INFORMATION ON EPILEPSY & AEDs

Epilepsy is a much misunderstood medical disorder, inspite of the illness being known to mankind for over 3000 years. There are many myths and fears about this eminently treatable condition. One of the common myths is that epilepsy is a mental illness which is not so.
We now know that with the available antiepileptic drugs, epilepsy can be well controlled in about 75 to 80% of patients and the drugs can be withdrawn if a person is fit-free for to 2-5 years period. However the disease which can be so well controlled is perceived as a great setback and great cause for misery, simply because of the wrong notions. To make matters worse the doctors have very little time to convey the total picture of epilepsy and they concentrate more on procedures and prescription of the drugs. In order to facilitate patients to gain information about various non-medical aspects of epilepsy, an organization known as International Bureau for Epilepsy (IBE) was formed in 1961 by Mr. George.Burden who was a non-medical person and who recognized the necessity of such an organization.

As written by Dr. K.K. Sinha

Dr. B S Singhal, Prof & Head - Dept of Neurology

Epilepsy is common. The treatment goal is to achieve total freedom from epileptic epileptic attacks. Failure to comply with treatment regimes is a common cause of seizure recurrence. In this case of antiepileptic drugs ( AEDs) non compliance means not taking the drug or not taking the recommended dosage or not taking the drug for the duration specified. Besides, there may also be noncompliant behaviour such as not altering the life style activities known to trigger seizures ( e.g not getting enough sleep and overindulgence in alcohol )
There can be several reasons for non compliance. Failure to educate the patient regarding the nature of illness, the drugs prescribed with their side effects and the need for regular and prolonged medication is an important cause for noncompliance. Regrettably this aspect is often neglected in our country. Being busy in patient care cannot be an excuse. Also the patients seek multiple consultations and the new doctor may presume that the patient has been briefed by the previous physician. In the past availability of the AED was an issue. Today a particular brand may not be available at all places. It would therefore be desirable to write the generic name and alternative brand names so that the patient gets the drug. The high cost of the drug can be a factor for discontinuation of AED and this should always be taken into consideration. Frequent dosing can be another cause for missing the drug, especially the afternoon dose. Fortunately many drugs are now available with controlled release preparations which enable them to be given in a convenient single or twice a day schedule. Complex drug regimens withmultiple drugs ( at times result in missing the all important AED. Patients also tend to become noncompliant when they feel better due to a good seizure control. On occasions, the patients discontinue the drug to see is they are cured. Fortunately in India the mother ensures that the child is given the drug at the scheduled time, but there can be a lapse on the part of the teenagers and mildly forgetful elderly patient.
Many a patient has apprehension about the long - term toxicity of AED which need to be dispelled. In particular, newly married women may have fear regarding the effect of AED on fertility and pregnancy and they need proper counseling. Regrettably too often, the firls get married ( in case of arranged marriages ) without disclosing the illness. After marriage the girl tries to avoid taking the drug at the scheduled time or in appropriate dose resulting in seizure recurrence. Many patients in India have faith in ayurvedic or homeopathic medication. Practitioners or alternative medicine often gives false assurance to the patients of achieving a ' cure' from epilepsy. There is unfortunately no governmental control for such persons. The results in switching to other drugs with recurrence of the seizures.
To conclude, non compliance is a major factors in seizure recurrence. In such a case, one should always enquire if the individual has missed the drug before escalating the dose or switching to another drug. One may also get some idea regarding non compliance by doing the pill count and going serum drug level. We can hope to achieve better seizure control by improving compliance through education of the patient, use of memory aids such as pill boxes, reinforcing good physician - patient relationship, by providing good family support, and help from the support groups.

