Holmes-Adie syndrome

Holmes-Adie syndrome (HAS) is a neurological disorder affecting the pupil of the eye and the autonomic nervous system.  It is characterized by one eye with a pupil that is larger than normal and constricts slowly in bright light  (tonic pupil), along with the absence of deep tendon reflexes, usually in the Achilles tendon.   HAS is thought to be the result of a viral or bacterial infection that causes inflammation and damage to neurons in the ciliary ganglion, an area of the brain that controls eye movements, and the spinal ganglion, an area of the brain involved in the response of the autonomic nervous system.  HAS begins gradually in one eye, and often progresses to involve the other eye.  At first, it may only cause the loss of deep tendon reflexes on one side of the body, but then progress to the other side.  The eye and reflex symptoms may not appear at the same time.  People with HAS may also sweat excessively, sometimes only on one side of the body.  The combination of these 3 symptoms – abnormal pupil size, loss of deep tendon reflexes, and excessive sweating – is usually called Ross’s syndrome, although some doctors will still diagnose the condition as a variant of HAS.  Some individuals will also have cardiovascular abnormalities.  The HAS symptoms can appear on their own, or in association with other diseases of the nervous system, such as Sjogren’s syndrome or migraine.  It is most often seen in young women.  It is rarely an inherited condition.

Is there any treatment?

Doctors may prescribe reading glasses to compensate for impaired vision in the affected eye, and pilocarpine drops to be applied 3 times daily to constrict the dilated pupil.   Thoracic sympathectomy, which severs the involved sympathetic nerve, is the definitive treatment for excessive sweating. 

What is the prognosis?

Holmes-Adie syndrome is not life-threatening or disabling.  The loss of deep tendon reflexes is permanent.  Some symptoms of the disorder may progress.   For most individuals, pilocarpine drops and glasses will improve vision. 

What research is being done?

The National Institute of Neurological Disorders and Stroke (NINDS), and other institutes of the National Institutes of Health (NIH), conduct research related to HAS in laboratories at the NIH, and also support additional research through grants to major medical institutions across the country.  Much of this research focuses on finding better ways to prevent, treat, and ultimately cure disorders, such as HAS.

NIH Patient Recruitment for Holmes-Adie syndrome Clinical Trials

• At NIH Clinical Center
• Throughout the U.S. and Worldwide
• NINDS Clinical Research Collaboration Trials

Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.

Last updated September 27, 2010

Amblyopia

Amblyopia Defined

What is amblyopia?

The brain and the eye work together to produce vision. Light enters the eye and is changed into nerve signals that travel along the optic nerve to the brain. Amblyopia is the medical term used when the vision in one of the eyes is reduced because the eye and the brain are not working together properly. The eye itself looks normal, but it is not being used normally because the brain is favoring the other eye. This condition is also sometimes called lazy eye.

How common is amblyopia?

Amblyopia is the most common cause of visual impairment in childhood. The condition affects approximately 2 to 3 out of every 100 children. Unless it is successfully treated in early childhood, amblyopia usually persists into adulthood, and is the most common cause of monocular (one eye) visual impairment among children and young and middle-aged adults.

Cause

What causes amblyopia?

Amblyopia may be caused by any condition that affects normal visual development or use of the eyes. Amblyopia can be caused by strabismus, an imbalance in the positioning of the two eyes. Strabismus can cause the eyes to cross in (esotropia) or turn out (exotropia). Sometimes amblyopia is caused when one eye is more nearsighted, farsighted, or astigmatic than the other eye. Occasionally, amblyopia is caused by other eye conditions such as cataract.

Treatment

How is amblyopia treated in children?

Treating amblyopia involves making the child use the eye with the reduced vision (weaker eye). Currently, there are two ways used to do this:

Atropine

A drop of a drug called atropine is placed in the stronger eye once a day to temporarily blur the vision so that the child will prefer to use the eye with amblyopia. Treatment with atropine also stimulates vision in the weaker eye and helps the part of the brain that manages vision develop more completely.

Patching

An opaque, adhesive patch is worn over the stronger eye for weeks to months. This therapy forces the child to use the eye with amblyopia. Patching stimulates vision in the weaker eye and helps the part of the brain that manages vision develop more completely.

Previously, eye care professionals often thought that treating amblyopia in older children would be of little benefit. However, surprising results from a nationwide clinical trial show that many children age seven through 17 with amblyopia may benefit from treatments that are more commonly used on younger children. This study shows that age alone should not be used as a factor to decide whether or not to treat a child for amblyopia.

