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Menon et al. Pediatric anti-GAD antibody mediated encephalitis

INTRODUCTION multifocal stimulus sensitive myoclonus. There was no
evidence of any behavioural or cognitive decline, limb
The spectrum of autoimmune encephalitis is ever weakness, seizures, opsoclonus or any extrapyramidal
expanding, with presentations outside the distinctively involvement with no history of drug/toxin exposure.
symptomatic groups being recognized every day. Blood biochemistry and serology were normal. Based
The array of intraneuronal and cell surface antibodies on the possibility of a post-infective or a paraneoplastic
are fairly well elucidated with the former associated immune mediated myoclonic ataxia syndrome, magnetic
with paraneoplastic etiology and poor response resonance imaging (MRI), cerebro-spinal fluid (CSF)
to immunosuppressive agents. While the clinical study including lactate levels, electroencephalogram (EEG)
[1]
spectrum of non-paraneoplastic encephalitis, like and somato-sensory evoked potentials were ordered
anti-N-methyl-D-aspartate receptor (NMDAR) and were normal. A search for a neoplastic focus
encephalitis and voltage-gated potassium channel with ultrasonography abdomen and chest X-ray was
(VGKC) encephalitis, has been well described, the negative. Twenty-four hours urine vallinly mandelic acid
[1]
presentations of anti-glutamic acid decarboxylase and metanephrine tests were conducted to exclude
antibody (GAD-ab) positive encephalitis are unclear. occult neuroblastoma and urine aminoacid estimation
GAD-ab is directed to an intracellular enzyme and to exclude alkaptonuria was also normal. He was
therefore considered to be the unlikely pathogenic empirically started on a course of intravenous (IV)
moiety in itself. However, epilepsy and cerebellar ataxia methylprednisolone after excluding any active infection.
represent the 2 most common neurological syndromes Over the period of the next 2 weeks, he had resolution of
described in adults with this antibody. In vitro, GAD-ab all his symptoms and the steroids were tapered off over
[2]
from patients with neurological syndromes induce a 6 weeks. However, he presented to us 6 months later
suppression of gamma amino-butyric acid (GABA) with recurrence of the same complaints with much more
release. The diagnostic value of low titres of GAD-ab severe symptoms along with irritability, hyperactivity and
[3]
in a patient with a neurological syndrome is unknown, temper tantrums. Considering his recurrent course and
as opposed to high titres as was seen in recently apparent steroid responsiveness, a further search was
described case series in patients with autoimmune done with repeat MRI, including MRI abdomen, CSF
endocrinopathies, like type 1 diabetes mellitus (DM1) oligoclonal bands and autoimmune panel of antibodies
or central nervous system (CNS) autoimmunity, such as including NMDA, VGKC, and GAD 65 as well as anti-
limbic encephalitis. [2,4] aquaporin antibodies. His antibody panel revealed an
elevated GAD 65-abtitre of 10.7 IU/mL (0.0-5.0 IU/mL)
The largest reported cohort of 9 adult patients with by enzyme-linked immunosorbent assay (ELISA) and
GAD-ab mediated limbic encephalitis was notable for a the rest of the investigations were negative including
poor response to treatment in comparison with VGKC blood tandem mass spectroscopy. Considering the
antibody positive encephalitis, however, only a minority severity of symptoms he was started on a simultaneous
had been given the benefit of immunomodulation with course of intravenous methylprednisolone (20 mg/kg
immuoglobulin. Currently, anti-GAD-ab disorders of for 5 days) and immunoglobulin (400 mg/kg for 5 days)
[4]
the CNS in the pediatric age-group are rarely reported. with which all his symptoms completed remitted in 1
Here we report a case series in the pediatric age week. He was maintained on oral steroids with plans for
group with variable clinical presentations, course and a longer duration of maintenance and slow taper. After
treatment response with the 2 patients demonstrating nearly 24 months of follow-up he is symptom free with
definite elevations in anti-GAD 65 antibody titres, adding preserved motor and cognitive abilities and is presently
to the evolving clinical conundrum of CNS autoimmunity off steroids.
in childhood.
Case 2
CASE REPORT A 7-year-old girl, product of a non-consanguineous
parentage with normal birth and development history,
Case 1 presented with habitual seizures since 2 years of age
A 3-year-old boy, product of a non-consanguineous without any initial precipitating event. Her seizure
parentage with normal birth and development presented semiology was suggestive of frontal lobe epilepsy
to us with subacute onset incoordination of upper and with more than 95% events being nocturnal events
lower limbs along with scanning dysarthria. A flu-like occurring out of sleep and characterized by head and
prodrome was noted nearly 20 days prior to onset. eye deviation to the right side with right upper limb
Around 10 days into illness parents had also noted abduction, clonic jerks and right facial jerks. Since the
sudden jerky movement of extremities. His examination onset of seizures parents noted delay in subsequent
was notable for pancerebellar involvement with development as well as a shift of handedness from
220 Neuroimmunology and Neuroinflammation ¦ Volume 3 ¦ September 28, 2016