Article abstractAcute right hemiplegia and transient expressive aphasia occurred in a 7-year-oldgirl a few days after nonspecific constitutional symptoms and the appearanceof a large right submandibular lymph node. Biopsy of this node and lack of other evident cause suggesteda diagnosis of cat-scratchdisease. Carotid arteriographyshowed a localized arteritis of the supraclinoid part of the left internal carotid artery and the left middle cerebral artery, involving also some lenticulostriate vessels. Computerizedtomography demonstrated infarction in the left internal capsule. The size of this infarct and the angiographic abnormalities improved 6 weeks after onset, and coincided with clinical recovery. Cat-scratch disease may have caused the localized arteritis. NEUROLOGY 29: 1413-1418, October 1979
Cerebral arteritis in cabscratch disease George Selby and Grant L. Walker Since cat-scratch disease (CSD)was first described by Debre' and co-workers,l some 600 papers have appeared throughout the world. A review by Warwick2deals fully with the difficulties in diagnosing this syndrome, its atypical features, and the variations in pathology of lymph nodes. The causative agent is still unknown3 despite intensive use of all common techniques of viral, bacteriologic, mycologic, and tissue culture, as well as antibody and complement fixation studies. The viruses of herpex simplex a n d of t h e psittacosis-ornithosis-lymphogranuloma venereum-trachoma (POLT) group, as well as atypical acid-fast mycobacteria, have been implicated,* but the findings were inconclusive. The histopathologic features of lymph nodes are not specific, but include granulomas surrounded by a mixture of inflammatory cells, which later progress to microabscesses. The histologic appearance is difficult to distinguish from atypical mycobacterial infections, tuberculosis, tularemia, pyogenic lymphadenitis, lymphogranuloma,venereum, and Hodgkin disease. The clinical diagnosis of CSD should be suspected from a history of a cat scratch or bite, or similar injury to the skin, followed in a few days by macular or vesicular skin lesions at the inoculation site and enlargement of regional lymph nodes. The nodes may enlarge progressively and suppurate; they may be tender or painless. Mild constitutional symptoms include fever, malaise, anorexia, abdominal pain, and myalgia. The criteria required for a diagnosis of CSD4 comprise lymphadenitis, a positive Hanger-Rose skin test using
sterilized pus, preferably from a pool of donors, as antigen (but false positives are not uncommon), a primary lesion at the inoculation site, contact with cats, and exclusion of other diseases, particularly atypical mycobaderial infections. Most cases run a benign course, but a few complications have been reported, including rash, erythema nodosum, erythema multiforme, thrombocytopenic purpura, osteolytic bone lesions in the metatarsal head, mesenteric lymphadenitis, and the oculoglandular syndrome of Parinaud (in which a single granulomatous lesion of the conjunctiva is accompanied by preauricular lymphadenitis and constitutional symptoms). The first case of encephalitis associated with CSD was reported by Stevens5in a 13-year-oldboy who had convulsions, focal cerebral signs, and coma, but recovered in a few days. Warwick2 found 33 reports of neurologic complications; 20 were definite cases of encephalitis or encephalomyelitis, and there were two deaths, but most patients recovered without neurologic residua. No cases of hemiplegia have been reported. In most instances, neurologic symptoms appeared 1to 6 weeks after the onset of lymphadenopathy. Lyon6 summarized the clinical features of 19 later cases of encephalitis or encephalomyelitis associated with CSD and added a further case; 19 patients made a complete recovery, and 1was left with mild residual symptoms. Apart from encephalitis, encephalomyelitis and isolated cases of radiculitis, we have been unable to find reports of other neurologic complications of CSD. No case of cerebral arterial disease has been
From the Department of Neurology, the Royal North Shore Hospital, Sydney, Australia. Accepted for publication March 10, 1979. Address reprint requests to Dr. Selby, Department of Neurology, Royal North Shore Hospital, Sydney, Australia.
October 1979 NEUROLOGY 29 1413
Cerebral arteritis in cat-scratch disease
Figure 1 . Cervical lymph node showing a stellate microabscess containing polymorph neutrophils and surrounded by pale histiocytes. x 60.
