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BETA-BLOCKERS IN ESSENTIAL TREMOR
533 PRE-ECLAMPSIA/ECLAMPSIA:
mathematical juggling can be used to discredit tests which may in fact be more sensitive. A prospective study of MCP may help to resolve this
problem.
Medical Department, Falkirk and District Royal Falkirk FK1 5QE
Infirmary,
W. S. J. RUDDELL
BETA-BLOCKERS IN ESSENTIAL TREMOR
SIR,-Leigh and others reported that atenolol, a beta-1selective blocker with low lipid solubility, was less potent than sotalol, a nonselective poorly lipid-soluble blocker, in essential tremor, but metoprolol, a beta-1 selective lipid-soluble blocker, did not significantly differ from placebo. The effect of metoprolol is controversial, however. Several case reports indicate a beneficial We have conducted a placebo-controlled, effect of double-blind cross-over study with atenolol (’Atenol’, ICI) 100 mg x I, metoprolol (’Seloken’, Hassle) 50 mg x 3, propranolol ’Inderal’, ICI) 80 mg x 3, and placebo in 24 patients with essential tremor (13 males and 11 females, mean age 44-7 years). Each treatment period was one week. Tremor and heart rate were measured at the beginning of the trial and after each medication period. The tremor was recorded with an accelerometer attached to the middle finger of the patient’s outstretched hand. The tremor
metoprolol.2-6
signal was amplified, full-wave rectified, and integrated. This value is referred to as tremor intensity. All the beta-blockers reduced the pulse rate. All also lessened tremor intensity, propranolol being most potent, metoprolol least (see table). Differences between the beta-blockers were not significant. EFFECTS OF BETA BLOCKERS AND PLACEBO ON TREMOR INTENSITY AND HEART RATE
(MEAN ± SEM)
*% decrease from drug-free state; fp<0-01 compared with placebo (MannWhttney U test); §p<0’05 compared with placebo (Mann-Whitney U test); Ip
A FATAL FATHER FACTOR
SIR,-In pre-eclampsia/eclampsia immunological alterations are being sought in the mother. A possible role for paternal immunogenetic factors is illustrated by the cases of two women who at
separate times
were
married to the
same
husband.
Case1 The first pregnancy of this 22-year-old, gravida 2, para 1, white female was uncomplicated before the delivery of a stillborn male infant with multiple congenital abnormalities at 36 weeks’ gestation. During her second pregnancy, the blood-pressure (BP) rose to 140/90 mm Hg and she had 3+ proteinuria at 24 weeks’ gestation. When admitted to a community hospital 2 weeks later the patient was oedematous, lethargic, hyperreflexic, and her BP was 250/150. She was treated with intravenous hydralazine and magnesium sulphate, and after an unsuccessful attempt to induce labour with intravenous oxytocin an immature infant that did not survive was delivered by caesarean section. Despite aggressive postpartum treatment for hypertension, cardiac failure, and pulmonary oedema she died on the eighth postoperative day. Necropsy showed extensive myocarditis, massive pericardial and pulmonary effusions, and congested kidneys with well-preserved glomeruli and arcuate arterial thickening presumably secondary to arterial spasm. Death was attributed to acute cardiomyopathy with
preceding pre-eclampsia. Case 2 This
21-year-old, gravida 1, para 0, white female had an uncomplicated antepartum course except for a transient episode of mildly raised BP and peripheral oedema during her last month of pregnancy. She reportedly underwent a normal spontaneous vaginal delivery in a community hospital but postpartum had tonic/clonic seizure despite administration of magnesium sulphate, sodium amytal, and diazepam. She remained comatose and was transferred to the University of Utah Medical Center. On admission with a BP of 130/90, the patient showed decerebrate posturing, deep tendon hyperreflexia, bilateral Babinski signs, and minimal response to pain. During an attempt at dialysis for anuria and azotaemia she became hypotensive and had a respiratory arrest. The necropsy report concluded that the patient had had respiratory failure secondary to a cerebral haemorrhage into the left caudate nucleus with subsequent rupture into the ventricles as the result of antecedent eclampsia. The chance that a man might marry and lose two consecutive wives to severe forms of pre-eclampsia/eclampsia is remote. There is no increase in the incidence of eclampsia in daughters-in-law of eclamptic mothers, suggesting that there are no mother-to-son inheritance patterns, but there are no published reports of fatherto-son inheritance patterns. Pre-eclampsia can occur in a woman who has had a normal pregnancy if she becomes pregnant by another mate,2,3 raising the possibility that the disease is the consequence of a pregnancy by the new husband rather than of specific underlying immunological abnormalities in the mother. Reduced fetomaternal incompatibility and immune response to fetoplacental antigens may contribute to the pathogenesis of preeclampsia.4Unfortunately, the circumstances of our cases provided us with only retrospective information. It was impossible to ,
better effect of metoprolol on essential tremor than The disparity may be due to differences in the methods of evaluating tremor and/or the range of dosage. Our results, together with those of others, I -6 show that the therapeutic effect of beta-blockers on essential tremor is not strictly beta-2 specific. Since low lipid solubility is thought to correlate with poor penetration of the central nervous system and metoprolol was less potent than atenolol, a central action of the beta-blockers does not seem to be of primary importance. Beta-1 selective blockers ;especially atenolol) seem worth trying in essential-tremor patients who cannot tolerate propranolol. We found
a
Leigh and others.
