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a family history of similar disorders. Another disorder that must be excluded is the autoimmune polyglandular syndrome type I, which comprises hypoparathyroidism, Addison's disease, and mucocutaneous candidiasis, at least two of which must be present to make the diagnosis. Once these syndromes are excluded and a serum intact PTH level is very low with concurrent hypocalcemia, a diagnosis of idiopathic hypoparathyroidism can be made. This disorder can be caused by an isolated autoimmune destruction of parathyroid tissue, which is a possible cause of the hypoparathyroidism in both of the cases presented. If there is no PTH activity, the serum calcium level will be near 1.25 mmol per liter (5.0 mg per dl), representing the solubility of bone mineral in the serum.1 Idiopathic hypoparathyroidism is rare, and it is not uncommon for patients to go for long periods of time without symptoms."l10 These two patients have had this disorder for several years as both had extensive intracranial calcifications. It can also cause notable ligamentous and soft tissue calcification. "l Before the common use of CT scanning, studies of patients who had undergone surgical parathyroidectomy have shown that 17 years elapse before radiographic evidence of intracranial calcifications.' Computed tomography is more sensitive than routine radiography in detecting intracranial calcifications.9 Because of the extensive intracranial calcifications in the two cases presented, however, both patients are likely to have had hypocalcemia for more than 17 years. Chronic hypocalcemia can present as seizures, cognitive or psychiatric alterations in CNS function, or extrapyramidal signs in the neonate to the elderly populations.0",2-" These symptoms can also wax and wane in older patients.'6 It is therefore important to evaluate serum calcium levels in all patients who present with new CNS symptoms. As seen in the two cases presented here, however, even those persons with asymptomatic hypoparathyroidism are likely to have a subclinical alteration in CNS function, and a concurrent CNS process can produce serious symptoms such as seizures, stupor, or coma. In both of the cases presented, the stuporous state resolved considerably with calcium repletion. Adaptation to chronic hypocalcemia can be accomplished by increasing the dietary intake of calcium, which was not historically present in these two patients. Unfortunately, calcium supplementation does not always prevent further intracerebral calcification or a progression of CNS dysfunction. 14 In summary, idiopathic hypoparathyroidism is considered a rare disease that can present with a variety of neurologic or psychiatric symptoms or be clinically silent. With the widespread use of multichannel biochemical screening tests and CT scans of the head, asymptomatic hypocalcemia and intracranial calcification may be recognized more commonly in clinical practice. In these cases, physicians must consider the possibility of parathyroid hormone abnormalities.

during infancy: X-linked recessive inheritance in a large Missouri kindred. J Pediatr 1981; 99:608-611 6. Thakker RV, Davies KE, Whyte MP, Wooding C, O'Riordan JLH: Mapping the gene causing X-linked recessive idiopathic hypoparathyroidism to Xq26-Xq27 by linkage studies. J Clin Invest 1990; 86:4045 7. Rao SD, Kleerekoper M, Tolia K, Matkovic V, Frame B, Parfitt AM: Hypoparathyroidism and biochemical screening (Letter). Ann Intern Med 1981; 95:655 8. Phillipson B, Angelin B, Christensson T, Einarsson K, Leijd B: Hypocalcemia with zonular cataract due to idiopathic hypoparathyroidism with a note on the prevalence of severe hypocalcemia in a health screening. Acta Med Scand 1978; 203:223229 9. Illum F, Dupont E: Prevalences ofCT-detected calcifications in the basal ganglia in idiopathic hypoparathyroidism and pseudohypoparathyroidism. Neuroradiology 1985; 27:32-37 10. Tordjman K, Rosenthal T, Apter S: Asymptomatic long-standing idiopathic hypoparathyroidism discovered following delivery of a healthy infant. Am J Med 1985; 78:853-856 11. Lambert RG, Becker EJ: Diffuse skeletal hyperostosis in idiopathic hypoparathyroidism. Clin Radiol 1989; 40:212-215 12. Graham K, Williams BO, Rowe MJ: Idiopathic hypoparathyroidism: A cause of fits in the elderly. Br Med J 1979; 1:1460-1461 13. Baker SL: Idiopathic hypoparathyroidism presenting as urinary and faecal incontinence. Br Med J 1982; 285:963-964 14. Cheek JC, Riggs JE, Lilly RL: Extensive brain calcification and progressive dysarthria and dysphagia associated with chronic hypoparathyroidism. Arch Neurol 1990; 90:1038-1039 15. Fonseca OA, Calverley JR: Neurological manifestations of hypoparathyroidism. Arch Intern Med 1967; 120:202-206 16. Ostlere L, Reeve J: A case of resolving idiopathic hypoparathyroidism. Postgrad Med J 1991; 67:179-182

