Thalamic Deep Brain Stimulation for Spasmodic Dysphonia: A Phase I Prospective Randomized Double-Blind Crossover Trial.

BACKGROUND: Adductor spasmodic dysphonia (SD) is a dystonia of the vocal folds causing difficulty with speech. The current standard of care is repeated botulinum toxin injections to weaken the adductor muscles. We sought to ameliorate the underlying neurological cause of SD with a novel therapy-deep brain stimulation (DBS). OBJECTIVE: To assess the safety of DBS in SD through phase I trial, and to quantify the magnitude of any benefit. METHODS: Six patients had left ventral intermediate nucleus (Vim) thalamic DBS and were randomized to 3 mo blinded-DBS "on" or "off" followed by a crossover. Primary outcomes were quality of life and quality of voice during the blinded phase. Patients continued with open-DBS "on." Secondary outcomes were comparisons of pre- and 1-yr cognitive, mood, and quality of life. This trial was registered with ClinicalTrials.gov (NCT02558634). RESULTS: There were no complications. Every patient reported an improvement in quality of life (P = .07) and had an improvement in quality of their voice (P = .06) when their blinded DBS was "on" versus "off." The trend did not reach statistical significance with the small sample size. Secondary outcomes showed no difference in cognition, an improvement in mood, and quality of life at 1 yr. CONCLUSION: This phase I randomized controlled trial confirmed that DBS can be performed safely in patients with SD. Blinded DBS produced a strong trend toward improved quality of life and objective quality of voice despite the small sample size. The cerebellar circuit, not the pallidal circuit, appears to be crucial for motor control of the vocal folds.

Hemi-laryngopharyngeal Spasm (HeLPS): Defining a New Clinical Entity.

OBJECTIVE: Hemi-laryngopharyngeal spasm (HeLPS) has recently been described in the neurosurgical literature as a cause of intermittent laryngopharyngeal spasm and cough due to vascular compression of the vagus nerve at the cerebellopontine angle. We present the diagnostic criteria for this syndrome. METHODS: A retrospective chart review of six patients with HeLPS and three patients misdiagnosed with this condition are presented. All patients were diagnosed and treated at a tertiary care academic centre from July 2013 to July 2017. RESULTS: Patients with HeLPS had five defining characteristics: 1) All patients had symptoms of episodic laryngopharyngeal spasm and coughing. Patients were asymptomatic between episodes and were refractory to speech therapy and reflux management. 2) Laryngoscopy showed hyperactive twitching of the ipsilateral vocal fold in two of the six patients. No other inter-episodic abnormalities were seen. 3) Botulinum toxin A injections into the thyroarytenoid muscle on the affected ipsilateral side reduced laryngopharyngeal spasms. Botulinum toxin injection in the contralateral thyroarytenoid muscle did not improve laryngopharyngeal spasm. 4) Magnetic resonance imaging revealed ipsilateral neurovascular compression of the vagus nerve rootlets by the posterior inferior cerebellar artery. 5) Microvascular decompression (MVD) surgery of the ipsilateral vagus nerve resolved all symptoms (follow-up 2-4 years). CONCLUSION: The diagnostic criteria for hemi-laryngopharyngeal spasm (HeLPS) are proposed. Otolaryngology recognition of this new clinical entity may lead to a surgical cure and avoid the unnecessary therapies associated with misdiagnosis. LEVEL OF EVIDENCE: 4.

Concurrent Glossopharyngeal Neuralgia and Hemi-Laryngopharyngeal Spasm (HeLPS): A Case Report and a Review of the Literature.

