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CASE REPORT
Year : 2013  |  Volume : 28  |  Issue : 2  |  Page : 108-111  

Somatostatin receptor positron emission tomography/computed tomography (PET/CT) in the evaluation of opsoclonus-myoclonus ataxia syndrome


Department of Nuclear Medicine and PET-CT, Jaslok Hospital & Research Centre, Worli, Mumbai, Maharashtra, India

Date of Web Publication16-Sep-2013

Correspondence Address:
Prathamesh Joshi
Department of Nuclear Medicine and PET-CT, Jaslok Hospital and Research Centre, Worli, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-3919.118236

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   Abstract 

Opsoclonus-myoclonus ataxia (OMA) syndrome is the most common paraneoplastic neurological syndrome of childhood, associated with occult neuroblastoma in 20%-50% of all cases. OMA is the initial presentation of neuroblastoma in 1%-3% of children. Conventional radiological imaging approaches include chest radiography and abdominal computed tomography (CT). Nuclear medicine techniques, in form of 123 I/ 131 I-metaiodobenzylguanidine (MIBG) scintigraphy have been incorporated in various diagnostic algorithms for evaluation of OMA. We describe use of somatostatin receptor PET/CT with 68 Gallium- DOTA-DPhe 1 , Tyr 3 -octreotate (DOTATATE) in diagnosis of neuroblastoma in two cases of OMA.

Keywords: Occult neuroblastoma, opsoclonus-myoclonus ataxia, somatostatin receptor PET/CT, 68 Gallium DOTATATE


How to cite this article:
Joshi P, Lele V. Somatostatin receptor positron emission tomography/computed tomography (PET/CT) in the evaluation of opsoclonus-myoclonus ataxia syndrome. Indian J Nucl Med 2013;28:108-11

How to cite this URL:
Joshi P, Lele V. Somatostatin receptor positron emission tomography/computed tomography (PET/CT) in the evaluation of opsoclonus-myoclonus ataxia syndrome. Indian J Nucl Med [serial online] 2013 [cited 2020 May 25];28:108-11. Available from: http://www.ijnm.in/text.asp?2013/28/2/108/118236


   Introduction Top


Opsoclonus-myoclonus ataxia (OMA) syndrome is the most common paraneoplastic neurological syndrome of childhood. It is an acute neurological disorder characterized by involuntary, chaotic eye movements (opsoclonus) and/or by myoclonus and ataxia of the limbs ("dancing feet"), the trunk, and the eyelids. [1] Other names of this syndrome are: Kinsbourne syndrome, dancing eyes syndrome and infantile myoclonic encephalopathy. [2],[3],[4] It is a rare presentation of neuroblastoma (1-3% of cases), but in as many as 50% of patients with this syndrome, neuroblastoma (NB) is the cause. [5] We describe use of somatostatin receptor PET/CT (SSR PET/CT) with 68 Gallium-DOTA-DPhe 1 , Tyr 3 -octreotate (DOTATATE) in diagnosis of NB in two cases of OMA.


   Case Reports Top


Case 1

A two year old male child presented with acute onset of ataxia. His parents reported involuntary eye movements in child of two weeks duration. There was no history of fever and other systemic complaints. On clinical examination, he was found to have OMA syndrome. His previous investigation included chest X-ray, urinary vanillylmandelic acid (VMA) measurement, brain MRI and CSF examination, which did not reveal any abnormality. With suspicion of underlying neuroblastoma, SSR PET/CT with 68 Gallium DOTATATE was performed. 1.5 mCi of 68 Gallium-DOTATATE was injected intravenously to the patient. After 1 hr of injection, patient was scanned on dedicated 16 slice PET /CT. Whole body diagnostic CT scan was obtained as part of PET/ CT protocol on Multislice CT with 3.5 mm slice thickness.

