Casebook of Clinical Neuropsychology Edited by Joel E. Morgan Ida Sue Baron Joseph H. Ricker OXFORD 201153 Serial Neuropsychological Assessment in a Case of Huntington Disease David E. Tupper Named after George Huntington (1850-1916), who first described the clinical manifestations of a hereditary chorea that involved twisting and grimacing (Huntington, 1872; Lanska, 2000), Huntington disease is a degenerative neuroge- netic disorder, Huntington disease has been found all over the world, prevalence estimates range from about 5-8 per 100,000, and there is no cure, with relentless progression of symp- toms. It has been seen variously as a subcortical dementia, as a movement disorder, or as a neu- ropsychiatric disorder, depending upon its pre- sentation and primary manifestations. However, toward the later stages of the disorder, many if not most individuals with Huntington will commonly demonstrate the prominent triad of choreic involuntary movements, marked cognitive impairments, and some type of affec- tive or psychiatric disturbance (Folstein, 1989), ‘As an example of the remarkable scientific advances in our un ‘-rstanding of neurogenetic disorders, more thn 100 years after being described as familial by Huntington, the gene responsible for Huntington disease was localized to the tip of the short arm of chromosome 4 in the 4p16.3 region in 1983, and it is now identified by having an excessive number of trinucleotide (CAG: cytosine, adenosine, guanine) repeats in the IT-15 gene. Exon 1 of the gene contains a stretch of the uninterrupted CAG trinucleoide repeats, which encode a protein called hunting- tin, whose function is presently unknown. ‘Huntington disease shows an autosomal dom- inant inheritance pattern, such that each child of isease an afflicted parent has a 50% chance of inherit- ing the gene, and all gene carriers will develop the illness if they live long enough. Normal or asymptomatic individuals have 35 or fewer CAG repeats, whereas Huntington disease is caused by expansions of 36 or more CAG repeats. There is an inverse relationship between CAG repeat number and age of onset, such that'a greatly expanded gene is associated with earlier onset of illness, as well as more rapid progression. A simple and accurate genetic blood test for the CAG repeat length abnormality in Huntington disease is available and is considered definitive for the diagnosis, although the ultimate diagno- sisof Huntington disease in an individual—because it is such a significant life event—should be con- sidered carefully and ethically, preferably with the support and assistance of a comprehensive assessment of relevant genetic, neurologic, emotional, and psychosocial factors (Nance & ‘Westphal, 2002). ‘The age of onset for Huntington disease is most commonly during midlife with symptoms typically beginning during the age range of 35 to 50 years, although both younger and older variants are seen. Adult-onset Huntington disease typically manifests as a triad of symp toms, including a choreic movement disorder, cognitive disturbance, and psychiatric or behav. ioral disorder, although each of these compo- nents separately may be the earliest presenting characteristic. Chorea is common in adults with Huntington disease, and the motor component is characterized by brief, irregular, nonrhythmic 567568 involuntary movements, particularly of the extremities, as well as variable oral motor dysfunction (dysarthria, dysphagia, or drool- ing). Clinically, although chorea is frequently the defining characteristic of Huntington disease, it ig often accompanied or preceded by a cognitive disorder that shows prominent memory and executive dysfunction, as well as by mood disturbance and other psychiatric features such as apathy, irritability, and obsessive-compulsive characteristics. Huntington disease isa disorder that especially involves the basal ganglia and regions in the cere~ bral cortex (Kremer, 2002). Neuropathologically, Huntington disease demonstrates diffuse and regional cerebral atrophy, which is most dramatic in the caudate nuclei and, to a lesser extent, the putamen. Loss of small, spiny, GABA-ergic neu- rons in the dorsomedial aspects of the head of the caudate are noted early in the disease progres~ sion, and later the putamen and complete caudate become involved. Postmortem examinations have revealed that as many as 80% of Huntington disease brains display atrophy of the frontal lobes, and the cerebellum and globus pallidus also show changes. As with some other trinucleotide repeat diseases, neurons show intraneuronal aggregates (inclusions) in nuclei and neuronal processes that are composed of truncated glutamine deriv- atives of the mutant huntingtin protein. ‘The neuropsychological presentation of Hun- tington disease is varied, depending upon the age of the individual, the age at onset of clinical manifestations, the advancement of the disease, and the severity of the genetic mutation (Brandt & Butters, 1996). Neuropsychological assess- ‘ment can assist in the