46 observation of no meaningful change in 5-H.I.A.A. during D.C.S., suggest that measures of c.s.F. monoamine metabolites are unlikely to provide a fruitful approach to the understanding of these sclerotic disorders, nor is precursor therapy likely to prove beneficial.
junction with
MONOAMINE ACCUMULATION AMONG SCLEROTIC PATIENTS RECEIVING DORSAL-COLUMN STIMULATION
our
c.s.F. H.V.A. or
SIR,-During our work on dorsal-column stimulation (D.C.S.) to improve motor impairment among patients with multiple sclerosis (M.S.) or amyotrophic lateral sclerosis (A.L.S.)l we have been studying the effect of D.c.s. on central nervous-system dopamine and serotonin (5-H.T.) metabolism by estimating their turnover through the measurement of their c.s.F. acid metabolites, homovanillic acid (H.V.A.) and 5-hy-
Department of Neurosurgery, Long Island College Hospital, Brooklyn, N.Y., U.S.A.
Long Island Research Institute,
droxyindoleacetic acid (S-H.i.A.A.), using the’probenecid procedure. Probenecid competes with the transport mechanisms which are involved in the egress of weak organic acids from the c.s.F., leading to increased concentrations of metabolites which may reflect central-nervous-system turnover of neurotransmitters.2 Probenecid-related accumulations of H.V.A. and 5-H.I.A.A. were determined among ten patients, six with M.S. and four with A.L.S. Our design called for metabolite assay before and during D.c.s. The six M.S. patients were the first to receive probenecid treatment (100 mg/kg/24 h) which was given orally; but severe probenecid side-effects (e.g., headaches, nausea, and vomiting) allowed completion of the twostage protocol in only two of these six M.S. patients. An intravenous probenecid procedure (40 mg/kg) was then used for the four A.L.s. patients, based upon the demonstration of the comparability of the oral and intravenous procedures, the intravenous procedure having fewer side-effects.3 However, the A.L.S. patients also experienced severe noxious side-effects, and the protocol could be completed for only two of them. These side-effects precluded further study. However, we thought our findings should be recorded. H.V.A. and 5-H.I.A.A. were assayed by spectrophotofluorimetric methods4,s modified to yield data on small volumes of c.s.F. Our modified method has been confirmed by gas-chromatography. Plasma and c.s.F. probenecid was measured by the method of Dayton et al.6 The table shows that no major change in c.s.F. accumulations of either H.v.A. or 5-H.I.A.A. occurred during D.c.s. in any of the patients, although all showed some symptom improvement. Several investigators have reported data indicating a 5-H.T. deficiency among M. s. patients, as inferred from measurement of c.s.F. 5-H.I.A.A. These findings led Hyypa et aU to try L-tryptophan in twelve M. s. patients, resulting in only modest and transient improvement. There is also evidence that 5-H.T. and D.A. synthesis may be deficient in patients with A.L.S. However, levodopa has no clinical benefit.8 These findings, in con-
Health Sciences Center, Stony Brook, N.Y.
ALBERT COOK FLORENCE NIDZGORSKI MARIA HURWIC BERTRAND WINSBERG ALBERT KLUTCH
EFFECT OF THYMECTOMY ON CELLULAR IMMUNITY IN MYASTHENIA GRAVIS
SIR,-The autoimmune response against the nicotinic choline receptor (AChR) of the neuromuscular junction seems to play a key role in the pathogenesis of myasthenia gravis. This immune aggression could be due both to antibodies or to a cellular mediated reaction against this molecule.1,2 To study the effect of thymectomy on the lymphocytic response to AChR we tested the peripheral-blood lymphocytes of eleven myasthenic patients against a postsynaptic membrane fraction rich in AChR, obtained from the electric organ of Torpedo marmorata.3 The test was done before and 1 week to 6 months after thymectomy. All the patients had a positive response before thymectomy, and in all the response fell or even became negative after thymectomy. We calculated a stimulation index (S.I.), defined as the ratio between the mitotic activity, measured by incorporation of 3H-thymidine, in the presence of AChR and in the absence of any stimulation. In twenty-five healthy controls matched for sex and age the mean S.I. was 0-95±0-06. In the patients the S.I. fell from 2.41±0.27 to 1.01±0-17 after thymectomy (P
junction with
MONOAMINE ACCUMULATION AMONG SCLEROTIC PATIENTS RECEIVING DORSAL-COLUMN STIMULATION
our
c.s.F. H.V.A. or
SIR,-During our work on dorsal-column stimulation (D.C.S.) to improve motor impairment among patients with multiple sclerosis (M.S.) or amyotrophic lateral sclerosis (A.L.S.)l we have been studying the effect of D.c.s. on central nervous-system dopamine and serotonin (5-H.T.) metabolism by estimating their turnover through the measurement of their c.s.F. acid metabolites, homovanillic acid (H.V.A.) and 5-hy-
Department of Neurosurgery, Long Island College Hospital, Brooklyn, N.Y., U.S.A.
