Affected patients develop severe gen-eralized or occipital headaches with abrupt onset, altered mental status, generalized motor seizures, neurologic defi cits and often some degree of v
Trang 1[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 thrombo-sis of a cortical vein [129] A prothrombotic risk factor (genetic
or acquired such as pregnancy/puerperium) or a direct mechani-cal 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 some-times 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
syn-drome, 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
syn-drome 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
gluco-corticoids 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
clini-cal 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
Trang 2tion (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% sur-vival and few persistent neurologic defi cits [147,19]
Postpartum c erebral v asculopathy General
Another potential masquerader or mimic of postpartum eclamp-sia 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 gen-eralized 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 consid-ered in a patient with what is thought to represent delayed post-partum 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 hyperin-tense 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 vascu-litis 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 vasculopa-thy 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] ,
anticoagu-lation with intravenous heparin is usually recommended to
arrest the thrombotic process and to prevent pulmonary
embo-lism [141] despite the potential risk that a venous infarct might
become hemorrhagic However, in three small randomized
clini-cal 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
molecu-lar 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
subse-quent 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
thrombo-lytic 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
rela-tively 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
Trang 3gesta-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, bleed-ing diatheses, trauma, tumors, and small vessel vasculitides are other known causes of ICH [175,176] Diagnosis and manage-ment of ICH is similar to that of SAH (see discussion to follow)
Subarachnoid h emorrhage General
Subarachnoid hemorrhage (SAH) is bleeding into the subarach-noid space (anatomically the area between the arachsubarach-noid 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 arterio-venous 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 com-municating (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 mortal-ity 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 esti-mated 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
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
car-diomyopathy [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
forma-tion 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
intracere-bral 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
Trang 4cally 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
symptom-atology Although the initial bleed may last only seconds,
rebleed-ing 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
hemor-rhages, 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
hem-orrhage 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
preg-nancy 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
Best verbal response (V) Oriented 5
Confused, disoriented 4 Inappropriate words 3 Incomprehensible 2 Sounds - none 1 Best motor response (M) Obeys 6
Flexion/withdraws 4 Abnormal fl exion posturing 3 Extension posturing 2
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
presence of hypertension and seizure can lead to diagnostic delay which worsens the prognosis by increasing the chance for rebleed-ing and cerebral vasospasm, along with prolongrebleed-ing 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
Trang 5fol-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 pro-portional 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 evalu-ation is also important to assess gestevalu-ational 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 antiplate-let agents are stopped [202] Reversal of any residual anticoagu-lant 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 recom-mended 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 moni-toring to avoid hypotension that could cause underperfusion of the uteroplacental circulation as well as decreased cerebral perfu-sion 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 associ-ated with severe pre - eclampsia or eclampsia [209 – 212] In addi-tion, 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
admin-istered to prevent seizure recurrence Following an eclamptic
seizure it is important to periodically assess the patient ’ s
neuro-logical status in order to avoid magnesium toxicity and to
deter-mine 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
magne-sium 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
sus-pected intracranial bleed should be denied CT scanning
regard-less 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
addi-tion, 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
diag-nostic tool for identifying any vascular abnormality In addition,
important anatomic (and therefore prognostic) information is
usually obtained with these invasive techniques However,
angi-ography 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
symp-toms [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/
Trang 6the 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 anesthe-sia 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 increas-ing uterine arterial vasoconstriction causincreas-ing 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
differ-ence 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
pres-sure (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
intra-cranial 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 followwast-ing
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
Trang 7coils, 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 aneu-rysm in 54% and 90% respectively, while 3.7% experienced com-plications 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 com-paring 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 infarc-tion, 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 preg-nant 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 neuro-logical condition, there is no neurosurgical contraindication to vaginal delivery in the future If an aneurysm ruptures postpar-tum, 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
asso-ciated 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
vaso-spasm 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
aneu-rysm 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
Trang 8events 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 recom-mendations promulgated by the National Institute of Neurological Disorders (NINDS) rt - PA Stroke Study Group [244] The inci-dence 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 contrain-dicated in pregnancy or within the fi rst postpartum week Patients must meet the established eligibility criteria in order to be con-sidered 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
manage-ment 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
mater-nal 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
puerpe-rium 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
anti-body 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
Trang 9combined 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
preg-nancy 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 throm-bolysis 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 preg-nancy 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
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13 Cantu C , Baringarrementeria F Cerebral venous thrombosis
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14 Grosset DG , Ebrahim S Stroke in pregnancy and the puerperium: what magnitude of risk? J Neurol Neurosurg Psych 1995 ; 58 :
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15 Sharshar T , Lamy C , Mas JL Incidence and causes of strokes associ-ated with pregnancy and puerperium: a study in public hospitals of
Ile de France Stroke in Pregnancy Study Group Stroke 1995 ; 26 :
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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
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20 Witlin AG , Mattar F , Sibai BM Postpartum stroke: a twenty - year
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21 Quereshi AI , Giles WH , Croft JB , Stern BJ Number of pregnancies and risk for stroke and stroke subtypes Arch Neurol 1997 ; 54 :
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22 Jaigobin C , Silver FL Stroke and pregnancy Stroke 2000 ; 31 :
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23 Dias MS , Sekhar LN Intracranial hemorrhage from aneurysms and arteriovenous malformations during pregnancy and the
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24 Trivedi RA , Kirkpatrick PJ Arteriovenous malformations of the
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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
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28 Liang CC , Chang SD , Lai SL , Hsieh CC , Chueh HY , Lee TH Stroke
complicating pregnancy and the puerperium Eur J Neurol 2005 ; 13 :
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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
acci-dents during pregnancy J Maternal - Fetal Neonatal Med 2007 ; 20 ( 3 ):
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31 Simolke GA , Cox SM , Cunningham FG Cerebrovascular accidents
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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
recur-rent 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
post-partum period Although the effi cacy of this in postpost-partum 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
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