- Email: [email protected]
Vigabatrin as spasmolytic drug
1603
information on continence by doctors, and to some extent by nurses, but also such information as is recorded is often inaccurate. Department of Geriatric Medicine, University of Liverpool, Royal Liverpool Hospital, Liverpool L69 3BX, UK
S. BENBOW G. SANGSTER D. BARER
DT, Hewer RL. Outlook after acute stroke: urinary continence and loss of consciousness compared in 532 patients. Q J Med 1985; 56: 601-08. 2. Barer DH. Continence after stroke: useful predictor or goal of therapy? Age Ageing 1989; 18: 183-91. 1. Wade
Malignant hyperthermia and Marinesco-Sjögren syndrome SIR,-Dr Elechi and Dr Dakaraju (Nov 9, p 1206) report malignant hyperthermia (MH) in three patients with Hirschsprung’s disease, and point out its association with other neuromuscular syndromes. Prompted by their contribution we report a clinical observation that is possibly related to MarinescoSjögren-syndrome-associated MH. The autosomal recessive Marinesco-Sjogren syndrome consists of congenital cataract, cerebellar ataxia (with or without cerebellar atrophy), and some mental retardation and neurogenic myopathy. 1,2 Among the published cases, MH developed in one child during cataract surgery.3 We are caring for two families of Romanian gypsy descent, both of which include two children with Marinesco-Sjogren syndrome. In one boy, the clinical course so far has been compatible with the myopathic type of the syndrome. At 8 years of age subsequent to an upper-respiratory-tract infection an acute generalised myopathy developed with profound muscle weakness and tenderness and a hundredfold increase from normal serum creatine kinase, which returned to normal values rapidly with steroid therapy. Muscle biopsy showed features of chronic neurogenic damage that had been noted previously, and inflammatory changes were absent. Muscle power was slowly regained in four months. During this time however, severe talipes developed. The other pair of siblings, who are unrelated to this boy but are of the same ethnic origin, were described by their parents as having muscle pain and weakness with every febrile illness; creatine kinase in these children was slightly raised on several occasions. These findings suggest that Marinesco-Sjogren syndrome should probably be added to the growing list of neuromuscular diseases carrying an increased risk of MH.4-7
J.-U. WALTHER D. ZAFIRIOU M. JENSEN
Kinderpoliklinik der Universitat, D-8000 Munchen 2, Germany 1. Superneau
D, Wertelecki W, Zellweger H, Bastian F. Myopathy in MarinescoSjogren syndrome. Eur Neurol 1987; 26: 8-16. 2. Serratrice G, Gastaut JL, Dubois-Gambarelli D. Amyotrophie neurogène périphérigue au cours du syndrome de Marinesco-Sjögren. Rev Neurol 1973; 128: 432-41. 3. Todorov A. Le syndrome de Marinesco-Sjoren: première étude anatomoclinique. J Génét Hum 1965; 14: 197-233. 4. King JO, Denborough MA. Anaesthetic-induced malignant hyperpyrexia in children. J Pediatr 1973; 83: 37-40. 5. Brownell AKW, Paasuke RT, Elash A, et al. Malignant hyperthermia in Duchenne muscular dystrophy. Anesthesiology 1983; 58: 180-82. 6. Proster-Iskenius U, Waterson JR, Hall JG. A recessive form of congenital contractures and torticollis associated with malignant hyperthermia. J Med Genet
1988; 25: 104-12. G, Isaacs H. An association between certain congenital abnormalities and the malignant hyperthermia trait. S Afr Med J 1990; 77: 570-74.