reported. We now present such a case. Case report. A 7-year-old schoolgirl was admitted on May 2, 1978. Her birth and development were normal, and there was no history of any allergic disorder or other relevant illness. There was no family history of cerebrovascular or allergic disease. During the 2 months preceding admission she had infrequent, mild, and nonspecific headaches, which required no medication. Five days before admission, a large and slightly tender mass appeared in the right submandibular region. For 2 days, she was lethargic and vaguely “off color,” but did not complain of headache. She was restless during sleep, and when she awoke on the morning of admission, she was unable to speak and had a complete right hemiplegia. There was a cat in the family but no history of recent bite or scratch. On admission, there was a complete expressive aphasia, but she understood and responded to verbal requests. Peripheral visual fields were full to confrontation. Optic disks and retinal vessels were normal, and no retinal hemorrhages or exudates were seen. A dense, flaccid right hemiplegia included the face. Tendon reflexes were increased in the right limbs, and the right plantar response was extensor. She appeared able to feel
1414 NEUROLOGY 29 October 1979
pain on both sides of the body. No cervical or cranial bruits were audible. There were no cardiac murmurs; blood pressure was 170/100 mm Hg, but fell within 24 hours and then remained at normal levels. She was lethargic but cooperative. A firm, mobile, and slightly tender mass measuring about 4 cm in diameter was felt in the right submandibular region. Mild bilateral cervical lymphadenopathy was also noted without obvious infection in the pharynx or tonsils. A slightly indurated area of erythema was found on her chin. A provisional diagnosis of thrombosis of a branch of the left middle cerebral artery was made. Computerized tomography (CT) 12 hours after the onset of hemiplegia showed an area of decreased density in the region of the left internal capsule. This did not enhance with contrast, and only a minimal deformity of the anterior horn and body of the left lateral ventricle was seen. Cerebrospinal fluid (CSF) pressure was 200 mm; the clear CSF contained no cells; protein, 19.0 mg per deciliter, and sugar, 3.4 mmol per liter were normal. Culture of the CSF was sterile. Radiograms of skull and chest were clear. The electrocardiogram showed sinus arrhythmia and an incomplete right bundle branch block, but no other abnormalities. Serum chemistry was entirely normal for her age. Blood count was normal, with a hemoglobin of 11.3 g per deciliter and a white cell count of 8900 per
Figure 2. Left carotid arteriogram showing "beading" and narrowing of terminal part of internal carotid artery and of middle cerebral artery.
cubic millimeter with a normal distribution. Platelet count was 215,000per cubic millimeter, but erythrocyte sedimentation rate (ESR)was 76 mm per hour and remained abnormal for 21 days. During the first 6 days, she had a spiking fever with temperatures of 38" C or more each evening. Repeated blood cultures were sterile. Mantoux test. and avian skin test were negative, as was the Monospot test for infectious mononucleosis and tests for hepatitis B antigen and antibody. An echogram of the right submandibular mass showed that it was solid. This mass was excised 9 days after admission and was found to be an enlarged deep cervical lymph node, measuring 2.5 by 2 by 1.5 cm. It contained creamy pus, and the walls were matted and
partly adherent to the right sternomastoid muscle, carotid artery, and jugular vein, indicative of chronic inflammation. On microscopic examination, it was a chronically inflamed lymph node with dense pericapsular fibrosis; the normal nodal architecture had been obliterated by an irregular proliferation of large, pale histiocytes surrounding microabscesses of a stellate configuration (figure 1).No granulomas were seen. The capsular vessels appeared normal. No acid-fast bacilli or other organisms were found in the histologic sections. The pathologist interpreted the histologic appearances of this lymph node as consistent with CSD or atypical mycobacterial infection. Culture of pus from the gland failed to grow acid-fast bacilli or other pathogens, and
October 1879 NEUROLOGY 29 1415
Cerebral arteritis in cat-scratch disease guinea-pig inoculation was negative. Serologic studies for psittacosisllymphogranuloma venereum organisms and €or herpes simplex, mumps, measles, and Coxsackie B1 to Bs virus showed no evidence of recent infection. When the diagnosis of CSD was suggested, we ascertained that there was a cat in the family. The small indurated area of erythema on the child‘s chin may have been the site of primary inoculation. The antigen for the Hanger-Rose skin test was not available. Bilateral carotid angiography was performed by femoral catheterization 6 days after admission. The intracranial part of the left internal carotid artery was “beaded,” and this marked irregularity continued into the narrowed left middle cerebral artery (figure 2). The contrast material later filled the left middle cerebral
artery through cortical anastomoses, indicating a “functional” occlusion of the left middle cerebral artery. The extracranial part of the left internal carotid artery and the right internal carotid artery and its branches showed no abnormality. The angiographic findings suggested cerebral arteritis, localized to the distal part of the left internal carotid artery and proximal part of the left middle cerebral artery. This motivated a search for a more widespread systemic arteritis or immune complex disease. After blood was drawn for immunologic investigations, the child was treated with adrenal steroids in decreasing doses for 4 weeks. Immunofluorescence studies of the excised lymph node showed no deposition of immunoglobulin in the blood vessels. No abnormalities in renal function
Figure 3. Left carotid arterwgram obtained 5 weeks after the first arteriogram. The left internal carotid and middle cerebral arteries are still narrow, but are no longer “beaded.”
