Brainstem encephalitis (BE) or rhombencephalitis refers to a rare infectious/inflammatory disease that affects the rhombular (pons, cerebellum, and medulla) secondary to multiple etiologies and different prognosis. This article summarizes the most common noninfectious causes of BE and their neuroimaging findings.
Other autoimmune diseases
Other autoimmune diseases, including relapsing polychondritis and Sjögren's syndrome, may also present with BE. Sjögren's syndrome is an autoimmune disease characterized by dry mouth and eyes (xerosia). However, in addition to the salivary and lacrimal glands, it may also involve the peripheral and CNS. Associated encephalitis may occur, especially in children. Radiographic findings are nonspecific lesions of parenchymal T2/FLAIR hyperintensity, which may also involve the brainstem (Fig. 8).
Figure 8. A 78-year-old woman with Sjögren's syndrome. Multiple abnormal signal foci (A) in the pons and cerebellar midfoot, patchy enhanced Susak syndrome on the left side of the ponsSusak syndrome (SS) is a relatively rare disorder that presents with typical encephalopathy, sensorineural hearing loss, and visual impairment with recurrent vascular occlusion. On imaging, SS shows a triad of deep gray matter lesions, white matter lesions, and leptomeningeal enhancement. The distribution of lesions in the corpus callosum is considered characteristic of SS because they are only visible in the central part of the CC (snowball lesions - best seen in sagittal T1; Figure 9). The presence of leptomeningeal augmentation may be associated with severe disease activity. Posterior fossa involvement manifests as punctate foci with altered signals in 70% of the cerebellar hemispheres and 55% of the brainstem. These lesions can limit spread during the acute phase.
Figure 9. A case of Susac syndrome. Multiple punctate FLAIR hyperintensity lesions in the cerebellar hemispheres and pons (A and B). Midline lesions involve the central portion of the corpus callosum, leaving the upper and lower fibers (arrow C). This "central" corpus callosum lesion is not typical of other causes of BE, including MS Neurosarcoidosis is characterized by chronic granulomatous inflammation and unexplained noncaseating granulomas, with CNS involvement in 3% to 10% of patients. Any part of the nervous system can be affected, however, the most common neurological manifestations are cranial neuropathy and leptomeningeal involvement. The most common neuroimaging findings of neurosarcoidosis are predominantly leptomeningeal enhancement around the pituitary stalk and basal cistern. Periventricular T2/FLAIR hyperintensity lesions are also common, but they are non-specific. Parenchymal enhancement foci can mimic demyelination and tumors. In BE secondary to sarcoidosis, the presence of leptomeningeal enhancement, particularly suprasellar cistern, dural enhancement, and periventricular T2 hyperintensity, suggests the diagnosis (Fig. 10).
Figure 10. Known cases of neurosarcoidosis, left cerebellar midfoot involvement, edema and FLAIR/T2 hyperintensity (A and B), left pontine surface enhancement, left CP angle, cavernous sinus, and Meckel cavity dural enhancement (C) Bickerstaff brainstem encephalitis (BBE)
The clinical presentation of BBE is a combination of Guillain-Barré and Miller Fischer syndrome, manifested by ataxia, ophthalmoplegia, and altered mental status following viral illness. The presence of altered mental status helps distinguish BBE from Miller Fischer. The incidence of BBE may be underestimated due to the lack of specific clinical criteria and biomarkers. On MRI, T2/FLAIR hyperintensity foci are common in the pons, medulla, thalamus, and cerebellum (Fig. 11). MRI findings are similar to those of CLIPPERS, but lesions are confined to the brainstem, no head and tail extension, and no punctate (peppery) enhancement foci are found. In addition, it has been reported that in many cases of clinical manifestations of BBE, MRI is normal in approximately two-thirds of patients. Ganglioside GQ1b3 antibody is common.
