$Unique_ID{BRK04031} $Pretitle{} $Title{Myoclonus, General} $Subject{Myoclonus, General Rhythmical Myoclonus (Segmental Myoclonus, including Nocturnal Myoclonus, Palatal Myoclonus and Respiratory Myoclonus) Arrhythmic Myoclonus (Stimulus-Sensitive Myoclonus, including Pathologic Myoclonus) Hereditary Essential Myoclonus (Paramyoclonus Multiple) Progressive Myoclonic Epilepsy Ramsay Hunt Syndrome (Dyssynergia Cerebellaris Myoclonica) Opsoclonus (Infantile Myoclonic Encephalopathy and Polymyoclonia) Familial Arrhythmic Myoclonus Intention Myoclonus (Action Myoclonus, including Postencephalitic Intention Myoclonus and Postanoxic Intention Myoclonus) Tourette Syndrome Jumping Frenchmen of Maine Huntington's Disease Torsion Dystonia Benign Essential Tremor} $Volume{} $Log{} Copyright (C) 1986, 1987, 1988, 1990, 1991, 1992, 1993 National Organization for Rare Disorders, Inc. 62: Myoclonus, General ** IMPORTANT ** It is possible that the main title of the article (Myoclonus) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Disorder Subdivisions: Rhythmical Myoclonus (Segmental Myoclonus, including Nocturnal Myoclonus, Palatal Myoclonus and Respiratory Myoclonus) Arrhythmic Myoclonus (Stimulus-Sensitive Myoclonus, including Pathologic Myoclonus) Hereditary Essential Myoclonus (Paramyoclonus Multiple) Progressive Myoclonic Epilepsy Ramsay Hunt Syndrome (Dyssynergia Cerebellaris Myoclonica) Opsoclonus (Infantile Myoclonic Encephalopathy and Polymyoclonia) Familial Arrhythmic Myoclonus Intention Myoclonus (Action Myoclonus, including Postencephalitic Intention Myoclonus and Postanoxic Intention Myoclonus) Information on the following diseases can be found in the Related Disorders section of this report: Tourette Syndrome Jumping Frenchmen of Maine Huntington's Disease Torsion Dystonia Benign Essential Tremor General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Myoclonus is a neurological movement disorder characterized by sudden, involuntary contractions of skeletal muscles. Based on the various symptoms, there are three types of Myoclonus: Intention Myoclonus, Rhythmical Myoclonus, and Arrhythmic Myoclonus. Intention Myoclonus (Action Myoclonus) includes Postanoxic Myoclonus and Postencephalitic Myoclonus. Arrhythmic Myoclonus (stimulus-sensitive myoclonus) includes: Hereditary Essential Myoclonus (paramyoclonus multiplex), Hyperexplexia (Essential Startle Disease), Opsoclonus (Infantile Myoclonic Encephalopathy, Polymyoclonia Familial Arrhythmic Myoclonus), Progressive Myoclonic Epilepsy, Ramsay Hunt Syndrome (Dyssynergia Cerebellaris Myoclonia). Rhythmical Myoclonus includes (Segmental Myoclonus), Nocturnal Myoclonus, Palatal Myoclonus, and Respiratory Myoclonus. Symptoms Intention Myoclonus is characterized by episodes of sudden, involuntary muscle contractions that are triggered by voluntary movements, such as a purposeful action. In Arrhythmic Myoclonus, the muscle jerks lack any particular rhythm (arrhythmic) and occur without warning. The jerking movements may be confined to a single muscle or involve all of the skeletal muscles. The severity of the muscle contractions may vary from episode to episode and may differ among patients. The jerking contractions may be very severe and involve both sides of the body at the same time. Muscle contractions may be brought on (stimulated) by something that the person sees (visual), hears (auditory), and/or touches (tactile). The stimulus may also be physical fatigue, stress, and/or anxiety. In women, Myoclonus is often more intense prior to the beginning of the menstrual flow (premenstrually). Hyperexplexia (Essential Startle Response) is a form of Arrhythmic Myoclonus characterized by an exaggerated muscular response to sudden loud noises or other stimulus (startle reaction). The muscle jerks of Hyperexplexia come and go. Opsoclonus is a form of Myoclonus that is limited to one area of the body (localized). Typically Opsoclonus affects the eyes which jerk irregularly and together. When