Critical Care Obstetrics part 26 pdf

Pregnancy-Related Stroke 239 [124,125] . Until the mid - 1980s, the diagnosis of CVT was usually made postmortem [126,127] . The development of better imaging techniques, particularly MRI/MRA, has considerably facilitated radiologic diagnosis in the patient suspected of the condition. Pathogenesis The cerebral venous system of the human brain is unique in that major veins are composed of dural folds called sinuses which lack muscular walls, valves or the ability to contract. Hence blood can pool and clots form in these veins in susceptible patients to cause a sinus thrombosis, occluding and obstructing venous return in the brain with variable degrees of increased venous pressure, impaired absorption of cerebrospinal fl uid, increased intracranial pressure, ischemia, infarction, cytotoxic edema, bleeding, and vasogenic edema [128,110] . The superior and inferior sagittal sinuses drain sequentially into the confl uence of sinuses, the cav- ernous sinus, the transverse sinus, the right and left sigmoid sinus and fi nally the internal jugular veins. The location and extent of the affected vein(s) contribute to the terminology used to describe the particular CVT in a given patient such as cortical venous thrombosis, cerebral sinus thrombosis, dural sinus thrombosis, and sagittal venous thrombosis. The most common sites involved in the pregnant patient are thrombosis of the sagittal sinus with secondary extension into the cortical veins or primary thrombosis of a cortical vein [129] . A prothrombotic risk factor (genetic or acquired such as pregnancy/puerperium) or a direct mechanical cause (head injury, lumbar puncture, jugular catheterization, neurosurgical procedure) led to 85% of CVT cases in one series of patients [111] . In another, all patients that developed a CVT during pregnancy or the puerperium had a hypercoagulable state identifi ed which was most often associated with elevated factor VIII [130] . Other hyperviscous states that can precipitate CVT with pregnancy include sickle cell anemia, malignancy, polycy- themia, and paroxysmal nocturnal hemoglobinuria. The higher prevalence of CVT in countries like India may be secondary to factors such as higher rates of systemic infection, anemia and severe dehydration [11] . Clinical p resentation Initial symptomatology is diverse and varied, sometimes sudden but more often vague and insidious in onset. Progressive, unusual headache that is resistant to analgesia develops in more than 90% of patients, usually increasing gradually over several days sometimes in association with nausea and/or vomiting. Headache may be the sole complaint in some patients. Rarely it can be misdiag- nosed as a postdural puncture headache if spinal analgesia was used for delivery [131] . The average time interval between symptom onset and eventual diagnosis is 7 days [132] . If all patients with CVT are considered as a group, approximately 50% develop cerebral lesions and neurologic signs and about 40% develop seizures (sometimes misinterpreted as an eclamptic con- vulsion). If thrombosis extends into the deep venous system of the thalami, behavioral symptoms such as delirium, amnesia, mutism and sometimes coma can be manifested [133] . Visual Corticosteroids The potential place of corticosteroids for stroke prevention in the hypertensive pregnant patient particularly with severe pre - eclampsia or HELLP syndrome is a worthy consideration [61] . Intravenous high - dose dexamethasone has been shown to reduce signifi cant maternal morbidity when given early or late during the course of disease development in patients with HELLP syndrome, and it probably reduces the likelihood of patients with this disorder developing cerebral sequelae to their disease [61] . Cerebral hemodynamic studies in patients with HELLP syndrome reveal similar fi ndings to patients with pre - eclampsia [109] . Almost all deaths due to stroke in patients with HELLP syndrome occur in the absence of aggressive pre - emptive cor- ticosteroid therapy for basic disease management [58,61] . A cornerstone of management for patients with hypertensive encephalopathy is the administration of this category of drugs in association with antihypertensive and diuretic agents. Experience with a recent patient who had severe gestational hypertension that quickly and repeatedly returned after treatment with small, frequent intravenous administrations of labetalol and who suffered a cerebral hemorrhage raises the question of whether obstetricians should be more aggressive with labetalol (or other agents) for blood pressure control or whether this approach alone is unlikely to succeed without another agent such as glucocorticoids to interrupt cerebral pathophysiology and thereby avert CVA. Because sudden hypertension can result from, rather than lead to, intracranial bleeding, the initiation of potent glucocorticoids or other agents may augment poorly effective antihypertensive therapy and potentially avoid adverse cerebral sequelae. It is important to recognize that steroid therapy in potential stroke patients is not believed to act through any effect on cerebral edema prevention or alleviation, as it does when used in the management of cerebral edema due to space occupying lesions. Cerebral v enous and s inus t hrombosis General Thrombosis of the cerebral veins (CVT) and sinuses is a distinct cerebrovascular disorder that is more often encountered in females than males, most often late in gestation or during the early puerperium [110 – 115] . The diagnosis is to be considered in a peripartum patient with persistent headache [116] . Thought to be caused by changes in the coagulation process of normal gravid patients or less often in others who have underlying thrombo- philias, either of which can be stressed by events and treatments surrounding delivery, CVT has been diagnosed as late as 3 months postpartum [117] . Almost 200 years ago M é ni è re [118] and Abercrombie [119] were the fi rst to demonstrate the relationship between pregnancy/puerperium and CVT. It was not until the early 1940s that the relationship was better publicized using clinical and autopsy studies [120 – 123] . Within 40 years, 273 puerperal CVT cases were reported by two groups of investigators in India where the incidence was approximately 1 : 250 obstetric admis- sions and the most common cause of stroke in young women Chapter 19 240 tion (see discussion later in chapter). Because the diagnosis of CVT is usually made many hours after the initial development of symptomatology, the potential for thrombolytic therapy for the patient with CVT probably holds less promise than with arterial ischemic stroke. Prognosis Despite remaining a diagnostic challenge and a potentially dis- abling or lethal disease, CVT associated with pregnancy and the puerperium overall has an excellent prognosis with 90 – 93% survival and few persistent neurologic defi cits [147,19] . Postpartum c erebral v asculopathy General Another potential masquerader or mimic of postpartum eclampsia is postpartum cerebral vasculopathy, a type of postpartum angiopathy caused by reversible multifocal brain ischemia and multilocular segmental narrowing of large and medium - sized cerebral arteries [148 – 151] . Affected patients develop severe generalized or occipital headaches with abrupt onset, altered mental status, generalized motor seizures, neurologic