initial diagnosis and func- tional characterization of individuals with Huntington disease, as well as to help track cognitive and other changes over time (Nance & Westphal, 2002). Recently, large-scale studies of the early neuropsychological presentation of individuals with gene-positive but undiagnosed Huntington disease have assisted in clarifying the early neurocognitive changes seen in this disorder and will likely lead to development of predictive batteries for clinical and research use , (Paulsen et al., 2006). Cognitive impairments in Huntington dis- ease may actually represent greater functional Neurodegenerative Disorders impairment for individuals than the motor symptoms, and the severity of the cognitive dis: order has been correlated with the disease dura- tion, extent of subcortical (especially caudate) atrophy, and striatal glucose metabolism rate (Brandt, 1991; Paulsen & Miko, 2008). Intellec- tual and mental status decline is associated with progression and duration of the illness, but the dementia of Huntington disease is frequently described as a subcortical dementia profile and Jacks traditional localizing features such as apha- sia and agnosia (Folstein, Brandt, & Folstein, 1990). Executive dysfunction is prominent and is often attributed to interruption of prefrontal cortex pathways as a result of dorsomedial cau- date degeneration. The memory dysfunction present is characterized by deficits in the reten- tion of new information, and improved perfor- mance is sometimes seen with cuing and on recognition tasks, Attention-demanding cogni- tive operations are ofien the first to deteriorate in Huntington disease, and complex attention tasks are among the most sensitive measures in carly stages. Clinically significant aphasia s rarely seen, but dysarthria and dysprosodia are com- ‘mon, and impaired fluency, naming, and narra- tive expression are often seen. Psychiatricaly, prominent emotional or behavioral symptoms are noted in many individuals with Huntington disease, with mood disturbance and depression most common, and suicidal ideation frequently reported. Apathy, irritability, and inertia are common psychiatric characteristics in Hunting- ton disease, and some individuals develop sig- nificant obsessive-compulsive characteristics, cognitive inflexibility, or even psychotic features (Woodcock, 1999). Case Study: H. D. History H. D. was a 42-year-old female when she was first referred for neuropsychological evaluation. She had a family history of Huntington disease in her father, who died the year before H. D's initial evaluation when he was in his late 605, and in an older brother, who was described at that time as having significant movement and speech problems for many years (he subsequentlySy eselecancisats Serial Neuropsychological Assessment also died). H. D. was sent to a comprehensive Huntington disease clinic for formal neurologi- cal and neuropsychological evaluation after having received a confirmatory genetic test for Huntington disease (CAG repeats = 44) several weeks earlier at a local medical clinic. A head computed tomography (CT) scan completed at an outside facility was described as within normal limits. Her workup for Huntington dis- ease was initiated subsequent to concerns at her job, as she was suspended for not getting her work done in a timely manner about 2 weeks prior to the assessment. With regard to her background, H. D. isin the middle in her family and also has a younger sister who does not have Huntington symptoma- tology. At the time of her initial assessment, she had been married to her husband for 21 years and they had no children. H. D. had a high school education, with no learning problems identified in school, and she also attended a vocational school for 2.5 years. She had worked prior to her assessment in a medium-sized man- ufacturing company providing computer assis- tance for 5 years, and she had worked since her education in similar jobs, with no previous vocational difficulties, Past medical history was basically unremarkable otherwise, with no major medical or psychiatric concerns; she had fainted once due to heat and wore eyeglasses for near- sightedness. She took no regular medications. H. D. spent mosi of her free time in activities with her husband, she walked and exercised frequently, and she liked to be active outdoors. She and her husband also lived in a rural setting, and she had a special interest in presenting show animals. HD. underwent a reasonably comprehensive initial evaluation and completed an interview as vwell as performance-based testing in @ number of neuropsychological domains. ‘The presenting complaint, as she and her husband reported it, was that she had recently been diagnosed with Huntington disease, and that it was causing problems for her at work. Her husband stated that he suspected her of showing changes con tent with Huntington disease several years earlier, and the changes he noted included slight twitching in her fingers, difficulty making deci sions, and sometimes