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Progression of Dysarthria and Dysphagia in Postmortem-Confirmed Parkinsonian Disorders
Jörg Müller, MD;
Gregor K. Wenning, MD, PhD;
Marc Verny, MD;
Ann McKee, MD;
K. Ray Chaudhuri, MD;
Kurt Jellinger, MD;
Werner Poewe, MD;
Irene Litvan, MD
Arch Neurol. 2001;58:259-264.
ABSTRACT
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Background Dysarthria and dysphagia are known to occur in parkinsonian syndromes
such as Parkinson disease (PD), dementia with Lewy bodies (DLB), corticobasal
degeneration (CBD), multiple system atrophy (MSA), and progressive supranuclear
palsy (PSP). Differences in the evolution of these symptoms have not been
studied systematically in postmortem-confirmed cases.
Objective To study differences in the evolution of dysarthria and dysphagia in
postmortem-confirmed parkinsonian disorders.
Patients and Methods Eighty-three pathologically confirmed cases (PD, n = 17; MSA, n = 15;
DLB, n = 14; PSP, n = 24; and CBD, n = 13) formed the basis for a multicenter
clinicopathological study organized by the National Institute of Neurological
Disorders and Stroke, Bethesda, Md. Cases with enough clinicopathological
documentation for the purpose of the study were selected from research and
neuropathological files of 7 medical centers in 4 countries (Austria, France,
England, and the United States).
Results Median dysarthria latencies were short in PSP and MSA (24 months each),
intermediate in CBD and DLB (40 and 42 months), and long in PD (84 months).
Median dysphagia latencies were intermediate in PSP (42 months), DLB (43 months),
CBD (64 months), and MSA (67 months), and long in PD (130 months). Dysarthria
or dysphagia within 1 year of disease onset was a distinguishing feature for
atypical parkinsonian disorders (APDs) (specificity, 100%) but failed to further
distinguish among the APDs. Survival time after onset of a complaint of dysphagia
was similar in PD, MSA, and PSP (15 to 24 months, P
= .7) and latency to a complaint of dysphagia was highly correlated with total
survival time ( = 0.88; P<.001) in all disorders.
Conclusions Latency to onset of dysarthria and dysphagia clearly differentiated
PD from the APDs, but did not help distinguish different APDs. Survival after
onset of dysphagia was similarly poor among all parkinsonian disorders. Evaluation
and adequate treatment of patients with PD who complain of dysphagia might
prevent or delay complications such as aspiration pneumonia, which in turn
may improve quality of life and increase survival time.
INTRODUCTION
DYSARTHRIA and dysphagia are well-recognized complications of parkinsonian
disorders such as Parkinson disease (PD),1
multiple system atrophy (MSA),2 dementia with
Lewy bodies (DLB),3 corticobasal degeneration
(CBD),4 and progressive supranuclear palsy
(PSP).5 However, to our knowledge, the temporal
evolution of dysarthria and dysphagia has never been explored systematically
in these disorders. Therefore, we retrospectively analyzed the temporal evolution
of dysarthria and dysphagia, as well as the median survival time of these
symptoms after symptom onset, and the correlation between latency to dysphagia
and total survival time in patients with postmortem-confirmed PD, MSA, DLB,
CBD, and PSP. Furthermore, we investigated whether the early appearance of
dysarthria or dysphagia (within 1 year of disease onset) could improve the
accuracy of diagnosis of these disorders as measured by sensitivity and specificity.
METHODS
SAMPLE AND DATA COLLECTION
Eighty-three pathologically confirmed parkinsonian disorders (PD, n
= 17; MSA, n = 15; DLB, n = 14; PSP, n = 24; and CBD, n = 13) formed the basis
for a multicenter clinicopathological study organized by the National Institute
of Neurological Disorders and Stroke, Bethesda, Md, to improve the differential
diagnosis of parkinsonian disorders.6 Eighty-three
of 144 clinicopathological cases selected from research and neuropathological
files of 7 medical centers in 4 countries (Austria, France, England, and the
United States) were included in the study because they had sufficient documentation
of the studied clinical features. The information considered was abstracted
from medical records by neurologists who were blinded to the pathological
diagnosis and who used predefined criteria recorded the information in standardized
forms. The cases met the neuropathological criteria of the National Institute
of Neurological Disorders and Stroke for the diagnosis of PSP and related
disorders7 and the guidelines of McKeith et
al8 for the diagnosis of DLB. Eighty percent
of the DLB cases were referred from a dementia clinic. Time to onset of a
speech disorder diagnosed by the treating neurologist and latencies to subjective
swallowing difficulties reported by the patients were recorded. Duration until
death was determined by retrospective chart review.
