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Magnetic Resonance Imaging Abnormalities in Cat-Scratch Disease Encephalopathy

Seah, Alvin B. H. MRCP; Azran, Marc S.; Rucker, Janet C. MD; Biousse, Valérie MD; Martin, Daniel F. MD; Newman, Nancy J. MD

Journal of Neuro-Ophthalmology: March 2003 - Volume 23 - Issue 1 - p 16-21
Original Contributions

A 23-year-old woman who presented with a branch retinal artery occlusion followed by encephalopathy showed, by brain magnetic resonance imaging, a nonenhancing lesion in the right parietal gray matter with normal diffusion-weighted imaging. Of 64 reported cases of cat-scratch encephalopathy with documented neuroimaging findings, only 12 (18.8%) have had abnormal imaging findings. The abnormalities have included cerebral white matter lesions, basal ganglia and thalamic lesions, and multifocal lesions in immunocompromised patients, but no gray matter lesions similar to those in this patient. The variety of neuroimaging findings supports multiple pathophysiologic mechanisms of central nervous system involvement in this disorder.

From the Departments of Ophthalmology (ABHS, MSA, JCR, VB, DFM, NJN), Neurology (VB, NJN), and Neurological Surgery (NJN), Emory University School of Medicine, Atlanta, Georgia.

Address correspondence to Nancy J. Newman, MD, Neuro-ophthalmology Unit, Emory Eye Center, 1365-B Clifton Road NE, Atlanta, GA 30322, USA; E-mail:

This study was supported in part by a departmental grant (Department of Ophthalmology) from Research to Prevent Blindness, Inc, New York, New York, and by core grant P30-EY06360 (Department of Ophthalmology) from the National Institutes of Health, Bethesda, Maryland.

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.

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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.

FIG. 1.

FIG. 1.

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.

FIG. 2.

FIG. 2.

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.

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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.

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