selected reports Pulmonary Embolism Presenting as Seizures* Joseph E. Marine, MD; and Samuel Z. Goldhaber, MD, FCCP Two patients with massive pulmonary embolism (PE) presented with generalized seizures. Pathophysiologic abnormalities that explain this clinical syndrome include respiratory acidosis, hypoxemia, and cerebral hypoperfusion due to decreased cardiac output. PE should he considered in the differential diagnosis of new-onset and otherwise unexplained seizures. (CHEST 1997; 112:840-42) nous administration of pressor agents. An echocardiogram showed a normal left ventricle and a dilated and hypokinetic right ventricle \vith preserved apical systolic function (McConnell's sign 3 ). Pulmonary artery catheterization revealed a pulmonary artery pressure of 52/30 mm Hg and multiple large bilateral pulmonaty emboli. In preparation for thrombolysis, aCT scan of the head was normal. He then received 100 mg of tissue plasminogen activator over a 3-h period followed by continuous intravenous administration of heparin sodium. Ultrasound of the lower extremities revealed a deep venous thrombosis of the calf. The follov.ing day, an inferior vena cava filter was placed. Gradual improvement was noted, the patient was extubated, and therapy with warfarin sodium was started. An EEG on the 4th postoperative day showed no significant abnormality. He was discharged home uneventfully on the lOth postoperative day. MRI of the head performed after discharge was normal. Key words: diagnosis; pulmonary e mbolism; seizures Case 2 Abbreviations: PE=pulmonary embolism A!though pulmonary embolism (PE) can present with syncope, 1 generalized seizure activity has not been reported.2 We, therefore, describe two patients with massive PEs in which the principal presenting features were generalized seizures (Table 1). REPORT OF CASES Case 1 A previously healthy 33-year-old man presented with acute appendicitis and under.vent an uncomplicated appendectomy on the night of admission. He did not receive prophylactic therapy for venous thromboembolism. On the second postoperative day, while ambulating, he suddenly felt nauseated, fe ll to the ground, and had approximately 30 s of generalized tonic-clonic seizure activity with urinary and fecal incontinence . Postictally, he complained only of incisional abdominal pain, and he denied chest pain or dyspnea. On initial examination after the seizure, he was confused, tachycardic, tachypneic, and normotensive; he had a pulse oximetry value of 88% while receiving 100% oxygen by face mask. Examination by a neurologist l h after th e seizure disclosed no abnormalities except for mild hyperreflexia in the left arm and leg. A chest radiograph showed low lung volumes and vague opacities in the lower lobes of both lungs. Initially, the diagnosis was a seizure due to general anesthesia followed by aspiration . In the ensuing 4 h ,the patient became progressively confused, hypoxic, and hypotensive and required intubation and intrave*From the Cardiovascular Division, Depattment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston. Dr. Matine was supported, in part, by the Sandra Bakalar Fund. Manuscript received December 26, 1996; revision accepted March 2, 1997. Rep rint requests: Samuel Z. Goldhaber, MD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston MA 02115 840 A 34-year-old woman previously in excellent health had several days of upper respiratory tract symptoms followed by l day of mild dyspnea on exertion, which she ascribed to a"cold." At home, her husband \vih1essed her having sudden nausea, followed by a 10-s spell characterized by tonic bilateral upgaze and extensor posturing of all four extremities associated \vith fecal incontinence. She regained consciousness but had four successive similar spells inte rrupted by brief periods of an awake confusional state. A CT study of the head and a lumbar puncture both revealed no abnormalities. She then had two episodes of transient hypotension, which prompted transfer to the ICU of a regional medical center. Upon arrival, she was in cardiogenic shock and hypercapneic respiratory failure. She was intubated and treated with pressors. An ECG and echocardiography revealed strain on the right side of the heart. A pulmonary angiogram showed an obstructing thrombus in the left main pulmonary trunk and multiple smaller PEs in the lower lobe of the right lung. The thrombus in the le ft pulmonary artery was mechanically fragmented with the pulmonary artery catheter, and the more distal branches were then visualized on angiography. She was subsequently treated with bolus urokinase (2,000 units/kg over a period of l h)followed by continuous