Journal of Neurology, Neurosurgery, and Psychiatry, 1976, 39, 367-374

Acetylcholine and choline in cerebrospinal fluid ofpatients with Parkinson's disease and

Huntington's choreaM. J. WELCH', C. H. MARKHAM, AND D. J. JENDEN

From the Departments of Neurology and Pharmacology, School of Medicine,University of California, Los Angeles, California, U.S.A.

SYNOPSIS Lumbar cerebrospinal fluid (CSF) acetylcholine (ACh) and choline (Ch) levels weremeasured in patients with Huntington's chorea (N= 11), Parkinson's disease (N= 8), and subjectsat risk for Huntington's chorea (N= 4), and all three groups were found not to differ significantlyfrom normal controls (N= 10). The values found for lumbar CSF ACh and Ch levels in the normalsubjects were comparable with previously reported values. The use of physostigmine, a cholinesteraseinhibitor, in collecting the CSF samples did not appear to make a difference with regard to ACh andCh concentrations. Evidence suggesting a ventricular-lumbar gradient, with lumbar CSF Chconcentration being less than ventricular CSF Ch concentration, was found. Finally, ACh levels inCSF did not correlate with corresponding Ch levels.

To date it has been very difficult to determinewhether acetylcholine (ACh) is a normal con-stituent of cerebrospinal fluid (CSF) in man.Some investigators found that ACh could bemeasured in the CSF of patients with epilepsy,craniocerebral trauma, and those receivingelectroshock treatment, but not in non-schizo-phrenic psychiatric patients who did not receiveelectroshock treatment, and not in other patientswho may have been neurologically normal(Tower and McEachern, 1949a, b). Others, onthe other hand, detected ACh in the CSF ofnormal subjects but not in certain neuro-psychiatric patients such as schizophrenics(Poloni, 1951). An important problem in settlingthis issue is that the neurotransmitter does notseem to accumulate in CSF to such a degree as tobe readily quantitated, and the fact that CSFcontains both non-specific and specific cholin-esterase activity (Tower and McEachern, 1949c;Jefferson, 1954) is probably important. WhenACh or ACh-like activity has been measured inCSF using various bioassay methods, its con-1 Address for correspondence: M. J. Welch, Department ofNeurology,School of Medicine, University of California, Los Angeles, California90024, U.S.A.(Accepted 11 November 1975.)

367

centration has been found to range from 0.0001to 1.0 FM, with most values centring around0.01 to 0.10 ,uM (Schain, 1960; Duvoisin andDettbarn, 1967).

Because of the difficulty in measuring ACh inCSF, some investigators have looked at themajor metabolite of ACh, choline (Ch). There isa certain amount of evidence to indicate that Chin CSF may be used as an indicator of AChturnover in the brain (Aquilonius et al., 1970).The average concentrations of Ch that have beenmeasured in human CSF range from 0.5 to 4.0,uM, depending on the investigator and the assayused (Aquilonius et al., 1970; Aquilonius et al.,1972). The assays include some type of bioassaysuch as was used by Bowers (1967), or anenzymatic-radioisotope method such as wasused by Jonsson et al. (1969). Recently, a highlysensitive technique, integrated gas chromato-graphy/mass spectrometry (GC/MS), has beenapplied by Jenden et al. (1973) to detect andaccurately quantitate small amounts of bio-chemical compounds such as ACh and Ch intissue samples.One aim of the present study was to utilize

the GC/MS technique to estimate not only Ch

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M. J. Welch, C. H. Markham, and D. J. Jenden

levels but also the very low ACh levels found inthe CSF of human subjects, and to comparethese results with previously obtained values. Asecond aim was to compare the ACh and Chlevels found in normal humans with thosevalues found in patients with Huntington'schorea and patients with Parkinson's disease.Evidence has been accumulating suggesting thatthe cholinergic activity of the striatum (thecaudate and the putamen) may be either rela-tively or possibly absolutely increased inParkinson's disease (Calne, 1970; Hornykiewicz,1971), and decreased in Huntington's chorea(Aquilonius and Sjostrom, 1971). In the case ofHuntington's chorea, a cholinergic hypofunc-tioning could result from the drop-out ofcholinergic striatal interneurones; with Parkin-son's disease, the postulated hyperactivity mightfollow the release of cholinergic neurones in thestriatum from dopaminergic inhibition. Further,Aquilonius et al. (1972) found a significantdifference in Ch between patients with Hunting-ton's chorea and controls, with the Huntington'schorea patients having lower values, but theyfound no difference between controls and patientswith Parkinson's disease.A third objective has been to determine if