Dr Sunil K Pandya, Neurosurgeon
Drugs used in the treatment of epilepsy in India : need for reappraisal
Fashions in drug therapy

There has been a marked increase in the number of drugs available for the treatment of epilepsy and new drugs are being added each year. At first sight this appears to be a reason for celebration. Drug companies introducing the latest drugs certainly lost no time extolling their virtues and marketing them aggressively to doctors likely to use them. Doctors, keen to follow the dictates of fashion, soon switch over from old, time-tested chemicals to the drug that is the ' flavour of the month'. In this in the best interests of patients ?
Drug manufacturers spend small fortunes highlighting the superiority of their latest offerings over those of rivals and denigrating the now unfashionable older drugs. Unfortunately, the majority of doctors accept what is dished our to them by the companies, their critical faculties having been dulled by years spent without visiting a medical library or studying recent issues of indexed medical journals. Sweeteners offered by pharmaceutical companies make acceptance easier. Visit any annual conference and you will see a variety of gifts on offer to doctors. These range from bags to suitcases, to trips, to tourist attractions within the state where the conference is being held. These companies also host liberal cocktail parties and gala dinners. Blatant advertisement of new drugs on conference screens and all around conference halls is not the norm.
The patient pays the price in more ways than one.Newer drugs are invariably much more expensive then those of yesteryear. Manufacturers are now reluctant to produce the 'cheap' drug, as the profit margin on them is much lower then that on the latest product. Over time, costs o f patients escalate as the inexpensive drugs become 'orphans' and are phased out.
The side effects or 'adverse reactions produced by drugs in use over decades are well documented, understood and easily detected. The unwelcome effects produced by the newer drugs are underplayed by the manufacturer and are poorly understood by the doctors. It is years before these become public knowledge in the medical fraternity. As a consequence, they may be missed. This is harmful to the patient. By the time these side-effects become public knowledge, the company has made profits from this drug and has shifted its spotlight on to its latest offering.
Why is a reappraisal of the prescription of drugs against epilepsy necessary ?
Most of our patients are poor. It is unfair to them and their families to foist expensive new drugs on them when an older preparation will suffice to control fits without causing harm. A case in point is the adult whose fits are controlled by phenobarbitone tablets without any side effects. Why should a more modern expensive drug be substituted in his case ? Why should phenobarbitone or phenytoin not be tried as the first drug when its use is appropriate on medical grounds ?
Where possible, the inexpensive drug must be preferred provided it is equally effective and causes no harmful effects.
The newer drugs against epilepsy - like new antibiotics - must be reserved for use in those patients where the older drugs are ineffective or have caused complications. The use of sodium valproate in a patient in whom phenytoin has produced the Steven-Johnson syndrome is unchallengeable.

New epilepsy prevention study findings have been reported by scientists at University of Bonn

August 10, 2007
Pain & Central Nervous System Week via NewsEdge Corporation :
2007 AUG 13 - (NewsRx.com) -- Investigators publish new data in the report "Diminished response of CA1 neurons to antiepileptic drugs in chronic epilepsy." According to a study from Bonn, Germany, "A substantial proportion of epilepsy patients (approximately 30%) continue to have seizures despite carefully optimized treatment with antiepileptic drugs (AEDs). One key concept to explain the development of pharmacoresistance is that epilepsy-related changes in the properties of CNS drug targets result in AED-insensitivity of these targets."
"These changes then contribute to drug-resistance on a clinical level. We have tested this hypothesis in hippocampal CA1 neurons in experimental epilepsy. Using patch-clamp techniques, we thoroughly examined the effects of carbamazepine (CBZ) and phenytoin (PHT) on voltage-gated Na( ) currents (I(Na)) in hippocampal CA1 neurons of sham-control and chronically epileptic rats. We find that there were significant changes in the effects of PHT, but not CBZ on the voltage-dependence of inactivation, resulting in a significant reduction in voltage-dependent blocking effects in chronically epileptic animals. Conversely, CBZ effects on the time course of recovery from inactivation of I(Na) were significantly less pronounced in epileptic compared to sham-control animals, whereas PHT effects remained unaltered. Our findings indicate that AED-sensitivity of Na( ) currents is reduced in chronic epilepsy. The reduction in sensitivity is due to different biophysical mechanisms for CBZ and PHT. Furthermore, comparison to published work suggests that the loss of AED-sensitivity is less pronounced in CA1 neurons than in dentate granule neurons. Thus, these results suggest that target mechanisms of drug resistance are cell type and AED specific," wrote C. Schaub and colleagues, University of Bonn.
The researchers concluded: "Unraveling these complex mechanisms is likely to be important for a better understanding of the cellular basis of drug-resistant epilepsy."
Schaub and colleagues published the results of their research in Epilepsia (Diminished response of CA1 neurons to antiepileptic drugs in chronic epilepsy. Epilepsia, 2007;48(7):1339-50).
For additional information, contact C. Schaub, University of Bonn Medical Center, Dept. of Epileptology, Bonn, Germany.
The publisher of the journal Epilepsia can be contacted at: Blackwell Publishing Inc., 350 Main St., Malden, MA 02148, USA.

