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Myasthenia and HELLP syndrome
European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 108–111
Case report
Myasthenia and HELLP syndrome Attilio Di Spiezio Sardoa,*, Alex Taylorb, Massimiliano Pellicanoa, Lucio Romanoa, Giuseppe Acunzoa, Giuseppe Bifulcoa, Giuseppe Cerrotaa, Carmine Nappia a
Department of Gynaecology, Obstetrics, and Pathophysiology of Human Reproduction, University of Naples ‘‘Federico II’’, Via S. Pansini 5, Naples 80131, Italy b Minimally Invasive Therapy Unit and Endoscopy Training Centre, University Department of Obstetrics and Gynaecology, Royal Free Hospital, Hampstead, London, UK Received 1 April 2003; received in revised form 1 October 2003; accepted 22 December 2003
Keywords: Myasthenia; HELLP syndrome; Preeclampsia; Corticosteroids
Myasthenia gravis (MG) is a chronic autoimmune disorder of neuromuscolar transmission. It is characterized by muscle weakness and fatiguability following repetitive activity, particularly of the face and extremities. The most common clinical features are dysarthria, ptosis, diplopia, dysphagia and respiratory distress [1]. MG occurs twice as often in women than in men, with a peak incidence in the third decade. Hence, it does not infrequently affects women during their childbearing years [2]. Although there is no evidence that MG adversely affects fertility, MG patients rarely become pregnant. As a consequence, the published literature on MG and pregnancy is scant and controversial. The course of MG is unpredictable during pregnancy [2]. Disease patterns vary and a myasthenic crisis can occur at any time during pregnancy. In a review of 322 pregnancies in 225 myasthenic patients, approximately one-third of MG patients deteriorated, one-third remained stable and onethird evolved in partial remission [3]. The first trimester of pregnancy and the first post-partum month seem to be the most critical periods for an MG exacerbation [2], whilst its signs and symptoms tend to improve throughout the second and third trimester coinciding with the immunosuppression which normally takes place during this period. The clinical course of MG during pregnancy appears to have no predictive value for subsequent gestations [2]. Preeclampsia is a not a single disease, but rather a clinical syndrome encompassing three distinct elements: (1) *
Corresponding author. Tel.: þ39-081-7462905; fax: þ39-081-7462903. E-mail address: [email protected] (A. Di Spiezio Sardo). 0301-2115/$ – see front matter # 2004 Published by Elsevier Ireland Ltd. doi:10.1016/j.ejogrb.2003.12.027
new-onset of hypertension (defined as a consistent elevation in blood pressure >140/90 in a previously normotensive woman); (2) new-onset proteinuria (defined as >300 mg/ 24 h or 2þ on a clean-catch dipstix) in the absence of urinary infection; and (3) new-onset non-dependent edema. The diagnosis of preeclampsia can only reliably be made after 20-week gestation. Preeclampsia complicates 6–8% of all pregnancy and is an important cause of maternal and perinatal mortality and morbidity worldwide. Preeclampsia in the pregnant myasthenic patient is exceedingly rare. Only five cases have been found in the English language medical literature [4,5]. The coexistence of these disorders produces a high degree of morbidity and mortality for both mother and fetus [4]. The reported complications include: acute respiratory insufficiency, advanced weakness, oliguria, hemorrhage and iatrogenic myasthenic crisis. ‘‘HELLP’’ is the acronym for the syndrome of hemolysis, elevated liver enzymes and low platelet count, which develops as an atypical complicated form of severe preeclampsiaeclampsia. It is a disease isolated to pregnancy and is associated with an increased risk of maternal and neonatal morbidity and mortality rates, particularly if occurring in the second trimester. We report what is, to the best of our knowledge, the first case in the international literature of the association between myasthenia and HELLP syndrome. A 27-year-old, nulliparous woman was referred to our hospital at 37-week gestation with a 2-week history of gross edemas of the lower extremities. Her past medical history was unremarkable except for her myasthenia gravis that was diagnosed at the age of 25. Following her thymectomy at the
