Heterogeneity in Spasmodic Dysphonia Neurologic and Voice Findings Kenneth D. Pool, MD; Frances J. Freeman, PhD; Terese Finitzo, PhD; Mari M. Hayashi, PhD; Sandra B. Chapman, PhD; Michael D. Devous, Sr, PhD; Lanny G. Close, MD; George V. Kondraske, PhD; Dianne Mendelsohn, MD; Steven D. Schaefer, MD; Ben C. Watson, PhD
\s=b\ Spasmodic dysphonia is a disturbance of phonation with laryngeal spasms. We report voice and neurologic examination findings in 45 subjects. Neurologic abnormalities were found in 32
subjects (71.1%). Rapid alternating movement abnormalities, weakness, and tremor Incoordination and spasLower extremity findings frequent. Abnormalities were bilat-
were common.
ticity were
were rare.
eral. Spasmodic dysphonia severity was related to age. Type, severity, and duration of vocal symptoms were not different for subjects with or without neurologic abnormalities. Vocal tremor was more frequent in neurologically abnormal subjects. Involvement of a pallidothalamic\p=m-\supplementary motor area system could account for neurologic findings, brain imaging findings, and clinical heterogeneity. The view emerging is that spasmodic dysphonia is a manifestation of disordered motor control involving systems of neurons rather than single anatomical sites. (Arch Neurol. 1991;48:305-309)
Çîpasmodic dysphonia (SD) turbance of
is
a
dis¬
phonation diagnosed
by perceptual voice characteristics.1
Accepted for publication August 1, 1990. From the Dallas (Tex) Center for Vocal Motor Control (Drs Pool, Freeman, Finitzo, Hayashi, Chapman, Devous, Close, Kondraske, Mendelsohn, Schaefer, and Watson); the Neuroscience Research Center (Drs Pool and Finitzo); The University of Texas at Dallas\p=m-\Callier Center (Drs Freeman, Finitzo, Hayashi, Chapman, and Watson); the Departments of Radiology (Drs Devous and Mendelsohn) and Otolaryngology (Drs Close and Schaefer), The University of Texas Southwestern Medical Center at Dallas; and the Department of Biomedical Engineering, The University of Texas at Arlington (Dr Kondraske). Reprints not available.
Existence of SD, type and severity of SD, and presence or absence of vocal tremor are determined by vocal fea¬ tures and laryngeal examination. As one might expect in a disorder without objective diagnostic criteria, there is substantial clinical heterogeneity. Three subtypes of SD are described by perceptual and acoustic vocal charac¬ teristics: adductor, abductor,2 and mixed.3 Adductor SD is associated with involuntary hyperadduction of the vocal folds, resulting in a "strained-strangled" voice quality. Abductor SD is characterized by in¬ voluntary abductions of the vocal folds, resulting in intermittent bursts of breathy phonation. Mixed SD has been applied to patients who exhibit a full range of these vocal characteris¬ tics. Hoarseness, pitch breaks, limited intensity range, and poor intensity control are present in all types. Cannito and Johnson3 proposed that SD is a "continuum disorder" in which both types of spasms occur with differing
frequencies.
Much of the early literature de¬ scribes the "typical" patient with SD as "normal" except for vocal symp¬ toms.46 However, Robe et al7 and Aronson et al8 reported frequent abnormal neurologic examination findings in subjects with SD. More recently, re¬ searchers have come to view SD as a movement control disorder affecting the larynx9·10 or as a form of adult-on¬ set, focal dystonia.1113 Others have sug¬ gested that SD may also be observed in a number of different movement disorders.1416 Aronson et al14 and Aron-
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son
and Hartman15 associated adduc¬
tor SD with essential voice tremor. Jankovic and Ford16 included 21 sub¬
jects with SD in a large (100-subject) study of blepharospasm and orofacialcervical dystonia, and characterized SD as an incomplete expression of Meige's disease. While observation of
SD in other movement disorders is well documented, the frequency and type of neurologic findings and their relation to the vocal characteristics remain ill defined. This study reports the findings of voice and neurologic (ie, motor and somatosensory) examina¬ tions in 45 subjects with SD and poses the following questions: 1. Are there neurologic abnormali¬ ties in subjects with SD? 2. If so, do some abnormalities occur more frequently than others? 3. Are type, duration, and severity of SD related to neurologic examina¬ tion findings? '
SUBJECTS AND METHODS
Subjects
Forty-five subjects with SD who were evaluated at the Dallas (Tex) Center for Vocal Motor Control between January 1987 and March 1989 were included in this study. Evaluation procedures are described in an article by Finitzo and Freeman.10 No sub¬ ject had a prior recognized stroke, demen¬ tia, or mental retardation. No subject had a prior diagnosed neurologic disorder. Otolaryngologic examinations were performed to exclude subjects with structural abnor¬ malities of the larynx and/or vocal tract. Fifteen potential normal control, agematched subjects were also examined. Two subjects were rejected for use as normal
controls because of memory deficits. One subject was rejected because of current use of psychoactive medication. The remaining 12 subjects had normal findings on all 29 features reported herein. These subjects also served as control subjects in other as¬ pects of our research.
Table 1.—Neurologie Abnormalities Among Type(s) extremity RAM rate Lower extremity RAM rhythm Upper extremity RAM rate Upper extremity weakness Upper extremity RAM rhythm Upper extremity reflexes
were conducted by speech-language pathologists. Evalua¬ tion sessions were videotaped for reliability checks. Type (ie, adductor, abductor, or mixed), severity (ie, mild, moderate, or se¬ vere), and presence of vocal tremor were evaluated perceptually and judged by a consensus of the two speech-language pa¬ thologists and one otolaryngologist. Acous¬ tic measures were also completed for all subjects. Indirect laryngoscopy for move¬ ment abnormalities was performed on all subjects. Fiberoptic video tape recordings of laryngeal, pharyngeal, and velar move¬ ments (as reported in Freeman et al17) were undertaken for 40% of these subjects. These approaches were used to evaluate re¬ liability of the independently derived per¬ ceptual categorizations.
