CLINICAL RADIOLOGY OF CEREBRAL TUBERCULOSIS

DR. PIYUSH OJHADM RESIDENT

DEPARTMENT OF NEUROLOGYGOVT MEDICAL COLLEGE, KOTA

• Approximately 10% of all patients with Tuberculosis have CNS involvement.

• Greater prevalence in immunocompromised patients and is seen in ~ 15-20 % of cases of AIDS-related TB.

• Synchronous Extraneural TB may be present in ~50% cases and may serve as an important clue to the diagnosis of CNS TB.

SPECTRUM OF LESIONS IN CNS TB• TB meningitis• Tuberculous granuloma (Tuberculoma)• Miliary and leptomeningeal granuloma• Tuberculous abscess• Tuberculous encephalopathy• Tuberculous cerebritis• Vasculitis and infarction• Cranial neuropathy• Calvarial tuberculosis, subdural and epidural abscess• Non-osseous spinal cord tuberculosis

TUBERCULAR MENINGITIS (TBM)

• Most common manifestation of CNS TB in all age groups.• Result from either haematogenous spread or rupture of

subpial or subependymal focus (Rich focus).• Enhancing exudate in the basal cisterns is the most common

and also a relatively specific manifestation of leptomeningeal tuberculosis on CT and MRI images.

• Meningeal enhancement has been found in up to 90% of cases and is considered to be the most sensitive feature of tubercular meningitis.

• On contrast enhanced CT images, the obliteration of the basal cisterns by isodense or mildly hyperdense exudates is the most common finding in TBM.

• The findings are better appreciated on MR imaging than on CT, especially on postcontrast MR images which show the enhancing cisternal exudates and leptomeningeal enhancement.

Tuberculous meningitis Contrast-enhanced CT in a patient with TBM demonstrating

marked enhancement in the basal cistern and meninges, with dilatation of the ventricles

Tuberculous meningitis Contrast-enhanced CT scan of a child with TBM demonstrating

acute hydrocephalus and meningeal enhancement.

• Magnetic resonance imaging (MRI) with gadolinium enhancement is the preferred method of initial investigation.

• MRI is the most sensitive test for detecting the extent of leptomeningeal disease and is superior to CT scan in detecting parenchymal abnormalities, such as tuberculomas, abscesses, and infarctions and also readily depicts hydrocephalus.

• Pre-contrast MRI cannot detect pathological signal from meningeal inflammation or basal exudates in early stages. However, in later stages there may be widening of subarachnoid spaces with associated T1 and T2 shortening of CSF.

• Post-contrast T1 images show diffuse meningeal enhancement around basal cisterns and Sylvian fissures .

• Appearance is nonspecific and has a wide differential diagnosis that includes meningitis from other infective agents, inflammatory diseases such as RA, Sarcoidosis and Carcinomatous Meningitis.

• Parmar et al. demonstrated that postcontrast fluid attenuation inversion recovery (FLAIR) images may have a higher specificity compared to contrast-enhanced T1-weighted images in detection of leptomeningeal enhancement.

• Magnetization transfer spin echo imaging following contrast injection is superior to the conventional postcontrast imaging in demonstrating meningeal inflammation.

• In later stages, there may be widening of subarachnoid spaces.

• Diagnostic triad of tubercular meningitis:- – Presence of basal exudates– Infarcts and – Hydrocephalus.

• It is considered almost 100% specific but has lower sensitivity,

Tuberculous meningitis Axial Contrast-enhanced T1-weighted MRI images shows florid meningeal enhancement that is most pronounced within the

basal cisterns

Tuberculous meningitis Axial Postcontrast T1-weighted MR images in a patient demonstrate

enhancing basilar exudates and leptomeningeal enhancement along with a small tuberculoma in right temporal region and hydrocephaly (more severe in

left ventricle).

• Magnetization transfer spin echo (MT-SE) imaging following contrast injection is superior to conventional post-contrast imaging in demonstrating meningeal inflammation.

• Quantitative MT ratio is also of value in differentiation of TB meningitis from other chronic meningitis.

• Significantly lower MT ratio is seen in TB meningitis than pyogenic and fungal meningitis and significantly higher MT ratio than viral meningitis.

