Cat-scratch disease (CSD) is a relatively benign systemic zoonosis, manifesting with fever, lymphadenopathy, and generalized malaise, usually with a history of prior contact with a cat or kitten (1). It is caused by Bartonella henselae in the majority of cases, although in a few reported cases, Bartonella quintana may be responsible (2). Clinically, CSD usually starts with a papule at the site of inoculation, goes on to involve the regional draining lymph nodes by causing lymphadenopathy, and often resolves without treatment within 2 to 3 months. However, CSD may be complicated by involvement of other organs, including the eye and brain (1,2). Although cat-scratch encephalopathy is relatively benign compared with encephalopathy from other causes, it is the most important complication of CSD (1,3,4). No review has focused on the neuroimaging findings in this disorder. We describe unusual neuroimaging findings in a patient with cat-scratch encephalopathy and review the literature regarding neuroimaging of this disease.
A 23-year-old woman complained of blurred vision, nasally in the OD. Two weeks earlier she had been ill with fever but did not recall any lymphadenopathy. She had been bitten and scratched many times by her 12-week-old kitten. On examination, she had normal visual acuity, with an inferonasal visual field defect in her OD. Funduscopy showed a small superotemporal branch retinal artery occlusion in the OD, with white spots in the inferonasal and inferotemporal retina, and 1 to 2+ vitreous cells (Fig. 1). The OS showed a single white spot. The work-up, which had negative findings, included transthoracic echocardiography, complete blood cell count, sedimentation rate, rapid plasma reagin, prothrombin time, partial thromboplastin time, factor VIII, protein C and S levels, antinuclear antibody, lupus anticoagulant, and Lyme and toxoplasma titers. Bartonella IgG titers were elevated at 1:1024, and the patient was prescribed a course of ciprofloxacin 500 mg twice a day for 10 days.
During the next month, the patient had two nocturnal seizures, clumsiness, and a decrease in memory and attention. Magnetic resonance imaging (MRI) of the brain (Fig. 2) performed 5 weeks after the onset of the branch retinal artery occlusion and 5 days after the onset of neurologic symptoms, showed increased signal intensity in the right parietal lobe on T2-weighted, fluid attenuation inversion recovery, and proton density sequences. The lesion did not become enhanced. Diffusion-weighted imaging findings were normal.
The complete blood cell count, sedimentation rate, prothrombin time, partial thromboplastin time, thyroid-stimulating hormone, and antinuclear antibody test results were again normal. A repeat Bartonella IgG titer was 1:2048. A lumbar puncture showed two white blood cells per microliter, no red blood cells per microliter, a protein level of 17 mg/dL, and a glucose level of 58 mg/dL. An awake and an asleep electroencephalogram did not reveal any epileptiform activity. Repeat MRI performed a week after the initial imaging showed that the lesion in the right parietal lobe gray matter was resolving, and diffusion-weighted imaging findings remained normal. A cervical and intracranial magnetic resonance angiography scan was also normal. The patient was treated with azithromycin 250 mg every day for 3 days, another course of ciprofloxacin 500 mg twice a day for 21 days, and enteric-coated aspirin. She recovered neurologic function and has remained seizure free. Her visual function remains unchanged.
Cat-scratch disease is a systemic infectious disease manifesting with fever, tender lymphadenopathy, and generalized malaise (1,5). The causative organism is a pleomorphic, gram-negative bacillus (6) initially thought to be Afipia felis (7) but recognized in 1992 to be a newly identified organism, Bartonella (formerly Rochalimaea) henselae (2,8–10). A closely related organism, B. quintana can also cause clinical CSD (2,11,12). Serologic testing (13) is currently the main investigational modality for confirming this diagnosis (2). The incidence of CSD in the United States has been estimated at approximately 22,000 cases per year (14).
The pathologic response is variable and depends on the patient's immune status. Immunocompetent patients show a suppurative, granulomatous response (6), and the CSD bacilli can be seen inside blood vessel walls with special stains (6) and electron microscopy (15). Immunocompromised patients show a vasculoproliferative response termed bacillary angiomatosis (16).
A typical case of CSD in the immunocompetent host has a characteristic clinical course (1,2). It starts with a scratch from a kitten, followed by development of a nontender papule at the site of the scratch over the next week, then regional lymph node enlargement over the next 2 weeks, which may be tender. Patients may be relatively well and afebrile or may experience a variety of systemic complaints, including fever, anorexia, malaise, arthralgia, myalgia, and abdominal, neck, and back pain. Other complications of CSD include ophthalmic, neurologic, bone, and abdominal involvement.
