Glossary

Alternating hemiplegia of childhood (AHC): a rare neurological disorder characterized by repeated attacks of hemiplegia affecting either side of the body, ocularmotor abnormalities, movement disorder and progressive developmental delay[1]. The diagnostic criteria for AHC are as follows[2]:

1. Symptoms before age 18 months
2. Repeated attacks of hemiplegia that alternate in laterality (meaning that the paralysis alternates from one side of the body to the other)
3. Episodes of quadriplegia as a separate attack or as a generalization of a hemiplegia attack
4. Relief from symptoms upon sleeping
5. Other paroxysmal symptoms including dystonic spells, oculomotor abnormalities, or autonomic symptoms which may occur in addition to the hemiplegia attacks or independently
6. Evidence of developmental delay or neurologic findings such as choreoathetosis, dystonia or ataxia

The incidence of AHC is estimated at roughly 1 in 1000000 births[3], however, the true incidence may be higher since the disorder is commonly misdiagnosed due to the lack of awareness about AHC and the variability of its clinical features.

AHC episodes: (see definition for “episode”) Abnormal ocular movements: Abnormal ocular movements, also known as “ocular motor abnormalities”, are often the first symptom observed in patients with AHC. They are generally seen within the first 3 months of infancy. The abnormal movements may include nystagmus, esotropia and/or exotropia.

• View abnormal ocular movements video 1
• View abnormal ocular movements video 2

Alternating Hemiplegia of Childhood Foundation (AHCF): The AHCF is a non-profit, tax exempt organization started by parents of children and adults with AHC. Ataxia: By definition, ataxia means “without coordination”. Patients with ataxia experience a lack of coordination when performing voluntary movements. Ataxia is usually caused by dysfunction in the cerebellum, the part of the brain that controls movement and balance.[4]

• View the Ataxia video

Autonomic Dysfunction: 
Children with Alternating Hemiplegia of Childhood may experience autonomic dysfunction. In order to fully understand the concept autonomic dysfunction, it’s important to understand the autonomic nervous system and the role that it plays in the nervous system as a whole. The nervous system is divided into 2 major parts: the central nervous system (CNS) and the peripheral nervous system (PNS).

• Central Nervous System (CNS): The CNS is made up of the brain and the spinal cord.
• Peripheral Nervous System (PNS): The PNS is made up of nerves outside the brain and spinal cord. There are two types of nerve cells in the PNS: sensory neurons, which send information from the body to the CNS and motor neurons, which send information from the CNS to the rest of the body. The PNS can be further divided into 2 major parts: the somatic nervous system and the autonomic nervous system, both of which have both sensory and motor neurons.
  • Somatic Nervous System: The sensory portion of the somatic nervous system conveys sensations from the body to the brain where it usually reaches our awareness, for example, when we touch something hot and feel pain. The motor portion of the somatic nervous system transmits impulses from the CNS to the body (namely the skeletal muscles), resulting in voluntary movements, for example when you move your hand off of the hot object in response to feeling pain. In other words, the SNS enables voluntary control of bones, joints, skin and skeletal muscle.
  • Autonomic Nervous System (ANS): While the SNS is responsible for voluntary control over the bones, joints, skin and skeletal muscles, the ANS is responsible for involuntary control of the heart, internal organs, glands and blood vessels. The sensory neurons of the ANS transmits messages from the body to the brain without our awareness[30]. In response, the motor neurons of the ANS transmits automatic or reflex responses to maintain homeostatis in the body amidst our changing environment. As you read this, your autonomic nervous system is busy monitoring and maintaining your blood pressure, heart beat, body temperature, breathing rate, posture, and many other bodily functions. There are 3 divisions of the autonomic nervous system: the sympathetic, parasympathetic nervous system and the enteric nervous system[31].
    • The Sympathetic Nervous System: The sympathetic nervous system stimulates the body. For example, it helps prepare the body to deal with emergency situations, which is why it is often referred to as the “fight or flight” response. Stimulation from sympathetic nerves dilates the pupils, accelerates the heartbeat, increases the breathing rate, and inhibits the digestive tract.
    • The Parasympathetic Nervous System: When there is little stress, the parasympathetic system tends to slow down the overall activity of the body. It causes the pupils to contract, it promotes digestion, and it slows the rate of heartbeat. This system is often referred to as the “rest and digest” response.
      • See a diagram comparing the effects of the parasympathetic vs. the sympathetic nervous system
    • The Enteric Nervous System: The digestive system is endowed with its own, local nervous system called the enteric nervous system. The enteric division contains neurons that control the digestive tract, pancreas, and gallbladder. Although the enteric nervous system can function independently, it is often regulated by the sympathetic and parasympathetic divisions.