1416 NEUROLOGY 29 October 1979
were discovered from serum chemistry and repeated microscopic examination of urinary sediment; 24-hour urine protein excretion was zero. Creatinine clearance was 114 ml per minute when corrected. Tests for antinuclear and rheumatoid factors were negative. Immunoelectrophoresis of serum proteins and serum complement levels were normal, and DNA antibody binding of 13 percent was within the normal range. Specific studies of Clq, C3, C4, factor B, C5, and CH50 were also normal; lymphocyte antibodies of 2 percent and Clq-BA of 8 percent were all within the normal range. Only the ASOT titer was raised to 625 units. Some recovery of speech appeared 5 days after admission, and the right hemiplegia began to improve a week later. When the child was discharged on June 23,1978 (52 days after admission), her speech was normal. The right central facial palsy had recovered completely. She still had a moderate right hemiparesis but could walk unaided, dragging the right leg. There was no objective sensory impairment. Tendon reflexes were increased in the right limbs, and the right plantar response was extensor. The ESR had fallen to 13mm in 1hour 3 weeks after admission, and was normal at 7 mm in 1hour after a further week. Bilateral carotid angiography 41 days after admission showed that the left internal carotid artery was still decreased in diameter but was no longer “beaded.” There was still marked narrowing of the left middle cerebral artery, but the outline was smooth (figure 3). Delayed filling of the left middle cerebral artery from cortical surface collaterals was still evident. A CT 52 days after onset showed a small area of decreased attenuation bordering on CSF density in the region of the left caudate nucleus; this was not enhanced by contrast injection. The left lateral ventricle had become slightly enlarged (figure 4). When she was examined again 5 months after onset, further improvement in the right hemiparesis was noted, but tendon reflexes were still increased on the right, and the right plantar response remained extensor. She was clumsy, with alternating movements of the right hand and foot. She had returned to school in July 1978, soon after discharge from the hospital, but had a short attention span and some restless and hyperactive behavior. (Similar behavior disorders in children recovering from focal cerebral infarction were mentioned by Gold and Carter.7) Psychometric tests 17 weeks after the ictus showed no intellectual impairment. Verbal Score I& was 109, Performance Scale I& 104, and Full Scale I& 107.
Discussion. The etiology, pathogenesis, and clinical varieties of acute hemiplegia of infancy and childhood have been the subjects of many reand Shillito9 drew attention t o carotid arteritis as a cause. A useful classification of primary nonembolic cerebral arterial occlusions in children, based on angiographic features, was proposed by Hilal and associates.1° In 17 hemiplegic children where the nonembolic arterial occlusion was not the result of trauma, inflammation, or neoplasia, they found five groups of cerebral arteriographic findings with specific features. Group I included seven chil-
Figure 4 . CT brain scan, showing area of decreased attenuation in the region of the left caudate nucleus.
dren whose arteriograms showed basal arterial occlusions without telangiectasia. The angiographic characteristics consisted of a unilateral severe stenosis or complete occlusion of the supraclinoid segment of the internal carotid artery with adaptive narrowing of this artery proximal to the occlusive lesions. In every case, the stenosis extended distally into the horizontal segment of the middle cerebral artery, and the anterior cerebral artery was involved in three of the four cases where it was opacified on the films. The lenticulostriate branches, particularly those near the internal carotid bifurcation, were usually affected. Follow-up angiography was performed in four of the seven children at intervals from 6 months to 7 years, and showed varying degrees of recanalization of the involved segment of the artery, which, however, remained smaller than the opposite internal carotid. The children were between 1and 12 years old. The predominant weakness of the arm compared to the leg was attributed to filling of the anterior cerebral artery from the normal internal carotid of the opposite side, and to the involvement of lenticulostriate arteries arising from the medial segment of the middle cerebral artery, which supply the parts of the internal capsule containing the corticospinal fibers to the upper limb and trunk. Although “beading” of the arterial segments was not noted by Hilal and associates,lo the clinical and angiographic features
October 1979 NEUROLOGY 29 1417
Cerebral arteritis in cat-scratch disease
