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Libro, Schulze, 2016 Disnomia en Pacientes Con Epilepsia
Libro, Schulze, 2016 Disnomia en Pacientes Con Epilepsia
AMYGDALOHIPPOCAMPECTOMY IN
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2016
ProQuest Number: 10164898
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ProQuest 10164898
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COMMITTEE IN CHARGE OF CANDIDACY: IE
Professor Jeffrey D. Gfeller,
Chairperson and Advisor
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Assistant Professor David A.S. Kaufman
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ACKNOWLEDGMENTS
implementation, and presentation of this project. First and foremost, I thank Dr. Jeffrey Gfeller
for his approachability and guidance throughout my graduate career. He has been an incredible
student advocate and an outstanding role model. Thank you to Dr. Nicole Werner for her
exceptional clinical training and fostering the development of testable research questions based
on keen clinical observation. I am thankful for Dr. David Kaufman who provided continuous
mentorship in research and clinical work throughout my time as a graduate student. I would also
like to acknowledge and thank the following individuals for their input and contributions
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throughout various points in the project: Dr. Adam Parks, Dr. Richard Laurent, Dr. Victoria
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Herberger, and Dr. Kristin Hinrichs. Lastly, I would like to thank my family for their
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TABLE OF CONTENTS
List of Tables..................................................................................................................................iv
List of Figures..................................................................................................................................v
CHAPTER 1: INTRODUCTION....................................................................................................1
Epilepsy....................................................................................................................4
Temporal Lobe Epilepsy..........................................................................................5
Neuropsychological Functioning in Persons with Temporal Lobe Epilepsy...........8
Language Functioning in Temporal Lobe Epilepsy...............................................11
Naming Abilities Post-Surgical Intervention in Temporal Lobe Epilepsy............18
Measuring Reliable Change in Neuropsychological Performance........................19
Present Study..........................................................................................................21
Hypotheses.............................................................................................................23
Research Questions................................................................................................24
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CHAPTER 2: METHOD
Participants.............................................................................................................25
Materials.................................................................................................................25
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Analyses.................................................................................................................32
Procedure................................................................................................................33
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CHAPTER 3: RESULTS
Pre-Surgical Sample Characteristics......................................................................34
Pre-Surgical Hypothesis Testing and Evaluation of Research Questions..............37
Post-Surgical Sample Characteristics....................................................................40
Post-Surgical Hypothesis Testing and Evaluation of Research Questions............42
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CHAPTER 4: DISCUSSION
Summary of Findings.............................................................................................48
Study Limitations...................................................................................................57
Conclusions and Future Directions........................................................................58
References......................................................................................................................................60
Vita Auctoris..................................................................................................................................72
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LIST OF TABLES
Table 5: Pre-Surgical and Post-Surgical z-Scores for the ANT and BNT...........................43
Table 6: Pre-Surgical and Post Surgical ANT and BNT Score Comparison.......................44
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LIST OF FIGURES
Figure 1: Group BNT Mean Raw Scores at Pre-surgical and Post-surgical Testing............44
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CHAPTER 1: INTRODUCTION
utilizing valid assessment tools becomes imperative. The impetus for the present study was to
investigate TLE pre-surgical and TLE post SAH language assessment by examining performance
on a well-established visually based measure of anomia, the Boston Naming Test – Second
Edition (BNT-2; Kaplan, Goodglass, & Weintraub, 2001) and a new auditory-based measure of
anomia, the Auditory Naming Test (ANT; Hamberger & Seidel, 2003). Prior to describing the
current study, relevant literature will be reviewed including a brief overview of epilepsy,
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language assessment in TLE, selective procedures and postoperative language outcomes, and
(Engel, 2013). The incidence of epilepsy tends to be highest at the extremes of age, with
of epilepsy (Lee, 2010). The burden of disease is high, especially due to the psychosocial
morbidity experienced among individuals with intractable epilepsies (Begley et. al., 2000).
