Alternating hemiplegia (also known as crossed hemiplegia) is a form of

hemiplegia Hemiparesis, or unilateral paresis, is weakness of one entire side of the body ('' hemi-'' means "half"). Hemiplegia is, in its most severe form, complete paralysis of half of the body. Hemiparesis and hemiplegia can be caused by different medic ...

that has an ipsilateral cranial nerve palsies and contralateral hemiplegia or hemiparesis of extremities of the body. The disorder is characterized by recurrent episodes of

paralysis Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...

on one side of the body. There are multiple forms of alternating hemiplegia, Weber's syndrome, middle alternating hemiplegia, and inferior alternating hemiplegia. This type of syndrome can result from a unilateral lesion in the

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...

affecting both

upper motor neuron Upper motor neurons (UMNs) is a term introduced by William Gowers in 1886. They are found in the cerebral cortex and brainstem and carry information down to activate interneurons and lower motor neurons, which in turn directly signal muscles t ...

s and

lower motor neuron Lower motor neurons (LMNs) are motor neurons located in either the anterior grey column, anterior nerve roots (spinal lower motor neurons) or the cranial nerve nuclei of the brainstem and cranial nerves with motor function (cranial nerve lower mo ...

s. The muscles that would receive signals from these damaged upper motor neurons result in spastic paralysis. With a

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

in the brainstem, this affects the majority of limb and trunk muscles on the contralateral side due to the upper motor neurons

decussation Decussation is used in biological contexts to describe a crossing (due to the shape of the Roman numeral for ten, an uppercase 'X' (), ). In Latin anatomical terms, the form is used, e.g. . Similarly, the anatomical term chiasma is named aft ...

after the brainstem. The

cranial nerves Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...

and

cranial nerve nuclei A cranial nerve nucleus is a collection of neurons (gray matter) in the brain stem that is associated with one or more of the cranial nerves. Axons carrying information to and from the cranial nerves form a synapse first at these nuclei. Lesions ...

are also located in the brainstem making them susceptible to damage from a brainstem lesion. Cranial nerves III (Oculomotor), VI (Abducens), and XII (Hypoglossal) are most often associated with this syndrome given their close proximity with the

pyramidal tract The pyramidal tracts include both the corticobulbar tract and the corticospinal tract. These are aggregations of efferent nerve fibers from the upper motor neurons that travel from the cerebral cortex and terminate either in the brainstem (''cort ...

, the location which upper motor neurons are in on their way to the spinal cord. Damages to these structures produce the ipsilateral presentation of paralysis or palsy due to the lack of cranial nerve decussation (aside from the

trochlear nerve The trochlear nerve (), ( lit. ''pulley-like'' nerve) also known as the fourth cranial nerve, cranial nerve IV, or CN IV, is a cranial nerve that innervates just one muscle: the superior oblique muscle of the eye, which operates through the pul ...

) before innervating their target muscles. The paralysis may be brief or it may last for several days, many times the episodes will resolve after sleep. Some common symptoms of alternating hemiplegia are mental impairment, gait and balance difficulties, excessive sweating and changes in body temperature.

Symptoms and signs

Superior alternating hemiplegia

Superior alternating hemiplegia (also known as Weber syndrome) has a few distinct symptoms: contralateral

hemiparesis Hemiparesis, or unilateral paresis, is weakness of one entire side of the body (''wikt:hemi-#Prefix, hemi-'' means "half"). Hemiplegia is, in its most severe form, complete paralysis of half of the body. Hemiparesis and hemiplegia can be caused ...

of limb and facial muscle accompanied by weakness in one or more muscles that control eye movement on the same side. Another symptom that appears is the loss of eye movement due to damage to the oculomotor nerve fibers. The upper and lower extremities have increased weakness.

Middle alternating hemiplegia

Middle alternating hemiplegia (also known as Foville Syndrome) typically constitutes weakness of the extremities accompanied by paralysis of the extraocular muscle specifically lateral rectus, on the opposite side of the affected extremities, which indicates a lesion in the caudal and medial pons involving the abducens nerve root (controls movement of the eye) and corticospinal fibers (carries motor commands from the brain to the spinal cord).

Inferior alternating hemiplegia

Inferior alternating hemiplegia (also known as medial medullary syndrome) typically involves a "weakness of the extremities accompanied by paralysis of muscles on the ipsilateral side of the tongue (seen as a deviation of the tongue on that side on protrusion). These symptoms indicate a lesion in the medulla involving the corticospinal fibers in the pyramid and the exiting hypoglossal nerve roots.

Causes

Note that this description is focused on alternating hemiplegia of childhood. Similar syndromes may develop following a brainstem infarction. The cause of alternating hemiplegia of childhood is the mutation of

ATP1A3 Sodium/potassium-transporting ATPase subunit alpha-3 is an enzyme that in humans is encoded by the ''ATP1A3'' gene. Function The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of ...

gene. In a study of fifteen female and nine male patients with alternating hemiplegia, a mutation in ATP1A3 gene was present. Three patients showed heterozygous de-novo missense mutation. Six patients were found with de-novo

missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense m ...

and one patient was identified with de-novo splice site mutation.

