Overview
Definition:
Opsoclonus-myoclonus-ataxia syndrome (OMAS), also known as Kinsbourne syndrome, is a rare, acquired neurological disorder characterized by the rapid, involuntary, conjugate, multidirectional, and chaotic eye movements (opsoclonus), myoclonic jerks (sudden, brief, involuntary muscle contractions), and gait or limb ataxia (incoordination)
It is often associated with an underlying malignancy, particularly neuroblastoma in children.
Epidemiology:
OMAS is a rare condition, with an estimated incidence of 1 in 10 million children per year
It predominantly affects children, with a peak incidence between 6 and 24 months of age
In approximately 50-70% of pediatric cases, OMAS is paraneoplastic, with neuroblastoma being the most common associated tumor
In adults, OMAS is more frequently associated with other malignancies like lung cancer or breast cancer, or with autoimmune conditions.
Clinical Significance:
OMAS is a critical diagnosis to consider in any child presenting with the triad of opsoclonus, myoclonus, and ataxia
Prompt recognition is crucial as it often signals an underlying malignancy requiring urgent treatment
Early and aggressive immunotherapy and oncological management are vital for improving neurological outcomes and prognosis
The condition can lead to significant developmental delays and long-term neurological deficits if not managed effectively.
Clinical Presentation
Symptoms:
Onset of symptoms is typically acute or subacute
Chief complaints may include: Rapid, erratic eye movements making vision difficult
Jerky, involuntary movements of limbs and trunk, often described as twitching
Difficulty walking, standing, or coordinating movements, leading to unsteadiness and falls
Irritability, behavioral changes, and sleep disturbances are also common
In infants, developmental regression may be observed.
Signs:
Ocular: Opsoclonus – chaotic, conjugate, high-amplitude, multidirectional, saccadic eye movements
Myoclonus – generalized or focal, often affecting trunk and limbs
Ataxia – truncal and limb ataxia, affecting gait and coordination
Neurological examination may reveal other signs like hypotonia, dysarthria, and tremor
Behavioral changes such as irritability, hyperactivity, or regression
Vital signs are usually normal unless complicated by other factors.
Diagnostic Criteria:
There are no universally agreed-upon formal diagnostic criteria, but the diagnosis is typically made based on the presence of the characteristic triad: opsoclonus, myoclonus, and ataxia, in the absence of other identifiable causes
A high index of suspicion is paramount, especially in young children
Association with a neuroendocrine tumor, particularly neuroblastoma, is a key feature in paraneoplastic OMAS.
Diagnostic Approach
History Taking:
Detailed birth history and developmental milestones
Onset and progression of ocular, motor, and behavioral symptoms
Any preceding viral illness or vaccination
Family history of neurological disorders or cancer
Detailed medication history
Red flags include sudden onset of neurological symptoms, presence of the classic triad, and any abdominal mass.
Physical Examination:
A thorough neurological examination is essential, focusing on: Ocular movements (eliciting opsoclonus)
Assessment of myoclonic jerks
Evaluation of gait and coordination (ataxia)
Assessment for other neurological deficits
A complete physical examination to detect any signs suggestive of an underlying malignancy, such as an abdominal mass, lymphadenopathy, or skin changes (café-au-lait spots).
Investigations:
Neuroimaging: MRI brain with gadolinium to rule out structural lesions and evaluate for neuroinflammation
MRI/CT abdomen and pelvis to search for neuroblastoma or other tumors
Urine catecholamines (VMA/HVA) and serum ferritin levels are crucial for neuroblastoma screening
Serum neuroblastoma markers may include NSE (neuron-specific enolase)
CSF analysis: May show mild pleocytosis or elevated protein, but often normal
EEG: Can show generalized slowing or spike-wave discharges, but not specific for OMAS
Autoimmune workup: Antibody testing (e.g., anti-Hu, anti-Yo, anti-Ri) in older children and adults if autoimmune etiology is suspected.
Differential Diagnosis:
Other causes of opsoclonus: Drug-induced ocular motor abnormalities, metabolic encephalopathies, encephalitis
Other causes of myoclonus: Epilepsy, hypoxic brain injury, metabolic disorders
Other causes of ataxia: Cerebellar vermian hypoplasia, inherited ataxias, post-infectious cerebellar ataxia
Conditions to differentiate include acute cerebellar ataxia, infectious encephalitides, metabolic disorders, and other paraneoplastic syndromes.
