Some Research Findings in AHC

(The following is an excerpt from Dr. Chugani’s summary of the workshop held in Seattle in May, 1997. The complete summary was printed in Issue 4 of the IFAHC newsletter. ) Dr. Kenneth Silver (Maywood, IL) has been using magnetic resonance spectroscopy (MRS), which uses the magnetic resonance imaging (MRI) machine to determine the concentrations of various chemicals in the brain, to study children with AHC and described the results he obtained when he was working in Montreal. He found that the muscles of children with AHC showed increased concentrations of inorganic phosphate and decreased phosphorylation potential. These findings suggested that AHC may be related to some disturbance in the functioning of mitochondria (structures within our cells which are responsible for generating energy to allow us to function). He also found a decrease of another chemical N-acetyl-aspartate (NAA) suggesting abnormal function (and perhaps damage) of brain cells. However, because the mitochondrial disorders are quite well studied, and these findings did not show all of the abnormalities seen in mitochondrial disorders, the participants agreed that AHC is probably not a primary disorder of mitochondria but rather, that the mitochondria are affected secondarily as a result of some other abnormality. Dr. Gregory Moore (Detroit, MI) has also been using MRS to study children with AHC and reported his findings on 13 children. Interestingly, the most consistent abnormality was in a brain region called the cerebellum which is involved in posture, muscle tone, eye movements and some cognitive functions. Disturbances in these functions are typically seen in AHC. Dr. Moore also found an increase in the brain chemical glutamate which is closely linked to calcium channels where the medication flunarizine has its effect. He did not find elevated lactate in the brain, again supporting the consensus of the participants that AHC is probably not a primary disorder of mitochondria. Dr. Mary Zupanc (Rochester, MN) cleared up a lot of confusion when she described her findings on AHC using SPECT scans which measure blood flow to the brain. The several papers published by various investigators appear to show conflicting results when using SPECT. Dr. Zupanc found decreased blood flow to the brain hemisphere opposite to the side of limb involvement during an attack, while others have reported an increased blood flow or no change at all. In reviewing the timing of the SPECT scan with relation to the onset of the attack, she found that the scans had been performed at various stages of the attack and thus could not be directly compared. She emphasized that a carefully controlled study using SPECT during different stages of the attack might provide useful information as to how the attack begins and spreads in the brain. Unlike SPECT scans, PET scans provide more clear images of the brain and are used to measure a variety of biochemical functions. Dr. Ednea da Silva (Detroit, MI) reported findings from 11 children with AHC. She found that PET scans of glucose metabolism (an indicator of the degree of activity in various regions of the brain) often showed one or more areas of decreased glucose consumption suggesting that they had been damaged. Other children were more likely to show more discrete regions of damage compared to younger children with AHC. A single child studied with PET scanning of benzodiazepine receptors (those sites on the surface of brain cells that are stimulated by medications such as ativan, klonopin or valium) during an attack showed increase activity of this receptor site opposite to the side of limb paralysis; following the attack, the glucose PET scan showed decrease activity in the same area of the brain. A third type of PET scan which measures how fast the chemical serotonin is being made in various regions of the brain has just been developed. Serotonin is increased in migraine and treatment of migraine is designed to block serotonin effects in the brain. The Detroit group has scheduled one AHC patient to undergo this test and plans to study more children in an effort to determine the relationship of AHC to migraine. It is possible that migraine medications might be useful in treating AHC.