Sunday 10 February 2019

Epilepsy, Parkinson’s, Multiple Sclerosis, Motor Neurone Disease, Alzheimer's

EPILEPSY:

Epilepsy


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Epilepsy is a disorder of the brain characterized by repeated seizures. A seizure is usually defined as a sudden alteration of behavior due to a temporary change in the electrical functioning of the brain. Normally, the brain continuously generates tiny electrical impulses in an orderly pattern. These impulses travel along neurons — the network of nerve cells in the brain — and throughout the whole body via chemical messengers called neurotransmitters.
In epilepsy the brain's electrical rhythms have a tendency to become imbalanced, resulting in recurrent seizures. In patients with seizures, the normal electrical pattern is disrupted by sudden and synchronized bursts of electrical energy that may briefly affect their consciousness, movements or sensations.
Epilepsy is usually diagnosed after a person has had at least two seizures that were not caused by some known medical condition, such as alcohol withdrawal or extremely low blood sugar.
If seizures arise from a specific area of the brain, then the initial symptoms of the seizure often reflect the functions of that area. The right half of the brain controls the left side of the body, and the left half of the brain controls the right side of the body. For example, if a seizure starts from the right side of the brain in the area that controls movement in the thumb, then the seizure may begin with jerking of the left thumb or hand.
Seizures vary so much that epilepsy specialists frequently re-classify seizure types. Typically, seizures belong in one of two basic categories: primary generalized seizures and partial seizures. The difference between these types is in how they begin. Primary generalized seizures begin with a widespread electrical discharge that involves both sides of the brain at once. Partial seizures begin with an electrical discharge in one limited area of the brain.
Epilepsy in which the seizures begin from both sides of the brain at the same time is called primary generalized epilepsy. Hereditary factors are important in partial generalized epilepsy, which is more likely to involve genetic factors than partial epilepsy — a condition in which the seizures arise from a limited area of the brain.
Some partial seizures are related to head injury, brain infection, stroke or tumor but, in most cases, the cause is unknown. One question that is used to further classify partial seizures is whether consciousness (the ability to respond and remember) is impaired or preserved. The difference may seem obvious, but there are many degrees of consciousness impairment or preservation.
The following factors may increase the risk of seizures in people predisposed to seizures:
  • Stress
  • Sleep deprivation or fatigue
  • Insufficient food intake
  • Alcohol use or drug abuse
  • Failure to take prescribed anticonvulsant medications
About half of the people who have one seizure without a clear cause will have another one, usually within six months. A person is twice as likely to have another seizure if there is a known brain injury or other type of brain abnormality. If the patients does have two seizures, there is about an 80 percent chance of having more. If the first seizure occurred at the time of an injury or infection in the brain, it is more likely the patient will develop epilepsy than if the seizure did not happen at the time of injury or infection.
According to the Epilepsy Foundation, epilepsy affects three million people in the U.S. and 50 million worldwide. Epileptic seizures may be tied to a brain injury or genetics, but for 70 percent of epilepsy patients, the cause is unknown. The Epilepsy Therapy Project notes that 10 percent of people will have seizures in their lifetime.
Epilepsy affects more than 300,000 children under the age of 15 — and more than 90,000 young people in this group have seizures that cannot be adequately treated. The onset rate starts to increase when individuals age, particularly as they develop strokes, brain tumors or Alzheimer's disease, all of which may cause epilepsy. Reports indicate that more than 570,000 adults over the age of 65 suffer from the disorder.
More men than women have epilepsy. Children and adolescents are more likely to have epilepsy of unknown or genetic origin. Brain injury or infection can cause epilepsy at any age. The Epilepsy Foundation also reports that 70 percent of children and adults with newly diagnosed epilepsy can be expected to enter remission after having gone five years or more without a seizure while on medication. In addition, 75 percent of people who are seizure-free on medication can be weaned from medication eventually. According to the National Institute of Neurological Disorders and Stroke, 20 percent of epilepsy patients have intractable seizures — seizures that do not respond to treatment.
The reasons why epilepsy begins are different for people of different ages. But what is known is that the cause is undetermined for about half of all individuals with epilepsy, regardless of age. Children may be born with a defect in the structure of their brain or they may suffer a head injury or infection that causes their epilepsy. Severe head injury is the most common known cause in young adults. For middle-age individuals, strokes, tumors and injuries are more frequent catalysts. In people age 65 and older, stroke is the most common known cause, followed by degenerative conditions such as Alzheimer's disease. Often, seizures do not begin immediately after a person has an injury to the brain. Instead, a seizure may occur many months later.
  • Premature birth or low birth weight
  • Trauma during birth (such as lack of oxygen)
  • Seizures in the first month of life
  • Abnormal brain structures at birth
  • Bleeding into the brain
  • Abnormal blood vessels in the brain
  • Serious brain injury or lack of oxygen to the brain
  • Brain tumors
  • Infections of the brain such as meningitis or encephalitis
  • Stroke resulting from blockage of arteries
  • Cerebral palsy
  • Mental disabilities
  • Seizures occurring within days after head injury
  • Family history of epilepsy or fever-related seizures
  • Alzheimer's disease (late in the illness)
  • Lengthy fever-related (febrile) seizures
  • Alcohol or drug abuse
A doctor makes his or her epilepsy diagnosis based on symptoms, physical signs and the results of such tests as an electroencephalogram (EEG), computed tomography (CT or CAT scan) or magnetic resonance imaging (MRI).
It is essential that the type of epilepsy and the type of seizures both are diagnosed properly. There are several major classifications of seizures and most are associated with specific forms of the disorder.
Epilepsy may be treated with antiepileptic medications the (AEDs)
Anticonvulsant/Anti-Seizure Medication from A to Z



