Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study.


We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities.


Reinstein, Eyal; Pariani, Mitchel; Bannykh, Serguei; Rimoin, David L; Schievink, Wouter I;


  • Adolescent
  • Adult
  • Aged
  • Cerebrospinal Fluid Leak
  • Cerebrospinal Fluid Rhinorrhea/ diagnosis
  • Cerebrospinal Fluid Rhinorrhea/ genetics
  • Child
  • Collagen Type III/ genetics
  • Collagen Type V/ genetics
  • Connective Tissue/ abnormalities
  • Connective Tissue Diseases/ diagnosis
  • Connective Tissue Diseases/ genetics
  • Female
  • Genetic Diseases, Inborn/ diagnosis
  • Genetic Diseases, Inborn/ genetics
  • Genetic Testing
  • Humans
  • Male
  • Microfilament Proteins/ genetics
  • Middle Aged
  • Prospective Studies
  • Proto-Oncogene Proteins/ genetics
  • Tumor Suppressor Proteins/ genetics

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