The scan demonstrated increased tracer uptake in left paravertebral region at the level of T3-T5 vertebrae [Arrow in [Figure 1]a. Maximum standardized uptake value SUV max of the lesion was 10.1. On CT and fused PET/CT images the uptake localized to a soft tissue density lesion with specks of calcification within [Figure 1]b and 1c, arrows]. Physiological tracer distribution was noted in the spleen, kidneys and urinary bladder. The paravertebral lesion was suggestive of NB. Surgical resection of lesion confirmed diagnosis of NB. Post surgery and short course of steroids, OMA resolved. At present, one year after the initial presentation; this child has no evidence of disease.
Figure 1: A 2-year-old male child underwent 68Gallium-DOTA-DPhe1, Tyr3- octreotatephoton emission tomography/computed tomography (PET/CT) for evaluation of opsoclonus-myoclonus ataxia syndrome. The scan shows increased tracer uptake in left paravertebral region at the level of T3-T5 vertebrae (black arrow in a). CT reveals a soft-tissue density lesion with specks of calcification within (b, red arrow). Fused PET/CT demonstrates increased tracer uptake in this lesion, SUVmax of uptake was 10.1 (c, white arrow). Physiological tracer distribution was noted in the spleen, liver, kidneys and urinary bladder. The paravertebral lesion was found to be neuroblastoma on surgical resection

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Case 2

A two and half year old male child presented with acute onset of myoclonus, occasional opsoclonus and ataxia. Previous evaluation included a lumbar puncture and brain MRI, both failing to show an abnormality. Suspicion of paravertebral mass was raised in a recent chest X-ray. Considering the possibility of the mass being neuroblastoma, the patient was referred to the nuclear medicine department for further evaluation. We evaluated the child with SSR PET/CT using 68 Gallium DOTATATE. 1.5 mCi of 68 Gallium-DOTATATE was injected intravenously to the patient. After 1 hr of injection, patient was scanned on dedicated 16 slice PET /CT (GE - STE 16). Whole body diagnostic CT scan was obtained as part of PET/CT protocol on Multislice CT with 3.5 mm slice thickness.

The SSR PET/CT revealed intense tracer uptake in chest which localized to a soft tissue density mass in the paravertebral region (T1-T4 levels) with SUV max of 21.0 [Figure 2]a, long arrow]. On CT the lesion showed evidence of calcification in it [Figure 2]b, arrow]. Considering patient's symptoms, these CT findings along with positivity for somatostatin receptor expression on PET, suggested diagnosis of NB. Additionally multiple areas of increased tracer uptake were noted in the bone marrow of long bones and almost entire axial skeleton with no obvious CT demonstrable abnormality [Figure 2]a and 2c. These features were indicative of widespread marrow metastases. Biopsy of the paravertebral mass confirmed the diagnosis of NB. Considering the extensive disease, the child is receiving chemotherapy for last four months. There is mild clinical improvement in the OMA.
Figure 2: Somatostatin receptor photon emission tomography/computed tomography (CT) of a 2½-old male child with opsoclonus-myoclonus ataxia, revealed intense tracer uptake in chest (a, long arrow), corresponding to a soft-tissue density mass with specks of calcification within, in the paravertebral region at T1-T4 levels (b, long white arrow). These findings suggested diagnosis of neuroblastoma. Multiple areas of increased tracer uptake seen in the bone marrow of long bones and axial skeleton with no CT demonstrable abnormality (short arrows in a) suggesting marrow metastases. Representative uptake in bone marrow of bilateral femora is shown(c, short white arrows)

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   Discussion Top


Though encountered rarely, identification of paraneoplastic syndromes is important for accurate management of the underlying malignancies. OMA is one such syndrome. In children this syndrome is typical for neuroblastoma and was first described by Kinsbourne in 1962. [2] OMA syndrome very rarely can also develop in association with viral infections or vaccination or without any noticeable reason. In idiopathic cases it is assumed that the syndrome could have developed in the course of neuroblastoma which had undergone a complete spontaneous regression. [6],[7] This syndrome develops very rarely in adult patients with breast cancer in association with Ri antibodies and patients with small cell lung cancer without any characteristic antibodies. [8] The pathogenesis of OMA is still unclear, although the presence of anti-neuronal antibodies against unknown membrane antigens of neuroblastoma cells and cerebellar neurons suggests that the disorder is immunologically mediated. [9] Children with OMA do not improve spontaneously and in order to improve their neurological status along with treatment of NB, therapy with steroids or immunosuppressive or cytotoxic drugs is required. [8]