A. Di Spiezio Sardo et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 108–111
109
age of 26 years, her MG had been successfully controlled with pyridostigmine 40 mg t.i.d. At the onset of pregnancy, the dose was lowered to 40 mg b.i.d. She previously had one first trimester miscarriage. A booking bloods revealed her to have a thalassemic treat. An ultrasound scan (USS) performed at 21 weeks showed a normal developing fetus with no obvious structural defects. In the second trimester, she developed a marked microcytic anemia that was corrected by blood transfusions. On admission at 37 weeks, the fundal height was consistent with dates, the fetal lie was longitudinal and the presentation cephalic. She was well but for her gross peripheral edema and a raised blood pressure of 160/110 mmHg. An admission cardiotocogram was normal and a USS revealed normal fetal biometry with a normal amniotic fluid index. Admission blood indices revealed a hemoglobin of 8.4 g/dl and increased levels of serum aspartate aminotransferase (90 U/l), alanine aminotransferase (75 U/l) and total bilirubin (2.1 mg/dl). Neurological examination was normal, in keeping with her good antenatal control of her MG. The patient was started on oral treatment with 250 mg methyldopa t.i.d. and maternal and fetal well being were intensively monitored. Her blood pressure was well controlled for the first 2 days, but on the third day it increased to 180/110 mmHg despite bed rest and orally administered methyldopa. In addition she became symptomatic complaining of headache, visual disturbances and nausea. A 24 h urine collection on the third day revealed 5 g of proteins. Comparable data were present on day 1 and day 2 (1.5 g/24 h and 3 g/24 h, respectively). The urine output fell from 50 ml/h on the first day to 26 ml/h by the third day and was noted to be orange (consistent with hemolysis). The most relevant data of the patient’s laboratory evaluation are shown in the Table 1. Given the clinical picture and laboratory evidences of hemolysis (LDH 600 U/l and total bilirubin 1.2 mg/
dl), low platelet (<150,000 cells/ml) and hepatic dysfunction (AST 40 U/l, ALT 40 U/l), a diagnosis of severe preeclampsia complicated by HELLP syndrome was made. The severity of the HELLP syndrome was determined with the Mississippi triple class system. Based on this system our patient was classified as class 2, with elevated liver enzymes, hemolysis and a platelet count of 50,000– 100,000 cells/ml platelets. In view of the worsening clinical picture a decision was made to expedite delivery by emergency cesarean section. The cesarean section was performed under regional anesthesia and resulted in the delivery of a healthy 3140 g male with Apgar scores of 8 and 9 at 1 and 5 min, respectively. The patient received immediately post-partum 10 mg of dexametasone intravenously, followed by 10 mg 12 h later and by 10 and 5 mg at 24 and 36 h respectively, monitoring closely all respiratory parameters. Post-operatively the patient’s vital signs were intensively monitored. In addition, her hematological indices were recorded every 6 h and her liver function every 12 h for the first 48 h post-partum. Both the systolic and diastolic pressure significantly improved within the first 24 h post-partum. Laboratory evaluation revealed a significant rise in platelets by 24 h and a significant decrease in LDH and aspartate aminotransferase by 36 h. Urine output increased up to 100 ml/h within the first 24 h. On the first post-operative day, the patient restarted to take pyridostigmine at her pre-pregnancy dosage, 40 mg t.i.d. She elected not to breast-feed her baby and no symptoms of neonatal MG were observed. Her resulting post-operative course was uneventful and both mother and baby were discharged home on the sixth post-operative day. Her medication on discharge was methyldopa 250 mg b.i.d. and 40 mg of pyridostigmine t.i.d. At her 6-week post-natal follow-up her blood pressure was normal, she was off medication and her myasthenia was well controlled.
