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Brain storming
Epilepsy, caused by an uncommon storm of electrical activity
in the brain, can be controlled but not cured. Besides physical challenges,
epilepsy patients have to bear a social stigma as well. Current medicines help
but the root cause remains elusive. Sachin Jagdale investigates
 Sir
Issac Newton, Vincent van Gogh, Neil Young, Napoleon Bonaparte, Leonarda Da
Vinci, Alexander the Great, Alfred Nobel, Julius Caser, Aristotle, Pythagoras,
Socrates are names that defined world history. How many of us know that besides
having the power and charisma to change the world these personalities have one
more thing in common: epilepsy! The minds that once ruled the world were themselves
ruled by this debilitating disease.
Recurrent unprovoked seizures are the characteristic of this chronic neurological
disorder. There are more than 50 million cases of epilepsy all over the world
of which a significant number reside in developing countries. Once called a
'sacred disease' and considered an attack of a demon, epilepsy can today be
treated with advanced medications. However, epilepsy can be controlled but not
cured. Surgery is always an option in extreme cases. The agony is that over
30 percent of patients do not have seizure control even with the best available
medications. Many epilepsy syndromes are not lifelong and are related to a particular
period of childhood.
What causes epilepsy?
 "Researchers
are working to find out novel, more efficacious drugs for better seizure
management and drugs for refractory epilepsy"
- Priya Hingorani
Marketing Head in a leading
pharma company
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 "Anything
that disturbs the
normal pattern of activity in the brain can trigger epilepsy. The cause
can be illness, brain damage, or abnormal development of the brain"
- Dr P N Renjen
Senior Consultant, Neurology Indraprastha Apollo Hospitals
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The smooth functioning of the brain comes from a finely orchestrated
balance between factors that start and stop electrical impulses. When this control
system breaks down, uncommon electrical discharges can occur and spread to whole
groups of neighbouring cells at once. This linkage of electrical discharges
results in a 'storm' of electrical activity in the brain leading to a seizure.
Two of such seizures are termed as epilepsy.
"Anything that disturbs the normal pattern of activity
in the brain can trigger epilepsy. The cause can be illness, brain damage, or
abnormal development of the brain. No cause can be determined for about three-quarters
of the cases of epilepsy. Because epilepsy has so many causes and can be linked
to a number of other conditions, it is sometimes very difficult to determine
the cause of a particular case," says Dr P N Renjen, Senior Consultant,
Neurology, Indraprastha Apollo Hospitals.
The reasons why epilepsy begins are different for people
of different ages. Adolescents and children are more prone to epilepsy classified
as of 'unspecified genetic origin'. With increasing age, chances of epilepsy
increases due to underlying brain diseases like cerebrovascular disease, tumour
or degenerative brain disorder. Brain infection and trauma is yet another cause
of epilepsy and it is not age bound. In India tuberculosis and neurocysticercosis
often credited to cause epilepsy. Brain damage of foetus during the development
phase may lead to epilepsy. Severe head injury is the most common known cause
in young adults whereas strokes, tumours, and injuries are frequent in middle
age. In people over 65 years, stroke is the most common known cause, followed
by degenerative conditions such as Alzheimer's disease. In many cases, seizures
do not begin immediately after the brain suffers injury. Instead, a seizure
may take place many months later.
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The treatment of epilepsy has evolved considerably
over the years from the use of standard AED to the addition of newer AEDs
to the treatment of the epilepsy. Most of these newer drugs have been
used as add on therapy in the treatment and have helped a lot to make
the patient seizure free. Neuroimaging has significantly changed the way
treatment of difficult epilepsy is approached. The epilepsy surgery has
gone a long way and has definite role to play in the select group of patients.
There are many ancient myths about epilepsy and unfortunately some of
them still remain. At various times, people were epilepsy were shunned,
locked up in mental institutions or forbidden to marry or have children.
Seizures were thought to be caused by witchcraft, insanity, possession
by demons etc. but the fact still remains that the epilepsy is caused
by an electrical discharge in the brain.
Source:Dr P N Renjen
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Drugs and Treatment
"The choice of anti epileptic drugs (AEDs) is increasing rapidly. The evidence
that guides the decision of which AED to start as monotherapy and aims to aid
the choice of treatment if monotherapy fails. Unfortunately, evidence supporting
the prescription of new drugs is sparse, because most randomised controlled
trials answer questions focused on regulatory requirements rather than on clinical
use. Ultimately, the choice of one AED will be determined by an individual risk-benefit
assessment in which the most effective drug for an individual patient is chosen,
and one that would have the lowest risk of significant harm," informs Renjen.
Understanding the need of the situation when a person is having a seizure is
an important part of treatment. However, this is not the core objective of treatment.
The neurologist should try to prevent the re-occurrence of seizures completely
and if that is not possible, then the next strategy is to at least control them
with the best possible medication available.
Today, modern pharmaceuticals have made it possible for epilepsy patients to
lead a relatively unrestricted life. "Treatment plans are individualised,
keeping in mind the different types and causes of epilepsy, differences in efficacy
and toxicity of AEDs and also patient profile," says an official of Glenmark
Pharmaceuticals. While talking about available medication he said, "Drugs
available for epilepsy include barbiturate and its derivatives (phenobarbital,
primidone), phenytoin, iminostillbenes (carbamazepine) valproate, ethosuximide,
and benzodiazepines. Several new drugs (oxcarbazepine, lamotrigine, topiramate,
gabapentin, zonisamide, tiagabine, fosphenytoin, and vigabatrin) have been added
in the past few years to the therapeutic armamentarium against epilepsy and
there are many more at various stages of development."
