Research Proposal

Sarah Abdellah
Intern/Mentor G/T
2016-2017
Research Title: Seizure Status: Status Epilepticus
Overview of Research
This research will address the application of neurology and neuroscience in seizures. I am
proposing to conduct a research paper through the use of document/data analysis in order to
investigate the various treatment options for status epilepticus and determine which drug
treatments would be considered the most effective, in order to formulate a treatment protocol
when treating refractory status epilepticus. The general areas of investigation include both
epilepsy and neurology while the specific areas of investigation can be identified as autoimmune
disease correlation with seizures, refractory status epilepticus, and treatments involved with both
status epilepticus and refractory status epilepticus. The current problem being investigated is:
Which treatment course should be undertaken when there is an elevated amount of antibodies
created in the immune system in the case of status epilepticus?

Background and History of the Issue

Over the course of history, the parameters that classify a seizure as being a case of status
epilepticus (SE) has changed drastically. As of 1973, Henri Gastaut defined status epilepticus as
a seizure lasting more than 30 minutes without any recovery of consciousness between seizures.
Gastaut also discovered a new seizure type classification known as complex partial status
epilepticus, which extended the scope of seizure-based research, leading to the discoveries of
other types of seizures. Treatments of status epilepticus when it was first discovered in 1824
included drug treatments such as: Chlordiazepoxide, Pentobarbital, and Amylene hydrate as well
as the alternative treatments of CSF drainage, saline infusions, and ATCH. Today, treatments of
status epilepticus are first and second-wave antiepileptic medications (AEDs), in this case,
benzodiazepines, such as diazepam, midazolam, and lorazepam. However, a new form of status
epilepticus, referred to as refractory status epilepticus (RSE) is not affected by the administration
of first or second-wave AEDs. In fact, it was observed that of the 150,000 cases of status
epilepticus reported in the United States alone each year, up to 30% of patients hospitalized for
status epilepticus will not respond to the AEDs administered while 15% of patients will continue
illustrating seizure activity despite the use of three waves of AEDs, resulting in 55,000 deaths
annually.
It has recently been tested on animal models that the resistance of drug treatment in the case of
RSE is due to an abnormal change in the GABA receptor in which GABA-R is internalized
during SE, making the benzodiazepines less effective since they are utilized via the GABA
receptors. This in turn changes the rate of the NMDA receptors, which puts the neurons in a state
of excitotoxicity, inevitably leading to neuronal death. Current studies show that Lorazepam, a
treatment option for RSE, was found to be successful in 64.9% of patients as a first line RSE
treatment compared to phenobarbital or Diazepam plus Phenytoin; however, there are many
complications such as hypotension, cardiac dysrhythmia, and hypoventilation emerging as soon
as three months after treatment. Another study promotes Midazolam as the most efficient
treatment option for RSE due to its low mortality rate of 17% to 61% whereas propofol ranged
from 57% to 88% and BBTs ranged from 20-50%.
Problem Statement and Rationale
Status epilepticus is a largely unknown type of seizure to the public, yet effects 150,000 people
in the United States each year alone, ranging to about 700,000 worldwide, in which more than
55,000 deaths are reported in the United States resulting from status epilepticus annually. This is
a significant issue since a patient could be exhibiting symptoms of SE, yes would be instead
diagnosed with another epileptic-related disease, such as tonic-clonic seizures, which exhibit
similar patterns; however, SE has certain parameters distinguishing it from other seizure types, in
order to allow the maximum time available to administer the proper treatment. However, since
the patient is unresponsive first and second-wave AEDs, there as a higher chance of the
development systemic autoimmune disorders, due to the bodys vulnerability to infection. This
includes was Systemic Lupus Erythematosus (SLE), which occurs from 25%-75% of RSE cases
and recur approximately about 12% to 43% of recurring seizures. This is due to the elevated
amount of antiphospholipid antibodies, increases both the probability of vascular disease and
Research Methodology
Research Question and Hypothesis
o Which treatment course should be undertaken when there is an elevated amount
of antibodies created in the immune system in the case of status epilepticus?
o Midazolam would be the most efficient treatment option in the case of refractory
status epilepticus (RSE) because the benzodiazepine allows for the lowest
mortality rate of the treatments currently being investigated, is easily titrated,
allowing a fast-acting seizure suppression on EEG, and less severe side effects

Basis of Hypothesis
I focused my hypothesis specifically on Midazolam since there is a lack of consistency
among neurologists to which what treatment should be used in the case of refractory
status epilepticus due to the different preferences and animal models in which they
conduct their studies on. The majority of the academic journal articles I have analyzed
collected data that could be used to prove my hypothesis that not only that other
treatment options are inferior to Midazolam, but to demonstrate how Midazolam is the
most effective and should be used as the primary drug administration in RSE.
Furthermore, I am interested in determining the pros and cons of each treatment option as
well as compile a safe treatment protocol for RSE.
 Research Design
I will be conducting a causal-comparative research design through the use, analysis, and
implementation of data from document/data analysis collection methods. My research
will consist of both quantitative and qualitative date from clinical trials, case studies, and
academic journals. Data analysis would allow to, in turn, determine the most effective
treatment(s) for RSE in order to develop a practical treatment proposal for RSE.

Operational Definitions
o Status Epilepticus: the rapid succession of epileptic seizures without intervals of
consciousness over a course of 30 minutes or longer
o Refractory Status Epilepticus: status epilepticus that continues despite treatment
with benzodiazepines and one antiepileptic drug
o Neurologist/Neuroscientist: A scientist focusing on the branch of medicine or
biology that deals with the anatomy, functions, and organic disorders of nerves
and the nervous system
o Midazolam: a medication used for anesthesia, procedural sedation, trouble
sleeping, and severe agitation
o Hypotension: an extremely low blood pressure, less than 90/60
o cardiac dysrhythmia: Life threatening abnormal heartbeat
o Hypoventilation: Occurs when ventilation is not sufficient to perform the needed
gas exchange as a result of the rapid increase of carbon dioxide (hypercapnia) and
respiratory acidosis
o Propofol: a short-acting medication that results in a decreased level of
consciousness and lack of memory for events
Product Overview
One product of my study includes creating a treatment protocol for RSE after evaluating the
positive and negative aspects of each medication and compile a proposal that would have the
least amount of side-effects as well have non-conflicting drug treatments in the same protocol.
Another product of my research would include a presentation to neurologists focusing on
epilepsy in order to promote the adaption of the newly created treatment proposal. The audience
may evaluate my product by filling out a performance sheet including accuracy, effectiveness of
the presentation, and feedback.

Logistical Considerations
The major logistical concerns for the final products include time, special permissions,
maintenance, materials, and costs. I plan to create a presentation to demonstrate my findings to
neurologists and neuroscientists based at my internship at the University of Maryland Medical
Center in order to make a difference in refractory status epilepticus research. However, this
would require special permissions to visit and present at the University of Maryland Medical
Center.
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G/T Resource Teacher Signature: _________________________ Date: _________________

Mentor Signature: _____________________________________ Date: _________________