Epileptiform activity negatively impacts behavior and cognition, which often results in
psychological functioning (Lee & Clason, 2008). Though many individuals may achieve seizure
control with use of antiepileptic drugs, an estimated 30% of individuals with epilepsy are
achieve seizure control after adequate trials of two or more antiepileptic medications (Lezak,
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Of the types of epilepsy syndromes, temporal lobe epilepsy (TLE) is particularly resistant
uncontrolled TLE have demonstrated risk for cognitive decline along with structural and
metabolic abnormalities (Nearing et al., 2007; Bernhardt et al., 2009), which are related to
seizure frequency and duration of epilepsy (Coan, Appenzeller, Bonilha, Li, & Cendes, 2009).
Further, neuroimaging studies using positron emission tomography (PET) and functional
magnetic resonance imaging (fMRI) have shown that functional abnormalities may extend
beyond the temporal lobes resulting in widespread dysfunction in chronic TLE (Arnold et al.,
1996; Mueller et al., 2004). Due to the deleterious psychosocial and cognitive effects associated
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with uncontrolled TLE, surgical intervention is often warranted to remove the site of seizure
tissue resected, more selective procedures that spare cortical tissue, such as the selective
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amygdalohippocampectomy (SAH) are often employed in epilepsy surgery (Brandt et al., 2013;
Oliver, 2000; Wiebe, Blume, Girvin, & Eliasziw, 2001). Post SAH outcome studies have
demonstrated that the procedure results in positive outcomes and decreased seizure burden for
individuals with medication refractory TLE (Brandt et al., 2013). As more selective procedures
are increasingly used for the treatment of refractory TLE, research concerning the outcome of the
procedures with respect to cognitive functioning has become more prevalent, though several key
As noted by Dodrill (2004), seizures are one indication of an abnormal brain, but they are
not the only indication. Indeed, characterizing the impact of seizure activity on cognition is of
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particular importance for managing treatment and choosing appropriate interventions for those
with epilepsy. Neuropsychological assessment allows for the measurement of brain integrity in
those with epilepsy, and provides a means of assessing the severity, type of deficit present, and
the relationship between disease and everyday adaptive functioning (Lee & Clason, 2008).
integral tool for treatment planning, especially in medication refractory cases. In the pre-surgical
cognitive functions affected by the area of seizure focus (Lee, 2010). Further, the assessment
can be used to indicate whether neurosurgical intervention may result in losing or diminishing
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the identified cognitive functions (Lee & Clason, 2008). Post-surgical assessment can identify
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changes in cognitive functioning from pre-surgical assessment, which can aid in directing
between language function and site of seizure focus. A major goal of the neuropsychological
evaluation is to characterize the impact of seizure activity on language functioning due to the
relationship between language impairment, activities of daily living, and quality of life. Further,
losing or diminishing the functions associated with the seizure focus, and thus site of tissue
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Epilepsy
Epilepsy is the term used to describe a brain disorder characterized by recurrent seizures
neuronal activity (Lee & Clason, 2008). The term epilepsy is differentiated from a seizure in that
seizure refers to a single event, whereas epilepsy is a recurrent and chronic disorder. As such, a
diagnosis of epilepsy requires the presence of at least two unprovoked seizures (Lezak et al.,
2012). Epilepsy refers to a heterogeneous class of disorders with varying etiology, anatomical
involvement, and seizure semiology. The underlying causes are many, such as lesions or brain
injury from birth trauma, traumatic brain injury, tumor, consequences of infection or illness,
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stroke, metabolic disorder, progressive degenerative brain disease, and many other factors
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including genetic predisposition (Lezak et al., 2012).
Epilepsies are generally classified along two dimensions - whether the seizures are focal
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or generalized, and whether their etiology is known, suspected, or unknown (Lezak et al., 2012;
International League Against Epilepsy, 1989). Seizures occurring in a constrained location, and
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beginning with symptoms of a localizable brain disturbance, are referred to as partial seizures.
