User:BSByrne/Athetoid Cerebral Palsy

Athetoid/ dyskinetic cerebral palsy (ADCP) is a movement disorder primarily associated with damage to the basal ganglia, in the form of lesions that occur during brain development due to bilirubin encephalopathy and hypoxic-ischemic brain injury. ADCP falls within the cerebral palsy (CP) group of disorders and comprises approximately 11-15% of all CP cases. Unlike spastic or ataxic cerebral palsies, ADCP is characterized by both hypertonia and hypotonia, due to the affected individual's inability to control muscle tone. Clinical diagnosis of ADCP typically occurs within 18 months of birth and is primarily based upon motor function and neuroimaging techniques. While there are no cures for ADCP, some medical treatments as well as speech and physical therapy have shown capacity for treating the symptoms.

Classification
ADCP is classified as a subdivision of cerebral palsy that accounts for 11.4% - 15% of all CP cases. . CP is classified based on the nature of the movement disorder as well as the anatomic, topographic distribution of motor abnormalities. Currently there is no broadly agreed upon topographic classification of cerebral palsy.

The most prevalent classification system is proposed by Surveillance for CP in Europe (SCPE) and classifies CP as either spastic, dyskinetic, or ataxic. Spastic CP is further subdivided into being either bilateral or unilateral. ADCP is further subdivided into dystonic or choreo-athetotic (also known as hyperkinetic). Choreo-athetotic ADCP is characterized by involuntary movements most predominantly found in the face and extremities. Dystonic ADCP is characterized by slow, strong contractions, which may occur locally or encompass the whole body. Ataxic CP is further subdivided into either spastic ataxic or non-classifiable cerebral palsy.

The motor disorder can also be classified according to its localization. This method classifies children as diplegia, (bilateral involvement with leg involvement greater than arm invovement), hemiplegia (unilateral involvement), or quadriplegia (bilateral involvement with arm involvement equal to or greater than leg involvement).

Signs & Symptoms
ADCP is specified by slow, uncontrolled movements of the extremities and trunk. These movements may include the flexion, extension, pronation, and supination of fingers, hands, toes, and feet. Small, rapid, random and repetitive uncontrolled movements known as chorea may also occur. Involuntary movements often increase during periods of emotional stress or excitement and disappear when the patient is sleeping or distracted. Patients experience difficulties in maintaining posture and balance when sitting, standing, and walking due to these involuntary movements and fluctuations in muscle tone. Coordinated activities such as reaching and grasping may also be challenging. Muscles of the face and tongue can be affected, causing involuntary facial grimaces, expressions, and drooling. Speech and language disorders, known as dysarthria, are common in athetoid CP patients. Impairments of speech can be attributed to disorders in controlling the tongue, breathing patterns, and larynx. Patients with dysarthria may have voices that are monotone or have abnormal pitch and rhythm, making them difficult to understand. In addition, ADCP patients may have trouble eating. Hearing loss is a common symptom of athetoid CP as well.

Causes/ Etiology
CP is a non-progressive, neurological condition that results from brain injury and malformation occurring before cerebral development is complete. ADCP is associated with injury and malformations to the extrapyramidal tracts in the basal ganglia or the cerebellum. Lesions to this region principally arises via hypoxic ischemic brain injury (HIBI) or bilirubin encephalopathy.

Hypoxic-Ischemic Brain Injury
Hypoxic-ischemic brain injury (HIBI) is a form of cerebral hypoxia in which oxygen cannot perfuse to cells in the brain. Lesions in the putamen and thalamus caused by HIBI are primary causes of ADCP and can occur during the prenatal period and shortly after. Lesions that arise after this period typically occur as a result of injury or infections of the brain.

Bilirubin Encephalopathy
Bilirubin encephalopathy, also known as kernicterus, is the accumulation of bilirubin in the grey matter of the central nervous system. The main accumulation targets of hyperbilirubinemia are the basal ganglia, ocular movement nucleus, and acoustic nucleus of the brain stem. Pathogenesis of bilirubin encephalopathy is multifactorial, involving the transport of bilirubin across the blood-brain barrier and into neurons. Mild disruption results in left cognition impairment, while severe disruption results in ADCP. Lesions caused by accumulation of bilirubin occur mainly in the global pallidus and hypothalamus. Disruption of the blood-brain barrier by disease or a hypoxic ischemic injury can also contribute to an accumulation of bilirubin in the brain. Bilirubin encephalopathy leading to cerebral palsy has been greatly reduced by effective monitoring and treatment for hyperbilirubinemia in preterm infants.

