Information on the following diseases can be found in the Related Disorders section of this report:

• Cerebral Palsy
• Moyamoya Disease
• Hemiplegic Migraine
• Epilepsy

The symptoms associated with alternating hemiplegia of childhood (AHC), which may vary greatly in number and severity in affected individuals, usually begin before 18 months of age. AHC is characterized by repeated temporary (transient) attacks of paralysis involving one side of the body (hemiplegia). In some cases, both sides of the body may be involved (diplegia). These attacks may last for a few minutes or up to several days. Hemiplegic attacks may occur or reoccur abruptly upon awakening, then often subside after the child has returned to sleep. Typically, an attack begins with restlessness, screaming (loud vocalizations), and the appearance of being in pain. This is frequently accompanied by excessive sweating, changes in skin color, and body temperature changes (autonomic nervous system dysfunction).

Other frequent symptoms may include lack of muscle control and function and/or loss of sensation (paresis). Reduced muscle tone (hypotonia) or, conversely, increased muscle tone (hypertonia) leading to abnormal postures (dystonic stiffening) may occur. Affected individuals may display abnormal, involuntary, slow flexion and extension of limbs, facial muscles, and/or hands and feet (choreoathetosis). Symptoms may also include an impaired ability to control movement and/or balance (ataxia).

Some individuals with AHC have episodes of brief, recurrent convulsive seizures (epilepsy). Such episodes may be characterized by periods of unconsciousness, sensory disturbances, and spasms. AHC may also be associated with severe head pain that is one-sided, throbbing, and immobilizing.

Some infants or children with AHC may also display other symptoms such as involuntary, rhythmic eye movements (nystagmus); hands and feet that appear cold or pale in color; temporary paralysis of the muscles that control eye movements (transient ocular palsies); decreased, tightened muscle tone of the legs and arms (spasticity); and/or a small head in relation to the body (microcephaly). Affected children may also display a delayed acquisition of skills requiring the coordination of physical and mental abilities (psychomotor retardation); speech impairment (aphasia); and/or mild, moderate, or severe mental retardation.

The exact cause of alternating hemiplegia of childhood (AHC) is unknown (idiopathic). It is believed that, in some cases, symptoms of AHC may develop due to injury or trauma to one of the brain's hemispheres before, during, or after birth, leading to brain complications such as an inflammatory condition (encephalitis) and abnormal blood vessels (cerebrovascular) of the brainstem and rear portion of the brain (cerebrum). In some cases, sudden exposure to loud noises, bright light, and/or emotional stress can bring on hemiplegic episodes that could last for minutes or days. Some researchers have suggested that there may be an association between AHC and a strong family history of migraine; however, this possible association is not fully understood.

In rare cases, this disorder may be inherited as an autosomal dominant trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Alternating hemiplegia of childhood (AHC) is a rare disorder affecting males and females in equal numbers. Symptoms are usually evident before 18 months of age and may vary greatly in number and severity. First recognized in 1971, at least 100 cases in the United States and 200 cases worldwide have been reported in the medical literature.

Symptoms of the following disorders can be similar to those of Alternating Hemiplegia of Childhood. Comparisons may be useful for a differential diagnosis:

Cerebral Palsy is a rare neuromuscular disorder. Infants with Cerebral Palsy may display developmental delays before the third year and may have weak muscle tone (hypotonia). Typical characteristics may include drooling, difficulty in gaining bladder or bowel control, convulsions, hand tremors, poor vision, and/or the inability to identify objects by touch. Intelligence may be average to above average, or there may be mild to severe mental impairment. Cerebral Palsy may be caused by brain injury during the early stages of fetal development, at birth, or after birth (postnatal). Injury may result from maternal/fetal infection, lack of oxygen (hypoxia), or bleeding into the brain. (For more information on this disorder, choose "Cerebral Palsy" as your search term in the Rare Disease Database.)

Moyamoya Disease is a progressive disorder that affects blood vessels in the brain (cerebrovascular) by narrowing and/or in some cases closing off the main artery to the brain (carotid). In children, symptoms may include seizures, involuntary body movements, and possible mental retardation. Affected individuals may have headaches; episodes of paralysis in the feet, legs, and upper extremities; difficulties in speech; cerebral bleeding (hemorrhage); and abnormally low levels of red blood cells that carry oxygen (anemia). Visual disturbances may also occur. The exact cause of Moyamoya Disease is not known. However, in some cases, it is thought to be inherited as an autosomal recessive trait. (For more information on this disorder, choose "Moyamoya" as your search term in the Rare Disease Database.)

The following disorders may be associated with Alternating Hemiplegia of Childhood as secondary characteristics. They are not necessary for a differential diagnosis:

Hemiplegic Migraine is a neurological disorder affecting infants, children, and adults. Characteristic episodes may involve severe head pain that is one-sided, throbbing, and immobilizing. Additional symptoms may include loss of feeling or muscle function in one side of the body (unilateral paralysis), a feeling comparable to motion sickness (nausea), visual disturbances, and/or symptoms similar to tension headache. Episodes may frequently be preceded by an "aura," which is described as a feeling of uneasiness or sensory discomfort that comes before a migraine. In some cases, affected children may have attacks of hemiplegic migraines on alternating sides of the head, lasting for a varying duration. Although the exact cause remains unknown, several families have been studied in which hemiplegic migraine appeared to be inherited as an autosomal dominant genetic trait.