Table 1 Biochemical and hematological data
1. Discussion
Ht Hb (g/dl) Total bilirubin (mg/dl) LDH (U/l) Platelet (cells/ml) ALT (U/l) AST (U/l) Fibrinogen (mg/dl) Creatinin (mg/dl) Uric acid (mg/dl) D-dimers (mg/dl) PT (s) APTT (s)
Admission
First day Second day Third day
26.2 8.4 2.1 543 200 75 90 310 1.2 5.2 – 10.8 29
25.5 7.9 2.1 600 150 80 95 280 1.6 5.9 – 11.5 34
25.1 7.8 2.2 720 110 93 135 260 1.7 6.3 35 11.7 35
24.7 7.6 2.4 760 90 101 150 220 1.8 7.1 45 12.8 38
Myasthenia gravis is an autoimmune disease. The exact underlying pathophysiology is not fully understood, but autoantibodies appear to block neuromuscular transmission probably via a complement-dependent model, at the postsynaptic portion of the neuromuscular junction. Similarly, despite intensive research efforts, the exact pathogenesis of preeclampsia remains unclear. However, some authors suggest an autoimmune component in the etiology. Redman et al. [6] suggested that pregnancy is normally associated with a maternal inflammatory response, and that preeclampsia simply represents an abnormal and/or exaggerated intravascular inflammatory response to the
110
A. Di Spiezio Sardo et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 108–111
presence of foreign genetic material, similar to graftversus-host disease (transplant rejection). So preeclampsia could be considered as a form of an autoimmune disorder, with the placenta as the source of the inflammatory stimulus. Myasthenia gravis is associated with other autoimmune disorders, such as rheumatoid arthritis and Hashimoto’s thyroiditis. It is therefore possible that there is an association between MG and preeclampsia, given the latter’s hypothesized autoimmune basis. However, this association is not proven and reports in the literature are rare. The first case was reported by Cohen et al. in 1976, with Duff [5], Bashuk, and Benshushan et al. [4] adding four further cases. Duff [5] hypothesized that MG and preeclampsia might share a common etiology. He suggested that because of the disordered immunologic status in patients with myasthenia, the ‘‘protection’’ mechanisms of pregnancy might not develop properly, and the rejection that develops is manifested as preeclampsia. However, some epidemiological data appear to disagree with this hypothesis. The prevalence of preeclampsia is 5–9% and that of myasthenia is 0.004%. Both disorders affect women of reproductive age, and therefore statistically one would expect it to have been reported more frequently. Furthermore, the exacerbations of myasthenia have been mostly observed during the first half of pregnancy [3] whereas preeclampsia is mainly a disease of the third trimester. In his paper Benshushan et al. [4] summarizes the complications that arose during the five reported pregnancies. Acute respiratory insufficiency was reported in three of the five cases. It appears a frequent complication of myasthenia exacerbation during pregnancy. In the preeclamptic myasthenic patient, it could be due to pulmonary congestion, developing especially in those myasthenics on high-dose steroid treatment. So it is very important to make a correct diagnosis as to the cause of respiratory failure in these patients, because an incorrect treatment might aggravate the patient’s condition (e.g. steroids in severe preeclampsia with pulmonary congestion; magnesium sulfate in myasthenia relapse with respiratory insufficiency). Other spontaneous complications reported were advanced weakness [5], oliguria [5] and hemorrhage whilst in two cases myasthenic crisis and advanced weakness arose as a consequence of the administration of magnesium sulfate. Magnesium sulfate, though drug of choice in the treatment of preeclampsia, is contraindicated in MG as it induces a neuromuscular blockage and may cause a severe myasthenic crisis. To our knowledge, we report a case of HELLP syndrome and myasthenia for the first time. Patients whose pregnancies are complicated by HELLP syndrome are at a higher risk for infection, eclampsia,
coagulopathy, hemorrhage, renal failure, adult respiratory distress syndrome, hepatic infarction and rupture and cardiopulmonary failure. A temporary stabilization or a reversal of HELLP syndrome after administration of antenatal corticosteroids has been reported in the literature leading to the hypothesis that such medication might reduce the severity of a hepatic cell injury. A recent study demonstrated that dexametasone given as 10 mg intravenous injections every 12 h was more effective than betamethasone given as 12 mg intramuscular injections every 24 h for the antepartum treatment of mothers with HELLP syndrome. Because delivery is the definitive cure for the women with HELLP syndrome, conservative management is justifiable only if the fetus has not already been compromised at the time of the diagnosis. In our case, given the deteriorating maternal condition, we elected for abdominal delivery under regional anesthesia. We were conscious that cesarean section is particularly hazardous for the myasthenic patient because the surgical stress and the combined administration of anesthetic might increase the risk of a myasthenic crisis. However, in our case, we believed that the surgical delivery was indicated given the worsening maternal condition. Once delivered, there is a significant post-partum morbidity and mortality associated with preeclampsia and HELLP syndrome. It has been shown that a short course of post-partum corticosteroids therapy can minimize maternal morbidity and accelerate post-partum recovery. We therefore administrated corticosteroids for the first 36 h post-partum and the HELLP syndrome rapidly resolved. However, as mentioned above, the use of corticosteroids in a myasthenic preeclamptic patient can be dangerous because of the risk of developing pulmonary congestion and consequent acute respiratory insufficiency. It is therefore important to monitor closely respiratory parameters and sometimes also to assess central venous pressure or pulmonary wedge pressures with a Swan-Ganz catheter. We administrated corticosteroids for 3 days. The absence of any respiratory difficulty and the well-controlled blood pressure convinced us corticosteroids were safe and effective in reducing the risk of post-partum HELLP complications. In summary, we recommend that the pregnant myasthenic patient who develops preeclampsia should be hospitalized, preferably in a tertiary care centre with access to respiratory support. The delivery of appropriate treatment requires a multidisciplinary approach with close collaboration between the obstetrician, neurologist, anaesthetist and neonatologist. The use of antenatal and post-partum corticosteroid is not without morbidity and must therefore be considered carefully.
