Benign paraspinal ganglioneuroma with paraneoplastic opsoclonus myoclonus syndrome

Abstract

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare immune-mediated movement disorder occurring as a paraneoplastic manifestation of neuroblastic tumours (NTs), especially neuroblastoma in infancy. Ganglioneuroma (GN), the benign tumour in the spectrum, is rarely associated with OMAS. We report the case of a child in her second year of life presenting with acute onset of progressive paraplegia and OMAS. MRI showed diffuse and infiltrating left paraspinal mass from T3–T9 levels with differentials of neuroblastoma or ganglioneuroblastoma. Histopathological and immunohistochemistry examination of the excised tumour showed maturing GN. The OMAS was managed with intravenous immunoglobulin and steroids. In the 6-month follow-up, the child has a residual motor weakness with myelomalacia in neuroimaging. The case report substantiates the occurrence of OMAS as paraneoplastic manifestation in NTs, including benign, in children younger than 2 years with a female predilection.

Background

Opsoclonus-myoclonus-ataxia syndrome (OMAS), also known as ‘Kinsbourne’ or ‘dancing eye’ syndrome, is a rare neuroimmunogenic movement disorder that often occurs as a paraneoplastic association.¹ It is characterised by opsoclonus (conjugate, multidirectional and chaotic eye movements), myoclonus (non-epileptic limb jerking that can also involve the head and face) and truncal ataxia. It is associated with cognitive dysfunction, behavioural abnormalities and sleep disturbances.^{2 3} The OMAS is typically seen by 2 years of age^{3 4} and can be the presenting feature of neuroblastic tumours (NTs).

The NT, originating from neural crest cells, comprises neuroblastoma, ganglioneuroblastoma and ganglioneuroma (GN) based on cellular differentiation, malignancy potential and Schwann stroma.^{5 6} Among the NTs, neuroblastoma is more common (73%) and more aggressive, while GN (4%) is rare and benign.² As the NT involves the sympathetic ganglion, the sites include the adrenals, retroperitoneum, posterior mediastinum and neck. GNs usually present before 10 years of age.^5–7 In nearly two-thirds of the patients, GNs have an intra-abdominal location.^5–7

GN is rarely associated with OMAS. In a large series of 73 patients with NT, only 5 (6.8%) had OMAS; neuroblastoma was diagnosed in 2 and GN in 1.⁸ In another series of 17 patients with NT and OMAS, neuroblastoma was diagnosed in 14, and GN in 1.⁹ In a meta-analysis of 364 patients with GN, OMAS was not listed as a common associated feature.⁷

We report the case of a young child with GN and OMAS for its rarity. We discuss the association of OMAS and GN, and its management.

Case presentation

A child in her second year of life, born to consanguineous parents, presented with progressive weakness of bilateral lower limbs of 3 months duration, and abnormal rhythmic jerky movements of the trunk, upper limbs and eyes for the past 1 month. There was a decline in social recognition, language regression, excessive irritability and reduced sleep.

On examination, the child’s vitals and anthropometry were normal. General physical examination showed a single cafe-au-lait lesion over the abdomen measuring >2 cm and an ill-defined swelling in the left lower thoracic paraspinal region. The child was irritable, not oriented, and had to be tube-fed. Ocular examination revealed continuous, random, irregular and conjugate, multidirectional eye movements suggestive of opsoclonus. She also had truncal ataxia, and high amplitude, random movements of bilateral upper limbs with no autonomic disturbances. These movements are reduced during sleep. These movements were myoclonus. A diagnosis of OMAS was made based on the Genoa diagnostic criteria.¹⁰ The diagnostic criteria for OMAS¹⁰ requires three out of the four following features to be present, that is, (1) opsoclonus, (2) myoclonus, (3) behavioural change or sleep disturbance and (4) neuroblastoma. In our child, the first three of the four criteria were met and a diagnosis of OMAS was made. The Mitchelle and Pike OMS rating scale was 17 of 18 suggesting severe impairment.⁴ Motor examination revealed bilateral flaccid paraplegia of the lower limbs, areflexia in the bilateral lower limbs and bilateral equivocal plantar response. Sensory system examination was within the normal limits and there were no abnormal bowel and bladder movements.

Investigations

1. Electroencephalogram was normal.

2. MRI (Magnetic Resonance Imaging) of the spine showed diffuse and infiltrating left paraspinal mass from T3 to T9 levels with heterogeneous enhancement in T2/STIR (Short Tau Inversion Recovery) sequences. The mass extended across the widened neural foramina into the spinal canal forming an epidural mass indenting the cord, leading to focal thinning with myelomalacia at segments T4–T8 (figure 1A,B). There was also infiltration along the posterior chest wall ipsilaterally forming an extra pleural mass filling the third to the eighth intercostal spaces with postcontrast enhancement (figure 2A,B). The imaging was suggestive of NT, likely neuroblastoma or ganglioneuroblastoma.

3. MRI brain was normal.

4. Histopathological examination of the excised tumour mass showed a moderately cellular tumour composed of neuromatous stroma admixed with immature and mature ganglion cells, benign Schwann cells and fibroblasts, with no blastic or malignant cells (figure 3A,B). Immunohistochemistry showed NeuN, synaptophysin, S100 and Ki-67 positivity, with the diagnosis of maturing GN.

5. MRI spine repeated after 6 months showed persistent thinning of the thoracic cord from T5 to T7 suggestive of myelomalacia along with postlaminectomy and paravertebral soft tissue changes (figure 4A,B).

