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Correlates of early disability in Huntington's disease.

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Correlates of Early
Disability in
Huntington’s Disease
Richard Mayeux, MD,’ Yaakov Stern, PhD,*
Andrew Herman, MA,? Linda Greenbaum, MD,*
and Stanley Fahn, MDX
Functional disability in Huntington’s disease usually results from a combination of the movement disorder, intellectual decline, and psychopathological changes, but
the unique contribution of each element has never been
investigated. The Shoulson-Fahn functional capacity
rating scale measures independence in such daily activities as eating, dressing, and managing personal finances,
and is used to stage the illness and follow its progression.
To determine which problems contribute most to reduced functional capacity as the disease evolves, we reviewed the records of 48 consecutive patients who were
evaluated for intellectual and emotional status and
motor disability. Each patient was staged and rated for
functional capacity at the time of the examinations.
Thirty-three of these patients were followed over several years with repeat evaluations at 6-month intervals.
Intellectual impairment and depression correlated significantly with reduced functional capacity. However,
when the somatic symptoms of depression were eliminated from the analysis, its relationship to functional
capacity was no longer significant. Duration of illness,
motor disability, and age at onset also had little impact.
Neuropsychological test performance and functional capacity deteriorated over time. Our data suggest that intellectual impairment is a major factor in reducing functional capacity in the early stages of Huntington’s
Mayeux R, Stern Y, Herman A, Greenbaum L,
Fahn S: Correlates of early disability in Huntington’s
disease. Ann Neurol 20:727-731, 1986
Dementia is an inevitable consequence of Huntington’s disease (HD), but physicians usually require the
presence of chorea to confirm the diagnosis [ S , 10, 11,
13, 15, 16, 18,231. As the disease progresses, involuntary movements and gait and postural changes contribute to the overall disability. Patients stop working and
require help with activities of daily life early in HD,
however, even though motor disability may be min-
From the Departments of *Neurology and $Medicine, College of
Physicians and Surgeons, Columbia University; and the tDepartment of Psychology, City College of New York, New York, NY.
Received Dec 27, 1985, and in revised form Feb 28 and Apr 4,
1986. Accepted for publication Apr 4, 1986.
Address reprint requests to Dr Mayeux, Neurological Institute, 710
West 168 St, New York, N Y 10032.
imal. It is not clear whether this difficulty in occupational and domestic skills is the result of impaired
motor function or due to changes in intellect or mood
[4, 10-131. Selective impairment of recent memory is
seen soon after diagnosis, suggesting that intellectual
impairment may be the first cause of disability, followed later by motor dysfunction (6-131.
Shoulson and Fahn [30} developed a scale to measure disability in HD by rating functional activities of
daily living, such as dressing, eating, and managing personal finances. The scale can also be used to describe
stages of the illness [30} by measuring the rate of decline in “functional units” per year f37 and evaluating
the response to medication 128); it may also be correlated with anatomical or radiological features (3 11.
The reliability and validity of this scale have been established (291.
All clinical manifestations of HD contribute to the
loss of functional capacity, but we wondered whether
changes in intellect or mood might impair activities of
daily life early in the illness.
Materials and Methods
The records of 48 patients with HD seen at the ColumbiaPresbyterian Medical Center by two neurologists (R. M. and
S. F.) over eight years were reviewed. Age at onset was
defined as the time when the first symptom was noted by
either the patient or the patient’s advocate; the symptoms
were either motor, cognitive, or emotional. Age at diagnosis
was defined as that recorded when the diagnosis was confirmed by a physician. Information about alcohol use and
head injury was obtained because either might affect cognitive function. We also arbitrarily defined head injury as a loss
of consciousness lasting a minute or more following trauma,
and alcohol abuse as greater than 90 ml of alcohol consumed
The examination format remained standard throughout
the period reviewed. At each examination mental status was
examined, chorea and other motor manifestations were
rated, and functional capacity was rated.
Nezlrological Examination
Each patient underwent a complete neurological examination
at every visit. Motor manifestations were rated on a 0 to 5
scale (0 = absent and 5 = greatest severity) that evaluated
speech, chorea (in each limb), gait, and postural stability.
Functional capacity was also determined at this time using
the Shoulson-Fahn scale 1301. This scale rates performance
in activities of daily living, such as capacity to work, manage
money, participate in domestic chores, dress, eat, bathe, and
remain independent.
Neuropsychological Assessment
A modified version of the Mini-Mental State Examination
(mMMS) 1171 was used at every examination. The modification to this test have been described [24]. We have found
that the mMMS correlates well with the original version of
this test ( r = 0.9).
Psychiatric Assessment
A semistructured interview, conducted by the two neurologists, was used to determine the presence of any psychiatric
symptoms (e.g., depression). The third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-111)
[1) was used as a guide. Twenty-six patients also completed
the Beck Depression Inventory (BDI) [2), and in 34 the
Brief Psychiatric Rating Scale (BPRS) [26J was used to rank
symptoms from the interview. Thirteen patients had neither
assessment, but were interviewed.
