- Email: [email protected]
FULMINANT HEPATITIS DUE TO CYPROTERONE ACETATE
215
Transverse section images at
comparable levels in patient with CJD (left and middle) and control (right). Left: CT scan of patient (February, 1987). Middle: SPET scan of patient (May, 1987). Right: Normal SPET scan (at about same level).
there was no history of myocardial infarction or cerebrovascular disease. His only medication was propranolol and isosorbide dinitrate. There were no focal neurological signs or evidence of hypertension or other cardiovascular abnormality. Laboratory tests were normal, as were chest and skull X-rays and EEG. A CT scan in February, 1987, showed no evidence of cerebral atrophy (figure). The diagnosis seemed to be presenile dementia of multi-infarct or Alzheimer type. In March, 1987, significant deterioration was noted; he was now perseveradve in answering questions, had great difficult in remembering where he lived, and could not name simple objects. There was evidence of right-left disorientation. His MMSE score was 9/30. 1 month later he needed continual help with bathing, toileting, feeding, and dressing. He had a shuffling gait and had difficulty climbing stairs. In May, 1987, he was admitted for further investigation. He was agitated and unable to cooperate with even simple psychological tests. He had severe expressive and receptive dysphasia. On a behavioural scale on which an independent, fit elderly person would be expected to score 0-3, he scored 17-23, consistent with severe impairment and dependency. SPET, with 99mTc-HMPAO (’Ceretec’, Amersham International) revealed much reduced uptake throughout the greymatter of the cerebral cortex (figure). Flow relative to occipital cortex in frontal regions was compared with that in age-matched controls and was much reduced-eg, right high frontal 0.55 (normal range O’88-l 40). These images of function are in striking contrast to the earlier, normal CT images. The patient died at home in
information when structural brain imaging macroscopic brain structure is preserved.
MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh EH10 5HF; Department of Neuropathology, Western General Hospital, Edinburgh, and Wellcome Neuroscience Group, Institute of Neurological Sciences, Glasgow
is normal and R. HUNTER A. GORDON R. MCLUSKIE D. WYPER J. PATTERSON J. E. CHRISTIE G. FINK G. M. GOODWIN
1. Neirinckx RD, Canning LR, Piper IM, et al. Technetium-99m d,l-HM-PAO. a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion.
J Nucl Med 1987; 28: 191-202 2. Herscovitch P, Auchus AP, Gado M, Chi D, Raichle ME. Correction of positron emission tomography data for cerebral atrophy.J Cerebral Blood Flow Metab 1986; 6: 120-24. 3. Chawluk JB, Alavi A, Dann R, et al. Positron emission tomography in ageing and dementia: effect of cerebral atrophy. J Nucl Med 1987; 28: 431-37. 4. Kuritzky A, Davidowitch S, Sandbank U, Bechar M. Normal EEG in CreutzfeldtJakob disease. Neurology 1980; 30: 1134-35. 5. Galvez S, Cartier L. CT findings in 15 cases of Creutzfeldt-Jakob disease with histological verification. J Neurol Neurosurg Psychiatry 1984; : 47: 1244-46. 6. Keshaven MS, Lishman WA, Hughes JT. Psychiatric presentation of CreutzfeldtJakob disease Br J Psychiatry 1987; 151: 260-63. 7. Pattie AH, Gilleard CJ. Manual of the Clifton assessment procedures for the elderly (CAPE). London: Hodder and Stoughton, 1985. 8. Costa DC, Ell PJ, Burns A, Philpot M, Lezy R. CBF tomograms with 99mTc-HMPAO in patients with dementia (Alzheimer type and HIV) and Parkinson’s disease: initial results. J Cerebral Blood Flow Metab 1988; 8: S109-15.