The eye is the most commonly affected nonlymphatic organ (17). Parinaud oculoglandular syndrome is the most common ocular manifestation, occurring in up to 5% of patients, and manifesting with unilateral eye redness, foreign body sensation, and tearing, with associated cervical or preauricular lymph node enlargement (1,2). Other ophthalmic manifestations include uveitis, vitreous inflammation, retinitis, neuroretinitis, and optic disc edema (18). Focal retinochoroiditis may occur in the absence of disc edema or macular exudates, and this may give rise to intraretinal hemorrhage, branch retinal artery or vein occlusions, or localized serous retinal detachment. Our patient's ocular involvement with branch retinal artery occlusion and associated vitreous cells is typical.
Neurologic complications occur in only about 2% to 3% of patients with CSD (4) and include encephalopathy, cranial nerve paresis, spinal cord involvement, and peripheral neuritis (3,4,19). Encephalopathy, first described in CSD in 1952 (20), is the most common, occurring in about 90% of all patients with neurologic manifestations (4,19). Although relatively benign compared with other causes of encephalopathy, it is an important complication, with patients presenting with seizures, often leading to status epilepticus, which may be difficult to control. The mental state of these patients ranges from lethargy or even coma to agitation and confusion (3,4,19). Carithers and Margileth (3) described a “transient combative behavior” in which patients reacted to physical contact by hitting out at medical staff and parents, a behavior that they claim was undocumented in other forms of encephalopathy. Focal neurologic signs such as weakness, numbness, or ataxia may be present. The prognosis for cat-scratch encephalopathy is generally good, and the vast majority of patients recover without sequelae (3,4,19). Some patients, however, have persistent seizures (19,21) or focal neurologic deficits (22), and a case has been described in which the patient became demented (23).
This report extends the range of intracerebral involvement and neuroimaging findings that can be attributed to bartonellosis. The majority of case series regarding cat-scratch encephalopathy date from before the modern era of neuroimaging. In the largest reported series, by Carithers and Margileth (3), 61 cases of patients with cat-scratch encephalopathy were collected from 1959 to 1987 (3). Of these, only 33 patients, slightly more than half, received a computed tomographic (CT) brain scan, and these scans were described as “not diagnostic or showed transient abnormalities.” Only six patients had MRI performed; five of these scans were normal and one abnormal. The abnormality was localized to the occipital lobe and was also noted on a CT scan of the brain. Unfortunately, there are no further descriptions of the lesion and no indication as to whether those patients who had normal MRI scans also had CT scans.
To date, 64 patients have been reported with cat-scratch encephalopathy about whom imaging information is documented (Table 1) (3,11,12,19,21–37). Only 12 of these patients (18.8%) had imaging abnormalities. (Two patients were subsequently proven by polymerase chain reaction to have B. quintana rather than B. henselae as the etiologic agent of CSD [11,12]). Of the 12 patients with imaging abnormalities (Table 1), 4 had abnormalities on CT scan, with MRI either not performed or not reported (19,22,30,31), 2 had abnormalities on both CT and MRI scans (3,11), 2 had abnormalities on MRI scan undetectable by CT (23,37), and 4 had abnormalities on MRI scan with no information provided regarding brain CT (12,21,34,36). Of the abnormalities, one was described as “focal changes in the occipital area” (3), two were believed to be occipital infarctions (19,22), two were diffuse white matter lesions (23,34), and three were abnormalities involving the basal ganglia and thalami (11,12,21). In three patients who were immunocompromised and, properly speaking, had cerebral bacillary angiomatosis rather than cat-scratch encephalopathy, imaging revealed a left temporal lesion in one patient (30), multifocal parenchymal and leptomeningeal involvement in another (36), and a left basal ganglia lesion in the third (31). There were no details on the MRI abnormalities in the last case (37). In none of the imaging reports is there a description of a gray-matter lesion similar to that of our patient—a lesion involving the gray matter, seen on T2-weighted, fluid attenuation inversion recovery, and proton density sequences, lacking enhancement or evidence of acutely restricted diffusion.
The wide range of cerebral pathologic lesions that may manifest in patients with cat-scratch encephalopathy has led to a number of theories regarding pathophysiology. It has been suggested that there are two forms of central nervous system involvement: (1) a diffuse, reversible encephalopathy with absence of focal neurologic findings, normal imaging, and benign outcome; and (2) a focal encephalopathy, with lateralizing findings on both examination and imaging, with the potential for long-term neurologic sequelae (19). The “diffuse encephalopathy” is thought to be the result of remote effects such as a neurotoxin or an immune-mediated process rather than from direct invasion of brain parenchyma. Other authorities (4,35) agree that direct invasion of the central nervous system seems unlikely, because cerebrospinal fluid analysis is usually normal and because recovery is generally rapid even in the absence of antibiotic therapy. Lewis and Tucker (19) favor a toxic mechanism because of the abrupt onset of neurologic dysfunction and equally prompt resolution of symptoms. To date, however, there have been no further data to support their hypothesis.
