Brucellosis Chapter 83

83.1 Clinical Features

and Laboratory Findings

Brucellosis is a zoonosis endemic in the eastern part of the Mediterranean, the Arabian peninsulas, and the Indian subcontinent. Infection of humans occurs by ingestion of raw meat, milk products, or direct con- tact with infected animals. Four species of Brucella can infect humans: Brucella melitensis, Brucella abor- tus, Brucella suis, and Brucella canis. After infection, bacteremia follows and the disease spreads to many organs and organ systems. Brucella species diffusely colonize the lymphoreticular system, with prolifera- tion of lymphocytes and macrophages. Formation of granulomas follows.

The clinical symptoms are protean. The disease usually starts with an episode of malaise, fever, and arthralgia, and progresses slowly to more severe con- stitutional symptoms, including headache, nausea, vomiting, otalgia, hearing loss, ophthalmoplegia, and cardiac and neurological symptoms. Involvement of the CNS occurs in three major forms: leptomeningeal involvement in the bacteremic phase of the disease, peripheral nervous system involvement with poly- radiculoneuropathy, and slowly progressive central nervous system involvement with mild confusion, focal neurological symptoms such as dysarthria, and cognitive impairment, but occasionally also with multifocal serious symptoms due to multiple brain abscesses. In children and occasionally in adults the clinical and MRI features may resemble those of acute disseminated encephalomyelitis (ADEM). In some cases diabetes insipidus is present as the result of granulomatous involvement of the sellar contents.

Spinal symptoms may result either from direct in- volvement of the spinal cord or from compression due to involvement of the vertebral column with for- mation of granulomas.

Laboratory confirmation of brucellosis may be dif- ficult. The CSF shows usually only mild pleocytosis and normal protein and glucose concentrations. IgG antibodies against Brucella may be found in the CSF, even with negative serum titers. Enzyme-linked im- munosorbent assay (ELISA) of the CSF may further assist in the diagnosis. In rare cases brain biopsy may lead to a correct diagnosis.

83.2 Pathology

There are few reports on the neuropathology of neu- robrucellosis. They describe various degrees of vas- cular inflammation, ranging from chronic infiltration with lymphocytes, plasma cells, and macrophages to acute polymorphic infiltration that may cause ab- scesses, necrosis, and aneurysm formation. Diffuse meningeal inflammation may occur as well as inflam- matory cell infiltration of the perineurium of nerve roots. Little has been published about the nature of the involvement of the cranial nerves and the inner ear. Inflammation of the inner ear seems a more prob- able cause of the progressive hearing loss than affec- tion of the eighth cranial nerve.

Although demyelination is presumed by several authors to be present in patients with white matter abnormalities, especially those presenting with the clinical picture of ADEM, no histopathological evi- dence of demyelination has been provided. Occasion- ally data have been obtained because a brain biopsy was performed. In a patient with diffuse white matter involvement and progressive encephalopathy, biopsy revealed abundant inflammatory cells in the white matter, with lymphocytic infiltrates in the lepto- meninges surrounding the cortical vessels (Seidel et al. 2003). No significant demyelination was found in the affected area. Reactive astrogliosis was found in the cortex. Marked activation of microglia was demonstrated by immune staining of MHC complex class II antigens. The infiltrates in the white matter consisted mainly of CD8+ T-cell lymphocytes.

83.3 Pathogenetic Considerations

Brucellae are intracellular, nonmobile, gram-negative coccobacilli capable of replication within mononu- clear phagocytes. Ingestion of infectious products, most often unpasteurized milk, is followed by hematogenous dissemination, residence of the bru- cellae in the reticuloendothelial system, and subse- quent involvement of multiple organs or organ sys- tems, resulting in a variety of clinical symptoms. In 4–15% of patients the CNS is involved. The presence of the brucellae leads to an inflammatory–granulo- matous response and, in the CNS, sometimes to mul- tiple brain abscesses. Involvement of venous struc- tures may lead to sinus thrombosis. The abundance of

Brucellosis

Chapter 83

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CD8+ T-cell lymphocytes in white matter lesions sug- gests that the white matter lesions are induced by T- cell-mediated toxic injury. This would imply that the pathogenesis of the lesions is different from lesions seen in autoimmune-related disorders such as acute disseminated encephalomyelitis. It is unclear why in some cases the sellar region is involved or the spinal cord in others.

83.4 Therapy

The correct diagnosis is essential because brucellosis is a treatable condition. Once diagnosed, neurobru- cellosis can be treated with a combination of antibi- otics. Most often this is done by an intravenous course for several weeks, followed by an oral course for many months.

Fig. 83.1. Brucellosis in a 70-year-old man. The FLAIR images (first and second rows) show frontoparietal involvement of the arcuate fibers and a hyperintense rim around the ventricles.

