Keith Wesley C.

Ybut BSN-III

GENETIC TESTING IN THE ADULT EPILEPSY CLINIC

Authors: Elizabeth Gerard, Feinberg School of Medicine, Northwestern University; Lisa Kinsley,
Feinberg School of Medicine, Northwestern University; Jeffrey D. Calhoun, Feinberg School of
Medicine, Northwestern University; William Nobis, Feinberg School of Medicine, Northwestern
University; Irena Belllinski, Feinberg School of Medicine, Northwestern University; and Gemma
L. Carvill, Feinberg School of Medicine, Northwestern University ( 2017 )

 ABSTRACT
RATIONALE: The genetic basis of epilepsy is now well established with over 100 genes
implicated and 30-50% of severe early-onset pediatric epilepsies being attributed to a genetic
cause. These advances have been invaluable in dissecting the genetic architecture of epilepsy, as
well as enhancing our understanding of pathogenic mechanisms. However, we have yet to fully
appreciate the contribution of genetic variants to more common types of epilepsy, including adult-
onset epilepsies. To begin to address this challenge, here we present our experience with clinical
and research genetic testing at an academic adult epilepsy center over a period of 14 months.
METHODS: To date, we have performed genetic testing in 30 individuals with epilepsy (10 with
adult-onset epilepsy, 20 with childhood-onset epilepsy). Testing included 9 single gene sequencing
tests, 6 phenotype-based gene panels, and 15 whole exome sequencing evaluations (typically trios
including parents when available). Variants were identified both by commercial analysis and by
further analysis of whole exome data on a research basis.
RESULTS: In 6/30 (20%) of the cases, genetic testing identified a pathogenic variant that likely
accounts for the patient’s epilepsy. These included pathogenic variants in LGI1 (2), PTEN (2),
KRIT1 (1), and NPRL3 (1). The majority (5/6) of probands with a positive genetic finding had
adult-onset epilepsy. In the sixth case, the proband’s seizure onset was in childhood, while other
affected members of her family had seizures beginning in adulthood. In the two patients with
pathogenic variants in PTEN, identification of the pathogenic variant prompted critical early
cancer screening and a diagnosis of bilateral in-situ breast carcinoma in one patient. In an
additional 5/30 (17%) individuals we identified variants in genes that are likely candidates for the
phenotype. These include variants in GABRA1 and SZT2 detected in patients with a milder
phenotype than previously reported, which may correlate with the specific variant and suggest
novel genotype-phenotype correlations. Further genetic and functional studies are ongoing to
determine the pathogenicity of candidate variants.
CONCLUSIONS: While still a relatively small and carefully selected cohort, this pilot study
illustrates how thorough investigation of individual adult patients with epilepsy and their families
can yield important insights into the genetic architecture of more common epilepsies. Moreover,
these genetic studies can reveal new genotype-phenotype correlations in known epilepsy genes
that contribute to our understanding of how alterations in these genes cause epilepsy. Finally these
findings highlight the value of clinical genetic testing and genetic counseling for adults with
epilepsy. The identification of pathogenic mutations plays an important role in the diagnosis and
management of these patients including risk assessment, family planning and, in some cases,
appropriate screening for systemic disease.
REFRACTORY CONVULSIVE STATUS EPILEPTICUS IN CHILDREN CAUSES,
RISK FACTORS AND OUTCOME

Authors: Boumendil, D.1; Negadi, M.A.1; Bouguetof, H.1; Elhalimi, K.1; Mentouri, Z.1 (2014)

Abstract

Background and aims: Refractory convulsive status epilepticus (RCSE) is a life-threatening

neurologic emergency with high mortality and morbidity, in which seizures do not respond to first
and second – line anticonvulsant drug therapy.

Aims: To determine the risk factors, and the impact on the outcome of RCSE in children.

Methods: In this prospective study we analyze 53 children with RCSE between January 2008 and
December 2010.

