2003 Chhetri Histology of Nerves and Muscles in Adductor Spasmodic

Ann Otol Rhinal Laryngol 112:2003 HISTOLOGY OFNERVES AND MUSCLES INADDUCTOR SPASMODIC DYSPHONIA DINESH K. CHHETRI, MD JOEL H. BLUMIN, MD LosANGELES, CALIFORNIA PHILADELPHIA, PENNSYLVANIA HARRY V. VINTERS, MD GERALD S. BERKE, MD LosANGELES, CALIFORNIA LosANGELES, CALIFORNIA To elucidate the etiology and pathophysiology ofspasmodic dysphonia, weexamined the adductor branch ofthe recurrent laryn geal nerve and the lateral cricoarytenoid muscle from 9 consecutive patients with this disorder who were previously treated with botulinum toxin. Histologic examination revealed average muscle fiber diameters ranging from 21 to5711m. Botulinum toxin treat ment-related muscle atrophy was observed up to 5 months after injection. Endomysial fibrosis was present in all samples. His tochemical analysis in8patients revealed type 2fiber predominance in7 patients and fiber type grouping in2.Type-specific muscle fiber size changes were notpresent. Nerve samples were examined in plastic sections. In 8 patients the nerves contained homoge neous, large-diameter myelinated nerve fibers and sparse small fibers. One patient had a relatively increased proportion of small myelinated nerve fibers. Overall, the nerve fiber diameter was slightly larger inpatients than incontrols. These findings may impli cate thecentral nervous system inthepathophysiology of adductor spasmodic dysphonia. KEY WORDS - histology, muscle, nerve, pathophysiology, spasmodic dysphonia. INTRODUCTION Bielamowicz and Ludlow> reported improved EMG The etiology and pathophysiology of spasmodic signals in contralateral thyroarytenoid (TA) muscles dysphonia (SD) remain elusive even after more than after unilateral botulinum toxin (BTX) injection, and a century of discussion in the literature. Spasmodic they hypothesized that a central reduction in moto dysphonia is classified into adductor and abductor neuron activity secondary to reduced sensorimotor 6 types based on the laryngeal muscle groups affected. feedback could explain their findings. Ded0 com Adductor spasmodic dysphonia (ASD) is an adult mented that proprioceptive abnormalities may exist onset voice disorder characterized by a "strain-stran in patients and that these may be relieved after uni gle" voice quality and abrupt vocal stops associated lateral section ofthe recurrent laryngeal nerve (RLN). with abnormal closure of the vocal cords during The most common treatment for ASD is injection speech. There is a slight female predilection, and the of BTX type A (Allergan Inc, Irvine, California) into disorder has a persistent course. 1 Electromyographic the TA muscle'? It causes flaccid paralysis by inhib (EMG) studies of laryngeal muscles ofpatients with iting the release of acetylcholine from nerve termi ASD reveal pitch and phonatory breaks coincident nals." A variety of surgical therapies for ASD have with muscle spasms during vowels in connected been proposed. They include unilateral RLN section.f speech. I On the basis of these EMG findings, ASD midline lateralization thyroplasty.? and selective bi is currently classified as a focal dystonia affecting lateral laryngeal adductor denervation and reinnerva the larynx during speech.I-' tion.!" Laryngeal denervation and reinnervation is the Many etiologic theories of SD have been proposed. procedure of choice at our institution for a more per A long-standing psychogenic theory introduced by manent treatment of ASD. Lateral cricoarytenoid Traube in 1871 was replaced by a neurogenic theory (LCA) muscle myotomy is also now concurrently when Aronson et all reported a high incidence of as performed. In this report we describe the histomor sociated neurologic signs (mainly voice tremor) in phology of the adductor branch of the RLN and the patients with SD. Subsequent discussions have fo LCA muscle from patients who received this surgi cused on whether the disorder lies in the central or cal therapy for ASD. the peripheral nervous system. Finitzo-Hieber et al4 MATERIALS AND METHODS suggested a central causation based on abnormal wave V latencies from auditory brain stem reflex testing. Patients and Controls. This research protocol was From the Department ofSurgery, Division ofHead and Neck Surgery (Chhetri, Blumin, Berke), and the Department ofPathology and Labora tory Medicine, Section ofNeuropathology (Vinters), University ofCalifornia, Los Angeles, California. Presented at the meeting ofthe American Laryngological Association. Boca Raton. Florida, May 10-11, 2002. CORRESPONDENCE - Gerald S. Berke. MD. 62-132 CHS, UCLA Medical Center. Los Angeles, CA 90095. 