Bedside diagnosis of mitochondrial dysfunction in aneurysmal subarachnoid hemorrhage

Acta Neurol Scand. 2014 Sep;130(3):156-63. doi: 10.1111/ane.12258. Epub 2014 May 3.

Abstract

Objectives: Aneurysmal subarachnoid hemorrhage (SAH) is frequently associated with delayed neurological deterioration (DND). Several studies have shown that DND is not always related to vasospasm and ischemia. Experimental and clinical studies have recently documented that it is possible to diagnose and separate cerebral ischemia and mitochondrial dysfunction bedside. The study explores whether cerebral biochemical variables in SAH patients most frequently exhibit a pattern indicating ischemia or mitochondrial dysfunction.

Methods: In 55 patients with severe SAH, intracerebral microdialysis was performed during neurocritical care with bedside analysis and display of glucose, pyruvate, lactate, glutamate, and glycerol. The biochemical patterns observed were compared to those previously described in animal studies of induced mitochondrial dysfunction as well as the pattern obtained in patients with recirculated cerebral infarcts.

Results: In 29 patients, the biochemical pattern indicated mitochondrial dysfunction while 10 patients showed a pattern of cerebral ischemia, six of which also exhibited periods of mitochondrial dysfunction. Mitochondrial dysfunction was observed during 5162 h. An ischemic pattern was obtained during 688 h. Four of the patients (40%) with biochemical signs of ischemia died at the neurosurgical department as compared with three patients (10%) in the group of mitochondrial dysfunction.

Conclusions: The study documents that mitochondrial dysfunction is a common cause of disturbed cerebral energy metabolism in patients with SAH. Mitochondrial dysfunction may increase tissue sensitivity to secondary adverse events such as vasospasm and decreased cerebral blood flow. The separation of ischemia and mitochondrial dysfunction bedside by utilizing microdialysis offers a possibility to evaluate new therapies.

Keywords: cerebral energy metabolism; ischemia; lactate; microdialysis; mitochondrial dysfunction; pyruvate; subarachnoid hemorrhage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / cerebrospinal fluid*
  • Brain Ischemia / cerebrospinal fluid
  • Brain Ischemia / diagnosis
  • Brain Ischemia / etiology
  • Energy Metabolism / physiology
  • Female
  • Glucose / cerebrospinal fluid
  • Glutamic Acid / cerebrospinal fluid
  • Glycerol / cerebrospinal fluid
  • Humans
  • Intracranial Aneurysm / complications*
  • Lactic Acid / cerebrospinal fluid
  • Male
  • Microdialysis / methods*
  • Middle Aged
  • Mitochondria / pathology*
  • Pyruvic Acid
  • Subarachnoid Hemorrhage / cerebrospinal fluid*
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / diagnosis*

Substances

  • Biomarkers
  • Lactic Acid
  • Glutamic Acid
  • Pyruvic Acid
  • Glucose
  • Glycerol