Athetoid Cerebral Palsy

Etiology

Unlike spastic cerebral palsy, which is more commonly associated with preterm delivery or prolonged moderate-intensity hypoxic events resulting in periventricular leukomalacia and diffuse white matter injury, dyskinetic cerebral palsy is related to basal ganglia and thalamic injuries. These injuries are usually seen with brief but profound hypoxic insults. Patients with dyskinetic cerebral palsy are more commonly termed infants versus those with spastic cerebral palsy.[4]

Another common cause is neonatal hyperbilirubinemia-induced kernicterus, as there is bilirubin deposition in the basal ganglia. As kernicterus has become less common because of preventive strategies in hyperbilirubinemia, there has been a decrease in the incidence of dyskinetic cerebral palsy. Additionally, any insults such as intracranial hemorrhage, stroke, or cerebral infection to the basal ganglia and thalamus can result in dyskinetic cerebral palsy.[5]

Epidemiology

Cerebral palsy overall is the most common cause of childhood disability, occurring in 1.5 to 2.5 per 1000 live births.[1] The most common subtype of cerebral palsy is the spastic type, which further divides into spastic diplegia, spastic hemiplegia, and spastic quadriplegia types. Dyskinetic or athetoid-type cerebral palsy, which we are discussing in this article, makes up 12% to 14% of cerebral palsy cases overall. This calculates to around 1.8 to 3.5 cases per 10000 live births for dyskinetic cerebral palsy. The least common subtype of cerebral palsy is the ataxic subtype, making up 4% to 13% of the total cases of cerebral palsy.[6][7] As mentioned previously, dyskinetic cerebral palsy occurs more commonly in term infants compared to the spastic subtype, which is more common and has a higher association with preterm birth.[4]

History and Physical

Dyskinetic cerebral palsy, like all forms of cerebral palsy, is a clinical diagnosis. The history should identify risk factors for athetoid cerebral palsy, such as perinatal asphyxia or severe hyperbilirubinemia in the perinatal period.[5] Other important parts of the history include detailed history regarding the prenatal and perinatal period and developmental history, which is important as patients with dyskinetic cerebral palsy have motor and other developmental delays. Family history can help determine if other neurological or movement disorders should be considered a differential diagnosis. Questions should also focus on finding comorbidities associated with dyskinetic cerebral palsy. Nonmotor comorbidities can be more common in dyskinetic cerebral palsy than spastic subtypes; these include intellectual impairment, which can be severe, speech problems, and epilepsy.[8] Common comorbidities include weight loss, poor feeding, sleep, respiratory disturbances, and musculoskeletal deformities are also common.[9]

The physical exam is important in evaluating a patient with dyskinetic cerebral palsy, especially in identifying the disease as the dyskinetic subtype versus the other subtypes of cerebral palsy. The distribution and the tone of the abnormal musculature characterize the subtypes.[1] Common clinical findings in dyskinetic cerebral palsy include the following:

• In early infancy: Delayed motor development, reduced spontaneous movements, variable tone with movements while hypotonic at rest, and persistence of primitive reflexes shown in early infancy.
• By age 2 to 3: Involuntary movements and abnormal posturing are more apparent; this includes persistently turning the head to one side, extending the head supine, flexing the shoulder, and retracting the shoulder while prone.

The involuntary movements can be characterized by the type of movements they are. Within dyskinetic cerebral palsy, there is choreathetotic cerebral palsy, which consists of chorea and athetosis. Chorea involves irregular and rapid contractions of muscles, including those of the face, proximal extremities, and toes and fingers. Athetosis involves slow, writhing movements of the distal extremities. Emotions, stress, and illness can induce or worsen these movements. Dystonic cerebral palsy consists of sustained repetitive and patterned movements, such as twisting limbs and trunk; these movements can be slow or fast. A sudden increase in tone occurs during movement or with emotions.[6][7]

Evaluation

Other than the clinical history and physical exam, as mentioned above, neuroimaging helps assess athetoid cerebral palsy. Seventy percent of patients with dyskinetic cerebral palsy have lesions found on magnetic resonance imaging of the brain in the basal ganglia or thalamus. Few patients have scans that look normal.[8][10] Other lesions can be found, as well. In those with kernicterus, lesions in the globus pallidus are usually seen.[11] 

Clinical scales and assessment tools also help measure the severity of dystonia and choreoathetosis, which are often complex and hard to measure. These include several measurement scales, such as the Barry-Albright Dystonia Rating scale, the Burke-Fahn-Marsden Dystonia Rating scale (BFMS), and the Dyskinesia Impairment Scale (DIS). These scales can help evaluate the severity of dystonia in dyskinetic cerebral palsy but have limitations in dyskinetic cerebral palsy as there is no measurement for choreoathetosis. This is resolved in the DIS, specifically for assessing patients with dyskinetic cerebral palsy.[12][13] DIS and BFMS are often used for outcome measurements in interventions such as deep brain stimulation.[14]

