New MRI Findings in Fukuyama Congenital Muscular Dystrophy: Brain Stem and Venous System Anomalies.

BACKGROUND AND PURPOSE: Leptomeningeal glioneuronal heterotopia of the brain stem and cerebral migration abnormality were pathologically reported in Fukuyama congenital muscular dystrophy, but the radiologic assessments of the brain stem and cerebral venous system (which may be involved in the development of the anomaly) were insufficient. Here, we evaluated the brain stem and cerebral veins on MR imaging in patients with Fukuyama congenital muscular dystrophy. MATERIALS AND METHODS: We retrospectively reviewed the MR imaging findings of 27 patients with Fukuyama congenital muscular dystrophy. We visually assessed the hypoplasia, superficial structures, and signal intensity of the brain stem on T2WI, FLAIR, and double inversion recovery images and the cerebral, superficial, and deep veins with and without hemorrhage on T2WI and SWI. RESULTS: Brain stem fluffy structures were seen in 96.3% of the cases on T2WI. Superficial high signal intensity on T2WI and FLAIR images was seen in 96.3% and 92.6%, respectively. Abnormally located superficial vessels beneath the cortex were seen in 11.1% on T2WI. Hypoplasia of the superficial cerebral veins was noted in all patients who underwent SWI. Dilated and tortuous subependymal veins were seen in 40.0% on SWI. Hemorrhages were seen in 11.1% on T2WI and in 60.0% on SWI. CONCLUSIONS: Superficial brain stem structural and signal abnormalities would be useful MR imaging findings to diagnose Fukuyama congenital muscular dystrophy as well as venous system abnormalities. Clinicians must keep in mind that this disease has a high risk of hemorrhage.

NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy.

Genetic abnormalities in mitochondrial complex assembling factors are associated with leukoencephalopathy. We present a 1-year-old girl with consciousness disturbance after a respiratory infection. Brain MRI revealed leukoencephalopathy with bilaterally symmetrical hyperintensity in the substantia nigra, medial thalamic nuclei, and basal nuclei, as well as cavities in the cerebral white matter and corpus callosum. Lactate levels in the spinal fluid were high, while magnetic resonance spectroscopy of the cerebral white matter and basal nuclei showed high peak lactate levels, suggesting mitochondrial dysfunction. The respiratory enzyme activity of complex I was reduced to 17% to 21% in skeletal muscle. Whole exome sequencing identified compound heterozygous variations in NDUFAF3, involved in the assembly of mitochondrial complex I (c.342_343insGTG:p.117Valdup, c.505C > A:p.Pro169Thr). Two-dimensional, blue-native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-PAGE revealed reductions in Q-module (NDUFS2, NDUFS3, and NDUFA9) and P-module (NDUFB10 and NDUFB11) subunits, indicating disruption of mitochondrial complex I assembly. Our report expands the spectrum of clinical phenotypes associated with pathogenic variants of NDUFAF3.

Blood-Labyrinth Barrier Permeability in Menière Disease and Idiopathic Sudden Sensorineural Hearing Loss: Findings on Delayed Postcontrast 3D-FLAIR MRI.

BACKGROUND AND PURPOSE: Menière disease and idiopathic sudden sensorineural hearing loss can have overlapping clinical presentation and may have similar pathophysiology. Prior studies using postcontrast 3D-FLAIR MR imaging suggest abnormal blood-labyrinth barrier permeability in both conditions, but the 2 diseases have not been directly compared by using the same imaging techniques. We hypothesized that delayed postcontrast 3D-FLAIR MR imaging would show differences in blood-labyrinth barrier permeability between Menière disease and idiopathic sudden sensorineural hearing loss. MATERIALS AND METHODS: Patients with unilateral Menière disease (n = 32) and unilateral idiopathic sudden sensorineural hearing loss (n = 11) imaged with delayed postcontrast 3D-FLAIR MR imaging were retrospectively studied. Signal intensities of the medulla and perilymph of the cochlear basal turns of both ears in each patient were measured in a blinded fashion. Cochlea/medulla ratios were calculated for each ear as a surrogate for blood-labyrinth barrier permeability. The ears were segregated by clinical diagnosis. RESULTS: Cochlea/medulla ratio was higher in symptomatic ears of patients with Menière disease (12.6 ± 7.4) than in patients with idiopathic sudden sensorineural hearing loss (5.7 ± 2.0) and asymptomatic ears of patients with Menière disease (8.0 ± 3.1), indicating increased blood-labyrinth barrier permeability in Menière disease ears. The differences in cochlea/medulla ratio between symptomatic and asymptomatic ears were significantly higher in Menière disease than in idiopathic sudden sensorineural hearing loss. Asymptomatic ears in patients with Menière disease showed higher cochlea/medulla ratio than symptomatic and asymptomatic ears in patients with idiopathic sudden sensorineural hearing loss. CONCLUSIONS: Increased cochlea/medulla ratio indicates increased blood-labyrinth barrier permeability in Menière disease compared with idiopathic sudden sensorineural hearing loss. Increased cochlea/medulla ratio in asymptomatic ears of patients with Menière disease also suggests an underlying systemic cause of Menière disease and may provide a pathophysiologic biomarker.

