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Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by congenital malformation of the great toes and by progressive heterotopic bone formation in muscle tissue. Recently, a mutation involving a single amino acid substitution in a bone morphogenetic protein (BMP) type I receptor, ALK2, was identified in patients with FOP. We report here that the identical mutation, R206H, was observed in

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We tested the hypotheses that with the onset of cerebral ischemia, massive cellular sodium influx does not occur until adenosine triphosphate is fully depleted and that on reperfusion, neuronal sodium efflux does not occur until adenosine triphosphate is fully restored. We examined the temporal relationships among transcellular sodium, energy metabolism, and intracellular pH with sodium and phosphorus magnetic resonance spectroscopy in a new, hemodynamically stable, brain stem-sparing model of reversible, complete cerebral ischemia in eight anesthetized dogs. Inflation of a neck tourniquet after placement of glue at the tip of the basilar artery resulted in decreased blood flow to the cerebrum from 29 ±5 to 0-3 ±0.5 ml/min/100 g. Medullary blood flow was not significantly affected, and arterial blood pressure was unchanged. Sodium signal intensity decreased and did not lag behind the fall in adenosine triphosphate. After 12 minutes of ischemia, reperfusion resulted in a more rapid recovery of sodium intensity (12.4±4.8 minutes) than either adenosine triphosphate (16.5±3.7 minutes) or intracellular pH (38.9±1.8 minutes). Because intracellular sodium has a weaker signal than extracellular sodium, the decreased sodium intensity is interpreted as sodium influx and indicates that sodium influx does not require full depletion of adenosine triphosphate. Rapid recovery of sodium intensity during early reperfusion may represent sodium efflux, although increased plasma volume and sodium uptake from plasma may also contribute. If our interpretation of the sodium signal is correct, delayed recovery of adenosine triphosphate may be due to the utilization of adenosine triphosphate for the restoration of transcellular sodium gradient (Stroke 1991^2:233-241) T he application of magnetic resonance spectroscopy (MRS) to in situ brain allows the time course of ischemically perturbed cerebral bioenergetics as reflected by adenosine triphosphate (ATP), phosphocreatine, and intracellular pH 1 -2 and transcellular sodium gradient 3 to be examined. The potential interactions of brain sodium gradients, intracellular pH, and bioenergetics are many. Maintenance of a normal sodium gradient, necessary for normal neurologic function, is an ATP- Received May 25, 1990; accepted October 17, 1990. dependent process and accounts for 40% of the metabolic demand of the brain as assessed by highdose lidocaine during barbiturate coma. 4 Maintenance of a normal intracellular pH is critical for proper functioning of most enzymatic processes. With the onset of complete ischemia, intracellular pH falls as glucose stores are converted to lactic acid and ATP is hydrolyzed.5 Soon after ATP depletion, extracellular Na + activity decreases. 6 However, Na + influx may precede the sudden decrease in extracellular Na + activity as measured by microelectrodes if this early Na + influx is accompanied by sufficient water to maintain a constant sodium activity. On reperfusion, limited ATP generation may be diverted into restoring ionic gradients instead of main...