Traumatic brain injury

Traumatic brain injury (TBI), traumatic injuries to the brain, also called intracranial injury, or simply head injury, occurs when a sudden trauma causes brain damage. TBI can result from a closed head injury or a penetrating head injury and is one of two subsets of acquired brain injury (ABI). The other subset is non-traumatic brain injury (i.e. stroke, meningitis, anoxia). Parts of the brain that can be damaged include the cerebral hemispheres, cerebellum, and brain stem (see brain damage). Symptoms of a TBI can be mild, moderate, or severe, depending on the extent of the damage to the brain. Outcome can be anything from complete recovery to permanent disability or death. A coma can also affect a child's brain.

Epidemiology

TBI is a major public health problem, especially among males ages 15 to 24, and among elderly people of both sexes 75 years and older. Children aged 5 and younger are also at high risk for TBI.
Each year in the United States:
approximately 1 million head-injured people are treated in hospital emergency rooms,
approximately 270,000 people experience a moderate or severe TBI,
approximately 60,000 new cases of epilepsy occur as a result of head trauma,
approximately 230,000 people are hospitalized for TBI and survive,
approximately 80,000 of these survivors live with significant disabilities as a result of the injury, and
approximately 70,000 people die from head injury.


Signs and Symptoms of TBI


Some symptoms are evident immediately, while others do not surface until several days or weeks after the injury.
With mild TBI, the patient may remain conscious or may lose consciousness for a few seconds or minutes. The person may also feel dazed or not like him- or herself for several days or weeks after the initial injury. Other symptoms include:

• headache,
  




• mental confusion,
  




• lightheadedness,
  




• dizziness,
  




• double vision, blurred vision, or tired eyes,
  




• ringing in the ears,
  




• bad taste in the mouth,
  




• fatigue or lethargy,
  




• a change in sleep patterns,
  




• behavioral or mood changes, and
  




• trouble with memory, concentration, attention, or thinking
  

symptoms remain the same or get better; worsening symptoms indicate a more severe injury.
With moderate or severe TBI, the patient may show these same symptoms, but may also have:

• loss of consciousness
  




• personality change
  




• a severe, persistent, or worsening headache,
  




• repeated vomiting or nausea,
  




• seizures,
  




• inability to awaken,
  




• dilation (widening) of one or both pupils,
  




• slurred speech,
  




• weakness or numbness in the extremities,
  




• loss of coordination, and/or
  increased confusion, restlessness, or agitation
  vomiting and neurological deficit (e.g. weakness in a limb) together are important indicators of prognosis and their presence may warrant early CT scanning and neurosurgical intervention.
  

Small children with moderate to severe TBI may show some of these signs as well as signs specific to young children, including:

• persistent crying,
  




• inability to be consoled, and/or
  




• refusal to nurse or eat.
  