Opsoclonus occurs in infants with generalized Myoclonus, the infant is said to have Infantile Myoclonic Encephalopathy or Polymyoclonia Familial. Progressive Myoclonic Epilepsy, which is potentially disabling, combines severe epilepsy with significant stimulus-sensitive Myoclonus. In advanced disease, dementia may appear. (For more information, choose "Hyperexplexia" as your search term in the Rare Disease Database.) Ramsay Hunt Syndrome comprises many disorders including epilepsy, myoclonus, and degeneration of part of the brain (cerebellum) and spinal cord. Other neurological impairments may also be present. (For more information, choose "Epilepsy" as your search term in the Rare Disease Database.) Rhythmical (segmental) Myoclonus has a distinctive symptom; the muscles jerk at a frequency of 10 to 180 jerks per minute. The affected muscles are generally those that get their nerve supply (innervated) from one or more of the spinal cord segments. Unlike Arrhythmic Myoclonus, Rhythmical Myoclonus is not relieved by sleep and is not triggered by sudden stimuli or voluntary movements. In Nocturnal Myoclonus (Restless Legs Syndrome) there is frequent jerking of the body and/or the extremities, particularly the legs. The legs may jerk 2 to 3 times a minute when falling asleep, sleeping, or during deep relaxation during the day. Insomnia frequently accompanies attacks of Nocturnal Myoclonus. (For more information about Nocturnal Myoclonus, choose "Restless Legs" as your search term in the Rare Disease Database.) In Palatal Myoclonus there are quick rhythmical contractions of a section of the roof of the mouth (soft palate). Sometimes other muscles contract including those of the throat (pharynx), voice box (larynx), eyes, face, and/or diaphragm. Respiratory Myoclonus causes rapid rhythmic contractions of the muscles of the diaphragm. This may lead to shortness of breath or difficulty breathing (dyspnea). Causes Several types of Arrhythmic Myoclonus are inherited. Hereditary Essential Myoclonus and Ramsay Hunt Syndrome are inherited as an autosomal dominant genetic trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is fifty percent for each pregnancy regardless of the sex of the resulting child. Progressive Myoclonic Epilepsy, whether alone or with another hereditary disease such as Tay-Sachs or Kufs Disease, is usually inherited as an autosomal recessive genetic trait. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent, and will be genetically normal. It is also possible that there is an X-linked form of Progressive Myoclonus Epilepsy. X-linked recessive disorders are conditions that are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a fifty percent risk of transmitting the carrier condition to their daughters, and a fifty percent risk of transmitting the disease to their sons. It is thought that in the majority of people with Myoclonus, symptoms develop due to abnormally high levels of electrical discharges along nerve cells. In Rhythmical or Segmental Myoclonus, local trauma to the nerves in the spinal cord that control muscles is usually responsible. Overactivity of certain areas within the brain (medullary reticular formation or cerebral cortex) causes Arrhythmic Myoclonus. Some types of Intention Myoclonus, Essential Myoclonus, and Progressive Myoclonus Epilepsy may be associated with decreased activity of serotonin, a chemical (neurotransmitter) in the brain. Viral infections, blood vessel disorders, benign growths, malignant tumors, and/or traumatic lesions to the central nervous system may precede either Rhythmical or Arrhythmic Myoclonus. A lack of oxygen to the brain, usually due to heart or respiratory failure, can cause Postanoxic Myoclonus. Certain toxins, including some drugs in high doses, and metabolic disorders have also been implicated as a cause of Myoclonus. Affected Population Myoclonus affects males and females in equal numbers. Some forms of Myoclonus are common and some forms are rare. Related Disorders