Anti-Hu Antibody Associated Paraneoplastic Cerebellar Degeneration in Head and Neck Cancer.

BACKGROUND: Paraneoplastic syndromes are most frequently associated with small cell lung carcinoma, hematologic and gynecologic malignancies while reports in head and neck cancer are rare. CASE PRESENTATION: We present the case of a 60-year old female patient who developed paraneoplastic cerebellar degeneration upon locoregional recurrence of a poorly differentiated spindle cell carcinoma of the nasal cavity and paranasal sinus. The neurological symptoms, especially ataxia, stabilized after resection of tumor recurrence and concomitant chemoradiotherapy whereas anti-Hu-antibodies remained positive. Despite the unfavorable prognosis of paraneoplastic neurological disorders associated with onconeural antibodies, the patient achieved long-standing stabilization of neurological symptoms. CONCLUSION: We report the first patient with anti-Hu antibodies and paraneoplastic cerebellar degeneration associated with a spindle cell carcinoma of the head and neck. We recommend that evaluation of neurological symptoms in patients with this tumor entity should also include paraneoplastic syndromes as differential diagnoses and suggest early extensive screening for onconeural antibodies.

CYP39A1 polymorphism is associated with toxicity during intensive induction chemotherapy in patients with advanced head and neck cancer.

BACKGROUND: Induction chemotherapy incorporating docetaxel, cisplatin and 5- fluorouracil before radiotherapy may improve the outcome of patients with advanced head and neck cancer. Nevertheless, the addition of docetaxel increases hematological toxicity and infectious complications. Therefore, genetic markers predicting toxicity and efficacy of this treatment regimen may help to identify patients, who would have the most benefit from this intensive treatment. METHODS: A cohort of 78 patients with advanced head and neck cancer treated with induction chemotherapy was assessed for clinical outcome and toxicity during treatment with curative intention. Genetic polymorphisms primary associated with treatment efficacy (ERCC2-rs13181, rs1799793, ERCC1-rs3212986, rs11615, XRCC1-rs25487) or with docetaxel caused toxicity (CYP39A1-rs7761731, SLCO1B3-rs11045585) were evaluated in all patients. The results of these analyses were correlated with the clinical outcome of the patients (loco regional control, progression free survival, overall survival) and treatment related toxicity during induction chemotherapy. RESULTS: Median progression free survival and overall survival was 20 and 31 months in an intention to treat analysis, respectively. Overall response rate to induction chemotherapy was high with 78.1 % of all patients. None of the polymorphisms tested was associated with the clinical outcome of the patients. Genotype A of the CYP39A1 rs7761731 polymorphism was associated with a higher incidence of leucopenia and infections or death during induction chemotherapy. CONCLUSIONS: Intensive induction chemotherapy results in a high response rate in the majority of patients. None of the polymorphisms tested was associated with the clinical outcome of the patients. The CYP39A1 polymorphism rs7761731 may help to identify patients at high risk for treatment related toxicity.

Cisplatin induced mitochondrial DNA damage in dorsal root ganglion neurons.

Cisplatin is a platinum-based chemotherapeutic agent that induces peripheral neuropathy in 30% of patients. Peripheral neuropathy is the dose limiting side effect, which has no preventative therapy. We have previously shown that cisplatin induces apoptosis in dorsal root ganglion (DRG) sensory neurons by covalently binding to nuclear DNA (nDNA), resulting in DNA damage, subsequent p53 activation and Bax-mediated apoptosis via the mitochondria. We now demonstrate that cisplatin also directly binds to mitochondrial DNA (mtDNA) with the same binding affinity as nDNA. Cisplatin binds 1 platinum molecule per 2166 mtDNA base pairs and 1 platinum molecule per 3800 nDNA base pairs. Furthermore, cisplatin treatment inhibits mtDNA replication as detected by 5-bromo-2'-deoxy-uridine (BrdU) incorporation and inhibits transcription of mitochondrial genes. The relative reduction in mtDNA transcription is directly related to the distance the gene is located from the transcription initiation point, which implies that randomly formed platinum adducts block transcription. Cisplatin treated DRG neurons exhibit mitochondrial vacuolization and degradation in vitro and in vivo. Taken together, this data suggests that direct mtDNA damage may provide a novel, distinct mechanism for cisplatin-induced neurotoxicity separate from the established nDNA damage pathway.

