Clinical Presentation, Investigation Findings, and Treatment Outcomes of Spontaneous Intracranial Hypotension Syndrome: A Systematic Review and Meta-analysis | JAMA Neurology | JAMA Network
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1.
Headache Classification Committee of the International Headache Society (IHS).  The International Classification of Headache Disorders, 3rd edition.   Cephalalgia. 2018;38(1):1-211. doi:10.1177/0333102417738202Google ScholarCrossref
2.
Schievink  WI.  Misdiagnosis of spontaneous intracranial hypotension.   Arch Neurol. 2003;60(12):1713-1718. doi:10.1001/archneur.60.12.1713PubMedGoogle ScholarCrossref
3.
Schievink  WI, Maya  MM, Moser  F, Tourje  J, Torbati  S.  Frequency of spontaneous intracranial hypotension in the emergency department.   J Headache Pain. 2007;8(6):325-328. doi:10.1007/s10194-007-0421-8PubMedGoogle ScholarCrossref
4.
Kranz  PG, Gray  L, Amrhein  TJ.  Spontaneous intracranial hypotension: 10 myths and misperceptions.   Headache. 2018;58(7):948-959. doi:10.1111/head.13328PubMedGoogle ScholarCrossref
5.
Schievink  WI, Maya  MM, Louy  C, Moser  FG, Tourje  J.  Diagnostic criteria for spontaneous spinal CSF leaks and intracranial hypotension.   AJNR Am J Neuroradiol. 2008;29(5):853-856. doi:10.3174/ajnr.A0956PubMedGoogle ScholarCrossref
6.
Schievink  WI, Dodick  DW, Mokri  B, Silberstein  S, Bousser  MG, Goadsby  PJ.  Diagnostic criteria for headache due to spontaneous intracranial hypotension: a perspective.   Headache. 2011;51(9):1442-1444. doi:10.1111/j.1526-4610.2011.01911.xPubMedGoogle ScholarCrossref
7.
Liberati  A, Altman  DG, Tetzlaff  J,  et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.   PLoS Med. 2009;6(7):e1000100. doi:10.1371/journal.pmed.1000100PubMedGoogle Scholar
8.
National Heart, Lung, and Blood Institute. Study quality assessment tools: quality assessment tool for case series studies. Accessed November 12, 2020. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools
9.
Nyaga  VN, Arbyn  M, Aerts  M.  Metaprop: a Stata command to perform meta-analysis of binomial data.   Arch Public Health. 2014;72(1):39. doi:10.1186/2049-3258-72-39PubMedGoogle ScholarCrossref
10.
Headache Classification Subcommittee of the International Headache Society.  The International Classification of Headache Disorders: 2nd edition.   Cephalalgia. 2004;24 suppl 1:9-160. doi:10.1111/j.1468-2982.2003.00824.xGoogle Scholar
11.
Headache Classification Committee of the International Headache Society (IHS).  The International Classification of Headache Disorders, 3rd edition (beta version).   Cephalalgia. 2013;33(9):629-808. doi:10.1177/0333102413485658Google ScholarCrossref
12.
Schievink  WI, Maya  MM, Jean-Pierre  S, Nuño  M, Prasad  RS, Moser  FG.  A classification system of spontaneous spinal CSF leaks.   Neurology. 2016;87(7):673-679. doi:10.1212/WNL.0000000000002986PubMedGoogle ScholarCrossref
13.
Ansel  S, Rae  A, Tyagi  A.  Efficacy of epidural blood patches for spontaneous low-pressure headaches: a case series.   J R Coll Physicians Edinb. 2016;46(4):234-237. doi:10.4997/JRCPE.2016.404PubMedGoogle ScholarCrossref
14.
Beck  J, Ulrich  CT, Fung  C,  et al.  Diskogenic microspurs as a major cause of intractable spontaneous intracranial hypotension.   Neurology. 2016;87(12):1220-1226. doi:10.1212/WNL.0000000000003122PubMedGoogle ScholarCrossref
15.
Schievink  WI, Maya  MM, Louy  C, Moser  FG, Sloninsky  L.  Spontaneous intracranial hypotension in childhood and adolescence.   J Pediatr. 2013;163(2):504-510. doi:10.1016/j.jpeds.2013.01.055PubMedGoogle ScholarCrossref
16.
Liu  FC, Fuh  JL, Wang  YF, Wang  SJ.  Connective tissue disorders in patients with spontaneous intracranial hypotension.   Cephalalgia. 2011;31(6):691-695. doi:10.1177/0333102410394676PubMedGoogle ScholarCrossref
17.