October, 1987. Post mortem examination revealed a normal sized brain but histopathological examination confirmed the later clinical suspicion that neither multi-infarct nor Alzheimer type dementia was the correct diagnosis. Widespread, severe neuronal depletion and vacuolation with rod cell infiltration and astrocytic gliosis was noted throughout the cerebral cortex. Spongiform degeneration was most striking in the supra-medial border of the frontal lobes. The basal ganglia and corticospinal tracts were also affected. The neuropathological findings were consistent with CJD. Since most investigations had been normal the speed of deterioration was the only real clinical clue. Even in advanced CJD the CT scan is often normalHere the CT appearances were consistent with the normal macroscopic appearance of the brain.
However, SPET images were grossly abnormal and were atypical of other dementias (Alzheimer’s,8 Korsakoff’s). Estimation of regional brain function with SPET can provide essential additional
FULMINANT HEPATITIS DUE TO CYPROTERONE ACETATE
SiR,—Cyproterone acetate (CPA) is a drug generally prescribed for female hirsutism, prostatic cancer, precocious puberty, advanced breast cancer, and acne, CPA is thought to be well tolerated. Only five cases of hepatic reactions have been published; two were of acute hepatitis and none were fulminant. A 78-year-old man was admitted on May 20,1988, for jaundice. A year earlier he had been in hospital for surgery for prostatic cancer without metastasis. In December, 1987, he received CPA 200 mg daily; liver function tests were normal. On May 16, 1988, jaundice appeared with dark urine and white stools but no pruritus. He was admitted with jaundice and a liver span of 9 cm on the right midclavicular line, but there was no hepatic encephalopathy or fever. Mild ascites was present. He was taking CPA and diosmine
216 total bilirubin was at 178 Eunol/1 alkaline phosphatase 153 IU/1 (normal below 120), aminotransferase activities were 720 IU/1 and 1015 IU’l (ALT). Prothrombin time was 45% of normal with factor V at 47%. Ultrasonography indicated a small and homogeneous liver. Serological markers of hepatitis virus, cytomegalovirus, and herpes viruses were negative. Antibodies to nuclei, smooth muscle, and mitochondria were negative. On May 24 liver biopsy revealed severe hepatic necrosis and infiltration with polymorphonuclear cells. On May 28 hepatic encephalopathy developed, the prothrombin time fell (22%), and there were biological signs of intravascular coagulation. The patient died on June 1. The fulminant hepatitis in this case can be ascribed to CPA because viral infections were excluded and there was no circumstantial evidence for a risk of non-A non-B hepatitis; the predominantly centrilobular distribution of the necrosis, suggests drug-induced hepatitis; and diosmine is not thought to be
300 mg
daily. His
(conjugated 145),
serum
serum
(AST)
hepatotoxic.3 Liver damage due to CPA is rare and only five other cases have been described. Three patients with advanced breast cancer (out of twenty) had a mild increase in aminotransferase activity during treatment with CPA. Two others had developed hepatitis 11 weeks (400 mg daily) or 21 weeks (200 mg daily) after the start of treatment. These two had acute hepatitis with bridging necrosis and liver tests returned to normal 9 weeks and 3 months, respectively, after CPA was stopped. The mechanism is obscure. The absence of clinical and biochemical manifestations of hypersensitivity in our patient and in the previous cases suggests that the hepatic lesions might be related to direct or to reactive metabolite mediated toxicity. We recommend that aminotransferase activities be monitored in patients
on
CPA. C. TRIVALLE N. D. MANCHON J. P. VINEL N. MOORE J. HÉMET H. COURTOIS E. BERCOFF J. BOURREILLE
H. LÉVESQUE CHU de Rouen, 76000 Rouen, France; and CHU de Toulouse-Purpan
1 Editorial Cyproterone acetate Lancet 1976; i: 1003. 2 Meijers WH, Willemse PHB, Sleijfer Th, Mulder
3
NH, Grond J. Hepatocellular damage by cyproterone acetate. Eur J Cancer Clin Oncol 1986; 22: 1121. Stncker BHCH, Spoelstra P Drug-induced hepatic injury. Amsterdam: Elsevier, 1985.