In support of the mechanism of direct bacterial invasion, recent polymerase chain reaction techniques have identified Bartonella DNA in cerebrospinal fluid, beyond the blood–cerebrospinal fluid barrier, in both immunocompetent (11) and immunocompromised (31) patients. In two immunocompromised patients, direct bacterial invasion has also been proven on brain biopsy, by the Warthin-Starry stain in one patient (30) and using polymerase chain reaction techniques in the other (36). Bartonella-specific immunoglobulin has also been found in the cerebrospinal fluid, clearly supporting the hypothesis that bacterial invasion can occur (31). These reports have included patients with both normal (11,30) and abnormal (36) cerebrospinal fluid, as well as normal (11) and abnormal neuroimaging findings (11,30,31,36).
A vasculitic process as a basis for “focal encephalopathy” was also proposed by Lewis and Tucker (19). Indeed, one patient reported with a “stroke” was the first case of cat-scratch encephalopathy with an imaging abnormality, presumably secondary to “vasculitis” (22). This 7-year-old girl presented with the sudden onset of expressive aphasia and a dense right hemiparesis. A brain CT scan showed a hypodense area around the left internal capsule consistent with an infarction. An angiogram performed 6 days later showed beading and irregularity of the left internal carotid artery and the left middle cerebral artery, suggestive of a localized cerebral arteritis. Another patient with a “stroke” underwent cerebral arteriography 14 days after the onset of symptoms (19), but this proved normal, and it was speculated that an earlier arteriogram might have demonstrated a transient arteritis. Certainly, in the retina, a vasculitic appearance with focal retinochoroiditis, cotton wool spots, and arterial and venous thrombosis, such as in our patient, is well described (17). One immunocompromised patient developed intraretinal hemorrhages and cotton wool spots in the retina consistent with B. henselae infection, and a retinal biopsy detected B. henselae DNA (38). Thus, it seems possible that a “vasculitis” may represent either an immunemediated phenomenon or direct invasion of the bacteria into the blood vessels. This would not be surprising, especially given the known affinity of B. henselae for epithelial cells (14) and the demonstrated presence of the bacilli within blood vessel walls on pathologic specimens (6,14). In our patient, the parietal lobe lesion demonstrated on imaging cannot represent acute ischemia, given the normal diffusion-weighted imaging findings 5 days after the onset of neurologic symptoms. There was no gross evidence of vasculitis by magnetic resonance angiography, but cerebral arteriography was not performed. The patient's MRI findings might be compatible with direct invasion of the cerebral cortex, but no biopsy confirmation is available. Our patient would also appear to be an exception to the generalization that patients with focal encephalopathy and with imaging abnormalities have permanent neurologic sequelae.
1. Carithers HA. Cat-scratch disease: an overview based on a study of 1200 patients. Am J Dis Child 1985; 139:1124–33.
2. Bass JW, Vincent JM, Person DA. The expanding spectrum of Bartonella
infections: II. Cat-scratch disease. Pediatr Infect Dis J 1997; 16:163–79.
3. Carithers HA, Margileth AM. Cat-scratch disease: acute encephalopathy and other neurologic manifestations. Am J Dis Child 1991; 145:98–101.
4. Marra CM. Neurologic complications of Bartonella henselae
infection. Curr Opin Neurol 1995; 8:164–169.
5. Carithers HA. Cat-scratch disease: notes on its history. Am J Dis Child 1970; 119:200–3.
6. Wear DJ, Margileth AM, Hadfield TL, et al. Cat-scratch disease: a bacterial infection. Science 1983; 221:1403–5.
7. Brenner DJ, Hollis DG, Moss CW, et al. Proposal of Afipia
gen. nov., with Afipia felis
sp. nov. (formerly the cat-scratch bacillus), Afipia clevelandensis
sp. nov. (formerly the Cleveland Clinic Foundation Strain), Afipia broomeae
sp. nov., and three unnamed genospecies. J Clin Microbiol 1991; 29:2450–60.
8. Regnery RL, Martin M, Olson J. Naturally occurring “Rochalimaea henselae
” infection in domestic cats. Lancet 1992; 340:557–8.
9. Regnery RL, Olson JG, Perkins BA, et al. Serological response to “Rochalimaea henselae
” antigen in suspected cat-scratch disease. Lancet 1992; 339:1443–5.
10. Dolan MJ, Wong MT, Regnery RL, et al. Syndrome of Rochalimaea henselae
adenitis suggesting cat-scratch disease. Ann Intern Med 1993; 118:331–6.
11. Parrott JH, Dure L, Sullender W, et al. Central nervous system infection associated with Bartonella quintana
: a report of two cases. Pediatrics 1997; 100:403–8.
