VGKC-complex antibody mediated encephalitis presenting withpsychiatric features and neuroleptic malignant syndrome – furtherexpanding the phenotype

Anand Iyer1, Amy MCTague1, Andrew Curran1, AnandhiInbasagaran2, Angela Vincent3, Rachel Kneen1,4

1 Littlewood Neurosciences Unit, Alder Hey Children's NHS Foundation Trust,Liverpool. 2 Dewi Jones Child Psychiatry Unit, Alder Hey Children's NHS FoundationTrust, Liverpool. 3 The Weatherall Institute of Molecular Medicine, John RadcliffeHospital, Oxford. 4 Institute of Infection and Global Health, University of Liverpool,Liverpool, UK.Correspondence to: rachel.kneen@alderhey.nhs.uk

doi: 10.1111/j.1469-8749.2012.04249.x.

SIR–We read with great interest the case reports by Illing-worth et al. and Suleiman et al. of two children with very dif-ferent presentations associated with voltage-gated potassiumchannel (VGKC) complex antibodies.1,2 As noted in the casereports, the clinical spectrum of VGKC-complex antibodymediated neurological conditions is widening and nowincludes limbic encephalitis, fever-induced refractory encepha-lopathy, and early-onset epileptic encephalopathy. We havealso treated a child with VGKC limbic encephalitis with somedifferent and additional features. Written consent for publica-tion was obtained from the parents.

A 13-year-old female with moderate learning difficultiespresented with a gradual onset personality change, reducedand repetitive speech content, altered sleep pattern, and epi-sodic extreme agitation following a flu-like illness. Examina-tion revealed no neurological signs except a slight tremor ofthe hands and intermittent extreme agitation. During briefperiods of alertness (lasting a few minutes at a time only), shecould talk, eat, drink, and walk. She was initially referred tothe child psychiatry team (Alder Hey Children’s Hospital),diagnosed with severe, agitated depression, and treated withfluoxetine and risperidone. She subsequently developed fea-tures consistent with neuroleptic malignant syndrome (NMS)requiring treatment with hydration, amantadine, and with-drawal of neuroleptics.

Over the next 5 weeks, she fluctuated between episodes ofagitation and catatonia. Aripiprazole was introduced and thesymptoms of NMS returned. Despite the lack of seizures,autoimmune limbic encephalitis was suspected and an empiri-cal 3-day course of methylprednisolone was given 8 weeks intoher illness. She responded well with symptomatic improve-ment starting a week after treatment and 2 weeks after treat-ment was felt to be back to her baseline.

Investigations revealed a normal brain magnetic resonanceimaging and cerebrospinal fluid studies. An electroencephalo-gram performed 6 weeks into the illness was of low amplitudebut showed no evidence of a diffuse encephalopathy or parox-ysmal activity. She was not hyponatremic and N-methyl-D-aspartate receptor (NMDAR) antibodies were negative.

VGKC-complex antibodies tested 6 weeks into her illnesswere mildly raised at 155pmol ⁄ L (range 0–100pmol ⁄ L). Insimilarity to the previously reported childhood cases ofVGKC-complex antibody encephalopathy, antibodies againstleucine-rich glioma-inactivated 1 (LGI1) and contactin-associ-ated protein 2 (CASPR2) were not detected. Repeat samplesfor VGKC antibody taken 12 weeks and 7 months after theonset of her illness were raised at 711 and 344 pmol ⁄ L respec-tively. However, as she had dramatically improved and did notreceive any further treatments. She remains well 6 monthsafter treatment.

Neuropsychiatric symptoms are an essential presentingfeature of VGKC antibody associated limbic encephalitis.All paediatric cases reported so far have had seizures. Inaddition, acute psychoses with NMS-like symptoms havenot been previously reported in VGKC antibody encephali-tis in adults or children; but have been reported in cases ofNMDAR antibody encephalitis (who had not receivedneuroleptic drugs).3 Although the clinical features in this caseoccurred after neuroleptic drugs, it is possible the featurescould have been a part of the underlying encephalitis. It isarguable this child’s premorbid learning difficulties may berelevant or could herald another neuropsychiatric syndrome,as previous cases have all been described in neurotypicalpatients. No underlying cause has been found for her learn-ing difficulties so far (karyotype, chromosomal microarrayanalysis, and metabolic screen were normal). However, herpreviously static course and clinical recovery would suggestthe issues are unrelated.

The other interesting feature of our case was the absence ofthe imaging abnormalities and hyponatremia which have beenreported previously in other cases.4–6 Although there were noother features to support an autoimmune aetiology, the rapidresponse and complete recovery following corticosteroids sup-ports an immune mediated recovery. It is thought that anti-bodies directed against proteins that are a part of VGKC playa role in the pathophysiology of this condition. In most cases,reduction in the VGKC antibody following immune therapycorrelates well with the clinical improvement. However, in thiscase there was a surge of the antibody titres following a clinicalimprovement leading to difficult decision-making about theneed for ongoing immunosuppressive treatment, and raisingthe possibility that in this patient the VGKC antibodies arosesecondarily to another, probably immune mediated, cause.

This case illustrates the increasing need for communicationbetween child neurologists and psychiatrists about the diversepresenting features of autoimmune encephalopathy, and inparticular VGKC antibody limbic encephalitis. The casealso further expands the phenotypic spectrum in children.

ª The Authors. Developmental Medicine & Child Neurology ª 2012 Mac Keith Press 575

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY LETTER TO THE EDITOR

VGKC-complex and NMDAR antibody testing should beconsidered in acute childhood psychosis especially if the fea-tures are unusual as early clinical suspicion and immune ther-apy might improve the outcome and prevent neurologicalcomplications.1,4,5 The case also demonstrates the difficulty

neurologists are faced with regarding decisions about treat-ment of this new group of conditions. Further studies arerequired to correlate antibody titres with clinical presentationand improvement as well as research into other proteins thatmay play a role in the pathogenesis.

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