Clinical features of Guillain-Barré syndrome patients with elevated serum creatine kinase levels.

BACKGROUND: It is not well defined whether Guillain-Barré syndrome (GBS) patients with elevated serum creatine kinase (CK) levels have characteristic clinical features and are related to the subgroups of GBS. METHODS: We retrospectively studied 51 consecutive patients with GBS, who visited our hospital, and compared clinical, laboratory and electrophysiological findings between patients with and without elevated CK levels. RESULTS: Of 51 patients, 14 patients (27%) showed an elevation of serum CK levels. When compared with patients with the normal CK levels, the ratios of male, antecedent infections, and anti-GM1 antibody positivity were significantly higher in patients with elevated CK levels. The ratios of hypoesthesia, cranial nerve involvement, and urinary retention were significantly less in patients with elevated CK levels. There were no significant differences in disability at peak between two groups. In the electrophysiological examination, sensory nerve abnormalities were not observed. Although some patients with elevated CK levels showed prolongation of distal motor latencies (DMLs) and increase of durations in the initial examination, development of the prolongation of DMLs and increase of durations was not observed in the follow-up examinations. The findings were consistent with acute motor axonal neuropathy (AMAN) with reversible conduction failure (RCF) but not acute inflammatory demyelinating polyneuropathy (AIDP). CONCLUSIONS: The results suggest that the GBS patients with elevated CK levels represent not a group of AIDP but a group of AMAN with axonal degeneration or RCF even though the initial electrophysiological examination shows AIDP pattern.

Diabetes mellitus does not influence results of hepatectomy in hepatocellular carcinoma: case control study.

INTRODUCTION: Patients with diabetes mellitus undergoing hepatectomy for hepatocellular carcinoma (HCC) are at high risk of acquiring perioperative infections. Herein, we investigate the peri-operative impact of diabetes on hepatectomy. MATERIAL AND METHODS: The surgical outcomes in 363 patients who underwent laparoscopic and open hepatic resection for HCC, with or without diabetes mellitus, were reviewed retrospectively. The association of diabetes mellitus with surgical outcomes and remnant liver regeneration was analyzed. The Student's t and χ2 tests, Mann-Whitney's U test, Wilcoxon's signed-rank test, or Fisher's exact test were used in the statistical analysis. RESULTS: Of the 363 patients, 136 (37.5%) had diabetes, while 227 (62.5%) did not. After propensity score matching, there were no significant differences between the groups in surgical outcomes such as surgery duration, bleeding amount, and postoperative complication rate. No significant differences were observed between the groups in terms of incidence rates of not only infectious complications, including surgical site infection and remote site infection, but also postoperative complication (Clavien-Dindo grade > IIIA), post-hepatectomy liver failure, and massive ascites. There were no differences in the remnant liver regeneration at 7 days and 1, 2, 5, and 12 months following the surgery between the groups (p = 0.076, 0.368, 0.864, 0.288, and 0.063, respectively). No significant differences between the groups in the overall and recurrence-free survival were observed (p = 0.613 and 0.937). CONCLUSIONS: Remnant liver regeneration in diabetic patients was not morphologically and functionally delayed compared to that in non-diabetic patients. Moreover, diabetes has no effect on the short- and long-term prognosis.

Clinical characteristics of long-term survival with noninvasive ventilation and factors affecting the transition to invasive ventilation in amyotrophic lateral sclerosis.

INTRODUCTION: We evaluated post-noninvasive ventilation survival and factors for the transition to tracheostomy in amyotrophic lateral sclerosis (ALS). METHODS: We analyzed 197 patients using a prospectively collected database with 114 patients since 2000. RESULTS: Among 114 patients, 59 patients underwent noninvasive ventilation (NIV), which prolonged the total median survival time to 43 months compared with 32 months without treatment. The best post-NIV survival was associated with a lack of bulbar symptoms, higher measured pulmonary function, and a slower rate of progression at diagnosis. The transition rate from NIV to tracheostomy gradually decreased over the years. Patients using NIV for more than 6 months were more likely to refuse tracheostomy and to be women. DISCUSSION: This study confirmed a positive survival effect with NIV, which was less effective in patients with bulbar dysfunction. Additional studies are required to determine the best timing for using NIV with ALS in patients with bulbar dysfunction. Muscle Nerve 58:770-776 2018.