of our patient were those described in group I of their series. Their other groups-moyamoya disease, stenosis of the cervical internal carotid artery, distal branch occlusion, and small artery disease-were not applicable to the case under discussion. There are many causes of cerebral arteritis. Ferris and Levinell mentioned that the arteriographic features are often nonspecific, and that the pathologic findings in childhood arteritis may include inflammatory changes consisting of perivascular infiltration with polymorphs and fibrinoid necrosis of the media. Inflammatory disease has been suggested as a cause of childhood arteritis, and one case of viral arteritis was reported in a young boy following herpes zoster ophthalmicus.12 Arterial “beading” was seen in the angiograms. Arterial “beading”was a spectacular feature in the first arteriogram of our patient (figure 21, but is not specific. Similar irregularities have been described in basal meningitis (tuberculousor fungal), meningovascular syphilis, intracranial neoplasm,13 trauma,’* migraine,’S atherosclerosis, polyarteritis nodosa, lupus erythematosus, allergic granulomatosis, and temporal arteritis. In most cases, in contrast to our patient, the vascular irregularities are bilateral. In some cases of inflammatory arteritis in childhood, the extracranial segment of the artery was in close contact with some infection in the throat or neck. Although our patient had mild bilateral lymphadenopathy, the large infected gland that was biopsied was on the side opposite the localized arteritis. Therefore, an immunologic reaction was considered. No specific immunologic abnormalities have been reported in CSD. Campbell16 expressed the view that cellmediated hypersensitivity develops in CSD. He observed acute arteritis in afYected lymph glands and suggested that immune complex reactions between antigen, antibody, and complement might be involved in these sites. These immune complexes could also be responsible for the local release of substances such as histamine and serotonin, which might cause the extranodal inflammatory changes of CSD. Schulkind and Ayoub17 investigated the cellmediated immune status of eight patients with CSD and age-matched control individuals. Only CSD patients had cutaneous responses to catscratch antigens, and the lymphocyte transformation responses to phytohemagglutininand Candida albicans were significantly depressed in all CSD patients with active disease when compared with the controls. They conclude that patients with CSD in the acute phase had a transient state of lymphocyte unresponsiveness, similar to that observed in other infections caused by viruses or mycop1asms. In the child reported here, there was a clear 1418 NEUROLOGY 29 October 1979
temporal association between the appearance of a large right submandibular lymph node, histologically consistent with CSD, and localized arteritis of the terminal left internal carotid artery and its branches. Recovery from all the clinical manifestations of the infection attributed to CSD and improvement in the aphasia and right hemiplegia also coincided. The child was treated only with prednisone, and no antibiotics were administered. Although CSD is not uncommon, localized arteritis of the type shown in the angiograms of our patient is infrequent. A causal connection between the two diseases appears to be more than a coincidence. Acknowledgments We thank Dr. Judith Fryer, Department of Anatomical Pathology, Royal North Shore Hospital of Sydney, for helpful advice on the histopathology of the excised lymph node, and Dr. James Roche, Department of Diagnostic Radiology, Royal North Shore Hospital of Sydney, for valuable comments and assistance in the preparation of illustrations from the angiograms.
References 1. Debre R, Lamy M, Jammet ML, e t al: La maladie des griffes de chat. Sem Hop Paris 26:1895-1904, 1950 2. Warwick WJ: The cat-scratch syndrome: Many diseases or one disease? h o g Med Virol 9:256-301, 1967 3. Emmons RW, Riggs JL, Schachter J: Continuing search for the etiology of cat-scratch disease. J Clin Microbiol4:112114, 1976 4. Carithers HA, Carithers CM, Edwards RO: Cat-scratch disease: Its natural history. JAMA 207:312-316, 1969 5. Stevens H: Cat-scratch fever encephalitis. Am J Dis Child 84218-222, 1952 6. Lyon LW: Neurologic manifestations of cat-scratch disease. Arch Neurol 25:23-27, 1971 7. Gold AP, Carter S: Acute hemiplegia of infancy and childhood. Pediatr Clin North Am 23:413-433, 1976 8. B i c k e r s M E R Aetiology of acute hemiplegia in childhood. Br Med J 282-87, 1964 9. Shillito J Jr: Carotid arteritis: A cause of hemiplegia in childhood. J Neurosurg 21:540-551, 1964 10. Hilal SK, Solomon GE, Gold AP,e t al: Primary cerebral arterial occlusive disease in children: Rrt 1. Acute acquired hemiplegia. Radiology 99:71-86, 1971 11. Ferris EJ, Levine HL: Cerebral arteritis: Classification. Radiology 109:327-341, 1973 12. Walker RJ 111,El Gamma1T, Allen MB