Partial seizures arise from a specific brain region, may involve only one mode of expression
(e.g., motor, somatosensory, autonomic, or psychic), and may occur with or without loss of
consciousness. When altered consciousness is associated with focal seizure activity, the seizures
are referred to as complex partial seizures. Epidemiological studies suggest nearly 60% of
individuals with epilepsy experience partial seizures (Lee, 2010). Seizure activity with the
Importantly, seizures may begin as a simple partial seizure, and then develop into a complex
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generalization. Generalized seizures are slightly less common than partial seizures, with
generalized seizures (Lee, 2010). Additionally, individuals may present with the clinical
symptoms of a seizure, but lack the detectable synchronous changes in EEG activity associated
with epileptic seizures. These are referred to as non-epileptic events, and often have a
seizure disorder. The majority of seizures are classified as idiopathic, which refers to having no
known etiology and not typically associated with another neurological disorder (e.g.,
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degenerative process). In practice idiopathic classification is commonly assumed to be
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associated with an underlying genetic etiology (Lee & Clason, 2008). Seizures are classified as
cryptogenic when an underlying pathology is assumed, but cannot be identified as in the case of
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some developmental anomaly, structural malformation, or lesion. Cryptogenic epilepsy is
generally thought to be the result of some form of developmental cortical abnormality that
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formed during fetal development (e.g., cortical dysplasia, polymicrogyria, neuronal migration
disorger; Lee, 2010). Finally, the etiology may be symptomatic when the etiology is known, and
The International League Against Epilepsy recognizes two main types of temporal lobe
epilepsy: mesial temporal lobe epilepsy (MTLE) characterized from seizure activity arising from
the hippocampus, parahippocampal gyrus, and amygdala, and the more rare lateral temporal lobe
epilepsy with seizure activity arising from the neocortex (Engel, 2013; Jackson, Briellmann, &
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Kuzniecky, 2005). The temporal lobes are the most frequent location for the occurrence of
partial seizures, and seizures arising from temporal lobe structures account for 40-60% of all
individuals with a diagnosis of epilepsy (Lee & Clason, 2008). Additionally, TLE is one of the
Seizures originating in the temporal lobe structures may be simple partial seizures often
secondarily generalized tonic-clonic seizures. Mesial temporal lobe seizures typically begin with
an aura, particularly when the etiological mechanism is hippocampal sclerosis (HS; Lee &
Clason, 2008). The most common simple partial seizure semiology in MTLE is an aura
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characterized by epigastric distress, often described as a rising sensation similar to nausea (Lee,
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2010). Other auras described as a strange bodily sensation or feeling, auras of fear, gustatory and
olfactory auras, and auras with experiential phenomenon have been reported but are less
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common (Lee, 2010). Quesney (1986) reported auras in 67% of patients with TLE. In
comparison, complex partial TLE seizures are typically characterized by an aura of epigastric
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rising, followed by altered awareness, arrested activity, head deviation or staring, and oral or
motor automatisms (e.g., lip smacking, blinking, rubbing of fingers, etc.). Though altered
consciousness is a characteristic of complex partial seizures, and may occur in right hemisphere
TLE or left hemisphere TLE, loss of awareness in more common in left MTLE. The postictal
particularly if the seizure is originating from the language dominant temporal lobe (Lee, 2010).
Also, contralateral upper extremity hypokinesia is common and tends to be short lasting
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The most common etiology of MTLE is due to mesial temporal lobe sclerosis (MTS),
with the hippocampus typically most affected. The mesial temporal lobe structures are highly
sensitive to noxious stimuli that may cause sclerosis (Lee & Clason, 2008). Sclerosis of the
mesial temporal lobe is characterized by hippocampal neuronal loss, hippocampal volume loss,
mesial temporal lobe gliosis, and variable neuronal loss in the amygdala, parahippocampal gyrus,
and entorhinal cortex (Lee, 2010). Mesial temporal sclerosis or hippocampal sclerosis is
generally considered to be a highly epileptogenic lesion (Jackson et al., 2005). The terms
‘hippocampal sclerosis’ and ‘mesial temporal sclerosis’ have been used interchangeably in the
TLE literature. In the present manuscript the term ‘hippocampal sclerosis’ will be use only when
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the hippocampus is being referred to, and ‘mesial temporal sclerosis’ will be use when referring
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to gross abnormalities of the mesial structures. Though signs of (MTS) can often be visualized
on clinical structural MRI, a diagnosis of MTS or HS is typically not given until pathology
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examination of the tissue excised from individuals with TLE.
