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Article ; Online: Neuralgia and Atypical Facial, Ear, and Head Pain.

Cutri, Raffaello M / Shakya, Dejan / Shibata, Seiji B

Otolaryngologic clinics of North America

2022 Volume 55, Issue 3, Page(s) 595–606

Abstract: Though there have been considerable strides in the diagnosis and care of orofacial pain disorders, facial neuralgias, and myofascial pain dysfunction syndrome remain incredibly cumbersome for patients and difficult to manage for providers. Cranial ... ...

Abstract	Though there have been considerable strides in the diagnosis and care of orofacial pain disorders, facial neuralgias, and myofascial pain dysfunction syndrome remain incredibly cumbersome for patients and difficult to manage for providers. Cranial neuralgias, myofascial pain syndromes, temporomandibular dysfunction (TMD), dental pain, tumors, neurovascular pain, and psychiatric diseases can all present with similar symptoms. As a result, a patient's quest for the treatment of their orofacial pain often begins on the wrong foot, with a misdiagnosis or unnecessary procedure, which makes it all the more frustrating for them. Understanding the natural history, clinical presentation, and management of facial neuralgias and myofascial pain dysfunction syndrome can help clinicians better recognize and treat these conditions. In this article, we review updated knowledge on the pathophysiology, incidence, clinical features, diagnostic criteria, and medical management of TN, GPN, GN, and MPDS.
MeSH term(s)	Cranial Nerve Diseases/diagnosis ; Facial Neuralgia ; Facial Pain/diagnosis ; Facial Pain/etiology ; Facial Pain/therapy ; Headache ; Humans ; Neuralgia/diagnosis ; Trigeminal Neuralgia/diagnosis
Language	English
Publishing date	2022-05-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	417489-6
ISSN	1557-8259 ; 0030-6665
ISSN (online)	1557-8259
ISSN	0030-6665
DOI	10.1016/j.otc.2022.02.006
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Article ; Online: Neomycin-induced deafness in neonatal mice.

Cutri, Raffaello M / Lin, Joshua / Nguyen, Nhi V / Shakya, Dejan / Shibata, Seiji B

Journal of neuroscience methods

2023 Volume 391, Page(s) 109852

Abstract: Background: Hearing impairment is a rising public health issue, and current therapeutics fail to restore normal auditory sensation. Animal models are essential to a better understanding of the pathophysiology of deafness and developing therapeutics to ... ...

Abstract	Background: Hearing impairment is a rising public health issue, and current therapeutics fail to restore normal auditory sensation. Animal models are essential to a better understanding of the pathophysiology of deafness and developing therapeutics to restore hearing. New methods: Wild-type CBA/CaJ neonatal mice P2-5 were used in this study. Neomycin suspension (500 nl of 50 or 100 mg/ml) was micro-injected into the endolymphatic space. Cochlear morphology was examined 3 and 7 days after injection; hair cell (HC) loss, supporting cell morphology, and neurite denervation pattern were assessed with whole-mounts. At 2 and 4 weeks post-injection, the spiral ganglion neuron (SGN) density was analyzed with cryostat sections. Audiometric responses were measured with auditory brain response (ABR) at 4 weeks. Results: Rapid and complete degeneration of the inner and outer HCs occurred as early as 3 days post-injection. Subsequently, time- and dose-dependent degeneration patterns were observed along the axis of the cochlear membranous labyrinth forming a flat epithelium. Likewise, the SGN histology demonstrated significant cell density reduction at 2 and 4 weeks. The ABR threshold measurements confirmed profound deafness at 4 weeks. Comparison with existing methods: Compared to previously described local and systemic aminoglycoside injections, this method provides a reliable, robust, and rapid deafening model with a single infusion of neomycin in neonatal mice. This model also allows for investigating the effects of inner ear damage during auditory maturation. Conclusions: A single injection of neomycin into the endolymphatic space induces robust HC loss and denervation in neonatal mice.
MeSH term(s)	Animals ; Mice ; Neomycin/toxicity ; Animals, Newborn ; Deafness/chemically induced ; Mice, Inbred CBA ; Cochlea ; Spiral Ganglion/pathology ; Evoked Potentials, Auditory, Brain Stem
Chemical Substances	Neomycin (I16QD7X297)
Language	English
Publishing date	2023-04-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	282721-9
ISSN	1872-678X ; 0165-0270
ISSN (online)	1872-678X
ISSN	0165-0270
DOI	10.1016/j.jneumeth.2023.109852
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Zs.A 1486: Show issues

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Article: The biological underpinnings of radiation therapy for vestibular schwannomas: Review of the literature.