Can amblyopia be treated in adults?

Studies are very limited at this time and scientists don’t know what the success rate might be for treating amblyopia in adults. During the first six to nine years of life, the visual system develops very rapidly. Complicated connections between the eye and the brain are created during that period of growth and development. Scientists are exploring whether treatment for amblyopia in adults can improve vision.

Current Research

What research is being done?

Findings from the clinical study, An Evaluation Of Treatment Of Amblyopia In Children 7 To (less than) 18 Years Old (ATS3), show that many children age seven through 17 with amblyopia (lazy eye) may benefit from treatments that are more commonly used on younger children. Previously, eye care professionals often thought that treating amblyopia in older children would be of little benefit. Read more about the ATS3.

The NEI is currently supporting the Amblyopia Treatment Study: Occlusion Versus Pharmacologic Therapy for Moderate Amblyopia (ATS) to determine whether patching or eyedrops is a better treatment for amblyopia. Recent results for the ATS found that the atropine eyedrops, when placed in the unaffected eye once a day, work as well as eye patching and may encourage better compliance. The study was conducted at 47 clinical sites throughout North America. Read more about the ATS.

In addition, A Randomized Trial Comparing Part-time Versus Minimal-time Patching for Moderate Amblyopia (Two v. Six) is being conducted to determine whether the visual acuity improvement obtained with part-time (6 hours) patching is equivalent to the visual acuity improvement obtained with minimal patching (2 hours) for moderate amblyopia. Recent findings show that patching the unaffected eye of children with moderate amblyopia for two hours daily works as well as patching the eye for six hours. Shorter patching time should lead to better compliance with treatment and improved quality of life for children with amblyopia. Read more about the Two v. Six study.

The NEI is also supporting other clinical studies on amblyopia.

More Information

• View Eye Health Organizations
• Tips on Talking to Your Doctor
• How to Find an Eye Care Professional

Content last reviewed in September 2009.

The National Eye Institute (NEI) is part of the National Institutes of Health (NIH) and is the Federal government's lead agency for vision research that leads to sight-saving treatments and plays a key role in reducing visual impairment and blindness.

What is Pelizaeus-Merzbacher Disease?

What is Pelizaeus-Merzbacher Disease?

Pelizaeus-Merzbacher disease (PMD) is a rare, progressive, degenerative central nervous system disorder in which coordination, motor abilities, and intellectual function deteriorate. The disease is one of a group of gene-linked disorders known as the leukodystrophies, which affect growth of the myelin sheath -- the fatty covering that wraps around and protects nerve fibers in the brain. The disease is caused by a mutation in the gene that controls the production of a myelin protein called proteolipid protein-1 (PLP1). PMD is inherited as an X-linked recessive trait; the affected individuals are male and the mothers are carriers of the PLP1 mutation. Severity and onset of the disease ranges widely, depending on the type of PLP1 mutation. PMD is one of a spectrum of diseases associated with PLP1, which also includes Spastic Paraplegia Type 2 (SPG2). The PLP1-related disorders span a continuum of neurologic symptoms that range from severe central nervous system involvement (PMD) to progressive weakness and stiffness of the legs (SPG2).
There are four general classifications within this spectrum of diseases. In order of severity, they are:

• Connatal PMD, which is the most severe type and involves delayed mental and physical development and severe neurological symptoms;
• Classic PMD, in which the early symptoms include muscle weakness, involuntary movements of the eyes (nystagmus), and delays in motor development within the first year of life;
• Complicated SPG2, which features motor development issues and brain involvement, and,
• Pure SPG2, which includes cases of PMD that do not have neurologic complications.

Noticeable changes in the extent of myelination can be detected by MRI analyses of the brain. Additional symptoms of PMD may include slow growth, tremor, failure to develop normal control of head movement, and deteriorating speech and mental function.

Is there any treatment?

There is no cure for Pelizaeus-Merzbacher disease, nor is there a standard course of treatment. Treatment is symptomatic and supportive and may include medication for movement disorders.

What is the prognosis?

The prognosis for those with the severe forms of Pelizaeus-Merzbacher disease is poor, with progressive deterioration until death. On the other end of the disease spectrum, individuals with the mild form, in which spastic paraplegia is the chief symptom, may have nearly normal activity and life span.

What research is being done?

NINDS supports research on gene-linked disorders, including the leukodystrophies. The goals of this research are to increase scientific understanding of these disorders and to find ways to prevent, treat, and ultimately cure them.

