Rhombencephalitis (plural: rhombencephalitides) refers to inflammatory diseases affecting the hindbrain (brainstem and cerebellum) and has a wide variety of aetiologies including infection, autoimmune disease, and paraneoplastic syndrome, with Listeria monocytogenes being the most common cause. Rhombencephalitis carries significant morbidity and mortality. 

For a specific discussion, please refer to articles:

• Listeria rhombencephalitis

• tuberculous rhombencephalitis

• paraneoplastic rhombencephalitis

Terminology

It is important to remember that both terms "rhombencephalitis" and "brainstem encephalitis”, despite being used as interchangeable terms, are anatomically different, as the former includes the cerebellum as well as the brainstem. 

Clinical presentation

Symptoms can vary due to the different causes of rhombencephalitis. When caused by a virus it usually presents with headache, vomiting, fever, and ill-defined neurological symptoms (the prodromal stage lasting for one to two weeks). Subsequently, patients develop a spectrum of brainstem symptomatology such as cranial nerve palsies (occur in ~75% of all cases), and cerebellar and long-tract motor and sensory deficits.

Pathology

• infectious

  • viral

    • enterovirus 71: is probably the second most common of infectious rhombencephalitis

    • herpes simplex virus (HSV): is the third most common

      • 80% are caused by HSV1 

      • 20% are caused by HSV2

    • Epstein-Barr virus (EBV)

    • human herpesvirus 6 (HHV6) 

    • flaviviruses (e.g. West Nile virus and Japanese encephalitis virus)

    • JC virus (i.e. progressive multifocal leukoencephalopathy)

  • bacterial

    • Listeria monocytogenes: the most common cause of infectious rhombencephalitis ⁷

    • Mycobacterium tuberculosis

    • Rickettsia, Borrelia burgdoferi, Salmonella typhi, Legionella bozemanii and Mycoplasma pneumoniae are agents that rarely cause encephalitis, but can involve the brainstem. 

• autoimmune ⁷

  • Behçet disease (most common autoimmune cause)

  • systemic lupus erythematosus

• paraneoplastic syndromes: associated with antibodies (e.g. anti-Yo, anti-Hu) and, in the majority of cases, having small cell lung cancer as the underlying cause ⁷

• malignancy

  • lymphoma (rare)

Radiographic features

Beam-hardening artifacts limit the visualisation of the brainstem on CT images. MRI with contrast is the imaging modality of choice for the assessment of patients with suspected pathology in that anatomic location.

MRI

When caused by infectious agents, rhombencephalitis usually has the following signal characteristics:

• T1: hypo- or isointense lesion

• T2/FLAIR: hyperintense

• DWI: hyperintense

• ADC: hypointense

• T1 C+ (Gd):     

  • linear cranial nerve enhancement

  • ring enhancement (abscess)

  • heterogeneous if extensive inflammation

• MR spectroscopy: allows differentiation between abscess from tumour

Treatment and prognosis

Rhombencephalitis requires early diagnosis and treatment to avoid neurological sequelae. The mortality rate is reported between 10-15% ³. 

History and etymology

It was first reported by Edwin Bickerstaff and Philip Cloake in 1951 ². The term is derived from the Greek: "rhombos" (lozenge-shaped figure) and "enkephalos" (brain).

Differential diagnosis

• brainstem tumour

• chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)

• neuromyelitis spectrum disorder (NMOSD)

• myelin oligodendrocyte glycoprotein​ antibody-associated disease (MOGAD)