Bilateral Keloid Formation after Otoplasty in the Presence of Prolonged Mask Wearing.

Prominent ears are the most frequently observed congenital deformity of the head and neck. Various techniques have been proposed for their aesthetic correction. Typically, surgical treatment for protruding ears involves a combination of suture, cutting, and scoring techniques. Herein, we present the clinical case of an 11-year-old child who developed bilateral keloid formations 12 months after otoplasty. Keloids and hypertrophic scars can result from extensive retroauricular skin excisions that do not allow for tension-free wound closure. In addition, skin tension and friction on immature surgical scars are common risk factors for keloid formation. To comply with school guidelines aimed at reducing the transmission of SARS-CoV-2, the patient has consistently worn FFP2 masks with ear loops positioned behind the concha. Although masks play a critical role in preventing the spread of infectious diseases, they can lead to friction in the postauricular area. In light of the presented case, it is important to examine potential cofactors that may contribute to keloid formation after otoplasty, as well as suggest a strategy to safeguard the retroauricular scar.

Risk and course of COVID-19 in immunosuppressed patients with myasthenia gravis.

BACKGROUND: Patients with myasthenia gravis (MG) are potentially prone for a severe COVID-19 course, but there are limited real-world data available on the risk associated with COVID-19 for patients with MG. Here, we investigate whether current immunosuppressive therapy (IST) influences the risk of SARS-CoV-2 infection and COVID-19 severity. METHODS: Data from the German myasthenia gravis registry were analyzed from May 2020 until June 2021 and included patient demographics, MG disease duration, comorbidities, current IST use, COVID-19 characteristics, and outcomes. Propensity score matching was employed to match MG patients with IST to those without, and multivariable binary logistic regression models were used to determine associations between IST with (1) symptomatic SARS-CoV-2 infection and (2) severe COVID-19 course, as measured by hospitalization or death. RESULTS: Of 1379 patients with MG, 95 (7%) patients (mean age 58 (standard deviation [SD] 18) presented with COVID-19, of which 76 (80%) received IST at time of infection. 32 patients (34%) were hospitalized due to COVID-19; a total of 11 patients (12%) died. IST was a risk factor for hospitalization or death in the group of COVID-19-affected MG patients (odds ratio [OR] 3.04, 95% confidence interval [CI] = 1.02-9.06, p = 0.046), but current IST was not associated with a higher risk for SARS-CoV-2 infection itself. DISCUSSION: In this national MG cohort study, current IST use was a risk factor for a severe disease course of COVID-19 but not for SARS-CoV-2 infection itself. These data support the consequent implementation of effective strategies to prevent COVID-19 in this high-risk group. TRIAL REGISTRATION INFORMATION: German clinical trial registry ( https://www.drks.de ), DRKS00024099, first patient enrolled: February 4th, 2019.

Better be prepared: the spectrum of neuropsychiatric impairment among Libyan war victims transferred to Germany for trauma rehabilitation.

BACKGROUND: The current Libyan civil war has originated many casualties, imposing medical challenges. War injuries are complex, requiring specialized knowledge and interdisciplinary assessment for adequate patient and intercultural management. METHODS: This retrospective study analyzed records of 78 Libyan patients admitted from July 2016 to November 2017 to neurological and trauma surgical departments of Krankenhaus Nordwest, Frankfurt, Germany. Issues of system preparation of the hospital, demographics, injury patterns and therapies were analyzed. The chi-squared test was used to analyze differences in injury patterns in explosion and gunshot injuries. RESULTS: Seventy-seven of seventy-eight patients were male (mean age 30.6 years). The patients received primary and secondary treatment in Tunisia (n = 39), Libya (n = 36) and Turkey (n = 23). Forty-eight patients had gunshot injuries, 37 explosion injuries, 11 both. Preparation for management of injuries included hygienic and isolation protocols, organization of interpreters and intercultural training. Patients presented with a broad variety of neurological, psychiatric and trauma surgical injuries. Fifty-six patients had sensory, 47 motor deficits. Nine reported headache, 5 vertigo, 13 visual impairment, 28 psychiatric symptoms. Eighteen patients had central nervous damage, 50 peripheral nervous damage. Central nervous damage was significantly more common in gunshot than explosion injuries (p = 0.015). Peripheral nervous damage was more common in explosion than gunshot injuries (p < 0.1). Fifty-one patients had polytrauma and 49 suffered from fractures. Therapy included surgical interventions (n = 56) and physiotherapy. Structured rehabilitation programs were often indicated. CONCLUSION: Specialized knowledge about war injuries and their management including hospital preparation and planning regarding infrastructure may be required anytime. Injuries include a broad variety of neurological, psychiatric and trauma surgical injuries. Therefore, an interdisciplinary approach is crucial.

