Opsoclonus Myoclonus Ataxia Syndrome

Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare neurological disorder predominantly affecting young children and causing severe neurological disability. Its early identification and treatment is advocated. Here we report a two year old child presenting with abnormal movements and subsequently developed features of OMAS and responding favourably to Adrenocorticotropic hormone (ACTH). J Nepal Paediatr Soc 2015;35(1):70-72


Introduction
O psoclonus myoclonus ataxia (OMA) syndrome, also called 'Dancing eye syndrome', is a rare, serious and o en chronic disabling neurological illness with onset in early childhood 1 .It was fi rst described by Kinsbourne  These fi ndings may not be present at onset and may develop sequen ally as seen in our case.

The Case
A two years age male child presented with complaints of abnormal movements of the body and inability to sit without support for past seven days.The abnormal movements were sudden shake like movements, ini ally started on right upper limb, and progressed to involve head and all other limbs over a period of one day.Parents no ced that these movements get aggravated on crying and ac vity and ceased on sleeping.They also found that child was unable to sit and stand without support and has diffi culty in reaching for objects or picking them up with hands.There was history of upper respiratory tract infec on three weeks ago, for which he received treatment with amoxicillin and chlorpheniramine maleate for three days.There was no history of concurrent fever, vomi ng, loss of consciousness, altered sensorium, swallowing diffi culty and devia on of head and neck, eyes with limb movements.He was born by normal vaginal delivery at term with no complica ons.Development was appropriate for age.
On examina on he was alert, conscious and oriented.No pallor, icterus cyanosis, lymphadenopathy, oedema was found.No evidence of any neurocutaneous markers was seen.His weight for age was 90 th cen le and height for age was 75 th cen le as per CDC growth charts.His vitals were normal.There were con nuous coarse tremors of head and limbs.Ataxias as well as dysmetria were present on both sides.Muscle tone, power and refl exes were normal.There were no signs of meningi s.His cardiovascular, abdominal, respiratory system examina on was normal.Subsequently on the third day of admission he became irritable and had sleep disturbances.This me child was found to have opsoclonus, as conjugate eye movements.Diagnos c possibility of Opsoclonus myoclonus ataxia (OMA) was kept and was inves gated thoroughly.
On inves ga ons, his haemoglobin was 12.8 gm/ dl, total leucocyte count -16000/μl, platelet count 4.53 lacs/μl.ESR was 5mm/ 1 st hour.Blood urea nitrogen -12 mg/dl, crea nine -0.25 mg/dl, SGOT-20 IU/L, SGPT-16 IU/L, S. lactate and ammonia were within normal limits.CSF analysis revealed cell count 55 with 88 % lymphocytes with glucose of 53mg/ dl and protein of 28.9mg/dl.CSF culture was sterile and CSF PCR for Enteroviruses and Herpes virus was nega ve.Serology for mycoplasma was nega ve.MRI Brain was normal and ultrasound abdomen, done for any abdominal mass or adrenal mass, was normal.CECT chest revealed mild right para and pre vertebral so ssue thickening at D4-D6 vertebrae.MRI Spine revealed right para-vertebral so ssue thickening at D4-D6 region with normal underlying vertebrae.MRI brain was normal.Urine 24-hour VMA levels and urine spot catecholamines were within normal limits.MIBG scan (iodine-131-meta-iodobenzylguanidine) was not done due to fi nancial reasons.
He was started on Methylprednisolone at 30mg/ kg/day for three days and then shi ed to injec on ACTH at dose of 40IU/m 2 /day, as symptoms persisted.With ACTH, a er two doses, child improved, irritability se led and intensity of myoclonus also decreased.He was discharged a er seven days in be er condi on on ACTH.A er two months of follow up, the intensity of myoclonus further decreased and child started to walk unaided.

Discussion
OMA is most commonly associated with neural crest derived tumours, (like neuroblastoma (up to 40%), ganglioneuroblastoma, ganglioneuroma), as a para-neoplas c presenta on 3 .The pathogenesis was thought to be immune mediated, with a cross-reac ve autoimmunity between neuroblastoma cells and the central nervous system 4 .Several serum autoan bodies against neurons and cerebellar Purkinje cells have been iden fi ed in pa ents with OMA with unknown specifi city 5 .However OMA is also a ributed to be due to other e ologies like Para-infec ous (Coxsackie B, EBV, Rubella, Herpes, Mumps, St. Louis encephali s, Salmonella, Hemophilus infl uenzae), Toxic, Metabolic (mul ple carboxylase defi ciency, ketamine, tricyclic an -depressants, mercury salts, phenytoin) 6 .
This condi on is one of the important diff eren als for acute post infec ous cerebellar ataxia and is mainly dis nguished by presence of irritability and opsoclonus in OMA, which are rare in the former.In contrast to cerebellar ataxia, the outcome is far disabling and requires more extensive work up as well as long term immunomodula on therapy 3 .
A er diagnosis, a thorough inves ga on for an occult neuroblastoma need to be done, like CT imaging of thorax, abdomen, func onal imaging using PET or MIBG scin graphy 7 .Urine should be tested for catecholamines apart from strict monitoring of blood pressure.Tes ng for serum auto an bodies have limited yield.Failures to fi nd tumours do not rule out paraneoplas c OMA as these tumours are known to regress spontaneously in some.If ini al screening is nega ve periodic follow up for at least two years and repeat inves ga ons every 3-6 months and if no neoplasm is detected ll two years of follow up and no obvious e ology is detected then it is labelled as idiopathic.CSF evalua on is required especially in children who do not have an iden fi able neuroblastoma for infec ous and para-infec ous e ology.Mild eleva on of protein and pleocytosis can be seen in both infec ous and paraneoplas c e ology.
Mainstay of treatment lies on immunomodula on 3 .Neuroblastoma, if present, needs tumour resec on with or without chemotherapy.Therapeu c op ons for immunomodula on are: Adrenocor cotrophic hormone (ACTH), Methyl prednisolone pulses followed by oral steroids, Intravenous immunoglobulin.Reports have shown that ACTH (40IU/m 2 /day) has faster ac on than methyl prednisolone 3 .Combina on therapy can be used for refractory cases and other refractory or relapsers may be benefi ted by Rituximab, Plasmapheresis, Azathioprine, Cyclophosphamide and Mycophenolate mofe l 8 .

Opsoclonus
myoclonus have substan al developmental sequelae includes cogni ve, motor, speech and language defi cits, and behavioural sequelae 9 .About 61% have chronic relapsing course, half have intellectual defi cit and more than half have residual motor and speech defi cits 10 .

Conclusion
It is important to consider Opsoclonus myoclonus ataxia syndrome whenever a child presents with an acute onset ataxia with irritability, facilita ng early evalua on and ini a on of treatment.Opsoclonus may present later emphasising need for close observa on.
and o en referred to as Kinsboune's syndrome.OMA is diagnosed by presence of ≥ 3 of the following: A. Opsoclonus (rapid, mul direc onal, conjugate eye movements), B. Myoclonus C. Behavioural changes and/or sleep disturbances and D. Neuroblastoma 2