Triggering essential head tremor with sustained phonation: A clinical phenomenon with potential diagnostic value

Here we report a clinical phenomenon that we have observed repeatedly in clinical research settings; namely, a triggering and/or exacerbation of head tremor during or immediately following sustained phonation. To our knowledge, it has not been reported previously nor has it been the subject of study. Here we: 1) report the phenomenon, 2) provide several visual illustrations, 3) estimate its prevalence, and 4) analyze its clinical correlates. Head tremor was assessed qualitatively, and scores were assigned pre-, during, and post-sustained phonation using the Tremor Research Group Essential Tremor Rating Assessment Scale. Seventy (68.6%) of 102 essential tremor (ET) patients exhibited a qualitative increase in head tremor amplitude during and/or immediately after sustained phonation; in 5 (4.9%), head tremor would not have been detected without the voice activation maneuver (i.e., it was not visible at any other point in the videotape aside from the period during/immediately following sustained phonation). Women were more likely than men to exhibit this phenomenon (p = 0.05), whereas age, age at onset, duration of tremor, and total tremor score did not predict responsiveness of head tremor to sustained phonation. Sustained voice activation is a useful examination maneuver that may elicit or amplify head tremor in ET. Head tremor is not reported to occur in patients with enhanced physiological tremor. Thus, this maneuver, by triggering head tremor, may be a useful diagnostic supplement, particularly in research/clinical settings where arm tremor is mild and the diagnosis (mild ET vs. enhanced physiological tremor) would otherwise be ambiguous.     

Voice quality of psychological origin

Variations in voice quality are essentially related to modifications of the glottal source parameters, such as: F0, jitter, and shimmer. Voice quality is affected by prosody, emotional state, and vocal pathologies. Psychogenic vocal pathology is particularly interesting. In the present case study, the speaker naturally presented a ventricular band voice whereas in a controlled production he was able to use a more normal phonation process. A small corpus was recorded which included sustained vowels and short sentences in both registers. A normal speaker was also recorded in similar tasks. Annotation and extraction of parameters were made using Praat's voice report function. Application of the Hoarseness Diagram to sustained productions situates this case in the pseudo-glottic phonation region. Analysis of several different parameters related to F0, jitter, shimmer, and harmonicity revealed that the speaker with psychogenic voice was capable of controlling certain parameters (e.g. F0 maximum) but was unable to correct others such as shimmer.     

Voice quality of psychological origin

Variations in voice quality are essentially related to modifications of the glottal source parameters, such as: F₀, jitter, and shimmer. Voice quality is affected by prosody, emotional state, and vocal pathologies. Psychogenic vocal pathology is particularly interesting. In the present case study, the speaker naturally presented a ventricular band voice whereas in a controlled production he was able to use a more normal phonation process. A small corpus was recorded which included sustained vowels and short sentences in both registers. A normal speaker was also recorded in similar tasks. Annotation and extraction of parameters were made using Praat's voice report function. Application of the Hoarseness Diagram to sustained productions situates this case in the pseudo‐glottic phonation region. Analysis of several different parameters related to F₀, jitter, shimmer, and harmonicity revealed that the speaker with psychogenic voice was capable of controlling certain parameters (e.g. F₀ maximum) but was unable to correct others such as shimmer.     

Voice tremor: dysregulation of voluntary expiratory muscles

We studied three patients: two with voice and hand tremor, and one with voice tremor. Voice tremor was associated with synchronous rhythmic contraction of cricothyroid and rectus abdominis muscles, but not always vocalis muscle. Voice tremor was manifested only in voluntary phonation or expiration, not in involuntary phonation, voluntary inspiration, or involuntary expiration and inspiration (breathing at rest). Impaired regulation of the CNS programs innervating the voluntary expiratory muscles probably causes voice tremor. Clonazepam and propranolol were helpful in blinded studies.     

