Amyotrophic Lateral Sclerosis Presenting During Pregnancy

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurologic disease affecting the anterior horn cells of the spinal cord. It is fatal after an average of three to five years [1,2]. The onset is usually in the fourth decade of life, and it is more common in men. The familial variant may be rapidly progressive. Characteristic of ALS is the loss of all voluntary motor function, with the exception of the ocular muscles and sphincters. Sensation and higher cortical function are unaffected. Its occurrence in women of reproductive age is exceedingly rare [2,3]. This report describes the management of a patient who developed ALS during pregnancy. Case Report A 31-yr-old primagravida, nulliparous female patient presented with progressive leg weakness at 8 wk gestation. She had a strong family history of ALS and a remote history of idiopathic thrombocytopenia purpura (ITP) treated by splenectomy. Physical examination and subsequent investigations confirmed ALS. She developed obvious quadriparesis by the end of the first trimester. Although pulmonary function tests showed only mild restriction at that time. (Forced vital capacity [FVC] 2.37 L and forced expiratory volume in 1s [FEV1] 2.12 L, 72% and 75% of predicted, respectively), long-term ventilation (LTV) was discussed, anticipating the possibility of precipitous respiratory failure during the pregnancy. By 32 wk gestation, she was dyspneic at rest. Pulmonary function tests then showed an FEV1 of 0.78 L (27% predicted) and FVC of 0.88 L (26% predicted). PaCO2 was 55 mm Hg and HCO3 was 31 mmol/L, with a normal pH and PaO2. Preterm delivery was planned because of maternal respiratory insufficiency. Amniocentesis confirmed fetal lung maturity. Because of the maternal history of ITP and splenectomy, cordocentesis was performed, which identified a fetal platelet count of 45,000/mm3. The patient's profound motor weakness greatly increased the probability of assisted delivery. The risk of operative vaginal delivery to the preterm thrombocytopenic fetus was uncertain [4]. After discussion with the patient and her family, cesarean delivery was planned, primarily because of concerns about potential fetal risk. Epidural anesthesia was planned with maternal monitors including electrocardiogram, pulse oximetry, and continuous blood pressure via a radial artery catheter. A lumbar epidural catheter was placed and avascular epidural positioning was confirmed with an epinephrine-containing test dose. Bupivicaine 0.5% with epinephrine (total 16 mL) was titrated over 20 min to the T6 dermatome. Although no clinical effect on the patient's respiration was noted, the fraction of inspired oxygen was 1.0, and blood gases were pH 7.22, PaCO2 70 mm Hg, PaO2 354 mm Hg, and HCO3 29 mmol/L after epidural titration. A healthy 2810-g female infant was delivered. Five minutes later, the patient was suddenly presyncopal and dyspneic. Arterial blood pressure was 50/0 mm Hg, and oxygen saturation was not measurable, but no hemorrhage was noted. The patient was resuscitated by administration of two IV boluses of epinephrine 500 [micro sign]g and 2.0 L of saline, but she did not require ventilatory support during the brief episode. The epidural extent was estimated at T4/5, the fraction of inspired oxygen was 1.0, and arterial blood gases were pHa 7.24, PaCO2 64 mm Hg, PaO2 344 mm Hg, and HCO3 28 mmol/L immediately after the episode. The patient remained stable until completion of the surgery and was transferred to the intensive care unit. Respiratory support was considered because of the acute on chronic respiratory failure seen from analysis of the arterial blood gases. Because the patient was able to protect her airway, noninvasive respiratory support was begun using biphasic positive airway pressure (BiPap). After 3 days of noninvasive ventilation, the patient had subjectively improved. Blood gases while breathing room air 24 h after stopping BiPap showed a pHa of 7.32, PaCO2 of 50 mm Hg, PaO2 of 65 mm Hg, and HCO (3) of 28 mmol/L. There was no objective motor recovery in her limbs, despite complete and prompt sensory recovery from the epidural. She suddenly developed hypercapneic respiratory failure 1 wk later and required emergency endotracheal intubation because of obtundation. In keeping with her previous wishes, tracheostomy and gastrostomy were performed. She was discharged