Exploring Neurophysiological Mechanisms and Treatment Efficacies in Laryngeal Dystonia: A Transcranial Magnetic Stimulation Approach.

Laryngeal dystonia (LD), known or termed as spasmodic dysphonia, is a rare movement disorder with an unknown cause affecting the intrinsic laryngeal muscles. Neurophysiological studies point to perturbed inhibitory processes, while conventional genetic studies reveal fragments of genetic architecture in LD. The study's aims are to (1) describe transcranial magnetic stimulation (TMS) methodology for studying the functional integrity of the corticospinal tract by stimulating the primary motor cortex (M1) for laryngeal muscle representation and recording motor evoked potentials (MEPs) from laryngeal muscles; (2) evaluate the results of TMS studies investigating the cortical silent period (cSP) in LD; and (3) present the standard treatments of LD, as well as the results of new theoretical views and treatment approaches like repetitive TMS and laryngeal vibration over the laryngeal muscles as the recent research attempts in treatment of LD. Neurophysiological findings point to a shortened duration of cSP in adductor LD and altered cSP duration in abductor LD individuals. Future TMS studies could further investigate the role of cSP in relation to standard laryngological measures and treatment options. A better understanding of the neurophysiological mechanisms might give new perspectives for the treatment of LD.

Expression of Connexins 37, 40 and 45, Pannexin 1 and Vimentin in Laryngeal Squamous Cell Carcinomas.

Approximately 60% of patients with squamous cell carcinoma (LSCC) have regional occult metastatic disease/distant metastases at the time of diagnosis, putting them at higher risk for disease progression. Therefore, biomarkers are needed for early prognostic purpose. The aim of this study was to analyze the expression pattern of connexins (Cx) 37, 40 and 45, pannexin1 (Panx1) and vimentin in LSCC and correlate with tumor grade (G) and outcome. METHODS: Thirty-four patients who underwent (hemi-)laryngectomy and regional lymphadenectomy due to LSCC from 2017 to 2018 in University Hospital Split, Croatia, were studied. Samples of tumor tissue and adjacent normal mucosa embedded in paraffin blocks were stained using the immunofluorescence method and were semi-quantitatively analyzed. RESULTS: The expression of Cx37, Cx40, and Panx1 differed between cancer and adjacent normal mucosa and between histological grades, being the highest in well-differentiated (G1) cancer and low/absent in poorly differentiated (G3) cancer (all p < 0.05). The expression of vimentin was the highest in G3 cancer. Expression of Cx45 was generally weak/absent, with no significant difference between cancer and the controls or between grades. Lower Panx1 and higher vimentin expression were found to be prognostic factors for regional metastatic disease. Lower Cx37 and 40 expressions were present in patients with disease recurrence after the three-year follow-up period. CONCLUSION: Cx37 and Cx40, Panx1, and vimentin have the potential to be used as prognostic biomarkers for LSCC.

The Cortical Silent Period in the Cricothyroid Muscle as a Neurophysiologic Feature for Dystonia Observation: E-Field-Navigated Transcranial Magnetic (TMS) Study.

The cortical silent period (cSP) is a period of electrical silence following a motor-evoked potential (MEP) in the electromyographic signal recorded from a muscle. The MEP can be elicited by transcranial magnetic stimulation (TMS) over the primary motor cortex site corresponding with the muscle. The cSP reflects the intracortical inhibitory process mediated by GABAA and GABAB receptors. The study aimed to investigate the cSP in the cricothyroid (CT) muscle after applying e-field-navigated TMS over the laryngeal motor cortex (LMC) in healthy subjects. Then, a cSP as a neurophysiologic feature for laryngeal dystonia was observed. We applied a single-pulse e-field-navigated TMS to the LMC over both hemispheres with hook-wire electrodes positioned in the CT muscle in nineteen healthy participants, which triggered the elicitation of contralateral and ipsilateral corticobulbar MEPs. The subjects were engaged in a vocalization task, and then we assessed the following metrics: LMC intensity, peak-to-peak MEP amplitude in the CT muscle, and cSP duration. The results showed that the cSP duration from the contralateral CT muscle was distributed from 40 ms to 60.83 ms, and from the ipsilateral CT muscle, from 40 ms to 65.58 ms. Also, no significant difference was found between the contralateral and ipsilateral cSP duration (t(30) = 0.85, p = 0.40), MEP amplitude in the CT muscle (t(30) = 0.91, p = 0.36), and LMC intensity (t(30) = 1.20, p = 0.23). To conclude, the applied research protocol showed the feasibility of recording LMC corticobulbar MEPs and observing the cSP during vocalization in healthy participants. Furthermore, an understanding of neurophysiologic cSP features can be used to study the pathophysiology of neurological disorders that affect laryngeal muscles, such as laryngeal dystonia.

The Patho-Neurophysiological Basis and Treatment of Focal Laryngeal Dystonia: A Narrative Review and Two Case Reports Applying TMS over the Laryngeal Motor Cortex.

Focal laryngeal dystonia (LD) is a rare, idiopathic disease affecting the laryngeal musculature with an unknown cause and clinically presented as adductor LD or rarely as abductor LD. The most effective treatment options include the injection of botulinum toxin (BoNT) into the affected laryngeal muscle. The aim of this narrative review is to summarize the patho-neuro-physiological and genetic background of LD, as well as the standard recommended therapy (BoNT) and pharmacological treatment options, and to discuss possible treatment perspectives using neuro-modulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and vibrotactile stimulation. The review will present two LD cases, patients with adductor and abductor LD, standard diagnostic procedure, treatments and achievement, and the results of cortical excitability mapping the primary motor cortex for the representation of the laryngeal muscles in the assessment of corticospinal and corticobulbar excitability.