Activation of the classical complement pathway in myasthenia gravis with acetylcholine receptor antibodies.

INTRODUCTION/AIMS: Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction (NMJ) of skeletal muscle. Complement activation is one of the mechanisms by which anti-acetylcholine receptor (anti-AChR) autoantibodies reduce synaptic transmission at the NMJ. In this study, we aimed to examine the activation of the complement pathways, including the classical pathway, as potential contributors to the pathogenesis of MG with anti-AChR antibodies. METHODS: In this single-center, observational study of 45 patients with anti-AChR-antibody-positive generalized MG, serum concentrations of major components of the complement pathways, including C1q, C5, C5a, soluble C5b-9 (sC5b-9), Ba, and complement factor H, were measured using an enzyme-linked immunosorbent assay. A total of 25 patients with a non-inflammatory neurological disorder served as controls. In addition, the relationships of complement activation with clinical characteristics were examined. RESULTS: The patients with MG exhibited lower serum levels of C5 (p = .0001) and higher serum levels of sC5b-9 (p = .004) compared with the control group. At about 6 months (range, 172-209 days) after the start of immunotherapy, serum levels of Ba were significantly higher than baseline levels (p = .002) and were associated with improvement in MG clinical scores. DISCUSSION: Herein, we provide evidence for the activation of the classical complement pathway and its association with disease activity in anti-AChR-antibody-positive generalized MG.

Immunoadsorption apheresis versus intravenous immunoglobulin therapy for exacerbation of myasthenia gravis.

Immunoadsorption apheresis (IA) or intravenous immunoglobulin (IVIg) is used to treat exacerbation of myasthenia gravis (MG). This study aimed to compare the efficacy and safety between IA and IVIg for MG patients with anti-acetylcholine receptor (AChR) antibodies. We retrospectively studied 19 AChR antibody-positive generalized MG patients who underwent IA (n = 9) or IVIg treatment (n = 10). We reviewed the MG activities of daily living profile (MG-ADL) scores at baseline, 1 and 3 months after the treatment. Adverse events during the treatment period were also reviewed. The MG-ADL scores showed significantly greater improvement from the baseline in the IA group than in the IVIg group (1 month: -7 vs -3, P = .035; 3 months -9 vs -2.5, P = .016). An adverse event that led to the discontinuation of the treatment was observed in only one patient in the IVIg group (anaphylactic reaction). Our data suggest that the IA treatment is safe and more efficacious than the IVIg treatment for aggravation of anti-AChR-positive MG. Larger prospective studies are required to confirm the finding.

Relationship between motor cortical and peripheral axonal hyperexcitability in amyotrophic lateral sclerosis.

BACKGROUND: Previous studies have shown that patients with amyotrophic lateral sclerosis (ALS) have hyperexcitability in both the motor cortex and peripheral motor axons, but the relationship between central and peripheral excitability has not been fully disclosed. METHODS: Threshold tracking transcranial magnetic stimulation (TMS) and motor nerve excitability testing were prospectively performed in 53 patients with ALS and 50 healthy subjects, and their relations to compound muscle action potential (CMAP) amplitude and revised ALS Functional Rating Scale were cross-sectionally analysed. RESULTS: Compared with controls, patients with ALS showed both cortical and peripheral hyperexcitability; TMS showed reduced short-interval intracortical inhibition (interstimulus interval 1-7 ms) (p<0.001) and shortened silent period (p<0.05), and median nerve excitability testing revealed greater changes in depolarising threshold electrotonus (TEd) and greater superexcitability (p<0.0001, both), suggesting reduced axonal potassium currents. Significant correlations between cortical and peripheral excitability indices were not found. Greater changes in TEd (90-100 ms) (R=-0.33, p=0.03) and superexcitability (R=0.36, p=0.01) were associated with smaller amplitude of CMAP, whereas cortical excitability indices had no correlation with CMAP amplitude. More rapid motor functional decline was associated with only greater TEd (90-100 ms) (ß=0.46, p=0.001). CONCLUSIONS: Our results suggest that in ALS, cortical excitability is continuously high regardless of the extent of the peripheral burden, but peripheral hyperexcitability is associated with the extent of the peripheral burden and disease evolution speed. Alterations of ion channel function may play an important role in ALS pathophysiology.