mixing up her words when a Case of Huntington Disease 569 talking. H. D. was described as being very func- tional and capable overall, with very subtle changes only. She was described as very inde- pendent and accepting of her disorder. No major functional concerns were described at home, although she was reported to be perhaps slightly more passive. H. D. presented with slightly choppy speech, with bursts of language, but otherwise showed no visible physical limitations or other problems in casual interactions. Results of H. D's assessment included low- average to mildly impaired intellectual cap- abilities, which were considered reduced from premorbid expectations. She showed well- preserved verbal vocabulary skills, with no overt language problems in most of the testing, but some difficulties with complex verbal reasoning, Motor testing revealed average bilateral grip strength, with marked reduction in motor speed and dexterity, and she was observed to demon- strate mild involuntary choreic movements with no evitlence of voluntary movement disorder seen in apraxia testing. H. D. showed problems with simple and divided attention, practical judgment, and overall organization and imple- mentation of more complex actions and sequences. Memory and learning for both verbal and visual information were moderately to severely impaired with difficulties in both acqui- sition and retention of information. Low-average planning and variable executive capabilities were noted, with some evidence of perseverative responding. No overt psychopathology was identified in either interview or by self-report endorsements, although H. D. reported very mild depressive tendencies, H. Di evaluation results were thought to suggest evidence of moderate intellectual impair- ment relative to premorbid levels, as well as more specific deficits in coordinated motor activities, earning and memory, and executive capabili She showed a rather unusual pattern of greater verbal than nonverbal dysfunction for an indi- vidual with Huntington disease, and this was interpreted as indicative of her problems with expressive language skills, fluency, and verbal memory, Her results were felt to be consistent with early-stage Huntington disease, and her impairments in memory and motor skills in particular were felt to present notable difficulties es.570 for her in her job performance. It was thought that she would not be capable of returning to her previous job, and that it may be difficult to develop a modified position that could com- pletely accommodate her deficits and needs. Based on the genetic confirmation of H. Dis Huntington disease, as well as the neuropsycho- logical documentation of her functional di abilities and her job performance problems (particularly slowness in task completion), she was considered disabled from her job. Following the evaluation, H. D. remained living with her husband, who provided supervi- sion for her on an informal basis, although he also worked a full-time job. H. D. and her hus- band continued to live together in a rural home, and they tried to participate in activities that optimized her quality of life, such as frequent traveling together. H. D. did not have very close contact with her other family members, so her husband was her major support system. She did not leave her home very often without him, and she spent most of her time caring for their show animals. When questioned about her usual activities, H, D. basically reported fairly ‘Table 53-1. Longitudinal Findings for Select Neuropsychological Measures in Case H. D. Neurodegenerative Disorders” repetitive and stereotyped daily activities, and otherwise she stated that she spent most of her time alone reading. ss Serial Assessments In rather unusual circumstances, H. D. has access to partial salary continuation as part of a long-term disability insurance plan that her company had and that she had purchased prior to becoming symptomatic. However, that program requires documentation of her con- tinuing functional vocational disability on an annual basis, which has occurred with neurop- sychological reevaluation. Beginning approxi. mately 41 months after her initial assessment, H. D. returned to complete annual neuropsycho- logical evaluations, which have taken place for about 10 consecutive years since then. Thus, HD. has been evaluated 11 different times to date, over a time frame of about 13% years, as she has aged from 42 to 56 years. ‘ Table 53-1 presents the data from select neuropsychological measures for all of the eval- uations H. D, has completed to the present time, Evaluation Number 123 4 5 6 7 8 9 0 W H. Dis Age at Testing a 47 48 49 50 Sl 52 53 St 55 56 (Wears) Intellectual Skills (WAIS-R, WASD) Pull Scale 1Q a1 85988910083 BF 9287 8B Verbal 1Q 82 87 100 92 103 «77 G88 HHL Performance 1Q 87 848589 H BOT BT HTT Complex Attention and Sequencing (Irail-Making Test, completion time in seconds) Trails A “4 41 4 60 65) «7308878977 Trails B 140-172-142 294-202-192, 472287300300 Manual Dexterity (Grooved Pegboard, completion time in seconds) Right Hand 98 97 128 99 «106 «110125105 18159 HAT Left Hand 94 114 105 117, «:105-—123-S137189 184195168 Verbal Expressive Fluency (COWA, no. of words) Letter Fluency 3025 «209 SH Category Fluency Op to 0 = tb Gin Constructional Skills (Rey-Osterreith Complex Figure) Copy Score 210 265 225 225 2.0 140 195 270 230 200 125 ‘Visual Memory (Rey Complex Figure) Delayed Recall Score __—sS—7.0_7.0 80403595 1308'S 0 (Continued)Serial Neuropsychological Assessment in a Case of Huntington Disease 571 Table 53-1. Longitudinal Findings for Select Neuropsychological Measures in Case H. D.