harboring  54  risk  alleles  exist.  Testing  for  susceptibility  alleles  is  not  yet  clinically  validated  to  diagnose  or  guide  management  of  Ms.  Genome-wide  association  studies  (GWASs)  of  disease  course  and  other  traits  such  as  resilience  and  repair  are  beginning,  but  there  is  no  variant  with  a  validated  role  for  these  traits.Pharmacogenomics:There  are  no  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/16
UR  - accessmedicine.mhmedical.com/content.aspx?aid=1102705081
ER  -