• Communicating hydrocephalus – Most common complication of TBM and is caused by blockage of the basal cisterns by inflammatory exudates.

• In some cases, the hydrocephalus may be noncommunicating, resulting from obstruction due to tuberculoma or rarely tubercular abscess.

• Ischemic infarcts are also common, seen in 20-40% cases, mostly within basal ganglia and internal capsule regions, resulting from vascular compression and occlusion of small perforating vessels, particularly Lenticulostriate and Thalamoperforating arteries. (Necrotizing Arteritis).

• Cranial nerve involvement is seen in 17-40% cases, most commonly affecting II,III,IV and VII th cranial nerves.

• Tuberculous meningitis may also cause dural venous sinus thrombosis with resultant hemorrhagic infarct.

• Rarely, tuberculosis may present as isolated dural venous sinus thrombosis without any evidence of meningitis or its complications.

Plain CT Brain showing infarcts involving right basal ganglia and internal capsule after the appearance of Vasculitis in the thalamoperforating arteries in a child treated for TBM.

Tuberculous meningitis complicated with B/L Infarcts Axial MR images demonstrate acute bilateral ischemic infarcts, which are hyperintense on the DW image and hypointense on

the ADC image

Coronal Postcontrast T1-weighted MR image demonstrates a filing defect within dilated left sigmoid sinus (black arrow)

Dural venous sinus thrombosis as an only imaging evidence of TBM in a 45-year-old male who presented with headache and cerebrospinal fluid PCR positive for Mycobacterium tuberculosis.

MR Venogram reveals non-visualization of Left transverse and sigmoid sinuses (white arrow).

PARENCHYMAL GRANULOMA (TUBERCULOMA)

• Tuberculomas -Most common parenchymal lesions in CNS TB. • Lesion may be solitary, multiple, or Miliary.• May be seen with or without meningitis.• May be seen anywhere within the brain parenchyma.• Most commonly occurs within the frontal and parietal lobes. • Predominance of Infratentorial lesions in children.

• Granulomas usually involve the cortico-medullary junction and periventricular region as expected from haematogenous dissemination.

• Histologically, the mature tuberculoma is composed of a necrotic caseous center surrounded by a capsule that contains fibroblasts, epithelioid cells, Langhans giant cells, and lymphocytes.

• On Non-contrast CT scans, tuberculoma may be isodense, hyperdense, or of mixed density.

• On contrast-enhanced CT, it may present a pattern of ring-like enhancement or, less likely, as an area of nodular or irregular nonhomogeneous enhancement.

• A central nidus of calcification with surrounding ring-like enhancement, known as the Target sign, suggests the diagnosis.

• Nonenhanced MR studies show a mixed, predominantly low signal intensity lesion with a central zone of high signal intensity and surrounding high signal intensity edema on T2-weighted or FLAIR images.

• The central high signal intensity zone corresponds to Caseating necrosis, and the low signal intensity of the capsule may be related to a layer of collagenous fibrosis with high protein concentration and low water content.

• Like contrast-enhanced CT, Post-contrast MR images usually show a pattern of ring-like enhancement

• Non-caseating granuloma: It is usually iso-/hypointense on T1 and hyper-intense on T2-weighted images. Homogeneous enhancement is seen with gadolinium.

• Caseating Solid granuloma: usually hypo-intense on T1 and strikingly hypo-intense on T2-weighted images. This relative hypo-intensity is attributed to the granulation tissue and compressed glial tissue in the central core resulting in greater cellular density than the brain parenchyma.

• Granuloma with central liquefaction: – appears centrally hypointense on T1, and hyperintense on

T2-weighted images with a peripheral hypointense rim on T2W images.

– The low signal intensity of the capsule may be related to a layer of collagenous fibers with high protein concentration and low water content and a layer of outer inflammatory cells.

– Gd-DTPA-enhanced T1W images show rim enhancement in Caseating Granulomas.

– The edema surrounding the granuloma is relatively less than pyogenic abscess. However, at times it is significant in the early stage.

