Brain miliary enhancement

Abstract

Purpose: Miliary enhancement refers to the presence of multiple small, monomorphic, enhancing foci on T1-weighted post-contrast MRI images. In the absence of a clear clinical presentation, a broad differential diagnosis may result in invasive procedures and possibly brain biopsy for diagnostic purposes.

Methods: An extensive review of the literature is provided for diseases that may present with miliary enhancement on T1-weighted brain MR images. Additional disease-specific findings, both clinical and radiological, are summarized and categorized by the presence or absence of perivascular space involvement.

Results: Miliary pattern of enhancement may be due to a variety of underlying causes, including inflammatory, infectious, nutritional or neoplastic processes. The recognition of disease spread along the perivascular spaces in addition to the detection or exclusion of disease-specific features on MRI images, such as leptomeningeal enhancement, presence of haemorrhagic lesions, spinal cord involvement and specific localisation or systemic involvement, allows to narrow the potential differential diagnoses.

Conclusion: A systematic approach to disease-specific findings from both clinical and radiological perspectives might facilitate diagnostic work-up, and recognition of disease spread along the perivascular spaces may help narrowing down differential diagnoses and may help to minimize the use of invasive diagnostic procedures.

Keywords: Brain; Contrast; Magnetic resonance imaging; Miliary; Virchow–Robin spaces.

Fig. 1

a Axial post-contrast T1-weighted MRI at the level of the corona radiata in a 39-years-old male affected by vitamin B₁₂ deficiency. Note the miliary-enhancing nodules in addition to linear enhancement along the pathway of perforating vessels, suggestive for PVS involvements. In this patient, brain abnormalities totally resolved after vitamin B₁₂ suppletion therapy. b Note on a T2-weighted MRI in a different and healthy subject the T2 hyperintense prominent PVS identical to the enhancement pattern

Fig. 2

Examples of diseases with brain miliary enhancement with PVS pattern. a, b Axial post-contrast T1-weighted MRI at the level of the corona radiata. a A 53-year-old female with skin biopsy–proven neurosarcoidosis. b A 24-year-old female affected by Erdheim–Chester disease. Both patients show miliary-enhancing nodules scattered in the brain parenchyma with a PVS pattern along the course of perforating vessels. c, d Axial post-contrast T1-weighted MRI at the level of the posterior fossa. Please note the different orientations of the PVS in the brainstem and cerebellum. c A 55-year-old male with CLIPPERS with miliary enhancement, ‘peppering’ the pons, with spread to the cerebellum and subtle linear enhancement along the PVS. Brain abnormalities totally resolved in this case after corticosteroid therapy. d A 57-year-old male with PACNS shows miliary enhancement in the pons, cerebellar peduncles and cerebellar hemispheres. Angiography (not shown) was unremarkable in this brain biopsy–proven case of primary CNS angiitis

Fig. 3

Examples of diseases with brain miliary enhancement without PVS pattern. Axial post-contrast T1-weighted MRI of the supratentorial region. a A 35-year-old female with neurotuberculosis (proven by bronchoalveolar lavage culture). Multiple miliary-enhancing nodules are visible at the white–grey matter junction. Note the faint leptomeningeal enhancement visible at the right parietal operculum (arrow) and the pachymeningeal involvement visible in this slice in the frontal and occipital right lobes (arrowheads). b A 20-year-old female affected by Susac’s syndrome. Note the typical corpus callosum involvement and small enhancing nodules without PVS distribution are scattered through the supratentorial brain. c A 72-year-old male with lung adenocarcinoma. Multiple miliary-enhancing nodules are detectable at the level of the basal ganglia, right temporal and occipital lobes and left parietal operculum in random distribution without clear PVS distribution. Please also note the slight variability size of nodules. d A 27-year-old male from Central America with lung biopsy–proven histoplasmosis. Multiple miliary-enhancing nodules are visible at the grey–white matter junction and in the cortex, besides few bigger enhancing nodules in the occipital right lobe. Leptomeningeal enhancement is recognizable in the left insula and left parietal operculum. Note the enlargement of the ventricle system, caused by secondary hydrocephalus due to basilar leptomeningeal involvement (not shown in this slice)