Symptoms of the following disorders can be similar to those of Myoclonus. Comparisons may be useful for a differential diagnosis: Tourette Syndrome is a neurologic movement disorder that is characterized by repetitive motor and vocal tics. The first symptoms are usually rapid eye blinking or facial grimaces. Symptoms may also include facial tics and involuntary movements of the extremities, shoulders, and the voluntary muscles. Inarticulate sounds or sometimes inappropriate words may occur. Tourette Syndrome is not a progressive or degenerative disorder; rather, symptoms tend to be variable and follow a chronic waxing and waning course. Symptoms usually begin before the age of 16 years. (For more information on this disorder, choose "Tourette" as your search term in the Rare Disease Database). Jumping Frenchmen of Maine is a very rare disorder characterized by an extreme startle response. The symptoms occur as a response to sudden, unexpected noise or movement. The extreme startle reaction includes jumping, raising the arms, hitting, yelling, unintelligible speech, and/or imitation or repetition of another person's body movements (echopraxia). The intensity of the response increases with fatigue and stress. (For more information on this disorder, choose "Jumping Frenchmen of Maine" as your search term in the Rare Disease Database.) Huntington's Disease (Huntington's Chorea) is a rare inherited, progressively degenerative neurological disorder characterized by involuntary muscle movements and dementia. Initially there are personality changes and uncontrolled rapid jerky muscle movements. In time, speech and memory become impaired and involuntary muscle movements become more frequent and severe. As Huntington's Disease progresses there is a further loss of cognitive abilities and dementia. The symptoms of this disorder usually begin during adulthood, generally after the age of forty. (For more information on this disorder choose, "Huntington's" as your search term in the Rare Disease Database.) Torsion Dystonia is a rare inherited neurological disorder characterized by involuntary contortions of the muscles in the neck, torso, arms, and legs. Occasionally only one or a few muscles are involved. People with Torsion Dystonia typically have an awkward, sideways gait. Other symptoms may include foot drag, cramps on the hands and feet, difficulty in grasping objects, and unclear speech. The involuntary movements of Dystonia are slow writhing movements. (For more information on this disorder, choose "Torsion Dystonia" as your search term in the Rare Disease Database.) Benign Essential Tremor is a rare neurological disorder characterized by a rhythmical tremor that may be pronounced. This disorder typically affects the upper extremities and the tremors usually has a frequency of 4 to 12 times per second. The tremors may be aggravated by stress, anxiety, fatigue, and/or cold temperatures. Relief from the tremors may be achieved by rest and sedation. The symptoms of Benign Essential Tremor generally stabilize after a period of progression. (For more information on this disorder, choose "Benign Essential Tremor" as your search term in the Rare Disease Database.) Therapies: Standard Clonazepam and other drugs known as benzodiazepine derivatives are commonly used to treat most forms of Myoclonus. These include Arrhythmic Myoclonus, including Progressive Myoclonus Epilepsy, Ramsay Hunt Syndrome, Myoclonus associated with Idiopathic Epilepsy, Infantile Spasms, and Postencephalitic and Postanoxic Intention Myoclonus. The drug diazepam is also used to treat these types of Myoclonus. People with this disorder may become tolerant to these drugs after a course of several months. Side effects such as sleepiness, unsteady gait (ataxia), lethargy, and/or behavioral changes may occur. Other anticonvulsant drugs with antimyoclonic activity may also be useful in the treatment of Myoclonus. Valproic acid is the most effective drug in the long-term treatment of Progressive