A. Di Spiezio Sardo et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 108–111
References [1] Daskalakis GJ, Papageorgiou IS, Petrogiannis ND, Antsaklis AJ, Stylianos KM. Myasthenia gravis and pregnancy. Eur J Obstet Gynecol Reprod Biol 2000;89:201–4. [2] Batocchi AP, Majolini L, Evoli A, Lino M, Minisci C, Tonali P. Course and treatment of myasthenia gravis during pregnancy. Neurology 1999;52:447–52.
111
[3] Plauche WC. Myasthenia gravis in mothers and their newborns. Clin Obstet Gynecol 1991;34:82–99. [4] Benshushan A, Rojansky N, Weinstein D. Myasthenia gravis and preeclampsia. Isr J Med Sci 1994;30:229–33. [5] Duff GB. Preeclampsia and the patient with myasthenia gravis. Obstet Gynecol 1979;54:355–8. [6] Redman CWG, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999;180:499–506.
Case report
Myasthenia and HELLP syndrome Attilio Di Spiezio Sardoa,*, Alex Taylorb, Massimiliano Pellicanoa, Lucio Romanoa, Giuseppe Acunzoa, Giuseppe Bifulcoa, Giuseppe Cerrotaa, Carmine Nappia a
Department of Gynaecology, Obstetrics, and Pathophysiology of Human Reproduction, University of Naples ‘‘Federico II’’, Via S. Pansini 5, Naples 80131, Italy b Minimally Invasive Therapy Unit and Endoscopy Training Centre, University Department of Obstetrics and Gynaecology, Royal Free Hospital, Hampstead, London, UK Received 1 April 2003; received in revised form 1 October 2003; accepted 22 December 2003
Keywords: Myasthenia; HELLP syndrome; Preeclampsia; Corticosteroids
Myasthenia gravis (MG) is a chronic autoimmune disorder of neuromuscolar transmission. It is characterized by muscle weakness and fatiguability following repetitive activity, particularly of the face and extremities. The most common clinical features are dysarthria, ptosis, diplopia, dysphagia and respiratory distress [1]. MG occurs twice as often in women than in men, with a peak incidence in the third decade. Hence, it does not infrequently affects women during their childbearing years [2]. Although there is no evidence that MG adversely affects fertility, MG patients rarely become pregnant. As a consequence, the published literature on MG and pregnancy is scant and controversial. The course of MG is unpredictable during pregnancy [2]. Disease patterns vary and a myasthenic crisis can occur at any time during pregnancy. In a review of 322 pregnancies in 225 myasthenic patients, approximately one-third of MG patients deteriorated, one-third remained stable and onethird evolved in partial remission [3]. The first trimester of pregnancy and the first post-partum month seem to be the most critical periods for an MG exacerbation [2], whilst its signs and symptoms tend to improve throughout the second and third trimester coinciding with the immunosuppression which normally takes place during this period. The clinical course of MG during pregnancy appears to have no predictive value for subsequent gestations [2]. Preeclampsia is a not a single disease, but rather a clinical syndrome encompassing three distinct elements: (1) *
Corresponding author. Tel.: þ39-081-7462905; fax: þ39-081-7462903. E-mail address: [email protected] (A. Di Spiezio Sardo). 0301-2115/$ – see front matter # 2004 Published by Elsevier Ireland Ltd. doi:10.1016/j.ejogrb.2003.12.027
new-onset of hypertension (defined as a consistent elevation in blood pressure >140/90 in a previously normotensive woman); (2) new-onset proteinuria (defined as >300 mg/ 24 h or 2þ on a clean-catch dipstix) in the absence of urinary infection; and (3) new-onset non-dependent edema. The diagnosis of preeclampsia can only reliably be made after 20-week gestation. Preeclampsia complicates 6–8% of all pregnancy and is an important cause of maternal and perinatal mortality and morbidity worldwide. Preeclampsia in the pregnant myasthenic patient is exceedingly rare. Only five cases have been found in the English language medical literature [4,5]. The coexistence of these disorders produces a high degree of morbidity and mortality for both mother and fetus [4]. The reported complications include: acute respiratory insufficiency, advanced weakness, oliguria, hemorrhage and iatrogenic myasthenic