Changes in the duration and frequency of deviant stimuli engender different mismatch negativity patterns in temporal lobe epilepsy.

Mismatch negativity (MMN) is an event-related potential (ERP) component that reflects preattentive sensory memory functions. Previous research revealed that MMN is generated by distinct sources in the frontal and temporal lobes. Event-related potential abnormalities have been shown in the vicinity of seizure foci in epilepsy. Additionally, no published study has investigated the MMN in response to variations in both frequency and duration deviants in patients with temporal lobe epilepsy (TLE). The aims of this study were to compare MMN changes between the frontocentral sites and the mastoid sites and to compare MMNs related to deviant stimuli with different durations and frequencies in patients with TLE. We recorded MMNs elicited by duration and frequency changes of deviant stimuli from 15 patients with TLE and 15 healthy control subjects. We found that mean MMN amplitudes related to duration deviants were lower in patients with TLE at the mastoid sites relative to controls, whereas the MMN amplitudes at the frontocentral sites did not differ between the two groups. There were no MMN differences related to frequency deviants between TLE subjects and controls at the frontocentral sites or the mastoid sites. Mismatch negativity parameters related to duration deviants did not correlate with those related to deviant frequencies in the group with TLE. The present findings suggest selective impairments among multiple mismatch generators in TLE and suggest that processing of temporal information of auditory stimuli is selectively disturbed in TLE. Changes in MMN amplitudes related to duration deviants at the mastoid sites may represent deficits in time-dependent processing in TLE.

Mismatch negativity for speech sounds in temporal lobe epilepsy.

The mismatch negativity (MMN) is an electrophysiological trace of change detection, measured by electroencephalography (EEG), and is a reliable marker for pre-attentive auditory sensory memory. We used a phonetic oddball paradigm in patients with temporal lobe epilepsy (TLE) to elicit the MMN response at fronto-central sites and the mismatch positivity (MMP) response at mastoid sites. The MMN in 26 patients was compared with that of 26 age- and gender-matched healthy control participants. Electroencephalography responses were recorded during the presentation of speech sounds: the vowels 'a' and 'o' in alternation. Average waveforms were obtained for standard and deviant trials. We found that the MMP response at bilateral mastoid sites was reduced, whereas the MMN response at fronto-central sites did not change significantly. These results support the view that the MMN is generated by separable sources in the frontal and temporal lobes and that these sources are differentially affected by TLE.

Effect of pneumococcal conjugate vaccine on prevalence of otitis media with effusion among children in Vietnam.

PURPOSE: Otitis media with effusion (OME) is common in young children and is associated with Streptococcus pneumoniae infection. We aimed to determine the impact of pneumococcal conjugate vaccine (PCV) introduction on the prevalence of OME and OME associated with vaccine-type (VT) or non-VT. METHODS: Population-based cross-sectional surveys were conducted in pre- (2016) and post-PCV periods (2017, 2018, and 2019) at selected communes in Nha Trang, Vietnam. For each survey, we randomly selected 60 children aged 4-11 months and 60 aged 14-23 months from each commune. Nasopharyngeal sample collection and tympanic membrane examination by digital otoscope were performed. S. pneumoniae was detected and serotyped by lytA qPCR and microarray. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using Firth's logistic regression, stratified by age group. RESULTS: Over the four surveys, 2089 children had a bilateral ear examination. Compared to pre-PCV, the prevalence of OME reduced in 2018 (OR 0.51, 95 %CI 0.28-0.93) and in 2019 (OR 0.53, 95 %CI 0.29-0.97) among the <12-month-olds, but no significant reduction among the 12-23-month-olds. The prevalence of OME associated with VT pneumococcus decreased in 2018 and 2019 (2018: OR 0.14, 95 %CI 0.03-0.55; 2019: OR 0.20, 95 %CI 0.05-0.69 in the <12-months-olds, 2018: OR 0.05, 95 %CI 0.00-0.44, 2019: OR 0.41, 95 %CI 0.10-1.61 in the 12-23-months-olds). The prevalence of OME associated with non-VT pneumococcus increased in the 12-23-month-olds in 2017 (OR 3.09, 95 %CI 1.47-7.45) and returned to the pre-PCV level of prevalence in 2018 and 2019 (OR 0.94, 95 %CI 0.40-2.43 and 1.40, 95 %CI 0.63-3.49). CONCLUSION: PCV10 introduction was associated with a reduction of OME prevalence in infants but not in older children.