there exists a gradient in Ch concentration in theCSF from a higher ventricular value to a lowerlumbar value as suggested by Bowers (1967). Wehave attempted to verify this in two differentways: (1) by comparing the average Ch levels inhuman ventricular CSF with the average Chlevels in lumbar CSF-that is, repeating whatBowers did-and (2) by comparing the Ch levelin a sample of CSF taken soon after the initiallumbar puncture on a given patient with thelevel in a sample taken from 1 to 30 ml after theearly sample. If a gradient truly exists, one mightexpect an early sample to contain less Ch than alater sample since a late sample represents CSFwhich, theoretically, more recently passedthrough the ventricles.

METHODS

PATIENTS Cerebrospinal fluid was obtained fromsix different patient populations:

1. Lumbar CSF from 11 patients with Huntington'schorea Ten were ambulatory outpatients, and onewas bedridden in a nursing home. The duration of

illness ranged from two to nine years with a mean of5.5 years. The patients' ages were from 43 to 64years (mean of 51 years) and six were males.Dementia and choreoathetosis were graded as beingabsent, mild, moderate, or severe by a neurologist.One of the patients was on haloperidol (Haldol),4 mg/day, and reserpine, 0.50 mg/day; another wason reserpine, 6 mg/day, but the drug was dis-continued two days before removal of CSF.

2. Lumbar CSF from four patients at-risk forHuntington's chorea They were the teenage childrenof a single patient who had Huntington's chorea,and thus each had a 5070 chance of ultimately mani-festing the disease. Their ages were 16, 18, 19, and 20years; three were males.

3. Lumbar CSFfrom eight patients with Parkinson'sdisease The patients' ages ranged from 43 to 77years (mean of 62 years) and four were males. Theduration of illness ranged from three to 21 years andaveraged 7.5 years. Five patients had mild bilateraltremor and/or rigidity (stage II in the classificationsystem of Hoehn and Yahr (1967)) and three hadmore severe tremor and rigidity and impaired right-ing reflexes (stage III). Five were on regular L-dopamedication ranging from 2.0 g/day to 7.5 g/day, andtwo were on Carbidopa, which is L-dopa plus aperipherally acting DOPA-decarboxylase inhibitor.One patient was taking 500 mg L-dopa and 50 mginhibitor daily, and the other was taking 750 mgL-dopa and 75 mg inhibitor per day. Three patientswere taking anticholinergic agents; one, trihexi-phenidyl (Artane), 6 mg/day; another, procyclidine(Kemidrin), 10 mg/day; and the third, benztropine(Cogentin), 4 mg/day. One patient had been off allanti-Parkinsonism drugs for four days at the time aCSF sample was taken.

4. Lumbar CSF from 10 control subjects Theseindividuals were either spouses or friends of thepatients with Huntington's chorea and were free ofneurological disease. The ages of the control subjectswere from 24 to 69 years (mean of 46 years) with fivebeing males.

5. Ventricular CSF from six patients undergoingventriculograms These individuals had the follow-ing diagnosis: neurofibromatosis, obstructive hydro-cephalus (two patients), pseudotumor cerebri,myelomeningocoele, and astrocytoma. Their agesranged from 2 weeks to 45 years (mean of 20 years)with four being males.

6. Lumbar CSFfrom 30 miscellaneous patients takenduring course of pneumoencephalogram or myelo-

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ACh and Ch in cerebrospinal fluid ofpatients with Parkinson's disease and Hiuntington's chorea 369

gram Ten patients were ultimately consideredneurologically normal, while 20 were found to havevarious neurological disorders including old polio-myelitis, presenile dementia, olivopontocerebellaratrophy, pituitary adenoma (two), cerebral palsy,seizure disorder (four), traumatic spinal cord injury(three), Guillain-Barre syndrome, cerebral atrophy(two), meningioma, headaches with elevated CSFprotein, viral encephalitis, and posterior fossateratoma. The 26 adults received ephedrine,droperidol, and/or meperidine as pretest medica-tions; the four children were anaesthetized withcyclohexamine (Ketamine). The ages of the patientsranged from 3 to 68 years (mean of 42 years) with 15being males.