defi cits and often some degree of visual impairment which if untreated can progress to ischemic or hemorrhagic stroke in the postpartum period [152] . Diagnosis Angiography is crucial to the diagnosis, especially to be considered in a patient with what is thought to represent delayed postpartum eclampsia. Individuals with Call – Fleming syndrome (benign postpartum angiopathy) may have no abnormalities on a standard MRI but exhibit characteristic angiopathic fi ndings on magnetic resonance angiography [153 – 155] . Patients with postpartum reversible encephalopathy syndrome have hyperintense lesions suggestive of vasogenic edema on both T2 - weighted images and diffusion - weighted images [151] . Other reported patients with cerebral angiopathy exhibited features of a vasculitis. Postpartum cerebral angiopathy may represent a contin- uum of vascular pathology which begins with vasospasm and progresses over time to a true vasculitis [156] , consistent with Varner ’ s suggestion that patient presentations represent different manifestations of similar underlying pathophysiology [157] . Treatment and p rognosis Distinguishing among the various subtypes of cerebral vasculopathy can be problematic, but prompt treatment is advised with antihypertensives, anticonvulsants, corticosteroids and mannitol or furosemide to reduce cerebral edema if present and prevent cerebral herniation [158] . In rare instances pulsed cyclophospha- mide is required to stop the process in patients that fail to respond to methylprednisolone. Prognosis is excellent for patients with evidence of a diffuse vasculopathy but is worse when there is clinical or laboratory evidence supportive of extracerebral or systemic vasculitis [159] . impairment as diplopia and blindness can result from very high intracranial pressure and severe papilledema [110] . Diagnosis The most sensitive examination technique is MRI with gadolin- ium in combination with magnetic resonance venography - MRV [112,134,135] . T1 - weighted and T2 - weighted MRI will show a hyperintense signal from the thrombosed sinuses especially if performed in the fi rst 5 days of thrombosis or after 1 month. Conventional CT scanning results can be entirely normal in the presence of CVT and mislead the physician into missing the diagnosis 60% of the time at initial presentation [136,115,117] . CT venography, however, is a promising new imaging technique to investigate the cerebral venous system. Cerebral angiography in experienced hands can provide better details of the cerebral veins, showing dilated and tortuous ( “ corkscrew ” ) veins that suggest downstream sinus thrombosis. Treatment Based upon the combined fi ndings of three small randomized clinical trials [137 – 139] and a large multicenter prospective observational study of 624 patients with CVT [140] , anticoagulation with intravenous heparin is usually recommended to arrest the thrombotic process and to prevent pulmonary embolism [141] despite the potential risk that a venous infarct might become hemorrhagic. However, in three small randomized clinical trials there were no new cerebral hemorrhages and no increase in already present ones following CVT treatment with heparin. Fixed high dose, subcutaneous heparin of low molecular weight might be a suitable alternative, but presently there are no studies comparing its effectiveness with fractionated heparin. Heparin therapy is generally continued during the acute phase “ until the patient stabilizes ” [126,127] which usually is 3 – 7 days of therapy. Oral anticoagulant therapy using vitamin K antago- nists (coumarin derivatives) is usually continued for 6 months [130] after a fi rst episode of CVT, or longer in the presence of predisposing factors, with a target international normalized ration of 2.5 [110] . Because of rare CVT recurrence in a subsequent pregnancy and insuffi cient data to suggest that prophy- lactic anticoagulation provides any patient benefi t, it is not recommended. Potential t hrombolytic t herapy In pregnant patients with a high - risk/poor - prognosis CVT associated with signifi cant neurologic defi cits and decline, endovascular thrombolysis can be attempted by experienced interventional radiologists using a combination of a thrombolytic enzyme such as rt - PA infused into the dural sinus, and mechanical intervention techniques to aspirate, disrupt and/or dislodge the thrombus [142 – 146] . Although tissue plasminogen activator thrombolysis in pregnancy has been regarded as relatively contraindicated, a number of case reports and series have been published recently to clarify maternal safety and effi cacy issues for the treatment of acute ischemic stroke during gesta- Pregnancy-Related Stroke 241 intraparenchymal) hemorrhage involves bleeding from small arteries or arterioles directly into the brain. Blood spreads along white matter pathways and localized hematoma formation is common. Accumulation of blood can be rapid, but is classically more insidious which coincides with its gradual symptom pro- gression over a few hours. Symptoms typically include worsening headache and focal fi ndings such as a progressively worsening unilateral hemiparesis. In pregnancy, ICH is most commonly due to severe hypertension associated with pre - eclampsia/eclampsia. Illicit drug use, especially cocaine and methamphetamines, bleeding diatheses, trauma, tumors, and small vessel vasculitides are other known causes of ICH [175,176] . Diagnosis and management of ICH is similar to that of SAH (see discussion to follow). Subarachnoid h emorrhage General Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space (anatomically the area between the arachnoid mem- brane and the pia mater) surrounding the brain. SAH can occur secondary to trauma, but is more commonly encountered due either to spontaneous leaking, ruptured aneurysm or an arteriovenous malformation (AVM). Aneurysms and AVMs develop secondary to congenital defects in cerebral vasculature formation at anatomically predictable sites [177] . An aneurysm is a sacular dilation of a blood vessel generally located at an angle of bifurca- tion in or near the circle of Willis – the internal carotid (37%), anterior communicating/anterior cerebral (23%), posterior communicating (23%), and vertebral/basilar (10%) arteries. An AVM develops as a tangled, interconnected complex of high pressure arteries and low pressure veins without an intervening capillary bed. Frequently weak and prone to bleeding, AVMs are most commonly located in the frontoparietal and temporal regions of the brain, but can be found at other sites in the brain and spinal cord. As many as 60% of patients with an AVM are found to have an aneurysm located within the AVM itself or nearby [178] . SAH d uring p regnancy SAH occurs at a frequency which averages 20 – 30 cases per 100 000 deliveries [7,14] . Maternal mortality is 13 – 35% and fetal mortality is 7 – 25% [179] . Pregnancy does not appear to increase the risk of maternal death from SAH due to aneurysmal bleeding, but it does with AVM probably due to the poor neurologic condition of these patients at presentation [180 – 183] . Presumably related to gestation - induced physiologic and anatomic changes in the mother, the risk of SAH increases as pregnancy progresses such that one - third occur in the second trimester and more than 50% are detected during the third trimester [7,179,177,183 – 