Case Presentation

A 30-year-old White European woman at six weeks of gestation presented with headache and abrupt onset of focal neurological symptoms. She had undergone in vitro fertilization and was receiving vaginal progesterone and oral estradiol therapy. Examination revealed forced deviation of the eyes and head to the left, severe right hemiparesis, hyperreflexia, and an extensor plantar response on the right. Computed tomography suggested a left hemispheric venous infarction, and treatment with low-molecular-weight heparin and anti-edema measures was initiated. Initially, her neurological deficits improved. However, three days later she developed a new syndrome characterized by left-right disorientation, autotopagnosia, and left-sided hyperreflexia. MRI subsequently demonstrated a left parietal arteriovenous malformation, superior sagittal sinus thrombosis, and bilateral hemorrhagic venous infarctions. Ten days after the onset of symptoms she developed focal motor status epilepticus consisting of repetitive clonic movements involving the right face and arm while consciousness remained preserved. Genetic testing later revealed multiple thrombophilic abnormalities, and after medical termination of pregnancy she underwent further management with anticoagulation, antiseizure medications, and ultimately stereotactic radiosurgery.

Clinical Reasoning

At first glance, this presentation might be mistaken for an arterial ischemic stroke involving the left hemisphere because of the sudden onset of right hemiparesis and gaze deviation. However, the subsequent development of new neurological deficits localizing to the opposite hemisphere should immediately raise suspicion that a process more diffuse or multifocal is occurring. Sequential involvement of both hemispheres is unusual for a single arterial infarction and suggests alternative possibilities such as cerebral venous sinus thrombosis, vasculitis, embolic disease, or multiple infarctions.

The presence of headache is an important clue. Headache accompanies approximately 80–90% of patients with cerebral venous sinus thrombosis and often precedes focal deficits. Pregnancy itself is a hypercoagulable state, and the patient's use of exogenous estradiol following in vitro fertilization further increased thrombotic risk. These features, combined with multifocal hemorrhagic lesions and subsequent seizures, strongly point toward cerebral venous sinus thrombosis rather than arterial ischemic stroke.

MRI confirmed thrombosis of the superior sagittal sinus together with bilateral hemorrhagic venous infarctions and incidentally identified a left parietal arteriovenous malformation. The combination of venous hypertension, impaired drainage, and the underlying AVM likely contributed to hemorrhagic transformation and increased cortical irritability. The subsequent development of focal status epilepticus is therefore understandable in retrospect.

Further evaluation demonstrated several inherited thrombophilic abnormalities affecting fibrinolysis and platelet aggregation. Thus, the patient represented a "perfect storm" in which pregnancy, hormonal therapy, inherited thrombophilia, cerebral venous thrombosis, and an underlying AVM interacted to produce multifocal cerebrovascular injury and recurrent seizures.

Diagnostic Discussion

One of the most important teaching points from this case is that hemorrhagic venous infarction should not deter anticoagulation. Unlike arterial hemorrhagic transformation, hemorrhage associated with cerebral venous thrombosis reflects venous congestion and elevated venous pressure. Multiple studies have demonstrated that anticoagulation improves outcomes even when hemorrhagic infarction is present. Thus, anticoagulation remains the standard of care.

Another important lesson concerns the relationship between cerebral AVMs and epilepsy. Approximately 20–40% of patients with AVMs present with seizures. Several mechanisms have been proposed, including hemorrhage, gliosis, hemosiderin deposition, chronic ischemia, and cortical irritation. In this patient, the location of epileptiform activity on EEG correlated with the location of the AVM, and seizure control improved after stereotactic radiosurgery reduced the size of the lesion.

Finally, counseling regarding future pregnancy illustrates the complexity of modern neurological practice. No universally correct answer exists. The risks of recurrent thrombosis, hemorrhage, seizure exacerbation, and pregnancy complications must be balanced against the patient's wishes. Such decisions require multidisciplinary collaboration involving neurology, maternal-fetal medicine, neuroradiology, and psychology.

Multiple Choice Questions

Question 1

A pregnant woman presents with headache, seizures, and multifocal hemorrhagic lesions involving both cerebral hemispheres. Which diagnosis should be strongly considered?