Anyone with signs of moderate or severe TBI should receive immediate emergency medical attention.


Causes of and risk factors for TBI

Half of all TBIs are due to transportation accidents involving automobiles, motorcycles, bicycles, and pedestrians. These accidents are the major cause of TBI in people under age 75.
For those 75 and older, falls cause the majority of TBIs.
Approximately 20 % of TBIs are due to violence, such as firearm assaults and child abuse, and about 3 % are due to sports injuries. Fully half of TBI incidents involve alcohol use.

Types of TBI

The damage from TBI can be focal, confined to one area of the brain, or diffuse, involving more than one area of the brain. Diffuse trauma to the brain is frequently associated with concussion (a shaking of the brain in response to sudden motion of the head), diffuse axonal injury, or coma. Localized injuries may be associated with neurobehavioral manifestations, hemiparesis or other focal neurologic deficits.
Types of focal brain injury include bruising of brain tissue called a contusion and intracranial hemorrhage or hematoma, heavy bleeding in the skull. Hemorrhage, due to rupture of a blood vessel in the head, can be extra-axial, meaning it occurs within the skull but outside of the brain, or intra-axial, occurring within the brain. Extra-axial hemorrhages can be further divided into subdural hematoma, epidural hematoma, and subarachnoid hemorrhage. An epidural hematoma involves bleeding into the area between the skull and the dura. With a subdural hematoma, bleeding is confined to the area between the dura and the arachnoid membrane. A subarachnoid hemorrhage involves bleeding into the space between the surface of the brain and the arachnoid membrane that lies just above the surface of the brain, usually resulting from a tear in a blood vessel on the surface of the brain. Bleeding within the brain itself is called an intracerebral hematoma. Intra-axial bleeds are further divided into intraparenchymal hemorrhage which occurs within the brain tissue itself and intraventricular hemorrhage which occurs into the ventricular system.
TBI can result from a closed head injury or a penetrating head injury. A closed injury occurs when the head suddenly and violently hits an object but the object does not break through the skull. A penetrating injury occurs when an object pierces the skull and enters brain tissue.
As the first line of defense, the skull is particularly vulnerable to injury. Skull fractures occur when the bone of the skull cracks or breaks. A depressed skull fracture occurs when pieces of the broken skull press into the tissue of the brain. A penetrating skull fracture occurs when something pierces the skull, such as a bullet, leaving a distinct and localized traumatic injury to brain tissue. Skull fractures can cause cerebral contusion.
Another insult to the brain that can cause injury is anoxia. Anoxia is a condition in which there is an absence of oxygen supply to an organ's tissues, even if there is adequate blood flow to the tissue. Hypoxia refers to a decrease in oxygen supply rather than a complete absence of oxygen, and ischemia is inadequate blood supply, as is seen in cases in which the brain swells. In any of these cases, without adequate oxygen, a biochemical cascade called the ischemic cascade is unleashed, and the cells of the brain can die within several minutes. This type of injury is often seen in near-drowning victims, in heart attack patients (particularly those who have suffered a cardiac arrest, or in people who suffer significant blood loss from other injuries that then causes a decrease in blood flow to the brain due to circulatory (hypovolemic) shock.