The less common neocortical lateral temporal lobe epilepsy cases tend to have a slightly
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different seizure semiology than that seen in MTLE. Lateral temporal lobe epilepsy typically
begins with a partial seizure experienced as an aura (Lee, 2010). The type of aura experienced is
dependent on the seizure location in the cortical tissue of the temporal lobe. Common auras
experienced in lateral temporal lobe epilepsy may include auditory hallucinations, visual
misperceptions, or dysphasia when seizure focus is the language dominant hemisphere (Lee &
Clason, 2008; Lee, 2010). The simple partial seizures may progress into more widespread
complex partial seizures, though impairment in consciousness is less common in lateral temporal
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Neuropsychological Functioning in Persons with Temporal Lobe Epilepsy
examined extensively (Taylor, Kolamunnage-Dona, Marson, Smith, Aldenkamp, & Baker, 2010;
Helmstaedter, Kurthen, Lux, Reuber, & Elger, 2003). Several factors that appear to contribute to
cognitive dysfunction in those with TLE include the side effects of antiepileptic medication (e.g.
cognitive slowing), the underlying etiology of the epilepsy, psychosocial issues, and the
accumulating effects of excitotoxicity from recurrent seizures (Lee, 2010; Kwan & Brodie, 2001;
Meador, 2002; Aldenkamp & Bodde, 2005). Other factors including age of onset (Baker, Taylor
& Aldenkamp, 2011) and subsequent degree of functional reorganization (Griffin & Tranel,
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2007) also appear to influence neuropsychological functioning. Importantly, a number of studies
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have implicated cognitive impairments are already present in individuals with epilepsy before
beginning antiepileptic drug (AED) treatment, and following few seizures (Prevey et al., 1998;
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Aikia et al., 2001, Pulliainene et al., 2000). These findings suggest cognitive impairment may
also be a result of eliptogenesis and not just seizure chronicity or AED use (Taylor et al., 2010).
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Although the cognitive deficits experienced by those with TLE are quite variable, TLE tends to
have a more consistent cognitive profile when compared to other epilepsy syndromes.
Generally, TLE is associated with deficits in learning and memory, expressive language (e.g.,
naming and fluency), psychomotor speed, and sustained attention (Lee & Clason, 2008; Lee,
2010).
Oyegbile et al. (2004) investigated the nature and degree of cognitive morbidity in
individuals with chronic TLE compared to demographically matched healthy individuals. Their
study included 96 individuals with a diagnosis of TLE and 82 healthy control participants who
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neuropsychological testing indicate that when compared to healthy controls, individuals with
TLE exhibited significantly worse memory functioning (WMS-III General Memory Index,
Immediate Memory, Auditory Memory Index, Visual Memory Index), and poorer performance
across indices of intelligence (WAIS-III VIQ, PIQ and FSIQ), language (Boston Naming Test,
COWAT), executive function (WCST-64, Stroop Test), psychomotor processing (Trail Making
Test A and B), and fine motor dexterity (Grooved Peg Board). Calculation of an Impairment
Index specifying the proportion of test measure outside the normal limits for each individual
indicated that 30% to 45% of all measures in the neuropsychological test battery were in the
impaired range in the TLE group. Further, the degree of impairment on these measures was
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always greater when compared to the healthy control group. The reported widespread cognitive
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impairment in TLE demonstrates the deleterious effect of chronic seizures on cognition beyond
those domains mediated by the temporal lobes. Consideration of moderating factors related to
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cognitive performance in TLE revealed chronicity of TLE was related to a worsening in overall
individual “cerebral reserve”, defined as yeas of formal education. Further, lower educational
neuropsychological deficits associated with left or right MTLE. In their study, a comprehensive
battery of neuropsychological tests was administered to 107 adults with a clear diagnosis of MTL
based on ictal EEG and neuroimaging. Study participants were clear of comorbid neurological
abnormalities on MRI, with the exception of probable MTS. The neuropsychological battery
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