When the dysarthria was first noted, all patients with PD were benefiting
from levodopa replacement therapy (median daily dose, 600 mg [range, 200-1000
mg/d]), whereas only 33% of the 49% patients with atypical parkinsonian disorders
(APDs) who were receiving levodopa benefited.
STATISTICS
Data are expressed as median values throughout the text. Pearson  2, nonparametric 1-way analysis of variance (Kruskal-Wallis test), Mann-Whitney U tests, and the Spearman test were used for statistical
analysis, as appropriate. Box-plots were applied to determine the distribution
of latency data across the groups. Analyses of covariance (general linear
model) were performed to investigate the possible effects of (1) diagnosis,
(2) age at onset, (3) severity of parkinsonism according to Hoehn and Yahr
stages at the last clinic visit (median, 5 months before death), (4) presence
of dementia according to Diagnostic and Statistical Manual
of Mental Disorders, Third Edition,9
criteria, (5) latency to onset of dysarthria, and (6) latency to onset of
dysphagia on total survival time after symptom onset. The diagnostic accuracy
of a predefined latency (clinical onset of dysarthria and dysphagia within
12 months from symptom onset) was evaluated by analyzing sensitivity and specificity.
RESULTS
The main demographic characteristics are shown in Table 1. The proportion of dysarthria was similar in all patient
groups (P = .50), ranging from 72% to 100% (DLB,
72%; PD, 88%; CBD, 92%; MSA, 93%; and PSP, 100%). However, the proportion
of subjective dysphagia differed significantly (P
= .01) among the 5 disorders (DLB, 21%; CBD, 31%; PD, 41%; MSA, 73%; and PSP,
83%); between-group differences were significant for DLB vs MSA (P = .005); DLB vs PSP (P = .001); CBD vs PSP
(P = .01); and PD vs PSP (P
= .005).
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Table 1. Demographic Characteristics and Median Latencies to Dysarthria
and Dysphagia in Postmortem-Confirmed Parkinsonian Disorders*
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Comparison of median latencies to onset of dysarthria revealed significant
differences among patient groups (P = .02). Dysarthria
latencies were short in PSP and MSA (24 months each), intermediate in CBD
and DLB (40 and 42 months), and long in PD (84 months). Direct group analysis
showed significantly longer latencies to dysarthria in patients with PD than
in those with PSP (P = .009) or MSA (P = .01) (Figure 1). Dysarthria
profiles differed among the disorders as follows: hypophonic/monotonous speech
predominated in DLB (70%) and PD (73%), whereas imprecise or slurred articulation
predominated in MSA (71%), CBD (75%), and PSP (88%). At the last clinical
visit (median, 5.0 months before death), severe speech impairment, defined
as unintelligible speech (score, 4) according to the Unified Parkinson's Disease
Rating Scale,10 was variably present in PD
(18%), DLB (29%), CBD (31%), PSP (46%), and MSA (60%).
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Figure 1. Latencies to dysarthria after
disease onset in postmortem-confirmed parkinsonian disorders. Frequencies
of dysarthria: corticobasal degeneration (CBD), n = 12; dementia with Lewy
bodies (DLB), n = 10; multiple system atrophy (MSA), n = 14; Parkinson disease
(PD), n = 13; and progressive supranuclear palsy (PSP), n = 24. The horizontal
lines indicate median values; boxes, 25th to 75th percentile; error bars,
lowest and highest values within 1.5 times the values observed in the percentile
boxes; and circles, single cases exceeding 1.5 times the values observed in
the percentile boxes.
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Median latencies to subjective dysphagia differed significantly among
patient groups (P = .04), with intermediate latencies
in PSP (42 months), DLB (43 months), CBD (64 months), and MSA (67 months)
and long latencies in PD (130 months, Figure
2). Post hoc analysis revealed significantly longer latencies to
dysphagia in patients with PD than in those with PSP (P = .006) or MSA (P = .02).
