Cerebrospinal fluid acetylcholine in man

LITTLE HAS BEEN ADDED to our knowledge of the acetylcholine (ACh) activity of human cerebrospinal fluid (CSF) since the subject was reviewed by Schain in 1960.l He noted that ACh or ACh-like activity had been reported in human CSF in a variety of disease states by a number of investigators. Because ACh has only been estimated by bioassay methods, it is not entirely certain-although it appears very probable-that the ACh-like activity which has been reported in human CSF actually represents acetylcholine. The significance of this ACh activity in the CSF remains conjectural. No evidence has yet been presented to indicate any physiological function of ACh in the CSF or that it reflects any particular functional state of the nervous system. It is not even certain that it is of neural origin. However, it appears reasonable to consider, as has been presumed, that minute amounts of ACh may leak from nerve cells and somehow escape enzymatic destruction in neural tissue or in the CSF. In any event, there seems to be good agreement in the pertinent literature that ACh is nearly always present in patients having idiopathic epilepsy and following craniocerebral trauma and that in these conditions it is found more frequently and in higher concentrations than in other circumstances. Whether or not the larger amounts of ACh found in the CSF following cranial trauma contribute to or in some way relate to the clinical manifestations has been a subject of particular interest and controversy.2-4 It has also been suggested that the presence of ACh in the CSF may be correlated with migraine,5 but this report remains unconfirmed. The only report of CSF acetylcholine in man published since Schain’s review is that of Sahare who assayed the lumbar spinal fluid ACh in 40 patients with a varie,ty of neurological disorders and in 20 patients who had undergone cranial surgery for brain tumor or abscess. ACh was found in 25 of his 40 neurological patients and in all but one of the postoperative cases in somewhat higher values. The higher values in the latter patients were presumed to reflect the trauma of surgery, but the author found no correlation with the clinical status. Elevated values were also found in two patients with polyneuritis. I t thus appears that ACh may be present in the CSF in a variety of conditions, and in this circumstance one may wonder whether it may not be a normal constituent of the CSF. There is, however, little agreement regarding the presence of ACh in the CSF of normal subjects. Tower and MacEachern,2,7 in a large and thorough study, found ACh in the CSF only in epileptics and following trauma. Kunkle5 found CSF ACh in 5 of 9 migrainous subjects but in only 2 of 37 patients without migraine; these 2 were epileptic. On the other hand, Polonis reported finding ACh in the CSF of 10 normal subjects and in a large number of patients with various neuropsychiatric disorders while it was present in only 2 of 50 schizophrenics. In contrast to the authors cited above, he considered the absence of acetylcholine-like activity in the CSF a significant find-