Effects on consciousness

Generally, there are six abnormal states of consciousness that can result from a TBI: stupor, coma, persistent vegetative state, minimally conscious state, locked-in syndrome, and brain death.
Stupor is a state in which the patient is unresponsive but can be aroused briefly by a strong stimulus, such as sharp pain. Coma is a state in which the patient is totally unconscious, unresponsive, unaware, and unarousable.
Patients in a persistent vegetative state are unconscious and unaware of their surroundings, but they continue to have a sleep-wake cycle and can have periods of alertness. A vegetative state can result from diffuse injury to the cerebral hemispheres of the brain without damage to the lower brain and brainstem. Anoxia, or lack of oxygen to the brain, which is a common complication of cardiac arrest, can also bring about a vegetative state.
Patients in a minimally conscious state have a reduced level of arousal and may appear, on the surface, to be in a persistent vegetative state but are capable of demonstrating the ability to actively process information. In the minimally conscious state a patient exhibits deliberate, or cognitively mediated, behavior often enough, or consistently enough, for clinicians to be able to distinguish it from the entirely unconscious, reflexive responses that are seen in the persistent vegetative state. Differentiating a patient in a persistent vegetative state from one in a minimally conscious state can be challenging but remains a critically important clinical task.
Locked-in syndrome is a condition in which a patient is aware and awake, but cannot move or communicate due to complete paralysis of the body.
Brain death is the lack of measurable brain function due to diffuse damage to the cerebral hemispheres and the brainstem, with loss of any integrated activity among distinct areas of the brain. Brain death is irreversible. Removal of assistive devices will result in immediate cardiac arrest and cessation of breathing.


Disabilities Resulting From TBI

Disabilities resulting from a TBI depend upon the severity of the injury, the location of the injury, and the age and general health of the patient. Some common disabilities include problems with cognition (thinking, memory, and reasoning), sensory processing (sight, hearing, touch, taste, and smell), communication (expression and understanding), and behavior or mental health (depression, anxiety, personality changes, aggression, acting out, and social inappropriateness).
Within days to weeks of the head injury approximately 40 % of TBI patients develop a host of troubling symptoms collectively called postconcussion syndrome (PCS). A patient need not have suffered a concussion or loss of consciousness to develop the syndrome and many patients with mild TBI suffer from PCS. Symptoms include headache, dizziness, memory problems, trouble concentrating, sleeping problems, restlessness, irritability, apathy, depression, and anxiety. These symptoms may last for a few weeks after the head injury. The syndrome is more prevalent in patients who had psychiatric symptoms, such as depression or anxiety, before the injury. Treatment for PCS may include medicines for pain and psychiatric conditions, and psychotherapy and occupational therapy.
Most patients with severe TBI, if they recover consciousness, suffer from cognitive disabilities, including the loss of many higher level mental skills. The most common cognitive impairment among severely head-injured patients is memory loss, characterized by some loss of specific memories and the partial inability to form or store new ones. Some of these patients may experience post-traumatic amnesia (PTA), either anterograde or retrograde. Anterograde PTA is impaired memory of events that happened after the TBI, while retrograde PTA is impaired memory of events that happened before the TBI.
Many patients with mild to moderate head injuries who experience cognitive deficits become easily confused or distracted and have problems with concentration and attention. They also have problems with higher level, so-called executive functions, such as planning, organizing, abstract reasoning, problem solving, and making judgments, which may make it difficult to resume pre-injury work-related activities. Recovery from cognitive deficits is greatest within the first 6 months after the injury and more gradual after that.
Patients with moderate to severe TBI have more problems with cognitive deficits than patients with mild TBI, but a history of several mild TBIs may have an additive effect, causing cognitive deficits equal to a moderate or severe injury.
Many TBI patients have sensory problems, especially problems with vision. Patients may not be able to register what they are seeing or may be slow to recognize objects. Also, TBI patients often have difficulty with hand-eye coordination. Because of this, TBI patients may seem clumsy or unsteady. Other sensory deficits may include problems with hearing, smell, taste, or touch. Some TBI patients develop tinnitus, a ringing or roaring in the ears. A person with damage to the part of the brain that processes taste or smell may develop a persistent bitter taste in the mouth or perceive a persistent noxious smell. Damage to the part of the brain that controls the sense of touch may cause a TBI patient to develop persistent skin tingling, itching, or pain. These conditions are rare and hard to treat.
Language and communication problems are common disabilities in TBI patients. Some may experience aphasia, defined as difficulty with understanding and producing spoken and written language; others may have difficulty with the more subtle aspects of communication, such as body language and emotional, non-verbal signals.
In non-fluent aphasia, also called Broca's aphasia or motor aphasia, TBI patients often have trouble recalling words and speaking in complete sentences. They may speak in broken phrases and pause frequently. Most patients are aware of these deficits and may become extremely frustrated.
Patients with fluent aphasia, also called Wernicke's aphasia or sensory aphasia, display little meaning in their speech, even though they speak in complete sentences and use correct grammar. Instead, they speak in flowing gibberish, drawing out their sentences with non-essential and invented words. Many patients with fluent aphasia are unaware that they make little sense and become angry with others for not understanding them. Patients with global aphasia have extensive damage to the portions of the brain responsible for language and often suffer severe communication disabilities.
TBI patients may have problems with spoken language if the part of the brain that controls speech muscles is damaged. In this disorder, called dysarthria, the patient can think of the appropriate language, but cannot easily speak the words because they are unable to use the muscles needed to form the words and produce the sounds. Speech is often slow, slurred, and garbled. Some may have problems with intonation or inflection, called prosodic dysfunction.
TBI patients have been described as the "walking wounded"owing to psychological problems. Most TBI patients have emotional or behavioral problems that fit under the broad category of psychiatric health. Family members of TBI patients often find that personality changes and behavioral problems are the most difficult disabilities to handle. Psychiatric problems that may surface include depression, apathy, anxiety, irritability, anger, paranoia, confusion, frustration, agitation, insomnia or other sleep problems, and mood swings. Problem behaviors may include aggression and violence, impulsivity, disinhibition, acting out, noncompliance, social inappropriateness, emotional outbursts, childish behavior, impaired self-control, impaired self-awareness, inability to take responsibility or accept criticism, egocentrism, inappropriate sexual activity, and alcohol or drug abuse/addiction. Some patients' personality problems may be so severe that they are diagnosed with organic personality disorder, a psychiatric condition characterized by many of the problems mentioned above. Sometimes TBI patients suffer from developmental stagnation, meaning that they fail to mature emotionally, socially, or psychologically after the trauma. This is a serious problem for children and young adults who suffer from a TBI. Attitudes and behaviors that are appropriate for a child or teenager become inappropriate in adulthood. Many TBI patients who show psychiatric or behavioral problems can be helped with medication and psychotherapy, although the effectiveness of psychotherapy may be limited by the residual neurocognitive impairment. Technological improvements and excellent emergency care have diminished the incidence of devastating TBI while increasing the numbers of patients with mild or moderate TBI. Such patients are more adversely affected by their emotional problems than by their residual physical disabilities.