185] . The remainder occur in the 1st trimester and postpartum [177] . Interestingly aneurysm rupture during actual labor and delivery is a rare event [180,182,186 – 191,28,32] even though it is estimated that between 20 000 and 40 000 women deliver successfully each year in the United States despite harboring intracranial aneurysms [192] . Protracted and repeated episodes of valsalva - type straining during the second stage of labor would theoreti- Miscellaneous c auses of p regnancy - a ssociated s troke A variety of other CVA etiologies related to the pregnancy itself can be encountered in the pregnant or puerperal patient [5,7 – 9,11] . These include the following: Cardioembolism The heart can be a source for cerebrovascular accident in patients with underlying cardiac disease (prosthetic heart valve, atrial fi brillation, mitral valve prolapse, subacute bacterial endocarditis, myocardial infarction, coronary dissection) or peripartum cardiomyopathy [9,20,22] . Left ventricular thrombus formation in the diseased heart of a patient with peripartum cardiomyopathy can cause embolic stroke in 5 – 10% of patients [160,161,7] . Paradoxical e mbolism The presence of a patient foramen ovale is a risk factor for embolic stroke in the pregnant or puerperal patient [162 – 164] who undergoes either vaginal or cesarean delivery. Choriocarcinoma Choriocarcinoma has been reported to develop in 1 of every 30 molar pregnancies, and frequently metastasize to the brain with thrombosis or aneurysm formation that results in ischemic stroke or intraparenchymal hemorrhage [165 – 168] . Amniotic fl uid e mbolism Acute hemodynamic collapse and consumptive coagulopathy in patients with amniotic fl uid embolism can cause brain insult either directly (hemorrhage, thrombosis), indirectly (cerebral hypoperfusion) or rarely by amniotic fl uid debris passage through a patent foramen ovale to the brain [169] . Air e mbolism When air enters the maternal venous circulation during cesarean (or rarely vaginal) delivery, bubbles can occlude pulmonary cap- illaries and lead to cardiovascular compromise or collapse. In addition to the potential for hypoperfusion of the brain in this clinical setting, air bubbles traveling to brain arteries can also lead to focal stroke - like defi cits [170] . Moyamoya d isease This rare cerebrovascular disease is characterized by bilateral steno - occlusion of the supraclinoid carotid arteries with formation of abnormal fi ne networks of collateral vessels at the base of the brain. Pregnancy, particularly during labor and delivery, places affected patients at increased risk for CVA with intracerebral hemorrhage [171 – 174] . Other s troke c ausation d uring p regnancy Intracerebral h emorrhage Hemorrhagic cerebrovascular accidents are categorized as either subarachnoid (SAH) or intracerebral (ICH). Intracerebral (or Chapter 19 242 cally stress any area of cerebrovascular weakness, but normal cerebral autoregulatory changes may provide compensatory relief in the non - hypertensive, healthy parturient [193,194] that are further augmented by epidural anesthesia when used. Clinical p resentation The signs and symptoms of SAH are neither altered by pregnancy nor specifi c to underlying cause. Intracerebral bleeding (ICH) in patients with hypertensive complications of severe pre - eclampsia (including HELLP syndrome) can present with clinically similar fi ndings. Rupture of an aneurysm sends blood under arterial pressure directly into the cerebrospinal fl uid that produces a rapid increase in intracranial pressure and immediate symptomatology. Although the initial bleed may last only seconds, rebleeding is common and if persistent can lead to deep coma and death. In contrast, bleeding from an AVM is typically less abrupt at onset and can continue over a longer period of time. The dominant symptom with SAH is sudden severe headache with associated immediate cessation of non - focal neurologic activity such as knees buckling, loss of memory and/or loss of focus. The maximal immediate symptoms of SAH at onset differ from ICH which is usually more of an insidious onset and frequently associated with unilateral or focal fi ndings that worsen over time. Up to half of patients with SAH report a severe headache several days before the acute bleeding episode [195] . Other symptoms due to SAH include nausea and vomiting, meningeal signs, ocular hemorrhages, decreased level of consciousness, hypertension, and seizures. These latter two fi ndings can obfuscate the diagnosis of SAH due to aneurysmal or AVM rupture because they may be ascribed to pre - eclampsia/eclampsia. Neurologic s tatus An important prognostic indicator of outcome is the patient ’ s neurologic condition at presentation. A number of scales have been developed to categorize neurologic status in order to guide management and determine prognosis. The Hunt and Hess (1968) scale as shown in Table 19.3 grades the patient ’ s condition based on level of consciousness, presence of meningeal signs, and focal neurologic signs which is subject to signifi cant intra - observer and inter - observer variation [196] . In addition, there is poor correlation between meningeal signs and neurologic outcome in the presence of normal consciousness [197] . To remedy these limitations, a committee of the World Federation of Neurologic Surgeons proposed the more objective WNFS Scale which combines the Glascow Coma Scale with the presence or absence of motor defi cits. Despite its advantages, the WNFS scale has yet to be widely incorporated into practice [197] . Maternal mortality in relation to initial clinical grade of aneurysmal hemorrhage is discussed below in the Prognosis section. Diagnosis Clinical The diagnostic approach to the pregnant patient does not differ from a patient who is not pregnant. The rarity of SAH in pregnancy and its potential for confusion with eclampsia due to the Table 19.3 Systems to assess central nervous system. A. Hunt & Hess Clinical Grading Scale [196] Grade Criteria I Asymptomatic, or minimal headache and slight nuchal rigidity II Moderate to severe headache, nuchal rigidity, no neurologic defi cit other than cranial nerve palsy III Drowsiness, confusion, or mild focal defi cit IV Stupor, moderate to severe hemiparesis, early decerebrate rigidity and vegetative disturbances V Deep coma, decerebrate rigidity, moribund B. Glasgow Coma Scale [268] Behavior Patient Response Component Score Eye opening (E) Spontaneous 4 To speech/loud noise 3 To pain 2 None 1 Best verbal response (V) Oriented 5 Confused, disoriented 4 Inappropriate words 3 Incomprehensible 2 Sounds - none 1 Best motor response (M) Obeys 6 Localizes 5 Flexion/withdraws 4 Abnormal fl exion posturing 3 Extension posturing 2 None 1 Coma score = E+V+M. Patients scoring 3 or 4 have an 85% chance of dying or remaining vegetative; scores above 11 indicate only a 5 – 10% likelihood of death or vegetative state and 85% chance of moderate disability or good recovery. Intermediate scores correlate with proportional chances of recovery. C. World Federation of Neurological Surgeons (WFNS) SAH Scale [269] WFNS Grade Glasgow Coma Scale Motor Defi cit I 15 Absent II 13 – 14 Absent III 13 – 14 Present IV 7 – 12 Present/Absent V 3 – 6 Present/Absent presence of hypertension and seizure can lead to diagnostic delay which worsens the prognosis by increasing the chance for rebleeding and cerebral