7. Gericke
Vigabatrin
as
spasmolytic drug
irreversible inhibitor of y-aminobutyric SIR,-Vigabatrin, acid (GABA) transaminase, is used in the treatment of epilepsy, especially complex partial seizures. We report here on our experience with this drug in the symptomatic treatment of spasticity due to metabolic diseases with leukodystrophyl in six childrenthree with metachromatic leukodystrophy, two with Krabbe disease (globoid-cell leukodystrophy), and one with Nieniann-Pick disease type C. These lysosomal diseases, at least in their spastic stage, are accompanied by decreased to borderline low CSF free
’GABA levels.2,3 This is most probably a secondary feature that could be responsible, at least in part, for the spasticity. The age of the patients at the start of the therapy ranged from 3 months to 5 years. Vigabatrin was given as monotherapy for 10-44 months. It was administered at a daily dosage of 25-100 mg/kg in two divided doses. In all patients this resulted in a significant and persistent reduction of spasticity and hyperexcitability, permitting better nursing of the children and greatly increasing their comfort. This effect was especially impressive in the patients with Krabbe disease. In two patients, weakness and drowsiness observed at 75 mg/kg disappeared when the dose was lowered to 50 mg/kg daily. This spasmolytic effect of vigabatrin needs evaluating in a larger series of patients. An important question is whether the drug is also beneficial in spasticity of other than metabolic origin.
Department of Paediatrics, University of Leuven, 3000 Leuven, Belgium
JAAK JAEKEN PAUL DE COCK PAUL CASAER
1. Scriver
CR, Beaudet AL, Sly WS, Valle D. The metabolic basis of inherited disease. New York: McGraw-Hill, 1989. 2. Jaeken J, Casaer P, Haegele K, Schechter PJ. Normal and abnormal central nervous system GABA metabolism in childhood. Inherited Metab Dis 1990; 13: 793. 3. Carchon HA, Jaeken J, Jansen E, Eggermont E. Reference values for free gamma-aminobutyric acid determined by ion-exchange chromatography and fluorescence detection in the cerebrospinal fluid of children. Clin Chim Acta 1991; 201: 83.
All-trans retinoic acid in leukaemia
myelogenous
SIR,-Dr Koller and colleagues (Nov 2, p 1154) describe the restoration of all-trans retinoic acid (ATRA) sensitivity by concurrent or alternating therapy with interferon-a-2b (INF&agr;) in a patient with acute promyelocytic leukaemia (APL). As in-vitro support for their observation they cite their 1990 paper on cultured myeloid leukaemia cell lines not our earlier evidence for an interaction between ATRA and INFa in fresh leukaemic cells from two patients with APL.1 Although we too are investigating this potentially useful combination in APL, we would mention as a warning our recent experience with a patient with a promyelocytic blastic crisis of chronic myelogenous leukaemia (CML). As in most cases of APL, this patient had a striking clinical response to ATRA,3but, after relapse on ATRA, there was no response to increased ATRA with or without INFfx. Clonogenic cells from this patient at the time of relapse remained sensitive to the inhibitory effect of ATRA and INFfx individually, but there was no evidence of a positive interaction between these agents in vitro, as we have noted in several other cases of CML in accelerated phase or blastic crisis.3 The variant results in advanced CML and APL may reflect different modes of action of ATRA and INFfx in these diseases and emphasise the need for further correlative clinical/laboratory studies in this promising area. Montefiore Medical Center and Albert Einstein Cancer Center, Bronx, NY 10467, USA 1.
ROBERT E. GALLAGHER PETER H. WIERNIK
Gallagher RE, Lune KL, Leavitt RD, et al. Effects of interferon and retinoic acid on the growth and differentiation of clonogenic leukemic cells from acute myelogenous leukemia patients treated with recombinant leukocyte- &agr;A interferon. Leukemia
Res 1987; 11: 609-19. 2. Wiernik PH, Dutcher JP, Paietta E. et al. Treatment of promyelocytic blast crisis of chronic myelogenous leukemia with all trans-retinoic acid. Leukemia 1991; 5: 504-09. 3. Sagayadan G, Dutcher J, Wiernik P, et al. Effect of trans-retinoic acid and interferon&agr; on clonogenic chronic myelogenous leukemia blast crisis cells. Proc Am Assoc Cancer Res 1991; 32: 32.
