Use of Minocycline in Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) remains a devastating neurological disorder with high mortality and poor prognosis with unchanged mortality rates (53-59%). Acute treatment options for ICH remain supportive with no available effective drug or surgical therapy. All trials so far have failed to improve clinical outcome in randomized, double-blinded trials. However, one area of interest has been maintaining the integrity of the blood-brain-barrier (BBB) and preventing the growth of vasogenic edema. Matrix metalloproteinases (MMP) are a family of ubiquitous zinc-dependent endopeptidase enzymes whose primary function is the digestion of collagen type IV, laminin, and fibronectin for the purpose of remodeling extracellular basal lamina. Elevated MMP-9 as a pathological process associated with larger hematoma volume, larger perihematomal edema, and poorer clinical outcome in intracerebral hemorrhage is well documented in animal models and patients. One particular MMP-9 inhibitor gaining usage in cerebrovascular disease is minocycline. Normally FDA-approved for bacterial infection and acne vulgaris, minocycline has also been found to be both a safe and effective treatment in ischemic stroke; its potential role as a neuroprotectant in ischemic stroke is currently being tested in a large, randomized, double-blinded trial. Minocycline's beneficial role as a neuroprotectant may also extend to ICH. By inhibiting MMP-9, minocycline may decrease BBB permeability, resulting in less perihematomal edema and decreased mass effect. Although numerous animal ICH models support minocycline's role as an inhibitor of MMP-9 and neuroprotectant, its use has never been studied in humans with ICH.

Inclusion criteria

• Age 18-80 yo
• Acute neurological deficit with corresponding ICH noted on head CT
• Glasgow Coma Scale (GCS) > 8
• Onset of symptoms within 12 hrs
• < 30 ml of blood noted on initial CTH (30 ml hematoma volume is a noted independent marker between good and poor clinical outcome)
• ICH score < 3
• English/ Spanish speaking

Exclusion criteria

• Allergy to tetracycline and tetracycline analogues
• Pregnancy or suspected pregnancy
• Hepatic and/or renal insufficiency (LFTs 3x greater than upper limit of normal; creatinine > 2 mg/dL)
• Thrombocytopenia (plt count < 75,000)
• History of intolerance to minocycline
• Baseline modified Rankin score > 1
• Stuporous or comatose (GCS < 8)
• Presence of concomitant serious illness that would confound study, including serious psychiatric disease or prior suicide attempts.