a minute decreased progressively to 75-80/min. The complex changed polarity progressively without intraventricular delay and promptly returned to normal at the end of
then after
QRS
the seizure. The seizures were resistant to treatment with intravenous diazepam and with oral phenobarbitone, nitrazepam, and clonazepam. During a long seizure, one of us intervened in an attempt to counteract the hypertonia: the patient was held by the head and legs and forcibly flexed toward the trunk. The seizure ceased immediately. The procedure was repeated several times and always proved effective. The parents easily learned this method but had to observe their daughter constantly. The family was then given a cardiorespiratory monitor with an apnoea alarm and thus the patient was able to leave the hospital at age 3t months. The seizures continued to occur daily up to 5 months of age. Later they became less frequent; at 12 months they occurred weekly, and monthly at age 1I 2 years. The last seizure was at age 2and the parents have now discontinued monitoring. Later the mother of a 12-year-old girl with startle disease reported that when her daughter had stiffness seizures in the first few years of life, she was able to stop them by forcibly bending the child’s head. In a new case at the department of paediatric neuropsychiatry of the University of Verona, our technique also stopped stiffness seizures. We do not know why the abrupt flexing of head and limbs stops stiffness seizures. Startle disease, although rare, is a potential cause of sudden death from respiratory arrest during prolonged stiffness seizures. However, death can be avoided by stopping the seizures with the method we describe. Department of Pediatric Neuropsychiatry, Bambino Gesū Children’s Hospital, Rome, Italy; FEDERICO VIGEVANO and Department of Pediatnc MATTEO DI CAPUA Neuropsychiatry, BERNARDO DALLA BERNARDINA University of Verona L, Silfverskiold B. A family with emotionally precipitated drop seizures. Acta Psychiat Scand 1958; 33: 471-76. 2. Suhren O, Bruyn GW, Tuynman JA. Hyperekplexia: a hereditary startle syndrome J Neurol Sci 1966; 3: 577-605. 3. Gastaut H, Villeneuve A. The startle disease or hyperekplexia. pathological surprise reaction. J Neurol Sci 1967; 5: 523-42. 4. Andermann F, Keene DL, Andermann E, Quesney LF. Startle disease or hyperekplexia: further delineation of the syndrome. Brain 1980; 103: 985-97. 5. Lingam S, Wilson J, Hart EW Hereditary stiff-baby syndrome. Am J Dis Child 1981; 1. Kirstein
135: 909-11.
Morley DJ, Weaver DD, Garg BP, Markand O. Hyperekplexia: an inhented disorder of the startle response. Clin Genet 1982; 21: 388-96. 7. Kurczynski TW. Hyperekplexia. Arch Neurol 1983; 40: 246-48. 8. Markand ON, Garg BP, Weaver DD. Familiar startle disease (hyperekplexia) electrophysiologic studies. Arch Neurol 1984, 41: 71-74. 9. Sáenz-Lope E, Herranz-Tanarro FJ, Masdeu JC, Chacòn Peña Jr. Hyperekplexia. a syndrome of pathological startle responses Ann Neurol 1984; 15: 36-41. 10 Andermann F, Andermann E. Startle disease or hyperekplexia. Ann Neurol 1984; 16: 6.