an
How many genetic diseases? SIR,—Claims that
genes are "the ultimate explanation for the and that being" they "define a human being", are "the blueprint for life", and may eliminate homelessness have been made.1,2 Such remarks may mislead the public about the limitations of and benefits to be derived from the study of human genetics. Another distortion needs discussion too. Paul Berg, Nobel
human
information on continence by doctors, and to some extent by nurses, but also such information as is recorded is often inaccurate. Department of Geriatric Medicine, University of Liverpool, Royal Liverpool Hospital, Liverpool L69 3BX, UK
S. BENBOW G. SANGSTER D. BARER
DT, Hewer RL. Outlook after acute stroke: urinary continence and loss of consciousness compared in 532 patients. Q J Med 1985; 56: 601-08. 2. Barer DH. Continence after stroke: useful predictor or goal of therapy? Age Ageing 1989; 18: 183-91. 1. Wade
Malignant hyperthermia and Marinesco-Sjögren syndrome SIR,-Dr Elechi and Dr Dakaraju (Nov 9, p 1206) report malignant hyperthermia (MH) in three patients with Hirschsprung’s disease, and point out its association with other neuromuscular syndromes. Prompted by their contribution we report a clinical observation that is possibly related to MarinescoSjögren-syndrome-associated MH. The autosomal recessive Marinesco-Sjogren syndrome consists of congenital cataract, cerebellar ataxia (with or without cerebellar atrophy), and some mental retardation and neurogenic myopathy. 1,2 Among the published cases, MH developed in one child during cataract surgery.3 We are caring for two families of Romanian gypsy descent, both of which include two children with Marinesco-Sjogren syndrome. In one boy, the clinical course so far has been compatible with the myopathic type of the syndrome. At 8 years of age subsequent to an upper-respiratory-tract infection an acute generalised myopathy developed with profound muscle weakness and tenderness and a hundredfold increase from normal serum creatine kinase, which returned to normal values rapidly with steroid therapy. Muscle biopsy showed features of chronic neurogenic damage that had been noted previously, and inflammatory changes were absent. Muscle power was slowly regained in four months. During this time however, severe talipes developed. The other pair of siblings, who are unrelated to this boy but are of the same ethnic origin, were described by their parents as having muscle pain and weakness with every febrile illness; creatine kinase in these children was slightly raised on several occasions. These findings suggest that Marinesco-Sjogren syndrome should probably be added to the growing list of neuromuscular diseases carrying an increased risk of MH.4-7
J.-U. WALTHER D. ZAFIRIOU M. JENSEN
Kinderpoliklinik der Universitat, D-8000 Munchen 2, Germany 1. Superneau
D, Wertelecki W, Zellweger H, Bastian F. Myopathy in MarinescoSjogren syndrome. Eur Neurol 1987; 26: 8-16. 2. Serratrice G, Gastaut JL, Dubois-Gambarelli D. Amyotrophie neurogène périphérigue au cours du syndrome de Marinesco-Sjögren. Rev Neurol 1973; 128: 432-41. 3. Todorov A. Le syndrome de Marinesco-Sjoren: première étude anatomoclinique. J Génét Hum 1965; 14: 197-233. 4. King JO, Denborough MA. Anaesthetic-induced malignant hyperpyrexia in children. J Pediatr 1973; 83: 37-40. 5. Brownell AKW, Paasuke RT, Elash A, et al. Malignant hyperthermia in Duchenne muscular dystrophy. Anesthesiology 1983; 58: 180-82. 6. Proster-Iskenius U, Waterson JR, Hall JG. A recessive form of congenital contractures and torticollis associated with malignant hyperthermia. J Med Genet
1988; 25: 104-12. G, Isaacs H. An association between certain congenital abnormalities and the malignant hyperthermia trait. S Afr Med J 1990; 77: 570-74.