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REFERENCES 1. Parfitt AM: Surgical, idiopathic, and other varieties of parathyroid hormonedeficient hypoparathyroidism, In DeGroot U (Ed): Endocrinology-Vol 2, 2nd Ed. Philadelphia, Pa, WB Saunders, 1989, pp 1049-1064 2. Barr DGD, Prader A, Esper U, Rampini S, Marraian VJ, Forfar JO: Chronic hypoparathyroidism in two generations. Helv Paediatr Acta 1971; 26:507-521 3. Bronsky D, Kialmko RT, Waldstein SS: Familial idiopathic hypoparathyroidism. J Clin Endocrinol Metab 1968; 28:61-65 4. Peden VH: True idiopathic hypoparathyroidism as a sex-linked recessive trait. Am J Hum Genet 1960; 12:323-337 5. Whyte MP, Weldon VV: Idiopathic hypoparathyroidism presenting as seizures

Cerebral Infarction as a Remote Complication of Childhood Haemophilus influenzae Meningitis LYNNE KERR, MD, PhD FRANCIS M. FILLOUX, MD Salt Lake City, Utah

STROKE IS RARE in children, and when it does occur it is associated with different causes than in adults. One of the most common causes of acquired cerebrovascular disease in children is central nervous system infection. For instance, in some selective studies, cerebral infarction developed in as many as 27% of children with complicated bacterial meningitis during their hospital stay. 1.2 The pathophysiology of infarction in these patients is not clear, but it is thought to involve, singly or in combination, vasculitis,'4 coagulopathy, or vasospasm.416 Vasculitis when it occurs may then have long-term structural consequences for blood flow in the brain.4'7 In this report we present a case of cerebral infarction that occurred six years after Haemophilus influenzae meningitis and that we think represents a delayed consequence of meningitis-associated arteriopathy. To our knowledge, delayed infarction from H influenzae meningitis has not been reported to date.

Report of a Case The patient, a 6-year 10-month-old boy, presented to the Primary Children's Medical Center Emergency Department (Salt Lake City, Utah) because in the previous 12 hours he (Kerr L, Filloux FM: Cerebral infarction as a remote complication of childhood Haemophilus influenzae meningitis. West J Med 1992 Aug; 157:179182) From the Departments of Neurology and Pediatrics (Dr Kerr) and Psychiatry (Dr Filloux), University of Utah School of Medicine, Salt Lake City. This work was supported in part by National Institutes of Health grant HD00912-

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Reprint requests to Francis M. Filloux, MD, Research Lab, Western Institute of Neuropsychiatry, 501 Chipeta Way, Salt Lake City, UT 84108.

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Figure 1.-A, An enhanced computed tomographic (CT) scan of the brain done shortly after admission shows a poorly defined area of hypodensity (arrows) in the vicinity of the right putamen and globus pallidus with a slight degree of mass effect. B, A magnetic resonance image taken 3 days after admission shows notably increased signal on T2-weighted images (arrow), confirming the presence of a right basal ganglia infarction. C, After neurologic deterioration on the 5th hospital day, a second (unenhanced) CT scan showed a small hemorrhage in the right basal ganglia (arrow).

had had transient episodes of left-sided weakness lasting about 2 to 40 minutes each, with complete resolution between episodes. The patient had been previously healthy except for a bout of H influenzae type B meningitis at the age of 41/2 months. On the day of admission for meningitis, the patient was noted to have a bulging fontanelle, vomiting, listlessness, and nuchal rigidity, with a maximum temperature of 39.6°C. Cerebrospinal fluid (CSF) analysis showed 9,258 leukocytes x 106 per liter with 0.66 polymorphonuclear leukocytes, 0.22 band forms, and 0.12 lymphocytes. There were 552 erythrocytes x 106 per liter. A CSF protein level was 3.26 grams per liter (326 mg per dl), and the glucose concentration was 1.1 mmol per liter (20 mg per dl). A regimen of ampicillin and chloramphenicol was started. Cultures of blood and CSF grew Hinfluenzae type B. On the evening of admission, the patient was noted to be in status epilepticus with tonic seizures, compromising his respiratory effort. He was intubated, given phenobarbital, and transferred to the intensive care unit where he stayed overnight. He was then transferred back to the floor, and the rest of his stay in the hospital (about two weeks) was uneventful. Neither an electroencephalogram nor a computed tomographic brain scan was obtained during this admission. The patient was described as having no appreciable neurologic deficit at the time of discharge. No further seizures occurred after discontinuation of the anticonvulsant several months later, and the only possible neurologic deficit was a mild speech delay, accompanied by an articulation disorder that may not have been related to his meningitis. By parental report, developmental milestones were otherwise achieved early or on time. After this illness, the patient had only minor colds until the occurrence of episodes of left hemiparesis. There was no family history or personal history of clotting disorders. The paternal grandmother was known to have migraines. Before and during the admission process, the patient had four episodes of left-sided weakness. The first, lasting ten minutes, occurred while he was sitting quietly. During this episode his left face, arm, and leg became weak and speech was slurred, although consciousness was not impaired. A