Long Island Research Institute,
droxyindoleacetic acid (S-H.i.A.A.), using the’probenecid procedure. Probenecid competes with the transport mechanisms which are involved in the egress of weak organic acids from the c.s.F., leading to increased concentrations of metabolites which may reflect central-nervous-system turnover of neurotransmitters.2 Probenecid-related accumulations of H.V.A. and 5-H.I.A.A. were determined among ten patients, six with M.S. and four with A.L.S. Our design called for metabolite assay before and during D.c.s. The six M.S. patients were the first to receive probenecid treatment (100 mg/kg/24 h) which was given orally; but severe probenecid side-effects (e.g., headaches, nausea, and vomiting) allowed completion of the twostage protocol in only two of these six M.S. patients. An intravenous probenecid procedure (40 mg/kg) was then used for the four A.L.s. patients, based upon the demonstration of the comparability of the oral and intravenous procedures, the intravenous procedure having fewer side-effects.3 However, the A.L.S. patients also experienced severe noxious side-effects, and the protocol could be completed for only two of them. These side-effects precluded further study. However, we thought our findings should be recorded. H.V.A. and 5-H.I.A.A. were assayed by spectrophotofluorimetric methods4,s modified to yield data on small volumes of c.s.F. Our modified method has been confirmed by gas-chromatography. Plasma and c.s.F. probenecid was measured by the method of Dayton et al.6 The table shows that no major change in c.s.F. accumulations of either H.v.A. or 5-H.I.A.A. occurred during D.c.s. in any of the patients, although all showed some symptom improvement. Several investigators have reported data indicating a 5-H.T. deficiency among M. s. patients, as inferred from measurement of c.s.F. 5-H.I.A.A. These findings led Hyypa et aU to try L-tryptophan in twelve M. s. patients, resulting in only modest and transient improvement. There is also evidence that 5-H.T. and D.A. synthesis may be deficient in patients with A.L.S. However, levodopa has no clinical benefit.8 These findings, in con-
Health Sciences Center, Stony Brook, N.Y.
ALBERT COOK FLORENCE NIDZGORSKI MARIA HURWIC BERTRAND WINSBERG ALBERT KLUTCH
EFFECT OF THYMECTOMY ON CELLULAR IMMUNITY IN MYASTHENIA GRAVIS
SIR,-The autoimmune response against the nicotinic choline receptor (AChR) of the neuromuscular junction seems to play a key role in the pathogenesis of myasthenia gravis. This immune aggression could be due both to antibodies or to a cellular mediated reaction against this molecule.1,2 To study the effect of thymectomy on the lymphocytic response to AChR we tested the peripheral-blood lymphocytes of eleven myasthenic patients against a postsynaptic membrane fraction rich in AChR, obtained from the electric organ of Torpedo marmorata.3 The test was done before and 1 week to 6 months after thymectomy. All the patients had a positive response before thymectomy, and in all the response fell or even became negative after thymectomy. We calculated a stimulation index (S.I.), defined as the ratio between the mitotic activity, measured by incorporation of 3H-thymidine, in the presence of AChR and in the absence of any stimulation. In twenty-five healthy controls matched for sex and age the mean S.I. was 0-95±0-06. In the patients the S.I. fell from 2.41±0.27 to 1.01±0-17 after thymectomy (P