Prevalence and characteristics of children with otitis media with effusion in Vietnam.

PURPOSE: Otitis media with effusion (OME) commonly occurs and persists in young children. It can cause hearing impairment and damage to the tympanic membrane without treatment. We aimed to determine the prevalence and association of Streptococcus pneumoniae in the nasopharynx of healthy children before the introduction of a pneumococcal conjugate vaccine. METHODS: In October 2016, nasopharyngeal swabs collection and otoscope examinations by an otolaryngologist were conducted in children aged less than 24 months in Nha Trang, Vietnam. OME was diagnosed as the presence of middle ear fluid using a digital otoscope equipped with a pneumatic otoscope. Quantitative PCR targeting pneumococci-specific lytA (the major autolysis gene) and bacterial culture were performed to detect S. pneumoniae. The point prevalence of OME in the study area was estimated. The association between OME and S. pneumoniae in the nasopharynx was evaluated using a multivariable logistic regression model. RESULTS: Among the 274 children who underwent bilateral ear examinations and nasopharyngeal swab collections, 47 had OME (17.2%, 95% confidence interval [CI] 12.9-22.1%) and 96 were colonized with S. pneumoniae (35.0%, 29.4-41.0%). OME and nasopharyngeal S. pneumoniae carriage were positively associated in children aged less than 12  months (adjusted odds ratio [aOR] 3.83, 1.40-10.51). Day-care attendance and living in a rural area were independently associated with OME (aOR 5.87, 2.31-14.91, and aOR 3.77, 1.58-8.99, respectively). CONCLUSIONS: The nasopharyngeal pneumococcal carriage was associated with OME among children aged  <12 months. A further study after introducing a pneumococcal conjugate vaccine (PCV) is required to better understand the effect of PCV and S. pneumoniae carriage on OME in young children.

Vowel-speech versus pure-tone processing in healthy subjects.

To investigate the characteristics of speech perception, we evaluated the differences in mismatch negativity (MMN) between vowel change and frequency change. Additionally, we examined the effects of gender, age, and educational length on MMN. Forty healthy adults (21 females), who were native Japanese speakers, participated in the study. A Japanese vowel-speech pair (standard/a/vs. deviant/o/) and a pure-tone pair (standard 1000 Hz vs. deviant 1050 Hz) were constructed. MMN elicited by vowel-speech sounds was larger and earlier compared with pure-tone sounds. Larger and earlier MMNs for vowel-speech sounds than for pure-tone sounds suggest different processing of linguistically relevant information at the early stage in the auditory cortex. In conclusion, the factors influencing on MMN are different between vowel-speech sounds and pure-tone sounds.

Association of HLA-A*31:01 Screening With the Incidence of Carbamazepine-Induced Cutaneous Adverse Reactions in a Japanese Population.

Importance: Carbamazepine, a commonly used antiepileptic drug, is one of the most common causes of cutaneous adverse drug reactions (cADRs) worldwide. The allele HLA-A*31:01 is reportedly associated with carbamazepine-induced cADRs in Japanese and European populations; however, the clinical utility of HLA-A*31:01 has not been evaluated. Objective: To assess the use of HLA-A*31:01 genetic screening to identify Japanese individuals at risk of carbamazepine-induced cADRs. Design, Setting, and Participants: This cohort study was conducted across 36 hospitals in Japan from January 2012 to November 2014 among 1202 patients who had been deemed suitable to start treatment with carbamazepine. Preemptive HLA-A*31:01 genetic screening was performed for 1187 participants. Patients who did not start treatment with carbamazepine or alternative drugs were excluded. Participants were interviewed once weekly for 8 weeks to monitor the development of cADRs. Data analysis was performed from June 8, 2015, to December 27, 2016. Exposures: Neuropsychiatrists were asked to prescribe carbamazepine for patients who tested negative for HLA-A*31:01 and alternative drugs for those who tested positive for HLA-A*31:01. Main Outcomes and Measures: Incidence of carbamazepine-induced cADRs. Results: Of the 1130 included patients who were prescribed carbamazepine or alternative drugs, the mean (range) age was 37.4 (0-95) years, 614 (54.3%) were men, and 198 (17.5%) were positive for HLA-A*31:01. Expert dermatologists identified 23 patients (2.0%) who had carbamazepine-induced cADRs, of which 4 patients required hospitalization. Drug-induced hypersensitivity syndrome was observed for 3 patients, maculopapular eruption for 9 patients, erythema multiforme for 5 patients, and an undetermined type of cADR for 6 patients. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis. Compared with historical controls, the incidence of carbamazepine-induced cADRs was significantly decreased (for BioBank Japan data: incidence, 3.4%; odds ratio, 0.60; 95% CI, 0.36-1.00; P = .048; for the Japan Medical Data Centre claims database: incidence, 5.1%; odds ratio, 0.39; 95% CI, 0.26-0.59; P < .001). Conclusions and Relevance: Preemptive HLA-A*31:01 genetic screening significantly decreased the incidence of carbamazepine-induced cADRs among Japanese patients, which suggests that it may be warranted in routine clinical practice.