Treatment / Management

Management of dyskinetic cerebral palsy centers around the management of symptoms and aims at improvement in the quality of life for the patient. This involves the management of dystonia and choreoathetosis, as well as helping with associated pain, disability, and discomfort.[15] There is also a focus on the treatment of non-motor comorbidities that include epilepsy and depression. Other issues involve ensuring optimal nutrition, possibilities of contractures, and orthopedic complications. Management of symptoms and all aspects of dyskinetic cerebral palsy should be done from an interprofessional team approach. This team often includes clinicians, therapists, and behavioral health specialists. Intervention focuses on decreasing disability burden and maximizing quality of life.[16](B3)

Some medications are often used in the treatment of dyskinetic cerebral palsy; however, most of them show low efficacy. The most commonly used drug in dyskinetic cerebral palsy is oral baclofen, a gamma-aminobutyrate (GABA)-B agonist, and trihexyphenidyl, which is often used for dystonia. Efficacy for both of these drugs in dyskinetic cerebral palsy is, however, low.[17][18] Adverse events include the possibility of worsened choreoathetosis. This can occur when dystonia is reduced as dystonia masks the expression of choreoathetosis.[8] Medications that are often used as an attempt to manage movement symptoms are as follows:(B3)

• For dystonia: Dopamine agonists (levodopa), anticholinergics (trihexyphenidyl, benztropine), benzodiazepine receptor agonists (diazepam, clonazepam), GABA-B receptor agonist (baclofen), monoamine blockers (tetrabenazine), and voltage-gated sodium channel blockers (carbamazepine) [17][19]
• For chorea: Benzodiazepine receptor agonists (diazepam, clonazepam), dopamine antagonists (pimozide, haloperidol), monoamine blockers, and calcium channel blockers (levetiracetam .[19][20]
(A1)

An alternative that is sometimes used instead of oral medication, which generally has low efficacy with more side effects, is intrathecal baclofen. It can be administered at a lower dosage and with fewer side effects. There have been studies demonstrating a decrease in dystonia.[21][22] Deep brain stimulation (DBS) has been used increasingly in those with dyskinetic cerebral palsy; this therapy is often used to decrease dystonia. Though it does decrease dystonia in those with dyskinetic cerebral palsy, there is less benefit in quality of life and functionality compared to that seen in patients with primary (inherited) dystonia.[23][24] Botulinum toxin is another treatment often used in the management of dystonia in dyskinetic cerebral palsy. There is some evidence that it decreases pain and dystonia in those with dyskinetic cerebral palsy. However, as with DBS, there is more evidence of its therapeutic value in those with primary dystonia.[25](B2)

Differential Diagnosis

Differential diagnoses include movement disorders, neuromuscular disorders, neurodegenerative disorders, and inborn errors of metabolism.[1] The predominant differential is based on other disorders with dystonia or chorea. This includes disorders such as:

• Glutaric aciduria type 1
• Lesch-Nyhan syndrome
• Niemann-Pick disease
• Pelizaeus-Merzhacher disease
• Rett syndrome
• Leigh disease
• Pyruvate dehydrogenase deficiency
• Dopamine-responsive dystonia
• Primary dystonia [1][26]

Prognosis

The life span of patients with cerebral palsy depends on the severity of disability as well as complications. Those who are more severely disabled usually have reduced life expectancy versus those who are less severely disabled.[1] There is a higher amount of early death in patients with dyskinetic cerebral palsy than in the other subtypes of cerebral palsy due to the increased amounts of complications and disability in comparison.[27] As with other types of cerebral palsy, the most common cause of death is respiratory failure, secondary to pneumonia and aspiration.[1]

For dyskinetic cerebral palsy, motor impairment is often more severe than other forms of cerebral palsy. Patients with dyskinetic cerebral palsy often score higher on the gross motor function classification system and manual ability classification system. There is a correlation between the amount of dystonia and disability level, more so than choreoathetosis.[10][28]

Complications

Many complications can exist with cerebral palsy, including intellectual disability, epilepsy, speech and hearing issues, orthopedic disorders, neurobehavioral disorders, and sleep disturbances.[1] In dyskinetic cerebral palsy, as the motor impairments are more severe than other types of cerebral palsy, as well as the characteristic involuntary movements, there are complications associated specifically with the severe motor impairments. This includes being underweight. Despite patients with dyskinetic cerebral palsy usually being born with normal birth weights, many are underweight on follow-up, and this is thought secondary to involuntary movement leading to higher energy expenditure as well as combined with poor feeding and dysphagia, which are other complications.[10] Patients with dyskinetic cerebral palsy are also less likely to be able to be independent of a caregiver, given the severity of the motor impairments as well as increased comorbidities, which are highlighted below.

Nonmotor complications of dyskinetic cerebral palsy include severe intellectual impairment, language disability, epilepsy, as well as a combination of these, which can occur in more than half of the patients with dyskinetic cerebral palsy.[10] Other complications include visual and hearing impairments, pain, and musculoskeletal deformities.[9] Mental health problems, including depression, are also common. The most common cause of death in dyskinetic cerebral palsy patients is respiratory comorbidities, which are aspiration and pneumonia, leading to respiratory failure.[27]