  • Acetazolamide.
  • Carbamazepine. Tegretol. Mazepine, Carbamazepine CR.
  • Clobazam. Frisium.
  • Clonazepam. Rivotril. Clonpam, Clonazepam-R.
  • Diazepam. Valium. Diastat, Diazemuls, Dipam.
  • Ethosuximide. Zarontin.
  • Gabapentin. Neurontin.
  • Lamotrigine. Lamictal.

  • and also beside the (AEDs), diet therapy and surgery. Medications are the initial treatment choice for almost all patients with multiple seizures. Some patients who only have a single seizure and whose tests do not indicate a high likelihood of seizure recurrence may not need medications. The medications treat the symptoms of epilepsy (the seizures), rather than curing the underlying condition. They are highly effective and completely control seizures in the majority (approximately 70%) of patients. The drugs prevent seizures from starting by reducing the tendency of brain cells to send excessive and confused electrical signals.
With many different antiepileptic drugs currently available, choosing the right medication for an individual patient has become complicated. Choice of medication depends on a variety of factors, some of which include the type of seizure and type of epilepsy, the likely side effects of the medication, other medical conditions the patient may have, potential interactions with the patient’s other medications, age, gender and cost of the medication.

Before any drug is prescribed, patients should discuss potential benefits, side effects and risks with their doctors.
Diet therapy may be utilized in some patients with specific forms of epilepsy. The most common diets utilized are the ketogenic diet and the modified Atkins diet. The ketogenic diet is a special high-fat, adequate protein and low carbohydrate diet that is initiated over three to four days in the hospital. The modified Atkins diet is similar to the ketogenic diet but is slightly less restrictive. It can be initiated as an outpatient. Both diets have been shown to reduce seizures in approximately half the patients that are identified to be appropriate candidates. These are mainly children with refractory epilepsy who are not surgical candidates.
While approximately 70 percent of patients have well-controlled seizures with these modalities, the remaining 30 percent do not and are considered medically-resistant. Patients with medically-resistant epilepsy are often treated at specialized epilepsy centers in a multi-disciplinary fashion.
The team of trained specialists that collaborate to provide these patients with comprehensive diagnosis and treatment of epilepsy may include:
  • Adult epileptologists
  • Pediatric epileptologists
  • Epilepsy nurse practitioners
  • Epilepsy neurosurgeons
  • EEG technicians
  • Clinical neuropsychologists
  • Psychiatrists
  • Neuroradiologists
  • Nuclear medicine radiologists
  • Dietitians
  • Neuroscience nurses
In patients whose seizures are medically resistant, surgery provides the best chance of complete control of seizures. However, not all patients with refractory epilepsy are suitable candidates for surgery. In addition to being refractory, they need to have partial, rather than generalized epilepsy (i.e. their epilepsy arises from a single part of the brain, rather than from both sides or from all over the brain).
Furthermore, the epileptic region should be in a part of the brain that, if removed, is unlikely to result in major neurological complications. Whether or not patients are likely to benefit from surgery is determined by detailed testing (pre-surgical evaluation).
Pre-surgical evaluation consists of a one- or two-phase process to determine if surgery is the best option and can provide good seizure control with minimal risk. Phase I involves all non-invasive (non-surgical) tests. Phase II testing involves invasive tests (requires surgery) that are used in select patients.
Not every patient requires every test available in the Phase I evaluation. Adult and pediatric epilepsy patients are evaluated by epileptologists who determine the necessary and appropriate tests on an individualized basis. The following tests may be required in the phase I evaluation:
This is the initial test performed in every patient and is usually done as an outpatient procedure (pictured here). It is used not only to diagnose epilepsy, but also to determine if the epileptic seizures are coming from a small part of the brain (partial seizures), or all over the brain ( generalized).
Although most patients do not have seizures when the EEG is being recorded, they often have abnormal brain activity in the EEG (spikes or sharp waves) that indicates they have a tendency to have seizures. The location of this activity allows the physician to determine whether patients have partial or generalized seizures.
This is the most important pre-surgical test and is performed with electrodes attached to the scalp (noninvasive monitoring). Patients are admitted to the hospital for several days and the purpose is to record seizures with simultaneous video and EEG. All the data are analyzed by a trained epileptologist. Detailed analysis of the symptoms during seizures as well as the location of EEG changes during seizures (ictal EEG onset), and abnormalities noted in between seizures (interictal), indicate the likely location where seizures originate within the brain.
This may detect an abnormality that could be the cause of the epilepsy (lesional epilepsy) or may be normal (non-lesional epilepsy). With more powerful MRI machines and use of special protocols and software, subtle brain abnormalities are increasingly being identified.
PET scans look at the metabolic activity of the brain and allow physicians to determine if the brain is functioning normally. In patients with epilepsy, decreased brain function is seen in the region where seizures originate, when the patient is not actually having a seizure. On the other hand, if the patient has a seizure during the test, increased brain function is seen. PET scan may show abnormalities even if the brain MRI is normal. PET scans are usually done in the outpatient setting.

