Key-words:
Central nervous system - corpus callosum lesion - intracranial tuberculosis - tuberculoma
Introduction
Tuberculosis (TB) is the clinical manifestation of the infection caused by Mycobacterium
tuberculosis with high morbidity and mortality reported each year. In recent years,
the infection has shown a re-emergent role even in non-endemic areas with the diffusion
of acquired immunodeficiency syndrome and increasing immigration from developing nations.
Central nervous system (CNS) involvement is a rare but dramatic consequence of the
infection and it accounts for roughly 1% of all TB cases and about 15% of the extrapulmonary
TB cases. Tuberculoma is the most common form of intracranial parenchymal TB which
accounts for approximately 40% of misdiagnosed brain lesions mimicking intracranial
tumors.[[1]]
Even if isolated CNS tuberculomas of the corpus callosum without systemic TB, as in
our case, are exceptional, they are usually misdiagnosed.
The authors present a case of a CNS tuberculoma in the corpus callosum mimicking a
butterfly glioma with no signs of systemic TB in immunocompetent patient. A review
of scientific literature has been performed, analyzing radiological features of corpus
callosum tuberculomas with the aim to raise awareness about taking into account intracranial
tuberculomas as a differential diagnosis in the solitary lesion of the corpus callosum.
Materials and Methods
Review of literature
We present a literature review using the National Library of Medicine based on the
keywords: “tuberculoma,” “intracranial TB,” “corpus callosum lesion,” and “CNS.” Only
English reports were considered. Among 157 articles, only 4 manuscripts describe a
single TB lesion in the corpus callosum.[[2]],[[3]],[[4]],[[5]]
Case report
A 44-year-old Senegalese man was admitted to our department of neurological surgery
complaining of headache, progressive confusion, memory impairment, behavior disorder
with tendency toward aggression, dysarthria, and right hemiparesis for a period of
2 weeks. The patient was immunocompetent, with no relevant past history; routine hematologic
examination, serology tests, and chest radiography were normal. The patient denied
any history of fever, TBC exposure, or respiratory tract infections.
The patient underwent brain magnetic resonance imaging (MRI) with and without contrast
administration. The examination showed a lesion of the rostrum of the corpus callosum
extended into the left frontal lobe, causing compression and dislocation of the frontal
horn of the lateral ventricle and an initial subfalcine herniation. The lesion appeared
on T1-weighted images (T1WI) after contrast administration (gadolinium) scans as hypointense
with nonhomogeneous rim contrast enhancement. On T2-weighted sequences (T2WI), a central
hypointense core surrounded by perilesional edema was distinctive [[Figure 1]]a, [[Figure 1]]c, [[Figure 1]]d, [[Figure 1]]e.
Figure 1: (a-e) Preoperative coronal T1-weighted, without and after contrast administration,
axial T1-weighted without and after contrast administration, axial T2-weighted magnetic
resonance images showing lesion of the rostrum of the corpus callosum extended into
the left frontal lobe, causing compression and dislocation of the frontal horn of
the lateral ventricle. (f) Postoperative computed tomography scan shows tumor gross
total resection
A high-grade “butterfly” glioma was suspected, given the young age of the patient,
his clinical history, the symptoms, the physical examination, and the laboratories
results. The patient underwent a left frontal craniotomy. Microscopical instrumentation
was set. The dura was opened preserving the superior sagittal sinus. The tumor, coming
on the medial surface of the left frontal lobe and originating from the rostrum of
the corpus callosum, appeared as a less vascular yellowish mass. Gross total resection
was achieved. Postoperative computed tomography (CT) scan was uneventful [Figure 1f].
As shown in [[Figure 1]]a, [[Figure 1]]b, [[Figure 1]]c, [[Figure 1]]d, [[Figure 1]]e, preoperative coronal T1WI, without and after contrast administration, axial T1WI
without and after contrast administration, and axial T2WI MRIs show lesion of the
rostrum of the corpus callosum extended into the left frontal lobe, causing compression
and dislocation of the frontal horn of the lateral ventricle. As shown in [[Figure 1]]f, postoperative CT scan shows tumor gross total resection.
Microscopic examination showed a caseous necrotic center surrounded by a granulomatous
reaction that included epithelioid and Langhans giant cells.
The overall features of the specimen were sufficiently characteristic to suggest the
diagnosis of intracranial tuberculoma.The Ziehl-Neelsen and periodic acid-Schiff stains
did not demonstrate acid-fast bacilli and bacteriologic cultures were negative. Anti-TB
treatment was immediately started with a five drug regimen (rifampin, isoniazid, ethambutol,
moxifloxacin, and pyrazinamide).
