Phillip C. Song

Human Choroid Plexus Growth Factors: What Are the Implications for CSF Dynamics in Alzheimer's Disease?

The choroid plexus plays a key role in supporting neuronal function by secreting cerebrospinal fluid (CSF) and may be involved in the regulation of various soluble factors. Because the choroid plexus is involved in growth factor secretion as well as CSF dynamics, it is important to understand how growth factors in CSF interact with the brain parenchyma as well as with cells in direct contact with the flowing CSF, i.e., choroid plexus and arachnoid villi. While the existence of growth factors in the choroid plexus has been documented in several animal models, the presence and distribution of growth factors in the human choroid plexus has not been extensively examined. This study describes the general distribution and possible functions of a number of key proteins in the human choroid plexus and arachnoid villi, including basic fibroblast growth factor, FGF receptor, and vascular endothelial growth factor. FGF and VEGF could both be readily demonstrated in choroid plexus epithelial cells. The presence of FGF and VEGF within the choroid plexus was also confirmed by ELISA analysis. Since Alzheimers disease (AD) is known to be associated with a number of growth factor abnormalities, we examined the choroid plexus and arachnoid villi from AD patients. Immunohistochemical studies revealed the presence of FGF and VEGF within the AD choroid plexus and an increased density of FGFr in both the choroid plexus and the arachnoid villi of AD patients. No qualitative changes in the distribution of FGF and VEGF were observed in the AD choroid plexus. The appearance of FGFr in AD arachnoid was associated with robust amyloid and vimentin immunoreactivity. These findings confirm the presence of FGF and VEGF within the normal and AD choroid plexus and suggest that the alteration of growth factors and their receptors may contribute to the pathogenesis of the hydrocephalus ex vacuo that is characteristically seen in AD.

Development and Validation of a High-Fidelity Porcine Laryngeal Surgical Simulator

Objective Design and validate a laryngeal surgical simulator to teach phonomicrosurgical techniques. Study Design Device development and prospective validation. Setting Tertiary medical center. Subjects and Methods A novel laryngeal fixation device and custom laryngoscope were produced for use with ex vivo porcine larynx specimens. Vocal fold lesions such as nodules and keratotic lesions were simulated with silicone injections and epithelial markings. A prospective validation using postsimulation surveys, global rating scales, and procedure-specific checklists was performed with a group of 15 medical students, otolaryngology residents, fellows, and attending laryngologists. Three procedures were performed: vocal fold augmentation, excision of a simulated vocal fold nodule, and excision of a simulated vocal fold keratosis. Results Participants overwhelmingly agreed that the simulator provided a realistic dissection experience that taught skills that would transfer to real operating scenarios. Expert performance was statistically superior to novice performance for excision of simulated vocal fold nodules and keratotic lesions, while no difference was observed for injection laryngoplasty. Conclusion The ability to learn and rehearse surgical procedures in a safe environment is invaluable, particularly for delicate and highly technical phonomicrosurgical operations. We have developed a high-fidelity laryngeal surgical simulator complete with pathological lesions such as nodules and keratoses to teach these procedures. A prospective study demonstrated validity of our global rating scale and checklist assessments for vocal fold nodule and keratosis excision procedures, allowing them to be confidently incorporated into phonomicrosurgical training programs for surgeons of all levels of expertise.

Voice Outcomes After Endoscopic Injection Laryngoplasty with Hyaluronic luronic Acid Stabilized Gel

OBJECTIVE A variety of materials as well as approaches have been used to treat glottic insufficiency, but the ideal procedure has yet to be determined. The goal of this study was evaluate the safety and efficacy of cross-linked hyaluronic acid (Restylane) for office-based injection laryngoplasty for the treatment of vocal fold (VF) immobility. STUDY DESIGN Retrospective chart review. METHODS Twenty-seven patients were with diagnosed VF immobility. Twenty-five received Restylane VF injections in the office setting via percutaneous, trans-thyrohyoid injection with distal chip endoscopic guidance. Two patients received injections using suspension microlaryngoscopy under general anesthesia. Voice outcomes were followed using the Voice-Related Quality of Life Survey and the Voice Outcome Survey. RESULTS Four patients were lost to follow-up immediately after injection. 20 of 23 patients (87%) reported subjective improvement in voice. Analysis of subjective surveys from nine patients revealed a trend toward improvement of V-RQOL from 34 to 23 (P = 0.083) but did not reach significance. After compilation of all VOS questions, 69% of all follow-up responses noted improvement of symptoms, 24% were unchanged and 7% were worse. CONCLUSIONS Office-based injection laryngoplasty with Restylane appears to be a safe procedure that improves vocal function in patients with glottal insufficiency due to impaired VF mobility. Further studies are required to quantify the benefits and to compare the effects with other injectable materials.