Lower
Upper extremity tremor Upper extremity sensory impairments Upper extremity rigidity Lingual weakness Head/neck sensory impairments Head/neck weakness
Head/neck involuntary movements
Upper extremity involuntary movements Upper extremity spasticity involuntary movements Head/neck rigidity Upper extremity incoordination Lower extremity tremor Lower extremity involuntary movements Lower extremity spasticity Orofacial sensory impairments Lower extremity rigidity Lower extremity incoordination Lower extremity sensory impairments RAM indicates rapid alternating movement. Orofacial
Neurologic Examination
Neurologic examinations were conducted by an experienced, board-certified neurolo¬ gist (K.D.P.). The neurologic examination findings reported here are limited to motor function, somatosensory thresholds, coor¬ dination, and reflexes. Twenty-nine fea¬
Table
Age,
RESULTS
Subject Description
Table 2 is a summary of subject de¬ mographic and vocal characteristics.
Twenty-one subjects (46.7%) were classified as having adductor SD; eight (17.8%), abductor SD; and 16 (35.5%), mixed SD. Twenty-eight subjects
Abductor
Mixed 16 39.8
28-70
20-70
Sex 16
M
10
Handedness
Right Left
Severity Mild
duration, severity,
accurate.
Adductor
45
y
Range
Statistical Analysis Two-tailed t tests, 2, and Fisher's Exact Test1819 were used to determine whether neurologic abnormalities in the subjects with SD were randomly distributed. Rela¬
significantly
and Vocal Characteristics
Mean
classified as either normal or abnor¬ mal. Abnormal indicates that the subject was outside the range of normal variation for age and gender.
were
and number of neurologic abnormalities were examined using F tests for compari¬ sons involving categorical variables and Spearman's rank correlation for compari¬ sons involving only continuous variables.19 "Classification and Regression Trees" (CART)20 was used to examine relation¬ ships among combinations of voice and neurologic examination findings. This anal¬ ysis procedure2022 is nonparametric and nonlinear. We used prior class frequencies, Gini's impurity function for tree construc¬ tion, and a 1.0 SE cutoff for tree selection from 10-fold cross validation. The tree, if any, meeting these criteria was classified as
2.—Demographic Overall
No. of subjects
tures were examined and are listed in Table 1. Features for each body part examined
among age,
.
Head/neck tremor extremity weakness Lingual RAM rate Orofacial reflexes
Voice examinations
two
tionships
No. (%) 19(42.2) 16(35.6) 16(35.6) 14(31.1) 13(28.9) 11 (24.4) 10 (22.2) 10 (22.2) 9 (20.0) 9 (20.0) 9 (20.0) 7 (15.6) 6(13.3) 5(11.1) 5 (11.1) 4(8.9) 3 (6.7) 3 (6.7) 3 (6.7) 2 (4.4) 2 (4.4) 1 (2.2) 1 (2.2) 1 (2.2) 1 (2.2) 1 (2.2) 0 (0) 0 (0) 0 (0)
Lower
Voice Evaluation
Subjects*
18
Severe
Duration,
y
Mean
7.9
Range
1-40
1-40
Tremor Present
ity
2-13
2-25
13
The absent category includes three of their spasmodic dysphonia.
subjects whose vocal
(62.2% ) had vocal tremor. Perceptual evidence of vocal tremor was not iden¬ tified in 14 subjects and could not be reliably determined in three subjects because of the severity of adductor-
type spasms. Severity
was
years). Family history data
were
judged
as
mild in 16 subjects (35.6%); moderate in 18 (40.0% ); and severe in 11 (24.4% ). Duration of SD symptoms ranged from 1 to 40 years (mean duration, 7.9 obtained
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tremor was unmeasurable because of the
sever¬
for 44 of 45 subjects with SD and are summarized in Table 3. A total of 13 (29.5%) of 44 subjects with SD had a family history of SD, essential tremor, or both. Five subjects with SD (11.4% ) had relatives with other movement disorders such as Parkinson's disease (6.7%), spasmodic torticollis (2.2%), and blepharospasm (2.2%). The sub¬ ject with blepharospasm in her family also had family members with SD and essential tremor.
Table 3.—Family History Data Obtained From 44 Subjects With
Spasmodic Dysphonia (SD) No. (%)
Abnormal Findings SD and essential tremor SD and essential tremor
(9.1) (2.2) 8(18.2) 13 (29.5) 4 1
SD only Essential tremor only Total Other movement disorders Parkinson's disease
(6.7) (2.2) 1 (2.2) 5(11.4) 3
Torticollis
1
Blepharospasm Total
There was no significant correlation between duration of SD and number of examination findings (r .28; 1.89; >.05) or between age and duration of SD (r .13; 0.86; > .05). Age, gender, type, severity, vocal tremor, and duration of vocal symp¬ toms were compared for the neurolog¬ ically abnormal (n 32) and normal (n 13) subjects with SD. Age and duration of SD were tested using twotailed t tests. Gender, type, and sever¬ ity of SD and vocal tremor were tested =
No. of
Findings
=
Fig 1.—Distribution of 203 positive neurologic examination findings in the 32 subjects with spas¬ modic dysphonia demonstrating neurologic examination abnormalities.
=
=
=
=
using 2.
