18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in glutaric aciduria type 1: clinical and MRI correlations

Alessa, Mohammed; Bakheet, Siema M.; Patay, Zoltán; Al-Watban, Jehad; Powe, John; Joshi, S; Özand, Pinar

doi:10.1016/s0387-7604(98)00033-3

Cited by 22 publications

(11 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glutamate depletion in this mouse model is consistent with reduced brain glucose utilization, as previously shown with immature rats (36). Reduced brain glucose utilization was previously shown in human GA-I using 18 fluoro-2-deoxyglucose uptake studies (37), indicating that glutamate levels may also be compromised in human GA-I with encephalopathy. Glutamate is the precursor for GABA (38), and reduced GABA levels in this mouse model and human GA-I (7) correlate with glutamate depletion and further indicate that glutamate levels may be compromised in human GA-I.…”

Section: Figuresupporting

confidence: 87%

“…Glutamate is the precursor for GABA (38), and reduced GABA levels in this mouse model and human GA-I (7) correlate with glutamate depletion and further indicate that glutamate levels may be compromised in human GA-I. GABA levels may be initially reduced along with glutamate as brain glucose utilization is compromised during encephalopathy (37). Glutaric acid accumulation suppresses GABA production (21), and the return of glutamate levels with restored brain glucose utilization may set up unopposed excitatory neurotransmission resulting in seizures and excitotoxic lesions found in this model and in human GA-I (9).…”

Section: Figurementioning

confidence: 85%

See 1 more Smart Citation

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Zinnanti¹,

Lazović²,

Housman³

et al. 2007

J. Clin. Invest.

View full text Add to dashboard Cite

Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance ( 1 H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I.

show abstract

Section: Figuresupporting

confidence: 87%

Section: Figurementioning

confidence: 85%

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Zinnanti¹,

Lazović²,

Housman³

et al. 2007

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…In the majority of treated patients, this frontotemporal underdevelopment was shown to normalize by 4-years of age [42]. In contrast, patients that experience encephalopathy are more likely to show frontotemporal atrophy and spongiform degeneration of white matter tracts [40-42]. Our current findings also show cortical involvement and parallel findings in GA1 patients include evidence of decreased perfusion and glucose uptake in frontocortical regions [4,28,40].…”

Section: Discussionsupporting

confidence: 67%

“…Extrastriatal neuropathology involving the cortical grey and white matter are also reported, but less recognized and studied [40,41]. Recent work by Harting and colleagues follows MRI changes in pre-symptomatic GA1 patients and shows delay in early frontotemporal cortical development that is already present at birth [42].…”

Section: Discussionmentioning

confidence: 99%

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

Zinnanti

Lazović

Housman

et al. 2014

acta neuropathol commun

View full text Add to dashboard Cite

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

show abstract

“…MRS shows decreased NAA/creatine ratio at the basal ganglia in encephalopathic patients (Pérez-Dueñas at al., 2009). Fluoro-2-deoxyglucose PET reveals decreased glucose uptake in the cerebral cortex, basal ganglia and thalami (Al-Essa et al, 1998).…”

Section: Glutaric Aciduria Type Imentioning

confidence: 99%

Neuroimaging in Inborn Errors of Metabolism

Casimiro¹,

Garcia²,

Cordeiro³

et al. 2012

Neuroimaging - Clinical Applications

View full text Add to dashboard Cite

18Fluoro-2-deoxyglucose (18FDG) PET scan of the brain in glutaric aciduria type 1: clinical and MRI correlations

Cited by 22 publications

References 24 publications

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

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

Neuroimaging in Inborn Errors of Metabolism

Contact Info

Product

Resources

About