Fig. 4

Leptomeningeal enhancement. a A 35-year-old male affected by skin biopsy–proven neurosarcoidosis. Axial post-contrast T1-weighted MRI at the level of the basal ganglia shows extensive parietal leptomeningeal enhancement (arrow), more evident on the right side, with multiple miliary-enhancing nodules with a distribution pattern suggestive of PVS involvement in the left occipital lobe (arrowhead). The same patient also shows extensive irregular leptomeningeal enhancement at the level of the cervical spinal cord. b A 26-year-old female with neurotuberculosis. Axial post-contrast T1-weighted MRI at the level of the 4th ventricle demonstrates an extensive leptomeningeal involvement at the ventral pons, fifth cranial nerves (arrows) and the petroclinoid ligaments. Note the non-PVS pattern of the miliary nodules scattered at random throughout the temporal lobes and cerebellum. Note the 4th ventricle dilatation, caused by secondary hydrocephalus due to the extensive basilar leptomeningeal involvement. c A 37-year-old female with cranial nerve VII neuritis due to Lyme disease. Axial magnification of the cerebellopontine angle post-contrast T1-weighted MRI shows intense contrast enhancement of the cisternal segment of the right facial nerve (arrow)

Fig. 5

Systemic involvement. a A 26-year-old female with neurotuberculosis. Sagittal post-contrast T1-weighted MRI with fat saturation shows collapse of thoracic vertebrae, destruction of the interposed vertebral disc, prevertebral and intervertebral fluid collection with peripheral enhancing margins and diffusely enhancing remainder of the thoracic vertebrae, suggesting spondylodiscitis with abscess formation, known as Pott’s disease. Due to displacement and mass effect narrowing of the spinal canal with compression of the spinal cord. b Axial high-resolution CT scan (right lung) in the same patient showing ‘miliary tuberculosis’ with innumerable small pulmonary nodules with centrilobular distribution. c A 37-year-old female with a typical erythema migrans, as a disease-specific finding in Lyme disease. d A 20-year-old female affected by Susac’s syndrome with branch retinal artery occlusion. Fundus photography of the left eye shows ischaemic retinal oedema and narrowed branches of the superior and inferior temporal arteries. e A 24-year-old female affected by Erdheim–Chester disease with a sclerotic metaphyseal lesion in the tibia as a disease-specific finding

Fig. 6

Different patterns of spinal cord involvement. A 39-year-old male with vitamin B₁₂ deficiency (see also Fig. 1 for brain images). a Sagittal T2-weighted MRI of the cervical spine showing an extensive multisegmental involvement of the dorsal column of the spinal cord without obvious swelling. b Axial T2-weighted MRI of the cervical spine in the same patient clearly shows the dorsal column involvement of the spinal cord, as a typical finding in vitamin B₁₂ deficiency. c Sagittal post-contrast T1-weighted MRI of the cervical and thoracic spine in a 27-year-old male from Central America with lung biopsy–proven histoplasmosis shows a nodular enhancement in the spinal cord at the C7–T1 level. d Sagittal post-contrast T1-weighted MRI of the thoracic spine in a 57-year-old male with brain biopsy–proven PACNS shows a miliary pattern of intramedullary spinal cord enhancement

Fig. 7

Preferentially infratentorial localisation. A 35-year-old male diagnosed with Behçet’s disease (small intestine biopsy proven) shows in a axial FLAIR MRI at the level of the crus cerebri a heterogeneous left mesodiencephalic lesion with oedema, typically sparing the red nucleus, and in b coronal post-contrast T1-weighted MRI at the level of the pons miliary enhancement and one larger nodule. c Axial post-contrast T1-weighted MRI of a 55-year-old male diagnosed with CLIPPERS, showing miliary-enhancing nodules and slight linear enhancement along the PVS in the pons, dentate nuclei and spreading through the cerebellum and a d complete resolution of the infratentorial lesions after corticosteroid therapy

Fig. 8

Diagnostic decision tree. Flow chart showing diseases with brain miliary enhancement according to age, PVS distribution patterns and the responsiveness in variable degrees to corticosteroid therapy (PACNS usually needs additional cyclophosphamide therapy)