The Additional Value of Endolymphatic Hydrops Imaging With Intratympanic Contrast for Diagnostic Work-Up-Experience From a Neurotology Center in Austria.

Objective: To illustrate the merit of hydrops imaging during clinical workup of dizziness and balance disorders. Background: Ever since the first description of in-vivo endolymphatic hydrops imaging in 2007, this diagnostic tool has been implemented in an increasing number of centers. The more experience in its clinical application is gathered, the more it is possible to critically assess its potential value for the diagnostic workup. This article intends to provide information about the experience of handling and utilization of endolymphatic hydrops imaging in one of the first centers in Austria. Methods: Retrospective analysis and review of clinical cases. Results: Based on our experience of endolymphatic hydrops imaging (EHI), which was established in cooperation between our departments of radiology and otorhinolaryngology in 2017, we have exclusively used intratympanic application of a contrast agent prior to magnetic resonance imaging, as this approach provides high quality imaging results. In 42.6% of cases, EHI could lead to the diagnosis of MD or HED. Since precise vestibular examination is still necessary, EHI is not a tool to replace the clinical examination but rather to add significantly to the interpretation of the results. Conclusion: Endolymphatic hydrops imaging represents a valuable, safe and well-applicable tool for evaluating cases with inconclusive clinical results. However, its potential additional diagnostic benefits rely on a correct indication based on prior thorough vestibular investigations.

Comparison of native myocardial T1 and T2 mapping at 1.5T and 3T in healthy volunteers : Reference values and clinical implications.

BACKGROUND: Myocardial native T1 and T2 mapping are promising techniques for quantitative assessment of diffuse myocardial pathologies; however, due to conflicting data regarding normal values, routine clinical implementation of this method is still challenging. METHODS: To evaluate this situation during daily clinical practice the characteristics of normal values obtained in 60 healthy volunteers who underwent magnetic resonance imaging (MRI) scans on 1.5T and 3T scanners were studied. The T1 modified look-locker inversion recovery (MOLLI; 5(3)3; modified for higher heart rates) and T2 navigator gated black-blood prepared gradient-spin-echo (GraSE) sequences were used. RESULTS: While age and body mass index did not affect relaxation times, a gender and heart rate dependency was found showing higher T1 and T2 values in females, whereas at higher heart rates a prolongation of T1 and a shortening of T2 relaxation times was found. Particularly prone to artifacts were T2 measurements at 3T and the inferolateral wall. In the individual setting mean relaxation times for T1 were 995.8 ± 30.9 ms at 1.5T and 1183.8 ± 37.5 ms at 3T and 55.8 ± 2.8 ms at 1.5T and 51.6 ± 3 ms at 3T for T2 indicating a high dependency of reference values on MRI protocol when compared to the literature. Furthermore, as presumed mean T1 and T2 values correlated in the same individual. CONCLUSIONS: The T1 and T2 relaxation times depend on physiological factors and especially on MRI protocols. Therefore, reference values should be validated individually in every radiological institution before implementing mapping protocols in daily clinical practice. Correlation of mean T1 and T2 values in the same proband at both field strengths indicates intraindividual reproducibility.

The Functional Anatomy of the Deep Facial Fat Compartments: A Detailed Imaging-Based Investigation.