Long-term Outcomes of Cochlear Implantation in Children With Congenital Cytomegalovirus Infection.

OBJECTIVE: To investigate the role of the developmental delay often observed in children with congenital cytomegalovirus (CMV) infection on the improvement of language understanding after cochlear implantation (CI). STUDY DESIGN: Retrospective chart review. PATIENTS: Sixteen children with severe and/or profound hearing loss due to congenital CMV infection (CMV group) and 107 congenitally deaf children (168 ears) without CMV infection as the cause of deafness (non-CMV group). Mean age at which patients underwent CI was 2.9 years in both groups. The mean follow-up period was 7.8 versus 8.2 years, respectively. INTERVENTIONS/MAIN OUTCOME MEASURES: The Enjoji Scale of Infant Analytical Development was used to evaluate/compare pre- and postoperative hearing level, word recognition score, speech discrimination score, and language production and perception skills. The Picture Vocabulary Test-Revised was used to assess vocabulary understanding skill. Correlation between the final vocabulary understanding skill assessment and several factors was also examined. RESULTS: Improvement in hearing thresholds (mean: 106.0 dB) was greater after the first CI, (27-45 dB; mean: 33.8 dB) compared with hearing aid (48-74 dB; mean: 63.1 dB). Similarly, language perception and production were better in the CMV group. However, in the long term, differences between good and poor cases became prominent, especially in children with motor or cognitive delay and brain abnormalities who performed poorly in the CMV group. CONCLUSION: Long-term language perception and production after CI were overall satisfactory in congenital CMV-deafened children. CI was effective, particularly in the absence of CMV-induced disorders. However, this effectiveness was limited in those with motor or cognitive delay.

IgG4-related disease with cavernous sinus and intra-orbital lesions diagnosed by nasal mucosa biopsy.

IgG4-related disease is a systemic disease characterized by lesions with IgG4 positive plasma cell infiltration in the involved organs and a raised serum IgG4 level. We report a patient of 70-year-old male presented orbital inflammation of IgG4-related disease. The patient developed right eye pain, double vision, and reduced eye sight. MRI image revealed mild right ocular proptosis and swelling of right carvenous sinus, bilateral intraorbital extraocular muscles and right optic nerve. Right optic nerve showed ring-like enhancement. IgG4-related disease was suspected with increased serum IgG4 level of 355 mg/dl, mediastinal lymphadenopathy and prostate enlargement. Transbronchial lung biopsy and prostate needle biopsy were administered with negative results. The eye related symptoms resolved with time, but serum IgG4 continuously increased. IgG4-related disease was diagnosed by nasal mucosa biopsy, which showed IgG4 positive plasma cells within the inflammatory infiltrate. This report emphasizes the usefulness of nasal mucosa biopsy for the diagnosis of IgG4 related disease with lesions difficult to approach.

Aroma helps to preserve information processing resources of the brain in healthy subjects but not in temporal lobe epilepsy.

PURPOSE: Inhalation of ylang-ylang aroma has been shown to reduce the auditory P300, an event-related potential thought to reflect higher-order processing. Because olfactory function is sometimes disturbed in temporal lobe epilepsy (TLE), the objective of the present study was to determine whether the effect of ylang-ylang aroma on the auditory P300 was impaired in patients with TLE. METHOD: Fourteen subjects with TLE and 14 healthy controls participated in this study. Electroencephalograms were recorded during an auditory oddball task, and ylang-ylang aroma or odorless air was delivered through a mask. RESULTS: We found that the ylang-ylang aroma prolonged the latencies of P300 in both groups. The ylang-ylang aroma significantly reduced the P300 amplitudes of healthy subjects as described previously. However, in TLE patients, the P300 was unaffected by the aroma. CONCLUSION: The current results show that exposure to the ylang-ylang aroma reduced information processing resources in healthy subjects but had limited effects in patients with TLE. We suggest that impaired higher-order olfactory processing in TLE patients may inhibit the effects of the ylang-ylang aroma on the P300.