The mean age of neurologically ab¬ normal subjects was 46.8 years vs 39.8 years for neurologically normal sub¬ jects. This difference was not signifi¬ cant (i 1.94; df= 43; > .05). Neuro¬ logically abnormal subjects had a higher frequency of vocal tremor than the neurologically normal subjects ( 2 8.70; df= 1; < .01). Of 28 sub¬ jects with vocal tremor, 24 were neu¬ rologically abnormal. Of 14 without vocal tremor, only five were neurolog¬ ically abnormal. All three subjects whose vocal tremor could not be deter¬ mined because of frequency and sever¬ ity of vocal spasms were neurologically abnormal. Gender ( 2 1.66; df=l P>.05) and type ( 2 1.97; d/= 2 =
=
RAM
Weakness Reflexes Tremor Sensory
Rigidity Spasticity Involuntary Incoordination Movements
Fig 2. Frequency of neurologic examination findings by type for 45 subjects with spasmodic dysphonia. RAM indicates rapid alternating movements. —
=
=
Neurologic Examination
2.13). Abnormali¬ were predominantly bilateral. Only six (18.8% ) of the 32 subjects with SD and neurologic abnormalities dem¬ onstrated asymmetries on examina¬ tion. In all six, the left side of the body was more impaired than the right side (P < .032; binomial distribution). The severity of SD was related to the age of the subject (F 5.2; df= 2,42; < .01); ie, SD tended to be more severe in the older subjects. Severity was not related to duration (F 0.5; df= 2,42; > .05) or number of neu¬ rologic examination abnormalities (F 2.03; d/=2,42; > .05). There was a significant correlation between jects ( ties
Neurologic abnormalities were found in 32 (71.1% ) of 45 subjects with SD. The mean number of neurologic abnormalities in these 32 subjects was 6.3 per subject, with a range from one to 17. Thirteen subjects (28.9% ) had no abnormal findings on the neurologic examination. Distribution of abnor¬ malities in the 32 subjects is shown in Figi.
Table 1 lists the occurrence of ab¬ normal findings. Rapid alternating
movement (RAM) abnormalities, weakness, and tremor were common (Fig 2). Incoordination and spasticity
rarely observed. Significant right-left asymmetry
were was
not characteristic of
these sub-
>
.05; 2
=
=
=
=
age and number of examination abnor¬ malities (r .47; = 3.15; < .008). =
There
was no
significant correlation
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.05), severity ( 2 2.19; df=2 .05), and duration (t .92; df= 43: .05) of SD did not differ between the two subject groups. To investigate relationships among vocal and neurologic findings, we at¬ tempted to construct classification trees. This was possible for severity > > >
but not for type
=
=
or
duration of SD. Se¬
verity was correctly classified for 71% of subjects. For three levels of severity (mild, moderate, and severe), the ex¬ pected chance accuracy for an individ¬ ual subject would be 33%. Correct
classification was achieved for 69% of the subjects with mild SD, for 56% of subjects with moderate SD, and for 100% of subjects with severe SD. The rules can be summarized as follows: • If the subject is 46 years or younger, and the lower extremity rate
is normal, then the SD is mild. Of 16 subjects meeting these criteria, 11 (65%) had mild SD, five (35%) had moderate SD, and none had severe SD. • If the subject is 46 years or younger, and the lower extremity rate is abnormal and the lingual rate is normal, then the SD is moderate. Of seven subjects with these characteris¬ tics, five (71%) had moderate SD, two (29%) had mild SD, and none had severe SD. If the lingual rate is also abnormal, then the SD is severe. Of two subjects with this finding, both (100%) had severe SD. • If the subject is older than 46 years, severity depends on the type of SD. If the subject has abductor SD, the SD will be moderate. Of five subjects with these characteristics, five (100% ) had moderate SD. If the type is mixed or adductor, and the subject is older than 46 years, the SD is severe. Of 15 subjects with these characteristics, three (20%) had mild SD, three had moderate SD, and nine (60% ) had se¬ vere SD. COMMENT
The majority (71.1%) of subjects with SD had abnormal neurologic ex¬ amination findings. Most frequent ab¬ normalities were of lower extremity RAM rate and rhythm, upper extrem¬ ity RAM rate and rhythm, upper ex¬ tremity strength, and upper extremity reflexes. This "clustering" refutes the hypothesis that neurologic abnormal¬ ities in SD are randomly distributed. These findings are a confirmation of the earlier work of Aronson et al8 and Robe et al7 despite the substantial clinical heterogeneity among subjects with SD and the methodological dif¬ ferences in study design. The fre¬ quency (71% vs 75% ) and pattern (Fig 3) of abnormal neurologic examination findings in our subjects is strikingly similar to those in the study of Aron¬ son et al.8 Vocal tremor was identified in 62.2% of our subjects and 51.8% of those in Aronson and colleagues' study. Abnormal neurologic examina¬ tion findings were more frequent in the subjects with SD who had perceptual vocal tremor. Although in our study we did not find a relationship between age and the presence of abnormal neuro¬ logic examination findings, in both studies age was related to the number of neurologic findings; ie, older sub¬ jects tended to have more abnormal findings than younger subjects. The combination of age and type of SD, in conjunction with the presence of spe¬ cific neurologic findings (lower extrem¬ ity RAM rate, and lingual diadokinetic rate), was significantly related to the
Fig 3.—Comparison of neurologic examination features reported by Aronson spasmodic dysphonia with parallel features in the current study.