When a person has a seizure, an increased amount of blood flows to the brain region where the seizure begins. SPECT scans performed during seizures can identify the brain region where blood flow increases and thus indicate where they begin. SPECT scans are performed when the patient is admitted to the hospital for video-EEG monitoring.
Neuropsychological evaluation, functional MRI: Neuropsychological evaluation and functional MRI are used to assess cognitive functions, especially language and memory function prior to surgery, to see which side of the brain is dominant for language and to determine if there is decreased memory function in the epileptic region. This allows prediction of cognitive deficits after surgery. Functional MRI (fMRI) measures blood flow changes in areas of the brain during the performance of specific cognitive tasks.
This test involves the injection of a medication such as sodium amobarbital or methohexital into one carotid artery at a time and is performed in selected cases. The medication causes temporary (1-5 minutes) paralysis of one half of the brain allowing independent testing of language and memory function in the other half. This test is also used to predict post-operative deficits in language and memory function.
Results of video-EEG monitoring are compared with those obtained from the other tests to see if they all point to the same region of the brain as being the origin of epileptic seizures. If all the test results are concordant, the patient is likely to be a good surgical candidate. Thus, the Phase I evaluation is designed to find the area of the brain that is likely to be generating the seizures (the focus), to determine if that area can be safely removed, and predict what kind of outcome might be expected with regard to seizure reduction or seizure freedom.
After the Phase I evaluation, the epilepsy team meets to discuss patient management options in a multi-disciplinary setting to individualize treatments. At that time, based on the results of the Phase I evaluation, patients may be deemed good or poor surgical candidates. In some cases, it may be unclear and more testing is needed. This additional testing is called Phase II evaluation and is performed in select cases, where despite all prior tests, the seizure focus is not defined well enough for surgical treatment.
Phase II evaluation involves video-EEG monitoring with electrodes that are placed inside the skull (invasive monitoring). As there is more risk from invasive monitoring, the decision about the necessity for a Phase II evaluation is usually made by the epilepsy team as a whole and discussed in detail with the patient.
There are several surgical implantation options. Each involves the implantation of electrodes either on the surface of the brain, or within the brain. The benefit of these electrodes is that they are closer to the area producing the seizures than those placed simply on the scalp. After surgical placement of electrodes, the patients are transferred to the epilepsy monitoring unit and epileptologists perform video- EEG monitoring in a similar fashion to the phase I monitoring.
The electrode types and implantation arrays differ and may include:
A subdural electrode grid is a thin sheet of material with multiple small (couple millimeters in size) recording electrodes implanted within it. These are placed directly on the surface of the brain and have the advantage of recording the EEG without the interference of skin, fat tissue, muscle and bone that may limit scalp EEG. Shapes and sizes of these sheets are chosen to best conform to the surface of the brain and the area of interest.
These are small wires which are implanted within the brain itself. Each wire has electrodes which surround it. These electrodes are able to record brain activity along the entire length of the implanted wire. They have the advantage of recording activity from structures deeper in the brain. They can be implanted through small skin pokes.
In a number of instances, it is beneficial to implant a combination of subdural electrodes and depth electrodes.
Increasingly common, invasive monitoring may be done using the stereoelectroencephalography approach (stereoEEG). With this approach, multiple depth electrodes are implanted in a specific pattern that is individualized to the patient. The three-dimensional space which is covered by the depth electrodes is designed to encompass the seizure focus.
This is usually performed in patients with implanted subdural electrodes while they are in the EMU. After a sufficient number of seizures are recorded, brief electrical stimulation is provided through each electrode separately to determine the normal function of the part of the brain underneath the electrode. This is painless. The purpose is to map out critically important areas of the brain such as those necessary for motor, sensory and language functions and to determine if there is any overlap with the seizure-generating regions. This allows tailoring of surgical resections to minimize the risk of major neurological deficits after surgery.
Surgery for the treatment of epilepsy involves resection, disconnection, stereotactic radiosurgery or implantation of neuromodulation devices. Within these categories, there are multiple options depending on the clinical scenario.
Surgical resection (removal of abnormal tissue) for epilepsy may fall into the following broad categories:
Lesionectomy
A lesion is a generic term for brain abnormalities that show up on imaging. Some types of lesions — such as cavernous malformations (blood vessel abnormality) and tumors — are prone to cause seizures. When the pre-operative testing indicates that these lesions are the cause of the epilepsy, they can be removed surgically.
Lobectomy
Each hemisphere, or half, of the brain is divided into four main lobes — the frontal, temporal, parietal and occipital. Seizures may arise within any of the lobes. A lobectomy is an operation to remove a lobe of the brain. Removal of one of the temporal lobes — called a temporal lobectomy — is the most common type of epilepsy surgery performed. Other types of lobectomies may rely on more specialized testing and surgery to prove a lack of vital function (such as speech, memory, vision, motor function).
Multilobar resection
A multilobar resection involves removal of parts or all of two or more lobes of the brain. It is reserved for more widespread abnormalities causing seizures, providing that no vital functions are in those regions.
Hemispherectomy
The brain is divided into a left and right hemisphere. In rare instances, children may have severe, uncontrollable and devastating seizures that can be associated with weakness on one side of the body. This may occur with a large amount of damage or injury to one of the hemispheres. Surgery to remove or disconnect a hemisphere, a hemispherectomy may be curative. There are many subtypes of this surgery, the two main divisions being anatomic and functional hemispherectomy. Anatomic hemispherectomy involves removing the entire half of the brain that is injured and is generating the debilitating seizures. This includes the four lobes of the hemisphere — frontal, temporal, parietal and occipital. Functional hemispherectomy involves separating the abnormal hemisphere from the normal one by disconnecting fibers that communicate between the two. Often, some portions of the abnormal brain are surgically removed in order to perform this disconnection.