The nasal valve: new insights on the static and dynamic NV with MR-imaging.

PURPOSE: We assessed the static nasal valve angle with MR imaging in healthy subjects and evaluated the complex mechanism of nasal valve dynamics during physiologic and forced inspiration. METHODS: In 17 healthy subjects, measurements of the static nasal valve angle were conducted on MR scans, using a TSE Axial T2-weighted sequence and a 3 mm slice thickness. The dynamic changes of nasal valve movement were detected using MR Cine-imaging techniques. RESULTS: The static median angle of the nasal valve was found to be 28.6° with a range of 12.7°-39.3°. The median degree of nasal valve collapse during forced inspiration was 68% (range 20-99%) of the baseline (static nasal valve angle). In the moderately forced inspiration (3 s) the median nasal valve angle declined to 76% of the baseline angle (range 42-100%). In the physiologic or unforced inspiration, the median nasal valve angle was reduced to 86.3% of the baseline angle (range 52-100%). CONCLUSION: MRI, as a non-invasive tool, is a reliable method for evaluation of the static nasal valve angle and for the illustration of the complex nasal valve dynamics.

Chemoradiation and local recurrence of head and neck squamous cell carcinoma and the risk of carotid artery blowout.

BACKGROUND: Carotid blowout syndrome (CBS) is a rare but life-threatening complication of head and neck squamous cell carcinoma (HNSCC). Chemoradiation (CRT) may make CBS more likely, but so far no longitudinal analysis of different treatment strategies has been conducted. METHODS: In the present study, 1072 patients with HNSCC were divided into groups depending on whether they had experienced CBS. Disease-related data were analyzed using chi-square test, Fisher exact test, and Student's t test. Survival rates were calculated using Kaplan-Meier test, log-rank test, and the Cox regression analysis for forward selection. RESULTS: Thirty-six patients suffering from CBS demonstrated significantly advanced T status (P = .001) and UICC stage (P = .004) when compared with unaltered counterparts. After adjustment for UICC stage, OS was comparable in both groups, whereas the mean recurrence-free survival (RFS) rate was better in unaltered patients (67 vs 24 months; P < .0001). Cox regression for forward selection revealed local recurrence (hazard ratio [HR], 1.9; P < .0001), T status (HR, 1.9; P = .03), and CRT (HR, 2.0; P < .0001) as independent risk factors for mortality related to CBS. CONCLUSION: CBS is a rare event in patients with HNSCC demonstrating reduced OS/RFS. Advanced T status, C/RT, and the recurrence of local tumors increase the risk of CBS-associated death.

Transoral laser microsurgery in early glottic cancer involving the anterior commissure.