The T

-weighted images after contrast (third row) show en-

hancement of the leptomeninges. From Al-Sous et al. (2004),

with permission

83.5 Magnetic Resonance Imaging

An MR inventory of suspected inflammatory–granu- lomatous disorders should aim at the depiction of the various disease manifestations of these disorders, guided by the clinical symptoms. The structures that should obtain special attention are:

∑ The leptomeninges, especially in the early phase of the disease (T

-weighted images, T

-weighted im- ages without and with contrast, in transverse and coronal planes) (Fig. 83.1)

∑ The white matter (proton density, T

-weighted, and FLAIR images, contrast-enhanced T

-weight- ed images) (Figs. 83.1–83.3)

∑ The sellar region (sagittal and coronal T1-weight- ed images with fat-suppression, without and with contrast enhancement (Fig. 83.4)

∑ The spinal cord (sagittal T

- and T

-weighted im- ages of the entire spinal canal, transverse images when lesions are present (Figs. 83.3 and 83.5)

Leptomeningeal involvement occurs usually in the early phase of the disease.

White matter involvement may occur in a number of different patterns. First of all, a multiple sclerosis or ADEM-like type of involvement may occur with asymmetrical large patchy hyperintense lesions on T

-weighted and FLAIR images (Figs. 83.1 and 83.2).

Secondly, a symmetrical pattern of diffuse involve- ment of subcortical white matter is sometimes seen without involvement of the corpus callosum. Some- times the abnormalities are more extensive and dif- fusely involve the subcortical and periventricular re- gions, again without participation of the corpus cal- losum (Fig. 83.3). Occasionally there are (asymmet- ric) lesions in the basal ganglia (Fig. 83.3). Some of these basal ganglia lesions may be hemorrhagic and some may enhance after contrast administration. In later phases lacunar infarctions may be seen, mainly in the basal ganglia. In all cases and especially in the early phase of the disease, leptomeningeal enhance- ment may occur (Fig. 83.1).

83.5 Magnetic Resonance Imaging 637

Fig. 83.2. Brucellosis in a 50-year-old man. The FLAIR images show a more irregular pattern of involvement of the arcuate fibers and a more prominent rim around the ventricles, with

extension into the deep frontal white matter, than seen in Fig. 83.1. In this case there are also lesions in the midbrain and pons. From Al-Sous et al. (2004), with permission

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Lesions in the perisellar, suprasellar, and intrasel- lar region may be the only intracranial manifestation of brucellosis (Fig. 83.4). They may also occur in com- bination with white matter lesions.

Spinal cord abnormalities may show enhancement in the acute phase. Nerve roots may also show en- hancement (Fig. 83.5). In the later phases spinal cord atrophy is usually found.

Unusual manifestations are superior sagittal sinus thrombosis and single or multiple brain abscesses (Fig. 83.3).

When multiple sclerosis-like white matter abnor- malities are present, the differential diagnosis in-

cludes inflammatory conditions like multiple sclero- sis, acute demyelinating encephalomyelitis, neu- roborreliosis, and systemic lupus erythematosus.

When more diffuse and symmetrical white matter ab- normalities are present, the differential diagnosis may be more difficult and may includes many inher- ited conditions, depending on the exact pattern of ab- normalities present. Leptomeningeal enhancement after contrast injection may support the diagnosis of neurobrucellosis. The peri-, intra-, and parasellar manifestations have to be differentiated from neu- rosarcoidosis, pituitary tumors, Langerhans cell histi- ocytosis, and Whipple disease.

Fig. 83.3. Brucellosis in a 65-year-old patient with both cere- bral and spinal abnormalities.The two upper images on the left, FLAIR and T

-weighted respectively, show symmetrical in- volvement of most of the cerebral white matter, most promi- nently of the arcuate fibers and the external capsule. The low- er left image, T

-weighted with contrast, shows meningeal in- volvement and abscess formation with a cyst-like component

and a more solid component in the deep frontal white matter.

The abscess is surrounded by an enhancing rim; the solid part of the lesions enhances in toto. The sagittal and transverse T

-weighted images of the thoracic spinal cord show a lesion in the center of the thoracic cord (arrow). From Seidel et al.

(2003), with permission

83.5 Magnetic Resonance Imaging 639

Fig. 83.4. Brucellosis in a 30-year-old woman. Coronal T

-weighted images with contrast show a suprasellar gran- uloma as the sole manifestation of the disease. The differential diagnosis of this phenomenon includes Langer- hans cell histiocytosis, Whipple disease, neurosarcoidosis, and Tolosa–

Hunt syndrome. From Al-Sous et al.

(2004), with permission

Fig. 83.5. T

-weighted images in the transverse and sagittal plane in a 32-year-old man with brucellosis. The images on the left are T

-weighted images without contrast, those on the right with contrast. After contrast administration, caudal roots show enhancement. From Al-Sous et al.

(2004), with permission

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