Epilepsy is a group of disorders of the central nervous system characterized by repeated convulsive electrical (paroxysomal) disturbances of the brain. Major symptoms may include loss of consciousness, convulsive seizures, spasms, sensory confusion, and disturbances in the nerves that control involuntary body functions (autonomic nervous system dysfunction). Episodes are frequently preceded by an aura, described as a feeling of uneasiness or sensory discomfort that comes before a seizure. The most common causes of recurring epilepsy in infants include genetic inborn errors of metabolism, developmental brain defects, injuries or trauma to the head before or after birth, and other metabolic or brain-related disorders. (For more information on this group of disorders, choose "Epilepsy" as your search term in the Rare Disease Database.)

Diagnosis
The diagnosis of alternating hemiplegia of childhood (AHC) may involve a procedure of recording electrical responses in the brain (electroencephalogram [EEG]) and other brain mapping techniques. Advanced diagnostic imaging techniques may also include single photon emission computer tomography (SPECT) and positron emission tomography (PET). Long- term diagnostic follow-ups are suggested for infants and children affected by AHC to help distinguish symptoms from those of epilepsy, migraine headache, and other related disorders.

Treatment
The treatment of AHC is directed toward the specific symptoms that are apparent in each individual. Drugs administered to treat epileptic seizures (anticonvulsants) and to help relieve migraines (antimigrainous) as well as the use of other calcium channel blockers have had varying unsatisfactory results in children with AHC. However, anticonvulsant drugs may help to control seizures in those children with AHC who also have epilepsy.

A supportive team approach for children with AHC may be of benefit and may include special education, physical therapy, and other medical, social, or vocational services. Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 104290; Last Update: 3/16/94.

TEXTBOOKS
Adams, RD, et al., eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill, Companies; 1997:52, 152-56.

JOURNAL ARTICLES
Kanavakis E, et al. Alternating hemiplegia of childhood: a syndrome inherited with an autosomal dominant trait. Dev Med Child Neurol. 2003;45:833-6.

Chaves-Vischer V, et al. Benign nocturnal alternating hemiplegia of childhood. Six patients and long-term follow-up. Neurology. 2001;57:1491-93.

Sone K, et al. Successful trial of amantadine hydrochloride for two patients with alternating hemiplegia of childhood. Neuropediatrics. 2000;31:307-09.

Sasaki M, et al. Long-term effect of flunarizine on patients with alternating hemiplegia of childhood. Brain Dev. 2000;23:303-05.

Mikati MA, et al. Alternating hemiplegia of childhood: clinical manifestations and long-term outcome. Pediatr Neurol. 2000;23:134-41.

Bursztyn J, et al. Alternating hemiplegia of childhood and oculomotor anomalies. J Fr Ophthalmol. 2000;23:161-64.

Rho JM, et al. Alternating hemiplegia of childhood: insights into its pathophysiology. J Child Neurol. 1998;13:39-45.

Andermann F, et al. Infantile hypotonia and paroxysmal dystonia: a variant of alternating hemiplegia of childhood. Mov Disord. 1994;9:227-29.

Nevsimalova S, et al. Alternating hemiplegia in childhood: a cross-sectional study. Brain Dev. 1994;16:189-94.

Silver K, et al. Alternating hemiplegia of childhood: a study of 10 patients and results of flunarizine treatment. Neurology. 1993;43:36-41.

Bourgeois M, et al. Alternating hemiplegia of childhood. J Pediatr. 1993;122:673-79.

Andermann E, et al. Benign familial nocturnal alternating hemiplegia of childhood. Neurology. 1994;44:1812-14.

Nishiki T, et al. Patient with unusual alternating hemiplegia. Neurology. 1993;10:153-56.

Siemes H, et al. Single-photon emission computed tomography investigations of alternating hemiplegia of childhood. Dev Med Child Neurol. 1993;35:346-58.

Mikati MA, et al. A syndrome of autosomal dominant alternating hemiplegia: clinical presentation mimicking intractable epilepsy; chromosomal studies; and physiologic investigations. Neurology. 1992;42:2251-57.

Bode H, et al. Abnormal cerebral hemodynamics during attacks of alternating hemiplegia. Child's Nerv Syst. 1992;8:231-33.

Alsup S, et al. Alternating hemiplegic migraine in childhood. J Neurosci Nurs. 1991;23:381-85.

Zupanc ML, et al. 123I-iodoamphetamine SPECT brain imaging in alternating hemiplegia. Pediatr Neurol. 1991;7:35-38.

Shirasaka Y, et al. Epileptic seizures difficult to differentiate from alternating hemiplegia in infants: a case report. Brain Dev. 1990;12:521-24.

Casaer P. Flunarizine in alternating hemiplegia in childhood. An international study in 12 children. Neuropediatrics. 1987;18:191-95.

Aicardi J. Alternating hemiplegia of childhood. International Pediatrics. 1987;2:115-19.