Endolymphatic Hydrops Reversal following Acetazolamide Therapy: Demonstration with Delayed Intravenous Contrast-Enhanced 3D-FLAIR MRI.

Endolymphatic hydrops, the primary pathologic alteration in Menière disease, can be visualized by using delayed intravenous contrast-enhanced 3D-FLAIR MR imaging. It is not known whether MR imaging-demonstrable changes of hydrops fluctuate with disease activity or are fixed. We describe the results of baseline and posttreatment MR imaging studies in a group of subjects with Menière disease with hydrops who were treated with acetazolamide. Seven subjects with untreated Menière disease with MR imaging evidence of hydrops had repeat MR imaging during acetazolamide treatment. Symptoms and imaging findings were assessed at each time point. Five subjects showed symptom improvement, of whom 3 had improvement or resolution of hydrops. One subject had recurrent symptoms with recurrent hydrops after discontinuing therapy. Two had unchanged hydrops despite symptom improvement. Subjects with unchanged symptoms had unchanged hydrops. Hydrops reversal may be seen with acetazolamide treatment in Menière disease. MR imaging may provide an additional biomarker of disease.

Endoscopic mucosal resection and endoscopic submucosal dissection for en bloc resection of superficial pharyngeal carcinomas.

BACKGROUND AND STUDY AIM: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are being used increasingly to treat superficial oropharyngeal and hypopharyngeal carcinomas. The aim of this study was to clarify whether ESD provided better results than EMR for en bloc and complete resection of superficial pharyngeal carcinomas. PATIENTS AND METHODS: A total of 76 superficial pharyngeal carcinomas in 59 consecutively treated patients were included. Patients underwent either conventional EMR (using a transparent cap or strip biopsy) (n = 45 lesions) or ESD (n = 31 lesions) between October 2006 and January 2011. The rates of en bloc resection, complete resection (defined as en bloc resection with tumor-free margins), major complications, and local recurrence were evaluated retrospectively as the therapeutic outcomes. RESULTS: ESD yielded significantly higher rates of both en bloc and complete resection compared with EMR (en bloc 77.4 % [24/31] vs. 37.8 % [17/45], P = 0.0002; complete 54.8 % [17/31] vs. 28.9 % [13/45], P = 0.0379). ESD was more frequently complicated by severe laryngeal edema (4/21 [19.0 %] vs. 1/31 [3.2 %], P = 0.1446) and was also more time-consuming (124.9 ± 65.1 minutes vs. 57.2 ± 69.6 minutes; P = 0.0014). Local recurrence was observed more often after EMR than after ESD (3/45 [6.7 %] vs. 0/31 [0 %]), although this difference did not reach statistical significance (P = 0.2658). CONCLUSIONS: ESD appears to be a superior method of endoscopic resection of superficial pharyngeal carcinomas for achieving both en bloc and complete resection, although these benefits were also associated with a higher incidence of complications and a significantly longer procedure time. Large prospective studies are needed to compare ESD with conventional EMR for superficial pharyngeal carcinomas.

Long-term outcomes of endoscopic submucosal dissection for undifferentiated-type early gastric cancer.

BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) of undifferentiated-type early gastric cancer (UD-EGC) is technically feasible; however, the long-term clinical outcomes of the procedure have not yet been fully investigated. The aim of our study was to elucidate long-term outcomes of ESD for UD-EGC. PATIENTS AND METHODS: Between September 2003 and October 2009, a total of 153 patients were diagnosed endoscopically as having UD-EGC fulfilling the expanded criteria for ESD. After informed consent was obtained, 101 patients were selected to undergo ESD and 52 to undergo surgical operation. We assessed the clinical outcomes of ESD in 101 consecutive patients with 103 UD-EGC lesions who were undergoing ESD for the first time. The overall mortality and disease-free survival rates after ESD were evaluated as the long-term outcomes. RESULTS: The rates of en bloc and curative resection were 99.0% (102/103) and 82.5% (85/103), respectively. We encountered one patient with nodal metastasis detected by computed tomography before diagnostic ESD, although curative resection of the primary lesion was achieved based on routine histological examination. Among the 78 patients without a past history of malignancy within the previous 5 years in whom curative resection of the primary lesion was achieved, no cases of local recurrence or distant metastasis were observed during follow-up; however, 1 synchronous and 2 metachronous lesions were detected in 2 patients (2.6%) after primary ESD. Thus, estimated over a median follow-up period of 40.0 months (range 19-92 months) and 36.0 months (range 9-92 months), the 3-and 5-year overall mortality rates were 1.9% and 3.9%, respectively, and the 3-and 5-year overall disease-free survival rates were both 96.7%. CONCLUSIONS: Although our single-center retrospective study may be considered to be only preliminary, our data indicate that ESD for UD-EGC may yield good long-term outcomes.

Intracochlear schwannoma presenting as diffuse cochlear enhancement: diagnostic challenges of a rare cause of deafness.

Intracochlear schwannoma is a rare, treatable, cause of unilateral hearing loss. Due to the small size, position, and variable clinical and imaging features, diagnosis presents a significant challenge and is often delayed. We present a case of a patient with an intracochlear schwannoma presenting as a diffuse enhancement of the cochlea, mimicking an infectious or inflammatory process. The absence of focal nodularity in this lesion on multiple high-resolution MRI examinations led to a delay of over 3 years from the patient's initial presentation to surgical diagnosis. Clinical history and examination, imaging features, pathologic findings, and surgical management options are described.

Screening of Thai medicinal plant extracts and their active constituents for in vitro antimalarial activity.

To discover antimalarial substances from plants cultivated in Thailand 80%-EtOH extracts from selected plants were screened for in vitro antimalarial activity against the drug resistant K1 strain of Plasmodium falciparum. In total, 86 Thai medicinal plant samples representing 48 species from 35 genera in 16 families were screened and two species (Polyalthia viridis and Goniothalamus marcanii) were found to show notable antimalarial activity (IC50: 10.0 and 6.3 microg/mL). Marcanine A and 16-hydroxycleroda-3,13(14)Z-dien-15,16-olide were identified as the respective major active constituents in P. viridis and G. marcanii, respectively.

Temporal bone histopathology in dominantly inherited audiovestibular syndrome.

OBJECTIVE: To describe the clinical and pathologic features of a new dominantly inherited audiovestibular syndrome. METHODS: History, examination, and audiometric testing in the proband, brother, and son; quantitative rotational testing in the proband and son; histopathology of the cochlea and vestibular labyrinth in the proband; sequencing candidate genes COCH and MYO7A in the brother and son. RESULTS: Affected family members developed slowly progressive hearing loss beginning in their late 30s and progressive imbalance in their early 70s. Three of four affected had brief (minutes) episodes of vertigo typically occurring a few times per year. Auditory and vestibular function testing documented a slowly progressive loss of auditory and vestibular function. Postmortem examination showed a loss of hair cells in the cochlea and vestibular receptor organs. There were no cellular infiltrates or acidophilic deposits. No mutations were found in the COCH or MYO7A genes. CONCLUSIONS: This dominantly inherited audiovestibular syndrome results in a selective loss of hair cells in the auditory and vestibular end organs. Finding the causative gene could have important implications for understanding the pathophysiology of presbycusis and dysequilibrium of aging.

