Neurol Med Chir (Tokyo) 41, 144¿148, 2001 Late Occurrence of Diffuse Cerebral Swelling After Intracerebral Hemorrhage in a Patient With the HELLP Syndrome —Case Report— Kimiaki HASHIGUCHI, Takanori INAMURA, Kazuo IRITA*, Michie ABE*, Eiichiro NODA*, Shigeaki YANAI**, Shosuke TAKAHASHI*, and Masashi FUKUI Departments of Neurosurgery, *Anesthesiology and Critical Care Medicine, and **Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka Abstract Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome can occur at any time in the course of pregnancy and is associated with many complications including fatal stroke. A 37-yearold female presented with HELLP syndrome causing an intracerebral hematoma, which was treated by evacuation and mild hypothermia. Unexpected diffuse cerebral swelling occurred on the 15th day of the initially favorable postoperative course. Considerable impairment of consciousness persisted despite conservative therapy. Serial computed tomographic findings indicated delayed cerebral vasospasm as the cause of the swelling. Particularly careful management is required even beyond the first 2 weeks for patients with stroke as a complication of HELLP syndrome. Key words: cerebral swelling, HELLP syndrome, hypothermia, Introduction curred on the 5th day of the 37th week. She was admitted to our hospital. The diagnosis was preeclampsia based on the findings of hypertension (160/ 100 mmHg) and proteinuria without edema. Cesarean section was performed since fetal distress was evident and sonography disclosed placental abruption of approximately 20%. The newborn child was healthy, but the patient's consciousness was impaired (Glasgow Coma Scale [GCS]: eyes [E] 3, verbal [V] 4, motor [M] 6). Computed tomography (CT) revealed intracerebral hemorrhage in the right frontal lobe (Fig. 1). Two hours later the patient lapsed into a coma (GCS: E1, V1, M4), and CT depicted enlargement and intraventricular extension of the hematoma (Fig. 2). CT after administration of contrast medium demonstrated two small enhanced profiles in the hematoma suggestive of abnormal vessels. Laboratory findings included elevated liver enzyme activities in the serum (aspartate aminotransferase 747 U/l, alanine aminotransferase 472 U/l, and lactate dehydrogenase 2987 U/l), a low platelet count (96000/ml), and burr cells in the peripheral blood smear. DIC was excluded by normal plasma concentrations of fibrinogen and fibrin degradation products, as well as normal prothrombin time. The Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a complication of pregnancy that sometimes occurs in combination with preeclampsia or eclampsia.1,21) HELLP syndrome manifests as various clinical features such as malaise, jaundice, upper abdominal pain, nausea, vomiting, renal failure, disseminated intravascular coagulation (DIC), pulmonary edema, abruptio placentae, and even rupture of the liver.2,7,10,14,17,21) Stroke involving cerebral vasospasm frequently complicates HELLP syndrome and severe eclampsia.3,6,8,12,19) We report a patient with intracerebral hemorrhage associated with HELLP syndrome in whom hematoma evacuation was unexpectedly followed by late diffuse cerebral swelling. Case Report A 37-year-old primigravida had an apparently normal course of pregnancy until amniorrhexis ocReceived 11, 2000 September 26, 2000; Accepted intracerebral hemorrhage December 144 Cerebral Hemorrhage and Late Swelling in HELLP Syndrome Fig. 1 Fig. 2 Computed tomography scan performed immediately after cesarean section showing intracerebral hemorrhage in the right frontal lobe. Computed tomography scans showing the hematoma in the right frontal lobe has enlarged and extended intraventricularly, and two structures were enhanced after administration of contrast medium. diagnosis was HELLP syndrome.2,10) Corticosteroid was immediately administered and the hematoma was evacuated with partial frontal lobectomy. The platelet count fell below 50000/ml, requiring intraoperative platelet transfusion. Abnormal vessels within the hematoma were identified and resected. Histological examination of these vessels suggested vascular malformation, but no definitive diagnosis could be made. Hemosiderin in the specimen indicated prior occurrence of hemorrhage. C) was induced after surMild hypothermia (349 gery because of her impaired consciousness (GCS: E3, V2, M4) and CT evidence of cerebral edema as- Neurol Med Chir (Tokyo) 41, March, 2001 Fig. 3 145 Computed tomography scan performed 4 days after the start of hypothermia demonstrating cerebral swelling with midline shift, and new intracerebral hemorrhage in the right occipital lobe. sociated with increased intracranial pressure (over 200 mmH2O). The increased liver enzyme activities and low platelet count gradually resolved over 7 days, although further platelet transfusion was required. Mild hypothermia was maintained for 5 days and body temperature was gradually increased to 379C over 4 days. CT performed 4 days after the start of hypothermia revealed small intracerebral hemorrhage in the right occipital lobe (Fig. 3), but