A schizophrenic patient with cerebral infarctions after hemorrhagic shock.

We herein report the fourth case of cerebral infarction, concomitant with hemorrhagic shock, in English literature. A 33-year-old male, who had been diagnosed with schizophrenia and given a prescription for Olanzapine, was discovered with multiple self-inflicted bleeding cuts on his wrist. On arrival, he was in hemorrhagic shock without verbal responsiveness, but his vital signs were normalized following infusion of Lactate Ringer's solution. The neuroradiological studies revealed multiple cerebral ischemic lesions without any vascular abnormality. He was diagnosed with speech apraxia, motor aphasia, and dysgraphia, due to multiple cerebral infarctions. As there was no obvious causative factor with regard to the occurrence of cerebral infarction in the patient, the hypoperfusion due to hemorrhagic shock, and the thromboembolic tendency due to Olanzapine, might have acted together to lead to the patient's cerebral ischemia.

INTRODUCTION

There have been a few reports of patients who experienced cerebral infarctions after hemorrhagic shock. We herein report a rare case of a schizophrenic patient with cerebral infarctions after hemorrhagic shock, and discuss the mechanism underlying its occurrence.

CASE REPORT

A 33-year-old male, who had been diagnosed with schizophrenia and given a prescription for 7.5 mg Olanzapine, was discovered to have multiple sites of self-inflicted bleeding after cutting his wrists. He had a past history of Kawasaki disease, which had completely resolved when he was a child. When the emergency medical technicians checked him, he was conscious, but in shock. He could understand what was being said, but he could not speak. He was transported to our department. On arrival, his vital signs were: blood pressure, 86/50 mmHg; pulse rate, regular at 110/minute; saturation of peripheral oxygen in room air, 98%; and tympanic temperature, 36.4°C. Spontaneous hematoemesis was performed for his left wrist cuts. He had no motor weakness or dysesthesia in any of his extremities. He had difficulty opening his mouth and sticking out his tongue. He could write his name slowly using his right hand, but his characters were poorly formed. He was suspected to be in hemorrhagic shock, so he received rapid infusion of 500 ml of Lactate Ringer's solution, and his wounds were closed. His vital signs returned to within the normal range after this treatment, without the need for a transfusion. The abnormal results of his blood biochemical analyses were as follows: white blood cell count, 21900/μl; glucose, 239 mg/ dl; blood urea nitrogen, 25 mg/dl; creatinine, 2.23 mg/dl, and HbA1c was 5.0%. A computed tomography (CT) scan of the head revealed a low density area in the right insular and external putamen. An electrocardiogram and sonography for evaluation of the heart, coronary artery, and carotid artery were negative for any pathological finding. Magnetic resonance imaging (MRI) of the head demonstrated multiple small high intensity areas in the right frontotemporoparietal lobe and left thalamus, in addition to the head CT findings [Figure 1]. A magnetic resonance angiogram showed no stenosis or occlusion of the cerebral arteries. The biochemical analyses of the cerebral spinal fluid were negative. A transcranial Doppler examination did not show any evidence of microemboli, even when using microbubble infusion with the Valsalva Maneuver. The patient subsequently received a diagnosis of speech apraxia, motor aphasia, and dysgraphia due to multiple cerebral infarctions. Olanzapine was changed to Perospirone. His deficits gradually improved, and he could speak again beginning on the fourth hospital day. As his D-dimer level had increased from 1.7 on arrival up to 12 μg/ml on the tenth day, warfarin and aspirin were prescribed. The results of the biochemical analyses of his blood were as follows: Antithrombin III, 105.0%; protein C, 93%; protein S, 79.8%; lupus anticoagulant, 0.8 seconds; anti-nuclear antibodies x 40; anti-cardiolipin IgG antibodies, 8 U/ml; von Willebrand factor, 200% (50 – 150%); X-factor, 94%; myeloperoxidase-anti-neutrophil cytoplasmic antibodies, negative; and cytoplasmic-anti-neutrophil cytoplasmic antibodies, negative. After his mental state was considered to have sufficiently stabilized, he was discharged on the twenty-fifth hospital day.