According to Dr H V Srinivas, Secretary General, Indian Epilepsy Association
(IEA), with the available AEDs, epilepsy today is an eminently treatable condition
in 75 to 85 percent conditions. The duration of the treatment is not life long
as was thought earlier, but anywhere from two to five years in this group of
75 to 80 percent and a good number of these patients can go off the drugs subsequently.
"Incidentally the word 'epileptic' is no more used and the politically
correct word is 'a Person with Epilepsy' (PWE)," informs Srinivas.
A Marketing Head in a leading pharma company, Priya Hingorani
says, "The epilepsy market in India is valued at Rs 6311 million, with
a growth of 9.7 percent (May MAT 2008). The global anti epileptic market is
estimated to be $15.2 billion, with a growth of 13.5 percent (Feb 26, 2008,
IMS data)."
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Research on epilepsy is focusing on the concept
of targeting underlying neural mechanisms of epileptogenesis and injury
that cause epilepsy and its complications. Recent advances in understanding
of mechanisms of epileptogenesis and seizure-induced brain injury, such
as related to neuronal death, glial activation (astrogliosis), neurogenesis,
axonal sprouting and changes in gene expression (especially of ion channels,
neurotransmitter receptors or other proteins directly affecting neuronal
excitability) have helped enormously in focusing on this concept.
Source-Glenmark official
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Research priorities
Efforts are on to make epilepsy treatment more patient friendly.
Though tremendous progress has been made in making epilepsy treatment more effective,
there is still no permanent cure to this disease. Expressing her personal views,
Hingorani lists current focus areas of research on epilepsy. She says, "Researchers
are working to find out novel, more efficacious drugs for better seizure management
and drugs for refractory epilepsy. Reducing side effects of AEDs that are currently
used through reformulations or enatiomers etc. is yet another priority of researchers.
Improving patient compliance through once daily/sustained release formulations
as antiepileptics are a chronic therapy is also on the priority list of researchers."
Today researchers have achieved a lot in terms of reducing or controlling seizures
to considerable extent. However, the root cause is still there. As long as basic
neurological mechanism that is responsible for seizures is not under control,
epilepsy will prevail and in turn it will affect the survival of patients. "Current
research involves structural modifications of pre-existing compounds to overcome
toxicity and resistance. Research with the specific objective of modifying neurotransmitter
function is also underway," informs the Glenmark official. He adds, "In
recent years a new field of cell and gene-based neuropharmacology has emerged,
aimed at either delivering endogenous anticonvulsant compounds to the brain
(by intracerebral transplantation—ex vivo gene therapy), or by inducing
epileptogenic brain areas to produce these compounds in situ. These cell and
gene therapies though infantile at this stage, are presently being studied extensively."
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Problems of social awareness are being answered
to some extent by various branches of our association - Indian Epilepsy
Association. We have 23 chapters in various cities including Bangalore,
Mumbai and various cities. Most of our chapters are actively involved
in public education and creating awareness through various methods. IEA
is affiliated to the world wide body international bureau for epilepsy
and we conduct National Epilepsy Day celebrations on 17th November of
every year by all the chapters of our country. The public awareness is
addressed through quarterly news letters published by the national body
and some of the chapters too. Annual conferences, National Epilepsy Day
celebrations, and at the ground level by lectures, radio talks, TV interviews,
street plays, talks organised in school, colleges, painting competitions,
seminars and other organisations like Rotary etc.
Source- Dr H V Srinivas
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Social sensitisation
Out of 50 million epilepsy patients, approximately 35 million do not have access
to medicines. Reasons are many but the first and foremost one is that at many
places epilepsy is not accepted as a medical problem. There are communities
or people that still consider epilepsy a gift of God, while other communities
see it as a attack of spirits. At some places epilepsy has been termed as a
religious phenomenon. Srinivas feels that inspite of the advances and the available
treatment 70 to 85 percent of PWEs do not receive AEDs. Outlining the reasons
for such a huge treatment gap, Srinivas says, "The reasons are many including
myths, misunderstandings surrounding epilepsy like epilepsy is a mental illness,
it cannot be cured, the treatment is life long, the AEDs dull the brain. The
stigma attached to epilepsy also prevents people from seeking treatment. If
others come to know about the PWE, then there may be differentiation in the
society with reference to admissions in the school, employmeny, marriage etc."
This is in huge contrast to the situation in Western countries where epilepsy
patients with well controlled seizures spend quite a comfortable life. There
is hardly any discrimination and PWEs are well accepted by society. An epileptic
in India faces many problems throughout his life. Srinivas informs, "In
Western countries, there are hardly any restrictions on the lifestyle of a person
with well controlled seizures and in fact, driving licenses are issued for driving
a personal vehicle if the person is free from seizures for a period of six months
to two years. In India the Motor Vehicle Act as it exists today does not issue
a driving license even a person is seizure free for a number of years."
IEA has repeatedly appealed to the concerned department of the Government to
consider modifying this Act to make it more like the laws currently practiced
in several advanced countries.
Promising future
According to Renjen, pharma companies are helping to develop newer molecules
which are becoming an important part in the overall treatment of epilepsy. This
is not to say that every patient's seizures can be fully controlled or that
side effects do not occur. Pharma companies and medical professionals have to
work together to zero in on safe, effective and drug with fewer side effects.
The unceasing process of drug development surely holds even more options for
future epilepsy treatment. Moreover, the newer gene based approach to research
helps researchers to understand the brain and its functions better in a more
precise manner. As the Glenmark official sums up, "New drugs based on structural
modifications of pre-existing compounds, cell based and gene therapies and focus
on targeting underlying brain mechanisms would be some of the future trends
in the management of epilepsy."
sachin.jagdale@expressindia.com
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