Preventive Effect of Cilostazol on Pneumonia in Patients with Acute Cerebral Infarction.

BACKGROUND: The antiplatelet drug cilostazol decreases the risk of ischemic stroke recurrence in patients with chronic cerebral infarction. Additionally, cilostazol reduces the occurrence of pneumonia in these patients. The purpose of this study was to investigate whether cilostazol is effective for preventing pneumonia in patients with acute cerebral infarction. MATERIALS AND METHODS: A total of 199 consecutive Japanese patients with noncardioembolic acute cerebral infarction, who visited our hospital from January 2010 to April 2016, were retrospectively assessed by using medical records. We compared changes in the occurrence of pneumonia between cilostazol (n = 127) and noncilostazol (n = 72) groups. RESULTS: A total of 76% of patients in the cilostazol group were not administered other antiplatelet drugs. The median duration until cilostazol administration was 5 days (interquartile range = 2-8 days) after the onset of cerebral infarction. A total of 8.0% of the cohort was accompanied by pneumonia. The incidence of pneumonia in the cilostazol group was significantly lower than that in the noncilostazol group (4.7% versus 13.9%, P = .02). Within 30 days after acute cerebral infarction, the presence of neurological deterioration in the cilostazol group tended to be lower compared with the noncilostazol group, but this difference was not significant (5.5% versus 12.5%, P = .08). CONCLUSIONS: These findings suggest that cilostazol is effective for preventing pneumonia in patients with acute cerebral infarction.

Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a primary EBV infection: a case report.

BACKGROUND: Anti-Myelin oligodendrocyte glycoprotein (MOG) antibodies are detected in various demyelinating diseases, such as pediatric acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, and aquaporin-4 antibody-seronegative neuromyelitis optica spectrum disorder. We present a patient who developed anti-MOG antibody-positive ADEM following infectious mononucleosis (IM) due to Epstein-Barr virus (EBV) infection. CASE PRESENTATION: A 36-year-old healthy man developed paresthesia of bilateral lower extremities and urinary retention 8 days after the onset of IM due to primary EBV infection. The MRI revealed the lesions in the cervical spinal cord, the conus medullaris, and the internal capsule. An examination of the cerebrospinal fluid revealed pleocytosis. Cell-based immunoassays revealed positivity for anti-MOG antibody with a titer of 1:1024 and negativity for anti-aquaporin-4 antibody. His symptoms quickly improved after steroid pulse therapy followed by oral betamethasone. Anti-MOG antibody titer at the 6-month follow-up was negative. CONCLUSIONS: This case suggests that primary EBV infection would trigger anti-MOG antibody-positive ADEM. Adult ADEM patients can be positive for anti-MOG antibody, the titers of which correlate well with the neurological symptoms.

ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19.

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder characterized by the degeneration of motor neurons and typically results in death within 3-5 years from onset. Familial ALS (FALS) comprises 5%-10% of ALS cases, and the identification of genes associated with FALS is indispensable to elucidating the molecular pathogenesis. We identified a Japanese family affected by late-onset, autosomal-dominant ALS in which mutations in genes known to be associated with FALS were excluded. A whole- genome sequencing and parametric linkage analysis under the assumption of an autosomal-dominant mode of inheritance with incomplete penetrance revealed the mutation c.2780G>A (p. Arg927Gln) in ERBB4. An extensive mutational analysis revealed the same mutation in a Canadian individual with familial ALS and a de novo mutation, c.3823C>T (p. Arg1275Trp), in a Japanese simplex case. These amino acid substitutions involve amino acids highly conserved among species, are predicted as probably damaging, and are located within a tyrosine kinase domain (p. Arg927Gln) or a C-terminal domain (p. Arg1275Trp), both of which mediate essential functions of ErbB4 as a receptor tyrosine kinase. Functional analysis revealed that these mutations led to a reduced autophosphorylation of ErbB4 upon neuregulin-1 (NRG-1) stimulation. Clinical presentations of the individuals with mutations were characterized by the involvement of both upper and lower motor neurons, a lack of obvious cognitive dysfunction, and relatively slow progression. This study indicates that disruption of the neuregulin-ErbB4 pathway is involved in the pathogenesis of ALS and potentially paves the way for the development of innovative therapeutic strategies such using NRGs or their agonists to upregulate ErbB4 functions.

