Discipline-specific consensus

A recent consensus statement on classification of tremors was published by the Task Force on Tremor by the International Parkinson and Movement Disorder Society (IPMDS).² This task force clinically defined ET as an “isolated tremor syndrome of bilateral upper limb action tremor with or without tremor in other locations (e.g., head, voice, lower limbs) and in the absence of other neurological signs like dystonia, ataxia, or parkinsonism for at least 3 years duration.”² A period of 3 years was selected as the minimum criterion based on the consensus that this time frame allows elucidation of progression of disease associated with eventual onset of other neurological signs such as ataxia, parkinsonism, or dystonia.^{2 (p.17)} For individuals describing duration of symptoms for less than 3 years, the term “indeterminate tremor” is recommended until the criterion of 3 years duration of symptoms is met.^{2 (p.6)} Isolated focal tremors involving the voice, head, orthostatic tremor (frequency > 12 Hz), task- and position-specific tremors, and report of sudden onset or step-wise deterioration are considered exclusion criteria for ET and ET plus. “ET plus” was proposed as a separate or extended classification to include those meeting the definition of ET exhibiting additional soft clinical signs of unclear significance possibly indicative of potential subgroupings.² As such, those with isolated onset of vocal tremor are no longer classified as a variant of ET unless they develop signs and symptoms commensurate with the new definition.

The most recent consensus related to movement disorders affecting the larynx was published in 2005 by a committee representing the Academy of Otolaryngology – Head and Neck Surgery (AAO-HNS).³ Although an earlier publication, the statement by this committee drives current standards of practice in the field of otolaryngology for evaluating and treating those with movement disorders affecting the larynx and other head and neck structures. Within this document, a description of clinical features of ET and variants affecting the larynx and other speech and respiratory structures involved in speech production were provided. This committee used the term, “laryngeal essential tremor,” rather than EVT since the larynx is the primary structure associated with voice production during speech. However, clinical features associated with laryngeal ET included observation of vertical oscillation of the larynx (i.e., tremor affecting strap musculature influencing the vertical position of the larynx) as well as tremor affecting articulators (e.g., pharyngeal constrictors, intrinsic laryngeal muscles, tongue, soft palate, jaw, and lips) and respiratory system musculature. This committee also highlighted the fact that tremor affecting the larynx would not be classified as “rest” tremor given that the laryngeal musculature is actively involved in respiratory posturing when it is not otherwise engaged in the activities of phonation and swallowing.^4–10 Differentiation between laryngeal tremor of the essential versus dystonic type was reliant on the task specificity of laryngeal behavior during volitional speech tasks compared to nonvolitional respiration (i.e., tidal breathing). Individuals with essential laryngeal tremor were described to exhibit oscillation of speech structures during both respiration and speech tasks (i.e., non-task specific). Those with a dystonic type of laryngeal tremor would demonstrate oscillation of speech structures during volitional tasks such as sustained phonation or speech production, and potentially exhibit improved signs/symptoms in response to sensory tricks, including placement of the nasoendoscope or application of topical anesthesia.

Unfortunately, no group publishing expert consensus-based documents integrated multi-disciplinary expertise on their panels. Representation of salient expertise across related disciplines beyond the primary sponsoring entity would improve generalizability and accuracy of the final classification system. Consequently, both consensus documents offer limited generalizability and accuracy related to the “isolated voice tremor” phenotype. The AAO-HNS group introduced a term, laryngeal ET that does not sufficiently represent involvement of the extra-laryngeal articulators. Although their intent was to link ET manifesting in the larynx, associated clinical features demonstrate that tremor is not typically restricted to the larynx and can involve the respiratory musculature. As such, reference to laryngeal ET is misleading. The IPMDS relied heavily on a systematic review of the literature to inform their updated classification system distinguishing between clinical phenomenology and etiologies (i.e., Axis I versus Axis II criteria). The new classification system accommodates change in the clinical phenotype of individuals diagnosed with ET. In this way, the new tremor classification system may provide new insights regarding the pathophysiology of focal or isolated forms of tremor that may be distinct from ET or ET plus forms. However, the current classification system of tremor referred to “isolated voice tremor” as a focal tremor in the same way as tremor affecting individual structures such as the jaw or head. However, voice production requires coordination across multiple structures innervated by cranial and spinal nerves. The idea that vocal tremor is focal, or “isolated,” may stem from the focus on acoustic measures as a surrogate to tremor patterns affecting speech structures. The voice is a radiating quasiperiodic and modulated airstream resulting from the coordinated contribution of respiratory and articulatory structures. However, studies of individuals with vocal tremor have not yet linked the affected speech apparatus kinematics to associated voice signal patterns. Although tremor has been observed in respiratory and articulatory structures, the larynx as the sound generator is typically the focus of study in those with vocal tremor. Yet, the literature demonstrates that those with EVT distinctly exhibit tremor across multiple structures coordinated and innervated through bilateral cranial and spinal nerve output.

