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NEUROTOXIC SIDE-EFFECTS OF PIPERAZINE
369 80 per sec. potentials of muscular response became depressed after initial facilitation; neostigmine depressed the initial of the muscular potentials and the depression evident after repetitive stimulation. Thus a pseudomyasthenic syndrome in the presence of a lowermotor-neurone lesion in the proximal (nuclear) region was confirmed and the diagnosis of M.G. excluded. We have found published reports on 16 patients with M.G. who had s.L.E.1-13 Some doubts remain about the diagnosis of S.L.E., since it was sometimes largely based on a positive L.E.-cell test in the absence of a characteristic clinical pattern.8On the other hand the diagnosis of M.G. was in some cases based only on clinical signs (fatigue, ptosis of the eyelids, relief after acetylcholinesterase inhibitors,69 whereas E.M.G.
amplitudes
became
even more
performed only exceptionally. our patient the pseudomyasthenic syndrome was the first sign of S.L.E. Since muscular atrophy was absent and the result of muscle biopsy was not characteristic, the diagnosis of M.G. was sustained by muscular weakness and fatigue, which were greatly relieved by pyridostigmine bromide, by the fatigue reaction shown by E.M.G., and to some extent also by radiological demonstration of slightly enlarged thymus. Nevertheless, there were some atypical signs: fatigue was already present in the morning and increased only insignificantly during the day, and the way of attaining the sitting position was suggestive of myopathy. The E.E.G. showed transitory focal changes and E.M.G. showed some features pointing to a lower-motor-neurone lesion. The diagnosis was made only after six years’ myasthenia, when further signs of S.L.E. developed and modern E.M.G. methods showed a lowermotor-neurone lesion combined with a pseudomyasthenic syndrome, which was in fact merely one sign of S.L.E. We think, therefore, that some reserve should be expressed as to the validity of those published reports on the simultaneous occurrence of S.L.E. and M.G. in one patient in which the diagnosis was not confirmed by thorough E.M.G. examination This would decrease the number of proven or by surgery. associations of M.G. and S.L.E., which might then be attributed was
In
to
chance. 1st and 2nd Medical Departments, Faculty of Medicine, Charles University, Prague, Czechoslovakia.
JIRI STREJCEK JAN FUCIK ADOLF SVOBODA.
NEUROTOXIC SIDE-EFFECTS OF PIPERAZINE SIR,-We were interested to read the letters by Dr. Miller and Dr. Carpenter 1-’ and by Schuch et al,15 We have observed 16 a four-year-old child who presented, on the third day of treatment with piperazine hydrate (100 mg. per kg. body-weight per day), with severe grave asthenia, tottering gait, poor balance, muscular weakness, and electroencephalographic (E.E.G.). changes This case induced us to examine by E.E.G. all children under treatment with piperazine. In 10 out of 111 extreme
R. F., Maldonado, J. E., Howard, F. M., Jr. Lancet, 1963, ii, 662. 2. Denney, D., Rose, R. L. Neurology, Minneap. 1961, 11, 710. 3. Downes, J. M., Greenwood, B. M., Wray, S. H. Q. Jl Med. 1966, 1.
Alarcón-Segovia, D., Galbraith,
35, 85. Galbraith, R. F., Summerskill, W. H. J., Murray, J. New Engl. J. Med. 1964, 270, 229. 5. Goldin, H., Robbins, W. C. Arthritis Rheum. 1963, 6, 272. 6. Harvey, A. M., Shulman, L. E., Tumulty, P. A., Conley, C. L., Schoenrich, E. H. Medicine, Baltimore, 1954, 33, 291. 7. Hess, E. V., Eliasson, S. G., Grigson, J. P., Ziff, M. The Thymus in Immunobiology (edited by R. A. Good and A. E. Gabrielsen); p. 668. New York, 1964. 8. Makelä, T. E., Ruosteenoja, R., Wager, O., Wallgren, G. R., Jokinen, E. J. Acta med. scand. 1964, 175, 777. 9. Piemme, T. E. Ann. intern. Med. 1964, 60, 130. 10. Rowland, L. P. Neurology, Minneap. 1955, 5, 612. 11. Simpson, J. A. Scott. med. J. 1960, 5, 419. 12. White, R. G., Marshall, A. H. E. Lancet, 1962, ii, 120. 13. Wolf, S. M., Rowland, L. P., Schotland, D. L., McKinney, A. S., Hoefer, P. F. A., Aranow, H., Jr. Ann. N.Y. Acad. Sci. 1966, 135, 517. 14. Miller, C. G., Carpenter, R. Lancet, 1967, i, 895. 15. Schuch, P., Stephan, U., Jacobi, Q. ibid. 1966, i, 1218. 16. Belloni, C., Rizzoni, G. Lattante (in the press). 4.
