title: Hemorrhagic primary CNS angiitis and vasoconstrictive drug exposure.
abstract: BACKGROUND
  Primary angiitis of the CNS (PACNS) typically manifests with accumulating neurologic deficits from ischemic strokes. Intracerebral hemorrhage (ICH) is an uncommon complication. There is limited knowledge about the risk factors and features of hemorrhagic PACNS.
  
  
  METHODS
  We identified 49 patients (20 biopsy-proven) with PACNS diagnosed at our hospital from 1993 to 2015. We compared the features of hemorrhagic and nonhemorrhagic PACNS and analyzed the hemorrhagic PACNS cases in detail.
  
  
  RESULTS
  The mean age was 51 ± 15 years; 13 patients were men. Five patients had ICH (mean age 52 ± 14 years; 4 men) including 4 where ICH was the first manifestation of PACNS. All ICH patients reported recent exposure to sympathomimetic drugs (e.g., diet pills, nasal decongestants). Patients with ICH had higher rates of headache (100% vs 43%,p= 0.022), especially thunderclap headache (60% vs 0%,p= 0.001), and eosinophilic vascular infiltrates on brain biopsy (50% vs 9%,p= 0.084). In all ICH patients, brain MRI showed lobar hemorrhages with concurrent punctate diffusion-restricted lesions, suggesting an acute inflammatory process. Four received a short course of immunosuppressive therapy. All patients showed complete clinical resolution or significant improvement within weeks.
  
  
  CONCLUSIONS
  In this study, hemorrhagic PACNS was exclusively associated with sympathomimetic drug exposure. The high rate of thunderclap headache, lobar hemorrhages, and the self-limited clinical course suggests a shared mechanism between hemorrhagic PACNS and the reversible cerebral vasoconstriction syndrome (RCVS), a PACNS mimic. This RCVS-PACNS overlap syndrome may result from sympathomimetic drug-induced prolonged distal vasoconstriction, culminating in inflammation.
authors.affiliation: Massachusetts General Hospital and Harvard Medical School (MAT, MPF, ABS), Boston; Neurology Department (MAT), Hacettepe University Hospitals, Ankara, Turkey; Safar Center for Resuscitation (RMJ), University of Pittsburgh Medical Center, PA; and Government Medical College (JG), Kottayam, India.
authors.forename: Mehmet A
authors.initials: MA
authors.lastname: Topcuoglu
authors.affiliation: Massachusetts General Hospital and Harvard Medical School (MAT, MPF, ABS), Boston; Neurology Department (MAT), Hacettepe University Hospitals, Ankara, Turkey; Safar Center for Resuscitation (RMJ), University of Pittsburgh Medical Center, PA; and Government Medical College (JG), Kottayam, India.
authors.forename: Ruchira M
authors.initials: RM
authors.lastname: Jha
authors.affiliation: Massachusetts General Hospital and Harvard Medical School (MAT, MPF, ABS), Boston; Neurology Department (MAT), Hacettepe University Hospitals, Ankara, Turkey; Safar Center for Resuscitation (RMJ), University of Pittsburgh Medical Center, PA; and Government Medical College (JG), Kottayam, India.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.affiliation: Massachusetts General Hospital and Harvard Medical School (MAT, MPF, ABS), Boston; Neurology Department (MAT), Hacettepe University Hospitals, Ankara, Turkey; Safar Center for Resuscitation (RMJ), University of Pittsburgh Medical Center, PA; and Government Medical College (JG), Kottayam, India.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.affiliation: Massachusetts General Hospital and Harvard Medical School (MAT, MPF, ABS), Boston; Neurology Department (MAT), Hacettepe University Hospitals, Ankara, Turkey; Safar Center for Resuscitation (RMJ), University of Pittsburgh Medical Center, PA; and Government Medical College (JG), Kottayam, India.
authors.forename: Aneesh B
authors.initials: AB
authors.lastname: Singhal