Jr: Cranial arteritis associated with herpes zoster: Case report with angiographic findings. Radiology 107:109-110, 1973 13. Leeds NE, Rosenblatt R Arterial wall irregularities in intracranial neoplasms: The shaggy vessel brought into focus. Radiology 103:121-124, 1972 14. Rumbaugh CL, Bergeron RT, Kurze T: Intracranial vascular damage associated with skull fractures: Radiographic aspects. Radiology 104:81-87, 1972 15. George AE, Kishore PRS,Chase NE: Primary diseases of the cerebral blood vessels. Semin Roentgen01 6:34-47,1971 16. Campbell JAH: Cat-scratch disease. In Sommers SC, Rosen PP (Editors): Pathology Annual Part 1. New York, Appleton-Century-Crofts, 1977, vol 12, pp 277-292 17. Schulkind ML, Ayoub E M Cell-mediated immunity in cat-scratch disease. J Pediatr 85199-203, 1974
Cerebral arteritis in cat−scratch disease George Selby and Grant L. Walker Neurology 1979;29;1413-1418 DOI 10.1212/WNL.29.10.1413 This information is current as of October 1, 1979 Updated Information & Services
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Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright ©1979Advanstar Communications, Inc.. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
Cerebral arteritis in cabscratch disease George Selby and Grant L. Walker Since cat-scratch disease (CSD)was first described by Debre' and co-workers,l some 600 papers have appeared throughout the world. A review by Warwick2deals fully with the difficulties in diagnosing this syndrome, its atypical features, and the variations in pathology of lymph nodes. The causative agent is still unknown3 despite intensive use of all common techniques of viral, bacteriologic, mycologic, and tissue culture, as well as antibody and complement fixation studies. The viruses of herpex simplex a n d of t h e psittacosis-ornithosis-lymphogranuloma venereum-trachoma (POLT) group, as well as atypical acid-fast mycobacteria, have been implicated,* but the findings were inconclusive. The histopathologic features of lymph nodes are not specific, but include granulomas surrounded by a mixture of inflammatory cells, which later progress to microabscesses. The histologic appearance is difficult to distinguish from atypical mycobacterial infections, tuberculosis, tularemia, pyogenic lymphadenitis, lymphogranuloma,venereum, and Hodgkin disease. The clinical diagnosis of CSD should be suspected from a history of a cat scratch or bite, or similar injury to the skin, followed in a few days by macular or vesicular skin lesions at the inoculation site and enlargement of regional lymph nodes. The nodes may enlarge progressively and suppurate; they may be tender or painless. Mild constitutional symptoms include fever, malaise, anorexia, abdominal pain, and myalgia. The criteria required for a diagnosis of CSD4 comprise lymphadenitis, a positive Hanger-Rose skin test using
sterilized pus, preferably from a pool of donors, as antigen (but false positives are not uncommon), a primary lesion at the inoculation site, contact with cats, and exclusion of other diseases, particularly atypical mycobaderial infections. Most cases run a benign course, but a few complications have been reported, including rash, erythema nodosum, erythema multiforme, thrombocytopenic purpura, osteolytic bone lesions in the metatarsal head, mesenteric lymphadenitis, and the oculoglandular syndrome of Parinaud (in which a single granulomatous lesion of the conjunctiva is accompanied by preauricular lymphadenitis and constitutional symptoms). The first case of encephalitis associated with CSD was reported by Stevens5in a 13-year-oldboy who had convulsions, focal cerebral signs, and coma, but recovered in a few days. Warwick2 found 33 reports of neurologic complications; 20 were definite cases of encephalitis or encephalomyelitis, and there were two deaths, but most patients recovered without neurologic residua. No cases of hemiplegia have been reported. In most instances, neurologic symptoms appeared 1to 6 weeks after the onset of lymphadenopathy. Lyon6 summarized the clinical features of 19 later cases of encephalitis or encephalomyelitis associated with CSD and added a further case; 19 patients made a complete recovery, and 1was left with mild residual symptoms. Apart from encephalitis, encephalomyelitis and isolated cases of radiculitis, we have been unable to find reports of other neurologic complications of CSD. No case of cerebral arterial disease has been
From the Department of Neurology, the Royal North Shore Hospital, Sydney, Australia. Accepted for publication March 10, 1979. Address reprint requests to Dr. Selby, Department of Neurology, Royal North Shore Hospital, Sydney, Australia.
October 1979 NEUROLOGY 29 1413
Cerebral arteritis in cat-scratch disease
Figure 1 . Cervical lymph node showing a stellate microabscess containing polymorph neutrophils and surrounded by pale histiocytes. x 60.