home 8 wk later, on LTV. Immediate neurobehavioural function of the infant was normal, and it remained so for the next 18 mo. The mother-child interaction was initially poor, probably because of the mother's respiratory failure. This interaction improved significantly after tracheostomy, ventilation, and discharge home. Discussion The published experience of similar patients with ALS in association with pregnancy is scant. The largest experience with ALS is probably in Guam, where the incidence is approximately 100 times greater than elsewhere [2]. No effect, either beneficial or detrimental, of ALS on pregnancy (or vice versa), has been noted from Guam. Only one patient in the literature is reported to have terminated a pregnancy because of concurrent ALS [2], and in that patient, termination had no apparent effect on the course of ALS. A non-reporting bias may affect other similar cases showing no benefit. Normal PaCO2 at term is 28-32 mm Hg [5], compared with 55 mm Hg in our patient at 32 wk. Although artificial respiratory support would have been appropriate at 32 wk and after delivery, some recovery of respiratory function was anticipated once the physiologic and mechanical stresses of pregnancy had begun to resolve [5-7]. Although this may take days to weeks, this patient improved significantly after three days of BiPap. Invasive ventilation, compared with noninvasive ventilation in the patient capable of airway protection, has been associated with an increased risk of complications [8]. The choice of vaginal or cesarean delivery is controversial. This patient was in incipient respiratory failure, and either route of delivery presented substantial risk. Labor increases cardiovascular and respiratory work, but the largest increase occurs after birth [4] and should be similar for either route of delivery. Lower abdominal surgery is associated with lung volume loss that is sustained for nearly two weeks [6], which would have favored a vaginal birth. Intraventricular hemorrhage has been seen with both spontaneous vaginal and cesarean delivery of fetuses with severe thrombocytopenia (platelets <50,000/mm3) [4]. The unique combination of significant fetal thrombocytopenia, prematurity, and anticipated operative vaginal delivery favored cesarean birth for this patient. Regional anesthesia (RA) offers advantages in its ability to provide sustained pain relief and to preserve bulbar function. RA and general anesthesia have been associated with similar reductions in lung volume and flow rates [9]. The effects of RA on intercostal muscles may impede expiratory flow, which would be of concern to the normal patient in respiratory failure, but these muscles were not functional in this patient. Choice of anesthetic technique for cesarean section based on pulmonary function alone did not favor either RA or general anesthesia convincingly. RA offers a greater potential for earlier establishment of mother-child bonding, which was a significant factor in the decision to provide RA in this case. This patient suffered a cardiovascular collapse shortly after delivery, and responded promptly to resuscitation. The broad differential diagnosis included the cardiovascular effects of oxytocin, venous air embolism (VAE), intravascular local anesthetic, amniotic fluid embolism, or a high epidural. The prompt response excluded amniotic fluid embolism, and subsequent assessment did not reveal a high block. The temporal course favored either the cardiovascular effect of oxytocin or VAE. Use of a precordial stethescope would have facilitated diagnosis of VAE. Lack of sustained myocardial effects made local anesthetic toxicity unlikely. LTV is chosen by 10% of patients with ALS, and 90% of patients on LTV report satisfaction with their decision [10-12]. It requires a large amount of family, financial, and community support. Early discussion of LTV in similar patients is warranted, as respiratory failure may develop precipitously, preventing an informed and uncoerced discussion of the implications of LTV. In summary, this case illustrates the unusual circumstance of a pregnant patient who developed rapidly progressive, familial ALS. The respiratory failure that developed during pregnancy did not resolve after delivery. LTV was begun when respiratory failure occurred, in keeping with the previously declared intent of the patient. Early discussion of LTV in similar patients is warranted.