Autoimmune Encephalitis in Pediatrics: Symptoms & Treatments

A group of inflammatory disorders of the brain with an autoimmune pathogenic basis. 

They can occur at any age, but most of these patients tend to occur in two age groups: adolescence and childhood. 

In most of the patients, no cause can be found but can be triggered by certain tumors or infections and by disruption of blood-brain barriers. Autoimmune Encephalitis is suspected when there is an acute onset of CNS symptoms like Psychosis, Chores-athetoid movements, Acute onset seizures, which are recurrent, Catatonia and Any sleep disturbances.

If one or more of these phenomena are present and they occur in the absence of any infection being directly implicated, this suspects a patient probably has autoimmune encephalitis. 

The entities which are included in autoimmune encephalitis are: 

• Acute demyelinating encephalomyelitis (ADEM)
• Anti-NMDAR Encephalitis
• Encephalitis associated with GABA_A receptor antibody.
• Ophelia syndrome (Anti-mGluR5 Antibodies).
• Opsoclonus-myoclonus syndrome (it is strongly associated with paraneoplastic phenomena).
• Bickerstaff Encephalitis 
• Rasmussen Encephalitis
• Basal ganglia Encephalitis
  • ROHHAD, CLIPPERS

In this blog we will discuss some of them, it is highly recommended that the video lecture from the SS Pediatrics section in the PrepLadder app.

Also read : Pediatric Epilepsy Syndromes with Favorable and Unfavorable Outcome

Anti-NMDAR Encephalitis

NMDA stands for N-methyl-D-aspartate, with two binding sites that can bind with glutamate and glycine. When they bind, the calcium channel opens and allows the movement of the calcium channel. It is considered to be an excitatory receptor in the patient. It is involved in neurotransmission, CNS plasticity  and learning disorders and controls the person's behavior, the emotional status of the patient, etc. The cause in most patients is idiopathic but can be triggered by tumors and by proceeding CNS viral infection.

The teratomas are the most common tumors, which can precipitate Anti-NMDAR Encephalitis and in viral infection, it can be triggered by HSV-1 infection. NMDA receptor has three subunits Glu N1, Glu N2, and Glu N3. An autoantibody is directed against the Glu N1 subunit, which is the IgG antibody. It is most commonly seen in females (80%). If the age is less than 12 years, males are more commonly affected. 

Clinical Presentation of Anti-NMDAR Encephalitis

• Acute Onset Psychiatric Illness/Psychosis includes:
  • Anxiety, agitation, mania, delusions, catatonia, insomnia, language disintegration, labile mood, aggression and bizarre behavior may or may not be associated with the preceding prodrome. 
• Many of these patients will be diagnosed as having probably recent-onset schizophrenia, recent onset Mania, etc.

Investigations in Anti-NMDAR Encephalitis

The investigation of choice is tested for Anti-NMDA receptor antibodies in both CSF and blood. Other investigations include an MRI brain in which 35% of patients will have abnormalities that are non-specific cortical or subcortical changes in T2 and Flair images. In CSF examinations, about 80% of patients will have an increase in the lymphocytic response. 

EEG is abnormal in 95% of patients with focal or generalized slow activity  and the Hallmark finding found in 30% of adult patients is called the extreme delta brush pattern. It is characteristic of Anti-NMDA receptor Encephalitis.

Treatment of Anti-NMDAR Encephalitis

• Tumor removal if detected.
• Immunotherapy is the mainstay of management (success rate to 50%), including Steroids, IVIG, and Plasmapheresis.
• Rituximab, when added, improves outcomes to upto 75%.
• In refractory cases, Cyclophosphamide can be tried.

Outcome & Prognosis of Anti-NMDAR Encephalitis

Recovery occurs in 80% of patients but is slow and can take 2 years or more. The last to improve is Social & Language functions. Relapses are seen in 15% of cases but are usually milder. The role of chronic immunosuppression is doubtful. Mortality occurs in 7% of cases.

Also read: Inherited Tubular Transport Disorders In Children

Encephalitis associated with Antibodies Against the Gaba-A Receptor

There are two types of GABA receptors: GABA A and GABA B. GABA A is present widespread all through the central nervous system. It is considered a type of pentamer as it contains two types of alpha chains, two types of beta chains and one gamma chain, but there are six types of alpha chains, three types of beta chains and three types of gamma chains that can be found. 

The autoantibody formed is directed against either the alpha 1 chain, beta 3 subunit or gamma 2 subunit of the GABA-A receptor. In most children, it is idiopathic, whereas in adults, 40% of cases are associated with thymic tumors or thymomas.

Treatment of Encephalitis associated with Antibodies Against the Gaba-A Receptor

Good response in about 80% of the cases with immunotherapy.

Ophelia Syndrome

Ophelia Syndrome is seen in both children & adults. Most cases are associated with underlying Hodgkin's Lymphoma. The type of autoantibody produced is Anti-mGluR5. 

mGluR5 is normally involved in new learning abilities & memory. Patients will develop CNS features along with memory loss. 