Myoclonus Epilepsy; it is less effective in other forms of Myoclonus. ACTH or prednisone may be effective in treating a few forms of Myoclonus. These include Infantile Spasms, Infantile Myoclonic Encephalopathy, and Opsoclonus that occurs along with a brain tumor (neuroblastoma). Rhythmical Myoclonus is more difficult to treat. Drugs that have shown some promising results in some patients include clonazepam, tetrabenazine, and haloperidol. Genetic counseling will be of benefit for patients with the inherited forms of Myoclonus and their families. Therapies: Investigational An experimental drug, L-5 hydroxytryptophan (L-5HTP), is being studied for use in the treatment of Myoclonus. This drug is chemically similar to the organic chemicals that form serotonin. L-5HTP is used in combination with the drug carbidopa. The combination treatment is being investigated for its use in the treatment of Postanoxic Intention Myoclonus, Progressive Myoclonus Epilepsy, Essential Myoclonus, and Palatal Myoclonus. The side effects of this treatment mainly affect the gastrointestinal tract and may include diarrhea and nausea. These may be minimized by carefully managing the amount of carbidopa that is given. Combinations of clonazepam, valproic acid, and L-5HTP with carbidopa may be the treatment of choice in some patients with Myoclonus. L-5HTP is being developed by: Circa Pharmaceuticals 130 Lincoln St. Copiague, NY 11726 The drug Acetazolamide is being studied as a treatment for people with Ramsay Hunt Syndrome and severe Action Myoclonus. This drug is used in combination with clonazepam, sodium valproate, primidone and piracetam. The addition of acteazolamide to this combination may reduce the severity of muscle contractions in some patients. The long-term safety and effectiveness of this treatment is under study. Piracetam (Nootripil) is a drug that has been approved in England for treatment of cortical Myoclonus. This drug is used in combination with other epilepsy drugs. More study is needed to determine the long-term safety and effectiveness of piracetam as a treatment for Myoclonus. This disease entry is based upon medical information available through April 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Myoclonus, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 National Pediatric Myoclonus Center Dept. of Neurology Children's Hospital 111 Michigan Ave., NW Washington, DC 20010-2970 Myoclonus Research Foundation 200 Old Palisade Avenue, Suite 17D Fort Lee, NJ 07024 (201) 585-0770 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 Epilepsy Foundation of America 4351 Garden City Dr. Landover, MD 20785 (800) 332-1000 (301) 459-3700 For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (301) 652-5553 (800) 336-GENE References MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 737, 1574, 1928. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 2136-2137. THE MERCK MANUAL, 16th Ed.: Robert Berkow Ed.; Merck Research Laboratories, 1992. P. 1492. PRINCIPLES OF NEUROLOGY, 4th Ed.; Raymond D. Adams, M.D. and Maurice Victor, M.D., Editors; McGraw-Hill Information Services Company, 1989. Pp. 269, 311, 808-811. MYOCLONUS. WHAT CAUSES IT, WHAT CONTROLS IT. Van Woert, M.H., Chung Hwang, E.; Consultant (April 1982). Pp. 263-273. TREATMENT OF MYOCLONUS, Van Woert, M.H., Chung Hwang, E.; Current Status of Modern Therapy, vol. 8., ed. A. Barbeau. MTP Press: Lancaster, England, 1980. HANDBOOK OF CLINICAL NEUROLOGY, Vol. 38; Vinken, P.J. and Bruyn, G.W. Ed.; North Holland Publishing Co., (Van Woert, M.H., Chung Hwang, E.) Myoclonus Pages 575-93. EFFECT OF ANTIEPILEPTIC AND ANTIMYOCLONIC DRUGS ON SEROTONIN RECEPTORS IN VITRO. M. R. Pranzatelli. Epilepsia (Jul-Aug 1988; issue 29 (4)). Pp. 412- 419. THE TREATMENT OF SEVERE ACTION MYOCLONUS. J. A. Obeso, et al.; Brain (Jun 1989; issue 112 (Pt 3)). Pp. 765-777. ACETAZOLAMIDE IMPROVES ACTION MYOCLONUS IN RAMSEY HUNT SYNDROME. L. Vaamonde et al., Clin Neuropharmacol (Oct 1992; 15(5)). Pp. 392-396.