crisis. ‘‘HELLP’’ is the acronym for the syndrome of hemolysis, elevated liver enzymes and low platelet count, which develops as an atypical complicated form of severe preeclampsiaeclampsia. It is a disease isolated to pregnancy and is associated with an increased risk of maternal and neonatal morbidity and mortality rates, particularly if occurring in the second trimester. We report what is, to the best of our knowledge, the first case in the international literature of the association between myasthenia and HELLP syndrome. A 27-year-old, nulliparous woman was referred to our hospital at 37-week gestation with a 2-week history of gross edemas of the lower extremities. Her past medical history was unremarkable except for her myasthenia gravis that was diagnosed at the age of 25. Following her thymectomy at the
A. Di Spiezio Sardo et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 108–111
109
age of 26 years, her MG had been successfully controlled with pyridostigmine 40 mg t.i.d. At the onset of pregnancy, the dose was lowered to 40 mg b.i.d. She previously had one first trimester miscarriage. A booking bloods revealed her to have a thalassemic treat. An ultrasound scan (USS) performed at 21 weeks showed a normal developing fetus with no obvious structural defects. In the second trimester, she developed a marked microcytic anemia that was corrected by blood transfusions. On admission at 37 weeks, the fundal height was consistent with dates, the fetal lie was longitudinal and the presentation cephalic. She was well but for her gross peripheral edema and a raised blood pressure of 160/110 mmHg. An admission cardiotocogram was normal and a USS revealed normal fetal biometry with a normal amniotic fluid index. Admission blood indices revealed a hemoglobin of 8.4 g/dl and increased levels of serum aspartate aminotransferase (90 U/l), alanine aminotransferase (75 U/l) and total bilirubin (2.1 mg/dl). Neurological examination was normal, in keeping with her good antenatal control of her MG. The patient was started on oral treatment with 250 mg methyldopa t.i.d. and maternal and fetal well being were intensively monitored. Her blood pressure was well controlled for the first 2 days, but on the third day it increased to 180/110 mmHg despite bed rest and orally administered methyldopa. In addition she became symptomatic complaining of headache, visual disturbances and nausea. A 24 h urine collection on the third day revealed 5 g of proteins. Comparable data were present on day 1 and day 2 (1.5 g/24 h and 3 g/24 h, respectively). The urine output fell from 50 ml/h on the first day to 26 ml/h by the third day and was noted to be orange (consistent with hemolysis). The most relevant data of the patient’s laboratory evaluation are shown in the Table 1. Given the clinical picture and laboratory evidences of hemolysis (LDH 600 U/l and total bilirubin 1.2 mg/
dl), low platelet (<150,000 cells/ml) and hepatic dysfunction (AST 40 U/l, ALT 40 U/l), a diagnosis of severe preeclampsia complicated by HELLP syndrome was made. The severity of the HELLP syndrome was determined with the Mississippi triple class system. Based on this system our patient was classified as class 2, with elevated liver enzymes, hemolysis and a platelet count of 50,000– 100,000 cells/ml platelets. In view of the worsening clinical picture a decision was made to expedite delivery by emergency cesarean section. The cesarean section was performed under regional anesthesia and resulted in the delivery of a healthy 3140 g male with Apgar scores of 8 and 9 at 1 and 5 min, respectively. The patient received immediately post-partum 10 mg of dexametasone intravenously, followed by 10 mg 12 h later and by 10 and 5 mg at 24 and 36 h respectively, monitoring closely all respiratory parameters. Post-operatively the patient’s vital signs were intensively monitored. In addition, her hematological indices were recorded every 6 h and her liver function every 12 h for the first 48 h post-partum. Both the systolic and diastolic pressure significantly improved within the first 24 h post-partum. Laboratory evaluation revealed a significant