PURPOSE: Treatment modalities for glottic cancer comprise surgery, (chemo-)radiation, and combined treatment options. Glottic cancer involving the anterior commissure (AC) requires special preoperative assessment and surgical skills, as it is commonly considered a risk factor for local recurrence. The aim of this study is to analyze the oncological effectiveness of transoral laser microsurgery (TLM) in the early glottic cancer involving the AC. METHODS: We retrospectively analyzed the data of all patients with primary, early staged (T1-2) glottic squamous cell carcinoma who were treated between 2004 and 2014. Patients were preferably treated by TLM (rather than open surgical techniques) if appropriated transoral exposure of the endolarynx was ensured. Voice outcomes were not assessed. RESULTS: 186 patients with early glottic cancer were included, 143 were treated by TLM and 43 by other therapy modalities [OT open surgical techniques (n = 32) or primary (chemo-)radiation (n = 11)], respectively. In 84 patients (59%) of the TLM cohort, the AC was involved (OT cohort n = 29 (73%), p = 0.143). The 1-, 3-, and 5-year local control rates after TLM were 91%, 86%, and 81% in patients without AC infiltration and 84%, 74%, and 70% in patients with AC infiltration, respectively, showing no statistical difference (p = 0.180). The 5-year disease-free survival and laryngeal preservation rate (LPR) did not differ with regard to AC infiltration (p = 0.215 and p = 0.261). Comparing the treatment modalities, the 5-year LPR was 90% for TLM and 83% for OT regardless of infiltration of the AC (p = 0,653 and p = 0.267, respectively). CONCLUSION: TLM is an effective surgical treatment for early glottic cancer with AC involvement in patients with adequate transoral laryngeal exposure.

Long-term Outcome for Open and Endoscopically Resected Sinonasal Tumors.

OBJECTIVE: Endoscopic resection of sinonasal cancer has become an alternative to open craniofacial surgery and leads to safe and satisfying results in emerging numbers. Randomized study data comparing outcomes between approaches are missing. Hence, it remains unclear which subgroups of patients might profit most from each technique. We aimed to identify such patient and tumor characteristics and gather information for future prospective study design. STUDY DESIGN: Case series with chart review. SETTING: Tertiary academic center. SUBJECTS AND METHODS: This study is based on a retrospective chart review of 225 patients undergoing open craniofacial or endoscopic resection for sinonasal malignancy between 1993 and 2015 at Munich University Hospital. Statistical analyses include t test, chi-square, Kaplan-Meier charts, and univariate and multivariate analyses. RESULTS: The sample size was similar between the endoscopic and open surgery groups. Tumors were significantly larger in patients who underwent open craniofacial resection. The risk of notable bleeding ( P = .041) was lower and hospital stay shorter ( P = .001) for endoscopic interventions of all tumor stages. Rates of overall ( P = .024) and disease-specific ( P = .036) survival were significantly improved for endoscopic cases; improved recurrence-free survival rates did not achieve statistical significance ( P = .357). For cases matched for tumor size, this improvement was confirmed for T3 tumors ( P = .038). Regional and distant metastatic tumor spread generally worsened survival in both surgical subgroups. Multivariate Cox regression analysis revealed independent prognosticators for overall survival. CONCLUSION: Endoscopic tumor resection remains a suitable option for distinct indications and showed improved outcome in intermediate-stage tumors in our collective. Further randomized studies acknowledging the here-identified factors are needed to improve future therapy guidelines and patient care.

Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma.

Current treatment options for advanced and recurrent head and neck squamous cell carcinoma (HNSCC) enclose radiation and chemo-radiation approaches with or without surgery. While platinum-based chemotherapy regimens currently represent the gold standard in terms of efficacy and are given in the vast majority of cases, new chemotherapy regimens, namely immunotherapy are emerging. However, the response rates and therapy resistance mechanisms for either chemo regimen are hard to predict and remain insufficiently understood. Broad variations of chemo and radiation resistance mechanisms are known to date. This study describes the development of a standardized, high-throughput in vitro assay to assess HNSCC cell line's response to various therapy regimens, and hopefully on primary cells from individual patients as a future tool for personalized tumor therapy. The assay is designed to being integrated into the quality-controlled standard algorithm for HNSCC patients at our tertiary care center; however, this will be subject of future studies. Technical feasibility looks promising for primary cells from tumor biopsies from actual patients. Specimens are then transferred into the laboratory. Biopsies are mechanically separated followed by enzymatic digestion. Cells are then cultured in ultra-low adhesion cell culture vials that promote the reproducible, standardized and spontaneous formation of three-dimensional, spheroid-shaped cell conglomerates. Spheroids are then ready to be exposed to chemo-radiation protocols and immunotherapy protocols as needed. The final cell viability and spheroid size are indicators of therapy susceptibility and therefore could be drawn into consideration in future to assess the patients' likely therapy response. This model could be a valuable, cost-efficient tool towards personalized therapy for head and neck cancer.

