Overview
Definition:
Opsoclonus–myoclonus syndrome (OMS), also known as myoclonic encephalopathy of childhood or "dancing eyes, dancing feet" syndrome, is a rare paraneoplastic neurological disorder characterized by rapid, conjugate, chaotic, multidirectional, and involuntary eye movements (opsoclonus) along with myoclonic jerks (brief, involuntary muscle contractions) affecting the trunk, limbs, and face
In a significant proportion of pediatric cases, it is strongly associated with an underlying neuroblastoma, typically an occult or low-stage tumor.
Epidemiology:
OMS is rare, with an incidence estimated at 1 in 10 million children per year
Approximately 30-50% of children with OMS have an associated neuroblastoma, making this association a critical diagnostic consideration
The peak age of onset for OMS associated with neuroblastoma is between 6 months and 3 years, though it can occur at any age
Neuroblastoma itself is the most common extracranial solid malignancy in childhood, accounting for about 15% of all pediatric cancers.
Clinical Significance:
Early and accurate diagnosis of OMS and its underlying cause, particularly neuroblastoma, is crucial for improving prognosis
Delays in diagnosis can lead to increased tumor burden, metastatic disease, and poorer treatment outcomes
Recognizing the constellation of symptoms is vital for pediatricians and neurologists to initiate prompt diagnostic workup, including oncological investigation, leading to timely cancer treatment and supportive neurological management
This knowledge is paramount for residents preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Sudden onset of abnormal eye movements, typically opsoclonus, often described as rapid, jerky, and uncontrolled
Development of myoclonic jerks affecting axial and appendicular muscles, leading to ataxia and gait disturbance
Irritability, lethargy, and behavioral changes
Developmental regression or plateau in previously achieved milestones
In some cases, preceding or concurrent symptoms of neuroblastoma like abdominal mass, pallor, fever, or bone pain may be present, although the tumor is often occult.
Signs:
Ocular examination reveals opsoclonus: rapid, conjugate, multidirectional, saccadic, non-rhythmic eye movements, often persisting during sleep
Myoclonic jerks are prominent, affecting the trunk ( opisthotonus-like posturing), limbs (jerking movements), and facial muscles
Ataxia and unsteadiness of gait, often leading to inability to walk
Muscle tone may be normal or reduced
Deep tendon reflexes may be diminished or absent
Neurological examination may also reveal cranial nerve palsies or other signs of central nervous system involvement, though typically absent in pure OMS
Palpable abdominal mass in cases of neuroblastoma.
Diagnostic Criteria:
There are no universally standardized diagnostic criteria for OMS specifically linked to neuroblastoma
However, a presumptive diagnosis is made based on the presence of opsoclonus and myoclonus in the absence of other known causes of these symptoms
The diagnosis is strongly supported by the detection of an underlying neuroblastoma, often via imaging and biochemical markers
Confirmation often involves ruling out infectious, metabolic, autoimmune, and other oncological causes.
Diagnostic Approach
History Taking:
Detailed birth history, developmental milestones, and history of recent illnesses or vaccinations
Inquire about the onset, progression, and nature of eye movements and jerks
Family history of neurological disorders or cancers
Specific questions about any abdominal masses, pain, pallor, fever, weight loss, or changes in bowel/bladder habits that could suggest neuroblastoma
Red flags include rapid onset of opsoclonus and myoclonus, developmental regression, and unexplained irritability in young children.
Physical Examination:
Comprehensive neurological examination focusing on eye movements (observation during fixation and gaze), assessment of myoclonus (location, timing, triggers), motor strength, tone, coordination, reflexes, and cranial nerve function
Thorough abdominal palpation for masses, hepatosplenomegaly, or ascites
Examination of the skin for any suspicious pigmented lesions or café-au-lait spots, which can be associated with neurofibromatosis but also sometimes seen in neuroblastoma contexts.
Investigations:
Biochemical markers: Urinary catecholamines (vanillylmandelic acid [VMA] and homovanillic acid [HVA]) are essential for detecting neuroblastoma, with elevated levels indicating tumor activity
Imaging: Abdominal ultrasound is the initial imaging modality for suspected neuroblastoma
CT scan of the abdomen and pelvis, and chest are usually performed to delineate tumor extent
MRI of the brain may be considered to rule out CNS involvement or other causes of opsoclonus
Bone marrow aspirate and biopsy are crucial for staging and detecting metastasis
MIBG (meta-iodobenzylguanidine) scintigraphy is highly sensitive for detecting neuroblastoma
Neurological investigations: EEG to rule out epilepsy
CSF analysis to exclude infection or inflammatory causes
MRI brain may be helpful to exclude structural lesions
Autoantibody testing for paraneoplastic antibodies may be considered in atypical or refractory cases, though less commonly positive in neuroblastoma-associated OMS.
Differential Diagnosis:
Other causes of opsoclonus: Brainstem encephalitis, post-infectious syndromes (e.g., post-viral), autoimmune disorders (e.g., opsoclonus-myoclonus syndrome without neuroblastoma, autoimmune encephalitis), drug-induced opsoclonus (e.g., phenothiazines), and other CNS tumors
Other causes of myoclonus: Epilepsy, metabolic disorders, hypoxic-ischemic encephalopathy, genetic disorders, neurodegenerative diseases
It is crucial to differentiate these from neuroblastoma-associated OMS.