BACKGROUND AND IMPORTANCE: Hemi-laryngopharyngeal spasm (HeLPS) has been recently described but is not yet widely recognized. Patients describe intermittent coughing and choking and can be cured following microvascular decompression of their Xth cranial nerve. This case report and literature review highlight that HeLPS can co-occur with glossopharyngeal neuralgia (GN) and has been previously described (but not recognized) in the neurosurgical literature. CLINICAL PRESENTATION: A patient with GN and additional symptoms compatible with HeLPS is presented. The patient reported left-sided, intermittent, swallow-induced, severe electrical pain radiating from her ear to her throat (GN). She also reported intermittent severe coughing, throat contractions causing a sense of suffocation, and dysphonia (HeLPS). All her symptoms resolved following a left microvascular decompression of a loop of the posterior inferior cerebellar artery that was pulsating against both the IXth and Xth cranial nerves. A review of the senior author's database revealed another patient with this combination of symptoms. An international literature review found 27 patients have been previously described with symptoms of GN and the additional (but not recognized at the time) symptoms of HeLPS. CONCLUSION: This review highlights that patients with symptoms compatible with HeLPS have been reported since 1926 in at least 4 languages. This additional evidence supports the growing recognition that HeLPS is another neurovascular compression syndrome. Patients with HeLPS continue to be misdiagnosed as conversion disorder. The increased recognition of this new medical condition will require neurosurgical treatment and should alleviate the suffering of these patients.

Vagus Associated Neurogenic Cough Occurring Due to Unilateral Vascular Encroachment of Its Root: A Case Report and Proof of Concept of VANCOUVER Syndrome.

OBJECTIVES: A patient is presented with neurogenic cough due to a unilateral vascular compression of a vagus nerve rootlet at the brainstem with complete resolution of cough following microvascular decompression of that nerve. This etiology of a neurogenic cough has not been previously reported to our knowledge. The proportion of patients with neurogenic cough refractory to all current therapies and suffering with this treatable condition remains to be defined. We introduce the concept of Vagus Associated Neurogenic Cough Occurring due to Unilateral Vascular Encroachment of its Root (VANCOUVER syndrome) and present the salient features of this condition. METHODS: A case review is presented with details of the patient's history, examination, imaging, laryngoscopy, intraoperative findings, and long-term clinical outcome. RESULTS: A 60-year-old man presented with a 15-year history of non-productive cough refractory to antibiotics, and anti-reflux medications. Investigations by an allergist, a cardiologist, a gastroenterologist, two pulmonologists, and an otolaryngologist were negative. MRI demonstrated a vascular compression of his left vagus nerve and microvascular decompression of that nerve resolved his symptoms. There were no surgical complications and the patient remains asymptomatic at 1 year. CONCLUSIONS: Neurogenic cough has been likened to a vagus nerve neuropathy in a similar way that trigeminal neuralgia is a trigeminal nerve neuropathy. Both cause intermittent sensory phenomena in their distribution and can be ameliorated with neuropathic medications. We demonstrate that neurogenic cough, like trigeminal neuralgia, may be caused by a vascular compression of its nerve root. A proposed mechanism of this type of neurogenic cough is presented along with a potential diagnostic paradigm for these patients.

Hemi-laryngopharyngeal spasm as a novel cause of inducible laryngeal obstruction with a surgical cure: report of 3 cases.

Inducible laryngeal obstruction has been described under at least 40 different monikers, including vocal cord dysfunction, paroxysmal vocal fold motion, and irritable larynx. The etiology of this condition is believed to be laryngeal hyperactivity in response to psychological issues or acid reflux. Most patients are treated with some combination of proton pump inhibitors, speech therapy, and psychotherapy. However, a small cohort of patients remains refractory to all medical interventions. The authors describe a novel condition, hemi-laryngopharyngeal spasm (HELPS), which can cause severe episodic stridor leading to unconsciousness in association with cough. The first recognized and surgically cured patient with HELPS was reported in an earlier issue of this journal. Three additional patients have been followed up for at least a year postoperatively, and their cases are reported here.Each patient presented with a similar pattern of episodic coughing and choking that increased in frequency, severity, and duration over years. The episodes eventually occurred while sleeping and could cause severe stridor with loss of consciousness. All three patients were initially misdiagnosed with a psychiatric illness and subjected to multiple intubations and one tracheostomy. Unilateral botulinum toxin injections in the vocal fold eased the severity of the throat contractions but not the cough. Magnetic resonance imaging showed a looping posterior inferior cerebellar artery juxtaposed to a vagus nerve in each case. Microvascular decompression (MVD) of that vessel relieved all symptoms.The introduction of this new medical condition may help a small cohort of patients with inducible laryngeal obstructions that have not responded to the current standard treatments. Patients are asymptomatic between episodes of progressively severe coughing and choking with stridor that may lead to intubation. Severe anxiety about the unpredictable symptoms is expected and may contribute to a psychiatric misdiagnosis. Microvascular decompression for HELPS is more difficult than that for trigeminal neuralgia because the involved nerve is more susceptible to manipulation. Ultimately, the final proof that HELPS is a real and distinct syndrome will require its recognition and successful treatment by colleagues around the world.

