Eric A. Mann

Mutant dynactin in motor neuron disease.

Impaired axonal transport in motor neurons has been proposed as a mechanism for neuronal degeneration in motor neuron disease. Here we show linkage of a lower motor neuron disease to a region of 4 Mb at chromosome 2p13. Mutation analysis of a gene in this interval that encodes the largest subunit of the axonal transport protein dynactin showed a single base-pair change resulting in an amino-acid substitution that is predicted to distort the folding of dynactins microtubule-binding domain. Binding assays show decreased binding of the mutant protein to microtubules. Our results show that dysfunction of dynactin-mediated transport can lead to human motor neuron disease.

Distal spinal and bulbar muscular atrophy caused by dynactin mutation.

Impaired axonal transport has been postulated to play a role in the pathophysiology of multiple neurodegenerative disorders. In this report, we describe the results of clinical and neuropathological studies in a family with an inherited form of motor neuron disease caused by mutation in the p150Glued subunit of dynactin, a microtubule motor protein essential for retrograde axonal transport. Affected family members had a distinct clinical phenotype characterized by early bilateral vocal fold paralysis affecting the adductor and abductor laryngeal muscles. They later experienced weakness and atrophy in the face, hands, and distal legs. The extremity involvement was greater in the hands than in the legs, and it had a particular predilection for the thenar muscles. No clinical or electrophysiological sensory abnormality existed; however, skin biopsy results showed morphological abnormalities of epidermal nerve fibers. An autopsy study of one patient showed motor neuron degeneration and axonal loss in the ventral horn of the spinal cord and hypoglossal nucleus of the medulla. Immunohistochemistry showed abnormal inclusions of dynactin and dynein in motor neurons. This mutation of dynactin, a ubiquitously expressed protein, causes a unique pattern of motor neuron degeneration that is associated with the accumulation of dynein and dynactin in neuronal inclusions. Ann Neurol 2005;57:687–694

The Effect of Neuromuscular Stimulation of the Genioglossus on the Hypopharyngeal Airway

Objectives To determine the effects of neuromuscular stimulation (NS) of the genioglossus muscle on hypopharyngeal airway size.

Laryngeal electromyography: an evidence-based review.

This article reports on an evidence‐based review of laryngeal electromyography (EMG) as a technique for use in the diagnosis, prognosis, and treatment of laryngeal movement disorders including the laryngeal dystonias, vocal fold paralysis, and other neurolaryngological disorders. The authors performed a systematic review of the medical literature from 1944 through 2001 on the clinical application of EMG to laryngeal disorders. Thirty‐three of the 584 articles met the predefined inclusion criteria. The evidence demonstrated that in a double‐blind treatment trial of botulinum toxin versus saline, laryngeal EMG used to guide injections into the thyroarytenoid muscle in persons with adductor spasmodic dysphonia was beneficial. A cross‐over comparison between laryngeal EMG‐guided injection and endoscopic injection of botulinum toxin into the posterior cricoarytenoid muscle in abductor spasmodic dysphonia found no significant difference between the two techniques and no significant treatment benefit. Based on the evidence, laryngeal EMG is possibly useful for the injection of botulinum toxin into the thyroarytenoid muscle in the treatment of adductor spasmodic dysphonia. There were no evidence‐based data sufficient to support or refute the value of laryngeal EMG for the other uses investigated, although there is extensive anecdotal literature suggesting that it is useful for each of them. There is an urgent need for evidence‐based research addressing the use of laryngeal EMG for other applications. Muscle Nerve 28: 767–772, 2003

Practice Parameter: Laryngeal Electromyography (An Evidence-Based Review):

This paper reports on an evidence-based review of laryngeal electromyography (EMG) as a technique for use in the diagnosis, prognosis, and treatment of laryngeal movement disorders including the laryngeal dystonias, vocal fold paralysis, and other neurolaryngological disorders. The authors performed a systematic review of the medical literature from 1944 through 2001 on the clinical application of EMG to laryngeal disorders. The review yielded 584 articles of which 33 met the predefined inclusion criteria. The evidence demonstrated that in a double-blind treatment trial of botulinum toxin versus saline, laryngeal EMG used to guide injections into the thyroarytenoid muscle in persons with adductor spasmodic dysphonia was beneficial. A cross-over comparison between laryngeal EMG-guided injection and endoscopic injection of botulinum toxin into the posterior cricoarytenoid muscle in abductor spasmodic dysphonia found no significant difference between the 2 techniques and no significant treatment benefit. Based on the evidence, laryngeal EMG is possibly useful for the injection of botulinum toxin into the thyroarytenoid muscle in the treatment of adductor spasmodic dysphonia. There were no evidence-based data sufficient to support or refute the value of laryngeal EMG for the other uses investigated, although there is extensive anecdotal literature suggesting that it is useful for each of them. There is an urgent need for evidence-based research addressing other applications in the use of laryngeal EMG for other applications. (Otolaryngol Head Neck Surg 2004;130: 770-9.)

Practice parameter: laryngeal electromyography (an evidence-based review).

This paper reports on an evidence-based review of laryngeal electromyography (EMG) as a technique for use in the diagnosis, prognosis, and treatment of laryngeal movement disorders including the laryngeal dystonias, vocal fold paralysis, and other neurolaryngological disorders. The authors performed a systematic review of the medical literature from 1944 through 2001 on the clinical application of EMG to laryngeal disorders. The review yielded 584 articles of which 33 met the predefined inclusion criteria. The evidence demonstrated that in a double-blind treatment trial of botulinum toxin versus saline, laryngeal EMG used to guide injections into the thyroarytenoid muscle in persons with adductor spasmodic dysphonia was beneficial. A cross-over comparison between laryngeal EMG-guided injection and endoscopic injection of botulinum toxin into the posterior cricoarytenoid muscle in abductor spasmodic dysphonia found no significant difference between the 2 techniques and no significant treatment benefit. Based on the evidence, laryngeal EMG is possibly useful for the injection of botulinum toxin into the thyroarytenoid muscle in the treatment of adductor spasmodic dysphonia. There were no evidence-based data sufficient to support or refute the value of laryngeal EMG for the other uses investigated, although there is extensive anecdotal literature suggesting that it is useful for each of them. There is an urgent need for evidence-based research addressing other applications in the use of laryngeal EMG for other applications.