Different patterns of sensory nerve involvement in chronic inflammatory demyelinating polyneuropathy subtypes.

INTRODUCTION/AIMS: Among subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP), different immune pathophysiologies have been proposed. In this study, sensory nerve conduction studies were compared among clinical subtypes to attempt to better understand the underlying pathophysiology. METHODS: A total of 138 patients with CIDP was classified into clinical subtypes: typical CIDP (N = 68), multifocal CIDP (N = 27), or other (N = 2). Patients with immunoglobulin M (IgM) neuropathy anti-myelin-associated glycoprotein neuropathy (MAG; N = 19) were also included as disease controls. Sensory nerve action potentials (SNAPs) were recorded in the median, ulnar, and superficial radial and sural nerves. RESULTS: SNAP amplitudes (P < .05) and conduction velocities (P < .01) in the median nerve and conduction velocities (P < .05) in the ulnar nerve were lower in typical CIDP than in multifocal CIDP, whereas those in the radial and sural nerves were comparable in each group. Low median and normal sural SNAP amplitudes were more common in typical CIDP (P < .005) than in multifocal CIDP, suggesting predominant involvement at terminal portions of the nerves. DISCUSSION: Terminal portions of sensory nerves are preferentially affected in typical CIDP compared with multifocal CIDP. These findings might be partially explained by the hypothesis of antibody-mediated demyelination in typical CIDP at the regions where the blood-nerve barrier is anatomically deficient, whereas multifocal CIDP predominantly affects the nerve trunks, largely due to cell-mediated demyelination, with disruption of the blood-nerve barrier.

Fasciculation intensity and limb dominance in amyotrophic lateral sclerosis: a muscle ultrasonographic study.

BACKGROUND AND PURPOSE: Muscle ultrasonography has been increasingly recognized as a useful tool for detection of fasciculations. Separately, concordance between dominant hand and onset side has been reported in amyotrophic lateral sclerosis (ALS). The aim of this study was to reveal the distribution of fasciculations in the whole body, focusing on handedness. METHODS: In 106 consecutive patients with ALS, muscle ultrasonography was systematically performed in 11 muscles (the tongue, and bilateral biceps brachii, 1st dorsal interosseous [FDI], T10-paraspinalis, vastus lateralis and tibialis anterior muscles). The fasciculation intensity was scored from 0 to 3 for each muscle. RESULTS: Fasciculations were more frequently found in the limb muscles than the tongue and paraspinalis. Side and handedness analyses revealed that fasciculation intensity in FDI was significantly more prominent on the right (median [inter-quartile range] 2 [0 - 3]) than left (1.5 [0 - 3]; p = 0.016), and in the dominant hand (2 [1 - 3]) than non-dominant side (1.5 [0 - 3]; p = 0.025). The differences were greater in patients with upper limb onset. There were no side differences in the lower limb muscles. Multivariate analyses showed that male patients had more frequent fasciculations in the dominant FDI (ß = 0.22, p < 0.05). CONCLUSION: More intensive fasciculations are present in the FDI in the dominant hand and gender might be associated with fasciculation intensities. This distribution pattern of fasciculations might be associated with pathogenesis of ALS.

Rate of change in acetylcholine receptor antibody levels predicts myasthenia gravis outcome.