Department of Neurology, University of Helsinki, SF-00290 Helsinki 29, Finland
T. ANDREO LARSEN* HEIKKI TERAVAINEN
’Present address Experimental Therapeutics Branch, NINCDS, National Institutes of Health, Building 10, Room 3D12, Bethesda, Maryland 20205, U.S A.
investigate whether HLA antigens were shared by this husband and his two wives. However, the existence of a genetically transmissible "father factor" (which in these instances proved to be fatal) in cases of pre-eclampsia remains an interesting possibility. Department of Obstetrics and Gynecology, University of Utah Medical Center, Salt Lake City, Utah 84132, U S.A
MARC ASTIN
JAMES R. SCOTT RICHARD J. WORLEY
1 Leigh PN, Marsden CD, Twomey A, Jefferson D. Beta-adrenoceptor antagonists and essential tremor Lancet 1981; i. 1106. 2 Britt CW Jr, Peters BH Metoprolol for essential tremor. N Engl J Med 1979; 301: 331. Liung O Treatment of essential tremor with metoprolol. N Engl J Med 1979; 301: 1005
4 Riley T, Pleet AB Metoprolol tartrate for essential tremor. N Engl J Med 1979; 301: 663
Turnbull DM, Shaw DA. Metoprolol in essential tremor. Lancet 1980; i: 95. Newman RP, Jacobs L. Metoprolol in essential tremor. Arch Neurol 1980; 37: 596-97.
Chesley LC, Annitto JE, Cosgrove RA. The familial factor in toxemia of pregnancy. Obstet Gynecol 1968; 32: 303. 2. Need JA. Pre-eclampsia in pregnancies by different fathers; immunological studies Br Med J 1975; i 548-49 3. Feeney JG. Pre-eclampsia and changed paternity. In Bonnar J, MacGillivray I, Symonds M, eds. Lancaster: MTP Press Limited, 1980: 41-44. 4 Jenkins DM, Need JA, Scott JS, et al Human leukocyte antigen and mixed lymphocyte reaction in severe pre-eclampsia. Br Med J 1978; i. 542-44. 1.
mathematical juggling can be used to discredit tests which may in fact be more sensitive. A prospective study of MCP may help to resolve this
problem.
Medical Department, Falkirk and District Royal Falkirk FK1 5QE
Infirmary,
W. S. J. RUDDELL
BETA-BLOCKERS IN ESSENTIAL TREMOR
SIR,-Leigh and others reported that atenolol, a beta-1selective blocker with low lipid solubility, was less potent than sotalol, a nonselective poorly lipid-soluble blocker, in essential tremor, but metoprolol, a beta-1 selective lipid-soluble blocker, did not significantly differ from placebo. The effect of metoprolol is controversial, however. Several case reports indicate a beneficial We have conducted a placebo-controlled, effect of double-blind cross-over study with atenolol (’Atenol’, ICI) 100 mg x I, metoprolol (’Seloken’, Hassle) 50 mg x 3, propranolol ’Inderal’, ICI) 80 mg x 3, and placebo in 24 patients with essential tremor (13 males and 11 females, mean age 44-7 years). Each treatment period was one week. Tremor and heart rate were measured at the beginning of the trial and after each medication period. The tremor was recorded with an accelerometer attached to the middle finger of the patient’s outstretched hand. The tremor
metoprolol.2-6
signal was amplified, full-wave rectified, and integrated. This value is referred to as tremor intensity. All the beta-blockers reduced the pulse rate. All also lessened tremor intensity, propranolol being most potent, metoprolol least (see table). Differences between the beta-blockers were not significant. EFFECTS OF BETA BLOCKERS AND PLACEBO ON TREMOR INTENSITY AND HEART RATE
(MEAN ± SEM)
*% decrease from drug-free state; fp<0-01 compared with placebo (MannWhttney U test); §p<0’05 compared with placebo (Mann-Whitney U test); Ip
A FATAL FATHER FACTOR
SIR,-In pre-eclampsia/eclampsia immunological alterations are being sought in the mother. A possible role for paternal immunogenetic factors is illustrated by the cases of two women who at
separate times
were
married to the
same
husband.