DIFFERENTIAL DIAGNOSIS• The differential of tuberculomas is essentially is the

differential of ring-enhancing lesions, and includes:• Other infections

– Neurocysticercosis– Cerebral toxoplasmosis– CNS cryptococcosis– Bacterial cerebral abscesses

• Neurosarcoidosis• Cerebral metastases• CNS lymphoma

Axial non-contrast CT image shows a calcified lesion in the left periventricular region, with associated hydrocephalus.

Contrast-enhanced axial CT image shows ring enhancement around the calcified lesion, suggestive of Target sign

T2-weighted MRI of a biopsy-proven, Right parietal tuberculoma. Note the low–signal-intensity rim of the lesion and the

surrounding hyperintense vasogenic edema.

T2-W axial MR image shows hypointense lesions in the bilateral gangliothalamic regions (R>L), with perilesional oedema and associated hydrocephalus

Post-contrastT1 W axial image shows multiple ring-enhancing lesions, along with abnormal leptomeningeal enhancement

Caseating tuberculoma without liquefaction

T2-W axial MR image shows a centrally hyperintense granuloma with a peripheral hypointense rim with associated perilesional oedema

Gadolinium-enhanced T1-W axial image shows peripheral ring enhancement of the same lesion.

Caseating tuberculoma with liquefaction

Multiple supra- and infratentorial tuberculomas in a 27-year-old female with history of Pulmonary tuberculosis.

Tuberculomas are seen as multiple small ring enhancing lesions without peripheral edema in Axial and Sagittal

postcontrast T1-weighted MR images

• MR spectroscopy(MRS) shows prominent lipid peaks in Tuberculomas as compared to other lesions such as metastasis and high-grade gliomas which shows lipid peaks in addition to other metabolite peaks like choline.

T2-weighted MRI of a patient with a tuberculoma in the

right parietal lobe.

MRS of a patient with an Intracerebral tuberculoma demonstrating an elevated lactate peak (LA) with diminished N-

acetyl aspartate (NAA) and choline (CH) peaks typical of an inflammatory mass in the brain.

• Disseminated / Miliary tuberculoma: – a subtle clinical event demonstrated in patients with miliary

pulmonary tuberculosis who have no clinical brain involvement. – May also occur in patients with TB meningitis. – Since the dissemination is hematogenous, the lesions are usually

located at the corticomedullary junctions. – The lesions are tiny (2-3 mm in diameter) scattered small

granulomas that may be invisible on noncontrast sequences. – These lesions occasionally can be seen as small hypodensities on

CT scan. – Post-contrast shows numerous round areas of intense

enhancement.– Leptomeningeal granulomas show similar appearance; however,

they are seen located in the sulcal spaces and basal cisterns.

• In visible lesions, MRI shows small lesions that are hypointense on T2-weighted sequences.

• Postcontrast T1-weighted MR images show numerous, round, small, homogeneous, enhancing (usually ring enhancement) lesions.

• Invisible lesions that may or may not enhance after intravenous injection of gadolinium can be clearly visible on magnetization transfer spin echo T1-weighted imaging with or without contrast.

Parenchymal tuberculosis Contrast-enhanced CT scan shows multiple bilateral ring-

enhancing lesions (Tuberculomas) in the frontal and parietal lobes

Parenchymal tuberculosis Axial Contrast-enhanced T1-weighted MR image demonstrates multiple enhancing Caseating and Non-Caseating tuberculomas,

predominantly within the left frontal and parietal lobes

Miliary CNS tuberculosisAxial Contrast-enhanced T1-weighted MR image shows multiplesmall high-signal-intensity foci within both cerebral hemispheres

T1-weighted gadolinium-enhanced MRI in a patient with multiple enhancing tuberculomas in both cerebellar hemispheres.

Miliary CNS tuberculosis Miliary brain tuberculosis in a 20-year-old female with 3-month history of cough, weight loss, newly added generalized headache, dizziness, nausea, and vomiting. No obvious abnormality in the T1- and T2-weighted images.

Miliary BRAIN tuberculosis Axial Postcontrast T1-weighted MR image shows numerous bilateral tiny enhancing nodules scattered throughout the brain parenchyma.

• Sometimes, healed tuberculomas appear as calcified foci on nonenhanced CT.