second episode, which also lasted ten minutes, occurred six hours later and was similar except that it was accompanied by a headache that could not be localized to any region of the head. No nausea or vomiting occurred, and again the patient remained fully alert. Some three hours later, on arrival at the emergency department, the patient sustained a similar episode lasting 40 minutes, followed by a final episode two hours later, lasting 2 minutes. In this episode his arm was profoundly weak and flaccid, and he could not stand well due to weakness of the left leg. Speech remained unaffected during this last episode. On physical examination he was alert and oriented with an occipitofrontal circumference of 52 cm (50th percentile), weight 25.5 kg (75th percentile), and height 126 cm (75th percentile). The findings of a general physical examination were completely normal. Pulses were strong, symmetric, and without bruits. Between episodes, the patient was noted to have a slight facial droop on the left (central seventh cranial nerve palsy) and mild weakness ofboth extremities on the left side. A Babinski's sign and ankle clonus could be elicited on the left, and clumsiness of movement was demonstrated with the heel-to-shin maneuver. Hopping and rapid alternating movements were likewise impaired on that side. Additional studies were done. A computed tomographic scan obtained at presentation (Figure 1-A) showed a vague region of hypodensity involving the right putamen and globus pallidus, accompanied by a minimal mass effect. A magnetic resonance imaging scan (Figure 1-B) confirmed the presence of a right basal ganglia infarction. Cerebral angiography revealed mild stenosis of the Ml segment of the right middle cerebral artery and a pronounced stenosis of the Al segment of the right anterior cerebral artery (Figure 2). The lenticulostriate branches were more prominent on the ipsilateral side, suggesting a chronic process or "luxury perfusion." Laboratory investigations did not elucidate any definite cause for these vascular events. A rapid plasma reagin test was nonreactive. An erythrocyte sedimentation rate was 1 mm per hour, cholesterol level was 4.14 mmol per liter (160 mg per dl), and triglycerides were 0.85 mmol per liter (75 mg

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per dl). Initial prothrombin and partial thromboplastin times were normal. Screening for homocystinuria was negative. Antithrombin III and protein C levels fell within the normal range. The protein S concentration was slightly diminished (0.58; normal range, 0.66 to 1.12). (This laboratory determination was rechecked months after discharge because it is thought that endogenous anticoagulant levels may be misleading in the acute phase of a vascular illness.8"9 When rechecked, the protein S value was in the normal range.) Anticardiolipin antibodies and lupus anticoagulant were undetectable. An echocardiogram was normal. The patient's hospital course was as follows: A regimen of intravenous heparin and oral warfarin sodium was instituted, with a long-term goal of oral anticoagulation. On the second hospital day, he had another episode of left-sided weakness lasting 12 minutes but then remained stable without similar episodes for three days. At this point, despite an appropriate degree of anticoagulation (prothrombin time 17.2 seconds, partial thromboplastin time 79 seconds), the patient had two more episodes similar in character to previous ones but leaving him with greater residual deficit. A second computed tomographic scan of the brain (Figure 1-C) obtained soon after these episodes showed small hemorrhages in the right globus pallidus and right caudate nucleus with a mild mass effect. Because of this complication, anticoagulation was discontinued. Over the next few days, his condition improved until he reached the functional level described at the time of

his admission. He was then started on aspirin therapy, 160 mg per day, and discharged. A week later his muscle strength had improved somewhat, but tone continued to be increased in his left upper and lower extremities. A Babinski's sign remained on the left, and ankle clonus could be elicited. No further episodes have occurred since discharge. A follow-up examination two years after his original stroke revealed symmetric muscle strength but continued increased tone on the left side, particularly in the lower extremity, and noticeably impaired gross and fine motor skills on this side.

