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Year : 2015  |  Volume : 63  |  Issue : 5  |  Page : 647--649

Autoimmune encephalitis - The evolving spectrum: An Indian case series

Saiju Jacob 
 Department of Neurology and Neuroimmunology, University Hospitals Birmingham and University of Birmingham, B15 2TH, United Kingdom

Correspondence Address:
Saiju Jacob
Department of Neurology and Neuroimmunology, University Hospitals Birmingham and University of Birmingham, B15 2TH
United Kingdom

How to cite this article:
Jacob S. Autoimmune encephalitis - The evolving spectrum: An Indian case series.Neurol India 2015;63:647-649

How to cite this URL:
Jacob S. Autoimmune encephalitis - The evolving spectrum: An Indian case series. Neurol India [serial online] 2015 [cited 2020 Jul 4 ];63:647-649
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Full Text

Immune-mediated encephalitis (often described as “limbic encephalitis” [LE]) has been described for nearly 50 years, although this was always thought to be paraneoplastic with a progressive course, with minimal recovery. However, with the description of voltage gated potassium channel (VGKC) antibodies in 2001,[1] neurologists have been made aware of a new group of treatment-responsive autoimmune encephalitides (AIE). Subsequently, the targets of these voltage-gated potassium channel (VGKC)-complex antibodies have been found to be the complexing proteins including leucine-rich glioma inactivated 1 (LGI1) protein, contactin-associated protein (Caspr2) etc.[2],[3] N-methyl D-aspartate receptor (NMDAR) antibodies were initially described as an exclusive paraneoplastic phenomenon in young women with ovarian teratoma,[4] but this is now seen in a much wider population with less frequent evidence of underlying malignancy.[5]

In this edition, 16 patients with AIE with antibodies against neuronal surface antigens are described. This is one of the largest series from India and shows that the phenotype is very similar to that described in the Western literature. NMDAR antibodies tend to be the most common, similar to that described in the California Encephalitis Project (although the California data was derived from a selected group of patients <30 years with otherwise unexplained encephalitis). Patients tend to be younger with prominent neuropsychiatric symptoms, often preceded by fever and headache that might suggest an infection. This is important in two aspects:

Patients may be treated as viral encephalitis without any immunotherapy, with subsequent worse prognosis, andOver diagnosing and treating for AIE should be avoided without excluding the infectious etiologies, especially in developing countries, where the likely viral (herpes simplex virus [HSV], Enterovirus, measles, Japanese B, dengue, etc.), bacterial, and mycobacterial causes should always be kept in mind. This is especially true with rabies where agitation, involuntary movements and excessive secretions can sometimes be confused with NMDAR encephalitis.

At the same time, physicians should also be aware that certain viral encephalitis like HSV can trigger production of antibodies causing AIE, which would have an unsatisfactory outcome if not treated with immunomodulatory therapy.[6] Also, polymerase chain reaction for HSV can sometimes be false negative within the first 48 h of the infection.

On the other hand, patients with LGI1 (VGKC-complex) antibody mediated encephalitis generally tend to be older, with more sub-acute onset of memory impairment, seizures, and often develop characteristic faciobrachial dystonic seizures. Patients with NMDAR encephalitis seem to have a stormier initial course and require more intensive immunomodulation, but often have a better long-term prognosis than the LGI1 patients who are frequently left with mild cognitive impairment. NMDAR encephalitis patients often get back to their premorbid occupation (frequently requiring high intellectual ability), although most patients with the LGI1 AIE have had to make some adjustments at their workplaces (personal observation, unpublished). It is likely that the delay in start of the immunosuppression, because of the relatively indolent nature of the VGKC-complex (LGI1) antibody-mediated encephalitis, leads to more irreversible damage.

Other antibodies which are less commonly identified include those against α-amino-3-hydroxy-5-methyl-4-isoxazo lepropionic acid receptor [AMPAR] (LE with psychiatric features), gamma-amino butyric acid b receptor [GABAbR] (LE with seizures), contactin- associated protein-like 2 [Caspr2] (LE with neuromyotonia or Morvan's syndrome), GABAaR (refractory seizures), metabotropic glutamate receptor 5 [mGluR5] (LE in patients with Hodgkin's lymphoma, also known as Ophelia syndrome), glycine receptors (stiff person syndrome, progressive encephalomyelitis with rigidity and myoclonus), dopamine 2 receptors (basal ganglia encephalitis with movement disorder), dipeptidyl peptidase-like protein 6 [DPPX] (encephalitis preceded by a diarrhoeal illness), and IgLON5 (parasomnia, ataxia, and chorea). It is likely that in all these disorders, cerebrospinal fluid (CSF) antibodies are more sensitive and specific for the diagnosis and are recommended, especially if the initial serum sample is negative.

Controversy exists regarding the entity of Hashimoto's encephalopathy, but it is well recognized that there is often a steroid responsive encephalopathy associated with Hashimoto's thyroiditis (SREAHT). Even if the thyroid peroxidase antibody is not directly pathogenic, it is likely to be a marker for this highly steroid-sensitive syndrome that is associated with prominent visual hallucinations along with encephalopathy. Hypothermia has been noticed in Hashimoto's and other AIE suggesting hypothalamic involvement[7] (also unpublished personal observation). Intravenous immunoglobulin (IVIG) has been found to be useful in occasional steroid-resistant patients.[8]

Another expanding interest is the role of neuronal surface antibodies in a variety of psychiatric diseases,[9] which is the basis of an on-going research in the UK. However, it is not clear which sub-type of psychotic disorders are more likely to have auto-antibodies, whether the low titers are pathologically relevant (i.e., are they a primary or secondary phenomenon), or whether CSF antibodies are a better marker than the serum ones. Hopefully, this would be clearer in the next few years.

The suggested treatment algorithm in these patients have been published before and essentially involves looking for an underlying tumor (and its removal, if found) followed by either intravenous (IV) steroids, IV immunoglobulin (IG) or plasma exchange, which is often decided based on the severity of the illness. For example, in a patient presenting with refractory status, it might be best to start treatment with plasma exchange (if facilities are available), so that follow-up treatments like IVIG or IV methylprednisolone are less likely to be washed off with subsequent plasma exchange [Figure 1].[9] Second-line treatments include cyclophosphamide and rituximab.[10]{Figure 1}

The current study from a large neuroscience center from South India identifies 16 patients with AIE over a three and a half year period, with neuronal surface antibodies (NMDAR and LGI1) seen in 12. It is reassuring to note that for all patients in whom follow-up data are available, the response to immunomodulation was good. It is entirely possible that patients with less aggressive disease, especially in the older age group (typically like that seen associated with LGI1/VGKC-complex antibodies), are under recognized and hence not referred for a neurology opinion, let alone tested for autoantibodies. With increasing awareness of this expanding field of treatable neurological conditions, it is likely that more patients would be treated leading to better clinical outcomes.


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