• Similarly, calcification in the basal cisterns has been demonstrated a few years after meningeal tuberculosis.

Treated tuberculoma Axial noncontrast CT image shows two calcified lesions in right

frontal lobe without edema or mass effect

TUBERCULAR ABSCESS• Occur in less than 10% of patients with CNS TB. • Characterized by a central area of liquefaction with pus.• More common in the elderly and immunocompromised. • May be solitary or multiple and are frequently multiloculated.

• Tuberculous abscess is different from tuberculomas which

contain central caseation and liquefaction mimicking pus.• On imaging, a TB abscess may be indistinguishable from a

Caseating tuberculoma or a pyogenic abscess.• However, TB abscess has thinner and smoother enhancing

walls, is larger (> 3 cm in diameter), and it has peripheral oedema and mass effect.

• The Tuberculous abscess is hypodense with peripheral edema and mass effect on CT.

• On T2-weighted MR images, central necrotic area has increased signal intensity.

• Postcontrast images demonstrate ring enhancement that is usually thin and uniform, although it may be irregular and thick, especially in immunocompromised patients

• Differentiation of TB abscess from pyogenic abscess can be done with MRS and Magnetization transfer (MT) imaging.

• On MR spectroscopy, TB abscess does not demonstrate amino acids peak at 0.9 ppm as compared to pyogenic abscess which shows amino acids peak at 0.9 ppm.

• MT ratio in a TB abscess is lower than that found in a pyogenic abscess.

Tubercular Abscess Multilobulated enhancement of the lesion is seen in the

Postcontrast CT images.

22-year-old female with Miliary pulmonary tuberculosis, right hemiparesis, left facial paresis, and sixth and seventh cranial nerves involvement -Tuberculous abscess mimicking a Cerebellopontine angle tumor

Tubercular Abscess Axial T1-weighted image shows a predominantly isosignal lesion in the left hemisphere of cerebellum with extension to CPA and prepontine cistern accompanied by marked peripheral edema

and mass effect

Tuberculous abscess mimicking a Cerebellopontine angle tumor in a 22-year-old female with Miliary pulmonary tuberculosis, right hemiparesis, left facial paresis, and sixth and seventh cranial nerves involvement

Tubercular Abscess Multilobulated enhancement of the lesion is seen in the

Postcontrast T1-weighted images

Tubercular AbscessT1-weighted gadolinium-enhanced MRI in a child with a

tuberculous abscess in the left parietal region. Note the enhancing thick-walled abscess.

Tubercular AbscessAxial Pre- and postcontrast T1-weighted MR images in a 38-year-old male with cognitive and speech disorders show two hypointense lesions in both

frontal lobes with peripheral edema having thick ring-like enhancement

Tubercular AbscessAxial postcontrast T1-weighted MR images in a 22-year-old female with

pulmonary miliary tuberculosis and 3-month history of headache, nausea, vomiting, and recent seizure demonstrate bifrontal irregularly enhancing

lesions with mild peripheral edema.

TUBERCULOUS ENCEPHALOPATHY

• A syndrome exclusively present in infants and children, described by Udani and Dastur in Indian children with pulmonary tuberculosis.

• Characteristic features of this entity are the development of a diffuse cerebral disorder in the form of convulsions, stupor, and coma, without signs of meningeal irritation or focal neurological deficit.

• Pathologically, there is diffuse oedema of cerebral white matter with loss of neurons in the grey matter.

• Neuroimaging shows severe unilateral or bilateral cerebral oedema.

• On T2-weighted images, hyperintensity is seen in white matter suggesting myelin loss.

• These patients also show diffuse alteration of MT ratio in white matter which reverts back to normal after clinical recovery.

TUBERCULOUS ENCEPHALOPATHYAxial T2-W MR images show diffused white matter oedema with gyral swelling with associated Hydrocephalus. The patient had a history of ATT therapy for cerebral tuberculosis about six months prior to this presentation.

TUBERCULOUS CEREBRITIS

• TB cerebritis is rare but has specific clinical, radiological, and pathological manifestations.

• The involved areas show extensive inflammatory exudates, Langerhans’ giant cells, reactive parenchymal changes, and diffuse Caseating and noncaseating microgranulomas in the cortex.

