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Comprehensive, sometimes contradictory, info on HSP:

From Medscape Today:

In a spinal cord injury resulting in paraplegia, there is significant remodeling of the central nervous system control of motor output. Normally descending cortical inputs (upper motor neuron) exert an inhibitory effect on local spinal circuits that control motor output. Such spinal elements include the spinal motor neuron (lower motor neuron) connection to the muscle as well as the afferent connections of sensory fibers originating from the muscle (motor unit), which synapse onto the lower motor neuron and ascend upward in the spinal cord to higher motor control centers. In general, control of the muscle at the spinal level is of a predominantly excitatory nature. Descending influences from the cortex via upper motor neuron pathways on spinal motor neurons provide an inhibitory influence on local spinal motor circuits. With the loss of this inhibitory input on the spinal cord (as occurs in spinal cord injury), local spinal reflex nerve networks lose inhibitory influences. The loss of this cortical inhibition gives way to hyperactivity of local reflex circuits leading to hyperactive motor output manifested as extensor and flexor spasms.

Treatment of flexor and extensor spasms involves the use of antispasticity agents. Included in this group of agents are baclofen (both via oral route and intrathecal via implanted pump), tizanidine, clonazepam, and gabapentin. At the muscle level local injections of botulinum toxin in extremely spastic, hyperactive muscle groups can be highly effective in controlling spasms and the pain associated with them. With the use of the agents mentioned above (both alone and in combinations) improved control of movement can be obtained. Reduction of spasticity may allow an individual to perform simple movement patterns (transfers, weight bearing) that might have been interfered with because of the hyperactive motor output.

  1. 1.From eHow Health :

  2. 2.The Facts

    1. Muscle spasms are common after upper motor neuron injuries, which is the technical term for hurting the nerves and nerve cells in your brain and spinal cord. This happens frequently to people with paraplegia, a condition in which the nerves of the spinal cord have been severely damaged and no longer fully control the legs. While the effects of spasms can be controlled or reduced with anti-spasticity medicines, spasms are often present to some degree for the duration of the paraplegic person's life.

  3. 3.Misconceptions

    1. When a paraplegic has a muscle spasm, it can sometimes look like a mini seizure, as the legs twitch and tremble, often causing the entire body to shake. Despite their scary appearance, they are generally not harmful and can usually be resolved with a change in position. Some spasms can send the legs into what is called an extensor pattern, in which the knees partially or completely straighten. While this can appear to a bystander like the person is straightening his legs on his own, it is actually a spontaneous nervous system reaction.

  4. 4.Risk Factors

    1. A spasm might not seem like such a bad thing to deal with, but when you are not able to fully control your legs it can be a safety hazard. When a paraplegic has to move from one surface to another, such as from the bed to wheelchair, he must position his legs in such a way that they remain stable until he reaches his wheelchair. If his legs go into a spasm during the transfer, they may shift so far forward that he actually slides onto the floor. If a caregiver is assisting a paraplegic transfer, a spasm can disrupt the process and create a potential hazard for both individuals as the body position suddenly changes.

  5. 5.Effects

    1. Even though many paraplegics do not have full sensation in their legs, spasms can still be uncomfortable and sometimes even painful. If spasms occur at night, they can make sleeping difficult. Most paraplegics are experienced enough with their own spasm patterns that they are able to control them by positioning their feet. However, newly paralyzed individuals may find the effects of spasms hard to manage for several months.
      Time Frame

    2. Most spasms do not last for more than a few moments; however, they can occur frequently during the day and sometimes through the night. Most paraplegics are aware of how often spasms occur and what is normal for them. However, they should take note if spasms are lasting longer than normal or if they are becoming more frequent. This might signify the need to change the dosage or the type of anti-spasticity medication.

  6. From Spastic Paraplegia Foundation, Inc.

  7. 6.What is HSP?

  8. 7.Hereditary Spastic Paraplegia (HSP) is a group of rare, inherited neurological disorders. Their primary symptoms are progressive spasticity and weakness of the leg and hip muscles. Researchers estimate that some 30 different types of HSP exist; the genetic causes are known for eleven. The HSP incidence rate in the United States is 20,000 people.

  9. 8.The condition is characterized by insidiously progressive lower extremity weakness and spasticity. HSP is classified as uncomplicated or pure if neurological impairment is limited to the lower body. HSP is classified as complicated or complex if other systems are involved or if there are other neurological findings such as seizures, dementia, amyotrophy, extrapyramidal disturbance, or peripheral neuropathy in the absence of other disorders such as diabetes mellitus.