334 Chhetri et al, Histology ofNerves & Muscles in Spasmodic Dysphonia 335 reviewed and approved by the Medical Institutional on a coverslip, and histologically and histochemically Review Board of the University of California, Los processed by routine procedures used almost daily in Angeles. Nine consecutive patients who received se the University ofCalifornia muscle diagnostic histo lective laryngeal adductor denervation, reinnervation, chemistry laboratory. The slides were observed and and LCA myotomy for ASD were enrolled in the photographed with a microscopeequippedwith a digi study. All had received prior BTX therapy. The rea tal camera system (Olympus BX40). Digital images son for surgery in all was either dissatisfaction with were taken at 200x to 400x and printed on a laser BTX therapy or loss ofBTX effectiveness, and a de printer. Muscle diameter was measured directly on sire for permanent surgical cure. Laryngoscopic ex the printed images by the "lesserfiber diameter" tech amination, acoustic analysis of voice, voice history nique described by Dubowitz and Brooke.l-' In this typical for ASD, and response to previous BTX treat technique the maximum diameter across the lesser ments were used to confirm the diagnosis ofASD. aspect of the muscle is measured, in order to over come the distortion that occurs when muscle fibers Five nerve specimens were analyzed as controls. are cut obliquely. At least 200 muscle fibers were The harvesting approach and location of control counted per muscle biopsy sample. Most of the his nerves were identical to those of the patient nerves. tologic information was obtained from sections that Two were from autopsies of adult patients who died had been stained with the modified Gomori trichrome, of cardiovascular disease. Other than short-term in because this stain demonstrates morphological fea tubation during intensive care, neither had a history tures of the muscle fibers well. The adenosine triphos oflaryngeal abnormalities. Two specimens were from phatase histochemical reaction was used to assess laryngectomies. The first was from a 47-year-old man fiber type. In this histochemical reaction, type 2 (fast) with a large supraglottic squamous cell carcinoma muscle fibers stain dark and type 1 (slow) muscle who had received no prior therapy. The right vocal fibers stain light when samples are preincubated at cord had impaired mobility, and therefore only the pH 9.6. 13 This staining pattern is reversed with prein left nerve branch was analyzed. The second was from cubation at pH 4.2 to 4.6. In some samples the whole a 73-year-old man with a history of radiotherapy for specimen did not undergo acid reversal; in these T3NOsupraglottic carcinoma who required laryngec cases, areas that reversed well were selected for anal tomy for epiglottic recurrence. The vocal cords were ysis. More than 75% prevalence of one fiber type mobile bilaterally. The fifth control specimen was was considered type predominance. from a 48-year-old woman with acute recurrent la ryngospasm (laryngeal adductory dystonia) who was Nerve Processing. The nerve biopsy specimens treated with laryngeal denervation, reinnervation, and were immediately immersion-fixed in 2% glutaral LCA myotomy. dehyde for at least 2 hours and post-fixed for 1 hour Nerve and Muscle Biopsy. Berke et apa have re in 1% osmium tetraoxide. The tissue was further pro ported the operative procedure for selective laryn cessedfor electron microscopy by standard techniques geal adductor denervation and reinnervation. The in and embedded in Epon. Sections I to 211mthick were tralaryngeal course of the adductor branch of the RLN cut and stained with toluidine blue for light micros has been reported by others. I I,12 A cartilage window copy. For electron microscopy, 50-nm ultrathin sec was created in the posterior inferior portion of the tions were cut, stained with uranyl acetate followed thyroid lamina. The anterior adductor branch of the by lead citrate, and examined and photographed at RLN was located, and a nerve stimulator was used 1,900x with atransmissionelectronmicroscope (JEOL to confirm the identification of the nerve. The nerve JEM-lOOCXII electron microscope). At least 3 pho branch was followed to the TA muscle and cut 5 mm tographs were taken per nerve sample. Each photo from its muscular insertion. A l-mm section was cut graph contained about 10 to 15 nerve fibers cut trans from the distal nerve stump and immediately im versely. mersed in 2% glutaraldehyde solution. The LCA Nerve fiber diameter was measured directly on the muscle was then identified and cut in its midsection photographs. The maximum diameter across the less with fine scissors. An approximately 5-mm-long sam er aspect of the fiber was measured by a technique ple of muscle was removed from the myotomy site similar to that described above for measurement of and immediately transported to the laboratory for muscle diameter. Nerve

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