Case records of the Massachusetts General Hospital. Case 17-2010 - a 29-year-old woman with flexion of the left hand and foot and difficulty speaking.

Dr. Nutan Sharma (Neurology): A 29-year-old right-handed woman was seen in the neurology clinic of this hospital because of involuntary flexion of the left hand and increasing difficulty moving the left foot. The patient had been well until 3 years earlier, when she noted that her left index finger was bent. During the subsequent 2.5 years, the fingers of the left hand began to flex, and the hand gradually curled into a tight fist. Approximately 1.5 years before this evaluation, she noted difficulty moving the left foot, and inversion at the ankle gradually developed. During the following year, flexion of her left elbow developed, and she was seen at another hospital, where brain imaging, an electroencephalogram, and electromyographic and nerve-conduction studies were reportedly normal. She was referred to the neurology clinic of this hospital. The patient reported weakness and flexion of the left hand and ankle. She had had normal growth and development. She had occasional migraine headaches (approximately every 2 to 3 months), without aura, for which she took ibuprofen. She was of African-Caribbean descent. She worked in education and did not smoke or drink alcohol. Her parents and daughter were well; there was no family history of neurologic illness. On examination, the patient appeared well. The muscle bulk of the left biceps was increased as compared with the right. The left fingers, wrist, and elbow were flexed, with rigidity that was worse with activation. The left arm occasionally extended at the elbow when her attention was directed elsewhere. Dorsiflexion, inversion and eversion of the left ankle, and muscle strength were normal. Deep-tendon reflexes were 3+ in the left biceps and the left patella and 2+ elsewhere. Plantar reflexes were neutral, neither extensor nor flexor. The left arm extended at the elbow during tandem gait; coordination was otherwise normal, with negative Romberg testing. The remainder of the neurologic examination was normal. During the next 4 months, additional testing was performed. Magnetic resonance imaging (MRI) scans of the cervical, thoracic, and lumbar spine were unremarkable. A complete blood count was normal, as were levels of electrolytes, glucose, total protein, albumin, globulin, calcium, and ceruloplasmin and tests of liver and renal function. Antinuclear-antibody testing was negative. Nerve-conduction studies of Case 17-2010: A 29-Year-Old Woman with Flexion of the Left Hand and Foot and Difficulty Speaking

Case 17-2010

Dr. Nutan Sharma (Neurology): A 29-year-old right-handed woman was seen in the neurology clinic of this hospital because of involuntary flexion of the left hand and increasing difficulty moving the left foot. The patient had been well until 3 years earlier, when she noted that her left index finger was bent. During the subsequent 2.5 years, the fingers of the left hand began to flex, and the hand gradually curled into a tight fist. Approximately 1.5 years before this evaluation, she noted difficulty moving the left foot, and inversion at the ankle gradually developed. During the following year, flexion of her left elbow developed, and she was seen at another hospital, where brain imaging, an electroencephalogram, and electromyographic and nerve-conduction studies were reportedly normal. She was referred to the neurology clinic of this hospital. The patient reported weakness and flexion of the left hand and ankle. She had had normal growth and development. She had occasional migraine headaches (approximately every 2 to 3 months), without aura, for which she took ibuprofen. She was of African-Caribbean descent. She worked in education and did not smoke or drink alcohol. Her parents and daughter were well; there was no family history of neurologic illness. On examination, the patient appeared well. The muscle bulk of the left biceps was increased as compared with the right. The left fingers, wrist, and elbow were flexed, with rigidity that was worse with activation. The left arm occasionally extended at the elbow when her attention was directed elsewhere. Dorsiflexion, inversion and eversion of the left ankle, and muscle strength were normal. Deep-tendon reflexes were 3+ in the left biceps and the left patella and 2+ elsewhere. Plantar reflexes were neutral, neither extensor nor flexor. The left arm extended at the elbow during tandem gait; coordination was otherwise normal, with negative Romberg testing. The remainder of the neurologic examination was normal. During the next 4 months, additional testing was performed. Magnetic resonance imaging (MRI) scans of the cervical, thoracic, and lumbar spine were unremarkable. A complete blood count was normal, as were levels of electrolytes, glucose, total protein, albumin, globulin, calcium, and ceruloplasmin and tests of liver and renal function. Antinuclear-antibody testing was negative. Nerve-conduction studies of Case 17-2010: A 29-Year-Old Woman with Flexion of the Left Hand and Foot and Difficulty Speaking