et alB as "linked"
to
severity of the disorder. Specific neurologic abnormalities, whether frequent or infrequent, pro¬ vide insight into the mechanisms of SD. Impaired RAM in terms of either rate or rhythm may be seen with
involvement of cerebellar, basal gan¬ glial, or upper motor neuron pathways. Absence of dysmetria or ataxia also argues against a primary cerebellar lesion. Further, Cannito,23-2'' in a study of quantitative motor performance in a subgroup of subjects with SD (female subjects with adductor SD), also failed to find evidence of cerebellar dysfunc¬
tion. Co-occurrence of tremor and ri¬
gidity with RAM abnormalities would support
a
localization to the basal
ganglia. This localization is in theoret¬ ical agreement with hypotheses that SD is a laryngeal dystonia and that dystonias 13 arise from the basal ganglia." Co-occurrence of weakness and hyperreflexia with RAM abnor¬ malities implicates upper motor neu¬ ron pathways. A model of SD is posited wherein known projections from basal ganglia to cortex provide a link between these disparate components. This model is
based on several documented brainbehavior relations and neural path¬ ways. Direct intraoperative electrocortical stimulation of the supplemen¬
area (SMA) produces speech arrest and perseverative utter¬
tary motor
ances.25 Acute lesions of the SMA in the dominant hemisphere in man re¬ sult in severe impairment of sponta¬
neous speech.26 Thalamocortical pro¬ jections to the SMA are greatest from
the pars oralis of the ventrolateral nu¬ cleus of the thalamus (VLJ.27 Affér¬ ents to the VL0 are primarily from basal ganglia (globus pallidus).27 Con-
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sequently, involvement of the globus pallidus, projections from the globus pallidus itself to the VL0, the VL0 itself, projections from the VL0 to the SMA, or the SMA itself might produce the speech impairments in SD. Our brain imaging studies agree
with localizations derived from these neurologic examination findings. Me¬ sial frontal cortex is one of the most frequent areas of abnormality in both our anatomical and functional brain imaging studies.10 The region of great¬ est anatomical signal change on mag¬ netic resonance imaging was subcortical white matter underlying mesial frontal cortex, an area traversed by thalamocortical projections to this cortical region.28 A significant correla¬ tion between electrophysiology and re¬ gional cerebral blood flow was seen in the left anterior cortical quadrant in the same subjects.2' Thus, a common region of abnormal neuronal function appears to be the mesial frontal lobe, as evidenced by findings on both neu¬ rologic examination and brain imag¬ ing studies. Our imaging technologies may be more sensitive to involvement of the SMA or its thalamocortical pro¬ jections than of the globus pallidus or thalamic nuclei. If involvement of this pallidothalamic-SM A system is at the level of the SMA, the examination findings should be dominated by cortical signs and the imaging measures should show corti¬ cal dysfunction. If the involvement is at the globus pallidus, the examination findings should be dominated by basal ganglial signs and the findings of the brain imaging studies should be nor¬ mal (a finding in 16% of our subjects10). Thus, involvement of a pallidothalamic-SMA system could account for the
bulk of the associated neurologic ex¬ amination and brain imaging findings, and result in the observed clinical het¬
erogeneity.
While we are far from unraveling the precise pathogenesis of SD, the view emerging from converging lines of investigation is that SD is a mani¬ festation of disordered motor control. The disordered motor control involves systems of neurons rather than single
anatomical sites. Thus, it cannot be referred to as a cortical or basal gan¬ glial disorder. The manner in which other lesion sites may modulate the primary manifestation is also com¬ plex, but hypotheses about these rela¬ tionships are now being formed. Ulti¬ mately, our ability to understand SD reflects the current state of examina¬ tions of the function and dysfunction of the nervous system and the power of
a
multidisciplinary approach
dress such
'
to ad¬
complex questions.
Funding for this project was provided by Na¬ tional Institute of Neurological Disorders and Stroke grant 18276 to the University of Texas at Dallas. The authors wish to acknowledge the contribu¬ tions of the subjects with spasmodic dysphonia and of the normal control subjects. Data entry was provided by Deborah Thomas; and statistical assistance, by our students Jackie Clark, Susan Reamy Rampy, and B. Alan Rampy.
References 1. Aronson AE. Clinical Voice Disorders: An
Interdisciplinary Approach. New York, NY: Thieme-Stratton Inc; 1980.
2. Aronson AE. Clinical Voice Disorders: An
Interdisciplinary Approach.
2nd ed. New York: Thieme-Stratton Inc; 1985. 3. Cannito MP, Johnson JP. Spastic dysphonia: a continuum disorder. J Commun Disord. 1981; 14:215-223. 4. Traube T. Cited by: Arnold EE. Spastic dysphonia, I: changing interpretation of a persistent affliction. Logos. 1959;2:3-14. 5. Brodnitz FS. Spastic dysphonia. Ann Otol.
1976;85:210-214.
6. Berendes J. Spastiche Dysphonie. Arch Sprach Stimmheilk. 1939;3:29, 86, 189. 7. Robe E, Brumlik J, Moore P. A study of spastic dysphonia: neurologic and electroencephalographic abnormalities. Laryngoscope. 1960;70:
219-245. 8. Aronson AE, Brown JR, Litin ME, Pearson JS. Spastic dysphonia, I: voice, neurologic, and psychiatric aspects. J Speech Hear Disord. 1968; 33:203-218. 9. McCall G, Skolnik L, Brewer D. A preliminary report of some atypical movement patterns in the tongue, palate, and hypopharynx and larynx of patients with spasmodic dysphonia. J Speech Hear Disord. 1971;36:466-470. 10. Finitzo T, Freeman FJ. Spasmodic dysphonia, whether and where: results of seven years of research. J Speech Hear Res. 1989;32:541-555. 11. Ludlow C, Connor N. Dynamic aspects of phonatory control in spasmodic dysphonia. J Speech Hear Res. 1987;30:197-206.
12. Grandas F, Elston J, Quinn N, Marsden CD. Blepharospasm: a review of 264 patients. J Neurol Neurosurg Psychiatry. 1988;51:767-772. 13. Blitzer A, Brin MF, Fahn S, Lovelace RE. Clinical laboratory characteristics of focal laryngeal dystonia: study of 110 cases. Laryngoscope.