Is Perineural Invasion of Head and Neck Squamous Cell Carcinomas Linked to Tobacco Consumption?

Perineural invasion (PNI) is an underrecognized path of cancer spread, and its causes and mechanisms are poorly understood. Recent research indicates a mutual attraction of neuronal and cancer cells, largely dependent on neurotrophic factors and their receptors. Interestingly, the release of neurotrophic factors occurs upon cigarette smoke/nicotine exposure in a dose-dependent manner, and serum levels correlate with current smoking, number of smoking years, and smoking severity. Among cell types capable of neurotrophic factors secretion are lung and oral fibroblasts. In our study of 178 patients with head and neck squamous cell carcinoma, tumors of current and former smokers showed PNI significantly more often than tumors of never smokers. Moreover, PNI was a marker for aggressive tumor growth. Surprisingly, PNI was more significant for survival than p16 status. Our study warrants further research on PNI in head and neck squamous cell carcinoma with special emphasis on the impact of tobacco consumption to identify suitable candidates for therapeutic interventions.

Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified for HPV-status.

OBJECTIVE: Lymph node ratio (LNR) was shown to be a prognostic factor in laryngeal and oral cavity primaries. The purpose of this study was to investigate the impact of the lymph node ratio in oropharyngeal squamous cell carcinoma (OPSCC) with a high incidence of HPV-related disease. Therefore, the role of LNR was evaluated as an additional predictive parameter to the 8th edition of AJCC TNM staging system. METHODS: From December 2009 to August 2015, patients diagnosed with primary oropharyngeal squamous cell carcinoma were prospectively enrolled. After tumor resection with uni- or bilateral neck dissection, patients with ≥ 1 nodal metastasis (pN+) were eligible for a retrospective LNR analysis. RESULTS: 137 patients underwent tumor resection with uni- or bilateral neck dissection. The proportion of HPV-associated disease was 42%. Most patients (n = 96; 70%) presented with involved neck nodes. In p16-positive OPSCC, the rate of pN + cases was significantly increased compared to p16-negative OPSCC (86% vs. 58%, p = 0.007). Patients with LNR ≤ 10% had a significant better overall survival (OS) and disease-specific survival (DSS). However, when stratified for p16-status, LNR ≤ 10% had a significant impact on OS only for HPV-associated tumors (p = 0.027), whereas LNR of ≤ 10% was not a significant predictor for better OS in p16-negative OPSCC (p = 0.143). CONCLUSION: The LNR with a cut-off value of 10% serves as an additional prognostic parameter in HPV-related OPSCC and may help to improve risk stratification in combination with the revised AJCC 8th edition TNM classification.

Head and neck reconstruction in the elderly patient: a safe procedure?