SAMPLE COLLECTION Samples of CSF were col-lected in tubes containing 0.05 ml 6 x 10-3 molarphysostigmine salicylate, a cholinesterase inhibitorwhich was added to protect the ACh from enzymaticbreakdown. Further analysis, however, suggestedthat this did not make a significant difference in AChor Ch values (see Results section), and thus was notdone in the patients with Huntington's chorea, thenormal controls, and in some patients with Parkin-son's disease. After collection, all samples were

immediately frozen and kept at 0°C until analysed.In the 30 miscellaneous patients who underwent

pneumoencephalograms or myelograms, sometimesup to 35 ml CSF was removed in small aliquots. Itwas therefore possible to obtain an early sample of

CSF taken soon after the initial lumbar puncture,and a late sample taken 1.0 to 30 ml later.

Ach AND ch ANALYSIS The samples were thawed andany samples that were grossly bloody were discarded.As Aquilonius et al. (1972) reported for choline, andas was confirmed in this study for ACh and Ch,microscopic blood contamination (range of 1 to145 cells/ml) did not appear to correlate with Ch or

ACh values. The samples were then centrifuged in a

clinical centrifuge and a 0.5 ml aliquot of CSFsupernatant was drawn off for analysis. Each samplewas run in duplicate. Levels of ACh and Ch were

measured using the GC/MS method used byFreeman et al. (1975). Simply put, the method is onein which endogenous amounts of ACh and Ch in a

tissue or fluid are determined by an isotope dilutionassay using known amounts of deuterium-labelledvariants of ACh and Ch as internal standards anddetermining the isotope ratio for each compoundby GC/MS.

RESULTS

The mean values of two trials for ACh rangedfrom 0.02 to 0.07 FM and from 2.31 to 3.35 ,uMfor Ch (Table 1). Choline was present, therefore,in a concentration about 50-60 times theconcentration of ACh. The presence or absenceof physostigmine, a cholinesterase inhibitor, in

TABLE 1SUMMARY OF ACh AND ch LEVELS IN VARIOUS PATIENT GROUPS STUDIED

Patient group Site of CSF Mean SEMt N Rangeremoval* (pLM) (GM)

AcetylcholineNormal controls L 0.07 0.02 10 0.00-0.13Huntington's chorea L 0.05 0.02 11 0.00-0.18At-risk for Huntington's chorea L 0.04 0.01 4 0.00-0.11Parkinson's disease L 0.07 0.04 8 0.00-0.32Ventriculogram V 0.04 0.01 6 0.00-0.10Miscellaneoust L 0.06 0.01 30 0.00-0.18

CholineNormal controls L 3.35 0.38 10 2.41-6.30Huntington's chorea L 2.92 0.24 11 1.79-4.03At-risk for Huntington's chorea L 3.07 0.13 4 2.67-3.27Parkinson's disease L 3.27 0.53 8 1.56-6.45Ventriculogram V 3.20 0.40 6 1.86-4.86Miscellaneous$ L 2.86 0.11 30 1.55-3.89

All groups not significantly different from normal controls using Student's t test with P= 0.05 as level of significance.* L = Lumbar. V = Ventricle.t SEM = standard error of the mean.

t Since each patient in this group had both an early and late sample of lumbar CSF taken, it was necessary to averagethe ACh (Ch) levels of the early and late samples to obtain a single ACh (Ch) level for that patient. These individualaveraged values were then used in calculating the mean for the group.

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M. J. Welch, C. H. Markham, and D. J. Jenden

the CSF collecting tube did not seem to make a

significant difference in the ACh and Ch levelsmeasured. This followed from the finding thatthose groups of patients whose CSF was notcollected using physostigmine-that is, theHuntington's chorea patients, the subjects at-risk for Huntington's chorea, and the normalcontrol subjects-did not tend to have lower AChor higher Ch levels in the CSF than those groups

whose CSF was collected using the cholinesteraseinhibitor-that is, the miscellaneous patients, theventriculogram patients, and most of thepatients with Parkinson's disease. Furthermore,there was no obvious relationship within theParkinson's disease group between CSF AChand Ch levels and the presence or absence ofphysostigmine in the collecting tubes.The normal control group had a mean value of