1988;98:636-640. 14. Aronson AE, Brown JR, Litin ME, Pearson
JS. Spastic dysphonia, II: comparison with essential (voice) tremor and other neurologic and psychogenic dysphonias. J Speech Hear Disord. 1968; 33:219-231. 15. Aronson AE, Hartman DE. Adductor spastic dysphonia as a sign of essential (voice) tremor. J Speech Hear Disord. 1981;46:52-56. 16. Jankovic J, Ford RN. Blepharospasm and orofacial-cervical dystonia: clinical and pharmacological findings in 100 patients. Ann Neurol.
1983;13:402-411. 17. Freeman FJ, Cannito MP, Finitzo-Hieber T. Classification of spasmodic dysphonia by perceptual-acoustic-visual means. In: Gates G, ed. Spastic Dysphonia: State of the Art 1984. New York, NY: The Voice Foundation; 1985:5-18. 18. Siegel S. Nonparametric Statistics for the Behavioral Sciences. New York, NY: McGraw\x=req-\ Hill International Book Co; 1956. 19. Miller I, Freund JE. Probability and Statistics for Engineers. Englewood Cliffs, NJ: Prentice\x=req-\ Hall International Inc; 1985. 20. Breiman L, Friedman JH, Olshen RA, Stone CJ. Classification and Regression Trees. Belmont, Calif: Wadsworth International; 1984. 21. Wong PKH, Bencivenga R, Gregory D. Statistical classification of spikes in benign rolandic
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epilepsy. Brain Topogr. 1988;1:123-129. 22. Finitzo T, Pool KD, Chapman SB. Quantitative electrophysiology and anatomo-clinical principles of aphasia: a validation study. Ann NY
Acad Sci. In press. 23. Cannito MP.
Extralaryngeal Functions in Spasmodic Dysphonia: Vocal Tract and Upper Extremity Control. Richardson, Tex: University of Texas at Dallas; 1986. Thesis.
24. Cannito MP. Vocal tract steadiness in spasmodic dysphonia. In: Yorkston K, Beukelman D, eds. Recent Advances in Clinical Dysarthria. Boston, Mass: College Hill Press; 1989:243-262. 25. Penfield W, Welch K. The supplementary motor area of the cerebral cortex: a clinical and experimental study. Arch Neurol Psychiatry.
1951;66:289-294.
26. Verfaellie M, Heilman KM. Response preparation and response inhibition after lesions of the medial frontal lobe. Arch Neurol. 1987; 44:1265-1271. 27. Goldberg G. Supplementary motor area structure and function: review and hypotheses. Behav Brain Sci. 1985;8:567-616. 28. Schaefer S, Freeman FJ, Finitzo T, et al. Magnetic resonance imaging findings and correlations in spasmodic dysphonia patients. Ann Otol Rhinol Laryngol. 1985;94:595-601. 29. Devous MD, Pool KD, Finitzo T, et al. Evidence for cortical dysfunction in spasmodic dysphonia: regional cerebral blood flow and quantitative electrophysiology. Brain Lang. 1990;35:331\x=req-\ 344.
\s=b\ Spasmodic dysphonia is a disturbance of phonation with laryngeal spasms. We report voice and neurologic examination findings in 45 subjects. Neurologic abnormalities were found in 32
subjects (71.1%). Rapid alternating movement abnormalities, weakness, and tremor Incoordination and spasLower extremity findings frequent. Abnormalities were bilat-
were common.
ticity were
were rare.
eral. Spasmodic dysphonia severity was related to age. Type, severity, and duration of vocal symptoms were not different for subjects with or without neurologic abnormalities. Vocal tremor was more frequent in neurologically abnormal subjects. Involvement of a pallidothalamic\p=m-\supplementary motor area system could account for neurologic findings, brain imaging findings, and clinical heterogeneity. The view emerging is that spasmodic dysphonia is a manifestation of disordered motor control involving systems of neurons rather than single anatomical sites. (Arch Neurol. 1991;48:305-309)
Çîpasmodic dysphonia (SD) turbance of
is
a
dis¬
phonation diagnosed
by perceptual voice characteristics.1
Accepted for publication August 1, 1990. From the Dallas (Tex) Center for Vocal Motor Control (Drs Pool, Freeman, Finitzo, Hayashi, Chapman, Devous, Close, Kondraske, Mendelsohn, Schaefer, and Watson); the Neuroscience Research Center (Drs Pool and Finitzo); The University of Texas at Dallas\p=m-\Callier Center (Drs Freeman, Finitzo, Hayashi, Chapman, and Watson); the Departments of Radiology (Drs Devous and Mendelsohn) and Otolaryngology (Drs Close and Schaefer), The University of Texas Southwestern Medical Center at Dallas; and the Department of Biomedical Engineering, The University of Texas at Arlington (Dr Kondraske). Reprints not available.
Existence of SD, type and severity of SD, and presence or absence of vocal tremor are determined by vocal fea¬ tures and laryngeal examination. As one might expect in a disorder without objective diagnostic criteria, there is substantial clinical heterogeneity. Three subtypes of SD are described by perceptual and acoustic vocal charac¬ teristics: adductor, abductor,2 and mixed.3 Adductor SD is associated with involuntary hyperadduction of the vocal folds, resulting in a "strained-strangled" voice quality. Abductor SD is characterized by in¬ voluntary abductions of the vocal folds, resulting in intermittent bursts of breathy phonation. Mixed SD has been applied to patients who exhibit a full range of these vocal characteris¬ tics. Hoarseness, pitch breaks, limited intensity range, and poor intensity control are present in all types. Cannito and Johnson3 proposed that SD is a "continuum disorder" in which both types of spasms occur with differing
frequencies.