STARTLE DISEASE: AN AVOIDABLE CAUSE OF SUDDEN INFANT DEATH
SIR,-Startle clisease (hyperekplexia),
a
pathological
mtensi-
fication of the startle response, is transmitted as an autosomal dominant trait with incomplete penetrance. About seventy cases have been described.I-9 The frequency is probably higher, since some cases are misclassified as epilepsy. The major form of startle disease," with neonatal onset, can be serious. Newborn infants can have repeated myoclonic jerks and increased muscle tone and sudden and prolonged seizures, with life-threatening apnoea due to contraction of respiratory muscles. These seizures are resistant to drugs. Two sudden infant deaths have been reported.2,7 A sudden death during a stiffness seizure, at age 3 months, also occurred in one of our six cases. Our patients had severe bradycardia during seizures and sometimes cardiac arrest which required resuscitation. The risk of death is limited because these seizures become progressively less frequent and disappear at about 2 years of age. By chance we discovered how to stop these seizures in a girl now 3 years old. Her mother has a strong startle response. The patient was admitted to Bambino Gesu Children’s Hospital at birth because of massive myoclonic jerks, both spontaneous and in response to tactile stimulation, especially on the face and nose. There were also frequent seizures marked by diffuse muscle stiffness with extension of the four limbs and intense cyanosis but no loss of consciousness. Seizures occurred while the patient was awake or asleep, and lasted 4-5 minutes. An electroencephalogram recorded during the longer seizures showed slow background activity due to alterations in cardiorespiratory activity. Contraction of respiratory muscles caused apnoea. Heart rate initially increased from 130 to 160’min,
367-68.
GANCICLOVIR FOR CYTOMEGALOVIRUS INFECTION IN RENAL TRANSPLANT RECIPIENTS
SIR,-Dr Rostoker and colleagues (Nov 12, p 1137), and Mr Nicholson and co-workers (Dec 24/31, p 1501) report success with ganciclovir in the treatment of severe cytomegalovirus (CMV) infection in renal transplant recipients. Between January, 1986, and December, 1988, we did 334 such transplant operations using powerful immunosuppressive agents (OKT3 monoclonal antibody, polyclonal anti-lymphocyte globulin, cyclosporin) that predispose to severe CMV disease, especially when the CMV status of recipient and donor are not taken into account. The frequency of CMV disease-defined as a positive blood culture with clinical symptoms’-was 12% (40 patients). Rostoker et al refer to our preliminary study2 on 12 patients treated with a 14-day course of ganciclovir. All patients experienced only moderate disease; all recovered fully, and none died despite immunosuppression, which was not withdrawn. Our preliminary experience suggested the need for early treatment with ganciclovir to avoid the transition to more severe CMV disease while maintaining adequate immunosuppression. We then decided to tackle CMV infection after transplantation with a prompt, 14-day
Transverse section images at
comparable levels in patient with CJD (left and middle) and control (right). Left: CT scan of patient (February, 1987). Middle: SPET scan of patient (May, 1987). Right: Normal SPET scan (at about same level).
there was no history of myocardial infarction or cerebrovascular disease. His only medication was propranolol and isosorbide dinitrate. There were no focal neurological signs or evidence of hypertension or other cardiovascular abnormality. Laboratory tests were normal, as were chest and skull X-rays and EEG. A CT scan in February, 1987, showed no evidence of cerebral atrophy (figure). The diagnosis seemed to be presenile dementia of multi-infarct or Alzheimer type. In March, 1987, significant deterioration was noted; he was now perseveradve in answering questions, had great difficult in remembering where he lived, and could not name simple objects. There was evidence of right-left disorientation. His MMSE score was 9/30. 1 month later he needed continual help with bathing, toileting, feeding, and dressing. He had a shuffling gait and had difficulty climbing stairs. In May, 1987, he was admitted for further investigation. He was agitated and unable to cooperate with even simple psychological tests. He had severe expressive and receptive dysphasia. On a behavioural scale on which an independent, fit elderly person would be expected to score 0-3, he scored 17-23, consistent with severe impairment and dependency. SPET, with 99mTc-HMPAO (’Ceretec’, Amersham International) revealed much reduced uptake throughout the greymatter of the cerebral cortex (figure). Flow relative to occipital cortex in frontal regions was compared with that in age-matched controls and was much reduced-eg, right high frontal 0.55 (normal range O’88-l 40). These images of function are in striking contrast to the earlier, normal CT images. The patient died at home in
information when structural brain imaging macroscopic brain structure is preserved.
MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh EH10 5HF; Department of Neuropathology, Western General Hospital, Edinburgh, and Wellcome Neuroscience Group, Institute of Neurological Sciences, Glasgow
is normal and R. HUNTER A. GORDON R. MCLUSKIE D. WYPER J. PATTERSON J. E. CHRISTIE G. FINK G. M. GOODWIN
1. Neirinckx RD, Canning LR, Piper IM, et al. Technetium-99m d,l-HM-PAO. a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion.
J Nucl Med 1987; 28: 191-202 2. Herscovitch P, Auchus AP, Gado M, Chi D, Raichle ME. Correction of positron emission tomography data for cerebral atrophy.J Cerebral Blood Flow Metab 1986; 6: 120-24. 3. Chawluk JB, Alavi A, Dann R, et al. Positron emission tomography in ageing and dementia: effect of cerebral atrophy. J Nucl Med 1987; 28: 431-37. 4. Kuritzky A, Davidowitch S, Sandbank U, Bechar M. Normal EEG in CreutzfeldtJakob disease. Neurology 1980; 30: 1134-35. 5. Galvez S, Cartier L. CT findings in 15 cases of Creutzfeldt-Jakob disease with histological verification. J Neurol Neurosurg Psychiatry 1984; : 47: 1244-46. 6. Keshaven MS, Lishman WA, Hughes JT. Psychiatric presentation of CreutzfeldtJakob disease Br J Psychiatry 1987; 151: 260-63. 7. Pattie AH, Gilleard CJ. Manual of the Clifton assessment procedures for the elderly (CAPE). London: Hodder and Stoughton, 1985. 8. Costa DC, Ell PJ, Burns A, Philpot M, Lezy R. CBF tomograms with 99mTc-HMPAO in patients with dementia (Alzheimer type and HIV) and Parkinson’s disease: initial results. J Cerebral Blood Flow Metab 1988; 8: S109-15.
October, 1987. Post mortem examination revealed a normal sized brain but histopathological examination confirmed the later clinical suspicion that neither multi-infarct nor Alzheimer type dementia was the correct diagnosis. Widespread, severe neuronal depletion and vacuolation with rod cell infiltration and astrocytic gliosis was noted throughout the cerebral cortex. Spongiform degeneration was most striking in the supra-medial border of the frontal lobes. The basal ganglia and corticospinal tracts were also affected. The neuropathological findings were consistent with CJD. Since most investigations had been normal the speed of deterioration was the only real clinical clue. Even in advanced CJD the CT scan is often normalHere the CT appearances were consistent with the normal macroscopic appearance of the brain.
However, SPET images were grossly abnormal and were atypical of other dementias (Alzheimer’s,8 Korsakoff’s). Estimation of regional brain function with SPET can provide essential additional
FULMINANT HEPATITIS DUE TO CYPROTERONE ACETATE
SiR,—Cyproterone acetate (CPA) is a drug generally prescribed for female hirsutism, prostatic cancer, precocious puberty, advanced breast cancer, and acne, CPA is thought to be well tolerated. Only five cases of hepatic reactions have been published; two were of acute hepatitis and none were fulminant. A 78-year-old man was admitted on May 20,1988, for jaundice. A year earlier he had been in hospital for surgery for prostatic cancer without metastasis. In December, 1987, he received CPA 200 mg daily; liver function tests were normal. On May 16, 1988, jaundice appeared with dark urine and white stools but no pruritus. He was admitted with jaundice and a liver span of 9 cm on the right midclavicular line, but there was no hepatic encephalopathy or fever. Mild ascites was present. He was taking CPA and diosmine
216 total bilirubin was at 178 Eunol/1 alkaline phosphatase 153 IU/1 (normal below 120), aminotransferase activities were 720 IU/1 and 1015 IU’l (ALT). Prothrombin time was 45% of normal with factor V at 47%. Ultrasonography indicated a small and homogeneous liver. Serological markers of hepatitis virus, cytomegalovirus, and herpes viruses were negative. Antibodies to nuclei, smooth muscle, and mitochondria were negative. On May 24 liver biopsy revealed severe hepatic necrosis and infiltration with polymorphonuclear cells. On May 28 hepatic encephalopathy developed, the prothrombin time fell (22%), and there were biological signs of intravascular coagulation. The patient died on June 1. The fulminant hepatitis in this case can be ascribed to CPA because viral infections were excluded and there was no circumstantial evidence for a risk of non-A non-B hepatitis; the predominantly centrilobular distribution of the necrosis, suggests drug-induced hepatitis; and diosmine is not thought to be