Voice acoustic changes during bilateral subthalamic stimulation in patients with Parkinson's disease

Objectives

The purpose of this study was to investigate the effects of bilateral subthalamic nucleus deep brain stimulation on the phonation of patients with Parkinson's disease in three drug-free conditions: (1) stimulation off, (2) with clinically optimised stimulation parameters, and (3) subthreshold overstimulation, in order to detect differences following voice analysis.

Patients and methods

Conversational speech and sustained vowel sounds /a/, /i/, /o/, /u/ and high /i/ were recorded from 22 PD patients. Perceptual analysis, perturbation jitter, shimmer, noise-to-harmonics ratio, and nonlinear dynamic analysis (NDA) with detrended fluctuation analysis and recurrence period density entropy were measured and compared to the above conditions. Quadratic discriminant analysis (QDA) was used to investigate stimulation conditions for given acoustic data.

Results

The changes of perturbation measurements for the above conditions were not significant. With differences between vowels, NDA showed more significant changes and more powerful correlation with perceptual scores than perturbation measurements. NDA was significantly more sensitive during the QDA of the conditions.

Conclusions

Acoustic voice analysis of sustained vowels can help with recognizing the overstimulated condition, and, with an appropriate test battery and software package including nonlinear dynamic analysis, it can be a valuable tool for fine adjustments of stimulation parameters.     

Cerebellar axial postural tremor

Three cases are presented with a predominantly axial postural tremor, without visible palatal tremor. Tremor varied in frequency between 3 and 10 Hz, often jumping from one frequency to another in this band. All three patients had evidence of cerebellar pathology. Cases 1 and 2 developed tremor in the setting of a lateLondon, Englandonset cerebellar degeneration and after excision of a right cerebellar haemangioblastoma, respectively. Etiology was unclear in Case 3. Nevertheless, this patient had a cerebellar dysarthria. The tremor was similar to that sometimes seen in conjunction with palatal tremor, and EMG studies in Case 3 demonstrated a subclinical modulation of palatal muscle activity simultaneous with the truncal tremor. It is suggested that an axial postural tremor may be due to pathology of the cerebellum and its outflow pathways, despite the absence of clinically apparent palatal tremor.     

Effects of smoking on respiratory capacity and control

The purpose of this study was to provide information concerning the possible early effects of smoking on measures of respiratory capacity and control in young adult female smokers vs. nonsmokers. In particular, maximum performance test results (vital capacity and maximum phonation time) and measures of air pressures and airflows during voiceless, stop‐plosive productions were analysed. Subjects were 45 female nonsmokers and 30 female smokers (total n = 75) between the ages of 18–30 years. For the purposes of this study, a smoker was defined as any subject who, at the time of this study, had smoked at least two cigarettes per day for at least 1 year. All of the subjects in the nonsmoker category were those who, at the time of this study, did not smoke and who had not smoked for at least 5 years prior to the study. Vital capacity measures were conducted using a hand‐held digital spirometer, while maximum phonation productions and voiceless, stop‐plosive pressures and flows were recorded and measured using the Aerophone II Model 6800 (Kay Elemetrics Corp., Lincoln Park, NJ). Results showed significantly lower vital capacities and maximum phonation times in smokers vs. nonsmokers. The maximum phonation time task was also produced with significantly higher mean airflow rates in smokers than nonsmokers. In addition, the smokers were observed to produce significantly greater peak and mean pressures during the voiceless stop‐plosive task than the nonsmokers. A weak, but significant correlation was observed between the number of days the subject had smoked and the mean pressure produced during the voiceless, stop‐plosive task. The findings of reduced respiratory capacity and control in smokers may be associated with factors such as increased bronchial reactivity secondary to exposure to cigarette smoke and/or mild airway obstruction, increased airflow secondary to increased glottal gap size during phonation, and increased vocal fold mass and/or inefficiency in vocal fold closure. The findings of this study indicate that decrements in respiratory capacity and control may occur even in relatively young smokers who have only been smoking for a comparatively short time     