ACh in lumbar CSF of 0.07 ,uM with all valuesranging from 0.00 to 0.13 FM. Two of the 10normal control subjects had no detectable levelsof ACh in their CSF. The mean level of Ch inthis same group was 3.35 ,uM; most of the valuesfell within the narrow range of 2.41 to 3.14 F.Mbut two samples were found to have 4.61 and6.30 ,uM, resulting in an overall mean of 3.35 ,uM.As shown in Table 1. both mean ACh and Ch

levels in lumbar CSF of patients with Hunting-ton's chorea (0.05 and 2.92 ,uM, respectively)were found to be less than the correspondinglevels found in the normal controls but thesedifferences were not significant at the P=0.05level. Duration of illness did not correlatesignificantly with individual CSF ACh or Chlevels in the patients with Huntington's chorea.Although the severity of the disease could notcompletely explain the individual differences inACh and Ch levels in these patients, there was

one patient with Huntington's chorea with thehighest combined dementia-chorea score whoalso had the second lowest CSF Ch level and thehighest ACh level. This same patient was the one

on haloperidol (4 mg/day) and reserpine (0.50mg/day). Finally, the four subjects at risk forHuntington's chorea all had ACh and Ch valuesthat varied little from each other and as a groupthey did not have ACh or Ch concentrationssignificantly different from the normal controls(Table 1).

In the group with Parkinson's disease therewas also no significant difference found between

TABLE 2STAGE OF PARKINSON'S DISEASEAND CSF ACh AND ch LEVELS

Acetylcholine Choline(riM) (gM)

Stage II Stage III Stage II Stage III

0.01 0.12 3.33 6.450.00 0.32 3.06 4.170.01 0.06 1.56 2.230.01 3.030.01 2.35

Mean0.01 0.17 2.66 4.28

P < 0.05 P > 0.05(by Student's t test) (by Student's t test)

the ACh or Ch concentrations in lumbar CSF ofpatients with Parkinson's disease (0.07 and 3.27,M respectively) when compared with normalcontrols (Table 1). The type of drug therapy-that is, the use of anticholinergics, the amount ofL-dopa, the use of a decarboxylase inhibitor-did not significantly influence individual AChand Ch levels. It should be noted, however, thatthe highest ACh value was found in the onepatient who was on no L-dopa or anticholiner-gics at the time CSF was obtained. The durationof illness did not correlate with individual levelsof CSF ACh and Ch. The severity of the disease,however, did seem to make a difference; two ofthe three patients with Parkinson's disease whowere rated as being stage III in severity of theirdisease had ACh and Ch concentrations con-

TABLE 3Ach AND ch LEVELS

IN EARLY LUMBAR CSF* VS VENTRICULAR CSFt

Mean S.E.M. N Range(gM) (IM) (IiM)

AcetylcholineEarly lumbar CSF 0.05 0.01 30 0.00-0.22Ventricular CSF 0.04 0.01 6 0.00-0.10

(P > 0.05 by Student's t test)

CholineEarly lumbar CSF 2.31 0.13 30 1.22-3.46Ventricular CSF 3.20 0.40 6 1.86-4.86

(P < 0.05 by Student's t test)

* As represented by CSF samples from miscellaneous patients (seedefinition in text) taken before 10 ml CSF had been drained off.t As represented by CSF samples from patients undergoing ventriculo-grams.

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ACh and Ch in cerebrospinal fluid ofpatients with Parkinson's disease and Huntington's chorea 371

5.00H

4.00F

C:0C-)-c_r

3.00k

1 .00k

5.0 10.0 15.0 20.0 25.0Volume Sequence in ml.

siderably higher than the five patients who wererated stage IL (Table 2).The mean level of Ch in samples of ventricular

CSF obtained from patients undergoing ven-triculograms was not significantly different fromthe mean lumbar Ch levels in the normal con-trols (Table 1). However, the CSF from thelatter group was taken in every instance after10 ml of fluid had been drained off and dis-carded. If one considered the early samples ofCSF-that is, samples taken before 10 ml offluid had been drained off-taken from themiscellaneous patients more accurately to repre-sent lumbar CSF, then the difference betweenventricular CSF Ch, and lumbar CSF Ch wassignificant (3.20 vs 2.31 ,uM, respectively, whichsignificantly differed with P <0.05) (Table 3).Unlike Ch, ACh levels in ventricular CSF werenot significantly different from ACh levels inearly lumbar CSF (Table 3).Of the 30 miscellaneous patients from whom

both an early sample and a late sample of CSFwas obtained, 24 had the early sample contain-ing a lower Ch concentration than the latersample. A chi squared test with a Yates correc-tion showed this to be significant with P < 0.01.In addition, the volume sequence of a CSFsample-that is, how many ml after the initiallumbar puncture the sample was taken-

FIGURE Relationship of CSF Chconcentration (V±M) to CSF volumesequence (ml) (N=30).