patients we noticed E.E.G. changes (similar to those described by other workers 17) during five-day courses of treatment (piperazine hydrate, 80 mg. per kg. body-weight per day). In a child with enlarged hard liver due to chronic cardiac failure, striking E.E.G. alterations were present by the second day of treatment, and clinical manifestations (vomiting, vertigo, tremor) appeared on the third day. In 6 of these children piperazine hydrate was given again in the same dose after the E.E.G. had returned to normal, together with prednisone, 1 mg. per kg. body-weight per day. The E.E.G. changes either did not appear or were very slight and less well developed. The child with the enlarged liver did not show clinical symptoms during this second course of therapy, and the E.E.G. alterations were less pronounced and appeared later. We think that these preliminary results entitle us to suggest the simultaneous administration of prednisone to prevent or limit the neurological effects of piperazine. As Dr. Miller and Dr. Carpenter and others 18 have shown, various pathological conditions may predispose to the neurotoxic effects of piperazine. Pædiatric Clinic, University of Pavia, Italy.
C. BELLONI G. RIZZONI.
TRIAL OF FIVE RESPIRATORY STIMULANTS
SIR,-From their assessment of five respiratory stimulants (July 29, p. 226) Dr. Edwards and Dr. Leszczynski commend doxapram as the most effective one in patients with acute ventilatory failure. Since the Extra Pharmacopaia suggests that doxapram should be used cautiously, if at all, in patients receiving monoamine oxidase inhibitors or other sympathomimetic agents ", it would be interesting to know which bronchodilator agents they used in the trial and whether they avoided the use of hand nebulisers containing isoprenaline or adrenaline compounds. The validity of the trial of Dr. Edwards and Dr. Leszczynski depends on the subjects having been similar in all important respects before treatment. Because the forced expiratory volume in one second (F.E.V.1) was higher in the group treated with doxapram, despite attempts at random allocation, the changes in the other indices of lung function are not strictly comparable. It would be helpful to know if their experience with this drug since 1965 has confirmed their early impression of its efficacy. "
M.R.C. Pneumoconiosis Research Unit,
Llandough Hospital, Penarth, Glamorgan.
HAZEL A. C. COCKBURN.
AMITRIPTYLINE AND SPUTUM VISCOSITY SIR,-Is it possible that amitriptyline, by virtue of its peripheral atropine-like effect 19 on the respiratory tract, could increase sputum viscosity ? An asthmatic woman doctor found that her sputum viscosity increased while she was on 150 mg. amitriptyline daily for depression. When the dosage of amitriptyline was halved, there was an increase in fluidity of the sputum and expectoration became easier. While she was on the higher dosage of amitriptyline her previously adequate ephedrine, 30 mg. t.d.s., had to be supplemented with choline theophyllinate 200 mg. b.d., and frequent resort to an isoprenaline sulphate aerosol, 0-4 mg. per dose. She was also on oxazepam 30-40 mg. daily throughout the whole period of treatment. As a result of these observations, amitriptyline was prescribed cautiously in the treatment of a mild depression in a Wechselberg, G. K. Dt. med. Wschr. 1956, 71, 632. Bettecken, F. Z. Kinderheilk. 1956, 80, 225. Cavalcante, M. N., De Mello, J. S. Bolm Inst. Pueric., Rio de J. 1968, 15, 183. Eliachar, E., Pavlotskj, D., Tassj, R. Archs fr. Pédiat. 1960, 17, 797. 18. Chaptal, J., Jean, R., Labauge, R., Bonnet, H., Aghai, E. Archs fr. Pédiat. 1963, 20, 17. Combes, B., Damon, A., Gottfried, E. New Engl. J. Med. 1956, 223, 254. Point, G. Pédiatrie, 1965, 20, 600. 19. Rees, L. Abstr. Wld Med. 1966, 39, 138. 17.