OBJECTIVE: To investigate the association between changes in anti-acetylcholine receptor antibody (AChR Ab) levels induced by immunosuppressive treatment and myasthenia gravis (MG) prognosis at 1-year post-treatment in patients with MG. METHODS: We included 53 consecutive AChR Ab-positive patients with MG whose AChR Ab levels were remeasured within 100 days of initiating immunosuppressive treatment (median remeasuring time post-treatment: 71 (55-84) days). The AChR Ab level reduction rate (RR-AChRAb, %/day) adjusted for the time between treatment initiation, and AChR Ab level remeasurement was calculated as follows: (pretreatment-post-treatment AChR Ab level)/pretreatment AChR Ab level/days between therapy initiation and AChR Ab level remeasurement ×100. Participants were divided into two groups based on the cut-off value of RR-AChR Ab, determined using receiver operating characteristic analyses for achieving minimal manifestation (MM) or better status at 1-year postimmunosuppressive treatment. The Myasthenia Gravis Foundation of America postintervention status and MG activity of daily living (MG-ADL) score at 1-year post-treatment were compared between the two groups. RESULTS: The RR-AChRAb cut-off value was 0.64%/day. The high RR-AChRAb group had a higher ratio of MM or better status (90% vs 65%, p=0.03) and lower MG-ADL score (median; 1 vs 2, p=0.04) than the low RR-AChRAb group. Kaplan-Meier analyses showed the early MM achievement in the high RR-AChRAb group (p=0.002, log-rank test). CONCLUSIONS: High RR-AChRAb is associated with a favourable outcome at 1-year post-treatment. AChR Ab remeasurement within 100 days of therapy may be useful for predicting AChR Ab-positive MG outcomes at 1-year post-treatment.

Dispersion of mean consecutive differences in single-fiber electromyography increases diagnostic sensitivity for myasthenia gravis.

INTRODUCTION: In this study we aimed to investigate the dispersion of mean consecutive difference (MCD) of concentric needle jitter studies of patients with myasthenia gravis (MG) and its effect on diagnostic sensitivity for MG. METHODS: One hundred fifty-three patients, including 76 patients with MG and 77 controls with possible MG who later received another diagnosis, underwent stimulated concentric needle jitter studies of the frontalis muscle. MCD mean, standard deviation (SD), and coefficient of variation (CV) were calculated. Diagnostic sensitivity and specificity were determined using receiver operating characteristic (ROC) analyses. RESULTS: MG patients showed a significantly greater MCD mean (MG: control, 26.3 µs; 13.5 µs [median]; P < .0001), MCD SD (MG: control, 12.8 µs; 5.1 µs [median]; P < .0001), and MCD CV (MG: control, 46.1; 37.5 [median]; P < .001) than those without MG. An ROC curve of SD showed a large area under the curve (0.88), and a cut-off value of 7.2 µs, which was calculated by maximum Youden index, exhibited high diagnostic sensitivity (86%) for MG. Combined MCD mean, outliers, and SD criteria showed higher sensitivity (88%) than conventional criteria alone (82%), at the expense of lower specificity. Five MG patients with normal MCD mean and abnormal MCD SD had only ocular symptoms. DISCUSSION: The dispersion of MCD as measured by MCD SD greater than 7.2 µs is significantly increased in patients with MG and may be a useful measure of abnormal jitter in the diagnosis of MG, especially for identifying patients with mild disease.

Association between the baseline frailty and quality of life in patients with prostate cancer (FRAQ-PC study).

BACKGROUND: The association between baseline frailty and health-related quality of life (HRQOL) in patients with prostate cancer (PC) remains unknown. METHODS: We retrospectively evaluated the association of pretreatment frailty with HRQOL in 409 patients with PC from February 2017 to April 2020. Frailty and HRQOL were evaluated using the geriatric 8 (G8) screening tool and QLQ-C30 questionnaire, respectively. The primary objective was comparison of G8 and QOL scores between the localized diseases (M0 group) and metastatic castration-sensitive PC (mCSPC group). Secondary objectives were to study the association of G8 and QOL scores in each group and effect of frailty (G8 ≤ 14) on worse QOL. RESULTS: The median age of patients was 70 years. There were 369 (surgery: 196, radiotherapy: 156, androgen deprivation therapy alone: 17) patients in the M0 and 40 patients in the mCSPC groups. There was a significant difference between the M0 and mCSPC groups in the G8 score (14.5 vs. 12.5), functioning QOL (94 vs. 87), global QOL (75 vs. 58), and 100-symptom QOL (94 vs. 85) scores. G8 scores were significantly associated with functioning, global, and 100-symptom QOL scores in both M0 and mCSPC groups. The multivariable logistic regression analyses showed that frailty (G8 ≤ 14) was significantly associated with worse global QOL, functioning QOL, and 100-symptom QOL scores. CONCLUSION: The baseline frailty and HRQOL were significantly different between the localized and metastatic disease. The baseline frailty was significantly associated with worse HRQOL in patients with PC.

