Cerebrovascular events, along with the early presentation of central poststroke pain (CPSP), during the peripartum period are uncommon. Studies have estimated the risk of stroke at between 21.2 and 46.2 per 100,000 pregnancies.1 Although most of them occur during the third trimester and up until 6 weeks postpartum, there have been reports of early pregnancy cases as well.1 Sensory abnormalities in body parts that correspond to the injured brain territory can give rise to neuropathic pain with central origin, defining CPSP.2 In this case report, we describe the management of a parturient with a history of ischemic stroke due to cerebral sinus venous thrombosis at 15 weeks of pregnancy, CPSP development at 20 weeks, who delivered via cesarean delivery at 35 weeks of gestation. Written informed consent was obtained.
A 33-year-old woman (G1, P0), at 15 weeks of gestation, was admitted to the emergency department after an episode of loss of consciousness for ≥3 hours. Neurological examination revealed an altered level of consciousness, partial memory loss, expressive but nonreceptive dysphasia, and left-sided hemiplegia. The magnetic resonance imaging revealed an absence of flow-related signal within the right transverse sinus, consistent with cerebral sinus venous thrombosis, with a thrombotic occlusion of the right middle cerebral artery. Laboratory tests showed protein S deficiency. A follow-up magnetic resonance imaging performed after 2 weeks of therapeutic treatment with low-molecular-weight heparin, revealed ischemia in the territory supplied by the middle cerebral artery. Because there was no evidence of fetal compromise, it was decided to continue pregnancy until fetal maturity. Four weeks later, the parturient began to experience constant central pain with neuropathic pruritus, along with a burning and aching sensation in the left side. As a result, she was referred to the chronic pain management service of our hospital, where she was initially prescribed with pregabalin 25 mg/d, then increased gradually to 75 mg/d for 1 week. During this period, she complained of drowsiness and dizziness, but the severity did not justify discontinuation of her medication. Due to her concern of neonatal opioid withdrawal syndrome, opioids were not prescribed. Moreover, due to the severity of the pain in the second week of CPSP development, pregabalin was further increased to 225 mg/d. At that time, the patient attempted suicide because she was suffering from intolerable pain and disability. In response, transdermal fentanyl patches were administered and her pain was eventually controlled with 25 μg/h every 3 days, in addition to pregabalin. Nonpharmacological interventions were also offered to reduce opioid requirements. Family support and several sessions with an expert clinical psychologist eventually helped her decrease pain catastrophizing.
After a multidisciplinary team consultation and due to intense CPSP refractory to pharmacotherapy, she was admitted for a cesarean delivery, at 35 weeks of gestation, with a height of 167 cm, term weight of 70 kg, and no signs of further neurological deterioration.
The choice of regional over general anesthesia was fully explained. On preanesthetic evaluation, heart rate was 88/min, blood pressure was 115/80 mm Hg, and oxygen saturation measured by pulse oximetry was 99%. She had an expressive but nonreceptive dysphasia, was able to respond to direct questioning by squeezing her right hand. She had a dense hemiplegia with motor strength evaluated as 1/5 on her left side. She had normal blood count, coagulation tests, electrocardiogram, and echocardiogram. Last doses of low-molecular-weight heparin had been given 24 hours earlier. Apart from American Society of Anesthesiologists standard monitoring, a radial artery line was placed not only to ensure optimal blood pressure monitoring, but also because she felt unbearable discomfort from cuff inflation. Α single dose of 50 μg fentanyl was administered IV for intolerable allodynia and hyperalgesia even on palpation of her left side of her body.
