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Keywords:

  • Epilepsy;
  • Pregnancy;
  • Cavernous angioma;
  • Status epilepticus;
  • Therapeutic abortion

Summary

  1. Top of page
  2. Case Report
  3. Discussion
  4. References

First-time seizure and status epilepticus during pregnancy have been previously reported as the initial manifestation of intracranial cavernous hemangioma. We report a woman with no history of seizures who presented with refractory status epilepticus at 10 weeks gestation. Cranial MRI revealed a right frontal cavernous hemangioma. The seizures remained refractory to conventional anticonvulsant medications and 48 h of general anesthetic. Termination of the pregnancy resulted in almost immediate resolution of the seizures. The dramatic response of the seizures to termination of the pregnancy suggests that hormonal factors were primarily responsible for the precipitous presentation in this patient.


Case Report

  1. Top of page
  2. Case Report
  3. Discussion
  4. References

A 34-year-old right-handed woman with no history of seizures presented to emergency room after being found lying on the floor confused and incoherent. In the emergency room, she was observed to have fluctuating levels of consciousness characterized by episodic confusion and unresponsiveness lasting up to 30 s with rapid recovery. She subsequently developed recurrent twitching of the legs, especially on the left side, with repetitive posturing of the trunk. The semiology of her seizures evolved into stereotypic eyelid fluttering for a few seconds followed by forced head deviation to the left with occasional versive eye deviation to the right. Generalized tonic–clonic convulsions were not observed.

Two weeks prior to presentation, the patient was admitted to psychiatry for a new-onset of delusions and auditory hallucinations. Despite a long-standing history of depression and eating disorder, she had never experienced any psychotic symptom. During this admission, the patient also was found to be pregnant. She was treated with risperdal and trazodone with resolution of the hallucinations and was discharged home. Detailed examination of the patient did not reveal any systemic process or stigmata of connective tissue disorder. Serological markers for systemic lupus erythematosus and other major connective tissue disorders, including antinuclear antibodies, anti double-stranded DNA antibodies, and antineurophil cytoplasmic antibodies were also negative.

She had a total of seven seizures within the first 12 h of her admission with each episode lasting approximately 1 min followed by a short period of postictal confusion and fatigue. An EEG demonstrated recurrent rhythmic bifrontal theta discharges, which evolved over 30–60 s (electrographic seizures) in association with these clinical events. The cranial MRI showed typical features of cavernous angioma in the right frontal lobe (Fig. 1). Marked blooming artifact of the lesion was observed on T2* sequence with no evidence of multiple cavernous angiomas (CAs) or another satellite lesion. A major venous thrombosis was not demonstrated on MR-Venogram sequences. A fetal ultrasound was performed and demonstrated a viable conceptus at the 10th week of gestation.

image

Figure 1. An Axial T2-weighted sequence demonstrating the mulberry appearance of the right mesial frontal cavernous malformation.

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She was initially loaded with intravenous phenytoin at 19 mg/kg (total dose of 1,200 mg followed by 100 mg every 8 h) and three doses of intravenous lorazepam at 2 mg. This combination resulted in transient seizure control over the next 12 h during which she experienced three brief self-limited seizures. Seizure frequency then increased to one complex partial seizure every 1–2 h after which clobazam at 10 mg twice daily was added to phenytoin without any additional benefit. Seizure frequency then escalated to one every 5–10 min without recovery of consciousness between episodes. The patient was subsequently transferred to the neurointensive care unit (NICU) where carbamazepine was introduced with gradual escalation of the dose up to 600 mg every 8 h. In addition, general anesthesia was induced using propofol infusion at a rate of 100 mg/h.

Eight hours later, the propofol infusion was held. Seizures returned every 10–15 min and general anesthesia was resumed for an additional 24 h. Following a second attempt to wean the propofol recurrent complex partial seizure were observed every 30 min. Following the failure of obtaining seizure control with general anesthetic, termination of the pregnancy was performed with the consent of the patient and her family. The anesthetic was subsequently discontinued with four brief complex partial seizures being observed in the 24 h after the termination of the pregnancy and no further seizures in the following 7 days.