A Longitudinal Study of Bidirectional Relationships between Sleep Disorder and Frequency of Nocturia: Results from the Iwaki Health Promotion Project.

INTRODUCTION: The causal relationship between sleep disorder and frequency of nocturia remains unclear. METHODS: We longitudinally evaluated sleep disorder and frequency of nocturia in 547 community-dwelling adults between baseline and 5-year follow-up. We included participants ≥50 years old who have no sleep disorder (the Pittsburgh Sleep Quality Index [PSQI] ≥ 5) nor nocturia (≥1). For 5 years, we evaluated the temporal changes in sleep disorder and nocturia and the bidirectional relationships between sleep disorder and nocturia. RESULTS: Of the 547 participants, we included 268 adults with a median age of 61 years in this study. Median PSQI and nocturia were significantly increased for 5 years from 2 to 3 and from 1 to 2, respectively. New onset of sleep disorder (PSQI > 5) and nocturia >1 was observed in 42 (16%) and 137 (51%) participants, respectively. The cross-lagged panel analysis showed that the path coefficient from PSQI to nocturia (ß = 0.22, p = 0.031) was significantly higher than that from nocturia to PSQI (ß = 0.02, p = 0.941). CONCLUSIONS: Our longitudinal study showed the effect of sleep disorder on nocturia was significant, although nocturia may not significantly worsen sleep disorder in community-dwelling adults.

Split hand and motor axonal hyperexcitability in spinal and bulbar muscular atrophy.

OBJECTIVE: The 'split hand' sign refers to preferential wasting of the thenar and first dorsal interosseous muscles with relatively sparing of the hypothenar muscles in amyotrophic lateral sclerosis (ALS) and both cortical and spinal/peripheral excitotoxic mechanisms have been proposed. We aimed to study split hand and axonal excitability in spinal and bulbar muscular atrophy (SBMA) in which cortical motor neurons are intact. METHODS: In 35 patients with genetically confirmed SBMA, 55 with ALS, 158 with other neuromuscular diseases and 90 normal controls; split hand was strictly determined by amplitudes of compound muscle action potentials. Nerve excitability testing of median motor axons was performed in 35 SBMA and 55 patients with ALS and 45 normal controls. RESULTS: Split hand was as frequently found for patients with SBMA (57%) and ALS (62%), compared with disease (20%) and normal (0%) controls. Excitability testing showed that in both SBMA and ALS, strength-duration time constant was longer, and threshold changes in depolarising threshold electrotonus and superexcitability in the recovery cycle were greater than in normal controls (p<0.01). CONCLUSIONS: Split hand is not specific to ALS and can be caused by the peripheral mechanism alone in SBMA, whereas the effect of upper motor neuron lesion cannot be excluded in ALS. Our results also suggest that SBMA and ALS share common axonal excitability changes; increased nodal persistent sodium and reduced potassium currents that may accelerate motor neuronal death and differently affect axons-innervating different muscles. Ion channel modulators could be a therapeutic option for both SBMA and ALS.

Charcot-Marie-Tooth disease type 1A: Longitudinal change in nerve ultrasound parameters.

BACKGROUND: This study aimed to elucidate the longitudinal changes in nerve ultrasound parameters of adult Charcot-Marie-Tooth disease type 1A (CMT1A) patients. METHODS: Fifteen adult patients with CMT1A prospectively underwent nerve ultrasound and clinical assessment (CMT neuropathy score [CMTNS]) at baseline and 5 y later. Nerve cross-sectional area (CSA) and echogenicity were measured in the median and sural nerves. Changes in ultrasound parameters and CMTNS and correlation between changes of ultrasound parameters and CMTNS were analyzed. RESULTS: Median and sural nerve CSAs did not change over 5 y, although CMTNS increased (P < .01). Nerve echogenicity in the sural nerve decreased over 5 y (P = .045). No correlations between changes in nerve ultrasound parameters and CMTNS were identified. CONCLUSIONS: No longitudinal changes in nerve size was detected in adult CMT1A. Exploring the factors that determine nerve size in childhood CMT1A may lead to the development of treatments.