NIH Patient Recruitment for Pelizaeus-Merzbacher Disease Clinical Trials

• At NIH Clinical Center
• Throughout the U.S. and Worldwide
• NINDS Clinical Research Collaboration Trials

Organizations

United Leukodystrophy Foundation 2304 Highland Drive Sycamore, IL   60178 office@ulf.org http://www.ulf.org Tel: 815-895-3211 800-728-5483 Fax: 815-895-2432	Hunter's Hope Foundation [A Leukodystrophy Resource] P.O. Box 643 Orchard Park, NY   14127 info@huntershope.org http://www.huntershope.org Tel: 716-667-1200 877-984-HOPE (-4673) Fax: 716-667-1212
National Organization for Rare Disorders (NORD) P.O. Box 1968 (55 Kenosia Avenue) Danbury, CT   06813-1968 orphan@rarediseases.org http://www.rarediseases.org Tel: 203-744-0100 Voice Mail 800-999-NORD (6673) Fax: 203-798-2291	Myelin Project P.O. Box 39 Pacific Palisades, CA   90272 margaret.weis@myelin.org http://www.myelin.org Tel: 800-869-3546 310-459-1071 Fax: 310-230-4298
PMD Foundation (Pelizaeus-Merzbacher disease) 1307 White Horse Road, Suite 603 Voorhees, NJ   08043 jeffleonard@pmdfoundation.org http://www.pmdfoundation.org Tel: 609-443-9623

Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.

Last updated September 16, 2008

Krabbe Disease

Table of Contents (click to jump to sections)

What is Krabbe Disease?
Is there any treatment?
What is the prognosis?
What research is being done?
Clinical Trials
Organizations
Additional resources from MEDLINEplus

What is Krabbe Disease?

Krabbe disease is a rare, inherited degenerative disorder of the central and peripheral nervous systems.  It is characterized by the presence of globoid cells (cells that have more than one nucleus), the breakdown of the nerve’s protective myelin coating, and destruction of brain cells.  Krabbe disease is one of a group of genetic disorders called the leukodystrophies.  These disorders impair the growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers, and cause severe deterioration of mental and motor skills.  Myelin, which lends its color to the “white matter” of the brain, is a complex substance made up of at least 10 different enzymes.  Each of the leukodystrophies affects one (and only one) of these substances.  Krabbe disease is caused by a deficiency of galactocerebrosidase, an essential enzyme for myelin metabolism.  The disease most often affects infants, with onset before age 6 months, but can occur in adolescence or adulthood.  Symptoms include irritability, unexplained fever, limb stiffness, seizures, feeding difficulties, vomiting, and slowing of mental and motor development.  Other symptoms include muscle weakness, spasticity, deafness, and blindness.

Is there any treatment?

There is no cure for Krabbe disease. Results of a very small clinical trial of patients with infantile Krabbe disease found that children who received umbilical cord blood stem cells from unrelated donors prior to symptom onset developed with little neurological impairment.  Results also showed that disease progression stabilized faster in patients who receive cord blood compared to those who receive adult bone marrow.  Bone marrow transplantation has been shown to benefit mild cases early in the course of the disease.  Generally, treatment for the disorder is symptomatic and supportive.  Physical therapy may help maintain or increase muscle tone and circulation.

What is the prognosis?

Infantile Krabbe disease is generally fatal before age 2.  Prognosis may be significantly better for children who receive umbilical cord blood stem cells prior to disease onset or early bone marrow transplantation.  Persons with juvenile- or adult-onset cases of Krabbe disease generally have a milder course of the disease and live significantly longer.

What research is being done?

The National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health (NIH), conducts research on the lipid storage diseases in laboratories at the NIH and also supports additional research through grants to major medical institutions across the country.

NIH Patient Recruitment for Krabbe Disease Clinical Trials

• At NIH Clinical Center
• Throughout the U.S. and Worldwide
• NINDS Clinical Research Collaboration Trials

Organizations

United Leukodystrophy Foundation 2304 Highland Drive Sycamore, IL   60178 office@ulf.org http://www.ulf.org Tel: 815-895-3211 800-728-5483 Fax: 815-895-2432	Hunter's Hope Foundation [A Leukodystrophy Resource] P.O. Box 643 Orchard Park, NY   14127 info@huntershope.org http://www.huntershope.org Tel: 716-667-1200 877-984-HOPE (-4673) Fax: 716-667-1212
National Organization for Rare Disorders (NORD) P.O. Box 1968 (55 Kenosia Avenue) Danbury, CT   06813-1968 orphan@rarediseases.org http://www.rarediseases.org Tel: 203-744-0100 Voice Mail 800-999-NORD (6673) Fax: 203-798-2291	Myelin Project P.O. Box 39 Pacific Palisades, CA   90272 margaret.weis@myelin.org http://www.myelin.org Tel: 800-869-3546 310-459-1071 Fax: 310-230-4298

Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.