Autonomic dysfunction (AD) can be described as a disorder of the autonomic nervous system[32]. Children with Alternating Hemiplegia of Childhood may experience AD, also known as dysautonomia, during an AHC episode. Symptoms of AD are wide ranging and may include problems with the regulation of heart rate, blood pressure, body temperature and perspiration[33]. Signs of AD may include cold hands and feet, skin blotching or discoloration, altered pain perception, altered sweating (excessive sweating or no sweating), feeding/swallowing problems, gastrointestinal problems, etc. See a full list of autonomic symptoms in children here. Channelopathy: Channelopathies are a group of diseases caused by the dysfunction of ion channels. Ion channels are passageways in the cell membranes (outer ) of all cells . They control the movement of ions in and out of the cells. Ions are electrically charged particles, such as calcium, potassium, sodium and chloride[5]. Ion channels control nerve function, heart contraction, movement, and various other important body processes, therefore ion channel dysfunction can cause many health problems. Ion channel dysfunction can affect any tissue in the body but it usually affects the muscular and nervous system[6].

• Image of an ion channel

Chorea/choreic movements: Chorea is a type of abnormal movement characterized by recurrent, brief, unpredictable and purposeless body movements that have a tendency to flow from one body part to another[7]. The movements are briefer than those seen with dystonia but more sustained and less “shocklike” than the movements seen with myoclonus. Choreic movements may be sudden and jerky or may be more continuous and flowing. When they are more continuous and flowing, the term choreoathetosis is used.

• View the choreic movements on the University of Utah Department of Neurology’s website

Choreoathetosis: Choreoathetosis refers to a type of movement disorder marked by 2 types of abnormal involuntary movements: chorea and athetosis[8] . Choreic movements are recurrent, brief, unpredictable and purposeless; they often appear to flow from one part of the body to another. Athetoid movements are continuous and flowing, resembling a twisting or writhing motion. When choreic movements are more continuous and flowing (athetoid-like), the term “choreoathetosis” is used. Dyskinesia: Dyskinesia is a broad term for any abnormal involuntary movement. Dystonia/Dystonic movements: Dystonic movements are abnormal movements that are usually rhythemic and repetitive, causing twisting movements and abnormal postures[8]. Dystonia occurs when opposing muscles are contracting at the same time. The activation of these muscles may “overflow” to other muscle groups unintentionally. EEG: An electroencephalogram (EEG) is a test used to detect abnormal electrical activity in the brain[9]. Small flat metal discs called electrodes are placed on the scalp to record the brain’s electrical activity. The brain cells constantly communicate through electrical impulses, even during sleep. Normal electrical activity results in a predictable pattern on an EEG recording so doctors will look for patterns that are unusual to identify abnormal electrical activity. An EEG is most commonly used to diagnose epilepsy and other types of seizure disorders. Epilepsy: Epilepsy refers to a neurological disorder that results from the generation of abnormal electrical signals inside the brain, causing recurring seizures. A person is only considered to have epilepsy if he or she has had two or more seizures. Treatment for epilepsy most commonly involves the use antiepileptic drugs. For patients whose seizures are not well controlled with these drugs, alternative therapies may include vagus nerve stimulation or the implementation of a ketogenic diet[14]. Each headache may last from a few hours to a few days. Roughly 20 percent of people with FHM develop mild but permanent ataxia and nystagmus. The two main features of AHC that distinguish it from FHM are 1) the onset of the characteristic symptoms during infancy and 2) the increased neurological deficits seen in AHC. Research has shown that FHM is caused by an underlying channelopathy, therefore the similarities between FHM and AHC may indicate that AHC is also caused by ion channel dysfunction[15]. The effectiveness of calcium channel blockers (such as Flunarizine) in managing AHC episodes further supports this hypothesis[16],[18] . Episode: With AHC, the term “episode” is used to describe a hemiplegic attack. Such episodes are seen within the first 6 months of infancy for most AHC patients[1]. Episodes may last anywhere from a few minutes to several days and may be associated with progressive neurologic deficits. AHC episodes are often associated with triggers that precede or induce the attack. Triggers for AHC episodes may include environmental conditions (such as temperature extremes or odors), water exposure, physical activities (exercise, swinging), lights (sunlight, fluorescent bulbs), and/or foods (chocolate, food dye) & medications. Esotropia: Esotropia is a type of strabismus (eye misalignment), where one eye looks straight ahead and the other is crossed or turned inward toward the nose.