(Continued) Evaluation Number 123 4 5 8 9 wo Verbal Memory (CVLT/CVLT-II) ‘Trials 1-5 Total Score 2 39 31 7 2 B13 2 Ww mM BR LDFR 2° 6 4 3 2 4 2 2 pies eae Executive Function/Mental Shifting (Wisconsin Card-Sorting Test) Perseverative Responses 32 80_—«13__—«d16 7 eer Rae 21 RRREE 17 PEN 47 ene GO ‘Note, Rav or calculated scores are provided to emphasize actual performances, with standardized scores as appropriate ‘The measures in the table provide consistent quantitative information about a number of neu- ropsychological domains and, although some variations in exact test versions have been used. from time to time, there has been fairly good consistency in the results obtained. The data in the table are provided in raw (or calculated) score form, to demonstrate the actual level of performances by H. D. over time. Perusal of the table suggests that H. D. has shown a great deal of variability in her perfor- mances over time, although there is a general downward trend (that is, poorer performances) for many but not all of the measures included. Thus, H. D. has shown relatively stable overall intellectual capabilities, as reflected in her Full Scale, Verbal, and Performance 1Q scores on the Wechsler scales; this stability probably repre- sents the fact that these scores are for more “crystallized” or well-learned capabilities, and also that H. D. actually showed some intellectual compromise compared to premorbid expecta- tions in her initial assessment. Clearly, any mea sures that are dependent on motor skill, speed, or verbal expression (e.g, COWA, Trail Making , Grooved Pegboard, Copy of Rey Complex Figure) have been impaired in all assessments but show genetally progressive decline longitu- dinally, with slower motor performances and greater impairment in fluency of verbal or manual expression, Memory is also a domain notably affected for H. D., and both verbal and visual memory are poor and have progressively deteriorated. Objective evidence of problems with mental shifting as a component of executive dysfunction is noted in H. D's increasing prob- Jems with divided attention on Trails B and increased perseverative responding on the ‘Wisconsin Card Sorting Test. Aside from the neuropsychological documen- tation of her condition over time, several other factors have potentially impacted the manifesta- tions of her Huntington disease during this 10-year time frame, H. D’s husband died sud- denly and unexpectedly between the time of her fifth and sixth evaluations. Because of their very close, and obviously dependent relationship, and the fact that she was living independently with his assistance, it was anticipated by clinic staff that she would need additional support and pos- sibly an out-of-home placement. Interestingly, H. D. has been able to maintain her own home with the assistance of several very devoted and kind neighbors who have assisted her. For sev- eral years after her husband's death, H. D. visited the home of a close friend and neighbor and assisted in a home-based sales business on a reg- ular, almost daily, basis, which provided her a way to remain active and productive, and also to receive informal assistance and supervision for her own needs. ‘This was not a formal relation- ship but served H. Dis needs for several years until her friend moved away and the business went bankrupt. Unfortunately, H. D. does not have similar close relationships with others (including family), and she has increasingly remained alone in her own home, as she does not leave the house on her own very frequently and does not often socialize. She reports that she continues to drive, although it is only during the summer months, and only to go to the store. In addition to H. Dis increasingly precarious psychosocial situation soon after her husband died, she self-initiated alternative treatments consisting of herbal drinks, vitamins, and monthly acupuncture. H. D. has become increas- ingly stuck on the idea that these alternative treatments not only are helping her, but have572 essentially stopped the progression of her Huntington disease symptomatology, in spite of the fact that others note continued progression of her disorder. Comparison between Initial and Most Recent Evaluations ‘The first and most recent evaluations for H. D.can be compared to show perhaps more qualitatively the overall deterioration evident in her findings. Table 53-2 shows