Data Storage and Analysis
All clinical information was placed in a database system
(CLINFO).Historical and demographic information was collected at the first evaluation. Motor disability rating, functional capacity and mMMS scores, and psychiatric data gathered at each visit were stored by date. Initial data analysis
focused on that data collected first on all 48 patients.
the somatic components of depression from the BPR
This calculation revealed no association between dl
pression and functional capacity. We chose to use tk
BPRS for this reanalysis because it is a reliable clinic.
rating, and unlike the BDI, it does not rely on a sel.
report format that could be contaminated by dementia
Significant relationships also existed between thc
mMMS score and age at first examination ( r =
- 0.37), duration from disease onset ( v = - 0.36), and
depression ( r = -0.56; p < 0.05 for each). Twenty
patients, taking phenothiazines, tetrabenazine, or reserpine for involuntary movements, had lower mMMS
scores (mean mMMS score on medication was 40.9
[’ ll.O}; no medication, 46.7 [ t 6 . 4 , p < 0.05}).
Motor Disability
The 48 patients included 28 men and 20 women
whose mean age was 48.4 years (range, 32 to 7 7 ) at the
first examination, and whose age at onset was 40.7
years (range, 21 to 71). The mean duration of symptoms was 7.3 years (standard deviation, -+4.7),but the
mean duration from diagnosis was 1.7 years (-+2.9).
Most subjects had completed high school. The mean
functional capacity score was 7.6 (-+3.8),placing this
group at Stage I11 1301. The mean mMMS score was
43.6 ( 2 9 . 7 ) ; previously we found a healthy older
group to have a mean of 52.3 ( t 4 . 3 ) 128). Thirty-two
met criteria for primary degenerative dementia {I}. In
31 patients, the first symptom was some change in
motor function. In 9, a psychopathological symptom
occurred first, and in 4 of these patients it was a major
depression syndrome [1}.
Functional Capacity
There was a significant correlation between mMMS
and the functional capacity total ( r = 0.725;p < 0.01).
Functional capacity also correlated with motor disability ( r = -0.33), age (r = -0.35;p < 0.05 for both),
duration of symptoms from onset ( r = -0.56; p <
0.01), and depression scores from the BDI or the
BPRS ( r = - 0.69, r = - 0.76, respectively; p < 0.01
for each). The unique contribution of mMMS, motor
dysfunction, and depression to the functional capacity
rating was calculated by partial correlations {14}.This
allowed us to determine how much of the variance in
functional capacity scores not estimated by two of the
variables could be estimated by the third. The mMMS
and BDUBPRS scores contributed significantly and
independently to determination of functional capacity (mMMS r = 0.491, p < 0.015; depression r =
- 0.468, p < 0.02 I), while motor dysfunction did not
( r = 0.026). We then reanalyzed the relationship between depression and functional capacity, eliminating
Severity of motor impairment, as previously described,
was related to time from onset of symptoms and to
time from diagnosis ( r = -0.57, r = -0.38, respectively; p < 0.05 for each). Some of the medications
used may have affected total motor disability scores,
obscuring the relationship to functional capacity 1201;
additional t tests compared the functional capacity
scores in those patients who were or were not using
these drugs. No differences were noted.
Four patients consumed alcohol in excess, by our definition, but this did not account for any difference in
functional capacity, mMMS scores, or motor disability.
Head Injury
The total motor disability score for those with head
trauma (n = 20) was 14.0 ( k 6 . 0 ) compared to 10.9
( k 5.9) for the other patients with HD (p < 0.05). No
significant differences were found in duration of illness, functional capacity, or mMMS scores.
Longitudinal Study
We calculated the deterioration in functional capacity
scores in 33 patients by subtracting the final rating
from the first and dividing by the time interval between these two assessments. The rate of change in
“functional units” per year was 0.86 ( & 1.02), ranging
from 0.53 to 4.48 per year. Subjects were seen at 6month intervals, but many were seen over a longer
period. Figure 1 illustrates the change in functional
capacity scores from the time of diagnosis and includes
scores from the first and final assessments. A decline in
functional capacity was seen in all but 3 subjects. Figure 2 shows the change in mMMS scores for the 33
patients over the same period. Only 4 patients did not
show a decline in intellectual function over the study
period. The two figures illustrate the progressive func-
728 Annals of Neurology Vol 20 No 6 December 1986
Time From Diagnosis (years)
Fig I . Functional capacity scores over the study period in 33
patients. The dots represent assessments of functional capacity,
and the lanes between indicate change over time. Patient numbers
are proyided t o distinguish overlapping scores.
Time From Diagnosis (years)
Fig 2. Mod&ed Mini-Mental State Examination (mMMS)
scores (19, 26) over the study period in 33 patients. The dots
represent mMMS scores, and the lines between indicate the
change over time. Patient numbers are provided t o distinguish
werkapping scores. The time of ascertainment of functional capacity (see Fig 1) and mMMS testing is not always identical in
this cohort.
Brief Communication: Mayeux et al: Early Disability in H D
tional and intellectual decline in HD, and support the
observations made in the total group of 48 patients.