Functional hemispherectomy
Functional hemispherectomy involves separating the abnormal hemisphere from the normal one by disconnecting fibers that communicate between the two. Often, some portions of the abnormal brain are surgically removed in order to perform this disconnection. This is, very often, surgically curative.
Surgical disconnection
These surgeries involve cutting and dividing fiber bundles that connect portions of the brain. The rationale is to separate the area of the brain generating the seizures from the normal brain.
Corpus callosotomy
The corpus callosum is one of the main fiber bundles that connect the two hemispheres. When debilitating generalized seizures or falling-type seizures start on one side of the brain and quickly spread to the other, patients may be candidates for this procedure. A large part of this fiber bundle may be cut. The procedure is palliative, meaning that although seizures may improve, they usually do not disappear.
Multiple subpial transections (MST)
In certain cases of epilepsy, where the seizures are deemed to be arising from an area of the brain that cannot be safely removed, multiple subpial transections can be performed. In this procedure, a small wire is placed into the brain to perform transections at multiple points in a given region which can decrease seizures by disconnecting the cross-communication of neurons.
Stereotactic radiosurgery
Stereotactic radiosurgery involves the delivery of a focused beam of radiation to a specific target area. Gamma Knife radiosurgery, one of the most common forms of radiosurgery, uses gamma rays to target the area to be treated. In epilepsy, it is generally reserved for small, deep-seated lesions that are visible on MR imaging.
Neuromodulation
There are currently two FDA-approved devices that modulate the nervous system with the goal of improved seizure control. This includes vagus nerve stimulation and responsive neurostimulation. Both devices are considered palliative in that the goal is improved seizure control, and rarely do patients become seizure free.
Vagus nerve stimulation
The vagus nerve stimulator (VNS) is an FDA-approved device for the treatment of epilepsy that is not controlled with antiepileptic medications. It involves the surgical placement of electrodes around the vagus nerve in the neck and a generator placed below the collar bone in the upper chest region. It requires two separate incisions, but is an outpatient procedure. Subsequently, a programmer can be used by the epileptologist (from outside the skin) to change the intensity, duration and frequency of stimulation to optimize seizure control. VNS decreases seizure frequency by at least half in 40 to 50 percent of patients, but rarely eliminates all seizures. It is an option for those who are not candidates for other types of surgery.
Responsive neurostimulation (RNS)
The NeuroPace responsive neurostimulation (RNS) device was approved by the FDA in 2014 as a treatment for adults with partial-onset seizures with one or two seizure onset-zones, whose seizures have not been controlled with two or more antiepileptic drugs. Surgery involves placing a neurostimulator in the skull and connecting to two electrodes that are placed either on the surface or into the brain, in or around the area which is deemed to be the likely onset region for the seizure. The device records brain waves (EEG), and is trained by the epileptologist to detect the electrical signature of the seizure onset and then deliver an impulse which can stop the seizure. Data collected by the neurostimulator can by uploaded by the patient with the use of a hand-held wand to a secure web-based application which can be accessed by the epileptologist. This surgery is generally reserved for patients who are not a candidate for surgical resection, since the RNS improves seizure control but rarely stops seizures from occurring.
Improved technology and testing has made it possible to identify more accurately where seizures originate in the brain (epileptogenic regions), and advances in surgery have made operative management safer for all forms of surgery for epilepsy. Of the surgeries presented, surgical resection offers the best chance of rendering a patient seizure-free. However, the benefits of surgery should always be weighed carefully against its potential risks.
People with epilepsy are at risk for two life-threatening conditions: tonic-clonic status epilepticus and sudden unexplained death in epilepsy (SUDEP). Tonic-clonic status epilepticus is a long-lasting seizure that's considered a medical emergency. If not stopped within about 30 minutes, it may cause permanent injury or death.
SUDEP is a rare condition in which young or middle-aged people with epilepsy die without a clear cause. It accounts for less than two percent of deaths among people with epilepsy. The risk is about one in 3,000 per year for all people with epilepsy. However, it can be as high as one in 300 for those who have frequent, uncontrollable seizures and take high doses of seizure medicines. Researchers are uncertain why SUDEP causes death. Some believe that a seizure causes an irregular heart rhythm. More recent studies have suggested that the person may suffocate from impaired breathing, fluid in the lungs and lying face down on bedding.
Although the risk is low, people with epilepsy also can die from inhaling vomit during or just after a seizure.
Most women with epilepsy can become pregnant, but they should discuss their epilepsy and the medications they are taking with their doctors before getting pregnant. Many patients with epilepsy take high doses of medication that may lead to potentially harmful drug exposure to unborn babies. In some cases, medications may be reduced before pregnancy, particularly if seizures are well-controlled. While seizure medications can produce birth defects, severe birth defects are rare in infants of women who receive regular prenatal care and whose seizures are carefully managed. Women with epilepsy have a 90 percent or better chance of having a normal, healthy baby.
Epilepsy is a chronic condition that affects people in different ways. Many people with epilepsy lead normal, active lives. Between 70 and 80 percent of people with epilepsy can successfully control their seizures through medication or surgical techniques.
Some people find that they rarely have to think about epilepsy, except when taking their medications or going to see the doctor. No matter how epilepsy affects a person, it is important to remember that being well-informed about the condition and keeping a positive attitude are important. Working closely with ahealthcare team and adhering to prescribed medications are essential to helping control seizures so that the patient can lead a full, balanced life.
These websites offer additional helpful information on epilepsy, its causes, treatment options, support and more (Note: these sites are not under the auspice of The American Association of Neurological Surgeons, and their listing here should not be seen as an endorsement of these sites or their content).
The AANS does not endorse any treatments, procedures, products or physicians referenced in these patient fact sheets. This information is provided as an educational service and is not intended to serve as medical advice. Anyone seeking specific neurosurgical advice or assistance should consult his or her neurosurgeon, or locate one in your area through the AANS’ Find 