vasospasm, along with prolonging the interval before neurosurgical evaluation and intervention can occur. Strong clinical suspicion of SAH is crucial. Eclampsia itself is associated with an increased likelihood of intracranial events. Tonic - clonic seizures associated with eclampsia are often fol- Pregnancy-Related Stroke 243 eclampsia/HELLP syndrome or thrombotic thrombocytopenic purpura (TTP)) or a predilection for a hemorrhagic or ischemic event. Initial testing includes a complete blood count, metabolic profi le, erythrocyte sedimentation rate (ESR), peripheral blood smear, lipid and triglyceride profi le, coagulation profi le, urine drug screen, antinuclear antibody (ANA) screen, thrombophilia work - up, and serologic testing for syphilis. A magnesium serum level may be warranted if the patient is receiving magnesium sulfate therapy and toxicity is suspected. Management i ssues Transfer to a tertiary care center or one with neurosurgical and critical care services is a necessity in the presence of a strong suspicion or a defi nitive diagnosis of SAH. Prognosis is directly related to level of consciousness upon arrival and condition before neurosurgical intervention. Prognosis is also inversely proportional to the patient ’ s age and the extent of hemorrhage on initial CT scan. An intensive care setting is crucial for constant hemodynamic monitoring. Immediate neurology/neurosurgical consultation and direction of care is imperative to assess the patient ’ s grade, initiate medical management and decide on timing/technique of surgical therapy. Immediate obstetric evaluation is also important to assess gestational age, fetal viability and maternal - fetal status. Bedrest, stool softeners and analgesia to diminish hemodynamic fl uctuations and lower the risk of rebleeding are appropriate [201] . All anticoagulant and antiplatelet agents are stopped [202] . Reversal of any residual anticoagulant effect may be required using appropriate agents such as vitamin K and fresh frozen plasma. DVT prophylaxis with pneumatic compressing devices should be initiated. Nimodipine The calcium channel blocker nimodipine has been used since the 1980s to vasodilate cerebral blood vessels and theoretically prevent vasospasm in the patient with SAH, although it has not been possible to demonstrate a drug effect on angiographic or symptomatic vasospasm. There is good evidence, however, that nimodipine improves outcomes by decreasing severe neurologic defi cit and death [203 – 205] . Compared to placebo, nimodipine was associated with a 24% risk reduction of poor outcome [206] . Therapy should be initiated within 4 days of SAH at a recommended dose of 60 mg orally (by nasogastric tube or mouth); IV and SQ routes are contraindicated. Despite relative site selectivity for cerebral vessels, peripheral blood pressure fl uctuations are common with nimodipine use which requires continuous monitoring to avoid hypotension that could cause underperfusion of the uteroplacental circulation as well as decreased cerebral perfusion pressure [207,208] . It is a category C medication without evidence of any fetal toxicity in humans. Nimodipine has been used in pregnancy for the treatment of cerebral vasospasm associated with severe pre - eclampsia or eclampsia [209 – 212] . In addition, it was studied in 800 patients with pre - eclampsia to compare its effi cacy against magnesium sulfate for seizure prophylaxis [213] . There was no difference in adverse fetal outcomes between lowed by a prolonged postictal period which can be potentiated by high serum concentrations of magnesium sulfate being administered to prevent seizure recurrence. Following an eclamptic seizure it is important to periodically assess the patient ’ s neurological status in order to avoid magnesium toxicity and to determine that intracranial hemorrhage has neither occurred nor is being masked by the magnesium. Eclampsia without intracranial hemorrhage permits the patient to exhibit normal papillary reac- tivity and response to painful stimuli in the absence of magnesium toxicity. Also, nausea and vomiting, nuchal rigidity, and focal motor weakness are rarely encountered in the eclamptic patient. Imaging A non - contrasted CT scan of the head is typically the fi rst step in radiologic diagnosis of SAH. No pregnant patient with a suspected intracranial bleed should be denied CT scanning regardless of gestational age or fear of potential adverse fetal effects from ionizing radiation scatter. Although shielding of the maternal abdomen and uterus is recommended during any radiographic examination especially during the fi rst trimester, lack of abdomi- nal shielding is not grounds for denial of CT scanning. A shielded CT scan results in 2 mrad of fetal exposure [7,10] . Use of the cerebral CT scanning facilitates prediction, with a high degree of accuracy, of the type of hemorrhage and its site of origin. In addition, cerebral CT can be useful in determining the presence of life - threatening hematomas that require surgical evacuation, as well as the development of hydrocephalus [195] . The ability of cerebral CT scanning to detect blood in the subarachnoid space decreases from up to 95% within 24 hours of acute hemorrhage to 50% 1 week later [198] . If the CT scan is normal and there is high clinical suspicion of SAH, lumbar puncture is performed to examine the cerebrospinal fl uid (CSF) for blood or xanthochro- mia. Non - clearing bloody CSF found at lumbar puncture sup- ports the diagnosis of SAH. Cerebral angiography, including magnetic resonance angiography (MRA), remains the best diagnostic tool for identifying any vascular abnormality. In addition, important anatomic (and therefore prognostic) information is usually obtained with these invasive techniques. However, angiography may fail to visualize the cause of SAH in 20% of patients [199] . In these cases, a repeat angiogram may be necessary to rule out false - negative results secondary to vasospasm or clot fi lling of the aneurysm. Some authors feel that MRI scanning lacks sensitivity to detect acute SAH [195] , but it may be helpful in situations where the initial angiogram fails to identify the lesion. However with technological advances in MRI, newer evidence suggests that it may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms [200] . This technique also can identify vascular lesions in the spinal cord [184] . Laboratory e valuation Several laboratory tests are performed to help identify if a patients has a pregnancy - associated condition (such as pre - eclampsia/ Chapter 19 244 the cardiac electrical system [218] . Electrocardiographic changes in patients with SAH are more likely to be refl ected in subsequent poor neurologic outcome than to poor cardiovascular outcome. Continous cardiac monitoring is necessary to monitor for more severe problems such as myocarditis, acute myocardial infarction, and left ventricular failure. Signifi cant cardiac events are rare and aneurysm repair should not be delayed unless there is severe pulmonary edema from cardiogenic shock [218] . Anesthetic m anagement Both endovascular intervention and extravascular exclusion through craniotomy should be performed under general anesthesia. Vigilant control of systemic and cerebral hemodynamics is important while considering the action of administered drugs that may induce uterine relaxation or fetal depression. Blood