Hemiplegic migraine

Title

Categories:

Congenital and Genetic Diseases; Nervous System Diseases

Summary Summary

Hemiplegic migraine (HM) is a rare type of migraine with aura that occurs with motor weakness during the aura. There are two types of HM which are distinguished based on the family history: familial hemiplegic migraine (FHM, in which at least one other family member has the condition) and sporadic hemiplegic migraine (SHM, in which there is no family history).^[1] Signs and symptoms vary but may include visual disturbances, sensory loss, difficulty with speech, weakness on one side of the body, confusion, and impaired consciousness.^[2] Severe attacks may occur in both types with prolonged hemiplegia, coma, fever and/or seizures.^[1] FHM may be caused by a mutation in any of several genes and is inherited in an autosomal dominant manner.^[1]^[2]

Last updated: 11/17/2014

Symptoms Symptoms

The symptoms and severity can vary considerably among people with hemiplegic migraine. Signs and symptoms associated with aura may include:^[3]

Visual disturbance (e.g. blind spots, flashing lights, zigzag pattern, and double vision)
Sensory loss (e.g., numbness or paresthesias of the face or an extremity)
Difficulty with speech (which usually occur along with right-sided weakness)

Motor weakness involves areas affected by sensory symptoms and varies from mild clumsiness to complete deficit. Affected people may also experience neurologic symptoms such as confusion, drowsiness, impaired consciousness, coma, psychosis, and/or memory loss. Neurologic symptoms can last for hours to days. Attention and memory loss can last weeks to months. However, permanent motor, sensory, language, or visual symptoms are extremely rare.^[3]

Last updated: 11/17/2014

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of movement	90%
Hemiplegia/hemiparesis	90%
Incoordination	50%
Nystagmus	50%
Abnormality of retinal pigmentation	7.5%
EEG abnormality	7.5%
Neurological speech impairment	7.5%
Sensorineural hearing impairment	7.5%
Seizures	5%
Tremor	5%
Agitation	-
Anxiety	-
Aphasia	-
Apraxia	-
Ataxia	-
Auditory hallucinations	-
Autosomal dominant inheritance	-
Blindness	-
Blurred vision	-
Cerebellar atrophy	-
Coma	-
Confusion	-
Diplopia	-
Drowsiness	-
Dysarthria	-
Dyscalculia	-
Dysphasia	-
Episodic ataxia	-
Fever	-
Hemiparesis	-
Hemiplegia	-
Heterogeneous	-
Incomplete penetrance	-
Intellectual disability	-
Migraine with aura	-
Photophobia	-
Psychosis	-
Transient unilateral blurring of vision	-
Vertigo	-
Visual hallucinations	-

Last updated: 9/1/2016

Cause Cause

There are two types of hemiplegic migraine (HM), which are distinguished based on the family history in affected people: familial hemiplegic migraine (FHM, in which at least one other close family member has the condition) and sporadic hemiplegic migraine (SHM, in which there is no family history).^[1]

FHM may be caused by changes (mutations) in the CACNA1A, ATP1A2, SCN1A, and PRRT2 genes. The first three of these genes give the body instructions for making proteins involved in moving charged atoms (ions) across cell membranes. This process is important for for normal signaling between nerve cells (neurons) in the brain and other parts of the nervous system. Researchers think that mutations in these genes may upset the balance of ions in neurons, affecting the release and uptake of certain neurotransmitters in the brain. The exact function of the PRRT2 gene is not yet understood but is also thought to play a part in controlling signals between neurons. When the genes involved in FHM do not work correctly, the signaling abnormalities between neurons lead to the development of severe headaches and auras in affected people.^[4] The genetic cause in many families with FHM remains unknown.^[3]

While SHM occurs in people with no history of the condition in their family, most cases are due to new (de novo) mutations that occur for the first time in the affected person. Some people with SHM do inherit a mutation from a parent who has the mutation but is not affected. The ATP1A2 and CACNA1A genes have been found to cause SHM in addition to FHM. Many people with SHM do not have a mutation in one of these genes; however, researchers think that mutations in other, unidentified genes are also involved in the condition.^[5]

