Pictures and texts | Neuroimaging manifestations of non-infectious brainstem encephalitis (Part 1)

Brainstem encephalitis (BE) or rhomboencephalitis refers to rhomboencephalitis secondary to multiple etiologies and varying prognosis Rare infectious/inflammatory diseases of the pons, cerebellum, and medulla oblongata). The rhomboencephalon consists of the hindbrain (pons, cerebellum, and ventral side of the fourth ventricle) and the spinal brain (medulla oblongata and dorsal side of the fourth ventricle). The midbrain (the diencephalon) is not part of the rhomboencephalitis, however, because it is continuous with the pons and is often involved, it is also classified as part of rhomboencephalitis. The most common causes of BE are infectious diseases, autoimmune diseases, demyelination, and paraneoplastic syndromes. Correct and early diagnosis is critical to management, as some of these causes can be serious or even fatal if not treated properly. BE initially presented with nonspecific fever, headache, nausea, and vomiting, followed by typical presentations including ataxia (69.1%), ocular dysfunction (58%), bulbar dysfunction (58%), and limb weakness (58%). The clinical presentation of BE and the distribution of lesions on MRI help narrow the differential diagnosis. This article summarizes the most common noninfectious causes of BE and their neuroimaging findings.

Behcet p>

Behcet’s disease is a rare vasculitis that mainly affects small blood vessels. Typical presentations are oral genital ulcers, uveitis, arthritis, and gastrointestinal manifestations. Neurobehcet’s disease consists of a parenchymal inflammatory syndrome that primarily affects the brainstem and BG. Neurobehcet’s disease is the most common autoimmune disease presenting with BE and has been reported to be present in up to 50% of patients with systemic Behcet’s disease. The characteristic imaging finding is T2 hyperintensity with vasogenic edema. T1C+ showed moderate patchy parenchymal enhancement, mainly in the acute phase of the disease (Figure 1). Lesions are most common in the brainstem (the most common site of involvement), followed by the BG, thalamus, and less frequently in the subcortical white matter and spinal cord. Neurobehçet lesions can mimic multiple sclerosis; however, involvement of the periventricular and corpus callosum interfaces is uncommon. Optic neuritis is common in this disease. In addition, vascular involvement can manifest as intracranial sinus thrombosis.

Figure 1. Two cases of Behcet’s disease with BE. In case 1 (A and B), abnormal signal intensities on FLAIR (A) and enhancement (B) were concentrated on the left side of the medulla. Case 2 (C and D) T2 pons with abnormal signal intensity and abnormal enhancement of right cerebral peduncle

• Systemic lupus erythematosus (SLE)

SLE is an autoantibody-producing and immune complex Autoimmune connective tissue disease characterized by formation. Laboratory abnormalities include abnormal white blood cell counts, presence of antinuclear antibodies, double-stranded (ds) DNA antibodies, anti-Smith (Sm), anti-ribonucleoprotein antibodies, anti-ribosomal phosphoprotein (anti-P), antiphospholipid antibodies, serum complement levels, serum immunoglobulins, and erythrocyte sedimentation rate. SLE involving the CNS is collectively referred to as neuropsychiatric lupus and can manifest as headache, seizures, cerebrovascular disease, psychosis, mood disturbances, cranial neuropathy, cognitive impairment, altered mental status, myelopathy, and movement disorders. CNS involvement includes supratentorial encephalitis, aseptic meningitis, stroke, demyelination, transverse myelitis, and rarely BE (Figure 2). Imaging findings are nonspecific; however, multisystem involvement can guide the correct diagnosis. Acute lesions manifested as edema, inflammatory infiltration, and demyelination, high signal on T2/FLAIR, low signal on T1, punctate or peripheral enhancement, and cytotoxic edema in some lesions, suggesting acute ischemic changes.

Fig. T2 (A) and FLAIR (B) punctate foci of high signal intensity in the superior pons and cerebellar hemisphere with punctate enhancement after contrast injection (C). Lesions smaller than 3mm

• multiple sclerosis

Multiple sclerosis (MS) is the most common autoimmune inflammatory disease of the CNS, with increasing incidence and prevalence over the past few decades. rise. T2/FLAIR and post-enhanced T1 are the main basis for the diagnosis and management of MS. The typical MS manifestations are FLAIR/T2 hyperintense foci mainly at the periventricular and corpus callosum interface. Brainstem involvement is also common. Isolated brainstem and cerebellar MS is challenging and difficult to distinguish from other causes of BE. The presence of the central venous sign has been reported to distinguish MS lesions from other causes of BE with great accuracy. The typical lesions of supratentorial, corpus callosum, optic nerve, optic chiasm, spinal cord and other parts are also helpful for diagnosis. In the brainstem, MS lesions are usually peripherally located (Figure 4). Sometimes cranial nerve nuclei and root entry areas can be involved, and specific cranial nerve symptoms, such as trigeminal neuralgia or hemifacial spasm, can occur.