p ressure c ontrol Tight operative control is crucial for mother and fetus. Low blood pressures decrease uterine perfusion and place the mother at risk of recurrent cerebral ischemia, while acute hypertension increases the risk of rebleeding and placental abruption. Nicardipine, a dihydropyridine calcium channel blocker, and remifentanil, a synthetic opiod with rapid onset and duration, are two agents that may be particularly advantageous for treating periods of acute hypertension [218] . Avoid f etal d epression Adequate maternal oxygenation and left uterine displacement are important to reduce aortacaval compression and prevent fetal asphyxia. Halothane should be avoided due to its potent ability to relax the uterine musculature. Avoid h yperventilation Second and third trimester pregnancies are states of respiratory alkalosis due to increased minute ventilation and the resultant P a CO 2 is typically 28 – 32 mmHg [219 – 220] . The combination of physiologic alkalosis with hyperventilation, which is commonly induced in neurosurgical procedures, may cause a blunted response of the cerebral vasculature to hypocarbia. Hyper- ventilation may also cause fetal hypoxia and acidosis by increasing uterine arterial vasoconstriction causing uteroplacental insuffi ciency [221] . SAH p rognosis Regardless of pregnancy status, patients in general with CVA due to SAH have a 33% chance to achieve a “ good result ” following treatment [222] . Prognosis can be altered according to numerous factors including type, location and extent of lesion. Hunt and Hess initial clinical grades I and II have a favorable prognosis following aneurysmal rupture with mortality rates less than 20% and 35% respectively. Maternal mortality increases signifi cantly with grade III lesion mortality to over 60% with the highest mortality of > 95% observed in association with patients having grade V lesions [7] . the two treatments. During the initial stages of the trial there was an increased incidence of eclamptic seizures in the nimodipine group when a dose of 30 mg every 4 hours was used. This difference disappeared when the dose was increased to that typically used for the prevention of vasospasm in SAH. Mannitol Hyperosmotic agents such as mannitol (pregnancy category C) are used to treat elevated intracranial pressure associated with intracranial hemorrhage [10] , cerebral venous thrombosis, and other causes of stroke. It is administered as an initial bolus of 1 g/ kg, followed by infusions of 0.25 – 0.5 g/kg every 6 hours. The primary goal of therapy is to achieve plasma hyperosmolality (300 – 310 mosmol/kg) while maintaining an adequate plasma volume. Intracranial p ressure Additional medical measures are instituted in the patient with SAH to maintain adequate cerebral circulation and prevent both ischemia and rebleeding. Elevations in intracranial pressure (ICP) from vascular engorgement and acute hydrocephalus occur following SAH. As ICP increases, cerebral perfusion decreases. Cerebral perfusion pressure (CPP) equals the mean arterial pressure (MAP) minus the ICP [CPP = MAP – ICP] [201] . To coun- teract increases in ICP, MAP must increase to maintain adequate CPP using what is termed “ triple - H ” therapy – hypertension, hypervolemia, and hemodilution. Colloid solutions are preferred for volume expansion. Vasopressors or inotropic agents are used judiciously to elevate the systolic blood pressure into the 150 – 200 mmHg range [214 – 216] . Because sustained systolic blood pressures above this level can worsen SAH via rebleeding, triple - H thereby is withheld until indicated surgical intervention is completed. Labetolol is the preferred agent to lower high blood pressure in this setting. Surgical m anagement The decision to operate upon a pregnant patient with an intracranial hemorrhage is a neurosurgical decision, while the decision to deliver and the type and timing of delivery is based upon obstetric considerations [177,8,9] . Lesion - specifi c neurosurgical management is addressed briefl y in the sections that follow. Preoperative/ o perative a ssessment and g eneral m anagement If the decision is made to proceed with neurosurgical operative intervention and continuation of pregnancy is planned, certain preoperative assessments are important for both mother and fetus. Evaluation and correction of electrolyte imbalances is crucial since metabolic derangements such as cerebral salt - wast- ing syndrome and glucose intolerance are common following SAH. Hypokalemia and hypocalcemia occur in 50 – 75% of patients [217] . Replacement of blood and clotting factors should be performed as needed. Cardiac abnormalities manifested pri- marily as rhythm disturbances are seen in 50 – 80% of patients post aneurysm rupture, due to impaired neurogenic control of Pregnancy-Related Stroke 245 coils, including one patient who went on to have a successful term vaginal delivery [231] . Coil embolization was studied in 1383 patients with complete and partial occlusion of a cerebral aneurysm in 54% and 90% respectively, while 3.7% experienced complications which led to permanent neurologic defi cits [233] . In the International Subarachnoid Hemorrhage Trial, endovascular coiling was associated with a signifi cant relative risk reduction (22.6%, 95% CI 8.9 – 34.2%) and absolute risk reduction (6.9%, 95% CI 2.5 – 11.3%) in dependency and death compared with neurosurgical clipping [234] . We are unaware of any data comparing treatment outcomes between neurosurgical clipping and endovascular approaches in the pregnant patient. Obstetric c onsiderations If gestational age is < 26 weeks at the time of aneurysm rupture, treatment is guided by neurosurgical recommendations that are based on clinical grade and prognosis of the lesion. If gestational age is ≥ 26 weeks, the aneurysm is treated in the context of need for delivery [179,235] . If the patient is not in labor and there is no evidence of fetal compromise, neurosurgical considerations take precedence over obstetric concerns [5] . If aneurysmal rupture has not been treated and there is risk of cerebral infarction, recurrent hemorrhage or hydrocephalus and delivery is imminent, cesarean delivery is recommended. Cesarean delivery is also recommended for delivery of a viable pregnancy in a pregnant patient with poor neurological status (Hunt and Hess grades 4,5], if there is concern for adequacy of prior aneurysm surgery, or if labor begins shortly after aneurysm surgery during the period at risk for symptomatic vasospasm and cerebral infarction [5] . In the patient in advanced labor for whom vaginal delivery is chosen, epidural anesthesia is recommended to shorten the second stage of labor and reduce the time spent “ bearing down. ” If aneurysm rupture occurs during labor, the patient may require cesarean delivery in order to reduce fetal exposure to anesthetics and other treatments followed by defi nitive aneurysm treatment [5] . If the aneurysm is treated and the patient is in good neurological condition, there is no neurosurgical contraindication to vaginal delivery in the future. If an aneurysm ruptures postpartum, the patient is treated as if she were not pregnant [179] . Subarachoid h emorrhage: a rteriovenous m alformations ( AVM s ) General The prevalence of AVMs in the United States is estimated at 1/1000 [236] . Approximately 53% of patients with an AVM will present with a hemorrhage [5] . The crude annual risk of fi rst hemorrhage from an unruptured AVM is approximately 2%, but the risk of recurrent hemorrhage may be as high as 18% the fi rst year, with uncertain risk thereafter [237 – 238] . The long - term crude annual case fatality rate is 1 – 1.5%. In two series, the rate of AVM rupture during pregnancy varied from 3.5% [239] to 9.3% [240] with the greatest risk during the second trimester. The risk may extend into the third trimester and may be exaggerated by the hemodynamic stresses of parturition [241] . Subarachnoid h emorrhage: a neurysm General The natural history of unruptured cerebral aneurysms varies clinically according to the presence or absence of symptoms. Most cerebral aneurysms are asymptomatic (95%) and usually identifi ed incidentally at the time of cerebral angiography (approximately 1% of adults) or autopsy (approximately 1 – 6% of adults) [195] . Asymptomatic cerebral aneurysms rupture at a rate of 1 – 2% per year [223 – 224] . Activities that reportedly precede aneurysm rupture include emotional strain, heavy lifting, coughing, coitus, urination, and defecation. These activities alter cerebral hemodynamics by increasing intracranial pressure. Symptomatic cerebral aneurysms present the greatest risk of rupture with an annual rupture rate of 6% [224] . Once bleeding occurs, mortality risk is high. More than 10% of patients will die before reaching the hospital and 40% of those who reach the hospital will die within the next 30 days. Approximately a third of survivors will sustain signifi cant lasting neurologic morbidity [195] . Signifi cant factors that impact eventual outcome include patient status at initial presentation, if rebleeding occurs, and if secondary vasospasm develops [224] . Patients with a history of autosomal dominant polycystic kidney disease are at increased risk for aneurysms [225 – 226] . Management Early aneurysm repair (within 48 – 72 hours after rupture) is associated with improved long - term survival and less morbidity in patients with Hunt and Hess grades 1 to 3 lesions. Approximately 70 – 90% of pregnant or non - pregnant patients following early repair of grade 1 – 3 lesions have good neurological recovery with low mortality rates between 1.7% and 8% [227] . Early repair permits the initiation of aggressive medical measures (triple - H therapy) and minimizes the potential for rebleeding and vasospasm. Patients with Hunt and Hess grade 4 and 5 lesions have a poor prognosis with (high operative mortality) or without early surgical intervention. Endovascular o cclusion t herapy Either neurosurgical clipping or the endovascular approach using Guglielmi detachable coils can provide defi nitive treatment for ruptured or unruptured aneurysms. The former technique has been shown to reduce maternal mortality from 63% to 11% and fetal mortality from 27% to 5% in non - surgically treated patients although fi gures are not adjusted for maternal clinical grade [177,183] . Temporary neurosurgical clipping may be preferable during pregnancy in order to avoid hypotension and hypother- mia which might cause placental insuffi ciency [228] . Endovascular occlusion therapy has become a promising and safe alternative technique to open clipping in the pregnant patient with reports of good maternal and fetal outcomes [229 – 233] . The procedure involves intravascular delivery of occlusive devices to the aneurysm or AVM. Metal coils are placed within the lesion in order accomplish thrombosis formation and occlusion. Recently two pregnant patients were treated successfully with endovascular Chapter 19 246 events. Importantly, the underlying cause of an ischemic CVA need not be known before consideration for, and initiation of, thrombolytic therapy. Thrombolytic t herapy The rare and unpredictable nature of CVA during pregnancy prevents the undertaking of any controlled trials of the effi cacy of thrombolytic therapy for ischemic stroke. Thus the scientifi c worth of even large numbers of recent case reports and case series related to this issue must be interpreted with caution because it is largely anecdotal. At this time, recombinant tissue plasminogen activator (rt - PA, Alteplase) is the most widely used drug for the treatment of acute ischemic stroke in the non - pregnant patient. It is FDA approved for this indication and the highest success rates are achieved when there is strict adherence to the recommendations promulgated by the National Institute of Neurological Disorders (NINDS) rt - PA Stroke Study Group [244] . The incidence of symptomatic intracranial hemorrhage was 11% when there were deviations of practice in contrast to only 4% in patients who were treated according to the NINDS guidelines [245] . Patients properly treated with rt - PA for acute ischemic stroke were at least 30% more likely to have minimal or absent disability at 3 months as compared to patients who received placebo. Other recognized uses of rt - PA include treatment of massive pulmonary emboli, myocardial infarction and thrombosis of prosthetic heart valves. rt - PA has become the preferred thrombolytic agent over other thrombolytics streptokinase and urokinase. This is due to its high fi brin specifi city, absence of antigenicity, short serum half - life and its demonstrated potential to establish reperfusion [40] . The large molecular weight of the drug prevents transit across the placenta, a desirable characteristic in the pregnant patient. In the non - pregnant patient, the use of rt - PA for thrombolysis of acute ischemic stroke is well established. In a meta - analysis of 15 published, open label studies involving 2639 patients, the primary complication was infrequent intracerebral hemorrhage in 5.2% of cases [246] . In contrast to successful experience with rt - PA, three trials of streptokinase for treatment of ischemic stroke were halted prematurely because of an excess of poor outcomes or deaths among treated patients [247 – 250] . rt - PA u tilization by p rotocol The FDA lists rt - PA as a category C drug; its use is not contraindicated in pregnancy or within the fi rst postpartum week. Patients must meet the established eligibility criteria in order to be considered as viable candidates for the administration of rt - PA ( Table 19.4 ). In the case of ischemic stroke the drug should be administered within 3 hours of symptom onset at a typical dose of 0.9 mg/kg of maternal body weight (maximum, 90 mg). The fi rst 10% of the dose is given as a bolus followed by delivery of the remaining 90% as a constant infusion over a period of 60 minutes [244] . Although rt - PA administration is typically intravenous, some experts advocate the microcatheter - directed intra - arterial route as reported recently during pregnancy with excellent maternal and fetal outcome [251 – 252] . Overall, a net benefi t of Management Management of a ruptured AVM follow similar medical management issues as enumerated previously for SAH in general. Although rebleeding of an AVM occurs in an estimated 27% of pregnant patients following an initial bleed [242] , there is no consensus guideline for the prevention of rebleeding with AVM during pregnancy [9] and the timing and mode of repair remain controversial. Before 1990 it was demonstrated that antepartum resection of AVM is not benefi cial to mother or fetus, with maternal mortality rates of 23 – 32% and fetal mortality rates from 