The Usefulness of Reconstructed 3D Images in Surgical Planning for Cochlear Implantation in a Malformed Ear with an Abnormal Course of the Facial Nerve.

OBJECTIVES: It is not unusual for a cochlear implantation (CI) candidate to have some type of ear malformation, in particular an abnormal course of the facial nerve (FN). In this study, we attempted to reconstruct a three-dimensional (3D) image of temporal bone structures with malformation using computed tomography (CT) imaging and examined its usefulness in the surgical planning of CI in a malformed ear. METHODS: We prepared 3D images for 6 separate CI cases before surgery. First, we manually colored preoperative CT images using Photoshop CS Extended. We then converted the colored CT images to 3D images using Delta Viewer, free-ware for Macintosh. Before surgery, we discussed any problems anticipated based on the 3D images and plans for surgery with those who would be performing the CI. RESULTS: Case 1: The subject was a 3-year-old boy with malformed ossicles, semicircular canal (SC) hypoplasia, internal auditory canal stenosis, and an abnormal course of the FN. 3D image indicated that the stapes were absent, and the FN was more anteriorly displaced, so that it was difficult to perform cochleostomy. The surgical findings were similar to those depicted on the 3D image, so we could insert an electrode based on the preoperative image simulation without complications. Case 2: The subject was a 7-year-old boy with malformed stapes, atresia of the round window, cochlear and SC aplasia, and an abnormal course of the FN with bifurcation. CI was performed with no problems, in the same manner as in Case 1. CONCLUSION: We were able to successfully depict the structures of the inner ear, ossicles, and FN as 3D images, which are very easy to understand visually and intuitively. These 3D images of the malformed ear are useful in preoperative image simulation and in surgical planning for those performing a CI procedure.

Bilateral cochlear implantation for children in nagasaki, Japan.

OBJECTIVES: The number of patients with bilateral cochlear implant (CI) has gradually increased as patients and/or parents recognize its effectiveness. The purpose of this report is to evaluate the efficacy of 29 bilateral CI out of 169 pediatric CI users, who received auditory-verbal/oral habilitation at our hearing center. METHODS: We evaluated the audiological abilities 29 Japanese children with bilateral CIs including wearing threshold, word recognition score, speech discrimination score at 1 m from front speaker (SP), 1 m from second CI side SP, speech discrimination score under the noise (S/N ratio=80 dB sound pressure level [SPL]/70 dB SPL, 10 dB) at 1 m from front SP, word recognition score under the noise (S/N ratio=80 dB SPL/70 dB SPL, 10 dB) at 1 m from front SP. RESULTS: Binaural hearing using bilateral CI is better than first CI in all speech understanding tests. Especially, there were significant differences between the results of first CI and bilateral CI on SDS at 70 dB SPL (P=0.02), SDS at 1 m from second CI side SP at 60 dB SPL (P=0.02), word recognition score (WRS) at 1 m from second CI side SP at 60 dB SPL (P=0.02), speech discrimination score (SDS) at 1 m from front SP under the noise (S/N=80/70; P=0.01) and WRS at 1 m from front SP under the noise (S/N=80/70; P=0.002). At every age, a second CI is very effective. However, the results of under 9 years old were better than of over 9 years old on the mean SDS under the noise (S/N=80/70) on second CI (P=0.04). About use of a hearing aid (HA) in their opposite side of first CI, on the WRS and SDS under the noise, there were significant differences between the group of over 3 years and the group of under 10 months of HA non user before second CI. CONCLUSION: These results may show important binaural effectiveness such as binaural summation and head shadow effect. Bilateral CI is very useful medical intervention for many children with severe-to-profound hearing loss in Japan as well as elsewhere.

What factors are associated with good performance in children with cochlear implants? From the outcome of various language development tests, research on sensory and communicative disorders project in Japan: nagasaki experience.