The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: interrogating cerebellar and pallidal neural circuits.

Spasmodic dysphonia (SD) is a neurological disorder of the voice where a patient's ability to speak is compromised due to involuntary contractions of the intrinsic laryngeal muscles. Since the 1980s, SD has been treated with botulinum toxin A (BTX) injections into the throat. This therapy is limited by the delayed-onset of benefits, wearing-off effects, and repeated injections required every 3 months. In a patient with essential tremor (ET) and coincident SD, the authors set out to quantify the effects of thalamic deep brain stimulation (DBS) on vocal function while investigating the underlying motor thalamic circuitry. A 79-year-old right-handed woman with ET and coincident adductor SD was referred to our neurosurgical team. While primarily treating her limb tremor, the authors studied the effects of unilateral, thalamic DBS on vocal function using the Unified Spasmodic Dysphonia Rating Scale (USDRS) and voice-related quality of life (VRQOL). Since dystonia is increasingly being considered a multinodal network disorder, an anterior trajectory into the left thalamus was deliberately chosen such that the proximal contacts of the electrode were in the ventral oralis anterior (Voa) nucleus (pallidal outflow) and the distal contacts were in the ventral intermediate (Vim) nucleus (cerebellar outflow). In addition to assessing on/off unilateral thalamic Vim stimulation on voice, the authors experimentally assessed low-voltage unilateral Vim, Voa, or multitarget stimulation in a prospective, randomized, doubled-blinded manner. The evaluators were experienced at rating SD and were familiar with the vocal tremor of ET. A Wilcoxon signed-rank test was used to study the pre- and posttreatment effect of DBS on voice. Unilateral left thalamic Vim stimulation (DBS on) significantly improved SD vocal dysfunction compared with no stimulation (DBS off), as measured by the USDRS (p < 0.01) and VRQOL (p < 0.01). In the experimental interrogation, both low-voltage Vim (p < 0.01) and multitarget Vim + Voa (p < 0.01) stimulation were significantly superior to low-voltage Voa stimulation. For the first time, the effects of high-frequency stimulation of different neural circuits in SD have been quantified. Unexpectedly, focused Voa (pallidal outflow) stimulation was inferior to Vim (cerebellar outflow) stimulation despite the classification of SD as a dystonia. While only a single case, scattered reports exist on the positive effects of thalamic DBS on dysphonia. A Phase 1 pilot trial (DEBUSSY; clinical trial no. NCT02558634, clinicaltrials.gov) is underway at the authors' center to evaluate the safety and preliminary efficacy of DBS in SD. The authors hope that this current report stimulates neurosurgeons to investigate this new indication for DBS.

Buckled Thyroid Cartilage: An Anatomic Variant.

OBJECTIVE: Anatomic abnormalities in the larynx can cause significant and bothersome symptoms. Identified here is an anatomical variant of the thyroid cartilage. STUDY DESIGN: This study is a retrospective case series of 11 subjects diagnosed with an anatomic variant of the thyroid cartilage. METHODS: Patients with an anatomic inward buckling of the thyroid cartilage, termed here as buckled thyroid cartilage, were identified through a 20-year retrospective chart review of a tertiary care laryngology practice. RESULTS: We describe 11 patients with fullness or asymmetry in the area of the false vocal fold and an associated inward buckling of the thyroid cartilage on computed tomography scan. All patients presented with a bothersome voice-related complaint. The most common presenting complaints were hoarseness (54%), globus sensation (45%), or vocal fatigue (27%). One patient was found to have a history of known laryngeal trauma. Surgical correction through an external approach on one patient was successfully performed with subsequent resolution of symptoms. CONCLUSION: We postulate that deformity and protrusion of the false vocal fold can result in a dampening effect on the vibratory capacity of the vocal fold that can lead to symptomatic hoarseness and vocal fatigue. Buckled thyroid cartilage is, therefore, an important anatomical variant to be aware of and be able to recognize.

