Alternating Hemiplegia of Childhood (AHC) is a rare, severe neurological disorder of infancy and early childhood, characterized by recurrent episodes of temporary paralysis affecting one or both sides of the body. It is considered an ultra-rare, life-long condition, with an estimated prevalence of approximately one in a million people worldwide. AHC causes a broad spectrum of neurological dysfunction, often leading to a significant impact on development and motor function. Due to the unusual nature of its symptoms, AHC is frequently misdiagnosed in its early stages.
Defining Characteristics and Clinical Presentation
The defining feature of AHC is the paroxysmal, temporary paralysis (hemiplegia) that typically shifts sides of the body. These episodes of weakness can range from mild numbness to complete, debilitating paralysis of an arm and a leg, lasting anywhere from minutes to several days. The paralysis may affect the left side during one attack and the right side during the next, which is the origin of the disorder’s name.
A distinctive characteristic of these paralytic episodes is that they often resolve completely when the child falls asleep, only to potentially recur shortly after waking. Numerous external and internal factors are known to trigger these attacks, including strong emotions (excitement or stress), extreme temperatures, exposure to water (such as bathing), bright lights, physical exertion, and illness.
Beyond temporary paralysis, individuals with AHC experience a constellation of other episodic, non-hemiplegic symptoms. These often include dystonia (involuntary, sustained muscle contractions causing twisting or repetitive movements) and abnormal postures. Nystagmus, a rapid, involuntary eye movement—often monocular—is also a common early symptom.
Patients may also experience autonomic disturbances, manifesting as changes in breathing patterns or skin color during an attack. Many children also develop epileptic seizures, sometimes later in childhood. Importantly, children with AHC are not symptom-free between these episodic attacks and often demonstrate persistent, non-episodic neurological impairments.
These permanent manifestations include varying degrees of global developmental delay and intellectual disability. Movement difficulties are common and may include ataxia (a lack of muscle coordination affecting balance, speech, and gait). These non-episodic symptoms contribute to the overall complexity of the disorder and require continuous supportive care.
Genetic Origin of Alternating Hemiplegia
The underlying cause of AHC is primarily rooted in genetic mutations, with the ATP1A3 gene identified in approximately 70 to 85% of cases. This gene provides instructions for making the alpha-3 subunit of the sodium-potassium pump (Na+/K+-ATPase). This protein pump is highly concentrated in the neurons of the central nervous system, particularly in areas like the basal ganglia and cerebellum.
The function of the Na+/K+-ATPase pump is to actively transport sodium ions out of the cell and potassium ions into the cell. This process maintains the electrochemical gradient across the neuronal cell membrane, which regulates electrical activity and neuronal excitability. A mutation in ATP1A3 impairs the pump’s function, disrupting the ion balance and making the neurons hypersensitive.
This neuronal hyperexcitability is thought to be the pathological mechanism leading to the recurrent, paroxysmal events characteristic of AHC. The vast majority of ATP1A3 mutations are de novo, meaning the mutation is a spontaneous change in the child’s DNA and was not inherited. In rare instances where it is inherited, the disorder follows an autosomal dominant pattern.
Diagnostic Pathway and Differential Diagnosis
The diagnosis of AHC is often challenging due to its rarity and the non-specific nature of early symptoms, frequently leading to misdiagnosis. The diagnostic process begins with a thorough clinical evaluation looking for a specific pattern of symptoms. Diagnostic criteria, such as the Aicardi criteria, rely heavily on observing characteristic alternating hemiplegia, symptom onset before 18 months of age, and symptom resolution with sleep.
Since AHC symptoms can closely resemble other neurological conditions, a comprehensive differential diagnosis is necessary. Physicians must systematically rule out more common paroxysmal disorders, such as various forms of epilepsy, complicated migraines, and transient ischemic attacks. Video electroencephalogram (EEG) monitoring is often used to distinguish between epileptic seizures and non-epileptic paroxysmal events, like dystonia.
Genetic testing provides the definitive diagnostic tool, specifically testing for pathogenic variants in the ATP1A3 gene. This confirmation allows for an accurate diagnosis, which helps avoid unnecessary treatments for conditions like epilepsy. The identification of an ATP1A3 mutation alongside the defining clinical features confirms the diagnosis of AHC.
Current Treatment Strategies and Symptom Management
There is currently no cure for Alternating Hemiplegia of Childhood. Treatment focuses on managing symptoms, reducing the frequency and severity of attacks, and providing supportive care. A primary non-pharmacological strategy involves rigorous avoidance of known triggers, such as excitement, temperature changes, and specific foods, although attacks can occur spontaneously. Careful monitoring of external stimuli helps minimize the risk of a debilitating episode.
Pharmacological management centers on agents that aim to stabilize neuronal excitability. Flunarizine, a calcium channel blocker, is the most commonly used medication. Anecdotal evidence suggests it can help reduce the frequency and duration of paralytic episodes for some individuals. However, its effectiveness varies widely among patients.
Other medications are utilized to manage the broad range of associated symptoms. Antiseizure medications, such as topiramate or benzodiazepines, may be prescribed to control epileptic seizures and other paroxysmal movements. Medications like trihexyphenidyl may be used to manage severe episodes of dystonia.
A multidisciplinary approach to supportive care is essential for addressing the persistent neurological impairments accompanying AHC. Physical therapy addresses movement disorders and maintains muscle strength and flexibility. Occupational therapy and speech therapy mitigate developmental delays and improve communication and daily living skills, maximizing the individual’s quality of life.