The FUNdamentals
These are the two main classifications of encephalitis in pediatric patients:
What is autoimmune and infectious?
-Encephalitis is inflammation of the brain vs encephalopathy which is just an altered mental state from a variety of causes
-The most common autoimmune type is NMDAR encephalitis, other common antibody is GAD65
-Infectious causes include: HSV, EV, WNV, LaCrosse Virus, Zika Virus
Enterovirus-particularly in those less than 1 year of age
West Nile-Culex mosquito, seen in the summer; <4% of cases <18 years of age
LaCrosse-midwestern and Appalachian cities, late spring-early fall, Aedes mosquito, 88% of all cases were in patients under age 18
Zika-prenatally or age >1; Aedes mosquito, summer or early fall, area with an outbreak
A 16 year old previously healthy female presents to the Emergency Department for a new onset seizure that was witnessed at school. Parents also state that she has experienced recent disturbing behavioral changes. She has demonstrated aggressive outbursts toward them within the last 4-6 weeks, and it is causing a significant strain on the family. She used to be an A student but her grades have declined in the past three weeks. CBC, CMP, and other metabolic labs are all negative. CSF shows a notable pleocytosis and high level of neopterin. MRI shows T2/FLAIR hyperintensities in the hippocampi. This condition is a primary psychiatric condition mimic but was deemed as "A brain on fire".
What is NMDA encephalitis?
-caused by antibodies to the GluN1 subunit of the NMDA receptor which mediates excitatory neurotransmitter glutamate in the brain; the down-regulation of these receptors cause symptoms such as memory loss(hippocampus) and limbic system (behavioral changes)
-in children, autoimmune encephalitis is less likely to present with acute psychosis but may present with seizures, ataxia, developmental regression, agitation, dyskinesia
-seizures are the most common initial presentation in the younger population(ipsilateral facial grimacing and arm posturing is pathognomonic)
Cellucci et al guidelines divide into possible AE, probable AE Ab-negative AE and definite Ab positive AE
1)onset of neurologic or psychiatric symptoms <3 months
2) 2 or more other features(movement disorder, developmental regression, focal deficits, new seizures, etc) or at least one MRI, CSF pleocytosis or oligoclonal bands, or brain biopsy
To be NMDAR encephalitis-need presence of antibodies but will treat before confirmation
You have a 13 year old female who presents with behavioral changes, decline in school work, and new onset seizures that now fits into the probable autoimmune encephalitis category. You are still waiting on antibodies to come back. The first line treatment options if you are choosing to start treatment will consist of these medications:
What is:
-IV methylprednisolone 3-5 days(1g/day maximum) with famotidine, calcium, and vitamin D supplements
-IVIG 1g/kg/day for 2 days particularly if not improved with methylprednisolone
-PLEX(5 treatments but up to 7)
2nd line:
Rituximab and cyclophosphamide
Other medications and adjunctive treatments:
Anti-epileptics:prn rescue meds
Psychiatry involvement
-need to avoid high potency dopamine agonists and NMDA agonists like ketamine, volatile anesthetics and NO
This virus is one of the viruses responsible for most of the cases of viral-induced encephalitis in children. It likes to hide dormant in the trigeminal ganglia. Responsible for significant mortality and morbidity in children.
What is HSV?