Management
Initial Management:
Prompt oncological workup upon suspicion of neuroblastoma
Stabilization of neurological symptoms to improve comfort and safety, although specific acute neurological management is less critical than addressing the underlying malignancy.
Medical Management:
Treatment of the underlying neuroblastoma is paramount
This typically involves surgery, chemotherapy, and/or radiation therapy depending on the stage, location, and aggressiveness of the tumor
Immunotherapy is also increasingly used
For the neurological symptoms (opsoclonus and myoclonus), treatment may include corticosteroids (e.g., high-dose methylprednisolone followed by oral prednisone), IVIG (intravenous immunoglobulin), and sometimes immunosuppressive agents like cyclophosphamide or rituximab
Symptomatic management of myoclonus may involve benzodiazepines or other antiepileptic drugs, although their efficacy is variable.
Surgical Management:
Surgical resection of the primary neuroblastoma is a cornerstone of treatment
Complete surgical removal of the tumor, if feasible, can lead to remission of OMS symptoms
Debulking of large tumors may also be considered
Surgical intervention is primarily directed at the malignancy, not the neurological manifestations directly.
Supportive Care:
Close neurological monitoring for changes in eye movements or myoclonus
Physical and occupational therapy to manage ataxia, improve motor skills, and support developmental progress
Speech therapy if there are communication difficulties
Nutritional support to maintain adequate intake, especially if there are feeding difficulties due to neurological impairment or gastrointestinal involvement
Psychological support for the child and family is essential throughout the treatment journey.
Complications
Early Complications:
Worsening neurological deficits due to tumor progression or treatment side effects
Infection, myelosuppression, and mucositis from chemotherapy
Post-operative complications from tumor resection.
Late Complications:
Long-term neurological sequelae including persistent ataxia, cognitive deficits, developmental delays, and behavioral problems
Recurrence of neuroblastoma
Secondary malignancies due to chemotherapy or radiation
Growth retardation
Hearing impairment from ototoxic chemotherapy
Infertility.
Prevention Strategies:
Early detection and prompt treatment of neuroblastoma is the primary strategy to prevent severe complications
Aggressive management of OMS symptoms with immunomodulatory therapy can improve neurological recovery
Close monitoring for treatment-related toxicities and timely intervention
Rehabilitation services to address functional deficits
Genetic counseling for families regarding heritable forms of neuroblastoma.
Prognosis
Factors Affecting Prognosis:
The prognosis of OMS associated with neuroblastoma is variable and depends heavily on the stage and resectability of the neuroblastoma, response to treatment, and the degree of neurological recovery
Tumors with favorable genetic markers (e.g., absence of MYCN amplification) and those diagnosed at an early stage generally have a better prognosis
Complete remission of the neuroblastoma and early intervention for OMS symptoms correlate with better neurological outcomes.
Outcomes:
Complete remission of OMS symptoms occurs in about 50-70% of patients, often following successful treatment of the neuroblastoma
However, some degree of neurological impairment, including ataxia, cognitive deficits, or behavioral issues, may persist in a significant proportion of survivors
Relapse of OMS can occur, sometimes independent of tumor relapse, and may be refractory to treatment
Neuroblastoma survival rates vary significantly by stage, ranging from >90% for stage 1 to <50% for stage 4S and stage 4.
Follow Up:
Long-term follow-up is essential for all survivors, including regular oncological surveillance to detect tumor recurrence, and comprehensive neurodevelopmental assessment to monitor for cognitive, motor, and behavioral deficits
Rehabilitation services should continue as needed
Screening for late effects of treatment such as secondary malignancies, endocrine dysfunction, and cardiac issues is also crucial
Regular ophthalmological and neurological examinations are necessary.
Key Points
Exam Focus:
The absolute association between opsoclonus, myoclonus, and neuroblastoma is a high-yield topic for DNB and NEET SS
Remember that neuroblastoma in OMS is often occult and may present with normal or minimally elevated catecholamines
MIBG scan is key for diagnosis and staging of neuroblastoma in these children
Management is multimodal, focusing on treating the malignancy and controlling neurological symptoms.
Clinical Pearls:
Always consider neuroblastoma in a child presenting with new-onset opsoclonus and myoclonus, even without an obvious abdominal mass
The "dancing eyes, dancing feet" syndrome is a classic presentation
Prompt initiation of urinary catecholamine testing and abdominal imaging can be life-saving
Recognize that neurological recovery can lag behind tumor remission and may require intensive rehabilitation.
Common Mistakes:
Misdiagnosing OMS as a primary neurological disorder without adequately investigating for an underlying malignancy
Delaying oncological workup due to focus solely on symptomatic neurological management
Underestimating the importance of urinary catecholamines and MIBG scans in the diagnostic pathway
Failing to consider long-term neurodevelopmental follow-up for survivors.