Aberrant N-Glycosylation Profile of Serum Immunoglobulins is a Diagnostic Biomarker of Urothelial Carcinomas.

The aim of this study to determine whether the aberrant N-glycosylated serum immunoglobulins (Igs) can be applied as a diagnostic marker of urothelial carcinoma (UC). Between 2009 and 2016, we randomly obtained serum available from 237 UC and also 96 prostate cancer as other cancer controls from our serum bank and also obtained-from 339 healthy volunteers (HV)-controls obtained from community-dwelling volunteers in Iwaki Health Promotion Project. A total of 32 types of N-glycan levels on Igs were determined by high-throughput N-glycomics and analyzed by multivariable discriminant analysis. We found five UC-associated aberrant N-glycans changes on Igs and also found that asialo-bisecting GlcNAc type N-glycan on Igs were significantly accumulated in UC patients. The diagnostic N-glycan Score (dNGScore) established by combination of five N-glycans on Igs discriminated UC patients from HV and prostate cancer (PC) patients with 92.8% sensitivity and 97.2% specificity. The area under the curve (AUC) for of the dNGScore was 0.969 for UC detection that was much superior to that of urine cytology (AUC, 0.707) and hematuria (AUC, 0.892). Furthermore, dNGScore can detect hematuria and urine cytology negative patients. The dNGscore based on aberrant N-glycosylation signatures of Igs were found to be promising diagnostic biomarkers of UCs.

Core 2 ß-1, 6-N-acetylglucosaminyltransferase-1 expression in prostate biopsy specimen is an indicator of prostate cancer aggressiveness.

INTRODUCTION: To avoid over-treatment of early stage prostate cancer (PCa), predictive biomarkers for PCa aggressiveness which can be obtained during pre-treatment evaluation are essential. Core 2 ß-1, 6-N-acetylglucosaminyl-transferase-1 (GCNT1) is a key enzyme that forms core 2 branched O-glycans, the expression of which is associated with aggressive potential of prostate cancer. We examined whether GCNT1 expression in prostate biopsy specimen can predict cancer recurrence after radical prostatectomy for the patients with with PCa. We then investigated molecular background for aggressive malignant potential mediated by GCNT1 expression. METHODS: Paraffin-embedded PCa biopsy specimens were immunohisto-chemically tested for GCNT1 expression using an anti-GCNT1 monoclonal antibody. We also examined the role of GCNT1 in PCa progression using cell lines which express high or low levels of GCNT1. RESULTS: GCNT1 expression correlated with D' Amico's recurrence risk classification. The GCNT1-positive rate in organ confined PCa was significantly lower than that in PCa with extra-prostatic extension. GCNT1-negative tumors were associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. Multivariate analysis revealed that GCNT1 expression status was an independent risk factor for PSA recurrence after radical prostatectomy. Subsequent basic study revealed that GCNT1-over-expressing cells produced a significantly larger amount of growth factors when co-cultured with prostate stromal cells compared with GCNT1-knocked down cells and formed larger tumors. CONCLUSIONS: GCNT1 expression in prostate biopsy specimen is a significant and independent predictor of recurrence after radical prostatectomy, which can be used in pre-treatment decision making for the patient. Further validation study is necessary to establish clinical implication of GCNT1 in management of PCa.

Preoperative butyrylcholinesterase level as an independent predictor of overall survival in clear cell renal cell carcinoma patients treated with nephrectomy.

The prognostic factors for the overall survival (OS) of clear cell renal cell carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the present study, we investigated the prognostic significance of preoperative butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or partial nephrectomy from 1992 to 2013 at our institution. Univariate and multivariate analyses were performed to determine the clinical factors associated with OS. Among the enrolled patients, 302 were diagnosed with organ-confined disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant metastases. The median preoperative BChE level was 250 U/L (normal range, 168-470 U/L), and median follow-up period was 36 months. The 3-year OS rate in patients with preoperative BChE levels of ≥100 U/L was significantly higher than in those with levels of <100 U/L (89.3% versus 77.7%, P = 0.004). On univariate analysis, performance status; anemia; hypoalbuminemia; preoperative levels of BChE, corrected calcium, and C-reactive protein; and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that preoperative BChE levels and distant metastasis status were significantly associated with OS. Our findings suggest a possible role of preoperative BChE levels as an independent predictor of OS after nephrectomy in ccRCC patients.