Effects of smoking on respiratory capacity and control

The purpose of this study was to provide information concerning the possible early effects of smoking on measures of respiratory capacity and control in young adult female smokers vs. nonsmokers. In particular, maximum performance test results (vital capacity and maximum phonation time) and measures of air pressures and airflows during voiceless, stop-plosive productions were analysed. Subjects were 45 female nonsmokers and 30 female smokers (total n = 75) between the ages of 18-30 years. For the purposes of this study, a smoker was defined as any subject who, at the time of this study, had smoked at least two cigarettes per day for at least 1 year. All of the subjects in the nonsmoker category were those who, at the time of this study, did not smoke and who had not smoked for at least 5 years prior to the study. Vital capacity measures were conducted using a hand-held digital spirometer, while maximum phonation productions and voiceless, stop-plosive pressures and flows were recorded and measured using the Aerophone II Model 6800 (Kay Elemetrics Corp., Lincoln Park, NJ). Results showed significantly lower vital capacities and maximum phonation times in smokers vs. nonsmokers. The maximum phonation time task was also produced with significantly higher mean airflow rates in smokers than nonsmokers. In addition, the smokers were observed to produce significantly greater peak and mean pressures during the voiceless stop-plosive task than the nonsmokers. A weak, but significant correlation was observed between the number of days the subject had smoked and the mean pressure produced during the voiceless, stop-plosive task. The findings of reduced respiratory capacity and control in smokers may be associated with factors such as increased bronchial reactivity secondary to exposure to cigarette smoke and/or mild airway obstruction, increased airflow secondary to increased glottal gap size during phonation, and increased vocal fold mass and/or inefficiency in vocal fold closure. The findings of this study indicate that decrements in respiratory capacity and control may occur even in relatively young smokers who have only been smoking for a comparatively short time.     

Orthostatic tremor associated with voice tremor.

We report a 67-year-old female with orthostatic and voice tremor. Her orthostatic tremor mainly affected her lower extremities, alternating between antagonist muscle groups at a frequency of 4.4-4.8 Hz. The voice tremor ranged between 4.8 and 8.8 Hz. In this case, the frequency of voice tremor was same as that of orthostatic tremor, suggesting a common origin from a tremor-generating mechanism. These tremors were diagnosed as 'forme fruste' of the essential tremor, not the incipient stage of Parkinson's disease. Medications including clonazepam, perphenazine, Dopa and trihexyphenidyl hydrochloride had no effect on both the orthostatic and voice tremors, but propranolol was somewhat beneficial on voice tremor.     

Essential tremor and cerebellar dysfunction: abnormal ballistic movements

BACKGROUND: Clinical characteristics reminiscent of cerebellar tremor occur in patients with advanced essential tremor. Ballistic movements are known to be abnormal in cerebellar disease. The hypothesis was proposed that ballistic movements are abnormal in essential tremor, reflecting cerebellar dysfunction. OBJECTIVE: To elucidate the role of the cerebellum in the pathophysiology of essential tremor. METHODS: Kinematic parameters and the triphasic electromyographic (EMG) components of ballistic flexion elbow movements were analysed in patients assigned to the following groups: healthy controls (n = 14), pure essential postural tremor (ET(PT); n = 17), and essential tremor with an additional intention tremor component (ET(IT); n = 15). RESULTS: The main findings were a delayed second agonist burst (AG(2)) and a relatively shortened deceleration phase compared with acceleration in both the essential tremor groups. These abnormalities were most pronounced in the ET(IT) group, which had additional prolongation of the first agonist burst (AG(1)) and a delayed antagonist burst (ANT). CONCLUSIONS: Abnormalities of the triphasic pattern and kinematic parameters are consistent with a disturbed cerebellar timing function in essential tremor. These abnormalities were most pronounced in the ET(IT) group. The cerebellar dysfunction in essential tremor could indicate a basic pathophysiological mechanism underlying this disorder. ET(PT) and ET(IT) may represent two expressions within a continuous spectrum of cerebellar dysfunction in relation to the timing of muscle activation during voluntary movements.     

