Locked-in Syndrome and Blue Toe Syndrome Caused by Cardiopulmonary Bypass TEHRAN HEART CENTER the basis pontis spares the pathways for somatic sensation and the non-specific ascending system of neurons and fibers responsible for arousal and wakefulness; nevertheless, it interrupts the cortico-bulbar and cortico-spinal pathways, depriving the patient of speech and the ability to respond in any other way. The locked-in syndrome has been reported after ventral pontine infarction following basilar artery occlusion, air embolism,3, 4 pontine hemorrhage,5 tumor, trauma, heroin abuse, encephalitis,6 hypoglycemia,7 and Basilar artery ectasia.8 We add here a new cause, which is severe inflammatory reaction due to cardiopulmonary bypass with the gangrene of the distal extremity or the blue toe syndrome. Case Report A 45-year-old woman was admitted to our heart center with severe mitral stenosis and left atrial clot. The patient gave a history of shortness of breath on minimal exertion for one week and no cerebral symptoms, including headache, dizziness, transient ischemic attacks, or strokes. She was found to be fully conscious, alert, and oriented with stable vital signs. Blood pressure was 110/80 mmHg, and diastolic murmur was audible over the mitral area. Physical examination revealed intact cranial nerves, motor power, and sensation. There was no evidence of vasculitis such as Osler’s nodes, Jane way pad, palmer erythema, or cyanosis of fingers. Blood investigation showed an erythrocyte sedimentation rate (ESR) of 4 mm with no leukocytosis and a white blood cell (WBC) of 10.000 mm3. The electrolytes and kidney and liver function were within normal limits. Chest X-ray showed prominence of the left cardiac border due to left atrial enlargement. Electrocardiography was indicative of no change, but two–dimensional echocardiography revealed a large bulky non-mobile thrombosis in the left atrium with severe mitral stenosis. The mitral valve area was 0.6 cm2, and the other cardiac valves were normal. Pre- and postoperative laboratory measurements included negative antinuclear antibodies and rheumatoid factor, and elevation of C4 & C3 components of complement; in addition, HBS Antigen (especially in polyarteritis nodosa) was negative. The patient underwent open heart surgery via the ascending aorta and bicaval cannulation. The aorta was cross-clamped, and the heart was arrested with cold cardioplegia by achieving systemic hypothermia at 30 °C on the cardiopulmonary bypass. Intraoperatively, the stenotic mitral valve was found to have a bulky clot attached to the valve and wall of the left atrium. The diseased mitral valve and the clot were excised, and the left atrial cavity was irrigated with copious amounts of normal saline and a valve was thereafter implanted. The left ventricle was then filled completely with saline and blood and fully deaired. The patient was weaned successfully off cardiopulmonary bypass with inotropic support and transferred to the intensive care unit. After 6 hours, blood pressure dropped and central venous pressure elevated and the extremity became cool and cyanotic. Inotropic support was commenced with dobutamine and adrenaline (2 and 1 mic/kg/min, respectively). On the third postoperative day, the inotropic drugs were tapered and blood pressure stabilized. By this point, however, the cyanosis had changed to gangrene and on the 12th postoperative day the acral part of the extremity was amputated and the specimen was sent for histopathological examination. In the histopathological examination, there was only non-specific vasculitis with thrombosis. The patient did not regain full consciousness on the following morning and was found to be quadriplegic with non-voluntary movements of the four limbs and face. The eyes could move only on the vertical plane, with both pupils having become small and fixed. After 72 hours, she managed to respond to questions only by blinking or moving her eyes vertically. Brain MRI revealed multiple infarction of the brainstem. Prolonged ventilatory support was maintained and eventually a tracheostomy was performed to facilitate tracheobronchial suctioning and weaning. Acute renal failure with anemia was managed and the kidneys recovered completely. However, the patient remained in this locked- in state for 4 weeks with no neurological improvement despite all ventilatory, nutritional, and nursing support. She eventually expired from hepatic failure and generalized sepsis. Discussion During cardiopulmonary bypass, the interaction of blood with non-biological surfaces results in a whole-body inflammatory response which may increase the morbidity and lead to multiple organ dysfunction.9 Be that as it may, brainstem involvement as the locked-in syndrome and gangrene of the acral part of the extremity as the blue toe syndrome is exceedingly rare. The locked-in syndrome was coined by Plum10 to denote the state of quadriplegia and mutism with preserved consciousness demonstrated by communication via intact vertical eye movements. It is considered to be devastating sequels of an occlusion of the main basilar artery11 or its para median branch causing pontine infarction as the occlusion of the basilar artery can rarely be compensated by collateral artery.12 Infarction of the brain stem evokes a variety of syndromes, including the locked-in syndrome, in which the lesion spares the pathways for somatic sensation and the non-specific ascending system of neurons and fibers responsible for arousal and wakefulness but interrupts the cortico-bulbar and cortico-spinal pathways, depriving the patient of motor power, speech, and capacity. The locked-in syndrome has never been reported earlier due to post cardiopulmonary bypass inflammatory reaction. Partial or full recovery has been reported in patients with The Journal of Tehran University Heart Center151