• CT imaging shows intense focal gyral enhancement• On MR imaging, focal cerebritis appears hypointense

on T1, hyperintense on T2 and small areas of patchy enhancement on post-contrast scan.

Post-contrast axial CT image showing intense focal gyral enhancement in the region of the left sylvian fissure, with

surrounding cerebral oedema, suggestive of Focal cerebritis

VASCULITIS & INFARCTION

• Intracranial Vasculitis is a common finding in patients dying from TB meningitis and a major factor contributing towards residual neurological deficits.

• Vasculitis is initiated by direct invasion of vessel wall by mycobacterium or may result from secondary extension of adjacent arachnoiditis.

• Infarction resulting from vascultits is more common in infants and children and is most frequently seen at basal ganglia, cerebral cortex, Pons, and cerebellum.

• The MCA territories are commonly affected and the infarcts are frequently bilateral.

• MR imaging shows areas of hyperintensities on T2-weighted images.

• Diffusion weighted images are the gold standard in acute infarctions.

CRANIAL NEUROPATHIES• Commonly seen in association with TBM. • Partly due to vascular compromise resulting in ischemia of

nerve or may be due to entrapment of nerves by the exudates.

• Large tuberculomas may also compress the nerves, resulting in compression neuropathy.

• Commonly affected are II, III, IV,and VII cranial nerves. • On MR imaging, the affected nerves appear thickened and

may show hyper-intensity on T2-weighted images. • On contrast, the proximal portion of the nerve root is

commonly affected and may show enhancement.

CALVARIAL TB• Calvarial involvement in tuberculosis is rare. • Before the advent of effective chemotherapy, calvarial

tuberculosis was estimated to represent 0.2 - 1.3% of all cases of skeletal tuberculosis.

• About 50% of the cases reported in the literature were in patients younger than 10 years, and 70-90% were younger than 20 years.

• The disease is rarely seen in infants. • It is believed that calvarial tuberculosis occurs by

haematogenous seeding of bacilli into the diploic space.

• Tuberculosis may present as a subgaleal swelling (Pott’s puffy tumour) with a discharging sinus when the outer table is involved.

• Involvement of the inner table is associated with formation of underlying extradural granulation tissue.

• MRI, in most cases, leads to a conclusive diagnosis.

• Proton density and T2-weighted images show a high-signal intensity soft-tissue mass within the defect in bone.

• This may project into the subgaleal and/or epidural spaces and show peripheral capsular enhancement on the contrast-enhanced image.

• MR imaging is sensitive in demonstrating changes in the meninges and the ventricular walls and in detecting parenchymal foci of involvement.

DURAL & SUBDURAL PATHOLOGY

• Tuberculous pus formation occurs between the duramater and the leptomeninges and may appear loculated.

• It appears iso- to hypo-intense on T1W images and hyperintense on T2W.

• The dural granulomas appear isointense on T1W images and hypo- to isointense on T2W.

• Rim enhancement can be seen on post-contrast images.

EPIDURAL TB• Lesions generally appear to be iso-intense on T1W images,

and have mixed intensity on T2W images.

• In post-contrast images, uniform enhancement can be seen if the TB inflammatory process is phlegmonous in nature whereas peripheral enhancement is seen if true epidural abscess formation or caseation has developed .

• Epidural Tuberculous abscess may occur as primary lesions or may be seen in association with an underlying tuberculous focus.

Tuberculous abscess with epidural and subdural empyema and calvarial osteomyelitis

Coronal and sagittal postcontrast T1-Wt MRI images demonstrate epidural and subdural collections over the bifrontal cerebral convexities with

intraparenchymal and calvarial extension. Peripheral edema, irregular marked enhancement of the lesion as well as dural enhancement are evident.

The bony destructive lytic lesions are seen in the bone window CT image

THANK YOU

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Review of a Reemerging Disease : Radiology Research and Practice Volume 2015

• Manifestations of cerebral tuberculosis : Singapore Med J 2011; 52(2) : 124

• Magnetic resonance imaging in central nervous system tuberculosis : Indian J Radiol Imaging. 2009 Nov; 19(4): 256–265