0% to 23% [177] . Subsequently some surgeons advocated operative intervention only to remove clinically signifi cant hematomas [243,177] . At this time, indications for AVM treatment include the patient considered to be at signifi cant risk of hemorrhage, medically refractory seizures, progressive neurologic defi cit, and intractable headaches [5] . As advances in endovascular therapy are made to provide an alternative mode of thereapy, this approach might be used successfully in the pregnant patient. Both open surgical excision and endovascular embolization are options, and most patients will benefi t from multimodal therapy. Neurosurgeons determine the most appropriate treatment strat- egy for a given patient by considering her age, neurologic status, lesion size and location, associated clinical risk factors, and angio- architectural features of the lesion. Despite its success outside pregnancy, radiosurgery is not considered useful during gestation because obliteration of the AVM may require 2 – 3 years. Ischemic s troke o ther t han c erebral v ein t hrombosis General The pregnant patient can suffer ischemic stroke other than in the central venous sinuses around delivery and during the puerperium. Because pregnancy is considered to be a “ hypercoagulable ” state to some degree, the incidence of thromboembolic phenom- enon is heightened. Cerebral infarctions from thromboses can therefore cause CVA theoretically at any time during pregnancy and the puerperium. The presence of a genetic or acquired thrombophilia further predisposes the gravid female to this type of event. The most common of these are antiphospholipid antibody syndrome; protein C, S, and antithrombin III defi ciency; and the Factor V Leiden mutation leading to activated protein C defi ciency. Elevated levels of homocysteine and a mutation in the prothrombin gene have been implicated in an increased risk of thrombosis. Symptomatology Presenting symptoms are non - specifi c and mimic those of pre - eclampsia which can delay diagnosis. As with hemorrhagic events, the most common symptom is headache. Sudden or progressively worsening focal neurological defi cits, visual changes, and seizures are also common. Imaging considerations are similar to those outlined for patients with suspected CVT. Any pregnant patient who suffers an acute thrombotic stroke is a candidate for a thor- ough thrombophilia evaluation. EEG, echocardiography, and/or carotid dopplers can further help to elucidate the cause of embolic Pregnancy-Related Stroke 247 combined intravenous and intra - arterial thrombolysis has been demonstrated in patients with acute ischemic stroke [251,253] . Any physician(s) considering rt - PA administration should be familiar with its use and follow the American Heart Association/ American Stroke Association “ Guidelines for the Early Management of Adults With Ischemic Stroke, ” recently updated at the website http://stroke.ahajournals.org/cgi/reprint/38/5/1655 [254] . Pregnancy u tilization The most recent review of rt - PA thrombolytic therapy in pregnancy included data from 28 patients who were treated for a variety of indications including CVA (n = 10), thrombosis of cardiac valve prosthesis (n = 7), pulmonary embolism (n = 7), deep vein thrombosis (n = 3), and myocardial infarction (n = 1) Table 19.4 Treatment considerations – rt - PA for acute ischemic stroke [270,271] . INCLUSION CRITERIA * Clinical diagnosis of acute ischemic stroke causing a measurable neurologic defi cit * Onset of symptoms within 3 hours of the initiation of treatment * Patient or family understand the potential risks and benefi ts from treatment EXCLUSION CRITERIA Head CT scan * Reveals evidence of hemorrhage * Reveals evidence of a multilobar infarction (hypodensity > 1/3 cerebral hemisphere) Clinical * Neurological signs/symptoms are minor/ isolated/ clearing spontaneously * Neurological signs/symptoms are suggestive of subarachnoid hemorrhage even if the CT is normal * Seizure(s) with postictal residual neurologic impairments * Evidence of active bleeding or acute trauma (fracture) * Persistent blood pressure elevation (systolic ≥ 185 mmHg, diastolic ≥ 110 mmHg) or requiring aggressive antihypertensive therapy History * Any history of a previous intracranial hemorrhage * Myocardial infarction, head trauma, or prior stroke within the previous 3 months * Gastrointestinal or urinary tract hemorrhage in the previous 21 days * Major surgery in the previous 14 days * Arterial puncture at a non - compressible site in the previous 7 days Laboratory * Platelet count < 100 000 mm 3 * Blood glucose concentration < 50 mg/dL (2.7 mmol/L) * INR > 1.7 if taking an oral anticoagulant * Elevated activated partial thromboplastin time (aPTT) if receiving heparin in the previous 48 hours [Adapted from Adams [270] and Caplan [271] ] [40] . Thrombolysis was successful in 25 of the 28 patients and two patients died (7%), but their deaths were not directly related to the application of rt - PA. In one case the underlying disease and in the other case the mechanical manipulation with subsequent vascular lesions were fatal factors. This compares favorably to the case fatality rate of 6.1 – 6.3% in the large randomized rt - PA stroke trials involving non - pregnant patients [255,256] . Six of 25 progeny in the surviving patients were lost (24%), three due to pregnancy termination for maternal indications and one prema- turity - related neonatal loss. Thus in only two cases at most (8%) is there potentially a causal relationship between fetal death and rt - PA utilization [40] . The complication rate for rt - PA thrombolysis in the pregnant gravid is comparable to that observed in large randomized controlled trials involving non - pregnant patients. Intracranial hemorrhage, something not yet reported in rt - PA treated pregnant patients, occurs in 10.8 – 19.8% of non - pregnant patients [255,256] . The rate of spontaneous abortion and stillbirth (8%) after thrombolytic therapy is slightly higher than the general population [257,258] . Permanent sequelae have not been observed in the surviving children and to this date there have been no postmarketing reports of teratogenicity associated with the rt - PA use. There are multiple case reports albeit no controlled studies which nevertheless demonstrate that thrombolysis with rt - PA can be used for the treatment of acute ischemic stroke in the pregnant patient with apparent safety, good maternal - fetal outcome and a relatively low complication rate. Presently there is insuffi cient data of high quality from which to derive guidelines for pregnancy use. At this time however it may not be justifi ed to with- hold rt - PA thrombolytic therapy from the pregnant patient if effective alternatives are lacking [40] . As demonstrated by the recent report of successful use of intra - arterial urokinase to treat a CVA immediately postpartum following cesarean delivery, thrombolytic therapy for ischemic stroke clearly becomes an option after the fetus leaves the uterus [259] . Risk of r ecurrence in s ubsequent p regnancy The risk of recurrent ischemic stroke in a subsequent pregnancy is very low. The French Study Group on Stroke in Pregnancy followed 441 women for 5 years following a pregnancy compli- cated by arterial ischemic stroke (n = 373) or CVT (n = 68) [260] . Approximately 50% of these women received antiplatelet therapy during at least a portion of the subsequent pregnancy. Women with a history of prior CVT received heparin in the postpartum period but no therapy during pregnancy itself. In 187 subsequent pregnancies there were only two recurrent strokes and no cases of recurrent CVT. Eleven CVAs occurred outside of pregnancy. Thus the absolute risk of recurrence outside of pregnancy was 0.5% (95% CI 0.3 – 0.9) and rose to 1.8% (95% CI 0.5 – 7.5) during subsequent pregnancy and the puerperium [260,11] . Similar results were reported for 23 women with a history of stroke who had 35 subsequent pregnancies without CVA recurrence despite only 11 patients receiving any form of anticoagulation during any portion of the subsequent pregnancy [261] . Pregnant patients Chapter 19 248 12 Hender J , Harris DG , Bu H , Richard B , Khanna PB . Stroke in pregnancy . Brit J Hosp Med 2006 ; 67 : 129 – 131 . 