The postoperative course was uneventful with no surgical morbidity and clinical improvement.
The 2-month postoperative follow-up MRI showed complete regression of the lesion with
complete resolution of the symptoms.
Results
[[Table 1]] shows detailed features of our literature review, included our case.
Table 1: Corpus callosum tuberculomas: Clinical and radiological features, histological characteristics,
treatment, and outcome
Table 1: Contd...
Montgomery[[4]] in 1933 described a case of 69-year-old man suffering from headache, dizziness,
and weakness, especially in the left leg. Since in 1933 there were not any medical
diagnostic devices such as CT or MRI, no information is available about the radiological
features of the lesion. The diagnosis was achieved through postmortem autopsy which
confirmed a lesion of the corpus callosum extended in the right frontal lobe of about
4 cm transversely and 2.25 cm vertically. This mass was composed of very soft material,
which on the left had a red color, while on the right, it was yellowish white. Microscopic
examination showed necrotic areas surrounded by cellular condensation arranged in
a radial fashion suggesting a tubercle.
Brismar et al.[[2]] in 1996 analyzed all patients affected by intracranial tuberculomas misdiagnosed
as brain tumors treated at their department. Among them, there were only 2 cases of
intraparenchymal corpus callosum tuberculoma resembling a high-grade glioma.
First case a 16-year-old female presented 8-month history of headache and vomiting
and 5-month history of retro-orbital pain and papilledema. CT scans described an isodense
corpus callosum lesion with ipodense center with irregular ring enhancement after
contrast administration. Cerebral angiography showed an avascular lesion causing occlusion
of left middle parietal Sylvain branches.
Similar radiological CT features were noted in a 56-year-old female admitted complaining
of 4-month history of mental changes and intermittent fever and of 2-month history
of inability to walk and incontinence.
Fath-Ordoubadi et al.[[3]] in 1997 described a single large with irregular enhancing lesion crossing the midline
arising from the corpus callosum at CT scans in a middle-aged male patient with gradual
onset of acute right-sided facial and limb weakness. Two weeks later, the patient
developed sudden deterioration with increasing weakness, headache, and dysphasia.
Psimaras et al.[[5]] in 2014 first reported the MRI features of a lesion involving the left side of
the frontal lobe, crossing the corpus callosum, and displacing the ventricles and
median line. On TIWI after gadolinium administration, the lesion appeared defined
by a central hypointense core with nonhomogeneous rim contrast enhancement. T2WI scans
shows peripheral hypersignal and a hypointense core. T2WI sequences (T2WI) show a
distinct central hypointense core surrounded by perilesional hyperintense signal due
to perilesional edema. Single-voxel spectroscopy (MRS) confirmed the characteristic
elevated choline peak and a decreased NAA and lipid peak.
Discussion
CNS tubercular involvement is related to hematogenous spreading from a distant primary
site, usually lungs to regions that are highly vascularized and oxygenated, such as
the brain.
HIV infection or other acquired forms of immunosuppression significantly increase
the risk for acquisition of TB, the rate of progression from latent to active disease,
and TB-associated morbidity and mortality. In particular, extrapulmonary manifestations
appear in 40% of HIV-infected patients with TB.[[6]] Nevertheless unexpected, CNS tuberculoma can affect also immunocompetent patients
with normal routine hematologic examination, serology tests, and chest radiography
as reported by the authors.
Most tuberculomas are found at the corticomedullary junction because of narrowing
of the arterioles as they enter the white matter or develop from the extension of
CSF infection into the adjacent parenchyma via cortical veins or perivascular Virchow–Robin
spaces around small penetrating arteries.[[7]] These lesions are generally multiple and hemispheric and associated with enhancing
exudates in basal and suprasellar cisterns, hydrocephalous with ventricular ependymal
enhancement, focal or diffuse leptomeningeal enhancement, focal cerebritis, and infarcts.[[8]] In the adults, the lesions are predominantly located supratentorially, while in
the pediatric counterpart, they are mainly distributed infratentorially. The most
common sites are cerebral hemispheres, basal ganglia, cerebellum, and brainstem.[[9]]
Although uncommon, intracranial tuberculomas can arise from the corpus callosum white
matter and extend to the adjacent brain parenchyma. The lesion can appear as a large-size
solitary lesion , as in our case, in recognition of the fact that cerebral tuberculoma
has to reach a certain critical size in this location before producing symptoms of
a space-occupying lesion. This process can take a long time explained by the fact
that tuberculoma is the expression of a chronic inflammatory response to M. TB infection.