30.0 35.0

correlated positively with the Ch concentrationin that sample with a Pearson-product-momentcorrelation coefficient of 0.576 which was signifi-cant with P<0.01 (Figure). Such a differencebetween early and late samples was not foundwith ACh concentrations.Ten of the 30 miscellaneous patients who

ultimately were shown to have no demonstrableCNS disease did not have significantly differentvalues for CSF Ch when compared with theremaining 20 patients who were known to have adefinite CNS disorder (3.05 vs 2.76 FM; t testshowed P > 0.05). Similarly, no appreciabledifference was found between these two groupswith regard to CSF ACh (0.06 vs 0.06 ,uM; t testshowed P > 0.05).

Finally, the possibility that there existed sometype of a relationship between ACh and Chlevels in CSF-for example, does ACh tend to behigh when Ch is high?-was investigated. Theresults of the Pearson-product-moment correla-tion analysis indicated that for each group ofpatients, as well as generally for all patients as awhole, the Ch level in a given CSF sampletended to be quite independent of the corre-sponding ACh level in that sample (P > 0.05).

DISCUSSION

It indeed appears that ACh is a normal con-

6.00F

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M. J. Welch, C. H. Markham, and D. J. Jenden

stituent ofCSF in human subjects as evidenced bythe definite although low level of ACh found inthe normal control subjects. This level is in goodagreement with that found by Duvoisin andDettbarn (1967) using a much improved bio-assay. Similarly, the mean Ch level in normallumbar CSF found in the present study confirmspreviously reported values for CSF Ch (Bowers,1967; Aquilonius et al., 1970; Aquilonius et al.,1972).Because cholinergic mechanisms in the caudate

nucleus and putamen appear to be involved inboth Huntington's chorea and Parkinson'sdisease, it was initially suspected that CSF AChand/or Ch in these two disorders might bedifferent from levels in normal subjects. It is wellestablished that ACh concentration in the stri-atum is significant (Campbell and Jenden, 1970;Butcher and Butcher, 1974) as is acetylcholin-esterase and choline acetylase. Striatal ACh isconcentrated in nerve endings, or at least in thesubcellular fraction on ultracentrifugation whichcontains synaptic vesicles (Laverty et al., 1963).It now appears that the cells of origin of theseACh-containing synaptic terminals belong en-tirely or almost entirely to one class of caudateinterneurones, for damaging the areas whichproject to the striatum (the thalamus, cerebralcortex, and ventral midbrain tegmentum) doesnot materially alter striatal choline acetylase(McGeer et al., 1971), an enzyme primarily con-fined to cholinergic neurones. In Huntington'schorea there is a major loss of striatal neurones(Bruyn, 1968), the brunt of the loss being tointerneurones. This conclusion stems from Golgiand electron microscopic studies of the catstriatum which show that about 98% of striatalneurones are interneurones, and about 96% ofthe total cells are of one morphological celltype, the medium spiny neurone (Kemp andPowell, 1971a, b). In Huntington's chorea thereis a reduction in choline acetylase of from 50-9900 in the striatum in most cases (Bird et al.,1973; McGeer et al., 1973; Stahl and Swanson,1974). A sizeable reduction in striatal ACh orCh might therefore be reflected in the lumbarCSF; we did not find either, although Aquiloniuset al. (1972) did find significantly lowered Ch ascompared with controls. The discrepancy be-tween their findings and those of the presentstudy might be explained by the fact that their

patients may have had more advanced disease.Their patients were all inpatients unlike most ofours; the average duration of illness in theirseries was 9.2 years as compared with 5.2 yearsfor ours; and more appeared to have severedementia. However, the lack of correlationbetween Ch levels and duration and severity ofillness in our own series makes this explanationunlikely.Assuming that our results are correct, how can

they be explained? There is little doubt that AChmetabolism is reduced in the striatum of patientswith Huntington's chorea. If this is so, thenlumbar CSF Ch and ACh do not reflect striatalACh metabolism.