BACKGROUND: Injection of soft-tissue fillers into the facial fat compartments is frequently performed to ameliorate the signs of facial aging. This study was designed to investigate the functional anatomy of the deep facial fat compartments and to provide information on the effects of injected material in relation to age and gender differences. METHODS: Forty fresh frozen cephalic specimens of 17 male and 23 female Caucasian body donors (mean age, 76.9 ± 13.1 years; mean body mass index, 23.6 ± 5.3 kg/m(2)) were investigated. Computed tomographic and magnetic resonance imaging procedures were carried out using colored contrast-enhanced materials with rheologic properties similar to commercially available soft-tissue fillers. Anatomical dissections were performed to guide conclusions. RESULTS: No statistically significant influences of age or gender were detected in the investigated sample. Increased amounts of injected contrast agent did not correlate with inferior displacement of the material in any of the investigated compartments: deep pyriform, deep medial cheek, deep lateral cheek, deep nasolabial (located within the premaxillary space), and the medial and lateral sub-orbicularis oculi fat. CONCLUSIONS: Increasing volume in the deep midfacial fat compartments did not cause inferior displacement of the injected material. This underscores the role of deep soft-tissue filler injections (i.e., in contact with the bone) in providing support for overlying structures and resulting in anterior projection.

Temporary Explant of a Transcutaneous Bone Conduction Hearing Implant for Imaging of the Pituitary Gland.

OBJECTIVE: Clinical report on feasibility and outcome of a surgical procedure. PATIENT: Nine-year-old child, supplied with a transcutaneous bone conduction hearing implant, requiring magnetic resonance imaging of the head to exclude a tumor of the pituitary gland. INTERVENTION: Temporal removal and subsequent reimplantation of the implant in a single surgical procedure. MAIN OUTCOME MEASURE: Postoperative audiometric results. CONCLUSION: Under specific clinical circumstances, temporary removal of the transcutaneous bone conduction implant described, is technically accomplishable.

The Functional Anatomy of the Superficial Fat Compartments of the Face: A Detailed Imaging Study.

BACKGROUND: The superficial (subcutaneous) facial fat compartments contribute to the signs of facial aging, but a comprehensive anatomical description of their location and their functional behavior during the application of soft-tissue fillers remains elusive. METHODS: The authors investigated 30 fresh frozen cephalic specimens from 13 male and 17 female Caucasian body donors (age, 78.3 ± 14.2 years; body mass index, 23.1 ± 5.3 kg/m(2)). Upright-position, contrast-enhanced computed tomographic scanning, and additional magnetic resonance imaging were performed. Three-dimensional reconstruction-based measures were conducted to evaluate the position of the applied contrast agent in each compartment separately. Successive anatomical dissections were performed to confirm the imaging findings. RESULTS: Positive correlations were detected between the amounts of injected material and the inferior displacement for the superficial nasolabial (rp = 0.92, p = 0.003), middle cheek (rp = 0.70, p = 0.05), and jowl (rp = 0.92, p = 0.03) compartments but not for the medial cheek (rp = 0.20, p = 0.75), lateral cheek (rp = 0.15, p = 0.75), or the superior (rp = -0.32, p = 0.41) or inferior superficial temporal compartment (rp = -0.52, p = 0.29). CONCLUSION: This study confirms the presence of distinct subcutaneous fat compartments and provides evidence for an individual behavior when soft-tissue fillers are applied: inferior displacement of the superficial nasolabial, middle cheek, and jowl compartments, in contrast to an increase in volume without displacement (i.e., an increase in projection) of the medial cheek, lateral cheek, and both superficial temporal compartments.

Updated anatomy of the buccal space and its implications for plastic, reconstructive and aesthetic procedures.