Retrospective studies such as this one may be criticized
because of possible bias in patient selection, because
patient information may be inaccurate or incomplete,
and because it may be difficult to generalize from the
observations. However, this approach is useful in generating hypotheses. We have found that intellectual
impairment and dementia are a major cause of disability during the early stages of HD. At first these
changes are subtle, but they interfere with functional
activities, disabling the patient within a few years after
diagnosis. Functional capacity, or the ability to maintain independence in activities of daily life, deteriorates
slowly in HD 13, 28), but until now the clinical correlates of this disability have not been investigated.
Functional capacity as defined by the Shoulson and
Fahn scale [301 may actually assess activities that require intellectual function rather than other skills.
However, staging the disease by that scale correlated
with the presence of involuntary movements and other
manifestations 128-31). The scale may represent a
global measure of the overail disability from the disease rather than the functional outcome resulting from
any specific manifestation.
Dementia is characteristic of HD but the onset is
often subtle, and it may not be apparent until there are
overt problems 15-11, 15, 16, IS}. Intellectual decline
evolves over a long period, but length of illness alone
does not reliably predict the severity of dementia in
HD [4). Neuropsychological studies 16-11] and the
observations of unaffected family members depict a
subtle deterioration of cognition and memory as the
disease begins. Short-term memory and the ability to
retrieve or search for important past memories are affected when overall intelligence is relatively normal
14, 81. Recently diagnosed patients perform as well
as healthy age-matched controls on most intellectual
tasks, except for those measuring memory and verbal
fluency 18). Caine and associates [ll} also found that
defective encoding and retrieval of new memories
were early manifestations of HD. The ability to perform tasks requiring sequential behavior or organization and manipulation of information, such as the
Stroop Word Color Test and the Wisconsin Card Sort,
may also be impaired early in HD 115, 16). In contrast, language impairment remains minimal until there
is severe dysarthria or mutism 1161.
Intellectual impairment in HD could be the result of
the degenerative changes found in the frontal and temporal cortex C51, and reduced cerebral blood flow in
that area correlates with intellectual decline in severely
demented HD patients [32). However, this relationship is not seen in mildly affected patients or those
with rlecently diagnosed HD 133). Positron emission
tomographc scans indicate reduced metabolism in the
caudate nucleus in some individuals at risk for HD and
in those in the earliest clinical stages [25, 271, implying
that deterioration of some intellectual skills could be
anticipated as early manifestations of HD when the
disease is restricted to the basal ganglia. Our observations may reflect the early changes in functional capacity because the mean duration from either symptom
onset or diagnosis is brief (7.3 years) compared to the
average duration of disease to death (14.3 years) [21,
Affective disorders are also prevalent in HD E12,
191; unipolar and bipolar syndromes are described as
early psychiatric manifestations. In a prospective investigation, Caine and Shoulson 112) found one of two
affective disorders-major
depression or dysthymic
disorder-in 37% of patients with HD. Antidepressants alleviate the somatic features of depression in
HD, but the depressed mood often persists 112) and
functional capacity continues to deteriorate 128). Our
study, while not conclusive, suggests that the somatic
features of depression may be difficult to distinguish
from the physical symptoms inherent to HD.
Out finding regarding head injury is of concern because of its relationship to motor disability. The prevalence was higher than expected and warrants further
study. Nonetheless, this study suggests that changes in
intellectual function are likely to be the cause of functional disability early in the course of HD.
This work was supported in part by a gift from the Lena Marcus
family and Federal Grant AG02802; data were stored and analyzed
on CLINFO, supported by Federal Grant RR00645.
This paper was presented in part at the 109th Annual Meeting of the
American Neurological Association, Baltimore, MD, Oct 9, 1984.
The authors wish to thank Drs Nancy Wexler and Lewis P. Rowland
for their thoughts and help with this manuscript, and Don McMahon
for his assistance with data management.
730 Annals of Neurology Vol 20 No 6 December 1986
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Correlates of a Paroxysmal
Movement Disorder
Camilo Toro, MD, and Fernando Torres, MD
Averaged electroencephalographic activity related to
rhythmic jerking movements was recorded in a patient
with a complex neurological symptomatology. The
diagnosis of a functional disorder was strongly suggested by his clinical course, inconsistent findings from
physical examination, and negative workup. His abnormal movements were associated with the same electrophysiological correlates as normal willed motion, suggesting that averaged movement potentials may provide
useful information in the study of patients with suspected functional movement disorders.
Toro C, Torres F: Electrophysiological correlates
of a paroxysmal movement disorder.
Ann Neurol 20:731-734, 1986
By back-averaging electroencephalographic (EEG) activity related to the onset of voluntary motor acts, one
may identify small but distinct shifts of electrical potentials in the scalp as early as l to 2 seconds before
the initiation of motion. These cortical potentials, initially described by Kornhuber and Deecke in 1965
From the Department of Neurology, University of Minnesota
School of Medicine, Minneapolis, MN.
Received Dec 18, 1985, and in revised form Apr 14, 1986. Accepted for publication Apr 14, 1986.
Address reprint requests to Dr Toro, Department of Neurology,
University of Minnesota Hospitals, Box 295, Mayo Building, 420
Delaware St, SE, Minneapolis, M N 55455.
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