reported. We now present such a case. Case report. A 7-year-old schoolgirl was admitted on May 2, 1978. Her birth and development were normal, and there was no history of any allergic disorder or other relevant illness. There was no family history of cerebrovascular or allergic disease. During the 2 months preceding admission she had infrequent, mild, and nonspecific headaches, which required no medication. Five days before admission, a large and slightly tender mass appeared in the right submandibular region. For 2 days, she was lethargic and vaguely “off color,” but did not complain of headache. She was restless during sleep, and when she awoke on the morning of admission, she was unable to speak and had a complete right hemiplegia. There was a cat in the family but no history of recent bite or scratch. On admission, there was a complete expressive aphasia, but she understood and responded to verbal requests. Peripheral visual fields were full to confrontation. Optic disks and retinal vessels were normal, and no retinal hemorrhages or exudates were seen. A dense, flaccid right hemiplegia included the face. Tendon reflexes were increased in the right limbs, and the right plantar response was extensor. She appeared able to feel
1414 NEUROLOGY 29 October 1979
pain on both sides of the body. No cervical or cranial bruits were audible. There were no cardiac murmurs; blood pressure was 170/100 mm Hg, but fell within 24 hours and then remained at normal levels. She was lethargic but cooperative. A firm, mobile, and slightly tender mass measuring about 4 cm in diameter was felt in the right submandibular region. Mild bilateral cervical lymphadenopathy was also noted without obvious infection in the pharynx or tonsils. A slightly indurated area of erythema was found on her chin. A provisional diagnosis of thrombosis of a branch of the left middle cerebral artery was made. Computerized tomography (CT) 12 hours after the onset of hemiplegia showed an area of decreased density in the region of the left internal capsule. This did not enhance with contrast, and only a minimal deformity of the anterior horn and body of the left lateral ventricle was seen. Cerebrospinal fluid (CSF) pressure was 200 mm; the clear CSF contained no cells; protein, 19.0 mg per deciliter, and sugar, 3.4 mmol per liter were normal. Culture of the CSF was sterile. Radiograms of skull and chest were clear. The electrocardiogram showed sinus arrhythmia and an incomplete right bundle branch block, but no other abnormalities. Serum chemistry was entirely normal for her age. Blood count was normal, with a hemoglobin of 11.3 g per deciliter and a white cell count of 8900 per
Figure 2. Left carotid arteriogram showing "beading" and narrowing of terminal part of internal carotid artery and of middle cerebral artery.
cubic millimeter with a normal distribution. Platelet count was 215,000per cubic millimeter, but erythrocyte sedimentation rate (ESR)was 76 mm per hour and remained abnormal for 21 days. During the first 6 days, she had a spiking fever with temperatures of 38" C or more each evening. Repeated blood cultures were sterile. Mantoux test. and avian skin test were negative, as was the Monospot test for infectious mononucleosis and tests for hepatitis B antigen and antibody. An echogram of the right submandibular mass showed that it was solid. This mass was excised 9 days after admission and was found to be an enlarged deep cervical lymph node, measuring 2.5 by 2 by 1.5 cm. It contained creamy pus, and the walls were matted and
partly adherent to the right sternomastoid muscle, carotid artery, and jugular vein, indicative of chronic inflammation. On microscopic examination, it was a chronically inflamed lymph node with dense pericapsular fibrosis; the normal nodal architecture had been obliterated by an irregular proliferation of large, pale histiocytes surrounding microabscesses of a stellate configuration (figure 1).No granulomas were seen. The capsular vessels appeared normal. No acid-fast bacilli or other organisms were found in the histologic sections. The pathologist interpreted the histologic appearances of this lymph node as consistent with CSD or atypical mycobacterial infection. Culture of pus from the gland failed to grow acid-fast bacilli or other pathogens, and
October 1879 NEUROLOGY 29 1415
Cerebral arteritis in cat-scratch disease guinea-pig inoculation was negative. Serologic studies for psittacosisllymphogranuloma venereum organisms and €or herpes simplex, mumps, measles, and Coxsackie B1 to Bs virus showed no evidence of recent infection. When the diagnosis of CSD was suggested, we ascertained that there was a cat in the family. The small indurated area of erythema on the child‘s chin may have been the site of primary inoculation. The antigen for the Hanger-Rose skin test was not available. Bilateral carotid angiography was performed by femoral catheterization 6 days after admission. The intracranial part of the left internal carotid artery was “beaded,” and this marked irregularity continued into the narrowed left middle cerebral artery (figure 2). The contrast material later filled the left middle cerebral
artery through cortical anastomoses, indicating a “functional” occlusion of the left middle cerebral artery. The extracranial part of the left internal carotid artery and the right internal carotid artery and its branches showed no abnormality. The angiographic findings suggested cerebral arteritis, localized to the distal part of the left internal carotid artery and proximal part of the left middle cerebral artery. This motivated a search for a more widespread systemic arteritis or immune complex disease. After blood was drawn for immunologic investigations, the child was treated with adrenal steroids in decreasing doses for 4 weeks. Immunofluorescence studies of the excised lymph node showed no deposition of immunoglobulin in the blood vessels. No abnormalities in renal function
Figure 3. Left carotid arterwgram obtained 5 weeks after the first arteriogram. The left internal carotid and middle cerebral arteries are still narrow, but are no longer “beaded.”