Thielen  KR, Sillery  JC, Morris  JM,  et al.  Ultrafast dynamic computed tomography myelography for the precise identification of high-flow cerebrospinal fluid leaks caused by spiculated spinal osteophytes.   J Neurosurg Spine. 2015;22(3):324-331. doi:10.3171/2014.10.SPINE14209PubMedGoogle ScholarCrossref
18.
Chazen  JL, Talbott  JF, Lantos  JE, Dillon  WP.  MR myelography for identification of spinal CSF leak in spontaneous intracranial hypotension.   AJNR Am J Neuroradiol. 2014;35(10):2007-2012. doi:10.3174/ajnr.A3975PubMedGoogle ScholarCrossref
19.
Schrijver  I, Schievink  WI, Godfrey  M, Meyer  FB, Francke  U.  Spontaneous spinal cerebrospinal fluid leaks and minor skeletal features of Marfan syndrome: a microfibrillopathy.   J Neurosurg. 2002;96(3):483-489. doi:10.3171/jns.2002.96.3.0483PubMedGoogle ScholarCrossref
20.
Schievink  WI, Gordon  OK, Tourje  J.  Connective tissue disorders with spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension: a prospective study.   Neurosurgery. 2004;54(1):65-70. doi:10.1227/01.NEU.0000097200.18478.7BPubMedGoogle ScholarCrossref
21.
Yoshida  H, Takai  K, Taniguchi  M.  Leakage detection on CT myelography for targeted epidural blood patch in spontaneous cerebrospinal fluid leaks: calcified or ossified spinal lesions ventral to the thecal sac.   J Neurosurg Spine. 2014;21(3):432-441. doi:10.3171/2014.5.SPINE13549PubMedGoogle ScholarCrossref
22.
Reinstein  E, Pariani  M, Bannykh  S, Rimoin  DL, Schievink  WI.  Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study.   Eur J Hum Genet. 2013;21(4):386-390. doi:10.1038/ejhg.2012.191PubMedGoogle ScholarCrossref
23.
Schievink  WI, Goseland  A, Cunneen  S.  Bariatric surgery as a possible risk factor for spontaneous intracranial hypotension.   Neurology. 2014;83(20):1819-1822. doi:10.1212/WNL.0000000000000985PubMedGoogle ScholarCrossref
24.
Wu  JW, Hseu  SS, Fuh  JL,  et al.  Factors predicting response to the first epidural blood patch in spontaneous intracranial hypotension.   Brain. 2017;140(2):344-352. doi:10.1093/brain/aww328PubMedGoogle ScholarCrossref
25.
Kranz  PG, Amrhein  TJ, Choudhury  KR, Tanpitukpongse  TP, Gray  L.  Time-dependent changes in dural enhancement associated with spontaneous intracranial hypotension.   AJR Am J Roentgenol. 2016;207(6):1283-1287. doi:10.2214/AJR.16.16381PubMedGoogle ScholarCrossref
26.
Idrissi  AL, Lacour  JC, Klein  O, Schmitt  E, Ducrocq  X, Richard  S.  Spontaneous intracranial hypotension: characteristics of the serious form in a series of 24 patients.   World Neurosurg. 2015;84(6):1613-1620. doi:10.1016/j.wneu.2015.07.002PubMedGoogle ScholarCrossref
27.
Kim  YJ, Cho  HY, Seo  DW,  et al.  Misdiagnosis of spontaneous intracranial hypotension as a risk factor for subdural hematoma.   Headache. 2017;57(10):1593-1600. doi:10.1111/head.13132PubMedGoogle ScholarCrossref
28.
Chung  SJ, Kim  JS, Lee  MC.  Syndrome of cerebral spinal fluid hypovolemia: clinical and imaging features and outcome.   Neurology. 2000;55(9):1321-1327. doi:10.1212/WNL.55.9.1321PubMedGoogle ScholarCrossref
29.
Ferrante  E, Olgiati  E, Sangalli  V, Rubino  F.  Early pain relief from orthostatic headache and hearing changes in spontaneous intracranial hypotension after epidural blood patch.   Acta Neurol Belg. 2016;116(4):503-508. doi:10.1007/s13760-016-0617-2PubMedGoogle ScholarCrossref
30.
Dobrocky  T, Mosimann  PJ, Zibold  F,  et al.  Cryptogenic cerebrospinal fluid leaks in spontaneous intracranial hypotension: role of dynamic CT myelography.   Radiology. 2018;289(3):766-772. doi:10.1148/radiol.2018180732PubMedGoogle ScholarCrossref
31.
Luetmer  PH, Schwartz  KM, Eckel  LJ, Hunt  CH, Carter  RE, Diehn  FE.  When should I do dynamic CT myelography? predicting fast spinal CSF leaks in patients with spontaneous intracranial hypotension.   AJNR Am J Neuroradiol. 2012;33(4):690-694. doi:10.3174/ajnr.A2849PubMedGoogle ScholarCrossref
32.
Kranz  PG, Tanpitukpongse  TP, Choudhury  KR, Amrhein  TJ, Gray  L.  How common is normal cerebrospinal fluid pressure in spontaneous intracranial hypotension?   Cephalalgia. 2016;36(13):1209-1217. doi:10.1177/0333102415623071PubMedGoogle ScholarCrossref