rise in platelets by 24 h and a significant decrease in LDH and aspartate aminotransferase by 36 h. Urine output increased up to 100 ml/h within the first 24 h. On the first post-operative day, the patient restarted to take pyridostigmine at her pre-pregnancy dosage, 40 mg t.i.d. She elected not to breast-feed her baby and no symptoms of neonatal MG were observed. Her resulting post-operative course was uneventful and both mother and baby were discharged home on the sixth post-operative day. Her medication on discharge was methyldopa 250 mg b.i.d. and 40 mg of pyridostigmine t.i.d. At her 6-week post-natal follow-up her blood pressure was normal, she was off medication and her myasthenia was well controlled.
Table 1 Biochemical and hematological data
1. Discussion
Ht Hb (g/dl) Total bilirubin (mg/dl) LDH (U/l) Platelet (cells/ml) ALT (U/l) AST (U/l) Fibrinogen (mg/dl) Creatinin (mg/dl) Uric acid (mg/dl) D-dimers (mg/dl) PT (s) APTT (s)
Admission
First day Second day Third day
26.2 8.4 2.1 543 200 75 90 310 1.2 5.2 – 10.8 29
25.5 7.9 2.1 600 150 80 95 280 1.6 5.9 – 11.5 34
25.1 7.8 2.2 720 110 93 135 260 1.7 6.3 35 11.7 35
24.7 7.6 2.4 760 90 101 150 220 1.8 7.1 45 12.8 38
Myasthenia gravis is an autoimmune disease. The exact underlying pathophysiology is not fully understood, but autoantibodies appear to block neuromuscular transmission probably via a complement-dependent model, at the postsynaptic portion of the neuromuscular junction. Similarly, despite intensive research efforts, the exact pathogenesis of preeclampsia remains unclear. However, some authors suggest an autoimmune component in the etiology. Redman et al. [6] suggested that pregnancy is normally associated with a maternal inflammatory response, and that preeclampsia simply represents an abnormal and/or exaggerated intravascular inflammatory response to the
110
A. Di Spiezio Sardo et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 108–111
presence of foreign genetic material, similar to graftversus-host disease (transplant rejection). So preeclampsia could be considered as a form of an autoimmune disorder, with the placenta as the source of the inflammatory stimulus. Myasthenia gravis is associated with other autoimmune disorders, such as rheumatoid arthritis and Hashimoto’s thyroiditis. It is therefore possible that there is an association between MG and preeclampsia, given the latter’s hypothesized autoimmune basis. However, this association is not proven and reports in the literature are rare. The first case was reported by Cohen et al. in 1976, with Duff [5], Bashuk, and Benshushan et al. [4] adding four further cases. Duff [5] hypothesized that MG and preeclampsia might share a common etiology. He suggested that because of the disordered immunologic status in patients with myasthenia, the ‘‘protection’’ mechanisms of pregnancy might not develop properly, and the rejection that develops is manifested as preeclampsia. However, some epidemiological data appear to disagree with this hypothesis. The prevalence of preeclampsia is 5–9% and that of myasthenia is 0.004%. Both disorders affect women of reproductive age, and therefore statistically one would expect it to have been reported more frequently. Furthermore, the exacerbations of myasthenia have been mostly observed during the first half of pregnancy [3] whereas preeclampsia is mainly a disease of the third trimester. In his paper Benshushan et al. [4] summarizes the complications that arose during the five reported pregnancies. Acute respiratory insufficiency was reported in three of the five cases. It appears a frequent complication of myasthenia exacerbation during pregnancy. In the preeclamptic myasthenic patient, it could be due to pulmonary congestion, developing especially in those myasthenics on high-dose steroid treatment. So it is very important to make a correct diagnosis as to the cause of respiratory failure in these patients, because an incorrect treatment might aggravate the patient’s condition (e.g. steroids in severe preeclampsia with pulmonary congestion; magnesium sulfate in myasthenia relapse with respiratory insufficiency). Other spontaneous complications reported were advanced weakness [5], oliguria [5] and hemorrhage whilst in two cases myasthenic crisis and advanced weakness arose as a consequence of the administration of magnesium sulfate. Magnesium sulfate, though drug of choice in the treatment of preeclampsia, is contraindicated in MG as it induces a neuromuscular blockage and may cause a severe myasthenic crisis. To our knowledge, we report a case of HELLP syndrome and myasthenia for the first time. Patients whose pregnancies are complicated by HELLP syndrome are at a higher risk for infection, eclampsia,