Figure 1

The MRI of the head, on arrival; The diffusion-weighted image showed multiple small high intensity areas in the right frontotemporoparietal lobe and left thalamus (arrow)

DISCUSSION

This is the fourth case of cerebral infarction concomitant with hemorrhagic shock in English literature. Generally, isolated hemorrhagic shock itself does not result in the occurrence of cerebral infarction.[1] For children, there is a clinical association between hemorrhagic shock and encephalopathy syndrome, however, this syndrome is due to the cerebrovascular injuries induced by disseminated intravascular coagulopathy triggered by infection, making this clinical entity different from cerebral infarction concomitant with hemorrhagic shock.[2] Takaoka et al. reported three adult cases of cerebral infarction after severe hemorrhagic shock, who required a large amount of blood via transfusion, ranging from 5 to 12 L.[3] They hypothesized that the mechanism responsible for these complications was a cerebral infarction induced by hemodynamic insufficiency triggered by hemorrhagic shock, because the location of the cerebral infarctions coincided with the boundary zones where functional anastomoses between the two arterial systems existed. However, two of the three cases had lung injures, so an air embolism could also have caused the cerebral infarction. The other patient had a past history of pulmonary embolism and already had a high d-dimer level on arrival, so paroxysmal cerebral infarction could have been the cause. Hasper et al. reported a case of cerebral infarction after hemorrhagic shock triggered by liver biopsy.[4] Their hypothesized mechanism underlying these complications was thromboembolic events induced by multiple large infusions of coagulants, such as, thrombocyte concentrates, fresh frozen plasma, antithrombin III, prothrombin complex, and recombinant factor VIIa, to obtain hematemesis. The present case did not undergo any treatment with coagulants, and his hemorrhagic shock was mild, so the previous theories did not apply to this case. One of possible causes of cerebral infarction was as a side effect of Olanzapine therapy. Olanzapine had a high affinity for the serotonin receptor 2A, and the serotonin-induced platelet aggregation could be affected following treatment.[5] Metabolic abnormalities such as dyslipidemia, hyperhomocysteinemia, and hyperglycemia were observed in subjects treated with Olanzapine, and were all associated with decreased fibrinolytic activity.[5] There is a controversy on whether Olanzapine is a risk factor for the occurrence of cerebral infarction, and in a meta-analysis to evaluate atypical antipsychotic medications, including Olanzapine, the odds ratio concerning cerebrovascular accidents was 1.50 (confidence interval 0.33 – 7.44).[6-8] Accordingly, hemorrhagic shock and Olanzapine could be considered weak causative factors for cerebral infarction, but working together, they might have been responsible for the present patient's infarctions.

This patient exhibited a delayed increase of the D-dimer value. The plasma D-dimer levels were neither sufficiently sensitive nor specific to be utilized in stroke diagnostics, but numerous studies showed that patients with various strokes and stroke-related diseases had acutely increased plasma D-dimer levels on arrival.[9] Although a high D-dimer level on arrival suggested cardioembolic stroke, the possibility of such a diagnosis was considered to be low in this case.[10] Generally, the mean D-dimer levels were slightly elevated during the first week and then increased during the next two weeks, after an ischemic stroke, possibly due to activated thrombin formation induced by the infarcted brain.[11] In addition, the high plasma D-dimer levels during the course of acute stroke suggested complications of deep vein thrombosis.[12] However, the D-dimer levels were markedly elevated on the day of admission, and thereafter, gradually decreased by day four in the trauma setting.[13] Accordingly, the delayed increase observed in the D-dimer values, in this case, may have been induced by either the natural course after a stroke or may signify a complication of deep vein thrombosis.

CONCLUSION

We have herein reported the fourth known case of cerebral infarction concomitant with hemorrhagic shock, and discussed the possible underlying mechanism.