300 mg
daily. His
(conjugated 145),
serum
serum
(AST)
hepatotoxic.3 Liver damage due to CPA is rare and only five other cases have been described. Three patients with advanced breast cancer (out of twenty) had a mild increase in aminotransferase activity during treatment with CPA. Two others had developed hepatitis 11 weeks (400 mg daily) or 21 weeks (200 mg daily) after the start of treatment. These two had acute hepatitis with bridging necrosis and liver tests returned to normal 9 weeks and 3 months, respectively, after CPA was stopped. The mechanism is obscure. The absence of clinical and biochemical manifestations of hypersensitivity in our patient and in the previous cases suggests that the hepatic lesions might be related to direct or to reactive metabolite mediated toxicity. We recommend that aminotransferase activities be monitored in patients
on
CPA. C. TRIVALLE N. D. MANCHON J. P. VINEL N. MOORE J. HÉMET H. COURTOIS E. BERCOFF J. BOURREILLE
H. LÉVESQUE CHU de Rouen, 76000 Rouen, France; and CHU de Toulouse-Purpan
1 Editorial Cyproterone acetate Lancet 1976; i: 1003. 2 Meijers WH, Willemse PHB, Sleijfer Th, Mulder
3
NH, Grond J. Hepatocellular damage by cyproterone acetate. Eur J Cancer Clin Oncol 1986; 22: 1121. Stncker BHCH, Spoelstra P Drug-induced hepatic injury. Amsterdam: Elsevier, 1985.
a minute decreased progressively to 75-80/min. The complex changed polarity progressively without intraventricular delay and promptly returned to normal at the end of
then after
QRS
the seizure. The seizures were resistant to treatment with intravenous diazepam and with oral phenobarbitone, nitrazepam, and clonazepam. During a long seizure, one of us intervened in an attempt to counteract the hypertonia: the patient was held by the head and legs and forcibly flexed toward the trunk. The seizure ceased immediately. The procedure was repeated several times and always proved effective. The parents easily learned this method but had to observe their daughter constantly. The family was then given a cardiorespiratory monitor with an apnoea alarm and thus the patient was able to leave the hospital at age 3t months. The seizures continued to occur daily up to 5 months of age. Later they became less frequent; at 12 months they occurred weekly, and monthly at age 1I 2 years. The last seizure was at age 2and the parents have now discontinued monitoring. Later the mother of a 12-year-old girl with startle disease reported that when her daughter had stiffness seizures in the first few years of life, she was able to stop them by forcibly bending the child’s head. In a new case at the department of paediatric neuropsychiatry of the University of Verona, our technique also stopped stiffness seizures. We do not know why the abrupt flexing of head and limbs stops stiffness seizures. Startle disease, although rare, is a potential cause of sudden death from respiratory arrest during prolonged stiffness seizures. However, death can be avoided by stopping the seizures with the method we describe. Department of Pediatric Neuropsychiatry, Bambino Gesū Children’s Hospital, Rome, Italy; FEDERICO VIGEVANO and Department of Pediatnc MATTEO DI CAPUA Neuropsychiatry, BERNARDO DALLA BERNARDINA University of Verona L, Silfverskiold B. A family with emotionally precipitated drop seizures. Acta Psychiat Scand 1958; 33: 471-76. 2. Suhren O, Bruyn GW, Tuynman JA. Hyperekplexia: a hereditary startle syndrome J Neurol Sci 1966; 3: 577-605. 3. Gastaut H, Villeneuve A. The startle disease or hyperekplexia. pathological surprise reaction. J Neurol Sci 1967; 5: 523-42. 4. Andermann F, Keene DL, Andermann E, Quesney LF. Startle disease or hyperekplexia: further delineation of the syndrome. Brain 1980; 103: 985-97. 5. Lingam S, Wilson J, Hart EW Hereditary stiff-baby syndrome. Am J Dis Child 1981; 1. Kirstein
135: 909-11.