  10. 9.Many different names are used for HSP. The most common are Hereditary Spastic Paraplegia (or Paraparesis), Familial Spastic Paraparesis (or Paraplegia), and Strümpell-Lorrain Disease. Others are Spastic Paraplegia, Hereditary Charcot-Disease, Spastic Spinal Paralysis, Diplegia Spinalis Progressiva, French Settlement Disease, Troyer syndrome, and Silver syndrome.

  11. 10.The disorder was first identified in the late 1800s by A. Strümpell, a neurologist in Heidelberg, Germany. He observed two brothers and their father, all of whom had gait disorders and spasticity in their legs. After the death of the brothers, Strümpell showed through autopsy the degeneration of the nerve fibers leading through the spinal cord. HSP was originally named after Strümpell, and later after two Frenchmen, Lorrain and Charcot, who provided more information.

  12. 11.What is (Apparently Sporadic) Spastic Paraplegia?

  13. 12.Many individuals with all the signs and symptoms of HSP do not appear to have similarly affected family members. Without proof of a hereditary link, some neurologists call the condition Spastic Paraplegia or Apparently Sporadic Spastic Paraplegia. Other clinicians may diagnosis the same condition as Primary Lateral Sclerosis (PLS), which mimics HSP in how it affects the lower body. However, current researcher indicates that PLS eventually affects the arms and speech and swallowing muscles as well as the leg muscles.

  14. 13.There are many reasons why someone with HSP may not have a family history. Recessive and x-linked forms skip generations, which means the disorder may pass silently for generations and then suddenly appear. In addition, the age of onset, progression rate and severity vary widely so that the disease could have gone undiagnosed in previous generations or an affected individual may have died before symptom onset. Mistaken parentage or new genetic mutations are also possible. Please see HSP and Heredity for more information on this and genetic testing.=

  15. 14.What are the symptoms?

  16. 15.The hallmark of HSP is progressive difficulty walking due to increasingly weak and stiff (spastic) muscles. Symptoms appear in most people between the second and fourth decade of life, but they can start at any age.

  17. 16.Initial symptoms are typically difficulty with balance, stubbing the toe or stumbling. Changes begin so gradually that other people often notice the change first. As the disease progresses, canes, walkers and eventually wheelchairs may become needed, although some people never require assistive devices.

  18. 17.Other common symptoms of HSP are urinary urgency and frequency, hyperactive reflexes, difficulty with balance, clonus, Babinski's sign, diminished vibration sense in the feet, muscle spasms, and congenital foot problems such as pes cavus (high arched foot). Some people may experience problems with their arms or fine motor control of their fingers but for most people, this is not significant.

  19. 18.Editor's Note: One of our community members, who is a primary care physician with HSP, submitted an article about pain management. Please see Articles - Pain.

  20. 19.Most people with HSP have uncomplicated HSP. There are also rare, complicated forms, which have additional symptoms, such as peripheral neuropathy, ichtyosis (a skin disorder) epilepsy, ataxia, optic neuropathy, retinopathy, dementia, mental retardation, deafness, or problems with speech, swallowing or breathing. These symptoms may have other causes though, unrelated to HSP. For example, someone with uncomplicated HSP may have peripheral neuropathy caused by diabetes.
    Back to IndexWhy are my symptoms different from others in my family?

  21. 20.As noted above, the severity of symptoms and age of onset can vary widely, even within the same family. One reason is that HSP is a group of genetically different disorders, not a single disorder. Some differences may be due to genetic mutations. A child may show symptoms before a parent and it's possible for some family members to have very mild symptoms while others have more severe symptoms. This may be due to other genes, environment, nutrition, general health, or factors not yet understood.

  22. 21.In some families, symptoms tend to start at younger ages with each generation. Although rare, HSP sometimes shows "incomplete penetrance". This means that occasionally, an individual may have the gene mutation, but for unknown reasons never develop symptoms of HSP. Such individuals can still pass HSP to their children.

  23. 22.How does HSP cause symptoms?

  24. 23.HSP is caused by degeneration of the upper motor neurons in the brain and spinal cord. Upper m otor neurons control voluntary movement.

  25. 24.The cell bodies of these neurons are located in the motor cortex area of the brain. They have long, hair-like processes called axons that travel to the brainstem and down the spinal cord. Axons relay the messages to move to lower motor neurons that are located all along the brainstem and spinal cord. Lower motor neurons then carry the messages out to the muscles. Click on the diagram at right to see how upper motor neurons connect to lower motor neurons that innervate leg muscles.

  26. 25.When upper motor neurons degenerate, the correct messages cannot reach the lower motor neurons, and the lower motor neurons cannot transmit the correct messages to the muscles. As the degeneration continues, spasticity and weakness increase. The legs are affected because degeneration occurs primarily at the ends of the longest nerves in the spinal cord, which control the legs. In some cases, the upper body can be minimally affected as well, leading to problems with the arms or speech and swallowing muscles.