Demographic changes strongly affect industrialized countries. While free tissue transfer was initially believed to be beneficial only for younger patients, there is an increasing number of elderly patients requiring microvascular operations in our aging society. Medical and surgical risks for head and neck cancer patients over a certain age who undergo free tissue transfer has hardly been investigated. A retrospective mono-center cohort study was performed. All patients with the age 75 or higher undergoing microvascular operations were reviewed. Patient characteristics including the ASA-status, the ACE-27-score, flap survival and postoperative medical and surgical complications were evaluated. The Clavien-Dindo-classification system for postoperative complications was applied to assess the severity of the complications. A total of 31 patients with an average age of 78.8 years were included. 4 patients suffered from venous congestion and had to undergo revision surgery. All flaps could successfully be salvaged. Higher ASA-status and ACE-score were significantly associated with postoperative medical and surgical complications and a higher severity of the complications. However , neither age nor operating time had influence on the complication rate. Microvascular free tissue transfer can be performed with a high degree of security in selected elderly patients. However, serious medical complications remain a concern, correlating strongly with high ASA and ACE-score. Careful patient selection is mandatory to reduce complications to a minimum.

Spheroid-based 3D Cell Cultures Enable Personalized Therapy Testing and Drug Discovery in Head and Neck Cancer.

BACKGROUND/AIM: Chemo-radiation currently serves as first-line therapy of advanced and recurrent head and neck cancer, while new chemotherapy regimens are emerging. However, response rates to any treatment are difficult to predict and underlie broad variation. This study shows the development of a standardized, high-throughput in vitro assay to assess patients' individual response to therapy regimens as a future tool for personalized tumor therapy. MATERIALS AND METHODS: Viability and proliferation analyses after chemo +/- radiation treatment of single spheroids (low adhesion plates/Hanging Drop (HD)) were generated from head and neck squamous cell carcinoma (HNSCC) cell lines and primary human cells from fresh tumor specimens. RESULTS: All cell lines showed reliable growth in all cell culture methods. The spheroids showed significant delay of growth and/or necrosis compared to control groups when exposed to current standard chemotherapeutic regimens. Single 3D spheroids ready for therapy susceptibility testing could be generated from actual tumor specimens after enzymatic and mechanical separation. CONCLUSION: In its current form, this single spheroid-based in vitro assay was able to test individual therapy susceptibility to current standard therapy regimens or, potentially, for testing new targeted drugs in HNSCC treatment. With recent discoveries regarding tumor heterogeneity and individual mutation status, a reliable assay is a prerequisite for personalized therapy in head and neck cancer.

Management of locoregional recurrence in cutaneous squamous cell carcinoma of the head and neck.

Cutaneous squamous cell carcinomas often affect elderly patients. Follow-up monitoring is difficult in these patients due to their multi-morbidity and reduced compliance. Tumour recurrence is consequently diagnosed in advanced tumour stages. Surgical therapy with curative intention often requires extended resections. The study at hand should determine whether surgical concepts are warranted in this collective. Sixty-seven patients who underwent surgical procedure due to recurrent disease of cutaneous head and neck squamous cell carcinoma were included. The cohort was divided in patients with/without adjuvant therapeutic regimens. Data were assessed retrospectively. Complete tumour resection was achieved in 85 % of our patients. Patients with adjuvant treatment demonstrated a favorable 5-year-recurrence-free interval (78 vs 30 %) and overall survival (79 vs 46 %). Complete surgical resection of advanced recurrent head and neck cutaneous squamous cell carcinomas is possible and yields favorable results in terms of survival, especially if combined with adjuvant treatment.

Impact of comorbidity and anemia in patients with oropharyngeal cancer primarily treated with surgery in the human papillomavirus era.

BACKGROUND: Comorbidity and anemia strongly influence treatment and outcome of oropharyngeal squamous cell carcinomas (SCCs), but respective data are frequently lacking in clinical studies. We evaluated 149 cases of oropharyngeal SCC primarily treated with surgery regarding the impact of these factors on disease-free survival (DFS) and overall survival (OS). METHODS: Data were recorded during treatment and follow-up visits. Human papillomavirus (HPV) association of oropharyngeal SCC was detected by p16 immunohistochemistry. RESULTS: Patients with p16-positive disease were significantly less comorbid and anemic, and treated more aggressively. Comorbidity and anemia, but not p16 status, significantly influenced DFS and had more impact on OS than p16 status. CONCLUSION: In our study, p16-positive seems a good surrogate marker for healthier patients. Patients with p16-positive disease showed improved survival, but this was limited to none/mild comorbid and/or nonanemic individuals in this group. On the basis of our results, we strongly suggest the inclusion of these factors in risk stratification for clinical studies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 7-16, 2017.