Morley DJ, Weaver DD, Garg BP, Markand O. Hyperekplexia: an inhented disorder of the startle response. Clin Genet 1982; 21: 388-96. 7. Kurczynski TW. Hyperekplexia. Arch Neurol 1983; 40: 246-48. 8. Markand ON, Garg BP, Weaver DD. Familiar startle disease (hyperekplexia) electrophysiologic studies. Arch Neurol 1984, 41: 71-74. 9. Sáenz-Lope E, Herranz-Tanarro FJ, Masdeu JC, Chacòn Peña Jr. Hyperekplexia. a syndrome of pathological startle responses Ann Neurol 1984; 15: 36-41. 10 Andermann F, Andermann E. Startle disease or hyperekplexia. Ann Neurol 1984; 16: 6.
STARTLE DISEASE: AN AVOIDABLE CAUSE OF SUDDEN INFANT DEATH
SIR,-Startle clisease (hyperekplexia),
a
pathological
mtensi-
fication of the startle response, is transmitted as an autosomal dominant trait with incomplete penetrance. About seventy cases have been described.I-9 The frequency is probably higher, since some cases are misclassified as epilepsy. The major form of startle disease," with neonatal onset, can be serious. Newborn infants can have repeated myoclonic jerks and increased muscle tone and sudden and prolonged seizures, with life-threatening apnoea due to contraction of respiratory muscles. These seizures are resistant to drugs. Two sudden infant deaths have been reported.2,7 A sudden death during a stiffness seizure, at age 3 months, also occurred in one of our six cases. Our patients had severe bradycardia during seizures and sometimes cardiac arrest which required resuscitation. The risk of death is limited because these seizures become progressively less frequent and disappear at about 2 years of age. By chance we discovered how to stop these seizures in a girl now 3 years old. Her mother has a strong startle response. The patient was admitted to Bambino Gesu Children’s Hospital at birth because of massive myoclonic jerks, both spontaneous and in response to tactile stimulation, especially on the face and nose. There were also frequent seizures marked by diffuse muscle stiffness with extension of the four limbs and intense cyanosis but no loss of consciousness. Seizures occurred while the patient was awake or asleep, and lasted 4-5 minutes. An electroencephalogram recorded during the longer seizures showed slow background activity due to alterations in cardiorespiratory activity. Contraction of respiratory muscles caused apnoea. Heart rate initially increased from 130 to 160’min,
367-68.
GANCICLOVIR FOR CYTOMEGALOVIRUS INFECTION IN RENAL TRANSPLANT RECIPIENTS
SIR,-Dr Rostoker and colleagues (Nov 12, p 1137), and Mr Nicholson and co-workers (Dec 24/31, p 1501) report success with ganciclovir in the treatment of severe cytomegalovirus (CMV) infection in renal transplant recipients. Between January, 1986, and December, 1988, we did 334 such transplant operations using powerful immunosuppressive agents (OKT3 monoclonal antibody, polyclonal anti-lymphocyte globulin, cyclosporin) that predispose to severe CMV disease, especially when the CMV status of recipient and donor are not taken into account. The frequency of CMV disease-defined as a positive blood culture with clinical symptoms’-was 12% (40 patients). Rostoker et al refer to our preliminary study2 on 12 patients treated with a 14-day course of ganciclovir. All patients experienced only moderate disease; all recovered fully, and none died despite immunosuppression, which was not withdrawn. Our preliminary experience suggested the need for early treatment with ganciclovir to avoid the transition to more severe CMV disease while maintaining adequate immunosuppression. We then decided to tackle CMV infection after transplantation with a prompt, 14-day