Autoimmune encephalitis

Radswiki et al.

Autoimmune encephalitis (also known as autoimmune limbic encephalitis) is an antibody-mediated autoimmune-mediated inflammation of the brain, typically involving the limbic system, although all parts of the brain can be involved. 

Autoimmune encephalitis can be divided broadly into two groups, based on whether or not antibodies are the result of an underlying tumour: 

  • paraneoplastic limbic encephalitis
  • non-neoplastic autoimmune limbic encephalitis

Unfortunately, there is considerable heterogeneity in how the term limbic encephalitis is used. Most authors limit the term to autoimmune limbic encephalitis, including both paraneoplastic and non-paraneoplastic causes. Some, however, include viral encephalitides (especially HSV encephalitis) under the broad term limbic encephalitis.

For the purpose of this article, we will restrict the term to autoimmune encephalitis, both paraneoplastic and non-paraneoplastic causes. HSV encephalitis is discussed separately. 

The epidemiology of tumour-related autoimmune encephalitis mimics that of the underlying malignancy.

Those with non-tumour related autoimmune encephalitis have a variable epidemiology but are mostly young patients with a female predilection 8.

In approximately 60% of cases, antineuronal antibodies are present such as anti-Hu antibody in small cell lung cancer, anti-Ta antibody in testicular cancers, anti-NMDA NR1 in ovarian teratomas or anti-NMDA NR2 in SLE patients.

Clinical presentation is variable but typically is gradual with short-term memory loss (anterograde memory impairment) and mental status changes. Psychiatric symptoms, including psychosis, depression and behaviour disorder, have also been reported in over half of cases 2,8. The presence of psychiatric symptoms is particularly helpful in distinguishing limbic encephalitis from herpetic encephalitis, which otherwise can present similarly, albeit usually more acutely 8.

Seizures and fever are also encountered with some frequency 8.

Autoimmune encephalitis can be divided according to the presence or absence of an underlying tumour, or on the type of antibody responsible.

Associated tumours

Causes of paraneoplastic autoimmune encephalitis include 8,9:

Causes of non-paraneoplastic autoimmune encephalitis include:

Specific antibodies

Another way of dividing autoimmune encephalitis is on the grounds of whether the antibodies are against intracellular antigens or cell surface antigens. The antibodies, in turn, correlate both to an underlying cause and pattern of involvement 8,9. As a general rule, antibodies targetted to intracellular antigens are more frequently associated with an underlying tumour 9

  • group I - antibodies to intracellular antigens
  • group II - antibodies to surface antigens
    • anti-NMDA antibodies
      • common
      • usually in children and young women with no underlying tumour
      • older patients may have underlying tumours (e.g. ovarian teratoma)
      • typically present with psychiatric symptoms
      • mild or often absent imaging changes
    • anti-VGKC (voltage-gated potassium channel) antibodies
      • common
      • classic features of "limbic encephalitis" with prominent seizures
      • extra-limbic involvement very uncommon
    • anti-GABA antibodies
      • similar to VGKC but less common
      • two subtypes:
    • anti-AMPA antibodies
      • predominantly psychiatric symptoms
      • imaging changes limited to hippocampi
    • anti-D2 dopamine antibodies
      • basal ganglia encephalitis
    • anti-GlyR1 antibodies
      • stiff leg syndrome or stiff person syndrome, or progressive encephalomyelitis with rigidity and myoclonus
    • anti-mGluR1 antibodies
      • lymphoma with cerebellar ataxia
    • anti-mGluR5 antibodies
    • anti-GluR3 antibodies
MRI

Many cases have no imaging findings, especially early in the course of the disease. Having said that, MRI with contrast is considered the most sensitive imaging modality, and findings are present in over half of individuals 8.   

As the older term limbic encephalitis implies, the most common location of involvement is the mesial temporal lobes and limbic systems, typically manifested by cortical thickening and increased T2/FLAIR signal intensity of these regions. Bilateral involvement is most common (60%), although often asymmetric 8. The lateral temporal lobe and insula are less commonly involved, whereas the basal ganglia, in contrast, are frequently involved, helpful in distinguish it from HSV encephalitis which characteristically spares the basal ganglia 8. Although far less common, essentially any part of the central nervous system can be involved 9

Patchy areas of enhancement can be seen.

True diffusion restriction (i.e. low ADC values) and haemorrhage are not common and suggest alternative diagnoses. 

The presence of haemorrhage on susceptibility weighted images is in favour of other diagnoses such herpes simplex encephalitis which has otherwise very similar imaging appearance to limbic encephalitis.

Nuclear medicine

PET-CT may show increased FDG uptake 4

General imaging differential considerations include:

  • herpes simplex encephalitis
    • acute, often dramatic time course
    • fever
    • psychiatric symptoms uncommon
    • basal ganglia spared
  • status epilepticus
    • acute, often dramatic time course
  • tumour
    • low grade astrocytoma
      • if localized to the temporal lobe, appearances can be very similar
    • gliomatosis cerebri
      • diffuse T2 hyperintensity involving multiple contiguous lobes
      • no predilection for the limbic system
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Article Information

rID: 12686
Section: Pathology
Synonyms or Alternate Spellings:
  • Limbic encephalitis
  • Paraneoplastic limbic encephalitis
  • Autoimmune limbic encephalitis

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    Case 3: PET scan
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