Unilateral Thalamic Deep Brain Stimulation for Voice Tremor.

BACKGROUND: Voice tremor (VT) is the involuntary and rhythmical phonatory instability of the voice. Recent findings suggest that unilateral deep brain stimulation of the ventral intermediate nucleus (Vim-DBS) can sometimes be effective for VT. In this exploratory analysis, we investigated the effect of Vim-DBS on VT and tested the hypothesis that unilateral thalamic stimulation is effective for patients with VT. METHODS: Seven patients with VT and previously implanted bilateral Vim-DBS were enrolled in the study. Each patient was randomized and recorded performing sustained phonation during the following conditions: left thalamic stimulation, right thalamic stimulation, bilateral thalamic stimulation (Bil-ON), and no stimulation (Bil-OFF). Perceptual VT ratings and an acoustic analysis to find the rate of variation of the fundamental frequency measured by the standard deviation of the pitch (f0SD) were performed in a blinded manner. For the purposes of this study, a "dominant" side was defined as one with more than twice as much reduction in VT following Vim-DBS compared to the contralateral side. The Wilcoxon signed-rank test was performed to compare the effect of the dominant side stimulation in the reduction of VT scores and f0SD. The volume of activated tissue (VAT) of the dominant stimulation side was modelled against the degree of improvement in VT to correlate the significant stimulation cluster with thalamic anatomy. Finally, tractography analysis was performed to analyze the connectivity of the significant stimulation cluster. RESULTS: Unilateral stimulation was beneficial in all 7 patients. Five patients clearly had a "dominant" side with either benefit only seen following stimulation of one side or more than twice as much benefit from one side compared to the other. Two patients had similar benefit with unilateral stimulation from either side. The Wilcoxon paired test showed significant differences between unilateral dominant and unilateral nondominant stimulation for VT scores (p = 0.04), between unilateral dominant and Bil-OFF (p = 0.04), and between Bil-ON and unilateral nondominant stimulation (p = 0.04). No significant differences were found between Bil-ON and unilateral dominant condition (p = 0.27), or between Bil-OFF and unilateral nondominant (p = 0.23). The dominant VAT showed that the significant voxels associated with the best VT control were located in the most ventral and medial part of the Vim nucleus and the ventralis caudalis anterior internus nucleus. The connectivity analysis showed significant connectivity with the cortical areas of the speech circuit. CONCLUSIONS: Unilateral dominant-side thalamic stimulation and bilateral thalamic stimulation were equally effective in reducing VT. Nondominant unilateral stimulation alone did not significantly improve VT.

Episodic hemilaryngopharyngeal spasm (HELPS) syndrome: case report of a surgically treatable novel neuropathy.

The authors describe a novel cranial neuropathy manifesting with life-threatening episodic hemilaryngopharyngeal spasm (HELPS). A 50-year-old woman presented with a 4-year history of intermittent throat contractions, escalating to life-threatening respiratory distress. Botulinum toxin injections into her right vocal cord reduced the severity of her spasms, but the episodes continued to occur. MRI demonstrated a possible neurovascular conflict involving the cranial nerve IX-X complex and the posterior inferior cerebellar artery. Microvascular decompression of the upper rootlets of the vagal nerve eliminated her HELPS without complication. The authors propose a mechanism of HELPS implicating isolated involvement of the upper motor rootlets of the vagus nerve.

The Reliability of the Reflux Finding Score Among General Otolaryngologists.

BACKGROUND: The reflux finding score (RFS) is a validated clinical severity scale for findings of laryngopharyngeal reflux (LPR) on fiberoptic laryngoscopy. To our knowledge, there have been no studies to determine whether severity of patient symptoms influence the RFS; in addition, the reliability of the RFS has not been tested for general otolaryngologists. OBJECTIVES: The objectives of this study were (1) to determine whether the RFS for LPR is influenced by symptoms of reflux and (2) to determine the inter-rater reliability for general otolaryngologists in diagnosing LPR using the RFS. METHODS: Ten general otolaryngologists were selected to participate. Participants were asked to complete an Internet survey consisting of flexible endoscopic videos of larynges with varying physical findings of reflux and grade the severity of reflux using the RFS. The videos were randomly shown with and without accompanying patient symptoms. RESULTS: Our data suggest that patient symptoms influence the RFS. Inter-rater reliability for general otolaryngologists using the RFS is fair. CONCLUSIONS: Among general otolaryngologists in our study, the reliability and objectivity of the RFS in diagnosing reflux cannot be demonstrated.