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Discussion This case is thought to represent a delayed consequence of vasculopathy due to H influenzae meningitis, although it is possible that the meningitis and subsequent stroke are coincidental. The proposed mechanism is a meningitis-induced vasculitis leading to a fixed but subclinical stenosis. This was then followed years later by an episode of hypoperfusion by any of several mechanisms (discussed later). The following observations support this contention. First, vascular involvement in childhood meningitis has been demonstrated histologically10-12 and angiographically.4'6'3 Second, cerebral infarction is a recognized complication of meningitis during the acute phase of the illness. 1-3, 14 15 Third, the vasculopathy accompanying childhood meningitis may be persistent,4'7 progressive, or both, thereby leading to vessel stenosis.5 7 The angiographic findings in this child (Figure 2) would be compatible with such long-term effects. Finally, no alterna-

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el, ......I Figure 2.-A. An anteroposterior angiogram reveals mild stenosis of the Ml segment of the right middle cerebral artery (arrowhead) and a marked attenuation of the Al segment of the right anterior cerebral artery (large arrow). Lenticulostriate arteries were enlarged (small arrows), indicating "luxury perfusion" or a chronic process with vascular proliferation. B, An anteroposterior view of the left carotid artery is shown for comparison. Note the absence of changes described for the right side.

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tive explanation for this boy's cerebral infarction could be found. Specifically, there was no apparent infection or inflammatory response and no evidence for a clotting disorder or source of embolic material. There are some questions about the degree of involvement of vasospasm versus organic stenosis or occlusion in the vasculopathy of meningitis and whether organic stenosis or occlusion is permanent. For example, two children with angiographic evidence of cerebral arterial stenosis during an acute meningitic illness and with persistent neurologic deficit were later found to have patent-apparently normalvessels on angiography.6 Another child, however, with angiographic evidence of pronounced stenosis of both internal carotid arteries was found at autopsy to have thickened carotid arteries with mural vasculitis, involvement of the intima, and "marked" luminal narrowing.4 Vasculitis accompanying meningitis is thought to evolve as follows: The intima of cerebral vessels is elevated by polymorphonuclear cell infiltration of the vessel wall, causing luminal narrowing. Long-term effects include the proliferation of connective tissue in the vessel wall with the destruction of smooth muscle fibers, often accompanied by partial or total destruction of the internal elastic lamina, producing a stenotic vessel lumen.7 Yamashita and co-workers have suggested that the initial damage to the media may in part be due to the intense contractions of smooth muscle fibers that accompany the vasospasm presumed to occur with meningitis.5 They too propose that the resultant mural thickening may lead to organic stenosis of major cerebral arteries.5 It is argued that the patient in this case had vasculitis associated with his early meningitis but that infarction did not occur initially or was insufficient to result in clinically detectable effects. Accompanying vasculitis did, however, lead to fixed, organic stenoses of the right anterior and middle cerebral arteries. This could have predisposed the patient to subsequent distal ischemia by several mechanisms. First and most likely, hypotension or hypovolemia might have produced hypoperfusion and ischemia distal to a fixed stenosis, perhaps from a trivial event such as neck bending or twisting.16 Second, an intraluminal thrombus could have developed in the stenotic artery due to turbulent or sluggish blood flow. Third, the stenosis might have progressed in this patient, leading to clinical symptoms. In this regard, Rorke has suggested that the stenotic process can occur over a protracted period of time.7 It is unclear in the present case whether the patient had a fixed stenosis through which flow was later compromised or an evolving stenosis, although because there appears to be no tendency after meningitis for repetitive infarcts, an evolving stenosis is unlikely. Because infarction is often minimal despite marked narrowing of the cerebral vasculature, Rorke suggests that in many cases collateral circulation develops.7 It is interesting that in the case reported here the right lenticulostriate branches were enlarged on angiography and might represent such collateral circulation. In addition, other vasculopathies such as those associated with cranial irradiation have occurred with delayed cerebral infarction.17 In conclusion, the case reported here represents only one of the diverse causes of stroke in children. This is arguably an example of delayed cerebral infarction due to the vasculopathy associated with H influenzae meningitis sustained in

infancy. Other than that this child was generally quite ill with his meningitis as an infant, as is common, he did not seem to