Potential impact of human papilloma virus on survival of basaloid squamous carcinoma of the head and neck.

OBJECTIVES: Basaloid-squamous-carcinomas (BSCC) have been considered as aggressive variants of common squamous-cell-carcinomas (HNSCC). Recent studies demonstrated a different clinical course depending on the tumour site. The aim of the study is to analyze the histopathologic/clinical features of BSCC/HNSCC resolved by the HPV-status. METHODS: We analysed the histopathologic/clinical features of BSCC (n=59) and HNSCC (n=981), subdivided due to the HPV status. Differences were analysed using Chi square, Fisher exact, and student's t-test. Survival rates were calculated by Kaplan-Meier and log-rank test. Prognostic variables were subsequently evaluated by Cox regression. RESULTS: Our cohort was congruent with the literature regarding sex, age, metastases, and a predilection in the oropharynx. HNSCC/BSCC did not show a different disease-specific-survival. After UICC matching, univariate analysis revealed a better survival of UICC stage IVa BSCC compared to HNSCC (69% vs. 42%, p=0.022) that was associated with a better response to radio-chemotherapy (p = 0.009). These results referred to the high prevalence of HPV+ (86%) oropharyngeal BSCC. Subgroup analysis demonstrated a better survival of HPV+ oropharyngeal BSCC than HPV- BSCC (p=0.017). CONCLUSION: The clinical outcome in BSCC depends on the tumour site and HPV-status. Prospective studies have to evaluate the beneficial application of postoperative radio-chemotherapy in HPV+ BSCC.

Enchondroma of the nasal septum due to Ollier disease: a case report and review of the literature.

BACKGROUND: Morbus Ollier is characterized by the presence of multiple enchondromas (ie, benign intraosseous cartilaginous lesions). Although their manifestation in the limb bones is well described, only a few cases with ear, nose, and throat (ENT) involvement, primarily arising from the skull, have been reported. The malignant transformation toward slowly growing low-grade chondrosarcomas is the most severe form of progression. METHODS: We report a unique case of a 54-year-old patient with Ollier disease with an extensive nasal enchondroma apparently eroding the middle nasal concha and expanding to the lateral nasal wall that raised suspicion of malignant transformation. RESULTS: Radiological and histological features of enchondromas can be controversial and seem to have limited sensitivity to exclude low-grade malignancy. The clinical symptoms play a decisive role in differentiation between enchondromas and low-grade chondrosarcomas. CONCLUSION: Surgery remains the only effective solution in removing an enchondroma and preventing the tendency toward malignant transformation.

Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders.

BACKGROUND: A new autoantibody (termed NMO-IgG, or AQP4-Ab) has recently been described in patients with neuromyelitis optica (NMO) and its formes frustes, longitudinally extensive transverse myelitis (LETM) and recurrent optic neuritis (rON). However, AQP4-Ab has been found also in patients with co-existing rheumatic diseases such as systemic lupus erythematosus (SLE) or Sjögren's syndrome (SS), conditions which are characterized by broad, polyspecific B cell activation. OBJECTIVES: In this study, we aimed at evaluating the syndrome specificity and frequency of AQP4-Ab in patients with rheumatic diseases and neurological symptoms. METHODS: For this purpose, serum samples from 109 neurological patients with established connective tissue disorders (CTD) (n = 54), possible CTD (n = 42), or vasculitis (n = 13) were analysed for the presence of AQP4-Ab by a cell-based assay employing recombinant human AQP4. RESULTS: AQP4-Ab was detectable in 31/40 (78%) patients with CTD and NMO spectrum disorders (median titre, 1:1000) but in none of the samples obtained from patients with CTD or vasculitis and neurological disorders other than NMO, LETM, or rON (n = 69). CONCLUSION: The high syndrome specificity of the antibody for neuromyelitis optica spectrum disorders (NMOSDs) in patients with CTD supports the concept of AQP4-Ab being involved in the pathogenesis of these neurological conditions, and argues against AQP4-Ab simply being part of the polyclonal B cell activation generally associated with rheumatic diseases. Moreover, the finding that AQP4-Ab is present in patients with CTD and co-existing NMOSD with approximately the same frequency as in patients without CTD strengthens the case of CTD and AQP4-Ab positive NMOSD representing two co-existing yet distinct entities in the majority of patients.