amplitudes
became
even more
performed only exceptionally. our patient the pseudomyasthenic syndrome was the first sign of S.L.E. Since muscular atrophy was absent and the result of muscle biopsy was not characteristic, the diagnosis of M.G. was sustained by muscular weakness and fatigue, which were greatly relieved by pyridostigmine bromide, by the fatigue reaction shown by E.M.G., and to some extent also by radiological demonstration of slightly enlarged thymus. Nevertheless, there were some atypical signs: fatigue was already present in the morning and increased only insignificantly during the day, and the way of attaining the sitting position was suggestive of myopathy. The E.E.G. showed transitory focal changes and E.M.G. showed some features pointing to a lower-motor-neurone lesion. The diagnosis was made only after six years’ myasthenia, when further signs of S.L.E. developed and modern E.M.G. methods showed a lowermotor-neurone lesion combined with a pseudomyasthenic syndrome, which was in fact merely one sign of S.L.E. We think, therefore, that some reserve should be expressed as to the validity of those published reports on the simultaneous occurrence of S.L.E. and M.G. in one patient in which the diagnosis was not confirmed by thorough E.M.G. examination This would decrease the number of proven or by surgery. associations of M.G. and S.L.E., which might then be attributed was
In
to
chance. 1st and 2nd Medical Departments, Faculty of Medicine, Charles University, Prague, Czechoslovakia.
JIRI STREJCEK JAN FUCIK ADOLF SVOBODA.
NEUROTOXIC SIDE-EFFECTS OF PIPERAZINE SIR,-We were interested to read the letters by Dr. Miller and Dr. Carpenter 1-’ and by Schuch et al,15 We have observed 16 a four-year-old child who presented, on the third day of treatment with piperazine hydrate (100 mg. per kg. body-weight per day), with severe grave asthenia, tottering gait, poor balance, muscular weakness, and electroencephalographic (E.E.G.). changes This case induced us to examine by E.E.G. all children under treatment with piperazine. In 10 out of 111 extreme
R. F., Maldonado, J. E., Howard, F. M., Jr. Lancet, 1963, ii, 662. 2. Denney, D., Rose, R. L. Neurology, Minneap. 1961, 11, 710. 3. Downes, J. M., Greenwood, B. M., Wray, S. H. Q. Jl Med. 1966, 1.
Alarcón-Segovia, D., Galbraith,
35, 85. Galbraith, R. F., Summerskill, W. H. J., Murray, J. New Engl. J. Med. 1964, 270, 229. 5. Goldin, H., Robbins, W. C. Arthritis Rheum. 1963, 6, 272. 6. Harvey, A. M., Shulman, L. E., Tumulty, P. A., Conley, C. L., Schoenrich, E. H. Medicine, Baltimore, 1954, 33, 291. 7. Hess, E. V., Eliasson, S. G., Grigson, J. P., Ziff, M. The Thymus in Immunobiology (edited by R. A. Good and A. E. Gabrielsen); p. 668. New York, 1964. 8. Makelä, T. E., Ruosteenoja, R., Wager, O., Wallgren, G. R., Jokinen, E. J. Acta med. scand. 1964, 175, 777. 9. Piemme, T. E. Ann. intern. Med. 1964, 60, 130. 10. Rowland, L. P. Neurology, Minneap. 1955, 5, 612. 11. Simpson, J. A. Scott. med. J. 1960, 5, 419. 12. White, R. G., Marshall, A. H. E. Lancet, 1962, ii, 120. 13. Wolf, S. M., Rowland, L. P., Schotland, D. L., McKinney, A. S., Hoefer, P. F. A., Aranow, H., Jr. Ann. N.Y. Acad. Sci. 1966, 135, 517. 14. Miller, C. G., Carpenter, R. Lancet, 1967, i, 895. 15. Schuch, P., Stephan, U., Jacobi, Q. ibid. 1966, i, 1218. 16. Belloni, C., Rizzoni, G. Lattante (in the press). 4.