33.
Wang  YF, Lirng  JF, Fuh  JL, Hseu  SS, Wang  SJ.  Heavily T2-weighted MR myelography vs CT myelography in spontaneous intracranial hypotension.   Neurology. 2009;73(22):1892-1898. doi:10.1212/WNL.0b013e3181c3fd99PubMedGoogle ScholarCrossref
34.
Watanabe  K, Hashizume  K, Kawaguchi  M, Fujiwara  A, Sasaoka  N, Furuya  H.  Fluoroscopically guided epidural blood patch with subsequent spinal CT scans in the treatment of spontaneous cerebrospinal fluid hypovolemia.   J Neurosurg. 2011;114(6):1731-1735. doi:10.3171/2011.1.JNS101326PubMedGoogle ScholarCrossref
35.
He  FF, Li  L, Liu  MJ, Zhong  TD, Zhang  QW, Fang  XM.  Targeted epidural blood patch treatment for refractory spontaneous intracranial hypotension in China.   J Neurol Surg B Skull Base. 2018;79(3):217-223. doi:10.1055/s-0037-1606312PubMedGoogle ScholarCrossref
36.
Ferrante  E, Rubino  F, Mongelli  M, Arpino  I.  Subarachnoideal blood spread following epidural blood patch given to treat spontaneous intracranial hypotension: can it cause neurological complications?   Clin Neurol Neurosurg. 2016;140:43-46. doi:10.1016/j.clineuro.2015.11.007PubMedGoogle ScholarCrossref
37.
Schievink  WI, Morreale  VM, Atkinson  JL, Meyer  FB, Piepgras  DG, Ebersold  MJ.  Surgical treatment of spontaneous spinal cerebrospinal fluid leaks.   J Neurosurg. 1998;88(2):243-246. doi:10.3171/jns.1998.88.2.0243PubMedGoogle ScholarCrossref
38.
Kranz  PG, Amrhein  TJ, Gray  L.  CSF venous fistulas in spontaneous intracranial hypotension: imaging characteristics on dynamic and CT myelography.   AJR Am J Roentgenol. 2017;209(6):1360-1366. doi:10.2214/AJR.17.18351PubMedGoogle ScholarCrossref
39.
Beck  J, Raabe  A, Schievink  WI,  et al.  Posterior approach and spinal cord release for 360° repair of dural defects in spontaneous intracranial hypotension.   Neurosurgery. 2019;84(6):E345-E351. doi:10.1093/neuros/nyy312PubMedGoogle ScholarCrossref
40.
Wang  TY, Karikari  IO, Amrhein  TJ, Gray  L, Kranz  PG.  Clinical outcomes following surgical ligation of cerebrospinal fluid-venous fistula in patients with spontaneous intracranial hypotension: a prospective case series.   Oper Neurosurg (Hagerstown). 2020;18(3):239-245.PubMedGoogle Scholar
41.
Schievink  WI.  A novel technique for treatment of intractable spontaneous intracranial hypotension: lumbar dural reduction surgery.   Headache. 2009;49(7):1047-1051. doi:10.1111/j.1526-4610.2009.01450.xPubMedGoogle ScholarCrossref
42.
Pagani-Estévez  GL, Cutsforth-Gregory  JK, Morris  JM,  et al.  Procedural predictors of epidural blood patch efficacy in spontaneous intracranial hypotension.   Reg Anesth Pain Med. 2019;rapm-2018-000021. doi:10.1136/rapm-2018-000021PubMedGoogle Scholar
43.
Schievink  WI, Maya  MM, Jean-Pierre  S, Moser  FG, Nuño  M, Pressman  BD.  Rebound high-pressure headache after treatment of spontaneous intracranial hypotension: MRV study.   Neurol Clin Pract. 2019;9(2):93-100. doi:10.1212/CPJ.0000000000000550PubMedGoogle ScholarCrossref
44.
Li  L, Gao  FQ, Zhang  B, Luo  BN, Yang  ZY, Zhao  J.  Overdosage of intrathecal gadolinium and neurological response.   Clin Radiol. 2008;63(9):1063-1068. doi:10.1016/j.crad.2008.02.004PubMedGoogle ScholarCrossref
45.
Dobrocky  T, Winklehner  A, Breiding  PS,  et al.  Spine MRI in spontaneous intracranial hypotension for CSF leak detection: nonsuperiority of intrathecal gadolinium to heavily T2-weighted fat-saturated sequences.   AJNR Am J Neuroradiol. 2020;41(7):1309-1315. doi:10.3174/ajnr.A6592PubMedGoogle ScholarCrossref
46.
Mokri  B, Hunter  SF, Atkinson  JLD, Piepgras  DG.  Orthostatic headaches caused by CSF leak but with normal CSF pressures.   Neurology. 1998;51(3):786-790. doi:10.1212/WNL.51.3.786PubMedGoogle ScholarCrossref
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    Original Investigation
    January 4, 2021