Management
Initial Management:
The cornerstone of management is a two-pronged approach: aggressive tumor treatment (if present) and immunosuppressive therapy
Early intervention is critical for better neurological recovery
Stabilization measures include managing seizures or severe myoclonus with appropriate anticonvulsants if needed.
Immunotherapy:
High-dose corticosteroids (e.g., IV methylprednisolone followed by oral prednisone) are typically the first-line treatment
Intravenous immunoglobulin (IVIG) is also a crucial component of therapy, often used in conjunction with or sequentially after steroids
Rituximab may be considered in refractory cases
Chemotherapy targeting the underlying neuroblastoma is essential and often includes agents like cyclophosphamide, vincristine, and platinum-based drugs, tailored to the stage and risk group of the tumor.
Tumor Eradication:
Surgical resection of the primary tumor is often performed
Adjuvant chemotherapy, radiation therapy, and bone marrow transplantation may be employed depending on the stage, risk stratification, and response to initial treatment of the neuroblastoma
Complete eradication of the tumor is paramount for long-term remission of OMAS.
Supportive Care:
Intensive supportive care is vital
This includes: Physiotherapy and occupational therapy to address motor deficits and improve coordination
Speech therapy for dysarthria
Behavioral therapy and educational support for cognitive and behavioral issues
Nutritional support and management of sleep disturbances.
Complications
Early Complications:
Status epilepticus related to myoclonus
Severe behavioral disturbances and sleep deprivation
Dehydration and malnutrition due to feeding difficulties
Respiratory compromise secondary to severe myoclonus
Infections due to immunosuppression.
Late Complications:
Long-term neurological sequelae are common and can include: Developmental delay and intellectual disability
Persistent motor deficits (ataxia, dysmetria)
Behavioral problems (ADHD, autism spectrum features)
Visual impairment due to opsoclonus
Recurrence of OMAS due to tumor relapse or incomplete remission.
Prevention Strategies:
Early and aggressive treatment of the underlying neuroblastoma is the most critical strategy to prevent OMAS recurrence
Close monitoring for tumor recurrence and prompt management of any relapses are essential
Ongoing neurorehabilitation and educational support are key to mitigating long-term neurological deficits.
Prognosis
Factors Affecting Prognosis:
Prognosis is variable and depends on: Age at onset (younger children tend to have better outcomes)
Promptness and aggressiveness of treatment (both oncological and immunological)
Presence and extent of the underlying tumor
Response to immunotherapy
Degree of neurological sequelae at diagnosis
Complete tumor resection and remission.
Outcomes:
With optimal treatment, some children can achieve significant neurological recovery, with improvement or resolution of opsoclonus, myoclonus, and ataxia
However, many will have residual neurological deficits
Long-term remission of OMAS is strongly correlated with successful treatment and sustained remission of the underlying neuroblastoma
Relapse of OMAS can occur if the tumor recurs.
Follow Up:
Lifelong follow-up is recommended
This should include: Regular oncological surveillance for tumor recurrence
Ongoing neurological assessment and neurorehabilitation
Developmental and educational monitoring and support
Management of any persistent symptoms like behavioral issues or motor deficits
Periodic assessment of visual function.
Key Points
Exam Focus:
Remember the classic triad: opsoclonus, myoclonus, ataxia
Neuroblastoma is the most common cause in children
Management involves both immunotherapy and tumor treatment
IVIG and corticosteroids are key to immunotherapy
Early tumor detection via urine catecholamines, ferritin, and imaging is crucial.
Clinical Pearls:
Always suspect OMAS in a child with unexplained opsoclonus, myoclonus, or ataxia
The absence of an abdominal mass does not rule out neuroblastoma
Neuroblastoma can be occult and may present with OMAS as the primary manifestation
Aggressive treatment is associated with better neurological outcomes.
Common Mistakes:
Delaying the tumor search in a child with unexplained OMAS
Underestimating the severity of neurological deficits and the need for intensive rehabilitation
Inadequate or delayed immunotherapy
Focusing solely on neurological symptoms without a comprehensive oncological workup.