In Parkinson's disease, no direct observationson striatal ACh or its metabolites or enzymeshave been shown to be abnormal. However,anticholinergic medication causes clear, mild tomoderate benefit to symptoms of Parkinsonism.In human Parkinson's disease the dopaminecontent of the substantia nigra (Hornykiewicz,1963) and the striatum (Bernheimer et al., 1963)is greatly decreased, and the large pigmentalnigral neurones are much reduced in number(Hassler, 1955). In animals it has been shown thatnigral neurones containing dopamine project tothe striatum and branch many times beforeterminating in irregular varicose endings. It isnot known precisely on which cells these endingssynapse, but the character of the endings, theirwidespread and dense distribution make itlikely that they terminate on the medium sizedspiny neurones which constitute some 96% ofstriatal cells. For reasons given above, some ofthese interneurones are almost surely cholinergic.A loss of dopamine, a neurotransmitter withpossibly inhibitory transmitter function, couldlead to overactivity of the post-synaptic cells,some of which contain ACh. If these severalhypotheses be correct, then in Parkinson'sdisease there may be a relative or absolute over-activity of striatal cholinergic cells; and an in-creased ACh or Ch might possibly be expected innearby CSF. However, we did not find a signifi-cant difference in CSF ACh and Ch levelsbetween patients with Parkinson's disease as agroup and the normal subjects, which is inagreement with Aquilonius et al. (1972) withregard to Ch. As with the inverse model ofHuntington's chorea, this strongly suggests that

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ACh and Ch in cerebrospinal fluid ofpatients with Parkinson's disease and Huntington's chorea 373

lumbar CSF ACh and Ch do not reflect striatalmetabolism of these substances. A finding that isdifficult to explain and should be noted is thatalthough as a group the patients with Parkinson'sdisease did not differ from normal subjects, twoof the three stage III patients with Parkinson'sdisease had Ch and ACh levels appreciablyhigher than both the normal subjects and theremaining Parkinson's disease patients who werestage II. Examination of the CSF from patientswith stage IV and V of Parkinson's disease wouldseem indicated.The evidence in favour of a major part of

CSF Ch being derived from ACh metabolism inthe brain has been summarized by Aquiloniuset al. (1970). However, recent evidence has beenfound to question this theory (Schuberth andJenden, 1975). It seems that other possibilitiessuch as CSF Ch being derived from plasma, orCSF Ch representing a breakdown product ofbrain phospholipids can still not be excluded.The negative findings in this study support theview that lumbar CSF Ch is not representativeof ACh metabolism in the brain.

There are some findings in the present studythat fit with the theory that CSF Ch is derivedprimarily from the brain, although not neces-sarily the striatum or ACh metabolism. It wasfound that 80% of the time a small sample ofCSF taken early after a lumbar puncture in agiven patient had a lower Ch level than did asample taken in the same patient anywhere from1.0 to 30 ml after the early sample. In addition,the Ch levels in the early lumbar CSF samplesfrom the miscellaneous patients were found to besignificantly lower than the Ch concentrations inventricular CSF samples of other patients. Boththese findings suggest, as did the finding ofBowers (I1967), that a ventricular-lumbar gradientexists in man with the ventricular CSF Ch beinghigher than lumbar CSF Ch. They also suggestthat an important source of Ch in CSF is thebrain surrounding the ventricles. The bio-chemical source within the brain, however, doesnot necessarily have to be ACh; it might beplasma Ch, brain phospholipids such as phos-phatidyl choline, or some other unknown source.Regardless of the chemical or anatomicalsource, a gradient such as was found could alsobe due to the removal of Ch from CSF as itpassed from the ventricles to the spinal sub-

arachnoid space. Such a transport process forCh in CSF has already been described andstudied in dogs and rabbits (Aquilonius andWindbladh, 1972).

In contrast with Ch, ventricular vs lumbar andearly lumbar vs late lumbar differences were notfound with CSF ACh. This finding agrees withthat of Turner and Mauss (1959) who also foundACh levels in ventricular CSF to be essentiallythe same as those levels in lumbar CSF, eachbeing about 0.04 AM. The most reasonableexplanation for this is the fact that cholinesteraseis present throughout the whole CSF system.Thus, ACh in ventricular fluid and in spinalfluid would be hydrolyzed to a universally lowlevel, reducing any differences which may haveexisted initially. A second possibility may bethat ACh levels in CSF are unrelated to Chlevels in CSF and just because Ch differenceswere found between lumbar and ventricular CSFdoes not mean that ACh differences should alsobe expected. Support for this notion is thefinding that ACh levels in lumbar CSF bore norelationship with Ch levels.As has been evident throughout this discus-

sion, the question of whether or not lumbar CSFACh and Ch truly reflect ACh turnover in thebrain must be answered before the results of thisstudy can be fully understood. Further studies inthis area, however, should take into account anapparent ventricular-lumbar gradient for CSFCh in man.

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Huntington's chorea.with Parkinson's disease andcerebrospinal fluid of patients Acetylcholine and choline in

M J Welch, C H Markham and D J Jenden

doi: 10.1136/jnnp.39.4.3671976 39: 367-374 J Neurol Neurosurg Psychiatry 

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