Results: Of 245 patients with convulsive status epilepticus, 53 developed RCSE (21, 6%), 37 of
whom were males (70%), with a mean age of 3 years (1 month-15 years). 11 patients (21%) had a
history of epilepsy. The most frequent etiologies’ were acute symptomatic (73, 6%). Encephalitis
13 patients (24, 5%), meningitis 8 patients (15%), septic shock 5 patients (9, 4%), were the main
acute etiologies. Acute symptomatic causes (odds ratio [OR] 9, 95% confidence interval [CI] 3.86–
24.168; p < 10–4), duration of CSE ≥ 6 hours (OR 5,8% [CI] 1.828–18.778; p = 0,0034),
complications (OR 13 [CI] 4.324–40.108; p < 10–4) and received > 2 doses of benzodiazepines (OR
5 [CI] 1.133–25.425; p = 0,034) were identified as independent risk factors for RCSE. During
hospitalization 24 patients (45%) died (p<10–4). On discharge from hospital, 14 patients (26.4%)
presented new neurological deficit or difficult-to-manage epilepsy.RCSE was associated with
prolonged hospital length of stay (> 3days) (p < 10–4).

Conclusions: GCSE termination and outcome seem clearly associated with adherence to treatment
protocol, etiologies and duration of the CSE.
TENSION-TYPE HEADACHE: A LIFE-COURSE REVIEW

Author(s):
Karen E Waldie, Jude Buckley, Peter N. Bull and Richie Poulton

Abstract

Background: Tension-type headache is the most prevalent primary headache type worldwide and
is associated with a wide spectrum of disability. Although progress has been made in
understanding the complex mechanisms that lead to the pathogenesis of tension-type headache, to
date there are no clear-cut markers of what makes tension-type headache unique. Due to a relative
lack of research (compared to migraine), the pathophysiology of tension-type headache is not well
understood and there are gaps in the epidemiological data, particularly from Australasia.
Objective: To provide a structured narrative review of the prevalence and correlates of tension-
type headache, with focus on a birth cohort of young adults from the Dunedin Multidisciplinary
Health and Development Study (DMHDS) in New Zealand.
Method: A review of the literature was conducted to identify the epidemiological, diagnostic,
methodological and pathophysiological factors that contribute to tension-type headache being a
specific entity.
Results: Findings suggest that prevalence rates of TTH vary across global region, age, gender and
method of assessment. A wide range of risk factors for TTH was identified, and recent advances
in genetic and neurobiological research have increased understanding of the etiology of TTH. Few
longitudinal studies have been conducted on TTH.
Conclusion: Further longitudinal epidemiological research is needed to help distinguish tension-
type headache from migraine, particularly in young people. Identifying the specific markers of
tension-type headache is a first step towards developing effective prevention and treatment
strategies.
Epilepsy

Introduction

Epilepsy is a disorder of the central nervous system characterized by recurrent

seizures unprovoked by an acute systemic or neurologic insult. Also known as convulsions,
epileptic seizures, and if recurrent, epilepsy. It is a sudden alteration in normal brain activity that
cause distinct changes in behavior and body function. They are thought to result from abnormal,
recurrent, uncontrolled electric discharges of neurons in the brain. Predisposing factors include
head or brain trauma, tumors, cranial surgery, metabolic disorders (hypocalcaemia,
hypoglycemia or hyperglycemia, hyponatremia, anoxia); central nervous system infection;
circulating disorders; drug toxicity; drug withdrawal states (alcohol, barbiturates); and congenital
neurodegenerative disorders. There are two basic types of seizures: Epileptic, which these seizures
have no apparent cause (or trigger) and occur repeatedly. These seizures are called a ³seizure
disorder´ or ³epilepsy.´ and No epileptic which these seizures are triggered (provoked) by a disorder
or another condition that irritates the brain. In children, a fever can trigger a no epileptic seizure.