A 3 C/SEC LEG TREMOR IN A "CEREBELLAR" SYNDROME

A unique leg tremor was found in patients with late (acquired) cerebellar atrophy. Such patients are classically said to show a cerebellar incoordination in the heel-knee test. The tremor was evoked in three sustained leg postures inducing bingle plane oscillations. In these tests the tremor occurred as leg extensions, adductions or torsions. Accelerometer records showed a simple 2.5–3.5 c/sec rhythm. The amplitude varied but the rate was remarkably Constant. The heel-on-knee position elicited tremor activity in muscles working in various planes; the resulting compound oscillation could be confused with irregular goal-seaking movements.     

Deep brain stimulation and tremor

Deep brain stimulation (DBS) has been used to treat various tremor disorders for several decades. Medication-resistant, disabling essential tremor (ET) is the most common tremor disorder treated with DBS. The treatment has been consistently reported to result in significant benefit in upper extremity, as well as head and voice tremor, all of which were improved more dramatically with bilateral procedures. These benefits have been demonstrated to be sustained for up to 7 years. DBS has also been shown to be beneficial for the tremor associated with multiple sclerosis and post-traumatic tremor; however, fewer cases have been reported and the benefit is less consistent, less dramatic, and more transient than that seen with ET. The ventral intermediate nucleus of the thalamus is the most common DBS target for tremor disorders, but more recent studies have demonstrated benefits in tremor from DBS of the subthalamic area, primarily the zona incerta. Surgical complications are relatively uncommon and are generally less frequent than those seen with thalamotomy. Stimulation-related effects are usually mild and resolve with adjustment of stimulation parameters. DBS is thus a relatively safe and effective treatment for tremor disorders, particularly for medication-resistant, disabling ET, but may also have some role in medication-resistant, disabling tremor associated with multiple sclerosis and traumatic head injury.     

Acoustic analysis of voice in dysarthria following stroke

Although perceptual studies indicate the likelihood of voice disorders in persons with stroke, there have been few objective instrumental studies of voice dysfunction in dysarthria following stroke. This study reports automatic analysis of sustained vowel phonation for 61 speakers with stroke. The results show: (1) men with stroke and healthy elderly men exhibited an identical voice profile, and men with stroke had only one significantly larger noise parameter (SPI—soft phonation index) than young healthy men; and (2) women with stroke and healthy elderly women exhibited an identical voice profile, except that women with stroke exhibited a significantly higher SPI than healthy elderly women. Although there were no significant differences in smoothed pitch perturbation quotient (sPPQ) and SPI between healthy elderly women and healthy young women, women with stroke exhibited significantly larger sPPQ and SPI than healthy young women. It is suggested that studies on sub‐groups of the stroke population that use a combination of perceptual and acoustic analyses will better illuminate the voice dysfunction in dysarthria following stroke.     

Analysis of selected parameters of tremor recorded by a biaxial accelerometer in patients with parkinsonian tremor, essential tremor and cerebellar tremor

BACKGROUND AND PURPOSE: Accelerometric registration of tremor with the subsequent estimation of its parameters allows objective collection of information. The aim of the study was an analysis and visualization of the signal of the recorded tremor, including assessment of spectral components at the dominant frequency and selection of those parameters that are most useful in differentiation of tremor types. MATERIAL AND METHODS: We examined 44 patients with parkinsonian tremor (PT), 39 patients with essential tremor (ET), and 13 patients with cerebellar tremor (CT), diagnosed clinically using the criteria of the Movement Disorders Society and the Tremor Investigation Group. The control group consisted of 26 healthy persons. A biaxial accelerometer mounted at the dorsal surface of the hand was used. Spectral analysis was performed. The analysis focused on determination of spectrum shape, frequency of spectral peaks, centre frequency, standard deviation of the centre frequency, harmonic index, as well as changes in frequency over time. RESULTS: In patients with pathological tremor (PT, ET, and CT), a single spectral peak was observed that persisted for the whole registration period. In the control group, tremor was characterized by a wide range of spectral frequencies with marked variability in time. Statistical analysis revealed significantly lower frequencies of the highest peak and of the central frequency, a significantly smaller standard deviation of the central frequency and a significantly higher harmonic index in cases of pathological tremors as compared to the control group. CONCLUSIONS: The presented method enables distinction between pathological and physiological tremor and helps in differentiation of various types of pathological tremor.     