Last updated June 13, 2011

Synonym(s):   Globoid Cell Leukodystrophy

Adrenoleukodystrophy

What is Adrenoleukodystrophy?

Adrenoleukodystrophy (ALD) is one of a group of genetic disorders called the leukodystrophies that cause damage to the myelin sheath, an insulating membrane that surrounds nerve cells in the brain. People with ALD accumulate high levels of saturated, very long chain fatty acids (VLCFA) in the brain and adrenal cortex because they do not produce the enzyme that breaks down these fatty acids in the normal manner. The loss of myelin and the progressive dysfunction of the adrenal gland are the primary characteristics of ALD. ALD has two subtypes. The most common is the X-linked form (X-ALD), which involves an abnormal gene located on the X-chromosome. Women have two X-chromosomes and are the carriers of the disease, but since men only have one X-chromosome and lack the protective effect of the extra X-chromosome, they are more severely affected. Onset of X-ALD can occur in childhood or in adulthood. The childhood form is the most severe, with onset between ages 4 and 10. The most common symptoms are usually behavioral changes such as abnormal withdrawal or aggression, poor memory, and poor school performance. Other symptoms include visual loss, learning disabilities, seizures, poorly articulated speech, difficulty swallowing, deafness, disturbances of gait and coordination, fatigue, intermittent vomiting, increased skin pigmentation, and progressive dementia. In the milder adult-onset form, which typically begins between ages 21 and 35, symptoms may include progressive stiffness, weakness or paralysis of the lower limbs, and ataxia. Although adult-onset ALD progresses more slowly than the classic childhood form, it can also result in deterioration of brain function. A mild form of ALD is occasionally seen in women who are carriers of the disorder. Symptoms include progressive stiffness, weakness or paralysis of the lower limbs, ataxia, excessive muscle tone, mild peripheral neuropathy, and urinary problems.

Is there any treatment?

Adrenal function must be tested periodically in all patients with ALD. Treatment with adrenal hormones can be lifesaving. Symptomatic and supportive treatments for ALD include physical therapy, psychological support, and special education. Recent evidence suggests that a mixture of oleic acid and erucic acid, known as "Lorenzo's Oil," administered to boys with X-ALD can reduce or delay the appearance of symptoms. Bone marrow transplants can provide long-term benefit to boys who have early evidence of X-ALD, but the procedure carries risk of mortality and morbidity and is not recommended for those whose symptoms are already severe or who have the adult-onset or neonatal forms. Oral administration of docosahexanoic acid (DHA) may help infants and children with neonatal ALD.

What is the prognosis?

Prognosis for patients with ALD is generally poor due to progressive neurological deterioration. Death usually occurs within 1 to 10 years after the onset of symptoms.

What research is being done?

The NINDS supports research on genetic disorders such as ALD. The aim of this research is to find ways to prevent, treat, and cure these disorders. Intensive basic research has proposed two new approaches, 4-phenylbutyrate and lovastatin, which could potentially lower levels of VLCFA in the brain. Therapeutic trials for both agents are planned.

NIH Patient Recruitment for Adrenoleukodystrophy Clinical Trials

• At NIH Clinical Center
• Throughout the U.S. and Worldwide
• NINDS Clinical Research Collaboration Trials

Organizations

National Organization for Rare Disorders (NORD) P.O. Box 1968 (55 Kenosia Avenue) Danbury, CT   06813-1968 orphan@rarediseases.org http://www.rarediseases.org Tel: 203-744-0100 Voice Mail 800-999-NORD (6673) Fax: 203-798-2291	National Tay-Sachs and Allied Diseases Association 2001 Beacon Street Suite 204 Boston, MA   02135 info@ntsad.org http://www.ntsad.org Tel: 800-90-NTSAD (906-8723) Fax: 617-277-0134
United Leukodystrophy Foundation 2304 Highland Drive Sycamore, IL   60178 office@ulf.org http://www.ulf.org Tel: 815-895-3211 800-728-5483 Fax: 815-895-2432	Myelin Project P.O. Box 39 Pacific Palisades, CA   90272 margaret.weis@myelin.org http://www.myelin.org Tel: 800-869-3546 310-459-1071 Fax: 310-230-4298

Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.

Last updated March 18, 2009