AUDITORY AND VISUAL NAMING IN TEMPORAL LOBE EPILEPSY: AN

EXAMINATION OF DYSNOMIA AT BASELINE NEUROPSYCHOLOGICAL

ASSESSMENT AND FOLLOWING SELECTIVE

AMYGDALOHIPPOCAMPECTOMY IN

PATIENTS WITH LEFT AND RIGHT

TEMPORAL LOBE EPILEPSY

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Evan T. Schulze, B.S., M.S.

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A Dissertation Presented to the Graduate Faculty of

Saint Louis University in Partial Fulfillment
of the Requirements for the Degree of
Doctor of Philosophy

2016
 ProQuest Number: 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

Associate Professor Nicole J. Werner

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 ACKNOWLEDGMENTS

I am very grateful for the support of my dissertation committee in the development,

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

unwavering support throughout my journey in pursuing a doctoral degree in clinical psychology.

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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 1: Pre-Surgical Temporal Lobe Epilepsy Sample Characteristics.............................35

Table 2: Pre-Surgical Scores on Neuropsychological Measures.........................................36

Table 3: Convergent and Discriminant Validity Evaluation................................................38

Table 4: Post-Surgical TLE Sample Characteristics............................................................42

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

Table 7: Reliable Change Analysis......................................................................................46

Table 8: Hippocampal Sclerosis Post-Surgical ANT and BNT Score Comparison............47

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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

Given the role of language assessment in determining neurosurgical candidacy, type of

neurosurgical intervention, and prediction of post-surgical language outcome, the importance of

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

methods for assessing cognitive change in TLE.

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Epilepsy is among the most prevalent of all neurological disorders for adults and
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children, affecting approximately 1-3% of the U.S. population or nearly 2.5 million Americans

(Engel, 2013). The incidence of epilepsy tends to be highest at the extremes of age, with

epidemiological studies reporting as high as 3% of the population by age 75 received a diagnosis

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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

downstream consequences on educational attainment, employment, social adjustment, and

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

pharmacoresistant, and are termed refractory or intractable epilepsies, defined as failure to

achieve seizure control after adequate trials of two or more antiepileptic medications (Lezak,

Howison, Bigler, & Tranel, 2012; Lee, 2010).

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 Of the types of epilepsy syndromes, temporal lobe epilepsy (TLE) is particularly resistant

to pharmacological treatments (Jokeit & Shacher, 2003). Studies of individuals with

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

activity (Kwan & Brodie, 2002).

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Recent advances in neuroimaging and surgical techniques have improved the surgical
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treatment of epilepsy. Because of the relationship between cognitive decline and amount of

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

areas, including naming outcome, have seen less investigation.

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).

Neuropsychological assessment is considered part of standard clinical care in TLE, and is an

integral tool for treatment planning, especially in medication refractory cases. In the pre-surgical

context, the goal of a neuropsychological assessment is to identify anatomical regions and

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

therapies in cases of cognitive decline.

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The assessment of language functions is a standard part of the neuropsychological

assessment for pre-surgical and post-surgical evaluations in refractory TLE. Language

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assessment is of particular importance in TLE due to the possible functional-anatomical overlap

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,

characterization of language functioning in TLE is important in determining candidacy for

surgical intervention in refractory TLE. Language assessment may be used to determine if

losing or diminishing the functions associated with the seizure focus, and thus site of tissue

removal, may result in aphasia (Lee & Clason, 2008).

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 Epilepsy

Epilepsy is the term used to describe a brain disorder characterized by recurrent seizures

as a result of excessive electrical discharge in the brain due to temporary synchronization of

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

simultaneous involvement of both brain hemispheres are called generalized seizures.

Importantly, seizures may begin as a simple partial seizure, and then develop into a complex

partial seizure, and progress to bi-hemispheric involvement, a process referred to as secondary

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generalization. Generalized seizures are slightly less common than partial seizures, with

epidemiological studies suggesting approximately 40% of individuals with epilepsy experience

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

psychiatric etiology (Lee & Clason, 2008).

Further classification of epilepsy is intended to reflect the proposed etiology of the

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

may be attributed to a structural abnormality or neurological illness (e.g., vascular malformation,

traumatic brain injury, progressive neurodegenerative diseases).

Temporal Lobe Epilepsy

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

most common medically intractable seizure disorders (Jackson, et al., 2005).

Seizures originating in the temporal lobe structures may be simple partial seizures often

termed an aura, complex partial seizures characterized by an alteration of consciousness, or

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

phase is characterized by gradual reorientation and possibly some language dysfunction

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

(Jackson, Briellmann, & Kuzniecky, 2005).

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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

lobe epilepsy compared to MTLE (Lee, 2010).

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 Neuropsychological Functioning in Persons with Temporal Lobe Epilepsy

The impact of chronic, uncontrolled TLE on neuropsychological functioning has been

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

were assessed with a comprehensive neuropsychological battery. Results of the

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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

neuropsychological status. This relationship appears to be partially mediated by the degree of

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individual “cerebral reserve”, defined as yeas of formal education. Further, lower educational

attainment and increased chronicity of TLE resulted in greater neuropsychological impairment.

These results point to the widespread neuropsychological impairment experienced in chronic

TLE despite the focal seizure process.

Similarly, Hermann, Seidenberg, Schoenfeld, and Davies (1997) investigated the

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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