Parkinson’s Disease


Parkinson’s disease is a progressive disorder that is caused by degeneration of nerve cells in the part of the brain called the substantia nigra, which controls movement. These nerve cells die or become impaired, losing the ability to produce an important chemical called dopamine. Studies have shown that symptoms of Parkinson's develop in patients with an 80 percent or greater loss of dopamine-producing cells in the substantia nigra.
Normally, dopamine operates in a delicate balance with other neurotransmitters to help coordinate the millions of nerve and muscle cells involved in movement. Without enough dopamine, this balance is disrupted, resulting in tremor (trembling in the hands, arms, legs and jaw); rigidity (stiffness of the limbs); slowness of movement; and impaired balance and coordination – the hallmark symptoms of Parkinson's.
The cause of Parkinson's essentially remains unknown. However, theories involving oxidative damage, environmental toxins, genetic factors and accelerated aging have been discussed as potential causes for the disease. In 2005, researchers discovered a single mutation in a Parkinson’s disease gene (first identified in 1997), which is believed responsible for five percent of inherited cases.
It is estimated that 60,000 new cases of Parkinson’s disease are diagnosed each year, adding to the estimated one to 1.5 million Americans who currently have the disease. There were nearly 18,000 Parkinson’s disease-related deaths in the United States in 2003. While the condition usually develops after the age of 55, the disease may affect people in their 30s and 40s, such as actor Michael J. Fox, who was diagnosed at age 30.
A partial list of famous people with Parkinson’s:
  • Muhammad Ali, boxer (boxing-induced)
  • Johnny Cash, singer
  • Michael J. Fox, actor
  • Estelle Getty, actress
  • Billy Graham, evangelist
  • Pauline Kael, film critic
  • Deborah Kerr, actress
  • Janet Reno, former U.S. Attorney General
  • George Roy Hill, 81, director
  • Michael Redgrave, 77, actor
  • Pope John Paul II, 84, pope
  • Terry-Thomas, 79, actor
  • Tremor or the involuntary and rhythmic movements of the hands, arms, legs and jaw
  • Muscle rigidity or stiffness of the limbs – most common in the arms, shoulders or neck
  • Gradual loss of spontaneous movement, which often leads to decreased mental skill or reaction time, voice changes, decreased facial expression, etc.
  • Gradual loss of automatic movement, which may lead to decreased blinking, decreased frequency of swallowing and drooling
  • A stooped, flexed posture with bending at the elbows, knees and hips
  • Unsteady walk or balance
  • Depression or dementia
Presently, the diagnosis of Parkinson's is primarily based on the common symptoms outlined above. There is no X-ray or blood test that can confirm the disease. However, noninvasive diagnostic imaging, such as positron emission tomography (PET) can support a doctor's diagnosis. Conventional methods for diagnosis include:
  • The presence of two of the three primary symptoms
  • The absence of other neurological signs upon examination
  • No history of other possible causes of parkinsonism, such as the use of tranquilizer medications, head trauma or stroke
  • Responsiveness to Parkinson's medications, such as levodopa
The majority of Parkinson's patients are treated with medications to relieve the symptoms of the disease. These medications work by stimulating the remaining cells in the substantia nigra to produce more dopamine (levodopa medications) or by inhibiting some of the acetylcholine that is produced (anticholinergic medications), therefore restoring the balance between the chemicals in the brain. It is very important to work closely with the doctor to devise an individualized treatment plan. Side effects vary greatly by class of medication and patient.
Developed more than 30 years ago, levodopa is often regarded as the gold standard of Parkinson's therapy. Levodopa works by crossing the blood-brain barrier, the elaborate meshwork of fine blood vessels and cells that filter blood reaching the brain, where it is converted into dopamine. Since blood enzymes (called AADCs) break down most of the levodopa before it reaches the brain, levodopa is now combined with an enzyme inhibitor called carbidopa. The addition of carbidopa prevents levodopa from being metabolized in the gastroinstenal tract, liver and other tissues, allowing more of it to reach the brain. Therefore, a smaller dose of levodopa is needed to treat symptoms. This advance also helps reduce the severe nausea and vomiting often experienced as a side effect of levodopa. For most patients, levodopa reduces the symptoms of slowness, stiffness and tremor. It is especially effective for patients that have a loss of spontaneous movement and muscle rigidity. This medication, however, does not stop or slow the progression of the disease.
Levodopa is available as a standard (or immediate) release formula or a long-acting or "controlled-release" formula. Controlled release may provide a longer duration of action by increasing the time it takes for the gastrointestinal tract to absorb the medication.