Dougherty, Mark C / Shibata, Seiji B / Hansen, Marlan R

Laryngoscope investigative otolaryngology

2021 Volume 6, Issue 3, Page(s) 458–468

Abstract: Objective: Radiation therapy is a mainstay in the treatment of numerous neoplasms. Numerous publications have reported good clinical outcomes for primary radiation therapy for Vestibular Schwannomas (VS). However, there are relatively few pathologic ... ...

Abstract	Objective: Radiation therapy is a mainstay in the treatment of numerous neoplasms. Numerous publications have reported good clinical outcomes for primary radiation therapy for Vestibular Schwannomas (VS). However, there are relatively few pathologic specimens of VSs available to evaluate post-radiation, which has led to a relative dearth in research on the cellular mechanisms underlying the effects of radiation therapy on VSs. Methods: Here we review the latest literature on the complex biological effects of radiation therapy on these benign tumors-including resistance to oxidative stress, mechanisms of DNA damage repair, alterations in normal growth factor pathways, changes in surrounding vasculature, and alterations in immune responses following radiation. Results: Although VSs are highly radioresistant, radiotherapy is often successful in arresting their growth. Conclusion: By better understanding the mechanisms underlying these effects, we could potentially harness such mechanisms in the future to potentiate the clinical effects of radiotherapy on VSs. Level of evidence: N/A.
Language	English
Publishing date	2021-03-30
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2378-8038
ISSN	2378-8038
DOI	10.1002/lio2.553
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Article ; Online: Incidence of Postoperative CSF Leaks in Class III Obese Patients Undergoing Middle Cranial Fossa Approach for Spontaneous CSF Leak Repair.

Cutri, Raffaello M / Shibata, Seiji B / Zhang, Huan / Gantz, Bruce J / Hansen, Marlan R

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology

2023 Volume 44, Issue 4, Page(s) 382–387

Abstract: Objective: To determine the safety and effectiveness of the middle cranial fossa (MCF) approach for spontaneous cerebrospinal fluid leak (sCSF-L) repair in class III obese patients. To also assess the need for prophylactic lumbar drain (LD) placement in ...

Abstract	Objective: To determine the safety and effectiveness of the middle cranial fossa (MCF) approach for spontaneous cerebrospinal fluid leak (sCSF-L) repair in class III obese patients. To also assess the need for prophylactic lumbar drain (LD) placement in this patient population. Study design: Retrospective cohort study. Setting: Tertiary Academic Center. Patients: All patients older than 18 years undergoing sCSF-L repair with an MCF approach. Intervention: An MCF craniotomy for sCSF-L repair. Main outcome measure: Rate of complications and postoperative leaks. Results: There were no perioperative complications in 78.9% (56/71) of cases. The surgical complication rate was 12.5% (2/16), 10% (2/20), and 22.2% (6/27) in class I, class II, and class III obese patients. There was no statistically significant difference in complications among these three groups. The most common postoperative complication was a persistent CSF leak in the acute postoperative period with an overall rate of 9.9% (7/71) with six of the seven patients requiring postoperative LD placement. The percentage of postoperative CSF leaks in nonobese, class I, class II, and class III patients were 25% (2/8), 12.5% (2/16), 0% (0/20), and 11.1% (3/27), respectively. There was no statistically significant difference in the rate of postoperative CSF leaks among the four groups (chi-square, p = 0.48). In all cases, the acute postoperative CSF leaks resolved in the long term and did not require further surgical repair. Conclusions: We determine that MCF craniotomy repair for sCSF-Ls is safe in patients with class III obesity, and the incidence of postoperative CSF leaks did not vary among other obesity classes. We also find that prophylactic placement of LDs is not routinely needed in this population.
MeSH term(s)	Humans ; Cranial Fossa, Middle/surgery ; Retrospective Studies ; Incidence ; Treatment Outcome ; Cerebrospinal Fluid Leak/epidemiology ; Cerebrospinal Fluid Leak/surgery ; Cerebrospinal Fluid Leak/etiology ; Obesity/complications ; Obesity/surgery ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology
Language	English
Publishing date	2023-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2036790-9
ISSN	1537-4505 ; 1531-7129
ISSN (online)	1537-4505
ISSN	1531-7129
DOI	10.1097/MAO.0000000000003827
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Zs.A 1554: Show issues

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Article ; Online: Comparative Analysis of Robotics-Assisted and Manual Insertions of Cochlear Implant Electrode Arrays.

