Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I

William J. Zinnanti, Jelena Lazovic, Cathy Housman, David A. Antonetti, David Koeller, James R. Connor, Lawrence Steinman

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

BACKGROUND: Metabolic stroke is the rapid onset of lasting central neurological deficit associated with decompensation of an underlying metabolic disorder. Glutaric aciduria type I (GA1) is an inherited disorder of lysine and tryptophan metabolism presenting with metabolic stroke in infancy. The clinical presentation includes bilateral striatal necrosis and spontaneous subdural and retinal hemorrhages, which has been frequently misdiagnosed as non-accidental head trauma. The mechanisms underlying metabolic stroke and spontaneous hemorrhage are poorly understood.

RESULTS: Using a mouse model of GA1, we show that metabolic stroke progresses in the opposite sequence of ischemic stroke, with initial neuronal swelling and vacuole formation leading to cerebral capillary occlusion. Focal regions of cortical followed by striatal capillaries are occluded with shunting to larger non-exchange vessels leading to early filling and dilation of deep cerebral veins. Blood-brain barrier breakdown was associated with displacement of tight-junction protein Occludin.

CONCLUSION: Together the current findings illuminate the pathophysiology of metabolic stroke and vascular compromise in GA1, which may translate to other neurometabolic disorders presenting with stroke.

Original languageEnglish (US)
Pages (from-to)13
Number of pages1
JournalActa neuropathologica communications
Volume2
DOIs
StatePublished - 2014

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Cerebral Hemorrhage
Stroke
Corpus Striatum
Cerebral Veins
Occludin
Retinal Hemorrhage
Tight Junction Proteins
Subdural Hematoma
Vacuoles
Glutaric Acidemia I
Diagnostic Errors
Blood-Brain Barrier
Craniocerebral Trauma
Tryptophan
Lysine
Blood Vessels
Dilatation
Necrosis
Hemorrhage

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I. / Zinnanti, William J.; Lazovic, Jelena; Housman, Cathy; Antonetti, David A.; Koeller, David; Connor, James R.; Steinman, Lawrence.

In: Acta neuropathologica communications, Vol. 2, 2014, p. 13.

Research output: Contribution to journalArticle

Zinnanti, William J. ; Lazovic, Jelena ; Housman, Cathy ; Antonetti, David A. ; Koeller, David ; Connor, James R. ; Steinman, Lawrence. / Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I. In: Acta neuropathologica communications. 2014 ; Vol. 2. pp. 13.
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