13 Cantu C , Baringarrementeria F . Cerebral venous thrombosis associated with pregnancy and the puerperium: review of 67 cases . Stroke 1993 ; 24 : 1880 – 1884 . 14 Grosset DG , Ebrahim S . Stroke in pregnancy and the puerperium: what magnitude of risk? J Neurol Neurosurg Psych 1995 ; 58 : 129 – 131 . 15 Sharshar T , Lamy C , Mas JL . Incidence and causes of strokes associated with pregnancy and puerperium: a study in public hospitals of Ile de France. Stroke in Pregnancy Study Group . Stroke 1995 ; 26 : 930 – 936 . 16 Kittner SJ , Stern BJ , Feeser BR et al. Pregnancy and the risk of stroke . NEJM 1996 ; 335 : 768 – 774 . 17 Lanska DJ , Kryscio RJ . Peripartum stroke and intracranial venous thrombosis in the national Hospital Discharge Hospital Survey . Obstet Gynecol 1997 ; 89 : 413 – 418 . 18 Lanska DJ , Kryscio RJ . Stroke and intracranial venous thrombosis during pregnancy and puerperium . Neurology 1998 ; 51 : 1622 – 1628 . 19 Lanska DJ , Kryscio RJ . Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis . Stroke 2000 ; 31 : 1274 – 1282 . 20 Witlin AG , Mattar F , Sibai BM . Postpartum stroke: a twenty - year experience . Am J Obstet Gynecol 2000 ; 183 : 83 – 88 . 21 Quereshi AI , Giles WH , Croft JB , Stern BJ . Number of pregnancies and risk for stroke and stroke subtypes . Arch Neurol 1997 ; 54 : 203 – 206 . 22 Jaigobin C , Silver FL . Stroke and pregnancy . Stroke 2000 ; 31 : 2948 – 2951 . 23 Dias MS , Sekhar LN . Intracranial hemorrhage from aneurysms and arteriovenous malformations during pregnancy and the puerperium . Neurosurgery 1990 ; 27 : 855 – 866 . 24 Trivedi RA , Kirkpatrick PJ . Arteriovenous malformations of the cerebral circulation that rupture in pregnancy . J Obstet Gynaecol 2003 ; 23 ( 5 ): 484 – 489 . 25 Bateman BT , Schumacher HC , Bushnell CD , Pile - Spellman J , Simpson LL , Sacco RL , Berman MF . Intracerebral hemorrhage in pregnancy . Neurology 2006 ; 67 : 424 – 429 . 26 Skidmore FM , Williams LS , Fradkin KD , Alonso RJ , Biller J . Presentation, etiology, and outcome of stroke in pregnancy and puerperium . J Stroke Cerebrovasc Dis 2001 ; 10 : 1 – 10 . 27 Sadasivan B , Malik GM , Lee C , Ausman JI . Vascular malformations and pregnancy . Surg Neurol 1990 ; 33 : 305 – 313 . 28 Liang CC , Chang SD , Lai SL , Hsieh CC , Chueh HY , Lee TH . Stroke complicating pregnancy and the puerperium . Eur J Neurol 2005 ; 13 : 1256 – 1260 . 29 Awada A , Al Rajeh S , Duarte R , Russell N . Stroke and pregnancy . Internat J Gynecol Obstet 1995 ; 48 : 157 – 161 . 30 Bashiri A , Lazer T , Burstein E , Smolin A , Lazer S , Perry ZH , Mazor M . Maternal and neonatal otucome following cerebrovascular accidents during pregnancy . J Maternal - Fetal Neonatal Med 2007 ; 20 ( 3 ): 241 – 247 . 31 Simolke GA , Cox SM , Cunningham FG . Cerebrovascular accidents complicating pregnancy and the puerperium . Obstet Gynecol 1991 ; 78 : 37 – 42 . 32 Jeng JS , Tang SC , Yip PK . Stroke in women of reproductive age: comparison between stroke related and unrelated to pregnancy . J Neurol Sci 2004 ; 221 : 25 – 29 . with a history of thrombophilia, however, are at some risk of CVA recurrence as shown in one recent patient series of 20 patients with thrombophilia and a 20% recurrence rate of stroke [262] . Thus in the absence of a known thrombophilia, the risk of recurrent stroke in subsequent pregnancy is 0 – 1% and should not be considered a contraindication to repeat pregnancy [260,261] . Prevention of r ecurrent i schemic s troke in a t - r isk p atients There is no consensus on how thromboprophylaxis should be used in the pregnant patient with a prior ischemic stroke and a reason (thrombophilia) to consider risk reduction for potential recurrence [263] . If the patient had a prior arterial ischemic stroke without a high - risk cardiac source of embolism, low - dose aspirin therapy ( < 150 mg/day) is recommended [11] . A number of studies have demonstrated that low - dose aspirin is safe for both mother and fetus in the second and third trimester [263 – 265] . Use in the fi rst trimester should only be undertaken after weighing the risks and benefi ts with the patient. Consideration should be given to continuing low - dose aspirin during the postpartum period. Although the effi cacy of this in postpartum stroke prevention has not been studied, the use of low - dose aspirin has been found to be safe during the postpartum/breastfeeding period [266,267] . The effi cacy of other antiplatelet agents such as ticlopidine, clopidigrel, and dypiridimole for recurrent stroke prevention has not been established. References 1 Donaldson JO , Lee NS . Arterial and venous stroke associated with pregnancy . Neurol Clin 1994 ; 12 ( 3 ): 583 – 599 . 2 Witlin AG , Friedman SA , Egerman RS , Frangieh AY , Sibai BM . Cerebrovascular disorders complicating pregnancy – beyond eclampsia . Am J Obstet Gynecol 1997 ; 176 : 139 – 148 . 3 James AH , Bushnell CD , Jamison MG , Myers ER . Incidence and risk factors for stroke in pregnancy and the puerperium . Obstet Gynecol 2005 ; 106 : 509 – 516 . 4 Kittner SJ , Stern BJ , Wozniak M et al. Cerebral infarction in young adults: the Baltimore - Washington Cooperative Young Stroke Study . Neurology 1998 ; 50 : 890 – 894 . 5 Sloan MA , Stern BJ . Cerebrovascular disease in pregnancy . Curr Treatment Options Neurol 2003 ; 5 : 391 – 407 . 6 Pettiti DB , Sidney S , Quesenberry CP , Bernstein A . Incidence of stroke and myocardial infarction in women of reproductive age . Stroke 1997 ; 28 : 280 – 283 . 7 Mas JL , Lamy C . Stroke in pregnancy and the puerperium . J Neurol 1998 ; 245 : 305 – 313 . 8 Pathan M , Kittner SJ . Pregnancy and stroke . Curr Neurol Neuroscience Rep 2003 ; 3 : 27 – 31 . 9 Turan TN , Stern BJ . Stroke in pregnancy . Neurol Clin 2004 ; 22 : 821 – 840 . 10 Sibai BM , Coppage KH . Diagnosis and management of women with stroke during pregnancy/postpartum . Clin Perinatol 2004 ; 31 : 853 – 868 . 11 Helms AK , Kittner SJ . Pregnancy and stroke . CNS Spectrums 2005 ; 10 : 580 – 587 . . [147,19] . Postpartum c erebral v asculopathy General Another potential masquerader or mimic of postpartum eclampsia is postpartum cerebral vasculopathy, a type of postpartum angiopathy. toxicity is suspected. Management i ssues Transfer to a tertiary care center or one with neurosurgical and critical care services is a necessity in the presence of a strong suspicion or. . Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis . Stroke 2000 ; 31 : 1274 – 1282 . 20 Witlin AG , Mattar F , Sibai BM . Postpartum stroke: a twenty