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Figure 2. Latencies to dysphagia after disease
onset in postmortem-confirmed parkinsonian disorders. Frequencies of dysphagia:
corticobasal degeneration (CBD), n = 4; dementia with Lewy bodies (DLB), n
= 3; multiple system atrophy (MSA), n = 11; Parkinson disease (PD), n = 7;
and progressive supranuclear palsy (PSP), n = 20. The horizontal lines indicate
median values; boxes, 25th to 75th percentile; error bars, lowest and highest
values within 1.5 times the values observed in the percentile boxes; and circle,
a single case exceeding 1.5 times the values observed in the percentile box.
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With the exception of 1 patient with CBD, dysphagia occurred only in
parkinsonian patients with concomitant dysarthria. Latencies to dysphagia
after onset of dysarthria were significantly longer in PD than in APDs (P = .05, Table 2).
The median survival time between onset of dysphagia and death was similarly
short in PD, MSA, and PSP, ranging from 15 to 24 months (P = .70, Table 2). Accordingly,
latency to dysphagia was significantly correlated with total survival time
(Spearman = 0.88; P<.001) in all parkinsonian
disorders (Figure 3), and analyses
of covariance revealed that total survival was associated only with latency
to dysphagia (P<.001). However, after dysphagia
latency as a covariate was eliminated, age at onset (P
= .002), latency to dysarthria (P = .005), and diagnosis
(P = .04) all showed a significant effect on survival,
while no significant effect of Hoehn and Yahr stage and survival was observed
(P = .80).
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Table 2. Median Latencies to Dysphagia After Onset of Dysarthria and
Duration Until Death in Postmortem-Confirmed Parkinsonian Disorders*
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Figure 3. Correlation between latency to
dysphagia and total survival time in postmortem-confirmed parkinsonian disorders
(Spearman = 0.88; P<.001).
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None of the patients with PD developed dysarthria within the first year
of disease onset. Therefore, early dysarthria ( 12 months after disease
onset) was a characteristic feature in APDs (specificity, 100%). In contrast,
diagnostic sensitivity was low in APDs (19%), and highest in MSA (27%), followed
by PSP (25%), CBD (8%), and DLB (7%). Dysphagia was reported by only 2 patients
with PSP and 1 patient with MSA during the first year of disease onset (specificity,
100% for APDs), representing a poor diagnostic sensitivity of 8% and 7%, respectively.
COMMENT
This study has several limitations. First, the different parkinsonian
disorders were diagnosed pathologically; therefore, data were obtained retrospectively
and the neurologists evaluating these patients did not follow a protocol that
had been agreed on. Second, because of the rarity of the APDs, the sample
was not population based, and may not be representative of patients with APDs
in the population. Despite these limitations, these data permitted the identification
of important differences in the frequency and time course of dysarthria and
dysphagia among parkinsonian disorders. In fact, to our knowledge, this study
is the first to investigate and compare the progression of dysarthria and
dysphagia in postmortem-confirmed parkinsonian disorders, including PD, CBD,
DLB, MSA, and PSP. Except in PSP,11, 12
the association between dysarthria and dysphagia and their correlation with
survival have not yet been investigated in parkinsonian disorders, and we
could find no published data on the frequency and progression of dysphagia
in DLB and CBD.
Our analysis in cases of postmortem-confirmed parkinsonian disorders
corroborates the theory that early dysarthria and perceived swallowing dysfunction
are not features of PD. However, when one or both features were present, the
sensitivity and specificity of their early occurrence within the first year
failed to further distinguish among the various APDs. In agreement with the
findings of previous studies, dysarthria was frequently observed in all patient
groups,2, 4, 13, 14, 15
with significantly longer latencies in PD than in MSA and PSP. Similar to
our findings, dysarthria as a presenting symptom has been described in clinical
series of CBD,4 MSA,14
and PSP.16 In PD and DLB, hypophonic/monotonous
speech represented the most frequent type of dysarthria, whereas imprecise
or slurred articulation predominated in CBD, MSA, and PSP, in accordance with
the literature.4, 17, 18
In a clinical study of CBD, Rinne et al4
described dysarthria as one of the initial symptoms in 11% of the patients,
which is close to our findings. At follow-up, on average 5.2 years, dysarthria
was diagnosed in 70% of the patients.4 In a
recent study of 147 CBD cases, including 7 autopsy-confirmed cases, dysarthria
was noted only in 29% of patients, but there was no information on disease
duration.19 According to our findings, dysarthria
occurred in almost every patient with CBD.