Figure 4. MS case with brainstem involvement. FLAIR hyperintense foci in the pons and right cerebellar peduncles. The lesions are superficial (A and B). Abnormal signal lesions are seen in the right trigeminal root entry zone (REZ) (A). Supratentorial lesions are typical of MS with Dawson finger morphology (C) and corpus callosum interface involvement (arrow D)ADEMacute disseminated Encephalomyelitis (ADEM) is another immune-mediated demyelinating disease of the CNS that occurs primarily in early childhood. ADEM usually occurs two weeks after viral infection or vaccination, and is usually a monophasic disease (as opposed to MS). The typical presentation is multifocal neurological deficit, sometimes with prodromal symptoms (fever, malaise, irritability, lethargy, headache, nausea, and vomiting). The clinical course of ADEM usually progresses rapidly, with maximum deficits occurring within 2-5 days. Common neurological manifestations include pyramidal signs, ataxia, hemiplegia, optic neuritis, seizures, and spinal cord syndrome. Respiratory failure secondary to brain stem involvement may be rare. On MRI, there are usually reversible, symmetric, ill-defined T2-FLAIR hyperintensity foci involving subcortical and deep white matter, BG, thalamus, brainstem, and cerebellum. Lesions can vary in size in one patient. Lesions may show enhancement. In addition, spinal cord injuries were seen in one-third of patients. In contrast to MS, the lesions are monophasic and synchronous, with no periventricular white matter lesions (Dawson’s
fingers). Furthermore, ADEM lesions are typically larger and have poorer margins compared to MS. The presence of brainstem involvement, matching clinical history (recent viral infection/vaccination), and indeterminate large patchy lesions in subcortical and deep white matter, BG, and thalamus facilitate accurate diagnosis (Figure 5).

Fig. Foci of FLAIR hyperintensity in the right middle cerebellar peduncle and pons (A), deep basal ganglia and periventricular areas are involved (B). The lesions are large and poorly demarcated (compared to MS). Lesions exhibit mild open-edge enhancement (C and D)

• neuromyelitis optica spectrum disorder

Neuromyelitis optica optic spectrum disorder (NMOSD) is another known disorder associated with demyelination Autoimmune CNS inflammation of the sheath, but the prevalence is 100-fold lower than in MS. It is a clinical manifestation of optic neuritis and myelitis occurring simultaneously or sequentially. It differs from MS in physiopathology, with the presence of serum IgG autoantibodies against astrocyte aquaporin 4 (AQP4) in up to 80% of cases. Most of the traditional immunomodulatory drugs used for MS treatment are ineffective or even harmful for NMOSD, so accurate diagnosis is crucial. In addition to optic neuritis and transverse myelitis, NMOSD can involve the brainstem (usually the hindbrain area), diencephalon, and cerebral hemispheres. Brainstem involvement can manifest as nausea and vomiting, hearing loss, diplopia, vertigo, and facial paralysis. MRI is critical for the diagnosis of NMOSD, especially in seronegative patients. MRI findings are characteristic, although not characteristic, of NMOSD. Classic imaging findings include unilateral or bilateral optic neuritis and complete transverse myelitis, which occur simultaneously or sequentially at different times. The distribution of lesions on MRI is parallel to any level of the highest AQP4 expression adjacent to the ventricular system, such as the hypothalamus, the third and periventricular regions, the cerebral aqueduct, the corpus callosum, and the dorsal brainstem near the fourth ventricle (Fig. 6). Diencephalic lesions and abnormal signal lesions in the dorsal brainstem, around the fourth ventricle, including the hindbrain region and the nucleus of the solitary tract, are highly specific for NMOSD. However, lesions were not limited to areas with high AQP4 concentrations. Up to 42% of patients can meet imaging criteria for MS, including corpus callosum involvement. Nonetheless, these lesions are usually located on the ventricular and ependymal surfaces, unlike MS, where lesions are predominantly periventricular. The involvement of gray matter is also essential to distinguish MS from NMOSD. Cortical lesions are reported more frequently in MS by using the 7T MR scanner; however, they are rare in NMOSD. Longitudinal extensive myelitis lesions (LETM) involving 3 or more vertebral segments are considered suggestive of NMOSD, usually involving more than 50% of the spinal cord and gray matter surface. LETM is more common in the cervical cord and may involve the brainstem. In contrast, MS spinal cord injuries are usually small and peripheral.

Fig. In the first case (A-C), there were patchy FLAIR hyperintense foci in the pons, cerebellar peduncle, and cerebellar hemispheres (A and B), with involvement of the right posterior optic nerve (arrow C). In the second case, FLAIR hyperintensity foci around the fourth ventricle (D), involving the thalamus (E) and the pontomedulla-cervical junction (F)

• Anti-MOG-Associated Encephalomyelitis

Serum immunoglobulin G antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been described for decades. However, its pathophysiology and association with demyelination have not been explained until recently. Anti-MOG antibody-associated encephalomyelitis/encephalitis is now considered a separate demyelinating disease. It is presented in a similar way to ADEM. However, anti-MOG-related demyelination may recur, and ADEM is usually a monophasic disease. Anti-MOG antibody-associated encephalomyelitis/encephalitis is more common in children. This condition may resemble NMOSD, and this antibody is positive in 40% of NMOSD patients who are seronegative for aquaporin 4 (AQP4) antibodies. The neuroimaging findings of anti-MOG demyelination were similar to ADEM, with diffuse T2/FLAIR signal abnormalities in cortical gray matter (GM)/subcortical white matter (WM), deep WM, and deep GM. Anti-MOG-related lesions are more defined and cortical-based than ADEM lesions. Optic neuritis (ON) pattern can differentiate anti-MOG encephalomyelitis from MS. Anti-MOG-related ON is usually bilateral and elongates with orbital involvement of the optic nerve without affecting the optic chiasm. Periorbital nerve enhancement and orbital tissue extension are also common in anti-MOG-related ON. On the other hand, ONs in MS typically extend shorter and involve crossings. Also in MS-related ON, optic nerve enhancement does not extend to adjacent soft tissue. BE was seen in one-third of patients with anti-MOG-associated encephalomyelitis (Figure 7).

Figure 7. A patient with anti-MOG syndrome involving the ventral medulla (A) and superior cerebellar peduncle

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☑ Pictures and texts | Neuroimaging manifestations of infectious brainstem encephalitis

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