1416 NEUROLOGY 29 October 1979
were discovered from serum chemistry and repeated microscopic examination of urinary sediment; 24-hour urine protein excretion was zero. Creatinine clearance was 114 ml per minute when corrected. Tests for antinuclear and rheumatoid factors were negative. Immunoelectrophoresis of serum proteins and serum complement levels were normal, and DNA antibody binding of 13 percent was within the normal range. Specific studies of Clq, C3, C4, factor B, C5, and CH50 were also normal; lymphocyte antibodies of 2 percent and Clq-BA of 8 percent were all within the normal range. Only the ASOT titer was raised to 625 units. Some recovery of speech appeared 5 days after admission, and the right hemiplegia began to improve a week later. When the child was discharged on June 23,1978 (52 days after admission), her speech was normal. The right central facial palsy had recovered completely. She still had a moderate right hemiparesis but could walk unaided, dragging the right leg. There was no objective sensory impairment. Tendon reflexes were increased in the right limbs, and the right plantar response was extensor. The ESR had fallen to 13mm in 1hour 3 weeks after admission, and was normal at 7 mm in 1hour after a further week. Bilateral carotid angiography 41 days after admission showed that the left internal carotid artery was still decreased in diameter but was no longer “beaded.” There was still marked narrowing of the left middle cerebral artery, but the outline was smooth (figure 3). Delayed filling of the left middle cerebral artery from cortical surface collaterals was still evident. A CT 52 days after onset showed a small area of decreased attenuation bordering on CSF density in the region of the left caudate nucleus; this was not enhanced by contrast injection. The left lateral ventricle had become slightly enlarged (figure 4). When she was examined again 5 months after onset, further improvement in the right hemiparesis was noted, but tendon reflexes were still increased on the right, and the right plantar response remained extensor. She was clumsy, with alternating movements of the right hand and foot. She had returned to school in July 1978, soon after discharge from the hospital, but had a short attention span and some restless and hyperactive behavior. (Similar behavior disorders in children recovering from focal cerebral infarction were mentioned by Gold and Carter.7) Psychometric tests 17 weeks after the ictus showed no intellectual impairment. Verbal Score I& was 109, Performance Scale I& 104, and Full Scale I& 107.
Discussion. The etiology, pathogenesis, and clinical varieties of acute hemiplegia of infancy and childhood have been the subjects of many reand Shillito9 drew attention t o carotid arteritis as a cause. A useful classification of primary nonembolic cerebral arterial occlusions in children, based on angiographic features, was proposed by Hilal and associates.1° In 17 hemiplegic children where the nonembolic arterial occlusion was not the result of trauma, inflammation, or neoplasia, they found five groups of cerebral arteriographic findings with specific features. Group I included seven chil-
Figure 4 . CT brain scan, showing area of decreased attenuation in the region of the left caudate nucleus.
dren whose arteriograms showed basal arterial occlusions without telangiectasia. The angiographic characteristics consisted of a unilateral severe stenosis or complete occlusion of the supraclinoid segment of the internal carotid artery with adaptive narrowing of this artery proximal to the occlusive lesions. In every case, the stenosis extended distally into the horizontal segment of the middle cerebral artery, and the anterior cerebral artery was involved in three of the four cases where it was opacified on the films. The lenticulostriate branches, particularly those near the internal carotid bifurcation, were usually affected. Follow-up angiography was performed in four of the seven children at intervals from 6 months to 7 years, and showed varying degrees of recanalization of the involved segment of the artery, which, however, remained smaller than the opposite internal carotid. The children were between 1and 12 years old. The predominant weakness of the arm compared to the leg was attributed to filling of the anterior cerebral artery from the normal internal carotid of the opposite side, and to the involvement of lenticulostriate arteries arising from the medial segment of the middle cerebral artery, which supply the parts of the internal capsule containing the corticospinal fibers to the upper limb and trunk. Although “beading” of the arterial segments was not noted by Hilal and associates,lo the clinical and angiographic features
October 1979 NEUROLOGY 29 1417
Cerebral arteritis in cat-scratch disease