Disgust and fear recognition in paraneoplastic limbic encephalitis.

Paraneoplastic limbic encephalitis (PNLE) affects limbic portions of the brain associated with recognition of social signals of emotions. Yet it is not known whether this perceptual ability is impaired in individuals with PNLE. We therefore conducted a single case study to explore possible impairments in recognising facially, vocally and bodily expressed emotions, using standardised emotion recognition tests. Facial expression recognition was tested with two forced-choice emotion-labelling tasks using static faces with either prototypical or morphed blends of basic emotions. Recognition of vocally and bodily expressed emotions was also tested with forced-choice labelling tasks, one based on prosodic cues, the other on whole-body movement cues. We found a deficit in fear and disgust recognition from both face and voice, while recognition of bodily expressed emotions was unaffected. These findings are consistent with data from previous studies demonstrating critical roles for certain brain regions - particularly the amygdala and insular cortex - in processing facially and vocally displayed basic emotions, and furthermore, suggest that recognition of bodily expressed emotions may not depend on neural structures involved in facial and vocal emotion recognition. Impaired facial and vocal emotion recognition may form a further neuropsychological marker of limbic encephalitis, in addition to the already well-described mnestic deficits.

Rippling muscle disease: variable phenotype in a family with five afflicted members.

We report a family with rippling muscle disease (RMD) who had an autosomal dominant mode of inheritance. The father, mother, and one daughter proved to be heterozygous, and two sons were homozygous for the A92T mutation of the caveolin-3 gene. The cardinal features of RMD, particularly percussion-induced rapid contractions, muscle mounding, and muscle rippling, varied considerably among these subjects. Moreover, all examined individuals showed muscle weakness; however, the patterns were inconsistent.

Intrathecal antibody production against Epstein-Barr and other neurotropic viruses in pediatric and adult onset multiple sclerosis.

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of multiple sclerosis (MS). Recent reports proposed an increased EBV-targeted humoral immune response in MS, which appears to be more pronounced in pediatric patients. However, little is known about the CNS-derived antibody production against EBV in patients with MS. The objective of this study was to assess the frequency and intensity of intrathecal antibody production against EBV as compared to other neurotropic viruses in pediatric and adult onset MS. In cohorts of 43 childhood, 50 adult onset MS patients, 20 children and 12 adults with other CNS disorders, paired CSF and serum samples were studied. Frequency and intensity of intrathecal antibody production against EBV as compared to measles, rubella, varicella zoster (VZV) and herpes simplex virus (HSV) were analyzed by determination of virus-specific CSF-to-serum Antibody Indices (AI). Intrathecally synthesized EBV antibodies were detectable in 26% pediatric and 10% adult onset MS patients, compared to frequencies ranging in both groups from 10 to 60% for the other viruses. Median AIs for EBV were lower than those for all other viruses, with more than twofold higher median AI for measles, rubella and VZV. The EBV-targeted humoral immune response in the CNS is only part of the intrathecal polyspecific antibody production in MS, directed against various neurotropic viruses. Our results do not rule out the possibility that EBV is involved in the pathogenesis of MS by triggering diverse cellular immune mechanisms, but they argue against a direct pathogenic role of EBV-targeted humoral immune response within the CNS.