7. Gericke
Vigabatrin
as
spasmolytic drug
irreversible inhibitor of y-aminobutyric SIR,-Vigabatrin, acid (GABA) transaminase, is used in the treatment of epilepsy, especially complex partial seizures. We report here on our experience with this drug in the symptomatic treatment of spasticity due to metabolic diseases with leukodystrophyl in six childrenthree with metachromatic leukodystrophy, two with Krabbe disease (globoid-cell leukodystrophy), and one with Nieniann-Pick disease type C. These lysosomal diseases, at least in their spastic stage, are accompanied by decreased to borderline low CSF free
’GABA levels.2,3 This is most probably a secondary feature that could be responsible, at least in part, for the spasticity. The age of the patients at the start of the therapy ranged from 3 months to 5 years. Vigabatrin was given as monotherapy for 10-44 months. It was administered at a daily dosage of 25-100 mg/kg in two divided doses. In all patients this resulted in a significant and persistent reduction of spasticity and hyperexcitability, permitting better nursing of the children and greatly increasing their comfort. This effect was especially impressive in the patients with Krabbe disease. In two patients, weakness and drowsiness observed at 75 mg/kg disappeared when the dose was lowered to 50 mg/kg daily. This spasmolytic effect of vigabatrin needs evaluating in a larger series of patients. An important question is whether the drug is also beneficial in spasticity of other than metabolic origin.
Department of Paediatrics, University of Leuven, 3000 Leuven, Belgium
JAAK JAEKEN PAUL DE COCK PAUL CASAER
1. Scriver
CR, Beaudet AL, Sly WS, Valle D. The metabolic basis of inherited disease. New York: McGraw-Hill, 1989. 2. Jaeken J, Casaer P, Haegele K, Schechter PJ. Normal and abnormal central nervous system GABA metabolism in childhood. Inherited Metab Dis 1990; 13: 793. 3. Carchon HA, Jaeken J, Jansen E, Eggermont E. Reference values for free gamma-aminobutyric acid determined by ion-exchange chromatography and fluorescence detection in the cerebrospinal fluid of children. Clin Chim Acta 1991; 201: 83.
All-trans retinoic acid in leukaemia
myelogenous
SIR,-Dr Koller and colleagues (Nov 2, p 1154) describe the restoration of all-trans retinoic acid (ATRA) sensitivity by concurrent or alternating therapy with interferon-a-2b (INF&agr;) in a patient with acute promyelocytic leukaemia (APL). As in-vitro support for their observation they cite their 1990 paper on cultured myeloid leukaemia cell lines not our earlier evidence for an interaction between ATRA and INFa in fresh leukaemic cells from two patients with APL.1 Although we too are investigating this potentially useful combination in APL, we would mention as a warning our recent experience with a patient with a promyelocytic blastic crisis of chronic myelogenous leukaemia (CML). As in most cases of APL, this patient had a striking clinical response to ATRA,3but, after relapse on ATRA, there was no response to increased ATRA with or without INFfx. Clonogenic cells from this patient at the time of relapse remained sensitive to the inhibitory effect of ATRA and INFfx individually, but there was no evidence of a positive interaction between these agents in vitro, as we have noted in several other cases of CML in accelerated phase or blastic crisis.3 The variant results in advanced CML and APL may reflect different modes of action of ATRA and INFfx in these diseases and emphasise the need for further correlative clinical/laboratory studies in this promising area. Montefiore Medical Center and Albert Einstein Cancer Center, Bronx, NY 10467, USA 1.
ROBERT E. GALLAGHER PETER H. WIERNIK
Gallagher RE, Lune KL, Leavitt RD, et al. Effects of interferon and retinoic acid on the growth and differentiation of clonogenic leukemic cells from acute myelogenous leukemia patients treated with recombinant leukocyte- &agr;A interferon. Leukemia
Res 1987; 11: 609-19. 2. Wiernik PH, Dutcher JP, Paietta E. et al. Treatment of promyelocytic blast crisis of chronic myelogenous leukemia with all trans-retinoic acid. Leukemia 1991; 5: 504-09. 3. Sagayadan G, Dutcher J, Wiernik P, et al. Effect of trans-retinoic acid and interferon&agr; on clonogenic chronic myelogenous leukemia blast crisis cells. Proc Am Assoc Cancer Res 1991; 32: 32.
an
How many genetic diseases? SIR,—Claims that
genes are "the ultimate explanation for the and that being" they "define a human being", are "the blueprint for life", and may eliminate homelessness have been made.1,2 Such remarks may mislead the public about the limitations of and benefits to be derived from the study of human genetics. Another distortion needs discussion too. Paul Berg, Nobel
human