Bayesian classification of myocardial excitation abnormality using magnetocardiogram maps for mass screening.

We propose a novel classification method based on the Bayes rule to utilize the magnetocardiogram (MCG) in noninvasive mass screening. The cardiac excitation is directly tracked by maps of the MCG field generated by myocardial excitation current through the excited wave front. To adopt the characteristics of the excited wave fronts as a parameter for the Bayes theorem, we developed a parameterization procedure that consists of a two-dimensional wavelet approximation and a cluster analysis of magnetic field maps. With the parameter determined by this procedure, the probability of a subject to belong to a disease group or to the normal group is estimated by the Bayes theorem. The subject is classified into the group of the highest probability. We applied the proposed method to ST-T period of MCG data of 6 old myocardial infarction (OMI) patients and 15 normal controls. The method showed sensitivity of 83%; specificity, 100%; positive predictive value, 100%; and negative predictive value, 94% in the classification of OMI patients and normal controls. The processing time is less than 5 seconds per one subject. It suggests a possible application of the proposed method in mass screening of abnormal MCG patterns.

Inhibition of the adherence of Escherichia coli strains to basement membrane by Lactobacillus crispatus expressing an S-layer.

AIMS: This study aimed to evaluate the efficiency with which Lactobacillus crispatus JCM 5810 inhibited the adhesion of enteric pathogens to a synthetic basement membrane and to elucidate the mechanism underlying the inhibition. METHODS AND RESULTS: Lactobacillus crispatus JCM 5810 inhibited the adhesion of three diarrhoeagenic Escherichia coli strains to a reconstituted basement membrane preparation called Matrigel, used as a model of a damaged intestinal tissue site. Inhibition was also observed with the use of immobilized laminin, a major component of Matrigel, but diminished after the removal of S-layer protein (CbsA) from JCM 5810 cells. The isolated CbsA inhibited the adhesion of E. coli to both Matrigel and immobilized laminin. Lactobacillus crispatus JCM 5810 and CbsA seem to inhibit pathogenic E. coli from adhering to basement membrane via competition with laminin molecules for binding sites. CONCLUSIONS: These results suggested that not only Lact. crispatus JCM 5810 cells but CbsA alone might prevent pathogens from colonizing damaged intestinal tissues. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to show the applied aspect of Lactobacillus S-layer protein.

Potent antimalarial activities of polyether antibiotic, X-206.

In the course of our screening program to discover antimalarial antibiotics, which are active against drug resistant Plasmodium falciparum in vitro and rodents infected with P. berghei in vivo, from the culture broth of microorganisms, we found a selective and potent active substance produced by an actinomycete strain K99-0413. It was identified as a known polyether antibiotic, X-206. We also compared the in vitro antimalarial activities and cytotoxicities of 12 known polyethers with X-206. Among them, X-206 showed the most selective and potent inhibitory effect against both drug resistant and sensitive strains of P. falciparum. Comparison of biological activities and ion-affinities of the above antibiotics suggests that monovalent cations play an important biological role for the intracellular growth of P. falciparum in parasitized erythrocytes. Moreover, X-206 showed potent in vivo antimalarial activity on the rodent model, though the therapeutic window was narrow compared with its selective toxicity in vitro. These observations are the first report of antimalarial activity of X-206.

Drop attacks in older patients secondary to an otologic cause.

The clinical features and treatment of seven patients with drop attacks attributable to inner ear disease presenting after age 65 are described. A neurologic or cardiovascular cause of drop attacks was initially suspected. Audiovestibular testing documented a unilateral inner ear disorder. The salient clinical features of these cases are discussed. The patients underwent ablative vestibular surgery, and all compensated well and were free of vertigo and falls up to 10 years postoperatively.

Otological manifestations of Churg-Strauss syndrome.