Other Long-Term Problems Associated With TBI

Other long-term problems that can develop after a TBI include Parkinson's disease and other motor problems, Alzheimer's disease, dementia pugilistica, and post-traumatic dementia.
Alzheimer's disease (AD) - AD is a progressive, neurodegenerative disease characterized by dementia, memory loss, and deteriorating cognitive abilities. Recent research suggests an association between head injury in early adulthood and the development of AD later in life; the more severe the head injury, the greater the risk of developing AD. Some evidence indicates that a head injury may interact with other factors to trigger the disease and may hasten the onset of the disease in individuals already at risk. For example, people who have a particular form of the protein apolipoprotein E (apoE4) and suffer a head injury fall into this increased risk category. (ApoE4 is a naturally occurring protein that helps transport cholesterol through the bloodstream.)
Parkinson's disease and other motor problems - Movement disorders as a result of TBI are rare but can occur. Parkinson's disease may develop years after TBI as a result of damage to the basal ganglia. Symptoms of Parkinson's disease include tremor or trembling, rigidity or stiffness, slow movement (bradykinesia), inability to move (akinesia), shuffling walk, and stooped posture. Despite many scientific advances in recent years, Parkinson's disease remains a chronic and progressive disorder, meaning that it is incurable and will progress in severity until the end of life. Other movement disorders that may develop after TBI include tremor, ataxia (uncoordinated muscle movements), and myoclonus (shock-like contractions of muscles).
Dementia pugilistica - Also called chronic traumatic encephalopathy, dementia pugilistica primarily affects career boxers. The most common symptoms of the condition are dementia and parkinsonism caused by repetitive blows to the head over a long period of time. Symptoms begin anywhere between 6 and 40 years after the start of a boxing career, with an average onset of about 16 years.
Post-traumatic dementia - The symptoms of post-traumatic dementia are very similar to those of dementia pugilistica, except that post-traumatic dementia is also characterized by long-term memory problems and is caused by a single, severe TBI that results in a coma.