Linking Essential Tremor to the Cerebellum—Animal Model Evidence

In this review, we hope to stimulate interest in animal models as opportunities to understand tremor mechanisms within the cerebellar system. We begin by considering the harmaline model of essential tremor (ET), which has ET-like anatomy and pharmacology. Harmaline induces the inferior olive (IO) to burst fire rhythmically, recruiting rhythmic activity in Purkinje cells (PCs) and deep cerebellar nuclei (DCN). This model has fostered the IO hypothesis of ET, which postulates that factors that promote excess IO, and hence PC complex spike synchrony, also promote tremor. In contrast, the PC hypothesis postulates that partial PC cell loss underlies tremor of ET. We describe models in which chronic partial PC loss is associated with tremor, such as the Weaver mouse, and others with PC loss that do not show tremor, such as the Purkinje cell degeneration mouse. We postulate that partial PC loss with tremor is associated with terminal axonal sprouting. We then discuss tremor that occurs with large lesions of the cerebellum in primates. This tremor has variable frequency and is an ataxic tremor not related to ET. Another tremor type that is not likely related to ET is tremor in mice with mutations that cause prolonged synaptic GABA action. This tremor is probably due to mistiming within cerebellar circuitry. In the final section, we catalog tremor models involving neurotransmitter and ion channel perturbations. Some appear to be related to the IO hypothesis of ET, while in others tremor may be ataxic or due to mistiming. In summary, we offer a tentative framework for classifying animal action tremor, such that various models may be considered potentially relevant to ET, subscribing to IO or PC hypotheses, or not likely relevant, as with mistiming or ataxic tremor. Considerable further research is needed to elucidate the mechanisms of tremor in animal models.     

The usefulness of accelerometric registration with assessment of tremor parameters and their symmetry in differential diagnosis of parkinsonian, essential and cerebellar tremor

Background and purposeThe aim of the study was to perform an analysis of the recorded tremor using accelerometry and select those parameters that are the most useful in differentiation of tremor types.Material and methodsWe examined 45 patients with parkinsonian tremor (PT), 39 patients with essential tremor (ET) and 35 patients with cerebellar tremor (CT). The control group consisted of 52 healthy persons. The analysis included tremor intensity, frequency of spectral peaks, centre frequency, standard deviation of the centre frequency, and harmonic index. Parameters of tremor were compared between particular groups of patients with pathological tremor and with the control group. The side-to-side symmetry of these parameters was also analysed.ResultsTremor intensity was significantly higher in patients than in controls. There was a significant side-to-side asymmetry of intensity in all patient groups. Significantly lower peak frequency, centre frequency and standard deviation of centre frequency were found in patients compared to the control group. The frequency was symmetric in ET and in controls, but asymmetric in other subjects. The differences between hands regarding the standard deviation of centre frequency were significantly greater in all patient groups than in controls, who revealed no difference of this parameter between sides. Harmonic index was significantly greater and asymmetric in all groups of patients when compared to the control group.ConclusionsStandard deviation of centre frequency and harmonic index are the most valuable variables in differentiation of tremor. The assessment of symmetry of tremor parameters is useful in discrimination of various types of pathological tremor.     