Case1 The first pregnancy of this 22-year-old, gravida 2, para 1, white female was uncomplicated before the delivery of a stillborn male infant with multiple congenital abnormalities at 36 weeks’ gestation. During her second pregnancy, the blood-pressure (BP) rose to 140/90 mm Hg and she had 3+ proteinuria at 24 weeks’ gestation. When admitted to a community hospital 2 weeks later the patient was oedematous, lethargic, hyperreflexic, and her BP was 250/150. She was treated with intravenous hydralazine and magnesium sulphate, and after an unsuccessful attempt to induce labour with intravenous oxytocin an immature infant that did not survive was delivered by caesarean section. Despite aggressive postpartum treatment for hypertension, cardiac failure, and pulmonary oedema she died on the eighth postoperative day. Necropsy showed extensive myocarditis, massive pericardial and pulmonary effusions, and congested kidneys with well-preserved glomeruli and arcuate arterial thickening presumably secondary to arterial spasm. Death was attributed to acute cardiomyopathy with
preceding pre-eclampsia. Case 2 This
21-year-old, gravida 1, para 0, white female had an uncomplicated antepartum course except for a transient episode of mildly raised BP and peripheral oedema during her last month of pregnancy. She reportedly underwent a normal spontaneous vaginal delivery in a community hospital but postpartum had tonic/clonic seizure despite administration of magnesium sulphate, sodium amytal, and diazepam. She remained comatose and was transferred to the University of Utah Medical Center. On admission with a BP of 130/90, the patient showed decerebrate posturing, deep tendon hyperreflexia, bilateral Babinski signs, and minimal response to pain. During an attempt at dialysis for anuria and azotaemia she became hypotensive and had a respiratory arrest. The necropsy report concluded that the patient had had respiratory failure secondary to a cerebral haemorrhage into the left caudate nucleus with subsequent rupture into the ventricles as the result of antecedent eclampsia. The chance that a man might marry and lose two consecutive wives to severe forms of pre-eclampsia/eclampsia is remote. There is no increase in the incidence of eclampsia in daughters-in-law of eclamptic mothers, suggesting that there are no mother-to-son inheritance patterns, but there are no published reports of fatherto-son inheritance patterns. Pre-eclampsia can occur in a woman who has had a normal pregnancy if she becomes pregnant by another mate,2,3 raising the possibility that the disease is the consequence of a pregnancy by the new husband rather than of specific underlying immunological abnormalities in the mother. Reduced fetomaternal incompatibility and immune response to fetoplacental antigens may contribute to the pathogenesis of preeclampsia.4Unfortunately, the circumstances of our cases provided us with only retrospective information. It was impossible to ,
better effect of metoprolol on essential tremor than The disparity may be due to differences in the methods of evaluating tremor and/or the range of dosage. Our results, together with those of others, I -6 show that the therapeutic effect of beta-blockers on essential tremor is not strictly beta-2 specific. Since low lipid solubility is thought to correlate with poor penetration of the central nervous system and metoprolol was less potent than atenolol, a central action of the beta-blockers does not seem to be of primary importance. Beta-1 selective blockers ;especially atenolol) seem worth trying in essential-tremor patients who cannot tolerate propranolol. We found
a
Leigh and others.
Department of Neurology, University of Helsinki, SF-00290 Helsinki 29, Finland
T. ANDREO LARSEN* HEIKKI TERAVAINEN
’Present address Experimental Therapeutics Branch, NINCDS, National Institutes of Health, Building 10, Room 3D12, Bethesda, Maryland 20205, U.S A.
investigate whether HLA antigens were shared by this husband and his two wives. However, the existence of a genetically transmissible "father factor" (which in these instances proved to be fatal) in cases of pre-eclampsia remains an interesting possibility. Department of Obstetrics and Gynecology, University of Utah Medical Center, Salt Lake City, Utah 84132, U S.A
MARC ASTIN
JAMES R. SCOTT RICHARD J. WORLEY
1 Leigh PN, Marsden CD, Twomey A, Jefferson D. Beta-adrenoceptor antagonists and essential tremor Lancet 1981; i. 1106. 2 Britt CW Jr, Peters BH Metoprolol for essential tremor. N Engl J Med 1979; 301: 331. Liung O Treatment of essential tremor with metoprolol. N Engl J Med 1979; 301: 1005
4 Riley T, Pleet AB Metoprolol tartrate for essential tremor. N Engl J Med 1979; 301: 663
Turnbull DM, Shaw DA. Metoprolol in essential tremor. Lancet 1980; i: 95. Newman RP, Jacobs L. Metoprolol in essential tremor. Arch Neurol 1980; 37: 596-97.
Chesley LC, Annitto JE, Cosgrove RA. The familial factor in toxemia of pregnancy. Obstet Gynecol 1968; 32: 303. 2. Need JA. Pre-eclampsia in pregnancies by different fathers; immunological studies Br Med J 1975; i 548-49 3. Feeney JG. Pre-eclampsia and changed paternity. In Bonnar J, MacGillivray I, Symonds M, eds. Lancaster: MTP Press Limited, 1980: 41-44. 4 Jenkins DM, Need JA, Scott JS, et al Human leukocyte antigen and mixed lymphocyte reaction in severe pre-eclampsia. Br Med J 1978; i. 542-44. 1.