Golbe et al11 reported comparable intervals
to dysarthria in a clinical series of 50 cases of PSP, including 4 pathologically
confirmed cases. In agreement with our results, Quinn17
described the speech of patients with MSA as more severely affected than that
of patients with PD, with slurring dysarthria, as well as the low volume and
monotone of parkinsonism. In both PSP and MSA, progressive dysarthria is believed
to represent a manifestation of brainstem and cerebellar involvement.18, 20 In fact, positron emission tomography
studies revealed marked hypometabolism in the cerebellum and brainstem of
patients with MSA, which correlated with dysarthria.21
In our study, dysphagia was associated with concomitant dysarthria in
all parkinsonian patients except one. This sequence of dysphagia following
dysarthria has also been reported in clinical series of PD, MSA, and PSP.11, 14 In a clinical study of swallowing
abnormalities in PSP, objective assessments of swallowing dysfunction were
also associated with overall speech impairment, and voice and articulation
were among other features identified as predictors of abnormal swallowing;
however, dysarthria was not always paired with dysphagia in the same patient.12 Comparable to our results, Golbe et al11
reported dysphagia after a median of 1 year after the onset of dysarthria
in PSP.
Median latencies to dysarthria and subjective dysphagia were at least
twice as long in PD than in APDs, including DLB (Table 1). Total survival time, as well as survival time after onset
of dysarthria, was significantly longer in PD; however, the onset of dysphagia
predicted a similarly short remaining median survival time in MSA, PSP, and
PD (Table 2). Furthermore, latencies
to dysphagia were highly correlated with overall survival time in all parkinsonian
disorders (Figure 3). These important
findings suggest that the perceived swallowing dysfunction in PD and APDs
indicates functionally relevant dysphagia. Indeed, in PD,22
DLB,3 CBD,23
MSA,24 and PSP,12
bronchopneumonia has been reported as a leading cause of death, which may
be subsequent to silent aspiration resulting from dysphagia.12
Evaluation and adequate treatment of parkinsonian patients who complain of
dysphagia might thus prevent or delay complications such as aspiration pneumonia
and increase survival time in these patients. Also, an appropriate and timely
swallowing evaluation may provide patients and caregivers with techniques
and resources that may in turn improve their quality of life (eg, straws,
food thickeners, and percutaneous endoscopic gastrostomy).12
Most of our patients with MSA and PSP complained of a swallowing dysfunction,
in contrast to patients with PD, CBD, and DLB. In PD, the reported prevalence
of dysphagia varies from 18.5% to 100%,24, 25, 26
depending on the measurement method. Investigators who carried out assessment
with barium swallow found abnormalities in all study patients with PD,1 and complaints of dysphagia in patients with PD were
found to correlate poorly with radiologic and videofluoroscopic findings.1, 27, 28 Impaired lingual proprioception
is hypothesized to contribute to the unawareness of swallowing difficulties
in PD and might in part explain significantly longer latencies to dysphagia
in our PD cases. In contrast, patients with PSP were reported to be keenly
aware of swallowing problems,18 including those
with cognitive impairment.12 In a clinical
study on swallowing abnormalities in PSP, Litvan et al12
reported abnormal results on modified barium swallow or ultrasound studies
in 96% of patients, which exceeds the 83% dysphagia in our PSP cases, a finding
that is probably related to the higher sensitivity of objective measurements.