Deficits in fine motor coordination in children with unintelligible speech

Summary An auditory and acoustic analysis was performed of the voice production of 24 children between 5 and 8 years of age with unintelligible speech and 24 children without speech or language deficits matched for age. Two aspects of voice production were assessed, prephonatory tuning and phonatory modulation. The categories used for the auditory assessment were preutterance vocalizations, abnormal initiation, rough voice, breathy voice, tense voice, voice tremor, intraphonemic disruption and pitch break. The acoustic analysis consisted of calculation of the mean fundamental frequency and the pitch perturbation factor in repetitions of the series of syllables |pa|, |ta|, |ka|. Intrasyllabic pitch breaks were also noted. The children with unintelligible speech had significantly more signs of abnormal prephonatory tuning and abnormal phonatory modulation than the control children. The findings suggest that voice production in unintelligible children has not yet become automatized. This possibility is discussed in relation to the central control of phonation.This work was supported in part by grant no. II B7 — AM 63/1–2 from the Deutsche Forschungsgemeinschaft     

Comparison of cerebellar intention tremor under isotonic and isometric conditions

The characteristics of cerebellar intention tremor were investigated by comparing the properties of tremor following movements about the elbow with that following isometric contractions of biceps and triceps brachii. Cerebellar dysfunction was produced by local, reversible cooling of the dentate and interposed nuclei in three Cebus monkeys. Cerebellar nuclear cooling disrupted isometric contractions to the aimed target and produced oscillations in torque. Whereas the cerebellar tremor that followed movements was regular and had a frequency of 3-5 Hz, the oscillations in the isometric task were irregular and were often of a lower frequency. In addition, cycles of tremor following movements were in phase from trial to trial, while the oscillations that occurred following isometric contractions did not show this phase-relationship. It is concluded that a cerebellar tremor can occur in an isometric situation but that movement about a joint is required for development of a rhythmic 3-5-Hz cerebellar intention tremor.     

3 Hz postural tremor: A specific and sensitive sign of cerebellar dysfunction in patients with cerebellar ataxia

Objective3 Hz postural tremor was described in patients with anterior cerebellar lobe atrophy, however sensitivity and specificity of this sign in degenerative cerebellar diseases has not yet been evaluated. Our aim was to assess the 3 Hz tremor in patients with cerebellar ataxia, compare its sensitivity and specificity with other posturography parameters and to find out a correlation of intensity of 3 Hz tremor with ataxia severity.Methods30 patients with degenerative cerebellar ataxia, a control group of 30 patients with compensated peripheral vestibulopathy and 40 healthy volunteers were examined by posturography. 3 Hz tremor was assessed both qualitatively and quantitatively, its sensitivity and specificity were compared with other standard posturography parameters.Results3 Hz postural tremor was detected in 90% of patients with cerebellar ataxia, with 100% specificity and 90% sensitivity. The sensitivity and specificity of quantitative analysis of 3 Hz tremor was largely superior to standard posturography parameters when differentiating patients with cerebellar ataxia from vestibular impairment and healthy controls.Conclusion3 Hz postural tremor is highly sensitive and specific sign of cerebellar impairment in patients with cerebellar ataxia.SignificanceEvaluation of 3 Hz postural tremor should be a standard part of posturography examination when considering a cerebellar impairment.     

Targeting the Red Nucleus for Cerebellar Tremor

Deep brain stimulation of the thalamus (and especially the ventral intermediate nucleus) does not significantly improve a drug-resistant, disabling cerebellar tremor. The dentato-rubro-olivary tract (Guillain-Mollaret triangle, including the red nucleus) is a subcortical loop that is critically involved in tremor genesis. We report the case of a 48-year-old female patient presenting with generalized cerebellar tremor caused by alcohol-related cerebellar degeneration. Resistance to pharmacological treatment and the severity of the symptoms prompted us to investigate the effects of bilateral deep brain stimulation of the red nucleus. Intra-operative microrecordings of the red nucleus revealed intense, irregular, tonic background activity but no rhythmic components that were synchronous with upper limb tremor. The postural component of the cerebellar tremor disappeared during insertion of the macro-electrodes and for a few minutes after stimulation, with no changes in the intentional (kinetic) component. Stimulation per se did not reduce postural or intentional tremor and was associated with dysautonomic symptoms (the voltage threshold for which was inversed related to the stimulation frequency). Our observations suggest that the red nucleus is (1) an important centre for the genesis of cerebellar tremor and thus (2) a possible target for drug-refractory tremor. Future research must determine how neuromodulation of the red nucleus can best be implemented in patients with cerebellar degeneration.