Claussen, Alexander D / Shibata, Seiji B / Kaufmann, Christopher R / Henslee, Allan / Hansen, Marlan R

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology

2022 Volume 43, Issue 10, Page(s) 1155–1161

Abstract: Hypothesis: Robotics-assisted cochlear implant (CI) insertions will result in reduced intracochlear trauma when compared with manual, across multiple users.: Background: Whether intracochlear trauma and translocations are two factors that may ... ...

Abstract	Hypothesis: Robotics-assisted cochlear implant (CI) insertions will result in reduced intracochlear trauma when compared with manual, across multiple users. Background: Whether intracochlear trauma and translocations are two factors that may contribute to significant variability in CI outcomes remains to be seen. To address this issue, we have developed a robotics-assisted insertion system designed to aid the surgeon in inserting electrode arrays with consistent speeds and reduced variability. This study evaluated the effect of robotics-assisted insertions on the intracochlear trauma as compared with manual insertions in cadaveric cochleae in a simulated operative environment. Methods: Twelve neurotologists performed bilateral electrode insertions into cochleae of full cadaveric heads using both the robotics-assisted system and manual hand insertion. Lateral wall electrodes from three different manufacturers (n = 24) were used and randomized between surgeons. Insertion angle of the electrode and trauma scoring were evaluated using high-resolution three-dimensional x-ray microscopy and compared between robotics-assisted and manual insertions. Results: Three-dimensional x-ray microscopy provided excellent resolution to characterize the in situ trauma and insertion angle. Robotics-assisted insertions significantly decreased insertional intracochlear trauma as measured by reduced trauma scores compared with manual insertions (average: 1.3 versus 2.2, device versus manual, respectively; p < 0.05). There was no significant difference between insertion angles observed for manual and robotics-assisted techniques (311 ± 131° versus 307 ± 96°, device versus manual, respectively). Conclusions: Robotics-assisted insertion systems enable standardized electrode insertions across individual surgeons and experience levels. Clinical trials are necessary to investigate whether insertion techniques that reduce insertional variability and the likelihood of intracochlear trauma also improve CI auditory outcomes.
MeSH term(s)	Humans ; Cochlear Implants ; Cochlear Implantation/methods ; Cochlea/surgery ; Electrodes, Implanted ; Cadaver
Language	English
Publishing date	2022-10-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2036790-9
ISSN	1537-4505 ; 1531-7129
ISSN (online)	1537-4505
ISSN	1531-7129
DOI	10.1097/MAO.0000000000003707
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Zs.A 1554: Show issues

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Article ; Online: An Osseous Destructive Mass of the Infratemporal Fossa.

Vesole, Adam S / Shibata, Seiji B / Hansen, Marlan R

JAMA otolaryngology-- head & neck surgery

2019 Volume 146, Issue 2, Page(s) 194–195

MeSH term(s)	Aged ; Humans ; Infratemporal Fossa/diagnostic imaging ; Infratemporal Fossa/pathology ; Infratemporal Fossa/surgery ; Magnetic Resonance Imaging ; Male ; Neoplasm Invasiveness ; Rhabdomyosarcoma/classification ; Rhabdomyosarcoma/diagnostic imaging ; Rhabdomyosarcoma/pathology ; Rhabdomyosarcoma/surgery ; Risk Factors ; Skull Base Neoplasms/classification ; Skull Base Neoplasms/diagnostic imaging ; Skull Base Neoplasms/pathology ; Skull Base Neoplasms/surgery ; Tomography, X-Ray Computed
Language	English
Publishing date	2019-12-27
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2701825-8
ISSN	2168-619X ; 2168-6181
ISSN (online)	2168-619X
ISSN	2168-6181
DOI	10.1001/jamaoto.2019.3390
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Article ; Online: Gene therapy for hearing loss.

Omichi, Ryotaro / Shibata, Seiji B / Morton, Cynthia C / Smith, Richard J H

Human molecular genetics

2020 Volume 28, Issue R1, Page(s) R65–R79

Abstract: Sensorineural hearing loss (SNHL) is the most common sensory disorder. Its underlying etiologies include a broad spectrum of genetic and environmental factors that can lead to hearing loss that is congenital or late onset, stable or progressive, drug ... ...