of our patient were those described in group I of their series. Their other groups-moyamoya disease, stenosis of the cervical internal carotid artery, distal branch occlusion, and small artery disease-were not applicable to the case under discussion. There are many causes of cerebral arteritis. Ferris and Levinell mentioned that the arteriographic features are often nonspecific, and that the pathologic findings in childhood arteritis may include inflammatory changes consisting of perivascular infiltration with polymorphs and fibrinoid necrosis of the media. Inflammatory disease has been suggested as a cause of childhood arteritis, and one case of viral arteritis was reported in a young boy following herpes zoster ophthalmicus.12 Arterial “beading” was seen in the angiograms. Arterial “beading”was a spectacular feature in the first arteriogram of our patient (figure 21, but is not specific. Similar irregularities have been described in basal meningitis (tuberculousor fungal), meningovascular syphilis, intracranial neoplasm,13 trauma,’* migraine,’S atherosclerosis, polyarteritis nodosa, lupus erythematosus, allergic granulomatosis, and temporal arteritis. In most cases, in contrast to our patient, the vascular irregularities are bilateral. In some cases of inflammatory arteritis in childhood, the extracranial segment of the artery was in close contact with some infection in the throat or neck. Although our patient had mild bilateral lymphadenopathy, the large infected gland that was biopsied was on the side opposite the localized arteritis. Therefore, an immunologic reaction was considered. No specific immunologic abnormalities have been reported in CSD. Campbell16 expressed the view that cellmediated hypersensitivity develops in CSD. He observed acute arteritis in afYected lymph glands and suggested that immune complex reactions between antigen, antibody, and complement might be involved in these sites. These immune complexes could also be responsible for the local release of substances such as histamine and serotonin, which might cause the extranodal inflammatory changes of CSD. Schulkind and Ayoub17 investigated the cellmediated immune status of eight patients with CSD and age-matched control individuals. Only CSD patients had cutaneous responses to catscratch antigens, and the lymphocyte transformation responses to phytohemagglutininand Candida albicans were significantly depressed in all CSD patients with active disease when compared with the controls. They conclude that patients with CSD in the acute phase had a transient state of lymphocyte unresponsiveness, similar to that observed in other infections caused by viruses or mycop1asms. In the child reported here, there was a clear 1418 NEUROLOGY 29 October 1979
temporal association between the appearance of a large right submandibular lymph node, histologically consistent with CSD, and localized arteritis of the terminal left internal carotid artery and its branches. Recovery from all the clinical manifestations of the infection attributed to CSD and improvement in the aphasia and right hemiplegia also coincided. The child was treated only with prednisone, and no antibiotics were administered. Although CSD is not uncommon, localized arteritis of the type shown in the angiograms of our patient is infrequent. A causal connection between the two diseases appears to be more than a coincidence. Acknowledgments We thank Dr. Judith Fryer, Department of Anatomical Pathology, Royal North Shore Hospital of Sydney, for helpful advice on the histopathology of the excised lymph node, and Dr. James Roche, Department of Diagnostic Radiology, Royal North Shore Hospital of Sydney, for valuable comments and assistance in the preparation of illustrations from the angiograms.
References 1. Debre R, Lamy M, Jammet ML, e t al: La maladie des griffes de chat. Sem Hop Paris 26:1895-1904, 1950 2. Warwick WJ: The cat-scratch syndrome: Many diseases or one disease? h o g Med Virol 9:256-301, 1967 3. Emmons RW, Riggs JL, Schachter J: Continuing search for the etiology of cat-scratch disease. J Clin Microbiol4:112114, 1976 4. Carithers HA, Carithers CM, Edwards RO: Cat-scratch disease: Its natural history. JAMA 207:312-316, 1969 5. Stevens H: Cat-scratch fever encephalitis. Am J Dis Child 84218-222, 1952 6. Lyon LW: Neurologic manifestations of cat-scratch disease. Arch Neurol 25:23-27, 1971 7. Gold AP, Carter S: Acute hemiplegia of infancy and childhood. Pediatr Clin North Am 23:413-433, 1976 8. B i c k e r s M E R Aetiology of acute hemiplegia in childhood. Br Med J 282-87, 1964 9. Shillito J Jr: Carotid arteritis: A cause of hemiplegia in childhood. J Neurosurg 21:540-551, 1964 10. Hilal SK, Solomon GE, Gold AP,e t al: Primary cerebral arterial occlusive disease in children: Rrt 1. Acute acquired hemiplegia. Radiology 99:71-86, 1971 11. Ferris EJ, Levine HL: Cerebral arteritis: Classification. Radiology 109:327-341, 1973 12. Walker RJ 111,El Gamma1T, Allen MB Jr: Cranial arteritis associated with herpes zoster: Case report with angiographic findings. Radiology 107:109-110, 1973 13. Leeds NE, Rosenblatt R Arterial wall irregularities in intracranial neoplasms: The shaggy vessel brought into focus. Radiology 103:121-124, 1972 14. Rumbaugh CL, Bergeron RT, Kurze T: Intracranial vascular damage associated with skull fractures: Radiographic aspects. Radiology 104:81-87, 1972 15. George AE, Kishore PRS,Chase NE: Primary diseases of the cerebral blood vessels. Semin Roentgen01 6:34-47,1971 16. Campbell JAH: Cat-scratch disease. In Sommers SC, Rosen PP (Editors): Pathology Annual Part 1. New York, Appleton-Century-Crofts, 1977, vol 12, pp 277-292 17. Schulkind ML, Ayoub E M Cell-mediated immunity in cat-scratch disease. J Pediatr 85199-203, 1974
Cerebral arteritis in cat−scratch disease George Selby and Grant L. Walker Neurology 1979;29;1413-1418 DOI 10.1212/WNL.29.10.1413 This information is current as of October 1, 1979 Updated Information & Services
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