  27. 26.How severe will my symptoms get?

  28. 27.There is no way to predict rate of progression or severity of symptoms. Generally, once symptoms begin, progression continues slowly throughout life. For some childhood-onset forms, symptoms become apparent, gradually worsen during childhood, and then stabilize after adolescence. HSP rarely results in complete loss of lower limb mobility.

  29. 28.How is HSP diagnosed?

  30. 29.HSP is diagnosed via a careful clinical examination, by excluding other disorders that cause spasticity and weakness in the legs, and by an observation period to see if other symptoms develop that indicate another condition, such as PLS. Disorders that can be ruled out with testing are ALS, tropical spastic paraparesis (TSP), vitamin deficiencies (B12 or E), thoracic spine herniated disks, and spinal cord tumors or injuries and multiple sclerosis. HSP can resemble cerebral palsy, however, HSP is degenerative and thereby causes increasing spasticity and weakness of the muscles. Two other disorders with spastic paraplegia symptoms termed Lathyrism and Konzo are caused by toxins in the plants Lathyrus sativus and cassava.

  31. 30.HSP is hereditary, and examining family history is important in diagnosing HSP. However, many individuals with all the signs and symptoms of HSP do not have a family history. See (Apparently Sporadic) Spastic Paraparesis.

  32. 31.What genetic testing is available?

  33. 32.Athena Diagnostics offers testing for five different types of HSP out of the 30 or more different forms of HSP. As more genes are discovered, it is hopeful that such information will lead to greater availability of testing.

  34. 33.Genetic counselors can be found at many major medical centers or by contacting the National Society of Genetic Counselors at (610) 872-7608. Gene tests can be used for prenatal testing.
    What is the treatment?

  35. 34.No treatments are currently available to prevent, stop, or reverse HSP. Treatment is focused on symptom relief, such as medication to reduce spasticity; physical therapy and exercise to help maintain flexibility, strength, and range of motion; assistive devices and communications aids; supportive therapy and other modalities. See treatment and therapies for additional detailed information.
    What is the life expectancy?

  36. 35.Life expectancy is normal. However, complications arising from falls or immobility caused by the symptoms of HSP may inadvertently shorten a person's life.

  37. 36.What is the risk of getting HSP?

  38. 37.There are some thirty different forms of HSP, with three different modes of inheritance: autosomal dominant, autosomal recessive and X-linked. Each mode has a different risk factor, which ranges from almost none to 50%. See Heredity and HSP for additional detailed information.

  39. 38.What other conditions cause spasticity and weakness of muscles?

  40. 39.Muscle spasticity and weakness can also be caused by other conditions including (but not limited to) Primary Lateral Sclerosis, spinal cord injury or tumors, cerebral palsy, multiple sclerosis, amyotrophic lateral sclerosis, vitamin absorption, and thoracic spine herniated disks.

  41. 40.There is a virus-caused disease called Tropical Spastic Paraparesis and conditions called Lathyrism and Konzo caused by toxins in the plants lathyrus sativus and cassava that also cause muscle spasticity and weakness.

  42. 41.Other questions

  43. 42.Does stress affect symptoms?

  44. 43.Many people find the tightness in their muscles worsens when they are angry, stressed, or upset. This may make it more difficult to walk and speak. It is unknown exactly how emotions affect muscle tone, but it may involve adrenalin levels. Most people also report increased stiffness in cold weather.

  45. 44.Is depression normal?

  46. 45.Periods of feeling down about having HSP are normal and expected. It is not uncommon for people to also experience periods of clinical depression.

  47. 46.Do people with HSP experience memory loss?

  48. 47.Memory disturbance has been reported in some individuals with HSP due to spastin gene mutations. In general, it was mild.

  49. 48.Before attributing memory disturbance to HSP, it is important to consider other causes: stress, anxiety, depression, lack of sleep, medications (including Baclofen), other health conditions including vitamin B12 deficiency.

  50. 49.If memory disturbance is significant, a cause of concern, or worsening, it would be important to discuss this with your primary physician and neurologist.

  51. 50.Are foot problems common?

  52. 51.Yes. Here are a few examples:

  53. 52.High arched feet (pes cavus). High arches occur because there is more weakness in the foot muscles that extend the foot backward and flatten the arch than in the muscles that flex the foot downward.

  54. 53.Shortened Achilles tendons. Achilles tendons are often short, and generally shorten further as HSP progresses.

  55. 54.Jumping feet (clonus). Clonus is an uncontrollable, repetitive jerking of muscles that makes the foot jump rapidly up and down. It occurs when the foot is in a position that causes a disruption of the signals from the brain, leading to an automatic stretch reflex.