Abstract	Sensorineural hearing loss (SNHL) is the most common sensory disorder. Its underlying etiologies include a broad spectrum of genetic and environmental factors that can lead to hearing loss that is congenital or late onset, stable or progressive, drug related, noise induced, age related, traumatic or post-infectious. Habilitation options typically focus on amplification using wearable or implantable devices; however exciting new gene-therapy-based strategies to restore and prevent SNHL are actively under investigation. Recent proof-of-principle studies demonstrate the potential therapeutic potential of molecular agents delivered to the inner ear to ameliorate different types of SNHL. Correcting or preventing underlying genetic forms of hearing loss is poised to become a reality. Herein, we review molecular therapies for hearing loss such as gene replacement, antisense oligonucleotides, RNA interference and CRISPR-based gene editing. We discuss delivery methods, techniques and viral vectors employed for inner ear gene therapy and the advancements in this field that are paving the way for basic science research discoveries to transition to clinical trials.
MeSH term(s)	Animals ; Biomarkers ; Clinical Trials as Topic ; Disease Management ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Gene Expression ; Genetic Predisposition to Disease ; Genetic Therapy/methods ; Genetic Vectors/genetics ; Hearing Loss/diagnosis ; Hearing Loss/genetics ; Hearing Loss/therapy ; Humans ; Transgenes ; Treatment Outcome
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-03-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddz129
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Article ; Online: Transmastoid and Transtemporal Drainage of Petrous Apicitis with Otitis Media.

Isaac, Heba / Liu, Andrew / Shibata, Seiji B / Hansen, Marlan R

The Annals of otology, rhinology, and laryngology

2020 Volume 130, Issue 3, Page(s) 314–318

Abstract: Background: Petrous apicitis (PA) is a serious infection involving the apical portion of the petrous temporal bone. The classic triad of purulent otorrhea, ipsilateral abducens nerve palsy and retroorbital pain is rarely seen due to early detection and ... ...

Abstract	Background: Petrous apicitis (PA) is a serious infection involving the apical portion of the petrous temporal bone. The classic triad of purulent otorrhea, ipsilateral abducens nerve palsy and retroorbital pain is rarely seen due to early detection and widespread use of antibiotics. Medical management is the primary treatment modality with surgery reserved for cases of recalcitrant petrous apex abscess. Methods and results: We presented a case of PA with previously untreated otitis media. After multidisciplinary evaluation, the patient was initially treated with intravenous antibiotics followed by drainage of the abscess using a combined transmastoid and middle cranial fossa (MCF) approach. The patient recovered well with no recurrence of the infection based on imaging and symptoms. Discussion: While a variety of different surgical approaches can be used in treatment of PA, we recommend the MCF approach in cases where access to the anterior petrous apex may be challenging via transcanal or transmastoid approach.
MeSH term(s)	Abscess/diagnostic imaging ; Abscess/therapy ; Anti-Bacterial Agents/therapeutic use ; Cerebral Ventriculitis/diagnosis ; Cerebral Ventriculitis/etiology ; Cerebral Ventriculitis/therapy ; Confusion/etiology ; Cranial Fossa, Middle ; Drainage/methods ; Earache ; Humans ; Male ; Mastoidectomy/methods ; Mastoiditis/diagnostic imaging ; Mastoiditis/therapy ; Meningitis/diagnosis ; Meningitis/etiology ; Meningitis/therapy ; Middle Aged ; Otitis Media, Suppurative/diagnostic imaging ; Otitis Media, Suppurative/therapy ; Petrositis/diagnostic imaging ; Petrositis/therapy ; Photophobia/etiology ; Streptococcus pneumoniae ; Tomography, X-Ray Computed
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2020-08-08
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	120642-4
ISSN	1943-572X ; 0003-4894
ISSN (online)	1943-572X
ISSN	0003-4894
DOI	10.1177/0003489420949591
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Article ; Online: Reduction of sporadic and neurofibromatosis type 2-associated vestibular schwannoma growth in vitro and in vivo after treatment with the c-Jun N-terminal kinase inhibitor AS602801.