Side effects may include nausea, vomiting, dry mouth and dizziness. Dyskinesias (abnormal movements) may occur as the dose is increased. In some patients, levodopa may cause confusion, hallucinations or psychosis.
Bromocriptine, pergolide, pramipexole and ropinirole are medications that mimic the role of chemical messengers in the brain, causing the neurons to react as they would to dopamine. They can be prescribed alone or with levodopa and may be used in the early stages of the disease or administered to lengthen the duration of effectiveness of levodopa. These medications generally have more side effects than levodopa, so that is taken into consideration before doctors prescribe dopamine agonists to patients.
Side effects may include drowsiness, nausea, vomiting, dry mouth, dizziness and feeling faint upon standing. While these symptoms are common when starting a dopamine agonist, they usually resolve over several days. In some patients, dopamine agonists may cause confusion, hallucinations or psychosis.
Entacapone and tolcapone are medications that are used to treat fluctuations in response to levodopa. COMT is an enzyme that metabolizes levodopa in the bloodstream. By blocking COMT, more levodopa can penetrate the brain and, in doing so, increase the effectiveness of treatment. Tolcapone is indicated only for patients whose symptoms are not adequately controlled by other medications, because of potentially serious toxic effects on the liver. Patients taking tolcapone must have their blood drawn periodically to monitor liver function.
Side effects may include diarrhea and dyskinesias.
This medication slows down the activity of the enzyme monoamine oxidase B (MAO-B), the enzyme that metabolizes dopamine in the brain, delaying the breakdown of naturally occurring dopamine and dopamine formed from levodopa. When taken in conjunction with levodopa, selegiline may enhance and prolong the effectiveness of levodopa.
Side effects may include heartburn, nausea, dry mouth and dizziness. Confusion, nightmares, hallucinations and headache occur less often and should be reported to the doctor.
Trihexyphenidyl, benztropine mesylate, biperiden HCL and procyclidine work by blocking acetylcholine, a chemical in the brain whose effects become more pronounced when dopamine levels drop. These medications are most useful in the treatment of tremor and muscle rigidity, as well as in reducing medication-induced parkinsonism. They are generally not recommended for extended use in older patients because of complications and serious side effects.
Side effects may include dry mouth, blurred vision, sedation, delirium, hallucinations, constipation and urinary retention. Confusion and hallucinations may also occur.
This is an antiviral medication that also helps reduce symptoms of Parkinson’s (unrelated to its antiviral components) and is often used in the early stages of the disease. It is sometimes used with an anticholinergic medication or levodopa. It may be effective in treating the jerky motions associated with Parkinson's.
Side effects may include difficulty in concentrating, confusion, insomnia, nightmares, agitation and hallucinations. Amantadine may cause leg swelling as well as mottled skin, often on the legs.
For many patients with Parkinson’s, medications are effective for maintaining a good quality of life. As the disorder progresses, however, some patients develop variability in their response to treatment, known as "motor fluctuations. During "on" periods, a patient may move with relative ease, often with reduced tremor and stiffness. During "off" periods, patients may have more difficulty controlling movements. Off periods may occur just prior to a patient taking their next dose of medication, and these episodes are called "wearing off." Uncontrolled writhing movements, called dyskinesias, may result. These problems can usually be managed with changes in medications. Based upon the type and severity of symptoms, the deterioration of a patient's quality of life and a patient’s overall health, surgery may be the next step. The benefits of surgery should always be weighed carefully against its risks, taking into consideration the patient’s symptoms and overall health.
Neurosurgeons relieve the involuntary movements of conditions like Parkinson's by operating on the deep brain structures involved in motion control – the thalamus, globus pallidus and subthalamic nucleus. To target these clusters, neurosurgeons use a technique called stereotactic surgery. This type of surgery requires the neurosurgeon to fix a metal frame to the skull under local anesthesia. Using diagnostic imaging, the surgeon precisely locates the desired area in the brain and drills a small hole, about the size of a nickel. The surgeon may then create small lesions using high frequency radio waves within these structures or may implant a deep brain stimulating electrode, thereby helping to relieve the symptoms associated with Parkinson's.