Injection laryngoplasty with hyaluronic acid for unilateral vocal cord paralysis. Randomized controlled trial comparing two different particle sizes.

The objective was to determine if particle size affects durability of medialization in patients undergoing injection laryngoplasty (IL) with hyaluronic acid (HA) for unilateral vocal cord paralysis (UVCP). We hypothesized that large particle-size HA (LPHA) persists longer after injection to produce a more durable vocal result. The study design used was a prospective randomized controlled single-blind trial. Patients underwent IL with Restylane (small particle-size HA, SPHA) or Perlane (LPHA) (Q-Med AB, Uppsala, Sweden). Injections were performed transcutaneously in the outpatient clinic. The Voice Handicap Index (VHI) at 6 months postinjection was the primary outcome measure. Secondary outcomes included videostroboscopic findings, and objective acoustic and aerodynamic measures. Seventeen patients (eight SPHA, nine LPHA) were available for follow-up at 6 months. Normalized VHI scores at 6 months after IL were significantly lower in the LPHA group compared to the SPHA group when not adjusted for age and sex (P=0.027). After adjustment, the difference was not significant (P=0.053) but the LPHA group trended toward lower normalized VHI scores. The findings support the hypothesis that the larger particle-size of LPHA makes this material more durable than SPHA for IL. This material may be considered for temporary medialization in patients with UVCP in whom medium-term improvement of at least 6 months is desirable. The transcutaneous route can be used safely in the office setting in non-anticoagulated patients.

Laryngeal candidiasis in the outpatient setting.

OBJECTIVES: We present the largest case series on laryngeal candidiasis and review the literature on the diagnosis and management of laryngeal candidiasis. SUBJECTS AND METHODS: Fifty-four patients were included in a retrospective chart review of all cases seen at the Pacific Voice Clinic, University of British Columbia, Vancouver, from 1995 to 2005. RESULTS: The most common presenting symptom was dysphonia (37 patients; 69%). Forty-eight patients (89%) were on steroid inhalers, and four patients (7%) were on oral prednisone. In terms of anatomic involvement, 18 patients (33%) showed Candida involvement in all three anatomic locations: the hypopharynx, the supraglottis, and the glottis. In 15 patients (28%), the Candida was isolated to the glottis. The remaining patients showed subglottic and glottic involvement. Fifty-two patients (96%) were successfully treated with a single course of an oral antifungal. CONCLUSION: The most common risk factor identified was inhaled steroids. Most often, laryngeal candidiasis is effectively treated with oral antifungal medications.

Vocal cord medialization by transcutaneous injection of calcium hydroxylapatite.

Transcutaneous vocal cord augmentation has increasingly become the method of choice when treating causes of vocal cord insufficiency. Many substances have accompanied this technique, but they all have problems. One newer substance is calcium hydroxylapatite (CaHA). CaHA may produce fewer problems and offer a longer-lasting treatment. Twenty-one patients were treated in the Pacific Voice Clinic with trancutaneous injection of CaHA for vocal cord paralysis (n = 19) and vocal scarring (n = 2). Maximum phonation time (MPT) was the measure of vocal performance. An improvement was seen in 20 patients with the MPT, who improved from 4.6 seconds before treatment to 10.8 seconds at posttreatment of 3 months (n = 15). This improvement was maintained at 6 months (MPT = 12 seconds, n = 12). Follow-up was incomplete because of the terminal nature of some diagnoses and the large geographical area covered by the clinic. Three subjects had submucosal injection of CaHA (two resolving spontaneously). Two other patients had extrusion of the material. With short-term and medial-term follow-up on a small group of patients, encouraging results were seen with transcutaneous injection of CaHA for vocal cord augmentation.

Raman spectroscopy for optical diagnosis in the larynx: preliminary findings.