patients we noticed E.E.G. changes (similar to those described by other workers 17) during five-day courses of treatment (piperazine hydrate, 80 mg. per kg. body-weight per day). In a child with enlarged hard liver due to chronic cardiac failure, striking E.E.G. alterations were present by the second day of treatment, and clinical manifestations (vomiting, vertigo, tremor) appeared on the third day. In 6 of these children piperazine hydrate was given again in the same dose after the E.E.G. had returned to normal, together with prednisone, 1 mg. per kg. body-weight per day. The E.E.G. changes either did not appear or were very slight and less well developed. The child with the enlarged liver did not show clinical symptoms during this second course of therapy, and the E.E.G. alterations were less pronounced and appeared later. We think that these preliminary results entitle us to suggest the simultaneous administration of prednisone to prevent or limit the neurological effects of piperazine. As Dr. Miller and Dr. Carpenter and others 18 have shown, various pathological conditions may predispose to the neurotoxic effects of piperazine. Pædiatric Clinic, University of Pavia, Italy.
C. BELLONI G. RIZZONI.
TRIAL OF FIVE RESPIRATORY STIMULANTS
SIR,-From their assessment of five respiratory stimulants (July 29, p. 226) Dr. Edwards and Dr. Leszczynski commend doxapram as the most effective one in patients with acute ventilatory failure. Since the Extra Pharmacopaia suggests that doxapram should be used cautiously, if at all, in patients receiving monoamine oxidase inhibitors or other sympathomimetic agents ", it would be interesting to know which bronchodilator agents they used in the trial and whether they avoided the use of hand nebulisers containing isoprenaline or adrenaline compounds. The validity of the trial of Dr. Edwards and Dr. Leszczynski depends on the subjects having been similar in all important respects before treatment. Because the forced expiratory volume in one second (F.E.V.1) was higher in the group treated with doxapram, despite attempts at random allocation, the changes in the other indices of lung function are not strictly comparable. It would be helpful to know if their experience with this drug since 1965 has confirmed their early impression of its efficacy. "
M.R.C. Pneumoconiosis Research Unit,
Llandough Hospital, Penarth, Glamorgan.
HAZEL A. C. COCKBURN.
AMITRIPTYLINE AND SPUTUM VISCOSITY SIR,-Is it possible that amitriptyline, by virtue of its peripheral atropine-like effect 19 on the respiratory tract, could increase sputum viscosity ? An asthmatic woman doctor found that her sputum viscosity increased while she was on 150 mg. amitriptyline daily for depression. When the dosage of amitriptyline was halved, there was an increase in fluidity of the sputum and expectoration became easier. While she was on the higher dosage of amitriptyline her previously adequate ephedrine, 30 mg. t.d.s., had to be supplemented with choline theophyllinate 200 mg. b.d., and frequent resort to an isoprenaline sulphate aerosol, 0-4 mg. per dose. She was also on oxazepam 30-40 mg. daily throughout the whole period of treatment. As a result of these observations, amitriptyline was prescribed cautiously in the treatment of a mild depression in a Wechselberg, G. K. Dt. med. Wschr. 1956, 71, 632. Bettecken, F. Z. Kinderheilk. 1956, 80, 225. Cavalcante, M. N., De Mello, J. S. Bolm Inst. Pueric., Rio de J. 1968, 15, 183. Eliachar, E., Pavlotskj, D., Tassj, R. Archs fr. Pédiat. 1960, 17, 797. 18. Chaptal, J., Jean, R., Labauge, R., Bonnet, H., Aghai, E. Archs fr. Pédiat. 1963, 20, 17. Combes, B., Damon, A., Gottfried, E. New Engl. J. Med. 1956, 223, 254. Point, G. Pédiatrie, 1965, 20, 600. 19. Rees, L. Abstr. Wld Med. 1966, 39, 138. 17.