12. Anonymous. Case records of the Massachusetts General Hospital. Weekly clinicopathologic exercises. Case 1–1998: an 11 year-old boy with a seizure. N Engl J Med 1998; 338:112–9.
13. Dalton MJ, Robinson LE, Cooper J, et al. Use of Bartonella
antigens for serologic diagnosis of cat-scratch disease at a national referral center. Arch Intern Med 1995; 155:1670–6.
14. Jackson LA, Perkins BA, Wenger JD. Cat-scratch disease in the United States: an analysis of three national databases. Am J Public Health 1993; 83:1707–11.
15. Hadfield TL, Malaty RH, Van Dellen A, et al. Electron microscopy of the bacillus causing cat-scratch disease. J Infect Dis 1985; 152:643–5.
16. Tsang WY, Chan JK. Bacillary angiomatosis. A “new” disease with a broadening clinicopathologic spectrum. Histol Histopathol 1992; 7:143–52.
17. Cunningham ET, Koehler JE. Ocular bartonellosis. Am J Ophthalmol 2000; 130:340–9.
18. Solley WA, Martin DF, Newman NJ, et al. Cat scratch disease: posterior segment manifestations. Ophthalmology 1999; 106:1546–53.
19. Lewis DW, Tucker SH. Central nervous system involvement in cat-scratch disease. Pediatrics 1986; 77:714–21.
20. Stevens H. Cat-scratch fever encephalitis. Am J Dis Child 1952; 84:218–22.
21. Hahn JS, Sum JM, Lee KP. Unusual MRI findings after status epilepticus due to cat-scratch disease. Pediatr Neurol 1994; 10:255–8.
22. Selby G, Walker GL. Cerebral arteritis in cat-scratch disease. Neurology 1979; 29:1413–8.
23. Revol A, Vighetto A, Jouvet A, et al. Encephalitis in cat-scratch disease with persistent dementia. J Neurol Neurosurg Psychiatry 1992; 55:133–5.
24. Torres JR, Sanders CV, Strub RL, et al. Cat-scratch disease causing reversible encephalopathy. JAMA 1978; 240:1628–9.
25. Pampe D, Holt RM. Cat-scratch disease with reversible encephalopathy. Tex Med 1984; 80:38–9.
26. Aldamiz-Echevarria L, Perez-Yarza EG, Morras I, et al. Enfermedad del aranazo de gato: forma atypica. An Esp Pediatr 1984; 20:395–9.
27. Melis K, Bochner A, Vandenberghe P, et al. Cat-scratch disease with reversible encephalopathy. Eur J Pediatr 1989; 149:24–5.
28. Yagupsky P, Sofer S. Cat-scratch encephalopathy presenting as status epilepticus and lymphadenitis. Ped Emerg Care 1990; 6:43–5.
29. Anonymous. Case records of the Massachusetts General Hospital. Weekly clinicopathologic exercises. Case 22–1992: A 6½-year-old girl with status epilepticus, cervical lymphadenopathy, pleural effusions, and respiratory distress. N Engl J Med 1992; 326:1480–9.
30. Spach DH, Panther LA, Thorning DR, et al. Intracerebral bacillary angiomatosis in a patient infected with human immunodeficiency virus. Ann Intern Med 1992; 116:740–2.
31. Schwartzman WA, Patnaik M, Barka NE, et al. Rochalimaea
antibodies in HIV-associated neurologic disease. Neurology 1994; 44:1312–6.
32. Hadley S, Albrecht MA, Tarsy D. Cat-scratch encephalopathy: a cause of status epilepticus and coma in a healthy young adult. Neurology 1995; 45:196.
33. Noah DL, Bresee JS, Gorensek MJ, et al. Cluster of five children with acute encephalopathy associated with cat-scratch disease in South Florida. Paediatr Infect Dis J 1995; 14:866–9.
34. Hopkins KL, Simoneaux SF, Patrick LE, et al. Imaging manifestations of cat-scratch disease. Am J Roentgenol 1996; 166:435–8.
35. Wheeler SW, Wolf SM, Steinberg EA. Cat-scratch encephalopathy. Neurology 1997; 49:876–8.
36. George TI, Manley G, Koehler JE, et al. Detection of Bartonella henselae
by polymerase chain reaction in brain tissue of an immunocompromised patient with multiple enhancing lesions. J Neurosurg 1998; 89:640–4.
37. Armengol CE, Hendley JO. Cat-scratch disease encephalopathy: a cause of status epilepticus in school aged children. J Pediatr 1999; 134:635–8.
38. Warren K, Goldstein E, Hung VS, et al. Use of retinal biopsy to diagnose Bartonella (formerly Rochalimaea) henselae
retinitis in a HIV infected patient. Arch Ophthalmol 1998; 116:937–40.