  56. 55.Hammer toes or bunions. These may occur due to imbalances in the strength and tone of muscles that maintain proper alignment of joints in the feet.

  57. 56.Cold feet and/or foot swelling. This is most likely caused by poor circulation. Normally, muscle contractions in the legs help pump blood from the legs back to the heart. If the muscles are weakened, or if the person is relatively inactive, the blood flow from the legs may be decreased, and fluids may accumulate. This can cause swelling, or a sensation of "cold feet".

  58. 57.

  59. 58.Can my arms be affected?

  60. 59.Some people may experience problems with their arms or fine motor control of their fingers. The degeneration in nerves that supply the arms is mild compared to that which occurs in the nerves that supply the legs. For most people, this is not significant.

  61. 60.Can HSP affect sexual function?

  62. 61.The short answer appears to be "yes", although it is important to remember that sexual desire and/or function can be affected by many other factors such as age, stress, depression, fatigue, medical disorders or medications.

  63. 62.Some people report that stiffness, spasms and cramps that are part of HSP may either inhibit (or intensify) orgasm, or that orgasm may bring on leg stiffness, spasms or clonus. Stiffness of the legs or arms may cause difficulty using certain positions for intercourse.

  64. 63.Is HSP an Ataxia?

  65. 64.No. The group of disorders known as Ataxias (such as Friedreichs Ataxia) are spino-cerebellar disorders in which there is a disturbance either in the part of the brain known as the cerebellum or in the connections to it. HSP does not involve the cerebellum. Ataxias can be hereditary or sporadic.

  66. 65.The term "ataxia" means without coordination, and can also refer to a symptom in which there is a lack of muscle control resulting in a jerky or unsteady movement. People with HSP may have incoordination as a symptom. This does not mean they have Ataxia.

  67. 66.Can I donate blood?

  68. 67.HSP cannot be passed to others through donation of blood. There is no medical reason why a person with HSP cannot donate blood.

  69. 68.When was HSP identified?

  70. 69.In the late 1800's, A. Strümpell, a neurologist in Heidelberg Germany, described this disorder. He observed two brothers and their father, who had gait disorders and spasticity in their legs. After the death of the brothers, Strümpell was able to show through autopsy the degeneration of the nerve fibers leading through the spinal cord. The disorder was originally named after Strümpell, and after two Frenchmen who later provided more information about the disorder, Lorrain and Charcot.

  71. 70.Is HSP more prevalent in certain ethnic groups?

  72. 71.There is no evidence that HSP is more prevalent in one ethnic group than another.

From News Medical

Hereditary spastic paraplegia (HSP) is a devastating motor disorder that relegates patients to walkers and, in more severe cases, wheelchairs. In work reported this week, researchers have taken our understanding of HSP to a new level with the development of an animal model for the disease.

The findings suggest that, in many cases, HSP may result from the improper regulation of microtubules, which make up a large part of a nerve cell's scaffolding. This could explain why the specific nerve cells that are preferentially affected in HSP – those that send signals from the brain's cerebral cortex to the motor neurons that initiate muscle contractions – show a progressive dysfunction that culminates in degeneration.

Genetic anomalies in more than 20 different genes have been associated with HSP, but mutations in one gene in particular, SPG4, are responsible for more than 40% of all cases. SPG4 encodes a protein called spastin, which previous research has shown to destabilize microtubules, the tiny hollow protein tubes that originate near the nucleus and extend into the long processes of neurons. Through their interactions with other proteins, microtubules essentially represent the dynamic scaffolding of the nerve cell. In neurons, microtubules' responsibilities include carrying cellular components to distant regions of the cell, regulating the growth of neuronal branches, and providing a substrate for important protein interactions. Microtubules grow and shrink, and their stability at a given time and place can be regulated by other proteins to facilitate specific cellular functions.

The new research, from the laboratories of Dr. Kendal Broadie (Vanderbilt University) and Dr. Andrea Daga (University of Padova, Italy), examines how spastin is involved in neuronal communication. Because the spastin gene is similar in the Drosophila (fruit fly) genetic model and in humans, the protein is predicted to perform the same function in both organisms. Therefore, to study how spastin functions in living neurons, the researchers designed transgenic flies that possess altered amounts of spastin protein in their neurons and assessed the effects. Using this approach, they found that spastin protein localizes to synapses, specialized sites of neuronal communication, where it acts to locally destabilize microtubules. Moreover, the researchers found that specific drugs that alter microtubule stability appear to remedy defects that occur in synaptic function as a result of changes in neuronal spastin levels. All told, the study provides intriguing new insight into how a genetic mutation that alters microtubule function may disrupt the way neurons communicate and offers a new line of thinking about possible treatments for the debilitating HSP condition.

http://www.cell.com/