Occlusion of the Internal Carotid Artery Complicating Haemophilus influenzae Meningitis Dennis L. Headings, MD, Lowell A. Glasgow, MD \s=b\ We report a patient with occlusion of the internal carotid artery complicating Haemophilus influenzae meningitis. The etiology of this complication is discussed, along with its role in the acute seizures of meningitis, and in the chronic neurological residua of this infection. (Am J Dis Child 131:854-856, 1977) The neurological complica¬ tions of Haemophilus influenzae type b meningitis have been well acute described.1- Increased intracranial pressure, altered consciousness, subdural effusions, seizures, cranial nerve signs, and venous thromboses are all seen with variable frequency during the course of this form of meningi¬ tis. Ten reported episodes of major cerebral arterial occlusions with H influenzae meningitis were found in the literature, but these reports were found exclusively in radiology and From the Department of Pediatrics and the Division of Infectious Diseases, University of Utah College of Medicine, Salt Lake City. Dr Headings is now with Baltimore City Hospital. Reprint requests to Department of Pediatrics, University of Utah Medical Center, Salt Lake City, UT 84132 (Dr Glasgow). neurology journals.3" The following case of internal carotid artery occlu¬ sion complicating the acute phase of H influenzae meningitis is reported to illustrate and review the occurrence of this complication. REPORT OF A CASE An 18-month-old male infant was admit¬ ted to another hospital because of seizures and fever. Four days prior to admission, he had had a flu-like illness with listlessness, fever, and diarrhea, and had been seen in the emergency room and treated with oral penicillin. On the day of admission he could not walk or sit, and suffered two tonic, clonic seizures. He was febrile, had marked nuchal rigidity, and had paralysis of the right arm and leg on arrival at the hospital. His CSF was cloudy with 12,700 WBCs (64% neutrophils), protein level was 190 mg/100 ml, CSF glucose level was 25 mg/ 100 ml, and blood glucose level was 103 mg/ 100 ml. A Gram stain of the CSF showed Gram-negative, pleomorphic rods, and although initial cultures were negative, a counterimmunoelectrophoresis (CIE) of the CSF was positive for H influenzae type b capsular antigen. The patient was initially treated with intravenously administered penicillin G potassium, 100,000 units/kg/day (in four equally divided doses) and chloramphenicol Downloaded From: http://archpedi.jamanetwork.com/ by a University of Iowa User on 06/19/2015 100 mg/kg/day (in four equally divided doses) although the penicillin was discon¬ tinued when the results of the CIE were obtained. Phénobarbital was begun for treatment of the seizures. Later on the day of admission, the patient experienced a right-sided seizure with deviation of the eyes to the right. He continued to be febrile, and the right hemiparesis and right facial paralysis characterized his hospital course. A repeat lumbar puncture on day 5 showed 50 WBCs, a protein level of 320 mg/100 ml, a CSF glucose level of 21 mg/100 ml, and a negative Gram stain. On the sixth hospital day, the patient was transferred to the University of Utah Medical Center because of persistent fever, right hemiparesis, and paralysis of the right third, sixth, and seventh cranial nerves. His CSF at this time showed 1,570 WBCs (62% neutrophils), a glucose level of 19 mg/100 ml, protein level of 195 mg/100 ml, and although the Gram stain was nega¬ tive, a type b, H influenzae, sensitive to both ampicillin sodium and chlorampheni¬ col, was isolated from this culture. The CIE for blood, urine, and CSF remained posi¬ tive for the H influenzae capsular antigen, and chloramphenicol was continued at a dose of 100 mg/kg/day. A sodium pertechnetate Tc 99m scan showed increased uptake in the left hemi¬ sphere compatible with a subdural effu¬ sion. An arteriogram failed to demonstrate effusion, but did show almost complete stenosis of the left internal carotid artery in the supraclinoid portion extending to the bifurcation of the middle cerebral artery (Fig 1). There was also slight nar¬ rowing of the supraclinoid portion of the right internal carotid (Fig 2). A left verte¬ bral artery injection demonstrated anastomotic flow into the distribution of the occluded left internal carotid. Therapy with chloramphenicol was con¬ tinued for a total of 13 days with resolution of fever and clinical improvement. A repeat lumbar puncture performed three days after discontinuing therapy had two WBCs, a glucose level of 45 mg/100 ml, a protein level of 100 mg/100 ml, and nega¬ tive cultures. He was discharged from the hospital on a regimen of phénobarbital, and although the right-sided hemiparesis had diminished somewhat, impairment of motor function remained. an COMMENT The striking features of this child's course were the occurrence of rightsided seizures, the persistence of a right hemiparesis, and a positive CSF culture on the sixth day of adequate therapy. Although focal seizures can be seen with the generalized process of me¬ ningitis, their occurrence is more suggestive of local phenomena such as subdural effusions, abscesses, or in¬ farction. Of the vascular processes resulting in focal seizures, generalized arteritis and venous or sinus throm¬ boses are the causes most frequently implicated. Large cerebral arterial occlusions have received little atten¬ tion. This child's course was compat¬ ible with any of these focal complica¬ tions, and the value of arteriography in such situations was again demon¬ strated. Arteriography has documented ma¬ jor cerebral arterial occlusions during the course of meningitis with a number of organisms including H influenzae.3'* In contrast, autopsy studies of patients dying of H influen¬ zae meningitis have not shown throm¬ bi of major cerebral arteries. This dichotomy of findings may be impor¬ tant in considering the mechanism of the arterial occlusion. Although the clinicopathological study of Adams et al10 of 14 patients with H influenzae meningitis included four patients with major venous thrombosis, five Fig 1.