Last updated: 11/18/2014

Inheritance Inheritance

The known types of familial hemiplegic migraine (FHM) that are due to a mutation in the CACNA1A, ATP1A2, or SCN1A genes are inherited in an autosomal dominant manner.^[6] When a person with an autosomal dominant condition has children, each child has a 50% (1 in 2) risk to inherit the mutated gene from the affected parent. FHM due to a mutation in one of these genes accounts for some, but not all, cases of FHM. It is likely that there are additional types of FHM caused by mutations in other genes.^[6]

People who are the first member of their family to have hemiplegic migraine are classified as having sporadic hemiplegic migraine (SHM). Some cases of SHM are caused by one of the genetic mutations that cause familial hemiplegic migraine (FHM), due to either having a new mutation, or from inheriting the condition from a parent with no signs or symptoms.^[6] In these cases, a person with SHM can still pass the condition on to a child.

Last updated: 11/18/2014

Diagnosis Diagnosis

Hemiplegic migraine is diagnosed based on the presence of specific signs and symptoms. Genetic testing is not necessary for all affected people.^[6]

The diagnosis is based on the presence of having at least 2 attacks with:

aura accompanied by fully reversible motor weakness and fully reversible visual, sensory, and/or speech/language symptoms; and
at least 2 of the following 4 characteristics:
- at least one aura symptom that spreads gradually over ≥5 minutes, and/or two or more symptoms that occur in succession
- each individual non-motor aura symptom lasting 5 to 60 minutes, and motor symptoms lasting <72 hours
- at least one unilateral (one-sided) aura symptom
- the aura being accompanied by headache, or followed by headache within one hour^[6]

Additionally, all other potential causes for the symptoms need to be ruled out (such as transient ischemic attack and stroke). While the criteria requires fully reversible symptoms, it is known that some people with severe attacks may have permanent neurological problems.^[6]

A diagnosis of familial hemiplegic migraine also requires that at least one first or second degree relative has had attacks that meet the above diagnostic criteria. A diagnosis of sporadic hemiplegic migraine requires that no first or second degree relative has had attacks that meet the above criteria.^[6]

Last updated: 11/18/2014

Genetic testing for familial hemiplegic migraine (FHM) is available in order to try to establish the genetic basis of the condition in a family.^[3] However, the genes currently known to cause FHM account for only a small proportion of cases,^[6] so most affected people will not have a positive genetic test result. Prenatal diagnosis and testing for at-risk family members is available if the disease-causing mutation in a family is already known.^[3]

The Genetic Testing Registry (GTR) provides information about the labs that offer genetic testing. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Last updated: 11/18/2014

Treatment Treatment

Treatment of hemiplegic migraine varies depending on severity and which symptoms are most problematic for the patient. In general, treatments aim to manage symptoms. Drugs that are effective in the prevention of common migraines may be used in hemiplegic migraine.^[3] Prophylactic management is applied to patients with frequent, long lasting, or severe attacks. Examples of migraine drugs that have been tried with variable success in people with hemiplegic migraine, include oral verapamil, acetazolamide, lamotrigine.^[3]

There are a few articles describing the use of nasal administration of ketamine, intravenous verapamil, and triptans for treatment of aura in people with hemiplegic migraine. Use of triptans in hemiplegic migraine is controversial and may be contraindicated in people with severe attacks.^[3]

For further information on these and other treatments, we recommend that you speak with your healthcare provider.

Last updated: 8/26/2013

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Hemiplegic migraine. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD. Suggest an organization to add.