Clinical features of vocal tremor and EVT

In contrast to the vast literature describing the clinical features and phenotypes of ET and other classifications of tremor, the literature describing vocal tremor does not offer comparable information regarding kinematic measures of speech structure tremor rate, or detailed characteristics of onset and progression of the disorder. More typically, studies describing those with EVT confirm that there is either an associated diagnosis of ET, or no other associated neurological diagnoses with onset of voice symptoms. The systematic description of participant’s duration of disease, family history, duration of vocal tremor, age of onset, activation condition(s), body distribution, and other important information for clinical phenotyping is absent in the majority of literature describing those affected with EVT. Alternatively, these individuals are commonly studied among the same cohort with those exhibiting vocal tremor associated with other neurological disorders, including spasmodic dysphonia. As such, it can be difficult to extract clinical features and phenotypes for those with EVT that distinguish them from other clinical phenotypes of vocal tremor.

Vocal tremor is generally considered a neurogenic voice disorder characterized by modulation of pitch and loudness.^11–16 Individuals with this disorder report increased effort during speaking and worsening of their vocal tremor during stressful activities that promote anxiety or require more concentration and effort.^3,17,18 Most individuals believe vocal tremor to be typical of age-related changes in the voice.^19,20 As such, many individuals with vocal tremor may not seek treatment, as suggested by community-based studies of ET²¹ and general population estimates of those with voice disorders.^22,23 Those seeking treatment for vocal tremor frequently have co-occurring neurological diagnoses with the majority having ET followed by dystonia (e.g., spasmodic dysphonia) and other neurodegenerative diseases (e.g., Parkinson’s disease, cerebellar degeneration, and myasthenia gravis).^24–26

Literature characterizing vocal tremor, in general, describes clinical features of tremor affecting the respiratory system,^4,27–29 tongue,^11,13,29,30 jaw,^29,31,32 soft palate,^10,29,33,34 and larynx.^{12,13,15–17,29,30,35} Clinical characteristics of vocal tremor are best identified and characterized during sustained phonation of a vowel.^{11,17,36–38} However, judgment of the severity of the vocal tremor should consider the degree of impact on connected speech rather than judgment limited to the sustained phonation condition.^11,38 Nasoendoscopic examination enables direct observation of upper airway structures such as the soft palate, base of the tongue, larynx, and pharyngeal walls during respiratory activity as well as during sustained phonation and connected speech-related tasks.^29,30 Additional direct observation of the face, lips, jaw, and palpation of the respiratory system can be used to identify other structures of the speech apparatus contributing to the perceived vocal tremor.²⁹ A thorough evaluation enables accurate documentation regarding the presence/absence of tremor across speech structures to determine whether tremor appears postural, kinetic, or dystonic (i.e., task specific).

EVT as a clinical variant of ET

The revised classification of tremors requires careful documentation of distinct clinical phenotypes. Based on a limited review of literature describing those classified as EVT, improved documentation of clinical phenotyping is needed. Only three of 30 published studies specific to EVT offered adequate clinical characterization to assure accurate classification. Based on the small number of carefully conducted studies documenting characteristics of those with EVT, the majority of affected individuals reported onset of vocal tremor prior to onset of tremor in the upper extremities required for classification as ET. Interestingly, the current classification criteria for ET include those exhibiting spread of tremor along the motor somatotopy of the body from the upper extremities to the neck (i.e., head) and respiratory/articulatory structures. This represents a spread from spinal to cranial (or midline) structures as a more common clinical phenotype. However, nearly 70% of those with EVT were reported by one study to exhibit the opposite spread of tremor beginning in the midline structures (i.e., cranial) to the upper extremities. This suggests a reverse clinical phenotype of tremor in ~1/3 of individuals eventually meeting inclusion criteria for ET originally classified as “isolated voice tremor.” Although further systematic work is needed regarding clinical characteristics of those with EVT, current evidence suggests an action tremor at a rate between 4 and 10 Hz and a similar family history rate as expected for those with ET. The primary distinction of individuals with EVT is the disproportionate representation of females and the direction of tremor spread from cranial to spinal motor somatotopy. Another topic for future consideration is to compare treatment responses between those classified with “isolated voice tremor” and those with ET and vocal tremor. Several published studies that did not meet inclusion criteria for this article provide evidence that those with vocal tremor due to EVT or ET may exhibit similar improvement in voice symptomatology as those with bilateral limb tremor classified as ET in response to pharmaceutical treatment^43–48 and deep brain stimulation (DBS).^49–52

Although “isolated voice tremor” may offer a unique clinical phenotype in onset and progression, it appears to be a variant of ET rather than a distinct clinical phenotype. Eventually, ET and EVT may be considered clinical phenotypic variants of tremor in the same way regional variants of amyotrophic lateral sclerosis (ALS) inform disease prognosis and pathophysiology.⁵³