—Left carotid arteriogram showing complete occlusion (arrow) of supraclinoid segment of left internal carotid artery without filling of anterior and middle cerebral arteries. Fig 2—Right carotid arteriogram showing slight stenosis (arrow) of supraclinoid segment of right internal carotid artery. Downloaded From: http://archpedi.jamanetwork.com/ by a University of Iowa User on 06/19/2015 with definite arteritis, and eight with focal cortical necrosis; no major arterial thromboses were seen. Simi¬ larly, Smith and Landing's11 review of 34 patients who died of H influenzae meningitis contained eight specimens with arteritis, but no arterial throm¬ boses were found: Whether arterial spasm or actual thrombus formation explains the ar¬ terial occlusions seen with cerebral arteriography has not been clear. Three general factors are considered to be the major determinants of any vascular thrombosis:1- (1) alterations in the vessel wall, (2) changes in the local pattern of blood flow, and (3) changes in the constitutents of the blood. At least two of theáe factors can be implicated in the generation of arterial thromboses during the course of H influenzae meningitis. The arteritis described in the pathology studies clearly demonstrates altera¬ tion of vessel walls and endothelium. Second, regardless of the type of underlying bacterial meningitis, al¬ most all the reported cases of arterial occlusion have involved the supracli¬ noid portion of the internal carotid artery. This may indicate that local flow factors also contribute to the development of inflammation, spasm, or arterial thromboses at this location. In this patient, and in nine of the ten influenzae meningitis from the literature that were studied with arteriography, the supraclinoid por¬ tion of the internal carotid was involved. Branches of this portion, the anterior and middle cerebral arteries, were also involved, but much less frequently. In addition, the supracli¬ noid was involved in nine of ten cases of tuberculosis meningitis whose ar¬ teriography was described by Mathew et al.'" The supraclinoid portion of the internal carotid artery lies at the base of the brain just distal to the vessel's S-shaped course through the layers of dura forming the cavernous sinus. It should not be surprising that this major vessel is affected with such frequency in an area where flow is more turbulent, slower, and where the inflammatory response may be great¬ est. Although thrombus formation is possible, circumstantial evidence im¬ plicates spasm secondary to arteritis as the major factor in the occlusions seen With H influenzae meningitis. No thromboses have been seen at autop¬ sy, and Gado et al" have demonstrated cases of H resolution of the internal carotid occlusion in two of three cases that were restudied. Repeat arteriography in the present case would be interest¬ ing and informative, but the contin¬ ued improvement in the patient's motor function does not justify this procedure. The residual effects of arterial occlusion, whether thrombotic in na¬ ture or due to even transient spasm, are severe. In the case presented here and in ten others from the literature whose clinical summaries included a description of the outcome, the results are depressingly bad. Of the ten patients observed, one died, eight had either major hemiparesis or decerebrate spasticity, and one apparently recovered. The anoxia, infarction, and necrosis that result from major arterial occlusion must certainly con¬ tribute to the long-term neurological sequelae of these patients. Nonproprietary Name and Trademarks of Drug Ampicillin sodium-Alpen-N, Amcill-S, Omnipen-N, Penbritin S, Polycillin-N, Prinicipen/N. References 1. Dodge PR, Swartz MN: Bacterial meningitis: A review of selected aspects. N Engl J Med 272:954-960, 1003-1010, 1965. 2. Nyhan WL, Richardson F: Complications of meningitis. Annu Rev Med 14:243-260, 1963. 3. Leeds NE, Goldberg HI: Angiographic manifestations in cerebral inflammatory disease. Radiology 98:595-604, 1971. 4. Thomas VH, Hopkins IJ: Arteriographic demonstration of vascular lesions in the study of neurologic deficit in advanced Hemophilus influenzae meningitis. Dev Med Child Neurol 14:783-787, 1972. 5. James AE, Hodges, FJ III, Jordon CE, et al: Angiography and cisternography in acute meningitis due to Hemophilus influenzae. Radiology 103:601-606, 1972. 6. Gado M, Axley J, Appleton DB, et al: Angiography in acute and posttreatment phases of Hemophilus influenzae meningitis. Radiology 110:439-444, 1974. 7. Levinson A, Hartenstein H: Intracranial calcification following pneumococcic meningitis. J Pediatr 38:624-629, 1951. 8. Mathew NT, Abraham J, Chandy J: Cerebral angiographic features in tuberculous meningitis. Downloaded From: http://archpedi.jamanetwork.com/ by a University of Iowa User on 06/19/2015 Neurology 20:1015-1023, 1970. 9. Gibson NF, Ball MM, Kelsey DS, et al: Anterior fontanelle herniation. Pediatrics 56:466\x=req-\ 469, 1975. 10. Adams RD, Kubic CS, Bonner FJ: The clinical and pathological aspects of influenzal meningitis. Arch Pediatr 65:354-376, 408-441, 1948. 11. Smith JF, Landing BH: Mechanisms of brain damage in H influenzae meningitis. J Neuropathol Exp Neurol 19:248-265, 1960. 12. Florey HW: General Pathology. Philadelphia, WB Saunders Co, 1970, pp 295-303.