Much of the early literature de¬ scribes the "typical" patient with SD as "normal" except for vocal symp¬ toms.46 However, Robe et al7 and Aronson et al8 reported frequent abnormal neurologic examination findings in subjects with SD. More recently, re¬ searchers have come to view SD as a movement control disorder affecting the larynx9·10 or as a form of adult-on¬ set, focal dystonia.1113 Others have sug¬ gested that SD may also be observed in a number of different movement disorders.1416 Aronson et al14 and Aron-
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/09/2015
son
and Hartman15 associated adduc¬
tor SD with essential voice tremor. Jankovic and Ford16 included 21 sub¬
jects with SD in a large (100-subject) study of blepharospasm and orofacialcervical dystonia, and characterized SD as an incomplete expression of Meige's disease. While observation of
SD in other movement disorders is well documented, the frequency and type of neurologic findings and their relation to the vocal characteristics remain ill defined. This study reports the findings of voice and neurologic (ie, motor and somatosensory) examina¬ tions in 45 subjects with SD and poses the following questions: 1. Are there neurologic abnormali¬ ties in subjects with SD? 2. If so, do some abnormalities occur more frequently than others? 3. Are type, duration, and severity of SD related to neurologic examina¬ tion findings? '
SUBJECTS AND METHODS
Subjects
Forty-five subjects with SD who were evaluated at the Dallas (Tex) Center for Vocal Motor Control between January 1987 and March 1989 were included in this study. Evaluation procedures are described in an article by Finitzo and Freeman.10 No sub¬ ject had a prior recognized stroke, demen¬ tia, or mental retardation. No subject had a prior diagnosed neurologic disorder. Otolaryngologic examinations were performed to exclude subjects with structural abnor¬ malities of the larynx and/or vocal tract. Fifteen potential normal control, agematched subjects were also examined. Two subjects were rejected for use as normal
controls because of memory deficits. One subject was rejected because of current use of psychoactive medication. The remaining 12 subjects had normal findings on all 29 features reported herein. These subjects also served as control subjects in other as¬ pects of our research.
Table 1.—Neurologie Abnormalities Among Type(s) extremity RAM rate Lower extremity RAM rhythm Upper extremity RAM rate Upper extremity weakness Upper extremity RAM rhythm Upper extremity reflexes
were conducted by speech-language pathologists. Evalua¬ tion sessions were videotaped for reliability checks. Type (ie, adductor, abductor, or mixed), severity (ie, mild, moderate, or se¬ vere), and presence of vocal tremor were evaluated perceptually and judged by a consensus of the two speech-language pa¬ thologists and one otolaryngologist. Acous¬ tic measures were also completed for all subjects. Indirect laryngoscopy for move¬ ment abnormalities was performed on all subjects. Fiberoptic video tape recordings of laryngeal, pharyngeal, and velar move¬ ments (as reported in Freeman et al17) were undertaken for 40% of these subjects. These approaches were used to evaluate re¬ liability of the independently derived per¬ ceptual categorizations.
Lower
Upper extremity tremor Upper extremity sensory impairments Upper extremity rigidity Lingual weakness Head/neck sensory impairments Head/neck weakness
Head/neck involuntary movements
Upper extremity involuntary movements Upper extremity spasticity involuntary movements Head/neck rigidity Upper extremity incoordination Lower extremity tremor Lower extremity involuntary movements Lower extremity spasticity Orofacial sensory impairments Lower extremity rigidity Lower extremity incoordination Lower extremity sensory impairments RAM indicates rapid alternating movement. Orofacial
Neurologic Examination
Neurologic examinations were conducted by an experienced, board-certified neurolo¬ gist (K.D.P.). The neurologic examination findings reported here are limited to motor function, somatosensory thresholds, coor¬ dination, and reflexes. Twenty-nine fea¬
Table
Age,
RESULTS
Subject Description
Table 2 is a summary of subject de¬ mographic and vocal characteristics.
Twenty-one subjects (46.7%) were classified as having adductor SD; eight (17.8%), abductor SD; and 16 (35.5%), mixed SD. Twenty-eight subjects
Abductor
Mixed 16 39.8
28-70
20-70
Sex 16
M
10
Handedness
Right Left
Severity Mild
duration, severity,
accurate.
Adductor
45
y
Range
Statistical Analysis Two-tailed t tests, 2, and Fisher's Exact Test1819 were used to determine whether neurologic abnormalities in the subjects with SD were randomly distributed. Rela¬
significantly
and Vocal Characteristics
Mean
classified as either normal or abnor¬ mal. Abnormal indicates that the subject was outside the range of normal variation for age and gender.
were
and number of neurologic abnormalities were examined using F tests for compari¬ sons involving categorical variables and Spearman's rank correlation for compari¬ sons involving only continuous variables.19 "Classification and Regression Trees" (CART)20 was used to examine relation¬ ships among combinations of voice and neurologic examination findings. This anal¬ ysis procedure2022 is nonparametric and nonlinear. We used prior class frequencies, Gini's impurity function for tree construc¬ tion, and a 1.0 SE cutoff for tree selection from 10-fold cross validation. The tree, if any, meeting these criteria was classified as
2.—Demographic Overall
No. of subjects
tures were examined and are listed in Table 1. Features for each body part examined
among age,
.
Head/neck tremor extremity weakness Lingual RAM rate Orofacial reflexes
Voice examinations
two
tionships
No. (%) 19(42.2) 16(35.6) 16(35.6) 14(31.1) 13(28.9) 11 (24.4) 10 (22.2) 10 (22.2) 9 (20.0) 9 (20.0) 9 (20.0) 7 (15.6) 6(13.3) 5(11.1) 5 (11.1) 4(8.9) 3 (6.7) 3 (6.7) 3 (6.7) 2 (4.4) 2 (4.4) 1 (2.2) 1 (2.2) 1 (2.2) 1 (2.2) 1 (2.2) 0 (0) 0 (0) 0 (0)
Lower
Voice Evaluation
Subjects*
18
Severe
Duration,
y
Mean
7.9
Range
1-40
1-40
Tremor Present
ity
2-13
2-25
13
The absent category includes three of their spasmodic dysphonia.