the complete evaluation data from H. D’s first and eleventh neuropsychologi- cal assessments, with all test data included. For additional qualitative perspective, Figure 53-1 provides examples of H. Dis performances for the copy trials of the Rey Complex Figure during both evaluations, and Figure 53-2 shows exam- ples of her current writing and copying capabili- ties during the most recent assessment. ‘A review of Table 53-2 clearly demonstrates that H. D. has shown substantial change over time in several domains of functioning, such as her verbal expressive skills, motor speed and dexter- ity, visuospatial organization and visual memory, retention of both verbal and visual information, and aspects of conceptual and executive function- ing. In formal testing, H. D. demonstrates impair- ments in any type of speeded activity, such as on the Trail Making Test, where her simple sequenc~ ing time on Part A doubled, and her Part B per- formance, reflective of the additional divided attentional component, not only became slower but she ultimately was unable to complete the task within the time limit and made three sequencing errors. Memory retention has decreased signifi- cantly over time, and now H. D. is only able to correctly recall several words from the CVLT-IL list after a delay and has limited accurate recall (less than 50%) of the Rey figure over time: She has become increasingly perseverative over time, and she now is more limited in her conceptual capabilities and practical judgment, as reflected in her limited category attainment on the WCST and her poorer performance on the Cognitive Estimation test. As previously, H. D. denied any significant symptomatology on her completion of . the Symptom Checklist-90 Revised and the Fron- tal Systems Behavioral Examination, while a neighbor endorsed mild problems with working memory and shifting her behavior. ‘Most Recent (#11) Evaluation Results in Case H. D: (Conducted 13 Years apart)* 3 Evaluation Evaluation’ #1 #1 General Cognitive/iIntelligence WAIS-R/WASI FSIQ VIQ PIQ Vocabulary Similarities Block Design Matrix Reasoning Attention WAIS-R/WAIS-IIT Digit Span ‘Trail Making Test (in seconds) Part A Part B Language Controlled Oral Word Association (no. of words) Letter Fluency Category Fluency Memory CVLTICVET-I ‘Trials 1-5 Total SDFR SDCR LDFR LDCR Recognition Hits alse Positives Rey Complex Figare Copy Score Immediate Recall Delayed Recall Recognition Total Motor/Visuo-Motor Dynamometer (grip strength in kg) Right Hand Left Hand Binger Tapping Test (mean no. of taps) Right Hand Left Hand 35(P=4r 84 7 2 31 87 7 10 7 7 BN 9(783B) 6 (5% 3B) 44( 140(T 3) 81 (T=26) 27) 300+ (T=9) © 33 9 15 7 22(T'=5) 4-4) 4(-5) 2(-5) 3(-8) 4) 4G) 21.0 125 110 50 us 60 = 15 36 (I'=59) 34 (T= 58) an(r=44) 21 (T= 24) 19(P=17) (Continued)© Table 53-2. Comparisons between Initial (#1) and Most Recent (#11) Evaluation Results in Case H. D. (Conducted 13 Years apart)*(Continued) Evaluation Evaluation #1 al Grooved Pegboard (completion time in seconds) Right Hand Left Hand 98(T=21) 141 (T=20) 94(T=30) 163 (T= 25) = Apraxia Screening 18 18 (maximum = 18) Conceptual/Executive ‘Tinkertoy Test 4 3 (complexity score) Cognitive Estimation Test 6 10 (deviation score) Porteus Mazes (Test 2 - Quotient) DKEFS Tower - 9 (achievement) Wisconsin Card-Sorting Test Categories achieved 6 1 Errors 51 "4 Perseverative responses 32 46 Behavioral/Emotional Ratings Frontal Systems Behavioral Examination (FrSBe)- self and informant ratings Symptom Checklist 90-Revised = : *Raw or calculated scores are listed, with standardized scores (5, T.2) as appropriate. At the time of this most recent evaluation, IL D. by observation also showed more promi- nent choreic movements than during her earlier assessments, and these have begun to affect her writing and drawing skills (see the repeated patterns copying, for example, in Figure 53-2), Interestingly, H. D. does not appear to demon- strate any clear apraxia or voluntary movement difficulties, as seen in her basically intact per formance for a brief quantitative screening measure, but her involuntary movements have increased in frequency and intensity and affect her motor coordination, dexterity, and speed. Serial Neuropsychological Assessment in a Case of Huntington Disease * 573 (b) Figure 53-1. Copy of the Rey-Osterreith Complex Figure by Case H. D. during the initial (a) and most recent (b) evaluations. hecy EF THES ANH OD © ye shoved THE Weaken G “tHE ARLIWES oo miTe Med OEP » © Pu PLU nw" mune w PAW Figure 53-2. Qualitative examples of Case H. D's graphomotor skills (a) and repeated patterns (B) ducing the most recent evaluation (#11).574 However, H. D. does show delayed responses and problems in motor initiation, noted by observation and during testing. No unusual motor asymmetries have been detected through- cout her various assessments. In. addition, H. D. is noted to be showing increasing dysarthria, which hhas made completion of some of her verbal test- ing rather difficult. She currently speaksin shorter