BACKGROUND AND OBJECTIVES: Raman spectroscopy (RS) provides information about molecular structure and is a potential tool for non-invasive tissue diagnosis. To determine if Raman spectra could be obtained rapidly from laryngeal tissue in vitro, and compare Raman spectra from normal, benign, and cancerous laryngeal tissue. STUDY DESIGN/MATERIALS AND METHODS: Forty-seven laryngeal specimens were studied using RS with signal acquisition times (SAT) between 1 and 30 second(s). Multivariate analysis was used to determine the diagnostic ability of RS compared to standard histology (n = 18, 13, and 16 respectively for normal tissue, carcinoma, and squamous papilloma). RESULTS: Good quality spectra were obtained with 5-second SAT. Spectral peak analysis showed prediction sensitivities of 89%, 69%, and 88%, and specificities of 86%, 94%, and 94% for normal tissue, carcinoma, and papilloma. CONCLUSIONS: In the larynx, spectral differences appear to exist between normal tissue, carcinoma, and papilloma. The ability to obtain spectra rapidly supports potential for future in vivo studies.

Selective denervation: reinnervation for the control of adductor spasmodic dysphonia.

OBJECTIVES: The objective of this study was to evaluate the efficacy of a new surgical procedure for adductor spasmodic dysphonia (AddSD). This surgery involves the bilateral selective division of the adductor branches of the recurrent laryngeal nerves with immediate reinnervation of the distal nerve trunks with branches of the ansa cervicalis (selective denervation-reinnervation). METHODS: Our first six patients to undergo this procedure were enrolled in the study. All patients suffered from AddSD and had previously received botulinum toxin A (Botox, Allergen, Markham, ON) therapy. Patients were recorded preoperatively and all underwent the same surgical procedure performed by the same lead surgeon. All patients were surveyed postoperatively and then re-recorded. Expert and untrained judges undertook perceptual evaluation of voice quality. Voice samples were also objectively evaluated for aphonic voice breaks. RESULTS: No major surgical complications were noted. Patient satisfaction was excellent, and five of the six patients no longer require botulinum toxin therapy. In five of the six patients, the majority of untrained and expert listeners perceived the postoperative voice to be superior. Objectively, the rate of aphonic voice breaks was also reduced in five of the six patients.

Raman spectroscopy for optical diagnosis in normal and cancerous tissue of the nasopharynx-preliminary findings.

BACKGROUND AND OBJECTIVES: Raman spectroscopy (RS), which can detect molecular changes associated with cancer, was explored as a means of distinguishing normal and cancerous nasopharyngeal tissue. STUDY DESIGN/PATIENTS AND METHODS: Tissue from six patients with normal and cancerous biopsies was studied using a rapid acquisition Raman spectrometer. RESULTS: Spectra were obtainable within 5 seconds. Consistent differences were noted between normal and cancer tissue in three bands 1,290-1,320 cm(-1) (P = 0.005), 1,420-1,470 cm(-1) (P = 0.006), and 1,530-1,580 cm(-1) (P = 0.002). CONCLUSIONS: Spectral differences appear to exist between normal and cancerous nasopharyngeal tissue. The ability to obtain spectra rapidly supports the potential for future in vivo application.

Extrinsic laryngeal muscular tension in patients with voice disorders.

The objective of this study was to establish a standard clinical evaluation tool for assessment by palpation of extrinsic laryngeal muscular tension (ELMT) and investigate the relationship between ELMT and different voice disorder diagnosis categories, particularly muscle misuse dysphonia (MMD), and the presence or absence of gastroesophageal reflux (GER). A palpation technique and tension grading system for four separate muscle groups (suprahyoid, thyrohyoid, cricothyroid, and pharyngolaryngeal) were established. 465 patients, 65% female and 35% male, were assessed sequentially and ELMT results were analyzed in relation to diagnosis and reflux status. A strong relationship was found between thyrohyoid muscle tension and both GER and MMD (p < or = 0.01). Thyrohyoid muscle tension is the only group that demonstrated a significant relationship with MMD. No significant difference in the ELMT scores was found between GER and non-GER patients, although a possible causal relationship was found between MMD type 3 and reflux. It is postulated that palpation of extrinsic laryngeal muscles can yield important information about internal laryngeal postures and diagnosis of muscle misuse voice disorders, particularly MMD type 3 (anteroposterior supraglottic compression). Integration of this technique into routine laryngeal examination can be a significant aid to diagnostic accuracy.