-Therefore, it is important to give acyclovir promptly
IV Acyclovir Q8H, dose varies by age, consult ID for duration, neonates always 21 days minimum
-To note, HSV encephalitis became more prominent with widespread vaccination
-Measles, polio, mumps, and varicella were common before widespread vaccination
-targets the temporal lobes
-can be primary infection or reactivation from the trigeminal ganglia
-HSV-1 most common post neonatal period
-Vancomycin and ceftriaxone are usually given to cover for meningitis at the same time, consider listeria coverage with ampicillin
You have just received sign out about a 17 year old male with new onset psychosis in the ED. You consult Neurology to get medical recommendations prior to admission. However, you would like to pend some autoimmune encephalitis labs that you remember they recommended in the past. The labs you pend include:
What is:
CBC, CMP, ESR, CRP, ferritin, Vitamin B12, Vitamin D, lactate/pyruvate, copper, ceruloplasmin, ammonia, TSH, fT4, anti-TPO. ANA, UDS, UA, CSF studies : opening pressure, CSF cell count, protein, glucose, CSF lactate/pyruvate, CSF oligoclonal bands, IgG index, CSF neopterin, save CSF(may need to send of for antibodies per Neurology later)
Differentials-Nutritional deficiencies-(B12, etc) Wilson's disease, lupus, Hashimoto's, SLE, mitochondrial diseases
These are labs that you want to order to rule out other conditions that may also present with behavioral changes, acute psychosis, or AMS. There are other suggested labs depending on other symptoms the patient may have but these are ordered on most patients.
*note- neopterin is noted to be very sensitive for CNS inflammation due to it being produced intrathecally. In pediatric populations it has been highly elevated in acute encephalitis. It has also been shown to be more sensitive than CSF pleocytosis for CNS inflammation
SREAT-Steroid Responsive Encephalopathy Associated with Autoimmune Thyroiditis-a speculative diagnosis because it is unknown if there is a target for thyroid antibodies TPO or thyroglobulin but pediatric patients have been responsive to steroids even without full clinical thyroid disease
DALE, R.C., BRILOT, F., FAGAN, E. and EARL, J. (2009), Cerebrospinal fluid neopterin in paediatric neurology: a marker of active central nervous system inflammation. Developmental Medicine & Child Neurology, 51: 317-323. https://doi.org/10.1111/j.1469-8749.2008.03225.x
AdamsAV, MooneyhamGC, Van MaterH, GallentineW. Evaluation of diagnostic criteria for hashimoto encephalopathy among children and adolescents. Pediatr Neurol. 2020;107:41–47
A family wants to know will their child ever be completely back to their baseline function after treatment for encephalitis. The prognosis is:
The patient could have persistent neurocognitive changes so they will need consistent neuropsychiatric follow-up.
-Over 40% of pediatric patients with encephalitis will not go back to their baseline neurologic function
-64% of those affected with HSV encephalitis have late neurocognitive effects
Autoimmune encephalitis prognosis: 1/3 completely recover, 1/3 partially recover, 1/3 have severe deficits with a very minimal improvement
Relapse is possible so prompt and adequate treatment is necessary
You have a 7 year old patient who presented with altered mental status for over 24 hours now, and you have done a full work up that has ruled out most metabolic causes. You are now concerned for encephalitis. You know she has met the first criteria, but name 2 or more other criteria that would make encephalitis even more likely.
First criteria deemed by the International Encephalitis Consortium:
1) Altered Mental Status for >24 hours without an alternative diagnosis
2)2 or more of the following below:
-fever >100 F within 72 hours
-seizures
-new focal neurologic findings
-CSF pleocytosis WBC >5/uL
- abnormal neuroimaging findings consistent with encephalitis
-EEG readings with encephalitis findings such as generalized or focal slowing
You are ready to order imaging for your female patient with suspected autoimmune encephalitis. The imaging modalities you order include:
What is:
-epilepsy protocol MRI w/wo contrast
It has been recommended to utilize an epilepsy protocol to better visualize the hippocampi
In general, here we typically order an MRI w/wo contrast of the brain
-CT is not as accurate for patients
Overall MRI findings: HSV encphalitis(unilateral medial temporal lobe) autoimmune(limbic system or hippocampi)
-abdominal US in all(*note:only 6% in patients younger than 12 will have a teratoma)
Males: scrotal US for a testicular teratoma(6%)
*CT abdomen, chest, pelvis if highly suspicious
Highly recommend the book Brain on Fire by Susannah Cahalan
or
Watch the movie Brain on Fire on Netflix