Effects of preceding antiplatelet agents on severity of ischemic stroke in patients with a history of stroke.

INTRODUCTION: Antiplatelet agents are effective for secondary prevention of ischemic stroke and can reduce the severity of first-ever ischemic stroke. However, it is uncertain if prophylactic antiplatelet therapy reduces the severity of recurrent ischemic stroke. The aim of this study was to determine the effect of preceding antiplatelet treatment on the severity of thrombotic stroke (TS) in patients with a prior history of stroke. METHODS: From a prospective hospital registry of 1338 consecutive patients with acute ischemic stroke, we identified patients with a prior history of stroke who were admitted for cardioembolic stroke (CE); TS including large-artery atherosclerosis, small vessel occlusion, and branch atheromatous disease; or other cause or cryptogenic stroke (OCS). Cases in each subtype were categorized based on preceding medication: antiplatelet agents (AP) and none (N). Severity of stroke (National Institutes of Health Stroke Scale: NIHSS) on admission was compared between AP and N cases. RESULTS: The total cohort of 252 patients included 83 with CE, 102 with TS, and 67 with OCS. After excluding those with prior anticoagulants, the median NIHSS on admission was lower in AP cases than in N cases (3 vs. 5, p = 0.002). In multivariate analysis, preceding AP treatment was independently associated with minor stroke (NIHSS ≤4) on admission in CE group (OR 8.48, 95% CI 1.71-62.9, p = 0.008) and TS group (OR 4.24, 95% CI 1.44-13.4, p = 0.009). CONCLUSION: Preceding antiplatelet treatment in patients with a prior history of stroke may reduce the severity of subsequent thrombotic and cardiogenic stroke.

Switching hemodialysis patients from sevelamer hydrochloride to bixalomer: a single-center, non-randomized analysis of efficacy and effects on gastrointestinal symptoms and metabolic acidosis.

BACKGROUND: Bixalomer (BXL) was developed to improve gastrointestinal symptoms and reduce constipation, relative to sevelamer hydrochloride, in hemodialysis patients. We prospectively evaluated the safety and effectiveness of switching maintenance dialysis patients from sevelamer hydrochloride to BXL. METHODS: Twenty-eight patients were switched from sevelamer hydrochloride to BXL (1:1 dose) from July to October 2012, whereas 84 randomly selected patients not treated with sevelamer hydrochloride were enrolled as a control group. The primary endpoint was improvement of gastrointestinal symptoms; secondary endpoints included improvement in metabolic acidosis, changes in blood biochemistry, and safety 12 weeks after the switch. We also surveyed patient satisfaction with switching to BXL 12 weeks after the switch. RESULTS: Before switching, symptoms of epigastric fullness were significantly worse in the switch than in the control group. Twelve weeks after the switch, reflux, epigastric fullness, and constipation had improved significantly in the switch group. Other factors, including stomach ache, diarrhea, and form of stool, did not change significantly. Blood gas analysis showed that metabolic acidosis was significantly improved by switching. Four patients (14%) experienced grade 1 adverse events, all of which improved immediately after stopping BXL. Major adverse events were diarrhea and abdominal discomfort. Mean satisfaction score was 3.1 ± 0.7, with 64% of patients reporting they were "neither satisfied nor dissatisfied" after switching. CONCLUSIONS: A switch from sevelamer hydrochloride to BXL improved symptoms of reflux, epigastric fullness, constipation, and metabolic acidosis in hemodialysis patients. TRIAL REGISTRATION: The study was registered as Clinical trial: (UMIN000011150).

[Successful control of hyper-cortisolemia due to ACTH-producing thyroid carcinoid by laparoscopic bilateral adrenalectomy : a case report].