De novo mutation A de novo mutation is any mutation/alteration in the genome of any organism (humans, animals, plant, microbes, etc.) that wasn't present or transmitted by their parents. This type of mutation (like any other) occurs spontaneously during the process ...

is a mutation that occurs in the germ cell of one parent. Neither parent has the mutation, but it is passed to the child through the sperm or egg.

Diagnosis

There is no diagnostic test for alternating hemiplegia, which makes it very difficult to diagnose. Also, because alternating hemiplegia is extremely rare, it is frequently missed and the patient is often misdiagnosed. Proper diagnosis, however, is critical for early treatment of the disorder. There are many criteria that can help in the proper general diagnosis of alternating hemiplegia.

Criteria for diagnosis

First, the symptoms must be observed before the patient is 18 months of age. Second, there must be frequent episodes of hemiplegia, involving either side of the body. Third, other paroxysmal disorders including tonic attacks,

dystonia Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often inten ...

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...

strabismus Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a ...

dyspnoea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...

, and other uncontrollable disorders are noticed to occur. Although common, the paroxysmal disorders involving the eye, nystagmus and strabismus, may not be apparent in older children and may not have been remembered in childhood so a lack of these symptoms does not rule out alternating hemiplegia. Fourth, all symptoms clear up directly after falling asleep and usually come back after waking during an attack. This occurrence is very indicative of alternating hemiplegia and as such those who display this are usually diagnosed with probable alternating hemiplegia. Fifth, indications of developmental delays, learning disability, or neurological irregularities are present. These issues may not be obvious in very young patients; however, it appears in almost all older patients. The final criteria before a diagnosis of alternating hemiplegia can be made is that all of these symptoms must not be due to another disorder. If the symptoms can be attributed to another disease or disorder, then a definitive diagnosis is difficult to make.

Diagnosis of Weber's syndrome

Weber's syndrome is the only form of alternating hemiplegia that is somewhat easy to diagnose beyond the general criteria. Although Weber's syndrome is rare, a child born with the disorder typically has a port-wine stain on the face around the eye. While the port-wine stain does not necessarily mean the child has Weber's syndrome, if the port-wine stain involves the ophthalmic division of the trigeminal nerve than the likelihood of it being weber's syndrome greatly increases. If a port-wine stain around the eye is found, the patient should be screened for intracranial leptomeningeal

angiomatosis Angiomatosis is a non-neoplastic condition characterised by nests of proliferating capillaries arranged in a lobular pattern, displacing adjacent muscle and fat. It consists of many angiomas. These tend to be cavernous hemangiomas, which are shar ...

Magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...

(MRI) can be used to determine the presence and severity while computed cranial tomography can be used to determine the effect. MRI is the preferred diagnostic test on children presenting with port-wine stain. Other imaging techniques can be used in addition to further determine the severity of the disorder. The initial diagnosis is made based on the presence of neurologic and ophthalmic disease but the disease progresses differently in each patient so after initial diagnosis the patient should be monitored frequently in order to handle further complications resulting from the syndrome.

Treatment

Medical treatment of hemiplegia can be separate into several different categories: * prophylactic treatment by avoiding triggers and long-term drug treatment * acute management of the episodes * management of the epilepsy * sleep as a management technique.
Seizure trigger include exposure to cold, emotional stress, fatigue, bathing, hyperthermia/hypothermia, and upper respiratory infection. A drug called

flunarizine Flunarizine, sold under the brand name Sibelium among others, is a drug classified as a calcium antagonist which is used for various indications. It is not available by prescription in the United States or Japan. The drug was discovered at Janss ...

, which is a calcium channel blocker can help to reduce the severity and the length of attacks of the paralysis.

Flunarizine

Many children affected by alternating hemiplegia also have epilepsy. Seizures may occur during an attack but more often occur between attacks. Anti-epilepsy drugs are given to prevent or lessen the seizures, but the drugs often don't work and have severe side effects that require the patient to discontinue use. Flunarizine, which blocks calcium channels, is an antiepilepsy drugs used in 50% of patients, and has been shown to shorten the duration of attacks as well as reducing the severity of the attacks. While Flunarizine does not stop the attacks, it is most common drug prescribed to treat those with alternating hemiplegia.

Sleep and diet

Sleep is also used as a management technique. An early indication of an episode is tiredness so medication such as

melatonin Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle. In vertebrates ...

or Buccal midazolam can be administered to induce sleep and avoid the episode. People with alternating hemiplegia are often underweight and with the help of dietitians, a meal plan should be developed for times of attack when consumption of food may be difficult.

References

External links

* {{DEFAULTSORT:Alternating Hemiplegia Genetic diseases and disorders Neurological disorders