Figure 1.

(A and B) Diffuse infiltration and heterogeneously enhancing altered signal intensity mass in STIR (Short Tau Inversion Recovery) and T1 phase in the left parashpinal region extending from T3 to T9 vertebral levels with extension across the widened neural foramina into the spinal canal. The white arrow indicates the focal thinning of the spinal cord from T4 to T8 indicating myelomalacia of the spinal cord.

Figure 2.

(A and B) Epidural mass is found indenting the cord with infiltration along the posterior chest wall ipsilaterally forming an extra pleural mass with infiltration of multiple ribs from the second to the seventh rib with the mass filling the intercoastal space from the third to the eighth intercoastal space on the left side.

Figure 3.

(A and B) Moderately cellular tumour composed of neuromatous stroma admixed with ganglion cells. The neuromatous stroma shows benign Schwann cells and fibroblasts arranged in irregular patterns surrounded by loose vascular myxoid to the collagenous stroma. The ganglion cells are seen in singles and clusters. Both mature and immature ganglion cells are present with no evidence of malignancy.

Figure 4.

(A and B) Non-visualisation of the posterior elements of T3–T10 vertebrae suggestive of postlaminectomy changes with significant thinning of the cord from the level of T4/5 disc to the level T7/8 disc with T2/STIR (Short Tau Inversion Recovery) high signal within, suggestive of myelomalacia.

Differential diagnosis

The acute onset of progressive paraplegia with diffuse swelling in the lower thoracic region suggested a retroperitoneal thoracolumbar mass infiltrating the spinal cord. The movement disorder along with social and language regressions suggested OMAS. The provisional clinical diagnosis was neuroblastoma or ganglioneuroblastoma with paraneoplastic OMAS. Differential diagnoses included GN or teratoma.

Treatment

The OMAS was managed with immunoglobulin infusion of 2 g/kg divided over 5 days, and methylprednisolone (30 mg/kg/day) for 5 days, followed up with oral prednisolone at 1 mg/kg/day. Following imaging, neurosurgery consultation was sought. The child underwent laminectomy and excision of the mass (the mass extending across the posterior chest wall between the third and the eighth intercostal spaces was excised) with spinal canal decompression. Following the tissue diagnosis of a benign NT, the child was started on physiotherapy, oral prednisolone was continued and the child was discharged.

Outcome and follow-up

The OMAS rating scale improved to 10 by 2 weeks, 7 by 4 weeks, and completely disappeared by 3 months. There was a significant improvement in social and language milestones by 4 weeks. However, at 6 months follow-up, the motor weakness is persistent with minimal improvement in power. The severe motor impairment is likely due to the persisting myelomalacia seen in the follow-up imaging.

Discussion

This case report highlights the presentation of benign GN with OMAS as a paraneoplastic manifestation in a young female child.

GNs account for only 6.4% of all NTs.¹¹ They are well-differentiated tumours, and thus the prognosis depends on the location and compression of the adjacent structures. The most common location is the abdominal (adrenal) or retroperitoneal (sympathetic chain) tumour as seen in our child.^5–7 Alexander et al,¹² in their case series of 50 patients with GN, report a median age of 7.5 years at diagnosis. In another series of 29 children with GN by Whitlock et al,⁷ the median age at diagnosis was 4.0 years. The diagnosis of GN is incidental when imaging is done for other reasons. Our child had an earlier presentation due to compression myelopathy and OMAS.

The OMAS is rare with reported incidences of 0.27 from Japan and 1.8 from the UK per million population.^{13 14} An Indian study showed that OMAS contributed to 7.6% of acute movement disorders in children.¹⁵ Childhood OMAS is included in the spectrum of acquired cerebellar ataxias.¹⁶ The initial presentation may be gait disturbance and the diagnosis is made when opsoclonus appears. Fifty per cent of all patients with OMAS have an underlying NT, of which GN constitutes only 4%.¹⁶ An autoimmune pathogenesis is postulated, and thus OMAS is seen with several infections, autoimmune encephalitis and other tumours such as hepatoblastoma and ovarian teratoma.^{3 4 17} In a case series of 356 children with OMAS, children with tumours presented by the second year of age with a female predilection.¹⁷

As GNs have a benign course, complete excision of the tumour is debated.^{5–8 12} Earlier studies advocated adrenalectomy or total excision of the tumour to prevent potential malignant transformation.^5–7 The current trend is to adopt a conservative approach to prevent postsurgical morbidity.^{8 12} Our child required a surgical approach due to compression symptoms. Immunomodulation plays a key role in OMAS management. Intravenous immunoglobulin and steroid therapy, along with rituximab, are the mainstay of treatment.^{4 9 16} The two different managerial strategies are an upfront aggressive approach using all three drugs simultaneously or an escalating regimen based on the clinical response.¹⁶ There is conflicting evidence on the role of tumorous removal on OMAS remission.⁴ In our case, we used the escalating approach for OMAS remission.

Learning points.

• Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a paraneoplastic manifestation of neuroblastic tumours (NTs) in young children.

• Children presenting with OMAS should undergo extensive evaluation for occult NTs.

• The mainstay of the management of OMAS is immunomodulation, and either an aggressive or escalating approach may be adopted based on the child’s condition.

Ethics statements

Patient consent for publication

Consent obtained from parent(s)/guardian(s).