coagulopathy, hemorrhage, renal failure, adult respiratory distress syndrome, hepatic infarction and rupture and cardiopulmonary failure. A temporary stabilization or a reversal of HELLP syndrome after administration of antenatal corticosteroids has been reported in the literature leading to the hypothesis that such medication might reduce the severity of a hepatic cell injury. A recent study demonstrated that dexametasone given as 10 mg intravenous injections every 12 h was more effective than betamethasone given as 12 mg intramuscular injections every 24 h for the antepartum treatment of mothers with HELLP syndrome. Because delivery is the definitive cure for the women with HELLP syndrome, conservative management is justifiable only if the fetus has not already been compromised at the time of the diagnosis. In our case, given the deteriorating maternal condition, we elected for abdominal delivery under regional anesthesia. We were conscious that cesarean section is particularly hazardous for the myasthenic patient because the surgical stress and the combined administration of anesthetic might increase the risk of a myasthenic crisis. However, in our case, we believed that the surgical delivery was indicated given the worsening maternal condition. Once delivered, there is a significant post-partum morbidity and mortality associated with preeclampsia and HELLP syndrome. It has been shown that a short course of post-partum corticosteroids therapy can minimize maternal morbidity and accelerate post-partum recovery. We therefore administrated corticosteroids for the first 36 h post-partum and the HELLP syndrome rapidly resolved. However, as mentioned above, the use of corticosteroids in a myasthenic preeclamptic patient can be dangerous because of the risk of developing pulmonary congestion and consequent acute respiratory insufficiency. It is therefore important to monitor closely respiratory parameters and sometimes also to assess central venous pressure or pulmonary wedge pressures with a Swan-Ganz catheter. We administrated corticosteroids for 3 days. The absence of any respiratory difficulty and the well-controlled blood pressure convinced us corticosteroids were safe and effective in reducing the risk of post-partum HELLP complications. In summary, we recommend that the pregnant myasthenic patient who develops preeclampsia should be hospitalized, preferably in a tertiary care centre with access to respiratory support. The delivery of appropriate treatment requires a multidisciplinary approach with close collaboration between the obstetrician, neurologist, anaesthetist and neonatologist. The use of antenatal and post-partum corticosteroid is not without morbidity and must therefore be considered carefully.
A. Di Spiezio Sardo et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 108–111
References [1] Daskalakis GJ, Papageorgiou IS, Petrogiannis ND, Antsaklis AJ, Stylianos KM. Myasthenia gravis and pregnancy. Eur J Obstet Gynecol Reprod Biol 2000;89:201–4. [2] Batocchi AP, Majolini L, Evoli A, Lino M, Minisci C, Tonali P. Course and treatment of myasthenia gravis during pregnancy. Neurology 1999;52:447–52.
111
[3] Plauche WC. Myasthenia gravis in mothers and their newborns. Clin Obstet Gynecol 1991;34:82–99. [4] Benshushan A, Rojansky N, Weinstein D. Myasthenia gravis and preeclampsia. Isr J Med Sci 1994;30:229–33. [5] Duff GB. Preeclampsia and the patient with myasthenia gravis. Obstet Gynecol 1979;54:355–8. [6] Redman CWG, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999;180:499–506.