Possible mechanisms in infants for selective basal ganglia damage from asphyxia, kernicterus, or mitochondrial encephalopathies.
Magnetic resonance imaging and neuropathologic studies have demonstrated remarkably selective patterns of injury to subregions of the basal ganglia in children. Examples are kernicterus and certain mitochondrial encephalopathies, which cause selective injury to the globus pallidus, and near-total perinatal asphyxia, which causes lesions in the putamen and thalamus. To explain the differential vulnerability of nuclei within millimeters of each other, we hypothesize that their locations within the neurotransmitter-specific circuitry of the basal ganglia motor loop are important. In severe hypoxic-ischemic encephalopathy, excitatory glutamatergic pathways into the putamen and thalamus are overactive, but the globus pallidus might be protected because its activity is silenced by inhibitory neuronal activity. In contrast, the relatively high resting neuronal activity in the globus pallidus might make it more vulnerable to less intense, subacute oxidative stresses from mitochondrial toxins such as bilirubin or from genetic mitochondrial disorders. This hypothesis has implications for designing neuroprotective therapies and for treating associated chronic movement disorders.
Johnston
M V
MV
Division of Neurology and Developmental Medicine, Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. johnston@kennedykrieger.org
Hoon
A H
AH
D001238:Asphyxia Neonatorum / Q000150:complications*; D001264:Athetosis / Q000175:diagnosis / Q000209:etiology; D001480:Basal Ganglia Diseases / Q000175:diagnosis / Q000209:etiology*; D001921:Brain / Q000473:pathology*; D004421:Dystonia / Q000175:diagnosis / Q000209:etiology; D005260:Female; D005917:Globus Pallidus / Q000473:pathology; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000150:complications; D007223:Infant; D007231:Infant, Newborn; D007647:Kernicterus / Q000150:complications*; D008279:Magnetic Resonance Imaging; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000150:complications*; D011699:Putamen / Q000473:pathology; D013788:Thalamus / Q000473:pathology