Dougherty, Mark C / Shibata, Seiji B / Clark, J Jason / Canady, Franklin J / Yates, Charles W / Hansen, Marlan R

Journal of neurosurgery

2022 Volume 138, Issue 4, Page(s) 962–971

Abstract: Objective: Vestibular schwannomas (VSs) are benign nerve sheath tumors that result from mutation in the tumor suppressor gene NF2, with functional loss of the protein merlin. The authors have previously shown that c-Jun N-terminal kinase (JNK) is ... ...

Abstract	Objective: Vestibular schwannomas (VSs) are benign nerve sheath tumors that result from mutation in the tumor suppressor gene NF2, with functional loss of the protein merlin. The authors have previously shown that c-Jun N-terminal kinase (JNK) is constitutively active in human VS cells and plays a central role in their survival by suppressing accumulation of mitochondrial superoxides, implicating JNK inhibitors as a potential systemic treatment for VS. Thus, the authors hypothesized that the adenosine 5'-triphosphate-competitive JNK inhibitor AS602801 would demonstrate antitumor activity in multiple VS models. Methods: Treatment with AS602801 was tested in primary human VS cultures, human VS xenografts, and a genetic mouse model of schwannoma (Postn-Cre;Nf2flox/flox). Primary human VS cell cultures were established from freshly obtained surgical tumor specimens; treatment group media was enriched with AS602801. VS xenograft tumors were established in male athymic nude mice from freshly collected human tumor. Four weeks postimplantation, a pretreatment MRI scan was obtained, followed by 65 days of AS602801 (n = 18) or vehicle control (n = 19) treatment. Posttreatment MRI scans were used to measure final tumor volume. Tumors were then harvested. Finally, Postn-Cre;Nf2flox/flox mice were treated with AS602801 (n = 10) or a vehicle (n = 13) for 65 days. Posttreatment auditory brainstem responses were obtained. Dorsal root ganglia from Postn-Cre;Nf2flox/flox mice were then harvested. In all models, schwannoma identity was confirmed with anti-S100 staining, cell proliferation was measured with the EdU assay, and cell death was measured with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. All protocols were approved by the local institutional review board and Institutional Animal Care and Use Committees. Results: Treatment with AS602801 decreased cell proliferation and increased apoptosis in primary human VS cultures. The systemic administration of AS602801 in mice with human VS xenografts reduced tumor volume and cell proliferation. Last, the AS602801-treated Postn-Cre;Nf2flox/flox mice demonstrated decreased cell proliferation in glial cells in the dorsal root ganglia. However, AS602801 did not significantly delay hearing loss in Postn-Cre;Nf2flox/flox mice up to 3 months posttreatment. Conclusions: The data suggest that JNK inhibition with AS602801 suppresses growth of sporadic and neurofibromatosis type 2-associated VSs. As such, AS602801 is a potential systemic therapy for VS and warrants further investigation.
MeSH term(s)	Humans ; Male ; Mice ; Animals ; Neurofibromatosis 2/complications ; Neurofibromatosis 2/drug therapy ; Neuroma, Acoustic/drug therapy ; Neuroma, Acoustic/pathology ; JNK Mitogen-Activated Protein Kinases/metabolism ; Mice, Nude
Chemical Substances	bentamapimod (TT3L4B4U0N) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2022-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3089-2
ISSN	1933-0693 ; 0022-3085
ISSN (online)	1933-0693
ISSN	0022-3085
DOI	10.3171/2022.7.JNS22934
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Article ; Online: Mutation-agnostic RNA interference with engineered replacement rescues

Iwasa, Yoichiro / Klimara, Miles J / Yoshimura, Hidekane / Walls, William D / Omichi, Ryotaro / West, Cody A / Shibata, Seiji B / Ranum, Paul T / Smith, Richard Jh

Life science alliance

2022 Volume 6, Issue 3

Abstract: Hearing loss is the most common sensory deficit, of which genetic etiologies are a frequent cause. Dominant and recessive mutations ... ...

Abstract	Hearing loss is the most common sensory deficit, of which genetic etiologies are a frequent cause. Dominant and recessive mutations in
MeSH term(s)	Mice ; Animals ; RNA Interference ; Mechanotransduction, Cellular ; Hearing Loss/genetics ; Hearing Loss/therapy ; Mutation/genetics ; Membrane Proteins/genetics
Chemical Substances	TMC1 protein, mouse ; Membrane Proteins
Language	English
Publishing date	2022-12-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202201592
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