In children with OMA, battery of diagnostic tests needs to be performed to diagnose occult NB. These include-chest radiography, abdominal CT, urinary VMA measurement. Nuclear medicine techniques, in form of 123 I/ 131 I- metaiodobenzylguanidine (MIBG) scintigraphy have been incorporated in various diagnostic algorithms for evaluation of OMA. [5] In most OMA cases the tumor is of a small size, without any clinical symptoms related to its primary location. Therefore at times repeated imaging examinations must be carried out. [4]

Somatostatin receptor (SSR) overexpression in NBs and many other neuroendocrine tumors (NETs) has enabled development of scintigraphy using radiolabeled somatostatin analogs. To date, 5 SSRs have been characterized, all of which are expressed in differing frequencies in NET. [10] In our patients, we used DOTATATE, an SSR-2 analog, [11] labeled with 68 Gallium, a positron emitter. 68 Gallium is produced from a 68 Germanium - 68 Gallium generator and therefore is not dependent on a cyclotron. The automated labeling of this radiopharmaceutical done according to good laboratory practice under sterile conditions in an isolator takes approximately 60 min. The yield of 68 Gallium-DOTATATE is more than 98% with this method. The PET/CT is performed 45 min- 1 hour after the injection of tracer. SSR PET/CT is known to be useful tools in evaluation of NB. [12],[13] A study by Kroiss et al., compared 123 I- MIBG with SSR PET/CT, which suggests that SSR PET/CT has equal sensitivity for NB detection on per-patient basis and higher sensitivity on a per-lesion basis. [12] Additionally SSR imaging could provide prognostic information; in fact a longer survival has been reported in patients with SS receptor-positive NB. [13]

The distinct advantages of SSR PET/CT over 123 I/ 131 I -MIBG scintigraphy are-superior resolution of PET/CT technology as compared to gamma camera imaging, comparable sensitivity with 123 I MIBG, no need of special patient preparation (such as blocking the thyroid uptake with iodine administration, need to stop interfering medications), prognostic information, round the clock availability due to generator production. [10],[11],[12],[13],[14] Unlike 123 I/ 131 I-MIBG, tracer administration and imaging is done on the same day and entire procedure takes only few hours. Considering all these factors SSR PET/CT appears to be an effective alternative to 123 I/ 131 I-MIBG in evaluation of patients with OMA.

Especially the availability factor is crucial in our country, where 131 I-MIBG is supplied on once/twice-a-month basis and usually a long waiting list makes it difficult to accommodate all the referred patients. In fact in the described cases, non-availability of 123 I/ 131 I -MIBG, prompted us to use SSR PET/CT as the modality to evaluate patients of OMA. In consideration of cost efficiency, the value of a sensitive and specific screening modality for patients with suspected neuroblastoma is extremely important. A single screening study which is sensitive, specific and able to identify both soft tissue and osseous metastatic disease would provide more rapid diagnosis, simultaneous staging and possibly improve outcome. 131 I/ 123 I -MIBG has shown its value in this regard. [5] SSR PET/CT has potential to become another efficient nuclear medicine technique for this purpose. SSR PET/CT can bring together anatomical information of CT and functional information of PET and hence will possibly result in better characterization of disease. In the second case described above demonstrates this point. In this case, SSR PET/CT not only characterized the mass seen on CT but also diagnosed CT negative marrow metastases. With advent of peptide receptor therapy with 177 Lu-DOTATATE, the SSR PETCT can also serve as selection criteria of patients for this targeted therapy. [15]

To conclude, we present valuable role played by SSR PET/CT in evaluation of children with OMA. SSR PET/CT can provide rapid diagnosis and staging in cases of OMA and hence guide optimal patient management.