A Window of hope after Research/Studies

• A 23 year old woman in a vegetative state was able to communicate with a team of British researchers at Cambridge University in England led by Neurologist Adrian Owen via functional magnetic resonance imaging (FMRI)(scan)[1]. Some researchers were cautious but note that the research was groundbreaking. "It's the first time we've ever seen something like this. It really is kind of shocking," said Nicholas Schiff, a neurologist at the Weill Cornell Medical College in New York.
  




• Brain injury patient While Wallis showed few outward signs of consciousness, his brain was methodically rebuilding the white-matter infrastructure necessary for him to interact with the outside world, researchers reported Monday in the Journal of Clinical Investigation.Using PET scans and an advanced imaging technique called diffusion tensor imaging, the researchers examined Wallis' brain after he regained full consciousness and found that cells in the relatively undamaged areas had formed new axons, the long nerve fibers that transmit messages between neurons.

Label for the figure on the top left side: Coronal MRI, brain (level: insert line D): AH-ant horn, BC-body caudate n, CC-corpus cal, CT-corticospinal tr, F-fornix, IH-inf horn, INC-int capsule, IR-intercerb v, L1-putamen, L2-ext seg gl pall, L3-int seg gl pall, MCA-mid cereb a, P-pons, SCA-sup cer a, SN-subst n, T-thalamus, TT-tent cereb.

How Brain Injury Leads To Seizures & Memory Problems

In a finding that may provide a scientific basis for eventual treatment, neurology researchers have shown that traumatic brain injury reduces the level of a protein that helps keep brain activity in balance. The resulting abnormal activity, in turn, is thought to be an underlying reason for seizures and memory defects experienced by people who have suffered a traumatic brain injury (TBI).

"A traumatic brain injury occurs to someone in the United States every 23 seconds," said study team leader Akiva S. Cohen, Ph.D., of The Children's Hospital of Philadelphia, adding that, "TBI is the leading cause of death among children and young adults in this country. There are no cures known for traumatic brain injury. Our hope is that our research may contribute to potential therapies for TBI patients."
Transportation accidents such as car crashes are responsible for the majority of TBIs in people under age 75. According to the National Institutes of Health, over 5 million Americans currently have permanent disabilities resulting from TBIs.
The study, which was done in animals, appears in the journal Neurobiology of Disease, published online on Oct. 10.
Using mice, the researchers showed for the first time that TBI reduces the levels of a protein called potassium-chloride co-transporter 2 (KCC2) within a portion of the brain called the dentate gyrus. The dentate gyrus controls overactivity from reaching seizure-prone brain cells further along the circuit.
The dentate gyrus is a gatekeeper in maintaining a balance between two systems of neurotransmitters in the brain: the glutamate system and the gamma-aminobutyric acid system, abbreviated GABA(A). Glutamate stimulates neurons to fire, while GABA(A) inhibits that activity. "When lower levels of the KCC2 transporter weaken the dentate gyrus's ability to act as a gatekeeper," said Dr. Cohen, "neurons become more excitable, and seizures can occur."
In addition to its role in inhibiting seizures, the dentate gyrus is also believed to be important in memory formation. Therefore, said Dr. Cohen, "Interfering with normal function in the dentate gyrus may impair memory formation--especially antegrade memory, the ability to learn new things." Epileptic seizures and impaired memory are two of the disabilities caused by TBI.
Further animal studies, said Dr. Cohen, will investigate whether supplying KCC2 directly to the dentate gyrus will restore normal functioning in that structure, and whether it may improve symptoms in brain-injured mice. If this proves to be the case, the protein may someday be used as a medical treatment for patients with TBI.
The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, supported this study. Dr. Cohen's co-authors were David P. Bonislawski and Elizabeth P. Schwarzbach. All three are from the University of Pennsylvania School of Medicine.