OBJECTIVES/HYPOTHESIS: To describe the clinical features, pathogenesis, and management of the otological complications in Churg-Strauss syndrome (CSS). STUDY DESIGN: Retrospective review of five patients with documented CSS who had otological manifestations in the later stages of CSS. METHODS: The history, treatment, and outcome were evaluated using office and hospital chart data in these five cases. RESULTS: In all cases, otological manifestations occurred during an advanced stage of CSS and was characterized by the presence of dense aural discharge, granulomatous eosinophilic infiltration into mastoid and middle ear, and subacute severe to profound hearing loss. In all cases, the recurrent aural discharge and granulomatous infiltrate was unresponsive to conventional treatment including repeated myringotomies and aggressive antibiotics. Systemic steroid administration resulted in a rapid, complete cessation of aural discharge and reversal or stabilization of hearing loss. Otological manifestations have been stable over a range of follow-up from 1 to 20 years on a maintenance regimen of steroids. CONCLUSIONS: Temporal bone involvement in CSS is rare. Surgical intervention of the temporal bone is relegated to complications that may include infectious mastoiditis and intracranial involvement. Recognition of the association between CSS and otological disease is important because it is highly responsive to systemic steroids, and early steroid treatment may prevent progression to irreversible hearing loss, infectious otomastoiditis, or intracranial complications.

Unbiased stereological quantification of neurons in the human spiral ganglion.

We applied an unbiased stereological technique, the optical fractionator, on five human archival temporal bone specimens to estimate the total number of spiral ganglion neurons. Available archival human temporal bone specimen has been serially sectioned at 20 microm and every tenth section was stained. All the stained sections passing through the spiral ganglion were used for the analysis. From each section sampled, the counting areas were systematically randomly sampled within the sectional area of the spiral ganglion. The neurons within the counting areas sampled were counted with the optical disector technique. The total number of the human spiral ganglion neurons was estimated by multiplying the number of neurons counted by the reciprocal of the aggregate sampling fraction. We found an average of 41700 neurons with a coefficient of variation of 0.14, which is a significant departure from the previously published data obtained with the assumption-based methods. The mean coefficient of error for the stereological estimates of the total number of human spiral ganglion neurons was 0.078. The present report presents unbiased stereological sampling and counting strategies for the future quantitative studies on the spiral ganglion neurons. The result of the present study provides the first unbiased baseline value of the human spiral ganglion neurons.

Age-related change in the number of neurons in the human vestibular ganglion.

Dysequilibrium of aging in humans has been speculated to arise from progressive deterioration within anatomical components of the vestibular system. An integral part of this system is vestibular ganglions, which are bipolar neurons that relay peripheral vestibular information to the central nervous system. To assess the effect of aging on the number of human vestibular ganglion neurons, assumption-free stereology in the form of the optical fractionator was used on 20 serially sectioned archival human temporal bone specimens. Donors had no history of vestibular pathology and ranged in age from 2 to 88 years. An average of 25,812 (coefficient of variation = 0.13) vestibular ganglion neurons was found throughout this age range, a significant departure from the results of past studies. Logistics-based regression analysis pointed to a nonlinear pattern of decline in the neuronal population: the number of cells remained roughly constant at about 28,952 cells in youth and then declined gradually between 30 and 60 years of age before leveling off at approximately 23,349 cells in older individuals. This study confirmed the existence of an age-related decline in the primary neurons of the human vestibular system, thus providing one anatomical basis for the increased incidence of imbalance seen with age.

Vertigo and the enlarged vestibular aqueduct syndrome.

An enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear bony malformations in children with sensorineural hearing loss of unknown cause. Most previous reports have focused on hearing loss, but individuals with EVA may also experience paroxysmal vertigo lasting minutes to hours. We report the clinical vestibular features and vestibular function testing of two children and one adult with EVA who had a history of sensorineural hearing loss and presented to our Neurotology Clinic for the evaluation of episodic vertigo. All the patients had an antecedent history of profound bilateral sensorineural hearing loss that had been present since early childhood. The onset of vertigo was delayed into adulthood in one patient. Episodes of vertigo could be triggered by minor head trauma or vigorous physical activity. Despite recurrent episodes of vertigo, vestibular function was normal or moderately impaired compared with the severe auditory deficit. Careful analysis of temporal bone CT demonstrated EVA. Associated enlargement of the membranous endolymphatic sac was evident on brain MRI. While hearing loss is a prominent symptom in patients with EVA, vestibular symptoms may cause referral to a neurologist. Although hearing loss occurs early in childhood, vestibular symptoms can be delayed into adulthood, a finding not previously reported.