OBJECTIVES: We conducted multi-directional language development tests as a part of the Research on Sensory and Communicative Disorders (RSVD) in Japan. This report discusses findings as well as factors that led to better results in children with severe-profound hearing loss. METHODS: We evaluated multiple language development tests in 33 Japanese children with cochlear implants (32 patients) and hearing aid (1 patient), including 1) Test for question and answer interaction development, 2) Word fluency test, 3) Japanese version of the Peabody picture vocabulary test-revised, 4) The standardized comprehension test of abstract words, 5) The screening test of reading and writing for Japanese primary school children, 6) The syntactic processing test of aphasia, 7) Criterion-referenced testing (CRT) for Japanese language and mathematics, 8) Pervasive development disorders ASJ rating scales, and 9) Raven's colored progressive matrices. Furthermore, we investigated the factors believed to account for the better performances in these tests. The first group, group A, consisted of 14 children with higher scores in all tests than the national average for children with hearing difficulty. The second group, group B, included 19 children that scored below the national average in any of the tests. RESULTS: Overall, the results show that 76.2% of the scores obtained by the children in these tests exceeded the national average scores of children with hearing difficulty. The children who finished above average on all tests had undergone a longer period of regular habilitation in our rehabilitation center, had their implants earlier in life, were exposed to more auditory verbal/oral communication in their education at affiliated institutions, and were more likely to have been integrated in a regular kindergarten before moving on to elementary school. CONCLUSION: In this study, we suggest that taking the above four factors into consideration will have an affect on the language development of children with severe-profound hearing loss.

Influence of effortful swallow on pharyngeal pressure: evaluation using a high-resolution manometry.

OBJECTIVE: To evaluate the effect of effortful swallow on pharyngeal pressure while swallowing saliva and water using a novel high-resolution manometry (HRM) system. STUDY DESIGN: Case series with planned data collection. SETTING: Nagasaki University Hospital. SUBJECTS AND METHODS: Eighteen asymptomatic Japanese adult volunteers were studied. A solid-state HRM assembly with 36 circumferential sensors spaced 1 cm apart was positioned from the velopharynx to the upper esophagus to record pressures while swallowing. The maximum values of the pressure while swallowing saliva (dry swallowing) and 5 mL of water were measured at the velopharynx, meso-hypopharynx, and upper esophageal sphincter (UES) with and without effortful swallows. RESULTS: The maximum values of dry swallowing pressures (mm Hg) at the velopharynx, meso-hypopharynx, and UES were significantly higher with effortful swallow (155.7 ± 59.7, 256.7 ± 78.7, and 276.5 ± 87.5, mean ± standard deviation) than without it (115.3 ± 60.8, 172.9 ± 57.0, and 195.8 ± 61.3). Those of water swallowing pressures were also statistically higher with effortful swallow (169.3 ± 69.1, 236.6 ± 77.2, and 267.3 ± 79.1) than without it (119.2 ± 59.7, 189.5 ± 70.7, and 221.3 ± 72.7). CONCLUSION: The present results provide quantitative evidence of effortful swallow as well as physiological information. It also is hoped to be an aid to future clinical and investigative studies.

Abnormal mismatch negativity for pure-tone sounds in temporal lobe epilepsy.

Auditory processing abnormalities in temporal lobe epilepsy (TLE) were assessed by investigating mismatch negativity (MMN) in a group of 20 TLE patients and 20 healthy control subjects. MMN is an event-related potential (ERP) component that reflects pre-attentive sensory memory function. A passive oddball paradigm using frequency changes in sinusoidal tones was employed to evoke MMN. MMN at frontocentral sites was enhanced in TLE patients relative to controls, while mismatch signals at mastoid sites (i.e., mismatch positivity; MMP) did not differ between the two groups. In the MMP temporal range, greater positivity at mastoid sites in response to standard stimuli was observed in TLE patients than in controls. Both MMN and MMP were significantly delayed in the TLE group. These findings demonstrate that TLE patients have impaired pre-attentive processing of pure-tone sounds. Enhanced frontocentral MMN may reflect hyperexcitability of the frontal lobes in compensation for dysfunction of the temporal lobes. Larger positivity at the mastoids in response to standard stimuli may be attributed to poor neuronal adaptation in the temporal lobe. Taken together, results suggest that evaluation of MMN/P is a useful physiological tool for identifying pre-attentive auditory memory dysfunction in TLE.