This procedure may be recommended for patients with aggressive Parkinson's or for those who do not respond to medication. Pallidotomy is performed by inserting a wire probe into the globus pallidus – a very small region of the brain, measuring about a quarter inch, involved in the control of movement. Most experts believe that this region becomes hyperactive in Parkinson’s patients due to the loss of dopamine. Applying lesions to the global pallidus can help restore the balance that normal movement requires. This procedure may help eliminate medication-induced dyskinesias, tremor, muscle rigidity and gradual loss of spontaneous movement.
Thalamotomy uses radiofrequency energy currents to destroy a small, but specific portion of the thalamus. The relatively small number of patients who have disabling tremors in the hand or arm may benefit from this procedure. Thalamotomy does not help the other symptoms of Parkinson's and is used more often and with greater benefit in patients with essential tremor, rather than Parkinson’s.
DBS offers a safer alternative to pallidotomy and thalamotomy. It utilizes small electrodes which are implanted to provide an electrical impulse to either the subthalamic nucleus of the thalamus or the globus pallidus, deep parts of the brain involved in motor function. Implantation of the electrode is guided through magnetic resonance imaging (MRI) and neurophysiological mapping, to pinpoint the correct location. The electrode is connected to wires that lead to an impulse generator or IPG (similar to a pacemaker) that is placed under the collarbone and beneath the skin. Patients have a controller, which allows them to turn the device on or off. The electrodes are usually placed on one side of the brain. An electrode implanted in the left side of the brain will control the symptoms on the right side of the body and vice versa. Some patients may need to have stimulators implanted on both sides of the brain.
This form of stimulation helps rebalance the control messages in the brain, thereby suppressing tremor. DBS of the subthalamic nucleus or globus pallidus may be effective in treating all of the primary motor features of Parkinson's and may allow for significant decreases in medication doses.
Embryonic stem cell research is a promising field that has created political and ethical controversy. Scientists are currently developing a number of strategies for producing dopamine neurons from human stem cells in the laboratory for transplantation into humans with Parkinson's disease. The successful generation of an unlimited supply of dopamine neurons may offer hope for Parkinson's patients at some point in the future.
Research currently being explored utilizes embryonic stem cells, which are undifferentiated cells derived from several day-old embryos. Most of these embryos are the product of in vitro fertilization efforts. Researchers believe that they may be able to prompt these cells, which can theoretically be manipulated into a building block of any of the body's tissues, to replace those lost during the disease’s progression.
There is hope that adult stem cells, which are harvested from bone marrow, may be utilized in a similar way to achieve results. Fewer ethical questions surround this sort of research, but some experts believe that adult stem cells may be more difficult to work with than those from embryos. Either way, the scientific community is nearly unanimous in arguing that research efforts and potential breakthroughs will be negatively impacted if they are not allowed to work on both types of stem cells.
Human studies of so-called neurotrophic factors are also being explored. In animal studies, this family of proteins has revived dormant brain cells, caused them to produce dopamine, and prompted dramatic improvement of symptoms.
This is a disorder with symptoms similar to Parkinson's, but caused by medication side effects, different neurodegenerative disorders, illness or brain damage. As in Parkinson’s, many common symptoms may develop, including tremor; muscle rigidity or stiffness of the limbs; gradual loss of spontaneous movement, often leading to decreased mental skill or reaction time, voice changes, or decreased facial expression; gradual loss of automatic movement, often leading to decreased blinking, decreased frequency of swallowing, and drooling; a stooped, flexed posture with bending at the elbows, knees and hips; an unsteady walk or balance; and depression or dementia. Unlike Parkinson’s, the risk of developing secondary parkinsonism may be minimized by careful medication management, particularly limiting the usage of specific types of antipsychotic medications.
Many of the medications used to treat this condition have potential side effects, so it is very important to work closely with the doctor on medication management. Unfortunately, secondary parkinsonism does not seem to respond as effectively to medical therapy as Parkinson's.
The AANS does not endorse any treatments, procedures, products or physicians referenced in these patient fact sheets. This information is provided as an educational service and is not intended to serve as medical advice. Anyone seeking specific neurosurgical advice or assistance should consult his or her neurosurgeon, or locate one in your area through the AANS’ Find a Board-certified Neurosurgeon online tool.