Double-bend needle modification for transthyrohyoid vocal fold injection.

Our objective was to describe an injection needle modification for awake in‐office vocal fold injections through a percutaneous transthyrohyoid approach. Two separate 45° angle bends are created at the hub and 1 cm from the needle tip of a 25‐gauge, 1.5‐inch needle. After adequate endolaryngeal anesthesia, the needle is passed via the thyrohyoid membrane into the airway. The needle tip is at a 90° angle to the syringe, providing access to the entire vocal fold surface, regardless of chin position or thyroid cartilage angulation. The bend at 1 cm also serves as a marker to measure the depth of the needle within the soft tissue. The double‐bend needle modification allows for complete access to the entire length of the true vocal fold in one pass as well as a marker to measure depth of the needle in the tissue. Limitations may include bleeding from the injection site, insufficient needle length in patients with a long anterior‐posterior dimension of the larynx, and potential difficulty passing a needle through a calcified thyrohyoid membrane. Laryngoscope, 2012

Clinical Manifestations of IgG4-Related Disease in the Pharynx Case Series and Review of the Literature

Objective: The objective of this report is to characterize IgG4-related disease (IgG4-RD) as it is manifested in the head and neck and describe a series of patients with a rarely described presentation in laryngopharyngeal subsites. Methods: Here, we illustrate the presentation and clinical course of 3 patients with laryngopharyngeal manifestations of IgG4-RD, including the manner of diagnosis and effective treatment. Results: Three patients with laryngopharyngeal lesions were ultimately diagnosed with IgG4-RD after lengthy work-up. The diagnostic criteria and treatment protocols are explained. Conclusion: IgG4-related disease is a fibroinflammatory disorder now described in almost every organ system. The head and neck regions are among the most common areas of involvement, however, reports of laryngopharyngeal involvement are rare. We also summarize current knowledge of this entity and discuss established diagnostic criteria and clinical findings.

Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold

A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer.

Interarytenoid botulinum toxin injection for recalcitrant vocal process granuloma.

This study evaluated the efficacy of botulinum toxin type A injected into the interarytenoid muscle to treat recalcitrant vocal process granulomas.

Unusual Fibromatosis of the Head and Neck

c u G a a a p ibromatosis, or desmoid tumor, has been a conusing entity for many years. Although it is a enign tumor, its aggressive characteristics and igh recurrence rate have made it difficult to dignose as well as to name. It was once referred to s fibrosarcoma grade I, but because the tumor arely, if ever, metastasizes and does not have alignant characteristics, this name was abanoned. It is an intermediate-grade tumor, whose ehavior is classified as being between that of a enign fibroma and a well-differentiated fibrosaroma. The tumor has been referred to as desmolastic fibroma, desmoma, aggressive fibromatois, and desmoid tumor. Desmo, a prefix that eans “fibrous connection” or “ligament,” seems o appropriately characterize this fibroblastic proiferation of cells that arises from musculoaponeuotic structures in the body. Here we present a case emonstrating many clinical features of this unsual entity. A 79-year-old woman presented with a 2-year istory of an enlarging left posterior neck mass. ne year earlier, she had undergone an excisional iopsy of a subcutaneous mass diagnosed as deral fibrosis, or healing scar. The mass increased n size since then. Examination revealed a large, rm, nontender fixed mass in the left posterior eck area (Fig 1A). The remainder of the head and eck examination was normal. The patient underwent incisional biopsy, which evealed a benign-appearing fibrous neoplasm, ithout definitive diagnosis. Computed tomograhy (CT) scan showed a large soft tissue mass ith ill-defined borders, deep to muscle, extending rom C2 to C7 with no bony erosion or patholog-