Discussion

  1. Top of page
  2. Case Report
  3. Discussion
  4. References

Status epilepticus during pregnancy has been reported in association with systemic lupus erythematosus, porphyria, pyridoxine-responsive seizures, and CAs (Eros et al., 1998; Engelhardt et al., 2004; Shulze-Bonhage et al., 2004). The presence of a structural lesion with close anatomical correlation to the recorded electrographic seizures in association with a negative rheumatologic work-up and the absence of a history of seizures during infancy (pyridoxine-responsive seizures) was strongly suggestive that the CA was the underlying etiology for this patient's refractory seizures.

CAs are abnormally dilated sinusoids of a single flattened endothelium surrounded by a ring of hemosiderin. The lack of tight junctions results in defective blood–brain barrier with recurrent leakage of red blood cells. Cavernous malformations are devoid of functioning neural parenchyma and are not intrinsically epileptogenic. Nevertheless, seizures are the initial presentation in 62% of supratentorial lesions due to the gliotic reactions of adjacent tissues to hemosiderin (Awad & Jabbour, 2006). CAs can manifest at any age or stage, but first-time presentation as seizures or stereotypic recurrent seizures appearing only during pregnancy have been documented in a few case reports (Awada et al., 1997). Several explanations for seizure exacerbations or new-onset seizures due to CAs in pregnancy have been suggested.

Despite the equal sex distribution of CA, the incidence of lesional hemorrhage is higher in women due to the hormonal influences. The physiological state of pregnancy aggravates the biological behavior of CA by enhancing growth, recurrent bleed, and de novo appearance of new lesions (Pozzati et al., 1996). The hyperdynamic circulation during pregnancy with increased extracellular fluid volume and cardiac output enhance the turbulent flow within these thin-walled sinusoids. The surge of βhCG, progesterones, and estrogens is associated with endometrial vascular proliferation, particularly during the first trimester. CAs do not escape these effects and neoangiogenesis of fragile vasculatures imposes the risk of hemorrhage. The pregnancy also predisposes for venous thrombosis, which may, within these low flow lesions, result in secondary hemorrhages and subsequent gliosis.

The proconvulsant properties of estrogen provide another potential explanation for enhanced epileptogenicity of CAs during pregnancy. Cyclic peaking of estrogen-to-progesterone ratios during preovulatory and premenstrual stages correlates with catamenial seizure patterns in nongravid states (Reddy, 2004). The proconvulsant properties of estrogen have been well established (Buterbaugh & Hudson, 1991; Cononaco et al., 1992; Murphy et al., 1998; Woolley, 2000). Alternatively, the progesterones raise the seizure threshold, suppress kindling, decrease induced-penicillin interictal spikes, and potentiate gamma-aminobutyric acid (GABA)-activated chloride currents (Reddy, 2004). In pregnancy, estrogens rise steadily to 1,000–10,000 times the baseline levels, and progesterones increase throughout pregnancy peaking at the 38th week of gestation. Seizure vulnerability during pregnancy has been related to the rising levels of estrogens and pregnancies with increased seizure frequency have significantly higher estrogen and lower progesterone levels (Bag et al., 1989).

In first-trimester-induced abortions, estrogen levels decline by 88% within 24 h (Murashko, 1978). Other potential pregnancy-induced changes such as vascular neoangiogenesis or acute lesional hemorrhage would not be expected to resolve over such a brief time period. While it is impossible to determine what factors precipitated the onset of seizures in this patient's case, the almost immediate cessation of seizures following termination of the pregnancy strongly suggests that pregnancy-induced hormonal changes were likely responsible for the patient's presentation with refractory status epilepticus.

Conflict of interest: We have no conflict of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

References

  1. Top of page
  2. Case Report
  3. Discussion
  4. References