A 22-year-old man was referred to our hospital because of facial edema and increasing body weight. Under the diagnosis of Cushing syndrome due to an adrenocorticotropic (ACTH)-producing thyroid tumor, thyroidectomy with regional lymph node dissection was performed. Histopathological diagnosis was thyroid carcinoid. In spite of the operation, serum ACTH and cortisol concentrations increased again due to mediastinal lymph node metastasis. His hyper-cortisolemia was resistant to drug therapy. Then, laparoscopic bilateral adrenalectomy was performed. After the operation, hyper-cortisolemia and clinical symptoms markedly improved. An additional chemotherapy is implemented because of new metastasis in the mediastinum lymph nodes.

[Testicular tumor arising in intra-abdominal testis which was not detected at prior orchidopexy : a case report].

A 35-year-old man with an intra-abdominal testicular tumor arising from the right unresolved intraabdominal testis is reported. At 10 years old, left orchidopexy was successfully performed for bilateral undescended testes. However, the right testis was not detected during the operation, and it was diagnosed as vanishing testis. Twenty-five years later, he was referred to our hospital with the complaint of right lower abdominal pain. Computed tomography revealed huge pelvic tumors and bulky para-aortic lymph node swellings. Histopathologic examination of the needle biopsy specimen obtained from the pelvic tumor revealed seminomatous germ cell tumor. Taking the results with a tumor marker study into consideration, the patient was tentatively diagnosed with non-seminomatous germ cell tumor NSGCT (stage IIB) arising from the unresolved intra-abdominal testis or extragonadal germ cell tumor. He received 3 courses of bleomycin, etoposide, cisplatin (BEP), and 4 courses of VP-16, ifosfamide, cisplatin (VIP). After chemotherapy, we performed tumorectomy and retroperitoneal lymphadenectomy because tumor markers were normalized and 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)-CT revealed normalization. We identified the pelvic tumor as an intra-abdominal testicular tumor arising from right unresolved intra-abdominal testis. Pathological examination revealed no residual tumor cells. There has been no recurrence 17 months after surgery.

Role of soluble forms of follicular helper T-cell membrane molecules in the pathogenesis of myasthenia gravis.

This study examined the role of Tfh and Treg associated molecules also known as checkpoint molecules, their ligands, and IL-21 in myasthenia gravis (MG) pathogenesis. Serum levels of sPD-1, sPD-L1, sICOS, sICOSLG, sCTLA4, and IL-21 were measured in 39 patients with acetylcholine receptor (AChR) antibody-positive generalized MG and 27 controls. sPD-1 and IL-21 levels were higher in MG patients than in controls. Additionally, sPD-1 levels correlated positively with the levels of IL-21, sICOSLG, sCTLA4, and AChR antibody titers. sICOS are correlated with MGADL and AChR antibody titers. These Tfh associated molecules could be used as biomarkers of MG disease activity.

Compound muscle action potential duration ratio for differentiation between Charcot-Marie-Tooth disease and CIDP.

OBJECTIVE: To elucidate the utility of the proximal to distal compound muscle action potential (CMAP) duration ratio to distinguish between demyelinating Charcot-Marie-Tooth disease (CMT) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) compared with nerve ultrasound. METHODS: Thirty-nine demyelinating CMT patients and 19 CIDP patients underwent nerve conduction studies (NCS) and nerve ultrasound. NCS parameters including CMAP duration ratio calculated by dividing the value at the proximal site by that at the distal site and nerve cross-sectional area (CSA) measured by ultrasound were compared between the two groups. The diagnostic sensitivity and specificity of each parameter were analysed. RESULTS: CMT patients showed a significantly lower CMAP duration ratio than CIDP patients (p < 0.05). The area under the curve (AUC) value of the CMAP duration ratio exceeded 0.95 when CMT was considered "positive", and a cut-off value of 1.13 resulted in high diagnostic sensitivity and specificity (84.6 and 100 % for median nerve, 97.4 and 85.7 % for ulnar nerve, respectively), whereas the AUC value of nerve CSA ranged from 0.70 to 0.81. CONCLUSIONS: The CMAP duration ratio could effectively distinguish between demyelinating CMT and CIDP. SIGNIFICANCE: Adding the CMAP duration ratio to a routine NCS may improve the accuracy of the diagnosis of demyelinating CMT.