subjects whose vocal
(62.2% ) had vocal tremor. Perceptual evidence of vocal tremor was not iden¬ tified in 14 subjects and could not be reliably determined in three subjects because of the severity of adductor-
type spasms. Severity
was
years). Family history data
were
judged
as
mild in 16 subjects (35.6%); moderate in 18 (40.0% ); and severe in 11 (24.4% ). Duration of SD symptoms ranged from 1 to 40 years (mean duration, 7.9 obtained
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tremor was unmeasurable because of the
sever¬
for 44 of 45 subjects with SD and are summarized in Table 3. A total of 13 (29.5%) of 44 subjects with SD had a family history of SD, essential tremor, or both. Five subjects with SD (11.4% ) had relatives with other movement disorders such as Parkinson's disease (6.7%), spasmodic torticollis (2.2%), and blepharospasm (2.2%). The sub¬ ject with blepharospasm in her family also had family members with SD and essential tremor.
Table 3.—Family History Data Obtained From 44 Subjects With
Spasmodic Dysphonia (SD) No. (%)
Abnormal Findings SD and essential tremor SD and essential tremor
(9.1) (2.2) 8(18.2) 13 (29.5) 4 1
SD only Essential tremor only Total Other movement disorders Parkinson's disease
(6.7) (2.2) 1 (2.2) 5(11.4) 3
Torticollis
1
Blepharospasm Total
There was no significant correlation between duration of SD and number of examination findings (r .28; 1.89; >.05) or between age and duration of SD (r .13; 0.86; > .05). Age, gender, type, severity, vocal tremor, and duration of vocal symp¬ toms were compared for the neurolog¬ ically abnormal (n 32) and normal (n 13) subjects with SD. Age and duration of SD were tested using twotailed t tests. Gender, type, and sever¬ ity of SD and vocal tremor were tested =
No. of
Findings
=
Fig 1.—Distribution of 203 positive neurologic examination findings in the 32 subjects with spas¬ modic dysphonia demonstrating neurologic examination abnormalities.
=
=
=
=
using 2.
The mean age of neurologically ab¬ normal subjects was 46.8 years vs 39.8 years for neurologically normal sub¬ jects. This difference was not signifi¬ cant (i 1.94; df= 43; > .05). Neuro¬ logically abnormal subjects had a higher frequency of vocal tremor than the neurologically normal subjects ( 2 8.70; df= 1; < .01). Of 28 sub¬ jects with vocal tremor, 24 were neu¬ rologically abnormal. Of 14 without vocal tremor, only five were neurolog¬ ically abnormal. All three subjects whose vocal tremor could not be deter¬ mined because of frequency and sever¬ ity of vocal spasms were neurologically abnormal. Gender ( 2 1.66; df=l P>.05) and type ( 2 1.97; d/= 2 =
=
RAM
Weakness Reflexes Tremor Sensory
Rigidity Spasticity Involuntary Incoordination Movements
Fig 2. Frequency of neurologic examination findings by type for 45 subjects with spasmodic dysphonia. RAM indicates rapid alternating movements. —
=
=
Neurologic Examination
2.13). Abnormali¬ were predominantly bilateral. Only six (18.8% ) of the 32 subjects with SD and neurologic abnormalities dem¬ onstrated asymmetries on examina¬ tion. In all six, the left side of the body was more impaired than the right side (P < .032; binomial distribution). The severity of SD was related to the age of the subject (F 5.2; df= 2,42; < .01); ie, SD tended to be more severe in the older subjects. Severity was not related to duration (F 0.5; df= 2,42; > .05) or number of neu¬ rologic examination abnormalities (F 2.03; d/=2,42; > .05). There was a significant correlation between jects ( ties
Neurologic abnormalities were found in 32 (71.1% ) of 45 subjects with SD. The mean number of neurologic abnormalities in these 32 subjects was 6.3 per subject, with a range from one to 17. Thirteen subjects (28.9% ) had no abnormal findings on the neurologic examination. Distribution of abnor¬ malities in the 32 subjects is shown in Figi.
Table 1 lists the occurrence of ab¬ normal findings. Rapid alternating
movement (RAM) abnormalities, weakness, and tremor were common (Fig 2). Incoordination and spasticity
rarely observed. Significant right-left asymmetry
were was
not characteristic of
these sub-
>
.05; 2
=
=
=
=
age and number of examination abnor¬ malities (r .47; = 3.15; < .008). =
There
was no
significant correlation
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.05), severity ( 2 2.19; df=2 .05), and duration (t .92; df= 43: .05) of SD did not differ between the two subject groups. To investigate relationships among vocal and neurologic findings, we at¬ tempted to construct classification trees. This was possible for severity > > >
but not for type
=
=
or
duration of SD. Se¬
verity was correctly classified for 71% of subjects. For three levels of severity (mild, moderate, and severe), the ex¬ pected chance accuracy for an individ¬ ual subject would be 33%. Correct
classification was achieved for 69% of the subjects with mild SD, for 56% of subjects with moderate SD, and for 100% of subjects with severe SD. The rules can be summarized as follows: • If the subject is 46 years or younger, and the lower extremity rate
is normal, then the SD is mild. Of 16 subjects meeting these criteria, 11 (65%) had mild SD, five (35%) had moderate SD, and none had severe SD. • If the subject is 46 years or younger, and the lower extremity rate is abnormal and the lingual rate is normal, then the SD is moderate. Of seven subjects with these characteris¬ tics, five (71%) had moderate SD, two (29%) had mild SD, and none had severe SD. If the lingual rate is also abnormal, then the SD is severe. Of two subjects with this finding, both (100%) had severe SD. • If the subject is older than 46 years, severity depends on the type of SD. If the subject has abductor SD, the SD will be moderate. Of five subjects with these characteristics, five (100% ) had moderate SD. If the type is mixed or adductor, and the subject is older than 46 years, the SD is severe. Of 15 subjects with these characteristics, three (20%) had mild SD, three had moderate SD, and nine (60% ) had se¬ vere SD. COMMENT
The majority (71.1%) of subjects with SD had abnormal neurologic ex¬ amination findings. Most frequent ab¬ normalities were of lower extremity RAM rate and rhythm, upper extrem¬ ity RAM rate and rhythm, upper ex¬ tremity strength, and upper extremity reflexes. This "clustering" refutes the hypothesis that neurologic abnormal¬ ities in SD are randomly distributed. These findings are a confirmation of the earlier work of Aronson et al8 and Robe et al7 despite the substantial clinical heterogeneity among subjects with SD and the methodological dif¬ ferences in study design. The fre¬ quency (71% vs 75% ) and pattern (Fig 3) of abnormal neurologic examination findings in our subjects is strikingly similar to those in the study of Aron¬ son et al.8 Vocal tremor was identified in 62.2% of our subjects and 51.8% of those in Aronson and colleagues' study. Abnormal neurologic examina¬ tion findings were more frequent in the subjects with SD who had perceptual vocal tremor. Although in our study we did not find a relationship between age and the presence of abnormal neuro¬ logic examination findings, in both studies age was related to the number of neurologic findings; ie, older sub¬ jects tended to have more abnormal findings than younger subjects. The combination of age and type of SD, in conjunction with the presence of spe¬ cific neurologic findings (lower extrem¬ ity RAM rate, and lingual diadokinetic rate), was significantly related to the
Fig 3.—Comparison of neurologic examination features reported by Aronson spasmodic dysphonia with parallel features in the current study.