Body

As the journal results, in 6/30 (20%) of the cases, genetic testing identified a pathogenic
variant that likely accounts for the patient’s epilepsy. In the sixth case, the proband’s seizure onset
was in childhood, while other affected members of her family had seizures beginning in adulthood.
In the two patients with pathogenic variants in PTEN, identification of the pathogenic variant
prompted critical early cancer screening and a diagnosis of bilateral in-situ breast carcinoma in
one patient. In an additional 5/30 (17%) individuals we identified variants in genes that are likely
candidates for the phenotype.

Conclusion

For me, these findings highlight the value of clinical genetic testing and genetic
counseling for adults with epilepsy. The identification of pathogenic mutations plays an important
role in the diagnosis and management of these patients including risk assessment, family planning
and, in some cases, appropriate screening for systemic disease. This study is important to know if
the epilepsy gene will contribute or this genes will cause epilepsy.
Status epilepticus

Introduction
Status epilepticus is a medical emergency that requires rapid diagnosis and treatment.
Nonconvulsive status epilepticus is frequently underdiagnosed and therefore undertreated, which
can lead to permanent neuronal damage resulting in disability or death. Despite the frequent
occurrence and morbidity associated with status epilepticus, this topic has received little attention
within the literature. A systematic approach to treatment should start with management of airway,
breathing, and circulation, followed by administration of benzodiazepines and intravenous
antiepileptic drugs, and rapid escalation of therapy to prevent morbidity and mortality. Armed with
the information in this article, nurses will have a higher-level understanding of what to do when
encountering a patient in status epilepticus.
Body
Refractory convulsive status epilepticus is a life-threatening neurologic emergency with
high mortality and morbidity, in which seizures do not respond to first and second – line
anticonvulsant drug therapy. And in the base in the result in the journal, Of 245 patients with
convulsive status epilepticus, 53 developed refractory convulsive status epilepticus which is 21,
6%, 37 of whom were males (70%), with a mean age of 3 years (1 month-15 years). 11 patients
(21%) had a history of epilepsy. The most frequent etiologies’ were acute symptomatic (73, 6%).
Encephalitis 13 patients (24, 5%), meningitis 8 patients (15%), septic shock 5 patients (9, 4%),
were the main acute etiologies. And during the hospitalization 24 patients (45%) died (p<10–4). On
discharge from hospital, 14 patients (26.4%) presented new neurological deficit or difficult-to-
manage epilepsy. refractory convulsive status epilepticus was associated with prolonged hospital
length of stay (> 3days) (p < 10–4).

Conclusion

This study determine the risk factors, and the impact on the outcome of refractory
convulsive status epilepticus in children. This prospective study we analyze 53 children with
RCSE between January 2008 and December 2010. And for it is very important to know how many
children are in this cases between 2008 to 2010. And this will the researchers to improve treatment
in treat patients has refractory convulsion status epilepticus especially in children.
Headache

Introduction

A headache simply means a pain or discomfort felt in the head region -whether it is the
face, back of the head (occiput), forehead, scalp, behind the eyes etc. A headache can also be
caused by referral from the upper neck or even teeth and sinuses. It can also be present even though
there is no actual organic cause for it example depression. This study was conducted to identify
the epidemiological, diagnostic, methodological and pathophysiological factors that contribute to
tension-type headache being a specific

Body

This study provide a structured narrative review of the prevalence and correlates of tension-
type headache, with focus on a birth cohort of young adults from the Dunedin Multidisciplinary
Health and Development Study in New Zealand. Base in the finding a wide range of risk factors
for tension-type headache was identified, and recent advances in genetic
and neurobiological research have increased understanding of the etiology of tension-type
headache. Few longitudinal studies have been conducted on TTH.
Conclusion
This study help to distinguish tension-type headache from migraine, particularly in young
people since young people nowadays are more prone or experiencing this problem. It also help to
identifying the specific markers of tension-type headache is a first step towards developing
effective prevention and treatment strategies.