the patient's consciousness cleared almost completely (GCS: E4, V4, M6) 12 days after the start of hypothermia, and no focal neurological deficits were present. On the 15th day after the initial hemorrhage, the patient's blood pressure suddenly rose to 220/110 mmHg and a convulsive seizure followed. She entered a deep coma and developed dilated pupils. Spontaneous respiration was preserved. CT showed diffuse cerebral swelling (Fig. 4 upper row). Laboratory examinations were unremarkable except for increased number of platelets (over 800000/ml). Conservative therapy with corticosteroid and infusion of hyperosmotic fluid resolved the diffuse cerebral swelling by the next day (Fig. 4 lower row), but the impairment of consciousness was permanent (GCS: E4, V3, M5). Discussion HELLP syndrome can occur, sometimes fatally, at any time during pregnancy or even in the postpartum period. Stroke is the most common K. Hashiguchi et al. 146 Fig. 4 Computed tomography scans performed immediately following the convulsive seizure that occurred 15 days after the first hemorrhage revealing massive cerebral swelling (upper row) that was no longer apparent the next day (lower row). cause of death in patients with the HELLP syndrome.3,5–7,10,14,17,21) The mechanisms underlying the HELLP syndrome are poorly understood, but arterial spasms induced by abnormal release of vasoactive agents are thought to be involved.4,17) However, nontraumatic intracerebral hemorrhage in a young patient is usually associated with vascular anomalies such as arteriovenous malformation or venous malformation, or with neoplasm or embolism. Multiple factors were thought to be involved in the present case. The major cause of the intracerebral hemorrhage was probably the group of abnormal vessels in the right frontal lobe clearly demonstrated by CT. Furthermore, the hypertension associated with preeclampsia and the bleeding tendency associated with the HELLP syndrome both promoted rupture of these abnormal vessels and resulted in enlargement of the intracerebral hematoma. Hypertension was not medically controllable, and further intracerebral hemorrhage occurred in the right occipital lobe during the hypothermia treatment after operation. Termination of pregnancy, usually by cesarean delivery, results in gradual resolution of the symptoms in most patients with HELLP syndrome.2,7,17) Some patients with HELLP syndrome associated with DIC require multiple transfusions,2,17) and corticosteroid therapy is recommended to reverse thrombocytopenia resulting from the HELLP syndrome.11,18,20,25) Our patient received corticosteroid for treating the acute cerebral edema, elevated liver enzyme levels, and thrombocytopenia, all of which resolved 7 days after the cesarean section. Hypothermia was induced to treat the increase in intracranial pressure to over 200 mmH2O after the evacuation of the intracerebral hematoma.16) Hypothermia sometimes inhibits the activities of enzymes concerned with platelet aggregation and coagulation, and therefore can cause hemorrhage in patients with tendency to bleeding.9,22,23) The intracerebral hemorrhage appearing in the occipital lobe during the hypothermia may have resulted from such inhibition. Neurol Med Chir (Tokyo) 41, March, 2001 Cerebral Hemorrhage and Late Swelling in HELLP Syndrome Our patient suffered a sudden and unexpected rise in blood pressure followed by convulsive seizure and coma 15 days after the first hemorrhage. Diffuse cerebral swelling was apparent on CT but resolved within 1 day. We suspect that cerebral vasospasm had occurred, but no angiographical evidence was obtained. HELLP syndrome and preeclampsia are frequently associated with cerebral vasospasm, and the severe subarachnoid hemorrhage occurring with the intracerebral hemorrhage at onset could also have induced diffuse cerebral vasospasm.6,8,12,15,19,24) Alternatively, cerebral venous or venous sinus thrombosis or embolism could have occurred because platelet count exceeded 800000/ml following her recovery from HELLP syndrome. Deep venous thrombosis has complicated another case of resolving HELLP syndrome.13) In our patient, CT with contrast medium performed on the day following diffuse brain swelling did not demonstrate diagnostic findings of venous or sinus embolism such as ``delta sign'' or abnormally dense cortical veins. Since marked blood pressure elevation occurred 1 hour prior to the convulsive seizure and the subsequent CT showing brain swelling, we suspect that a rapid vasomotor event such as cerebral vasospasm was the cause of the seizure and swelling, although occurrence of transient hypertensive encephalopathy is another possible cause. Symptomatic cerebral vasospasm may occur at up to 11 days after the onset of HELLP syndrome and preeclampsia.6,8,19,24) Hypothermia, which systemically suppresses metabolism, may have delayed the onset of vasomotor dysfunction in our patient. Thrombocytopenia and cerebral vasospasm contribute to the high incidence of stroke associated with HELLP syndrome. 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