Note: This story has been adapted from a news release issued by Children's Hospital of Philadelphia.

Famous People with Epilepsy

Famous people with epileptic seizures Epilepsy has nothing to do with mental disease or retardation. This has been proved beyond all doubt by the "epileptic geniuses", people who achieved great things in spite of suffering from epilepsy.The following selection shows people who had epileptic seizures at a certain stage in their life or who suffered from a chronic form of epilepsy for many years. Some historical researchers believe there is evidence to suggest that the following famous figures may have also suffered from seizure disorders:

Some historical researchers believe there is evidence to suggest that the following famous figures may have also suffered from seizure disorders:-

• Alexander the Great, king of Macedonia
  
• Aristotle, Greek philosopher/scientist
  
• Napoleon Bonaparte, French general/emperor
  
• Buddha, founder of Buddhism
  
• Julius Caesar, Roman emperor
  
• Hannibal, Carthaginian general
  
• Michelangelo, Italian painter/sculptor
  
• Mohammed, prophet of Islam
  
• Sir Isaac Newton, British mathematician
  
• Pythagoras, Greek mathematician
  
• Saint Paul the Apostle, a father of the early Catholic Church
  
• Socrates, Greek philosopher
  
• Leonardo da Vinci, Italian painter, draftsman, sculptor, architect and engineer

Many famous people have suffered from the disorder and excelled in spite of it. They include:-

• Bud Abbott, American comedian of Abbott and Costello fame
  
• Richard Burton, Welsh actor
  
• Truman Capote, American author
  
• Lewis Carroll, English author and mathematician
  
• Dante Alighieri, Italian author
  
• Charles Dickens, English author
  
• Fyodor Dostoyevsky, Russian author
  
• Danny Glover, American actor
  
• Vincent van Gogh, Dutch painter
  
• Margaux Hemingway, American actress, granddaughter of author Ernest Hemingway
  
• Elton John, English pop singer
  
• James Madison, fourth U.S. president
  
• Guy de Maupassant, French author
  
• Alfred Nobel, Swedish chemist, engineer and founder of the Nobel Prize awards
  
• Niccolo Paganini, Italian violinist
  
• Peter the Great, Russian czar
  
• Edgar Allen Poe, American author
  
• Neil Young, Canadian rock musician
  
• Jonathan Swift, English author
  
• Peter Ilich Tchaikovsky, Russian composer
  
• Alfred Lord Tennyson, English poet
  
• Lord Byron, English poet
• Vladimir Ilyich Lenin, Russian Revolutionist
• Socrates, Greek Philosopher
• Hansjakob

Research done on the information available about the 'famous people with epilepsy' who are usually listed in literature on the subject has shown that some of them definitely did suffer from epilepsy (e.g. Caesar, Grand Duke Karl, Pope Pius IX., Flaubert, Dostoyevsky). Other people (e.g. King Saul, Napoleon, van Gogh, St. Paul) are suspected of having had epilepsy, but research cannot prove this definitively.It is clear that some famous people (e.g. Lord Byron, Nobel) did not have a chronic form of epilepsy but temporarily suffered epileptic seizures at certain periods in their lives.


The interest shown in famous people who had epilepsy once again makes it clear that people with the chronic disease epilepsy or who suffer occasional epileptic seizures can still be highly intelligent and achieve great things.