intravenous administration of heparin, which resulted in clinical and electrocardiographic improvement. Ultrasound of the lower extremities revealed a right popliteal deep venous thrombosis. A follow-up lung scan showed only minimal nonsegmental perfusion defects. She was discharged on hospital day 18, neurologically intact, on a regimen of aspirin and acenocoumarol. On a follow-up visit 1 month after discharge, she remained well and had no further seizures or neurologic sequelae. DISCUSSION Several cardiopulmonary conditions have been reported to present with seizures. These include torsade de pointes, 4 long QT inte1val syndrome, 5 severe bradycardia,6 asystole, 7 and systemic arterial hypertension.8 The two cases described h erein are the first reported, as best as can Selected Reports Table !-Clinical Features of Cases* Clinical Data Case l Case 2 Risk factors for PE Type of seizure No. of seizures Neurologic studies Clinical features ofPE Recent surgety Oral contraception, family history Generalized tonic Five CT, lumbar puncture Tachycardia, hypoxia, hypotension Confirmation of PE RV failure on echocardiogram Treatment Neurologic sequelae Cardiopulmonary sequelae Generalized One CT, MRI, EEG Tachycardia, tachypnea, hypoxia, hypotension Angiogram Angiogram Present Present TP A and filter placement None Urokinase; disruption of embolus with pulmonmy artery catheter None None None *RV = right ventricular; TPA = tissue plasminogen activator be determined, in which PEs presented wi.th seizure activity. In each case, initial clinical attention focused upon the neurologic condition of the patient and only later, when hemodynamic compromise ensued, was the diagnosis of PE pursued. In both cases, electrocardiographic or echocardiographic evidence of failure of the right side of the heart played a key role in detecting PEs. The first patient responded well to tissue plasminogen activator alone. In the second case, a combination of mechanical clot fragmentation and thrombolysis was utilized, as previously described by Essop et al. 9 Initial disruption of thrombus \vith the catheter converted the clot from totally obstructive to nonobstructive in this patient, thereby permitting urokinase to lyse emboli in the distal branches of the pulmonary arterial tree. Seizures that are associated vvith PEs raise several important clinical issues. First, clinical evaluation may be compromised by the patient's postictal confusional state. Second, well-established clinical signs of PE , such as tachypnea, tachycardia, and hypoxia, may likewise be attributed to a postictal state vvith or without aspiration pneumonitis. In addition, new-onset seizure activity usually leads to a neurologic workup, which may distract the clinician from consideration of cardiovascular causes of seizure. Finally, treatment for massive PEs usually involves immediate systemic anticoagulation when the diagnosis is suspected, followed by thrombolysis when the diagnosis is confirmed. In a patient presenting vvith seizures, however, such therapy must be delayed until intracranial hemorrhage is excluded. Furthermore, since embolic stroke and small tumors may present with seizure and a normal CT scan, treatment of PEs in association FIGURE 1. Proposed pathophysiologic features of seizure in PE. V\i.th new seizures probably entails some increased risk of intracranial bleeding. In each case described previously, CT scanning was performed prior to thrombolysis; however, this test does not guarantee immunity from intracranial hemorrhage.l 0 While the exact cause of seizures in the two patients described herein cannot be established definitively, the most likely contributing factors include transient cerebral ischemia, hypoxia, and acidosis (Fig 1). In each case, a further workup and follow-up revealed no intrinsic neurologic pathologic findings , indicating that PE was the plimary cause of seizure in each case. In conclusion, clinicians should consider PEs in the differential diagnosis of new-onset unexplained seizures, particularly if tachycardia, tachypnea, and hypoxemia are present, regardless of whether or not aspiration occurred. Furthermore, patients who have had both seizures and PEs require careful and rapid neurologic evaluation for contraindications to anticoagulant and thrombolytic therapy. REFERENCES 1 Thames MD, Alpert JS, Dalen JE. Syncope in patients with pulmonary embolism. JAMA 1977; 238:2509-ll 2 Stein PD, Te rrin ML, Hales CA, et a!. Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients without pre-existing cardiac or pulmonary disease. Chest 1991; 100:598-603 3 McConnell MV, Solomon SD, Rayan ME , et a!. Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism . Am J Cardiol 1996; 78:469-73 4 Sundaram MBM , McMeekin JD , Gulamhusein S. Cardiac tachyarrhythmias in hereditary long QT syndromes presenting as a seizure disorder. Can J Neurol Sci 1986; 13:262-63 5 Herman LL, Stoshak M, Rittenbaum TJ. Long QT syndrome presenting as a seizure. Am J Emerg Med 1992; 10:435-38 6 Mendes LA, Davidoff R. Cardiogenic seizure with bradyarrhythmia: documentation of the mechanism during asystole. Am Heart J 1993; 125:1786-88 7 Howell SJL, Blumhardt LD. Cardiac asystole associated with epileptic seizures: a case report with simultaneous EEG and CHEST/112/3/SEPTEMBER, 1997 841 ECG. J Neurol Neurosurg Psychiatry 1989; 52:795-98 8 Ng SKC, Hauser WA, Brust JCM , eta!. Hypertension and the risk of new-onset unprovoked seizures. Neurology 1993; 43:425-28 9 Essop MR, Middlemost S, Skoularigis J, et al. Simultaneous mechanic;al clot fragmentation and pharmacologic thrombolysis in acute massive pulmonary embolism. Am J Cardiol 1992; 69:427-30 10 Kanter DS , Mikkola KM , Patel SR, et al. Thrombolytic therapy for pulmonary embolism: frequency of intracranial hemorrhage and associated risk factors. Chest 1997; 111: 1241-45 Left Main Coronary Artery Compression During Primary Pulmonary Hypertension* Jean-Fnideric Patrat, MD; Guillaume Jondeatt, MD, PhD, FCCP; Olivier Dubourg , MD, FCCP; Pascal Lacombe, MD; Michel Rigaud, MD; Jean-Pierre Bourdarias, MD; and lracij Gandjbakhch, MD ular ischemia or pulmonary artery (PA) dilation. We herein describe a patient in whom compression of the left main coronary artery (LMCA) by the severely dilated pulm onary trunk produced severe left ventricular (LV) myocardial ischemia. CASE REPORT A 37-year-old woman with severe PPH complain ed of anginal pain both at rest and exercise. According to New York Heart Association classification, her functional status was class IV and she was referred to be investigated before heart-lung transplantation. ECG showed right bundle-branch block, right ventricular hypertrophy, and during chest pain episodes, ST segment and T wave c hanges in the left precordial leads. Right atrial pressure was 27 mm Hg, PA pressure was 132/60 mm Hg (mean , 90 mrn Hg), wedge pressure was 12 mm Hg, and cardiac index was 1.50 Urninlrn 2 . Pulmonary angiography ruled out postembolic disease. On 201 thallium scintigraphy, an anterior perfusion defect was noted at rest, which was reversible after 4 h. Coronmy angiography showed severe stenosis of the LMCA (Fig 1) with distal filling of the left anterior descending mte1y (LAD ) by collaterals from the right coronary artery (RCA), and a competitive flow was visuali zed during le ft coronary arte ry opacification (Fig 2). Th e LV ante rior wall was slightly hypokin etic and LV ejection fraction was 0.58 . Th e pati ent underwent success- Primary pulmonary hypertension (PPH) is often associated with angina-like chest pain, the mechanism of which is controversial. A 37 -year-old woman with severe PPH and angina had transient ischemic ECG changes and reversible anterior perfusion defect on 2 01 thallium scintigraphy. Coronary angiography revealed severe stenosis of the left main coronary artery (LMCA) and otherwise normal vessels. After heart-lung transplantation, examination of the explanted heart showed normal coronary arteries. Compression of the LMCA by the dilated pulmonary artery trunk was responsible for myocardial ischemia. This mechanism should be considered in patients with PPH and angina and might contribute to the high sudden death rate. (CHEST 1997; 112:842-43) Key words: angina; chest pain; heart-lung transplantation; left coronary artery; primary pulmonary hypertension Abbreviations: LAD= left anterior descending artery; LMCA=left main coronary artery; LV=left ventricle; PA = pulmonary artery; PPH = primary pulmonary hypertension; RCA=right coronary arte1y About 50% of patients with severe primary pulmonary artery hypertension (PPH) complain of precordial pain, 1 which has been ascribed either to right ventric*From the Departments of Cardiology (Drs. Patrat, Jondeau, Dubourg, Rigaud, and Bourdarias) and Radiology (Dr. Lacombe), Hopi tal Ambroise Pare, and the Department of Cardiac Surgery (Dr. Gandjbakhch), Hopital de la Pitie, Boulogne, France. Manusc1ipt received Janumy 22, 1997; accepted March 2. 842 FIGURE 1. Top: Left coronary artery angiography (left anterior oblique view) shows severe stenosis of the LMCA. The left circum flex artery is completely opacifled wh ile only the proximal part of the LAD is visuali zed. Bottom: On RCA angiography (right anterior oblique view), the LAD is well opacified by collaterals from the RCA. Selected Reports