Alternating Hemiplegia of Childhood
Alternating hemiplegia of childhood is a rare brain disorder that causes sudden, temporary paralysis in young children, along with developmental challenges and other symptoms that can significantly impact their quality of life.
Table of contents
- What is Alternating Hemiplegia of Childhood?
- Identification Codes and Synonyms
- Signs and Symptoms
- What Causes This Condition
- How is it Diagnosed?
- Treatment Options
- How Common is This Condition
- Pattern of Inheritance
- Living with the Condition
What is Alternating Hemiplegia of Childhood?
Alternating hemiplegia of childhood (AHC) is a brain disorder involving paralysis and muscle stiffness that starts in early infancy. The condition is called “alternating” because episodes of paralysis can affect one side of the body and then switch to the other side, or sometimes affect both sides at the same time.[1][2]
The disorder is characterized by recurring episodes of temporary paralysis. These episodes begin in infancy or early childhood, usually before 18 months of age, and the paralysis can last from minutes to days.[1] During these episodes, children may experience hemiplegia (paralysis affecting one side of the body) or paralysis of all arms and legs together.[2]
A unique and important feature of this condition is that all symptoms disappear while the affected person is sleeping but can reappear shortly after awakening.[1][2] This relief with sleep is one of the characteristic signs that helps doctors recognize the condition.
Identification Codes and Synonyms
AHC, Alternating hemiplegia syndrome
G98
MB53.0
C536589
10077948
Signs and Symptoms
Most children with alternating hemiplegia of childhood will develop symptoms before 18 months of age.[2] The symptoms can last for minutes or for days, and they vary in severity from one person to another.
Main Symptoms
All children with this condition experience three main problems:[2]
- Episodes of paralysis that alternate between one side of the body and the other
- Occasional total paralysis of all arms and legs together
- Developmental delays affecting learning, movement, and behavior
Common Additional Symptoms
Most patients will also have:[2]
- Episodes of painful muscle stiffness
- Episodes of abnormal, jerky eye movements
- Trouble with balance or walking
- Gastrointestinal issues, such as constipation
- ADHD (attention-deficit/hyperactivity disorder)
Other Possible Symptoms
About half of patients will have:[2]
- Epileptic seizures
- Episodes of reduced awareness of surroundings
- Behavioral issues, such as aggression
- Sleep disorders
Fewer than half of patients will have:[2]
- Episodes of flushing, sweating, and color change
- Swallowing disorders
- Autism spectrum disorder
- Involuntary jerky or worm-like movements of the arms and legs
Triggers for Episodes
The episodes of hemiplegia or uncontrolled movements can be triggered by certain factors, although the trigger is not always known. Common triggers include stress, extreme tiredness, cold temperatures, bathing, psychological stress or excitement, and exposure to water, heat, or cold.[1][2]
Changes Over Time
The number and length of the episodes initially worsen throughout childhood but then begin to decrease over time. The uncontrollable muscle movements may disappear entirely, but the episodes of hemiplegia occur throughout life.[1]
Cognitive and Developmental Impact
Alternating hemiplegia of childhood also causes mild to severe cognitive problems. Almost all affected individuals have some level of developmental delay and intellectual disability (limitations in intellectual functioning and adaptive behavior). Their cognitive functioning typically declines over time.[1]
What Causes This Condition
Alternating hemiplegia of childhood is primarily caused by changes (mutations) in the ATP1A3 gene. Very rarely, a mutation in the ATP1A2 gene is involved in the condition.[1] Around 75% to 80% of people with alternating hemiplegia of childhood have a mutation in the ATP1A3 gene.[3][7]
How the Genes Work
These genes provide instructions for making proteins that function as part of a larger protein complex called Na+/K+ ATPase. This complex is found in different parts of the brain and plays a critical role in the normal function of nerve cells (specialized cells that transmit signals throughout the body). The Na+/K+ ATPase transports charged atoms (ions) into and out of nerve cells, which is an essential part of the signaling process that controls muscle movement.[1]
The mutation causes cells in the brain to function differently than normal. They become unable to move sodium and potassium across the wall of the cell as usual. This leads to the symptoms of the condition.[2]
What Happens When Genes Are Mutated
Mutations in the ATP1A3 or ATP1A2 gene reduce the activity of the Na+/K+ ATPase, impairing its ability to transport ions normally. It is unclear exactly how a malfunctioning Na+/K+ ATPase causes the episodes of paralysis or uncontrollable movements characteristic of alternating hemiplegia of childhood.[1]
How is it Diagnosed?
The sooner alternating hemiplegia of childhood is identified, the sooner doctors can help manage symptoms and coordinate treatments that maximize developmental potential.[3] Because it is rare, with symptoms that mimic other conditions, an accurate diagnosis is essential.