bursts of language than she did during earlier assessments, and she is only about 50%-75% intelligible overall, although there are some times in which she has perfectly clear speech for brief durations. To help compensate, she sometimes subvocalizes a response repetitively before pro- ducing it in louder form. Her prominent motor difficulties therefore are increasingly affecting not only her manual activities and gait but also her verbal communication. Psychologically, H. D. has been demonstrat- ing increasing concerns. During the interview as part of her most recent assessment, she directly denied any increasing symptoms, including any of the motor, cognitive, or other changes that were notable to the examiner who had worked with her in previous assessments. H. D. appeared to downplay the significance of her pronounced symptoms at this more progressed point and stated that she had no safety issues living by herself, Although frequently seen in individuals with Huntington disease, H. D. has consistently denied any depression or suicidal ideation. Her affect—although difficult to assess accurately— was rather flat, and she had rigid facial expres sion. Repetitive actions such as repeatedly looking into her mailbox were described by her neighbor for her, although H. D. denied similar concerns. As noted previously, HD. has become mentally stuck on the idea that her symptoms have been stopped with her alternative treat- ments, and her cognitive inflexibility is apparent in her denials of current concerns. H_D. is currently in the mid to later stages of the progression of her Huntington disease. She currently continues to live independently but is rather precarious, and she could be considered somewhat ofa recluse. At the time of this most recent assessment, it was felt that she showed further advancement in the progression of her Huntington disease, and that she was moderately to severely disabled by the combination of impairments she demonstrated. Greater risk of Neurodegenerative Dison safety-related problems was felt to be presen with H. D. advancing to the point where: would soon need greater daily supervision assistance, and where independent livin 8 soon not be possible: a Comments world. The clinical presentation and progression of her Huntington disease demonstrates notable variability, but yeta course of steady decline oyer. the years, H. D. has been evaluated neuropsy= © chologically during the early and middle stages of the progression of her disorder and-has. shown both objective quantitative changes con: sistent with advancing Huntington disease and qualitative motor and psychological changes that are typical in this condition. H. D. was mildly. to moderately disabled at the time of her initial © = neuropsychological assessment, and she hada family history and genetic testing evidence of > the presence of Huntington disease. ‘Thus, the serial neuropsychological evaluations conducted for H. D. have not been for diagnostic purposes, but rather for descriptive purposes to docu: ment the progression of her disorder. To date, = = although she has continued to live fairly inde= = pendently, H. D. will soon be advancing to the: = later stages of the disorder, which will create" = more significant functional disability in her daily. life and may lead to loss of her ability to live on her own. : H. D. has demonstrated the triad of motorig, = cognitive, and psychological impairments that is on frequently seen in individuals with Huntington disease. Her dementia would be considered @ subcortical dementia as she shows a combina= tion of attentional, memory, and executive dys-- function, along with her involuntary movement disorder, but has less affected crystallized intel: lectual skills, Formal neuroimaging has not beet completed recently for H. D., but the usual neu: ropathological changes in striatal structures and connections would be expected for her, along. with likely developing cortical pathology. It i8 anticipated that H. D. will soon become more difficult to assess quantitatively, so additional comprehensive neuropsychological evaluations may not occut.Serial Neuropsychological Assessment in a Case of Huntington Disease 575 References Brandt, J. (1991). Cognitive impairments in Hunting- tonls disease: Insights into the neuropsychology of the striatum. In F, Boller & J. Grafman (Eds.), Handbook of neuropsychology (Vol. 5, pp. 241-264). Amsterdam: Elsevier. Brandt, J, & Butters, N. (1996). Neuropsychological characteristics of Huntington’ disease. In I. Grant & K. M, Adams (Rds), Neuropsychiatric assessment of neuropsychiatric disorders (2nd ed., pp. 312-341). New York: Oxford University Press. Folstein, S. E. (1989). Huntingtons disease: A disorder of families, Baltimore: Johns Hopkins University Press Folstein, S. E. Brandt, J., & Folstein, M. B. (1990). Huntington’ disease. In J. L, Cummings (Ed.), Sub- cortical dementia (pp. 87-107). New York: Oxford University Press. Huntington, G. (1872). 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