In addition, cerebral tuberculoma could be the only pathological expression of CNS
TB, making the radiological diagnosis more challenging.
Tuberculomas may also be variable in size. As long as there is no clear definition
about the definition of “giant” tuberculoma, the authors agree with Kumar et al.[[8]] defining “giant” a lesion of more than 1 cm size. In our case, the lesion was 60
mm × 51 mm × 36 mm; Brismar et al.[[2]] did not report any information about size, but in their report, single lesions
were typically of about 3 cm in diameter and surrounded by moderate or marked edema.
In Montgomery's report,[[4]] postmortem autopsy confirmed a lesion of about 4 cm transversely and 2.25 cm vertically.
In conclusion, the authors presented the largest corpus callosum tuberculoma described
up to now.
At the moment of the clinical presentation and then of the diagnosis, analyzing, and
comparing the radiological findings of our literature review,[[2]],[[3]],[[4]],[[5]] the authors report that all CT scans showed an isodense corpus callosum lesion
with ipodense central core; MRI revealed a lesion with a mass effect characterized
by central hypointense core and nonhomogeneous contrast enhancement after gadolinium
administration on T1WI images, while on T2WI scans, the corpus callosum tuberculoma
appeared defined by peripheral hypersignal and a hypointense core surrounded by edema.
All these features are consistent with the radiological findings of our case and are
summarized in [[Table 1]].
Pathologically, the initial lesion consists of a typical granuloma with epithelioid
cells, Langhans giant cells, and a peripheral rim of lymphocytes called noncaseating
tuberculoma. Central caseous necrosis and liquefaction develop in subsequent stages.
Tuberculoma development occurs in four stages (noncaseating granuloma, caseating granuloma,
caseating granuloma with central liquefaction, and calcified granuloma) and the MRI
features change as well as the histopathology.
In the first “non caseating” stage, tuberculoma appears hyperintense on T2WI images,
isointense or hypointense on T1, and shows nodular or ring enhancement on postcontrast
studies.
Caseating tuberculomas are usually isointense or hypointense surrounded by a hyperintense
rim on both T2WI and T1WI with rim contrast enhancement after gadolinium administration.
The solid caseation core is high in lipid contents, with macrophage infiltration responsible
for the T2WI hypointensity.
When liquefaction of the core occurs within a tuberculoma, it appears as a T2 hyperintense
lesion with a peripheral hypointense rim. On T1WI images, the center is hypointense
with rim enhancement on postcontrast studies.
In the final stage, tuberculomas often undergo calcification with a consensual reduction
of the perilesional edema noticeable on T1WI and T2WI images by the lack of the peripheral
hyperintensity and of rim enhancement.
On CT scan, occasionally, tuberculomas show up a central calcification surrounded
by a hypodense area; this pattern defines that “target sign” is highly suggestive
of TB, although not specific.[[10]]
MRI is highly sensitive but has low specificity for the diagnosis of tuberculomas
and the differential diagnosis of ring-enhancing lesions includes several possibilities.
The major ones include high-grade glioma, metastasis and neurocysticercosis.
Metastases and high-grade gliomas are usually hyperintense on T2W in contrast to the
T2W hypointense tuberculomas except in the first non-caseating stage. In this stage,
1H proton spectroscopy is also helpful because it shows a choline peak at 3.2 ppm
in metastases, while tuberculoma shows a lipid peak. In addition, the extent of perilesional
edema is disproportionately high in metastases as compared to tuberculomas.[[9]]
Neurocysticercosis lesions are generally multiple, placed in the sulcal subarachnoid
spaces and usually size <2 cm; they appear as T2 hyperintense cysts lacking of rim
enhancement on TIWI postcontrast administration.[[11]]
Conclusion
CNS tuberculoma is a rare expression of the extrapulmonary TB disease usually misdiagnosis.
This lesion can develop in any region of the brain, also in unusual locations, such
as the corpus callosum and can occur in immunocompetent patients with no history of
systemic TB, leading to a wrong diagnosis.
The evolution of the neuroimaging tools such as MRI and spectroscopy aids the differential
diagnosis with other more common conditions. Careful evaluation of the neuroradiological
images with adequate clinicoradiological correlation allows for accurate diagnosis
and ensures the proper care.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