    Clinical Presentation, Investigation Findings, and Treatment Outcomes of Spontaneous Intracranial Hypotension Syndrome: A Systematic Review and Meta-analysis

    Author Affiliations
    • 1Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, London, United Kingdom
    • 2UCL Queen Square Institute of Neurology, London, United Kingdom
    • 3Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom
    • 4Headache and Facial Pain Group, National Hospital for Neurology and Neurosurgery, London, United Kingdom
    JAMA Neurol. 2021;78(3):329-337. doi:10.1001/jamaneurol.2020.4799
    Key Points

    Question  What are the clinical presentation, investigation findings, and treatment outcomes of spontaneous intracranial hypotension?

    Findings  This systematic review and meta-analysis of 144 articles provides a summary of the evidence on spontaneous intracranial hypotension and demonstrates that a significant minority of patients may have nonorthostatic headache, normal lumbar punctures, or normal imaging results. Treatment with 1 epidural blood patch is often successful, with large-volume blood patches giving better outcomes.

    Meaning  A diagnosis of spontaneous intracranial hypotension should not be excluded based on the absence of one of its typical features; large epidural blood patches should be attempted if conservative treatment has failed.

    Abstract

    Importance  Spontaneous intracranial hypotension (SIH) is a highly disabling but often misdiagnosed disorder. The best management options for patients with SIH are still uncertain.

    Objective  To provide an objective summary of the available evidence on the clinical presentation, investigations findings, and treatment outcomes for SIH.

    Data Sources  Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline–compliant systematic review and meta-analysis of the literature on SIH. Three databases were searched from inception to April 30, 2020: PubMed/MEDLINE, Embase, and Cochrane. The following search terms were used in each database: spontaneous intracranial hypotension, low CSF syndrome, low CSF pressure syndrome, low CSF volume syndrome, intracranial hypotension, low CSF pressure, low CSF volume, CSF hypovolemia, CSF hypovolaemia, spontaneous spinal CSF leak, spinal CSF leak, and CSF leak syndrome.

    Study Selection  Original studies in English language reporting 10 or more patients with SIH were selected by consensus.

    Data Extraction and Synthesis  Data on clinical presentation, investigations findings, and treatment outcomes were collected and summarized by multiple observers. Random-effect meta-analyses were used to calculate pooled estimates of means and proportions.

    Main Outcomes and Measures  The predetermined main outcomes were the pooled estimate proportions of symptoms of SIH, imaging findings (brain and spinal imaging), and treatment outcomes (conservative, epidural blood patches, and surgical).

    Results  Of 6878 articles, 144 met the selection criteria and reported on average 53 patients with SIH each (range, 10-568 patients). The most common symptoms were orthostatic headache (92% [95% CI, 87%-96%]), nausea (54% [95% CI, 46%-62%]), and neck pain/stiffness (43% [95% CI, 32%-53%]). Brain magnetic resonance imaging was the most sensitive investigation, with diffuse pachymeningeal enhancement identified in 73% (95% CI, 67%-80%) of patients. Brain magnetic resonance imaging findings were normal in 19% (95% CI, 13%-24%) of patients. Spinal neuroimaging identified extradural cerebrospinal fluid in 48% to 76% of patients. Digital subtraction myelography and magnetic resonance myelography with intrathecal gadolinium had high sensitivity in identifying the exact leak site. Lumbar puncture opening pressures were low, normal (60-200 mm H2O), and high in 67% (95% CI, 54%-80%), 32% (95% CI, 20%-44%), and 3% (95% CI, 1%-6%), respectively. Conservative treatment was effective in 28% (95% CI, 18%-37%) of patients and a single epidural blood patch was successful in 64% (95% CI, 56%-72%). Large epidural blood patches (>20 mL) had better success rates than small epidural blood patches (77% [95% CI, 63%-91%] and 66% [95% CI, 55%-77%], respectively).

    Conclusions and Relevance  Spontaneous intracranial hypotension should not be excluded on the basis of a nonorthostatic headache, normal neuroimaging findings, or normal lumbar puncture opening pressure. Despite the heterogeneous nature of the studies available in the literature and the lack of controlled interventional studies, this systematic review offers a comprehensive and objective summary of the evidence on SIH that could be useful in guiding clinical practice and future research.

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