Medical History and Physical Examination
A thorough medical history is key to diagnosing alternating hemiplegia of childhood.[3] The diagnosis includes identifying the onset of symptoms before 18 months of age, episodes of hemiplegia, paralysis of all limbs, other disturbances, disappearance of symptoms upon sleep, and developmental delay.[7]
Genetic Testing
Genetic testing can confirm the presence of the ATP1A3 gene mutation, which is associated with most cases. This testing can also rule out mutations associated with other neurological disorders.[3] Genetic screening should be offered early on clinical suspicion.[7]
Brain Activity Tests
Electroencephalogram (EEG) tests measure electrical activity in the brain. They help confirm or rule out epilepsy, which can occur in up to half of children with this condition.[3] Video EEG is valuable for distinguishing epileptic from other attacks.[7]
Heart Tests
An echocardiogram (an imaging test that uses sound waves) looks for structural abnormalities of the heart. An electrocardiogram (a test that records the electrical activity of the heart) may look for heart rhythm abnormalities, since people with this condition have a higher risk of developing heart problems later in life.[3]
Sleep Studies
Sleep studies can identify sleep abnormalities such as obstructive sleep apnea, central sleep apnea, restless legs, and others.[3]
Imaging Tests
Tests like MRI scans (magnetic resonance imaging, which uses magnets and radio waves to create detailed pictures of the inside of the body) can detect or rule out structural brain problems and other medical conditions that can cause episodes of paralysis or muscle stiffness.[3] There is no specific biomarker and MRI is usually normal.[7]
Distinguishing from Other Conditions
The condition can mimic other conditions, particularly epilepsy. Most patients are initially misdiagnosed with epilepsy because the stiffening during episodes resembles epileptic seizures, and paralysis resembles the weakness that often follows epileptic seizures.[2]
Treatment Options
Although there is no cure for alternating hemiplegia of childhood, certain treatments help control symptoms and address physical or mental challenges.[3] The cornerstone of care is the use of multidisciplinary approaches that can address a variety of needs.[2]
Medications for Attack Prevention
Flunarizine is the main medication used to help reduce the frequency, severity, and duration of attacks of paralysis and muscle stiffness. Studies have demonstrated that flunarizine reduces the duration, severity, and frequency of the hemiplegic attacks in up to 80% of patients.[10] While it is not FDA approved in the United States, anecdotal reports of benefit are compelling.[10]
Other medications that have been tried with various rates of success include benzodiazepines, topiramate, and other agents.[10]
Managing Acute Episodes
Acute attack management includes benzodiazepines (administered orally, rectally, or via nasal administration) and sleep inducers such as chloral hydrate and phenobarbital.[10] Since symptoms are relieved by sleep, inducing sleep can be an effective strategy during severe episodes.[2]
Managing Related Conditions
Epilepsy, which develops in about half of children with alternating hemiplegia of childhood, is often reasonably managed with standard antiepileptic agents. However, it is important to try to distinguish nonepileptic from epileptic episodes and treat appropriately.[10]
Behavioral and mood disturbances become increasingly prevalent in later childhood and adolescence, and antipsychotic agents and mood stabilizing medications may be of value.[10]
Avoiding Triggers
A variety of strategies targeted toward episode prevention can be helpful, including avoidance of specific stressors or triggers.[10]
Multidisciplinary Care
Because alternating hemiplegia of childhood affects so many aspects of a child’s development, people with this condition benefit when they are diagnosed and managed by a team of specialists with a deep understanding of the disorder.[3] This requires lifelong care from a team of specialists.[2]
Future Treatments
While currently there is no cure for this condition, there is active research on new kinds of therapies. These new therapies could potentially have major impacts on the symptoms and quality of life of these patients.[2]
How Common is This Condition
Alternating hemiplegia of childhood is a very rare condition. It seems to occur in only one in a million people.[1][2] However, recent research suggests that there may be upwards of 28,000 cases in the world, with only about 1,500 cases currently known, which means there are likely thousands of undiagnosed cases.[15]
Pattern of Inheritance
Alternating hemiplegia of childhood is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder.[1]
Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. The gene mutation is usually spontaneous (de novo), meaning it rarely runs in families and was not inherited from the parents, but rather happened at or shortly after conception.[3][15]
However, the condition can also run in families. For unknown reasons, the signs and symptoms are typically milder when the condition is found in multiple family members than when a single individual is affected.[1]
Living with the Condition
Alternating hemiplegia of childhood requires lifelong care. Problems may increase with time.[2] The condition causes long-term problems that can include developmental issues affecting learning, movement, and psychological development, which are often severe.[2]
Quality of Life
Quality of life for the vast majority of those suffering from this condition is generally not good. Most do not live independently, depending on relatives or group home care as adults.[15] However, there is a broad spectrum of severity ranging from children and adults who are wheelchair-bound, non-verbal, feeding tube dependent, with little to no cognitive development, to those who live semi-independent lives and participate to some degree in society.[15]
There are a growing number of individuals who are gaining more skills, and even some who are participating in normal adult scenarios (holding a job, getting married, writing a book, artistry), thanks in part to advances in technology, mobility, and treatment of symptoms.[15]
Not Considered Progressive or Life-Shortening
Alternating hemiplegia of childhood is not considered to be progressive in nature, nor life-shortening per se. However, some individuals have lost their lives prematurely from complications of the disease (loss of ability to breathe, seizure, heart issues, injury from loss of motor control).[15]
Special Considerations for Medical Procedures
People with this condition have a higher risk of developing heart problems later in life. Special precautions need to be taken if patients undergo sedation or anesthesia, as they have a higher risk of respiratory or heart problems during these procedures.[2]
Importance of Early Diagnosis
There is currently increasing awareness of alternating hemiplegia of childhood, which has made early diagnosis more common than before. An early diagnosis is essential because it can avoid misdiagnosis and unhelpful medications which may have negative side effects, and get children the help and medications they need more quickly.[2]
Hope for the Future
However, there are many treatments that can make a big difference in patients’ lives. While currently there is no cure, there is active research on new kinds of therapies that could potentially have major impacts on the symptoms and quality of life of these patients.[2]