et alB as "linked"
to
severity of the disorder. Specific neurologic abnormalities, whether frequent or infrequent, pro¬ vide insight into the mechanisms of SD. Impaired RAM in terms of either rate or rhythm may be seen with
involvement of cerebellar, basal gan¬ glial, or upper motor neuron pathways. Absence of dysmetria or ataxia also argues against a primary cerebellar lesion. Further, Cannito,23-2'' in a study of quantitative motor performance in a subgroup of subjects with SD (female subjects with adductor SD), also failed to find evidence of cerebellar dysfunc¬
tion. Co-occurrence of tremor and ri¬
gidity with RAM abnormalities would support
a
localization to the basal
ganglia. This localization is in theoret¬ ical agreement with hypotheses that SD is a laryngeal dystonia and that dystonias 13 arise from the basal ganglia." Co-occurrence of weakness and hyperreflexia with RAM abnor¬ malities implicates upper motor neu¬ ron pathways. A model of SD is posited wherein known projections from basal ganglia to cortex provide a link between these disparate components. This model is
based on several documented brainbehavior relations and neural path¬ ways. Direct intraoperative electrocortical stimulation of the supplemen¬
area (SMA) produces speech arrest and perseverative utter¬
tary motor
ances.25 Acute lesions of the SMA in the dominant hemisphere in man re¬ sult in severe impairment of sponta¬
neous speech.26 Thalamocortical pro¬ jections to the SMA are greatest from
the pars oralis of the ventrolateral nu¬ cleus of the thalamus (VLJ.27 Affér¬ ents to the VL0 are primarily from basal ganglia (globus pallidus).27 Con-
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sequently, involvement of the globus pallidus, projections from the globus pallidus itself to the VL0, the VL0 itself, projections from the VL0 to the SMA, or the SMA itself might produce the speech impairments in SD. Our brain imaging studies agree
with localizations derived from these neurologic examination findings. Me¬ sial frontal cortex is one of the most frequent areas of abnormality in both our anatomical and functional brain imaging studies.10 The region of great¬ est anatomical signal change on mag¬ netic resonance imaging was subcortical white matter underlying mesial frontal cortex, an area traversed by thalamocortical projections to this cortical region.28 A significant correla¬ tion between electrophysiology and re¬ gional cerebral blood flow was seen in the left anterior cortical quadrant in the same subjects.2' Thus, a common region of abnormal neuronal function appears to be the mesial frontal lobe, as evidenced by findings on both neu¬ rologic examination and brain imag¬ ing studies. Our imaging technologies may be more sensitive to involvement of the SMA or its thalamocortical pro¬ jections than of the globus pallidus or thalamic nuclei. If involvement of this pallidothalamic-SM A system is at the level of the SMA, the examination findings should be dominated by cortical signs and the imaging measures should show corti¬ cal dysfunction. If the involvement is at the globus pallidus, the examination findings should be dominated by basal ganglial signs and the findings of the brain imaging studies should be nor¬ mal (a finding in 16% of our subjects10). Thus, involvement of a pallidothalamic-SMA system could account for the
bulk of the associated neurologic ex¬ amination and brain imaging findings, and result in the observed clinical het¬
erogeneity.
While we are far from unraveling the precise pathogenesis of SD, the view emerging from converging lines of investigation is that SD is a mani¬ festation of disordered motor control. The disordered motor control involves systems of neurons rather than single
anatomical sites. Thus, it cannot be referred to as a cortical or basal gan¬ glial disorder. The manner in which other lesion sites may modulate the primary manifestation is also com¬ plex, but hypotheses about these rela¬ tionships are now being formed. Ulti¬ mately, our ability to understand SD reflects the current state of examina¬ tions of the function and dysfunction of the nervous system and the power of
a
multidisciplinary approach
dress such
'
to ad¬
complex questions.
Funding for this project was provided by Na¬ tional Institute of Neurological Disorders and Stroke grant 18276 to the University of Texas at Dallas. The authors wish to acknowledge the contribu¬ tions of the subjects with spasmodic dysphonia and of the normal control subjects. Data entry was provided by Deborah Thomas; and statistical assistance, by our students Jackie Clark, Susan Reamy Rampy, and B. Alan Rampy.
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