 
   References Top

1.Hayward K, Jeremy RJ, Jenkins S, Barkovich AJ, Gultekin SH, Kramer J, et al. Long-term neurobehavioral outcomes in children with neuroblastoma and opsoclonus-myoclonus-ataxia syndrome: Relationship to MRI findings and anti-neuronal antibodies. J Pediatr 2001;139:552-9.  Back to cited text no. 1
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2.Kinsbourne M. Myoclonic encephalopathy of infants. J Neurol Neurosurg Psychiatry 1962;25:271-9.  Back to cited text no. 2
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3.Tate ED, Allison TJ, Pranzatelli MR, Verhulst SJ. Neuroepidemiologic trends in 105 US cases of pediatric opsoclonus-myoclonus syndrome. J Pediatr Oncol Nurs 2005;22:8-19.  Back to cited text no. 3
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4.Telander RL, Smithson WA, Groover RV. Clinical outcome in children with acute cerebellar encephalopathy and neuroblastoma. J Pediatr Surg 1989;24:11-4.  Back to cited text no. 4
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5.Parisi MT, Hattner RS, Matthay KK, Berg BO, Sandler ED. Optimized diagnostic strategy for neuroblastoma in opsoclonus-myoclonus. J Nucl Med 1993;34:1922-6.  Back to cited text no. 5
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6.Klein A, Schmitt B, Boltshauser E. Long-term outcome of ten children with opsoclonus-myoclonus syndrome. Eur J Pediatr 2007;166:359-63.  Back to cited text no. 6
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7.Pranzatelli MR. The neurobiology of the opsoclonus-myoclonus syndrome.Clin Neuro pharmacol 1992;15:186-228.  Back to cited text no. 7
    
8.Graus F, Dalmau J. Paraneoplastic neurological syndromes: Diagnosis and treatment. Curr Opin Neurol 2007;20:732-7.  Back to cited text no. 8
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9.Bataller L, Rosenfeld MR, Graus F, Vilchez JJ, Cheung NK, Dalmau J. Autoantigen diversity in the opsoclonus-myoclonus syndrome. Ann Neurol 2003;53:347-53.  Back to cited text no. 9
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10.Srirajaskanthan R, Kayani I, Quigley AM, Soh J, Caplin ME, Bomanji J. The role of 68 Ga-DOTATATE PET in patients with neuroendocrine tumors and negative or equivocal findings on 111 In-DTPA-octreotide scintigraphy. J Nucl Med 2010;51:875-82.  Back to cited text no. 10
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11.Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68 Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG. Cancer 2008;112:2447-55.  Back to cited text no. 11
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12.Kroiss A, Putzer D, Uprimny C, Decristoforo C, Gabriel M, Santner W, et al. Functional imaging in phaeochromocytoma and neuroblastoma with 68 Ga-DOTA-Tyr3-octreotide positron emission tomography and 123 I-metaiodobenzylguanidine. Eur J Nucl Med Mol Imaging 2011;38:865-73.  Back to cited text no. 12
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13.Briganti V, Sestini R, Orlando C, Bernini G, La Cava G, Tamburini A, et al. Imaging of somatostatin receptors by indium-111-pentetreotide correlates with quantitative determination of somatostatin receptor type 2 gene expression in neuroblastoma tumors. Clin Cancer Res 1997;3:2385-91.  Back to cited text no. 13
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14.Maurice JB, Troke R, Win Z, Ramachandran R, Al-Nahhas A, Naji M, et al. A comparison of the performance of 68 Ga-DOTATATE PET/CT and ¹²³I-MIBG SPECT in the diagnosis and follow-up of phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging 2012;39:1266-70.  Back to cited text no. 14
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15.Gains JE, Bomanji JB, Fersht NL, Sullivan T, D'Souza D, Sullivan KP, et al. 177 Lu-DOTATATE molecular radiotherapy for childhood neuroblastoma. J Nucl Med 2011;52:1041-7.  Back to cited text no. 15
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    Figures

  [Figure 1], [Figure 2]


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