Treatment of Ophelia Syndrome

Treatment is Tumor Management + immunotherapy. In Hodgkin's Lymphoma with Reed-Sternberg cells which are CD20+, Rituximab is highly effective in controlling tumors and Ophelia syndrome.

Hashimoto Encephalitis

Hashimoto Encephalitis is also known as SREAT -Steroid Responsive Encephalitis with Autoimmune Thyroiditis. Patients have acute/subacute encephalitis and also form Anti-TPO. Special features include Stroke, Ataxia, tremors, myoclonus, and aphasia. EEG shows Generalized slow activity, and MRI is usually normal/non-specific. The lesion is highly responsive to Corticosteroids.

Bickerstaff Encephalitis

Bickerstaff Encephalitis is more common in adults compared to children. The three Cardinal features are Ataxia, Bilateral external ophthalmoplegia and depression of the Consciousness. They always have an acute onset and the onset happens within four weeks. The auto-antibody found is Anti GQ1b antibody in 66% of these patients. If the patient also has areflexia and muscle weakness, it can mimic or overlap with (MFS) Miller Fisher Syndrome, a variant of Guillain-Barre syndrome. MRI shows about 30 percent signal abnormalities in Thalamus, brainstem, etc. 

Rasmussen Encephalitis

Rasmussen Encephalitis is an inflammatory Encephalopathy involving one part of the brain with gradual progressive atrophy of one part.  It produces refractory focal seizures. It produces focal neurological deficits and Progressive loss of cognition called Rasmussen Encephalitis.

All these features appear because of progressive unilateral atrophy of one cerebral hemisphere. The exact autoantibody causing these has not been found. The age during which it happens is six to eight years however, it can occur in adults also. Non-specific viral infections can precipitate it. In imaging, significant atrophy and enlargement of the ventricles on one side cause focal seizures, focal neurological deficits and progressively declining cognitive function. 

Treatment of Rasmussen Encephalitis

Treatment comprises immunotherapy and if immunotherapy is ineffective, rituximab or intraventricular injections of Interferon-gamma have also been tried and shown to reduce the occurrence. To decrease the progression of the disease, Tacrolimus can be added.

Also read: Community Pediatrics Indices

Autoimmune Limbic Encephalitis

Autoimmune Limbic Encephalitis is rare in children, mostly seen in adults. Inflammation occurs in the limbic system. Autoantibodies formed here are:

• Anti-VGKC[voltage-gated potassium channel]; Now identified as Anti-LGI(Leucine-rich Glioma Inhibited 1 Ab) where Hyponatremia is present.
• Anti-Caspr2: Produce Morvan Syndrome.

Opsoclonus-Myoclonus Syndrome

Opsoclonus-Myoclonus Syndrome is Seen in children & adults, with differing etiology.  In Children, 50% of cases are associated with neuroblastoma and occur in Age <2 yrs. While in adults the disease is Idiopathic, Post-infectious, and associated with Ovarian Teratoma.

In adults, included in the ambit of Brainstem-Cerebellar Encephalitis. A specific autoantibody is unknown; Excess B-Cell Activation & Anti-neuronal antibodies are sometimes found.

Early features of Opsoclonus-Myoclonus Syndrome are ataxia, irritability, tremors, drooling, hypotonia and myoclonus. The Later features are Opsoclonus- rapid, chaotic multi-directional eye movements without saccadic intervals.

Treatment of Opsoclonus-Myoclonus Syndrome

Immunotherapy treats opsoclonus, but behavioral, language/cognitive abnormalities persist. Relapses are seen in 50% of cases.

Frequently asked Questions:

Q: A 3-year-old child developed HSV Encephalitis and was successfully managed and discharged. 6 weeks later, he presented with a recurrence of symptoms, this time with choreoathetosis and dyskinesia's. What should be suspected?

Ans: It is likely relapsed, but the pattern of relapse was different. So it is post HSV infection causing Anti-NMDA-R Encephalitis as HSV-1 infection can be a trigger factor for this Anti-NMDA-R Encephalitis. It is identified that children aged less than four years will have prominent movement disorders and if it is an older child, behavioral disorders occur. Post-HSV can cause Anti-NMDA-R Encephalitis after 2-12 weeks of HSV infection.

Q: Which is the most common type of Autoimmune Encephalitis?

Ans: ADEM/Acute demyelinating encephalomyelitis is the most common type of Autoimmune Encephalitis.

Q: What is the Treatment of Rasmussen Encephalitis?

Ans: The Treatment of Rasmussen Encephalitis comprises immunotherapy and if immunotherapy is ineffective, rituximab or intraventricular injections of Interferon-gamma have also been tried and shown to reduce the occurrence.

Hope you found this blog helpful for your NEET SS Pediatrics Neurology Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.