Figure 11. Known case of Bickerstaff brainstem encephalitis with positive anti-GQ1B antibodies. Symmetrical involvement of the pons and cerebellar mid-foot with cerebellar hemisphere swelling (A), periventricular multifocal, and deep white matter abnormal signal intensity (B) paraneoplastic syndrome
Paraneoplastic neurological syndrome (PNS) is a neurological syndrome associated with systemic malignancy. It is estimated that it occurs in 1% of patients with malignant neoplasms. PNS is a heterogeneous disorder with different sites of involvement, including neuromuscular junctions, peripheral nerves, ganglia, myelin sheaths, and brain. PNS in the brain may involve isolated parts or systems of the brain, causing localized symptoms such as cerebellar degeneration, limbic encephalitis, and BE. In addition, it can occur as a widespread encephalomyelitis. Memory loss, altered mental status, psychological features, ataxia, dysarthria, nystagmus, and seizures are common clinical manifestations. The most common underlying malignancy in PNS is small cell lung cancer, followed by testicular cancer, breast cancer, thymus cancer, and ovarian cancer.
The diagnosis of PNS syndrome is challenging because PNS may precede the diagnosis of underlying malignancy. Diagnosis is mainly made by clinical symptoms, brain MRI, electroencephalogram (EEG), especially in combination with serology of blood and spinal fluid. Serology plays a crucial role in the management of PNS, and different anti-neuronal autoantibodies are associated with PNS, including anti-Hu, anti-Ri, and anti-Ma2. Antibodies against intracellular neuronal proteins (anti-Hu, anti-Ri, anti-Yo, anti-double-loaded proteins, anti-Ma2 and anti-Tr, anti-collapse proteins, and anti-recovery proteins) are almost always associated with the presence of malignancy. Antibodies against neuronal cell surface or synaptic proteins (anti-NMDA, anti-AMPA, anti-GABA-A, anti-GABA-B, and anti-Caspr2) may or may not be associated with malignancy. Limbic encephalitis is the most common form of PNS and is characterized by behavioral changes and memory impairment. Isolated paraneoplastic BE is rare and presents primarily with lower cranial nerve injury. On MRI, BE showed a T2/FLAIR hyperintensity foci (Fig. 12). Lesions are occult or mildly hypointense on T1.
Figure 12. Known cases of paraneoplastic encephalitis. Symmetrical FLAIR hyperintensity foci in the cerebellar hemisphere (A), abnormal signal intensity in the left temporal lobe anteromedial and midbrain (B), abnormal signal intensity in the medial thalamus and basal ganglia, worse on the right side than on the left (D). The patient underwent examination for malignancy, followed by abdominal CT showing a right ovarian dermoid cyst (arrow E) of unknown etiology
Despite extensive medical and laboratory testing, the exact illness remains unknown in approximately 30% of BE cases (Figure 13). There is evidence that these unknown cases are secondary to autoimmune diseases, so immunosuppression is recommended in these patients.
- Figure 13. Cases of BE of unknown etiology. A 48-year-old woman with progressive neurological deficits, cranial nerve palsy and altered mental status. Extensive medical testing has not found any underlying cause. The patient received palliative care and eventually died. Presence of a wide range of abnormal signal intensities (A-C) in the brainstem (pons, cerebellar midfoot, midbrain, cerebral foot, and thalamus)
Illustrated | Neuroimaging findings of noninfectious brainstem encephalitis (below) - ConclusionBE is a heterogeneous group of diseases with different etiologies, among which infection, autoimmune diseases, demyelination, and paraneoplastic diseases are the most common causes. Despite careful medical examination, the underlying cause remains unknown in many patients. The distribution of lesions on neuroimaging is essential for the diagnosis of the etiology. MRI is always positive in the most common BE disorders, such as MS, listeria infection, and Behcet's disease. MS typically presents with infratentorial and supratentorial lesions, but is generally associated with subtentorial lesions secondary to Listeria infection or Behcet's disease. MRI after contrast is useful, and the presence of meningeal enhancement suggests other differential diagnoses such as granulomatous infection (TB) and sarcoidosis. In addition, paraneoplastic encephalitis remains an important consideration even if the patient does not have a known history of malignancy. Spinal cord imaging and lumbar puncture are essential to guide further treatment.
- 医脉通编译自：Sotoudeh H, Razaei A, Saadatpour Z, Gaddamanugu S, Choudhary G, Shafaat O, Singhal A. Brainstem Encephalitis. The Role of Imaging in Diagnosis. Curr Probl Diagn Radiol. 2021 Nov-Dec; 50(6):946-960. doi: 10.1067/j.cpradiol.2020.09.004. Epub 2020 Sep 24. PMID: 33032853.