Jolie L. Chang

A voxel-based morphometry study of patterns of brain atrophy in ALS and ALS/FTLD

Objective: To investigate the patterns of MRI brain atrophy in patients with ALS with and without clinically evident frontotemporal lobar dementia (FTLD) using voxel-based morphometry (VBM). Methods: Voxel-based morphometry was used to compare T1-weighted MRI images obtained from ten ALS patients with FTLD, ten ALS patients who were cognitively and behaviorally normal, and 22 control subjects. Images from patients and controls were spatially pre-processed using a study-specific, customized template and a priori images. A statistical threshold of p < 0.05 corrected for multiple comparisons determined significance. Results: A common pattern of gray matter atrophy was seen in both ALS and ALS/FTLD patients when compared to controls that involved the bilateral motor/premotor cortices, the left middle and inferior frontal gyri, the anterior portion of the superior frontal gyri, the superior temporal gyri, the temporal poles and left posterior thalamus. Most of the frontal regions were significantly more atrophied in the ALS/FTLD group than in the ALS group. No significant differences were found in white matter volumes. Conclusions: Patients with ALS and ALS associated with frontotemporal lobar degeneration exhibit widespread gray matter atrophy in frontotemporal regions. This finding supports the idea of a clinical and anatomic continuum between ALS and frontotemporal lobar degeneration.

Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-β and Runx2 in bone is required for hearing

Physical cues, such as extracellular matrix stiffness, direct cell differentiation and support tissue‐specific function. Perturbation of these cues underlies diverse pathologies, including osteoarthritis, cardiovascular disease and cancer. However, the molecular mechanisms that establish tissue‐specific material properties and link them to healthy tissue function are unknown. We show that Runx2, a key lineage‐specific transcription factor, regulates the material properties of bone matrix through the same transforming growth factor‐β (TGFβ)‐responsive pathway that controls osteoblast differentiation. Deregulated TGFβ or Runx2 function compromises the distinctly hard cochlear bone matrix and causes hearing loss, as seen in human cleidocranial dysplasia. In Runx2+/− mice, inhibition of TGFβ signalling rescues both the material properties of the defective matrix, and hearing. This study elucidates the unknown cause of hearing loss in cleidocranial dysplasia, and demonstrates that a molecular pathway controlling cell differentiation also defines material properties of extracellular matrix. Furthermore, our results suggest that the careful regulation of these properties is essential for healthy tissue function.

A comparison of parotid imaging characteristics and sialendoscopic findings in obstructive salivary disorders

To examine how preoperative imaging characteristics correlate with sialendoscopic findings and operative outcomes in patients with obstructive parotid symptoms.

Limited distal sialodochotomy to facilitate sialendoscopy of the submandibular duct.

INTRODUCTION Salivary gland obstruction can lead to recurrent and painful gland swelling, typically with eating and drinking, and can be complicated by bacterial sialadenitis and abscess formation. The common causes of obstructive sialadenitis are sialolithiasis, stenosis, inflammation, external compression, foreign bodies, or anatomical variation of the major salivary gland ducts. Prior to the advent of sialendoscopy, classic management of salivary duct obstruction involved conservative medical management followed by surgical transoral excision for stones or sialadenectomy. Sialendoscopy is a relatively new technique that is well described in the literature. It provides a minimally invasive, gland-sparing approach for obstructive salivary duct disease diagnosis and management. The advent of endoscopic visualization of the major salivary ducts has reduced the need for sialadenectomy, thus avoiding the associated surgical risks of nerve injury, unattractive scar, salivary fistula, sialocele, and wound infection. Luers et al. showed the learning curve for sialendoscopy was manageable, with a decrease in operative time and an increase in performance rating over 30 to 50 cases. During sialendoscopy, the papilla of Wharton’s duct is typically dilated with probes of increasing diameter. For surgeons just starting to perform sialendoscopy, the time to identify and cannulate Wharton’s duct papilla is longer than for the larger papilla of Stensen’s duct. Submandibular papilla dilation failure has been described in 20% of cases for beginner sialendoscopists. Only a few techniques have been described for managing difficult submandibular papilla dilation and sialendoscope insertion. Application of methylene blue can help with identification of the papilla. Once the papilla has been cannulated, a guidewire can be placed into the duct lumen, followed by progressively larger dilators and the endoscope, which can be inserted over the wire. Others have described incising the papilla approximately 5 mm for duct cannulation; however, papillotomy risks the development of papilla stenosis and secondary iatrogenic obstruction. We describe a technique for limited distal submandibular sialodochotomy to allow for consistent endoscope introduction into the duct when standard papilla dilation is not possible. This technique is intended to provide both beginners and experts of sialendoscopy with an alternative method to allow access to Wharton’s duct without the need for papillotomy. It also allows for endoscopic-assisted stone extraction without the need for a papillotomy to release a stone. We examined our use of limited distal sialodochotomy in 139 consecutive submandibular sialendoscopies performed at our institution.

Sialendoscopy-assisted surgery and the chronic obstructive sialadenitis symptoms questionnaire: A prospective study.