Under aseptic conditions, a combined spinal-epidural was performed in the left lateral position. During skin disinfection with chlorhexidine, she complained of intense cold hyperalgesia and allodynia, especially on the left affected side, when excess of antiseptic solution dripped down to her back. Because of this, a paramedian approach from the right lateral side was done, introducing an epidural Tuohy needle (Portex; 18-gauge, 80 mm in length; Smiths Medical ASD, Inc, Keene, NH) at the L2–L3 interspace. When loss of resistance to air was encountered at 60 mm, she experienced pain on the left with even a small amount of air. The subarachnoid space was located with a 27-gauge pencil point spinal needle using the needle-through-needle technique. After aspirating clear cerebrospinal fluid with the bevel of the spinal needle facing in a cephalic direction, 1.6 mL of 0.75% of ropivacaine with 15 μg of fentanyl was administered intrathecally. No pain or paresthesia was noted. Finally, the epidural catheter was easily inserted and secured at the skin, leaving 6 cm in the epidural space. The patient was subsequently placed in a wedged, supine position, and a T3 sensory block to pinprick was achieved after 5 minutes. Neuropathic pain disappeared below T3, but persisted in the left upper arm. All cardiovascular parameters remained stable. A healthy boy of 2300 g was delivered with normal Apgar scores of 7 and 9 at 1 and 5 minutes, respectively. Postoperative analgesia was achieved with 2 epidural doses of 1.5 mg of morphine at 12-hour intervals as well as supplemental epidural doses of 6 mL ropivacaine 0.2% at 6-hour intervals, for a total of 3 days, until the epidural catheter was removed. Paracetamol 1000 mg orally 3 times per day and ibuprofen 200 mg twice a day were administered. Her pregabalin dosage was increased to 450 mg/d, in combination with fentanyl patch 50 μg/h. Amitriptyline was recommended for further management and initiated in a dose ranging from 25 mg/d orally and continued at a daily maintenance dose of 75 mg/d orally. The patient experienced significant pain relief with minimal side effects. She recovered well from the cesarean delivery and was discharged home on the fifth postsurgical day. She was referred for neurorehabilitation, physiotherapy, and follow-up pain relief sessions with pain specialists and a clinical psychologist. The baby did not exhibit signs or symptoms of opioid withdrawal syndrome or any congenital malformations. On follow-up, after 2 months and then 1 year after, she was able to walk with support and to look after her baby with assistance.
There are few relevant published cases,3,4 but none discuss the presentation of CPSP in early pregnancy.
Although thrombolysis has historically been contraindicated during pregnancy, several studies document successful use of revascularization therapy even in early pregnancy.5 The IV administration of recombinant tissue-type plasminogen activator has a theoretical risk of uterine or fetal hemorrhage that may preclude use of this agent, although it does not cross the blood-placenta barrier. Given the severity of her neurological deficits, thrombolytic therapy was considered, but the time elapsed from the onset of symptoms was significantly >4.5 hours.6
The pharmacological treatment of CPSP7 may pose the risk of congenital malformations and opioid withdrawal syndrome.8 There is evidence that pregabalin in the first trimester is linked to a higher risk of birth defects.9 In our case, the benefits of pregabalin outweighed the risks. A higher dose of folic acid (up to 5 mg daily) is recommended in pregnant patients taking antiepileptic drugs.10
Although the prenatal use of opioids may be linked to birth defects or opioid withdrawal syndrome,7 an association between first-trimester maternal intake of codeine and congenital abnormalities has not been clearly demonstrated.11 Moreover, a meta-analysis comparing methadone and buprenorphine found no significant differences with respect to congenital malformations than in non-opioid–dependent parturients,12 while prolonged administration of fentanyl has been associated with a mild opioid withdrawal syndrome, not requiring drug therapy and with no apparent long-term effects for the infant.13
Anesthesia within 6 weeks of a cerebrovascular event is associated with a 20-fold increase in mortality in nonpregnant population.3 We performed a combined spinal-epidural to allow a constant neurological evaluation. Furthermore, effective postoperative analgesia was achieved due to the epidural catheter in situ. The paramedian approach limited the intense 1-sided cold allodynia and hyperalgesia the patient experienced.
Finally, the issue of a valid informed consent is of major importance, and the capacity to make an autonomous decision must be ensured.3
Name: Konstantina Kalopita, MD, MSc.
Contribution: This author helped write and review the manuscript.
Name: Vasiliki Skandalou, MD.
Contribution: This author helped care for the patient and review the manuscript.
Name: Dimitrios Valsamidis, MD, PhD.
Contribution: This author was the supervising anesthesiologist of this case, and helped provide expert opinion and review the manuscript.
This manuscript was handled by: BobbieJean Sweitzer, MD, FACP.
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