Multiple Sclerosis


Multiple Sclerosis (MS) is an inflammatory disease affecting the central nervous system (CNS). The CNS consists of the brain, spinal cord and the optic nerves. Surrounding and insulating the nerve fibers of the CNS is a fatty tissue called myelin. Myelin protects nerve fibers and allows them to function normally. MS causes myelin to be lost, and scar tissue, called sclerosis, forms in its place, causing plaques or lesions to form. Damaged nerve fibers disrupt the ability of the nerves to conduct electrical impulses to and from the brain. The damaged areas, known as plaques or lesions, produce the various symptoms of MS.
Many experts believe that MS is an autoimmune disease – one in which the body, through its immune system, launches a defensive attack against its own tissues. With MS, it is the nerve-insulating myelin that comes under attack. Such attacks may be linked to an external factor, such as a viral infection.
MS is the most common neurological disorder diagnosed in young adults. According to the National Multiple Sclerosis Society, there are approximately 400,000 reported cases of MS in the United States. This estimate suggests that nearly 200 new cases are diagnosed each week. There are an estimated 2.5 million people worldwide with the disease. MS is five times more prevalent in cooler climates – such as those found in the northern U.S., Canada and Europe. The closer one lives to the equator, the less prevalent MS appears to be.
Although MS can strike anyone, most people experience their first symptoms of MS between the ages of 20 and 40. Women are affected two to three times more often than men. The average risk of developing MS is one in 1,000, but this risk increases to 3 to 4 percent if you have a first-degree relative with MS. Caucasians are more than twice as likely as other races to develop MS.
The symptoms of MS vary greatly from person to person, depending on the area of the nervous system affected. Some people experience symptoms for a short period of time and then may remain symptom-free for years, while others may experience a more steady progression of the disease. Symptoms may be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision.
Common symptoms may include:
  • Balance and coordination problems
  • Bladder and bowel problems
  • Blurred vision
  • Chronic pain
  • Depression
  • Dizziness (vertigo)
  • Fatigue
  • Impaired mobility
  • Mild cognitive/memory problems
  • Muscle spasticity (leg stiffness)
  • Numbness
  • Sexual dysfunction
  • Slurred speech
  • Swallowing disorders
  • Tremor
  • Weakness
Periods of active MS symptoms are called attacks, exacerbations or relapses. These can be followed by quiet periods called remissions.
MS ranges from very mild and intermittent to steadily progressive. At diagnosis, about 80 percent of people have the relapsing-remitting form of MS. People at this stage have attacks followed by periods of partial or total remission, which may last months or even years. Others experience a progressive disease course with steadily worsening symptoms. The disease may worsen steadily from the onset (primary-progressive MS) or may become progressive after a relapsing-remitting course (secondary-progressive MS).
No single neurological or laboratory test can confirm or rule out MS. Before a doctor can recommend a course of treatment, he or she will:
  • Review medical history, and perform a general physical examination
  • Ask specific questions to determine if symptoms may be caused by MS
  • Perform a complete neurological examination, identifying the neurological signs of MS, such as damage to the optic nerve, abnormal reflexes or poor coordination
  • Perform diagnostic testing as needed
The doctor may recommend a spinal tap. In this procedure, a needle is inserted into the spinal column and spinal fluid is removed for analysis. The presence of white blood cells in the fluid may be indicative of an inflammatory reaction resulting from MS. The presence of a pattern of antibodies called oligoclonal bands in the spinal fluid is also common in MS.
In addition, more specialized diagnostic procedures may be performed such as evoked potential tests that record the brain's response to visual, auditory and pain stimuli; computed tomography (CT or CAT scan) that can detect areas of demyelination; and magnetic resonance imaging (MRI) that provides a specialized image of the CNS that cannot be captured through traditional X-rays or a CT scan.
At present, there is no cure for MS. There are, however, effective treatments that can help reduce the severity and frequency of attacks and help manage the symptoms. Two common courses of treatment include drug therapy or alternative healing modalities, commonly known as holistic treatments. The earlier one is treated, the more effective treatment appears to be. Early treatment may potentially limit the amount of nerve damage incurred and also delay the onset of subsequent attacks.
Currently, there are five FDA-approved drugs utilized to treat MS. Avonex® (interferon beta-1a), Betaseron® (interferon beta-1a) and Copaxone® (glatiramer acetate). Research has shown that these medications are effective for many patients over long periods of time. The fourth drug, Novantrone® (mitoxantrone) is used for relapsing-remitting and secondary-progressive MS. The fifth drug, Rebif® is the same drug as Avonex, but is injected differently, in more frequent and higher doses.
All of these drugs have side effects, but they are usually manageable. Novantrone has a set number of doses, as heart damage may occur when doses are administered over too long a period of time. It is only administered via intravenous injection once every three months for a maximum of three years.
The other four drugs are injected via syringes, and many patients may self-administer these in the comfort of their own home. These four drugs are injected anywhere from once a week to once a day, depending on which one is prescribed.
For severe attacks, a high-dose, short-term course of corticosteroids may be prescribed. This can help reduce the severity and length of the attack by decreasing inflammation and potentially minimize the damage caused by the attack.
For MS patients who develop trigeminal neuralgia, a severe facial pain syndrome, there are several drug therapies or surgeries that may help reduce pain. When MS affects the cerebellum or the cerebellum's connections to other parts of the brain, severe tremor can result. Tremor may be treated using deep brain stimulation (DBS), a surgical procedure in which a hair-thin wire is implanted in the thalamus and connected to a neurostimulator implanted under the collarbone. The neurostimulator sends electrical impulses along the wire to the thalamus, interrupting signals that cause tremor.
Some MS sufferers opt for alternative therapies including acupuncture, osteopathy, homeopathy, aromatherapy and reflexology. Many people find a combination of drug therapy, physical therapy and alternative methods achieve the best results. There are local support groups throughout the United States that can help patients and family members address problems that arise from coping with MS.
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7 comments:

  1. Anonymous5 March 2020 at 16:26

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    2. Daniel Lan24 March 2021 at 21:45

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