Organizations Supporting this Disease

American Headache Society Committee for Headache Education (ACHE)
19 Mantua Road
Mt. Royal, NJ 08061
Telephone: 856-423-0043
Fax: 856-423-0082
E-mail: achehq@talley.com
Website: http://www.achenet.org
American Migraine Foundation (AMF)
19 Mantua Rd.
Mount Royal, NJ 08061 United States
Telephone: 856-423-0043
Fax: 856-423-0082
E-mail: amf@talley.com
Website: https://americanmigrainefoundation.org/
M.A.G.N.U.M. (The National Migraine Association)
100 N Union Street
Suite B
Alexandria, VA 22314
Website: http://www.migraines.org/
Migraine Research Foundation
300 East 75th Street
Suite 3K
New York, NY 10021
Telephone: 212-249-5402
Fax: 212-249-5405
E-mail: contactmrf@migraineresearchfoundation.org
Website: http://www.migraineresearchfoundation.org
National Headache Foundation
820 North Orleans
Chicago, IL 60610-3132
Toll-free: 888-643-5552
E-mail: info@headaches.org
Website: http://www.headaches.org
The Migraine Trust
52-53 Russell Square
London, WC1B 4HP United Kingdom
Telephone: 020 7631 6970
Fax: 020 7436 2886
E-mail: info@migrainetrust.org
Website: http://www.migrainetrust.org/

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Hemiplegic migraine. This website is maintained by the National Library of Medicine.
Sporadic hemiplegic migraine
Familial hemiplegic migraine
The National Institute of Neurological Disorders and Stroke (NINDS) (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Familial hemiplegic migraine 1
Familial hemiplegic migraine 2
Familial hemiplegic migraine 3
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Hemiplegic migraine. Click on the link to view a sample search on this topic.

Related Diseases Related Diseases

The following diseases are related to Hemiplegic migraine. If you have a question about any of these diseases, you can contact GARD.

Familial hemiplegic migraine

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My husband has been having issues for about 3 years now. His left side extremities go numb/tingly. It's debilitating. No headache but does have auras. He's had numerous tests, including MRIs and a spinal tap. We've been told possible MS and saw a local doctor as well as a neurologist at a major medical center. We were told it was 'nothing' and to live with it. It seems the barometric pressure really triggers his symptoms. Would weather changes cause symptoms like this? We have no answers but would welcome any theories. See answer
I am curious how accurate hemiplegic migraine testing is. Standardly they test for 3 genes. Familial Hemiplegic Migraine and Sporadic. If I'm correct it is CACNA1A, ATP1A2 and SCN1A. Does everyone with hemiplegic migraine test positive for these mutations and if not, do you know the percentage? See answer
I experienced a headache followed by left sided numbness. I believe my doctor said I had hemiplegic migraine. During these episodes the left side of my body will feel like tiny pinpricks and go completely numb. When it gets really bad it spreads over to my right side and i cannot operate my car. When this happens I do not always get headaches. Is there any information you can give me? See answer

References References

Anne Ducros. Familial or sporadic hemiplegic migraine. Orphanet. April, 2008; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=569. Accessed 11/17/2014.
Russell MB, Ducros A. Sporadic and familial hemiplegic migraine: pathophysiological mechanisms, clinical characteristics, diagnosis, and management. Lancet Neurol. May, 2011; http://www.ncbi.nlm.nih.gov/pubmed/21458376. Accessed 8/26/2013.
Jen JC. Familial Hemiplegic Migraine. GeneReviews. September 2009; http://www.ncbi.nlm.nih.gov/books/NBK1388/#fhm.Clinical_Description.
Familial hemiplegic migraine. Genetics Home Reference. January, 2014; http://ghr.nlm.nih.gov/condition/familial-hemiplegic-migraine. Accessed 11/18/2014.
Sporadic hemiplegic migraine. Genetics Home Reference. February, 2014; http://ghr.nlm.nih.gov/condition/sporadic-hemiplegic-migraine. Accessed 11/18/2014.
Black DF, Robertson CE. Hemiplegic migraine. In: Swanson JW ed.,. UpToDate. Waltham, MA: UpToDate; 2015; Accessed 11/18/2014.