BACKGROUND: The buccal space is an integral deep facial space which is involved in a variety of intra- and extra-oral pathologies and provides a good location for the harvest of the facial artery. The age-related anatomy of this space was investigated and compared to previous reports. METHODS: We conducted anatomic dissections in 102 fresh frozen human cephalic specimens (45 males, 57 females; age range 50-100 years) and performed additional computed tomographic, magnetic resonance and 3-D surface volumetric imaging studies to visualize the boundaries and the contents of the buccal space after injection of contrast enhancing material. RESULTS: The mean vertical extent of contrast agent injected into the buccal space was 25.2 ± 4.3 mm and did not significantly differ between individuals of different age (p = 0.77) or gender (p = 0.13). The maximal injected volume was 10.02 cc [range: 3.09-10.02] without significant influence of age (p = 0.13) or gender (p = 0.81). The change in surface volume was 3.64 ± 1.04 cc resulting in a mean surface-volume-coefficient of 0.87 ± 0.12 without being statistically significant influenced by age (p = 0.53) or gender (p = 0.78). CONCLUSIONS: The facial artery was constantly identified within the buccal space whereas the facial vein was found to course within its posterior boundary. The buccal space did not undergo age-related changes in volume or size which highlights this space is a reliable and predictable landmark for various plastic, reconstructive and aesthetic procedures.

An Update on the Anatomy of the Forehead Compartments.

BACKGROUND: The forehead is one of the most frequent locations for neuromodulator and soft tissue filler applications; however, the underlying anatomy is still poorly understood. Thus far, the presence of deep forehead compartments has not been confirmed. METHODS: Twenty Caucasian cephalic specimens, 15 fresh frozen (six female and nine male) and five with formalin-phenol embalmment (three female and two male) were investigated using contrast-enhanced computed tomographic scans, dye injections, and anatomical dissections. RESULTS: Three superficial (one central and two lateral) and three deep (one central and two lateral) forehead compartments were identified. The superficial fat compartments were found within the subcutaneous fat tissue (layer 2) and measured 2.1 × 4.6 mm for the superficial central forehead compartments and the right superficial lateral forehead compartments and 2.6 × 3.2 cm for the left superficial lateral forehead compartments, with a mean volume of 2.5, 3.1, and 3.4 cc, respectively. The deep fat compartments were identified deep to the frontalis muscle but superficial to the periosteum with an extent of 6.4 × 5.9 cm for the deep central forehead compartments, 2.6 × 5.8 cm for the right deep lateral forehead compartments, and 2.7 × 5.8 cm for the left deep lateral forehead compartments, and a mean volume of 9.1, 1.6, and 1.4 cc, respectively. CONCLUSIONS: The results presented in this study increase the understanding of the forehead anatomy. Understanding the presence of the superficial and the deep forehead compartments allows one to change the signs of frontal aging. The deep forehead compartments are in general avascular planes and permit blunt dissection for access to the supraorbital region.

The Anatomy of the Facial Vein: Implications for Plastic, Reconstructive, and Aesthetic Procedures.

BACKGROUND: Anatomical knowledge of the facial vasculature is crucial for successful plastic, reconstructive, and minimally invasive procedures of the face. Whereas the majority of previous investigations focused on facial arteries, the precise course, variability, and relationship with adjacent structures of the facial vein have been widely neglected. METHODS: Seventy-two fresh frozen human cephalic cadavers (32 male and 40 female cadavers; mean age, 75.2 ± 10.9 years; mean body mass index, 24.2 ± 6.6 kg/m; 99 percent Caucasian ethnicity) were investigated by means of layer-by-layer anatomical dissection. In addition, 10 cephalic specimens were investigated using contrast agent-enhanced computed tomographic imaging. RESULTS: The facial vein displayed a constant course in relation to the adjacent anatomical structures. The vein was identified posterior to the facial artery, anterior to the parotid duct, and deep to the zygomaticus major muscle. The angular vein formed the lateral boundary of the deep medial cheek fat and the premaxillary space, and the medial boundary of the deep lateral cheek fat and the sub-orbicularis oculi fat. The mean distance of the inferior and superior labial veins, of the deep facial vein, and of the angular vein from the inferior orbital margin was 51.6 ± 3.1, 42.6 ± 2.3, 27.4 ± 3.0, and 4.2 ± 0.7 mm, respectively. CONCLUSIONS: This work provides detailed information on the course of the facial vein in relation to neighboring structures. The presented clinically relevant anatomical observations and descriptions of landmarks will serve as helpful information for plastic, reconstructive, and aesthetic surgeons.