To prospectively assess symptoms of obstructive sialadenitis before and after sialendoscopy‐assisted salivary duct surgery (SASDS) using the chronic obstructive sialadenitis symptoms (COSS) questionnaire to determine and predict impact of interventions.

Sialadenitis without sialolithiasis: Prospective outcomes after sialendoscopy-assisted salivary duct surgery

To prospectively assess symptoms before and after sialendoscopy‐assisted salivary duct surgery (SASDS) in patients with symptomatic sialadenitis without sialolithiasis.

The Chronic Obstructive Sialadenitis Symptoms Questionnaire to assess sialendoscopy‐assisted surgery

Introduce the Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire to quantify chronic sialadenitis symptoms and assess the impact of sialendoscopic‐assisted salivary duct surgery (SASDS).

Effectiveness and costs of sialendoscopy in pediatric patients with salivary gland disorders

This study aimed to characterize the common salivary gland disorders presenting in the pediatric population and to describe the diagnostic and therapeutic outcomes of sialendoscopy in this population.

Disrupted Bone Remodeling Leads to Cochlear Overgrowth and Hearing Loss in a Mouse Model of Fibrous Dysplasia

Normal hearing requires exquisite cooperation between bony and sensorineural structures within the cochlea. For example, the inner ear secretes proteins such as osteoprotegrin (OPG) that can prevent cochlear bone remodeling. Accordingly, diseases that affect bone regulation can also result in hearing loss. Patients with fibrous dysplasia develop trabecular bone overgrowth resulting in hearing loss if the lesions affect the temporal bones. Unfortunately, the mechanisms responsible for this hearing loss, which could be sensorineural and/or conductive, remain unclear. In this study, we used a unique transgenic mouse model of increased Gs G-protein coupled receptor (GPCR) signaling induced by expression of an engineered receptor, Rs1, in osteoblastic cells. These ColI(2.3)+/Rs1+ mice showed dramatic bone lesions that histologically and radiologically resembled fibrous dysplasia. We found that ColI(2.3)+/Rs1+ mice showed progressive and severe conductive hearing loss. Ossicular chain impingement increased with the size and number of dysplastic lesions. While sensorineural structures were unaffected, ColI(2.3)+/Rs1+ cochleae had abnormally high osteoclast activity, together with elevated tartrate resistant acid phosphatase (TRAP) activity and receptor activator of nuclear factor kappa-B ligand (Rankl) mRNA expression. ColI(2.3)+/Rs1+ cochleae also showed decreased expression of Sclerostin (Sost), an antagonist of the Wnt signaling pathway that normally increases bone formation. The osteocyte canalicular networks of ColI(2.3)+/Rs1+ cochleae were disrupted and showed abnormal osteocyte morphology. The osteocytes in the ColI(2.3)+/Rs1+ cochleae showed increased expression of matrix metalloproteinase 13 (MMP-13) and TRAP, both of which can support osteocyte-mediated peri-lacunar remodeling. Thus, while the ossicular chain impingement is sufficient to account for the progressive hearing loss in fibrous dysplasia, the deregulation of bone remodeling extends to the cochlea as well. Our findings suggest that factors regulating bone remodeling, including peri-lacunar remodeling by osteocytes, may be useful targets for treating the bony overgrowths and hearing changes of fibrous dysplasia and other bony pathologies.

Temporal Cortical Plasticity in Single-Sided Deafness: A Functional Imaging Study.

Hypothesis To refine and extend the knowledge on cortical plasticity in single-sided deafness (SSD) by assessing magnetoencephalographic imaging in a well-defined group of subjects. Background SSD causes difficulties with directional hearing, signal extraction in noise, and multispeaker identification and separation. In SSD, the ipsilateral auditory cortex is never powerfully driven by sound, which may lead to plastic change and contribute to higher-order psychoacoustic dysfunction beyond loss of a peripheral sound sensor. Study Design A cross-sectional study on 12 subjects with long-term, adult-onset, nontraumatic SSD and 12 normal-hearing controls was conducted using magnetoencephalographic imaging, magnetic resonance imaging, and validated hearing instruments. Pure-tone stimuli at five frequencies were presented to each hearing ear individually. M100 activation peak times of the ipsilateral and contralateral auditory cortices were analyzed. Results Controls showed an M100 interhemispheric mean latency difference of 6.6 milliseconds. In contrast, subjects with SSD exhibited a mean of 1.7 milliseconds. This loss of interhemispheric latency difference was statistically significant (p < 0.05, analysis of variance with repeated measures). SSD subjects confirmed degraded hearing function on both Hearing Handicap Inventory for Adults (p < 0.001) and Speech, Spatial, and Qualities of Hearing Scale instruments (p < 0.001). Conclusion SSD disrupts M100 latency difference between the two hemispheres to sound stimulation. This finding may represent maladaptive temporal cortical plasticity because of loss of a peripheral sensor. Based on this premise, a new generation of neurophysiologically inspired auditory treatments to correct or mitigate central consequences of SSD may be considered to optimize hearing in individuals with only one functional ear.