ALERTS, NOTICES, AND CASE REPORTS

have any particular predisposing factor for infarct. It is also unclear if the H influenzae organism causes more vasculitis than others. A prospective or retrospective study to determine the frequency of late vascular events in children following meningitis would be interesting and helpful to sort out these questions. Many such sequelae may now be preventable with the vaccination of infants with the H influenzae type B polysaccharide vaccine. This case suggests that inquiring about a history of early infections is important in children with stroke, much as a history of the Kawasaki syndrome is important in childhood myocardial infarction.'8 REFERENCES 1. Dunn DW, Daum RW, Weisberg L, Vargas R: Ischemic cerebrovascular complications of Haemophilus influenzae meningitis. Arch Neurol 1982; 39:650-652 2. Snyder RD, Stovring J, Cushing AH, Davis LE, Hardy TL: Cerebral infarction in childhood bacterial meningitis. J Neurol Neurosurg Psychiatry 1981; 44:581-585 3. Taft TA, Chusid MJ, Sty JR: Cerebral infarction in Hemophilus influenzae type B meningitis. Clin Pediatr 1986; 25:177-180 4. Lyons EL, Leeds NE: The angiographic demonstration of arterial vascular disease in purulent meningitis. Radiology 1967; 88:935-938 5. Yamashita T, Kashihara K, Ikeda K, Kubota T, Yamamoto S: Three phases of cerebral arteriopathy in meningitis: Vasospasm and vasodilatation followed by organic stenosis. Neurosurgery 1985; 16:546-553 6. Gado M, Axley J, Appleton DB, Prensky AL: Angiography in the acute and post-treatment phases of Hemophilus influenzae meningitis. Radiology 1974; 110:439444 7. Rorke LB: Pathology of cerebral vascular disease in children and adolescents, In Edwards MSB, Hoffman JH (Eds): Cerebral Vascular Disease in Children and Adolescents. Baltimore, Md, Williams & Wilkins, 1989, pp 95-138 8. Camerlingo M, Finazzi G, Casto L, Laffranchi C, Barbui T, Mamoli A: Inherited protein C deficiency and nonhemorrhagic arterial stroke in young adults. Neurology 1991; 41:1371-1373 9. Dolan G, Ball J, Preston F: Protein C and protein S. Bailliere's Clin Haematol 1989; 2:999-1042 10. Adams RD, Kubik CS, Bonner FJ: The clinical and pathological aspects of influenzae meningitis. Arch Pediatr 1948; 65:354-376, 408-441 11. Smith JF, Landing BH: Mechanisms of brain damage in H. influenzae meningitis. J Neuropathol Exp Neurol 1960; 19:248-265 12. Dodge PR, Swartz MN: Bacterial meningitis-A review of selected aspects. N Engl J Med 1965; 272:1003-1010 13. Igarashi M, Gilmartin RC, Gerald B, Wilbum F, Jabbour JT: Cerebral arteritis and bacterial meningitis. Arch Neurol 1984; 41:531-535 14. Pomeroy SL, Holmes SJ, Dodge PR, Feigin RD: Seizures and other neurologic sequelae of bacterial meningitis in children. N Engl J Med 1990; 323:1651-1657 15. Cabral DA, Flodmark 0, Farrell K, Speert DP: Prospective study of computed tomography in acute bacterial meningitis. J Pediatr 1987; 111:201-205 16. Schuman RM: The molecular biology of occlusive stroke in childhood. Neurol Clin 1990; 8:553-570 17. Mitchell WG, Fishman LS, Miller JH, et al: Stroke as a later sequela of cranial irradiation for childhood brain tumors. J Child Neurol 1991; 6:128-133 18. Shackelford PG, Strauss AW: Kawasaki syndrome (Editorial). N Engl J Med

1991; 324:1664-1666

Ehrlichiosis in a Visitor to Virginia ROBERT W. ARMSTRONG, MD Los Gatos, California

HUMAN EHRLICHIOSIS has only recently been described in the United States. Of the more than 100 cases reported, almost all have occurred in the Southeast or the South Central states.23 We describe a case in a California resident who almost certainly acquired the disease in Virginia. This case, which as of this date is the first reported from California, illustrates the severity of the illness and the multiple manifestations that can occur, including pneumonitis, meningoencephalitis, hepatitis, hyponatremia, and hematologic abnormalities. (Armstrong RW: Ehrlichiosis in a visitor to Virginia. West J Med 1992 Aug; 157:182-184) From the Department of Medicine, Community Hospital and Rehabilitation Center, Los Gatos, California. Reprint requests to Robert W. Armstrong, MD, 340 Dardanelli Ln, Ste 26, Los Gatos, CA 95030.

Cerebral infarction as a remote complication of childhood Haemophilus influenzae meningitis.

THE WESTERN JOURNAL OF MEDICINE AUGUST 1992 157 2 179 a family history of similar disorders. Another disorder that must be excluded is the autoim...
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