A. Posterior reversible encephalopathy syndrome

B. Multiple sclerosis

C. Cerebral venous sinus thrombosis

D. Migraine with aura

E. Moyamoya disease

Answer

C. Cerebral venous sinus thrombosis

Explanation

Cerebral venous sinus thrombosis should be suspected whenever headache, focal deficits, seizures, and hemorrhagic lesions occur in a pregnant woman. Venous infarcts often involve multiple vascular territories and may appear hemorrhagic because venous obstruction leads to increased capillary pressure and extravasation of blood. In this patient, pregnancy, estrogen exposure, and inherited thrombophilia all predisposed to venous thrombosis. Posterior reversible encephalopathy syndrome may produce seizures and headache but usually affects the posterior white matter and is often associated with severe hypertension or preeclampsia. Multiple sclerosis rarely causes hemorrhagic lesions or acute seizures. Migraine with aura does not explain bilateral hemorrhagic infarctions, and moyamoya disease characteristically produces ischemic events and collateral vessel formation rather than superior sagittal sinus thrombosis.

Question 2

Which of the following factors most likely contributed to this patient's hypercoagulable state?

A. Hyperthyroidism

B. Estrogen therapy following IVF

C. Vitamin B12 deficiency

D. Parkinson disease

E. Migraine

Answer

B. Estrogen therapy following IVF

Explanation

Estrogen promotes thrombosis by increasing levels of clotting factors and reducing natural anticoagulant activity. Pregnancy itself is already associated with a hypercoagulable state, and exogenous estrogen used after in vitro fertilization further magnifies this risk. In this patient, estrogen exposure acted synergistically with inherited thrombophilia and pregnancy-related physiological changes. None of the other listed conditions are major causes of cerebral venous thrombosis.

Question 3

Which statement regarding hemorrhagic venous infarction is correct?

A. Anticoagulation is contraindicated

B. Hemorrhage mandates neurosurgical evacuation

C. Hemorrhage excludes the diagnosis of CVST

D. Anticoagulation remains standard treatment despite hemorrhage

E. Corticosteroids alone are sufficient treatment

Answer

D. Anticoagulation remains standard treatment despite hemorrhage

Explanation

This principle is one of the most important clinical lessons regarding cerebral venous sinus thrombosis. The hemorrhage seen in venous infarction results from venous congestion rather than from primary vessel rupture. Therefore, the underlying problem remains thrombosis, and anticoagulation is necessary to prevent clot propagation and restore venous drainage. Neurosurgical intervention is reserved for selected cases with mass effect or impending herniation. Corticosteroids are not routinely indicated and do not address the underlying thrombotic process.

Question 4

After intracranial hemorrhage, what is the second most common presentation of cerebral arteriovenous malformations?

A. Dementia

B. Parkinsonism

C. Epileptic seizures

D. Peripheral neuropathy

E. Myopathy

Answer

C. Epileptic seizures

Explanation

Approximately 20–40% of patients with cerebral AVMs present with epilepsy. Hemorrhage remains the most common presentation, but seizures represent the second most frequent manifestation. The mechanisms underlying epileptogenesis include hemosiderin deposition, gliosis, cortical irritation, edema, and local ischemia. Dementia, parkinsonism, peripheral neuropathy, and myopathy are not characteristic manifestations of cerebral AVMs.

Question 5

Which antiseizure medication among the following has one of the most favorable safety profiles during pregnancy?

A. Valproic acid

B. Topiramate

C. Phenobarbital

D. Levetiracetam

E. Primidone

Answer

D. Levetiracetam

Explanation

Levetiracetam has become one of the preferred antiseizure medications for women of childbearing age because observational studies and pregnancy registries have demonstrated relatively low rates of major congenital malformations. In contrast, valproic acid carries substantial risks of neural tube defects and adverse neurodevelopmental outcomes. Topiramate is associated with oral clefts, and phenobarbital has been linked to congenital malformations and cognitive effects. Consequently, current practice favors agents such as levetiracetam and lamotrigine whenever clinically appropriate. In this case, levetiracetam successfully controlled status epilepticus initially and remained the foundation of long-term treatment.

Clinical Pearls

This case demonstrates how multiple risk factors may interact synergistically rather than independently. Headache and seizures in pregnancy should always raise suspicion for cerebral venous sinus thrombosis. Multifocal neurological deficits involving opposite hemispheres are unusual for a single arterial stroke and should prompt consideration of venous disease. Hemorrhagic venous infarction is not a contraindication to anticoagulation. Finally, the management of women with epilepsy, cerebrovascular disease, and a desire for future pregnancy requires individualized, multidisciplinary decision making.

Clinical Take-Home Message

This remarkable case illustrates how pregnancy, exogenous estrogen therapy, inherited thrombophilia, cerebral venous sinus thrombosis, hemorrhagic venous infarction, and an underlying cerebral arteriovenous malformation can interact to produce multifocal stroke syndromes and recurrent focal status epilepticus. Successful treatment required anticoagulation, antiseizure therapy, radiosurgery, and careful multidisciplinary counseling, emphasizing that complex neurological disorders in pregnancy demand individualized rather than protocol-driven management.

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