• Images: Esotropia

There are 4 main types of esotropia:

1. Congenital (Infantile) Esotropia: This form develops within the first 6 months of infancy

• Image of Congenital (Infantile) Esotropia

1. Accommodative Esotropia: This form of esotropia is due to farsightedness and can usually be corrected with the use of farsighted glasses.

• Images: Accomodative esotropia

1. Acquired Non-Accommodative Esotropia: This form of esotropia develops after infancy but does not correct with the use of farsighted glasses, thereby not falling into either of the first 2 categories.
2. Pseudoesotropia: Pseudoesotropia is not a true form or esotropia/strabismus and the eyes are actually aligned correctly. The eyes appear crossed due to a broad bridge of the nose. As the child grows and the face matures, the crossed-eye appearance generally goes away.

• Image of pseudoesotropia

Exotropia: Exotropia is a type of strabismus (eye misalignment), where one eye looks straight ahead and the other turns outward, away from the nose. This can occur when looking at distance objects, close objects or both. If this occurs at all times, it is referred to as “constant exotropia” and if it occurs only sometimes, such as when the person is tired or when they are looking at distant objects, this is called “intermittent exotropia” http://www.pedseye.com/strabismus_exotropia.htm http://www.strabismus.org/exotropia.html Etiology: Etiology refers to the origin of a disease. Etiology may refer to the cause of the disease or may describe certain factors that predispose someone to the disease. The etiology of AHC is generally random, meaning that there is no known cause and no family history of the disease[2]. There is some evidence that AHC may be genetic and there is one family reported that has 3 generations of family members with AHC. However, there has yet to be conclusive research to support a common genetic origin for all patients with AHC. Familial hemiplegic migraine (FHM) aka familial migraine: Familial hemiplegic migraine (FHM) is a genetic form of migraine headache. Migraines may begin in childhood or adolescence and can be triggered by certain foods, emotional stress, and minor head trauma[3]. Each headache may last from a few hours to a few days. Roughly 20 percent of people with FHM develop mild but permanent ataxia and nystagmus. The two main features of AHC that distinguish it from FHM are 1) the onset of the characteristic symptoms during infancy and 2) the increased neurological deficits seen in AHC. Research has shown that FHM is caused by an underlying channelopathy, therefore the similarities between FHM and AHC may indicate that AHC is also caused by ion channel dysfunction[4]. The effectiveness of calcium channel blockers (such as Flunarizine) in managing AHC episodes further supports this hypothesis^15,16. Flunarizine: Flunarizine is a type of anticonvulsant drug known as a calcium channel blocker. It is traditionally used for the treatment of seizures, vertigo and migraines but is also used in the management of AHC patients. Flunarizine (5–20 mg/day) has been shown to decrease the severity, duration and frequency of AHC episodes in some patients with AHC[5],[6]. Sodium Oxybate: Sodium oxybate is another term for the drug Xyrem. It is used to prevent attacks of cataplexy (sudden, brief episodes of muscle weakness) in patients with narcolepsy[1]. The use of sodium oxybate is highly controlled and it should only be used under medical supervision. A former clinical study, run by Dr. Kathryn Swoboda from the University of Utah, investigated the ability of sodium oxybate to decrease AHC episodes and improve the quality of life for individuals with AHC. Strabismus: Strabismus describes a misalignment of the eyes, where both eyes do not look at the same place at the same time[25]. The eyes may turn inward (referred to as esotropia), outward (referred to as exotropia), upward (hypertropia) or downward (hypotropia). Strabismus may be caused by problems of the actual eye muscles, dysfunction of the nerves that send information to the eye muscles or impairment of the brain area that controls eye movements. Misalignment may be constant or intermittent, it may be unilateral (one eye) or bilateral (both eyes) and it may alternate from eye to eye (alternating). Trigger: In AHC, the term “trigger” or “triggering event” is used to describe circumstances which precede or cause an lead to an AHC episode[28]. Specific triggers may include:

• Environmental conditions (such as temperature extremes or odors),
• Water exposure (About 1/3 of AHC patients have had an attack provoked by bathing, unrelated to the temperature of the water[29])
• Physical activities (exercise or motion, such as swinging)
• Lights (bright sunlight or fluorescent lightbulbs)
• Foods (such as chocolate or food dye)
• Emotional response (anxiety, stress, fright)
• Odors (foods, fragrances)
• Fatigue
• Medications

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