Genetic Factors
Although genetic factors play a lesser role in the development of ADCP, a risk of recurrence in siblings is suggested. Familial cases of ADCP can be explained by either an autosomal-recessive or X-linked-recessive inheritance.

Diagnosis
ADCP is typically diagnosed within 18 months of birth. Prior to the development of neuroimaging techniques, an assessment of motor limitations associated with the inability to control muscle tone was the primary diagnostic tool in recognizing ADCP. Magnetic resonance imaging (MRI) is now used in addition to motor assessments to aid in diagnosing the disease.

Motor Function
Movement and posture limitations are aspects of all CP types and as a result, CP has historically been diagnosed based on parental reporting of developmental motor delays such as failure to sit upright, reach for objects, crawl, stand, or walk at the appropriate age. Diagnosis of ADCP is chiefly based on clinical assessment used in conjunction with milestone reporting. The majority of ADCP assessments now use the gross motor function classification system (GMFCS) or the International Classification of Functioning, Disability and Health (formerly the International Classification of Impairments Disease, and Handicaps), measures of motor impairment that are effective in assessing severe CP. ADCP is typically characterized by an individual’s inability to control their muscle tone, which is readily assessed via these classification systems.

Neuroimaging
Magnetic Resonance Imaging (MRI) is used to detect morphological brain abnormalities associated with ADCP in patients that are either at risk for ADCP or have shown symptoms thereof. The abnormalities chiefly associated with ADCP are lesions that appear in the basal ganglia. The severity of the disease is proportional to the severity and extent of these abnormalities, and is typically greater when lesions appear elsewhere in the deep grey matter or white matter. MRI also has the ability to detect brain malformation, periventricular leukomalacia (PVL), and areas affected by hypoxia-ischemia, all of which may play a role in the development of ADCP. The MRI detection rate for ADCP is approximately 54.5%, however this statistic varies depending on the patient’s age and the cause of the disease and has been reported to be significantly higher.

Medical
Medications that impede the release of excitatory neurotransmitters have been used to control or prevent spasms. Treatment with intrathecal baclofen, a gamma-aminobutyric acid (GABA) agonist, decreases muscle tone and has been shown to decrease the frequency of muscle spasms in ADCP patients. The anticholinergic trihexyphenidyl has been used to decrease the contraction of striated muscle and has been used to treat various dystonias, including ADCP. Tetrabenazine, a drug commonly used in the treatment of Huntington's Disease, has also shown to treat the hyperkinetic aspects of ADCP.

Deep Brain Stimulation
Deep brain stimulation is a technique that uses electrodes placed in the brain to modify brain activity by sending a constant electrical signal to the nearby nuclei. Treatment of dystonia via DBS typically targets the global pallidus and has shown to significantly improve symptoms associated with ADCP.

Physical Therapy
Physical therapy is a staple treatment of ADCP. Physical therapy is initiated soon after diagnosis and typically focuses on trunk strength and maintaining posture. Physical therapy helps to improve mobility, range of motion, functional ability, and quality of life. Specific exercises and activities prescribed by a therapist help to prevent muscles from deteriorating or becoming locked in position and help to improve coordination.

Speech Therapy
Athetoid Cerebral Palsy affects all muscles of the body, including the muscles of the mouth, neck, and larynx. Communication is often difficult for patients with all forms of cerebral palsy including ADCP. Speech therapy is the treatment of communication diseases, including disorders in speech production, pitch, intonation, respiration and respiratory disorders. Exercises advised by a speech therapist or speech-language pathologist help patients to improve oral motor skills, restore speech, improve listening skills, and use communication aids or sign language if necessary.

Prognosis
Studies suggest a poor prognosis for patients with ADCP. Mortality is strongly associated with both the level of functional impairments as well as associated non-motor impairments. Speech problems, such as dysarthia, are common to these patients. 30%-78% are predicted to have normal intelligence. Up to 50% of patients will achieve some degree of ambulation. The severity of the disease and related prognosis is dependent on the location and severity of brain lesions.

Epidemiology
The prevalence of cerebral palsy is about 2%-3% worldwide and within cerebral palsy, dyskinetic accounts for 11.4% - 15%. However, approximations vary based on diagnostic techniques. . Individuals with a family history of ADCP are at a higher risk for developing the disease.