Suppression of Thyroarytenoid Muscle Responses during Repeated Air Pressure Stimulation of the Laryngeal Mucosa in Awake Humans

Repeated stimulation of the laryngeal mucosa occurs during speech. Single stimuli, however, can elicit the laryngeal adductor response (LAR). Our hypothesis was that the LAR to repeated rapid air pressure stimuli is centrally suppressed in humans. Hookedwire electrodes were inserted into the thyroarytenoid and cricothyroid muscles on both sides and into the posterior cricoarytenoid muscle on one side. Pairs of air puff stimuli were presented to the mucosa over the arytenoids at pressure levels three times threshold with interstimulus intervals from 250 to 5,000 ms. Bilateral thyroarytenoid responses occurred at around 150 ms to more than 70% of the initial stimuli. With repeated presentation at intervals of 2 seconds or less, the percent occurrence decreased to less than 40% and response amplitudes were reduced by 50%. Central suppression of adductor responses to repeated air puff stimuli may allow speakers to produce voice without eliciting reflexive spasms that could disrupt speech.

Influences of laryngeal afferent blockade on laryngeal muscle activity during speech

Problem: A previous study determined that sensory blockade reduced symptoms in spasmodic dysphonia. The purpose of this study was to determine how laryngeal afferent feedback blockade alters laryngeal muscle activity during speech, to explain this benefit in patients with spasmodic dysphonia. Methods: We used hooked wire electrodes to record from intrinsic laryngeal muscles (thyroarytenoid, cricothyroid, and posterior cricoarytenoid) during sentence production in subjects with either adductor and abductor spasmodic dysphonia before and after bilateral superior laryngeal nerve blockade with lidocaine. Prior to the block, sensory thresholds were determined for air puff stimuli presented to the mucosa overlying the arytenoid cartilages. Following the block, laryngeal muscle activity during production of the same sentences was recorded again and sensory testing confirmed blockade on both sides. Measures included the mean muscle activity during the first syllable of each sentence, syllable duration, and the pre-phonatory interval between muscle activity onset and voice onset for the first syllable of each sentence. Results: No changes occurred in mean muscle activity level following afferent blockade in all 3 muscles. Significant within-subject reductions were found in the duration of the first syllable of the sentence and in the pre-phonatory interval between thyroarytenoid muscle activity onset and vocalization onset for speech. The pre-phonatory interval decreased in 7 of the 8 subjects. No significant changes in pre-phonatory interval were found in the posterior cricoarytenoid or cricothyroid muscles. Conclusion: Symptom benefits following a reduction in afferent feedback are not a result of reduced muscle activity level but may reflect changes in central patterning of muscle activity in patients with spasmodic dysphonia. Significance: These results provide further understanding of the pathophysiology of symptom generation in spasmodic dysphonia. Support: The research was supported by the National Institute of Neurological Disorders and Stroke, 1 Z01 NS002980-05.

112: Spontaneous Internal Jugular Vein Thrombosis in a Woman Receiving Estrogen Replacement

Since its introduction as a topical hemostatic agent in 1943, bovine thrombin has been used extensively in cardiovascular and neurosurgical procedures. The primary adverse reaction associated with its use has been acute hypersensitivity. However, there have been increasing reports of patients developing antibodies to the topical bovine thrombin and bovine clotting factor V, an impurity of the isolated animal thrombin. These antibodies then cross-react with their human counterparts to cause prolonged thrombin time, prothrombin (PT), and partial thromboplastin times (PTT). The clinical course can be extremely variable, from totally asymptomatic to life-threatening hemorrhage. A case is presented in which a 66-year-old white man with a previous history of a coronary artery bypass graft underwent mediastinoscopy and biopsy. One week after the procedure, he developed severe epistaxis. He required traditional anterior and posterior nasal packing, intensive care monitoring, and blood transfusions. The diagnosis and medical management of the acquired bleeding diathesis is presented, along with the pathophysiology behind its development. Graphical depictions of the bleeding cascade and immunologic reactions will be displayed.

110: Severe Epistaxis Secondary to an Acquire Bleeding Diathesis from Topical Bovine Thrombin

Since its introduction as a topical hemostatic agent in 1943, bovine thrombin has been used extensively in cardiovascular and neurosurgical procedures. The primary adverse reaction associated with its use has been acute hypersensitivity. However, there have been increasing reports of patients developing antibodies to the topical bovine thrombin and bovine clotting factor V, an impurity of the isolated animal thrombin. These antibodies then cross-react with their human counterparts to cause prolonged thrombin time, prothrombin (PT), and partial thromboplastin times (PTT). The clinical course can be extremely variable, from totally asymptomatic to life-threatening hemorrhage. A case is presented in which a 66-year-old white man with a previous history of a coronary artery bypass graft underwent mediastinoscopy and biopsy. One week after the procedure, he developed severe epistaxis. He required traditional anterior and posterior nasal packing, intensive care monitoring, and blood transfusions. The diagnosis and medical management of the acquired bleeding diathesis is presented, along with the pathophysiology behind its development. Graphical depictions of the bleeding cascade and immunologic reactions will be displayed.