However, the similarly short remaining survival time in PD and PSP after the
onset of perceived dysphagia suggests that this symptom represents a reliable
marker for the onset of functionally relevant swallowing abnormalities in
both disorders. Similar to PSP, dysphagia within the first year of disease
onset was observed in MSA, and dysphagia represented a frequent complaint
in MSA. Comparable to our results, dysphagia was among the first clinical
symptoms in 1 of 18 cases of probable MSA.13
In DLB, dysphagia was noticed by only 21% of patients, but after a median
latency of 43 months since disease onset, which was similar to the latency
in PSP and only one third of the median latency to dysphagia in PD (Table 1). In a study of 9 postmortem-confirmed
DLB cases, Hely et al3 reported dysphagia in
only 1 patient (11%); similarly, Burkhard et al,29
in a review of 34 postmortem cases, including 4 previously unpublished DLB
cases, reported dysphagia in 12% of the cases, without information on symptom
latency. However, in most clinicopathological studies, dysphagia was not mentioned.8, 30, 31, 32, 33
The short latency to dysphagia in our DLB cases might be explained by the
fact that there are more widespread Lewy body lesions in DLB than in PD; however,
a higher prevalence of swallowing disturbances should be expected. The discrepancy
between the low proportion and short latency to subjective dysphagia might
in part be attributable to dementia interfering with the perception or reporting
of swallowing dysfunction in DLB. Notably, the median survival time after
the onset of subjective dysphagia in DLB was only 10 months and was thus shorter
than in all other parkinsonian disorders. These findings indicate that some
patients with DLB develop early and severe dysphagia with reduced survival
time. However, these latency data should be interpreted cautiously due to
the limited number of cases and deserve further investigation.
In CBD, dysphagia was noticed in 31% of our cases after a median disease
duration of 64 months. Dysphagia in CBD is believed to result from bulbar
dysfunction, which is uncommon initially, but often appears after several
years of disease.34 Accordingly, none of our
patients with CBD noticed early dysphagia (Table 1). To our knowledge, dysphagia has not yet been investigated
systematically in CBD, and the 2 largest studies of CBD, by Kompoliti et al19 (147 cases) and Rinne et al4
(36 cases), provided no data on frequency or latency of dysphagia.
Our findings of increased latency to dysarthria and dysphagia and similar
time interval from onset of dysphagia to death in patients with PD compared
with patients with APDs suggest that extrastriatal and nondopaminergic lesions
represent an important factor for the development of dysarthria and dysphagia.
Indeed, Bonnet et al35 reported that dysarthria,
gait, and postural stability had a decreased levodopa response in patients
with long-standing PD who still benefited from the levodopa effects on tremor,
rigidity, and akinesia. Whereas the APDs are characterized by multiple system
neuronal degenerations, in PD disease progression is determined by a progressive
dopaminergic deficit arising from the selective neuronal degeneration of the
substantia nigra pars compacta. It may be the overall degenerative lesion
load in excess of the dopaminergic projection that shortens the onset of axial
features, such as dysarthria and dysphagia, and therefore predicts poor survival
in patients with PD. However, the presence of distinct neuropathological lesion
patterns in these disorders suggests that disease-specific factors may contribute
to the pathophysiological processes underlying dysarthria and dysphagia.
In conclusion, our study demonstrates that the latency to the onset
of dysarthria and dysphagia, as well as the duration of dysarthria, differentiates
patients with PD from those with APDs, but not among those with APDs, while
survival after onset of a complaint of dysphagia was similarly poor in those
with PD and APDs.
AUTHOR INFORMATION
Accepted for publication March 29, 2000.
The authors thank Jean-Jacques Hauw, MD, Susan Daniel, MD, Dennis W.
Dickson, MD, Dikran S. Horoupian, MD, and Peter L. Lantos, MD, for providing
the cases for the database of the National Institute of Neurological Disorders
and Stroke, National Institutes of Health, Bethesda, Md.
From the Department of Neurology, University Hospital Innsbruck, Innsbruck,
Austria (Drs Müller, Wenning, and Poewe); Raymond Escourolle Neuropathology
Laboratory, Hôpital de la Salpétrière, Paris, France (Dr
Verny); the Veterans Administration Medical Center Geriatric Research Education
Clinic Center, Bedford, Mass, and the Departments of Neurology and Pathology,
Boston University Medical School, Boston, Mass (Dr McKee); the Department
of Neurology, Institute of Psychiatry, London, England (Dr Chaudhuri); Ludwig
Boltzmann Institute of Clinical Neurology, Vienna, Austria (Dr Jellinger);
and the Cognitive Neuropharmacology Unit, Defense and Veteran Head Injury
Program, Henry M. Jackson Foundation and Medical Neurology Branch, National
Institute of Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, Md (Dr Litvan).
Corresponding author: Irene Litvan, MD, Cognitive Neuropharmacology
Unit, The Champlain Building, 6410 Rockledge Dr, Suite 600, Bethesda, MD 20817-1844.
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