Evaluation of Vestibular Functions in a Case of Vestibular Migraine With Successful Treatment With Erenumab.

This is the first report of vestibular examinations before and after the successful treatment of vestibular migraine (VM), a common cause of recurrent vertigo, with calcitonin gene-related peptide (CGRP) receptor inhibitor. We evaluated a 42-year-old female with VM and concomitant probable Meniere's disease, whose headache and dizziness have improved promptly with the administration of erenumab, a CGRP receptor inhibitor. The sensorineural hearing loss in pure-tone audiometry, dysfunctions shown in vestibular examinations (cervical and ocular vestibular evoked myogenic potentials), and mild endolymphatic hydrops shown in gadolinium-enhanced inner ear magnetic resonance imaging, all in the right ear, revealed no change compared with those observed before treatment. This case suggests that VM may be treated by blocking CGRP in the trigeminal ganglion, which suppresses the effects on the vestibular nucleus; herein, no effects were observed in the inner ear despite the clear amelioration of dizziness.

Interferon-ß1b increases Th2 response in neuromyelitis optica.

A Japanese randomized controlled study showed that Interferon â (IFN-â1b) therapy is clinically effective in decreasing the frequency of attacks in multiple sclerosis (MS), even in optico-spinal MS (OSMS). However, recent studies have shown that IFN-â (IFN-â1a/IFN-â1b) treatment was not effective in neuromyelitis optica (NMO) patients and that the diminished benefit of IFN-â treatment in NMO may be due to different immune responses to IFN-â. We determined longitudinally the expression of CCR5, CXCR3 and CCR4 on CD4+ T and CD8+ T cells in the blood from patients with NMO and MS treated with IFN-â1b. During a 12-month period of IFN-â1b therapy, the annualized relapse rate decreased in MS patients but not in NMO patients. There was no significant difference in the expression of the chemokine receptors between NMO and MS at baseline. The percentages of CD4+CCR5+ and CD4+CXCR3+ T cells, representative of the Th1 response, were decreased in both NMO and MS after treatment. The percentage of CD4+CCR4+ T cells, representative of the Th2 response, was decreased in MS, but those for NMO was significantly increased compared with the pretreatment levels. Our results indicate that IFN-â1b-induced up-modulation of the Th2 response in NMO patients may be the source of differences in the therapeutic response to IFN-â1b therapy. In the present study, Th2 predominance is involved in the pathogenesis of NMO.

Does repeat laparoscopic hepatectomy without extracorporeal Pringle manoeuvre worsen treatment outcomes?

Introduction: The Pringle manoeuvre is used in most hospitals to counteract intraoperative haemorrhage in laparoscopic hepatectomy by occluding the flow of blood to the liver. However, in laparoscopic repeat hepatectomy (LRH), outcomes of previous surgery and the influence of other factors frequently make it difficult to occlude the inflow of blood. Aim: To discuss the value of inflow occlusion during LRH and provide tips for its performance. Material and methods: Sixty-three patients who underwent LRH with or without the Pringle manoeuvre were analysed retrospectively. We investigated the efficacy and safety of the Pringle manoeuvre in LRH. Student's t and χ2 tests, Mann-Whitney's U test, Wilcoxon's signed-rank test, and Fisher's exact test were used in the statistical analysis. Results: Nineteen patients underwent LRH with the Pringle manoeuvre, and 44 patients underwent LHR without the Pringle manoeuvre. After propensity score matching, there were no significant differences in terms of operative time, estimated blood loss, and postoperative complication rate (p = 0.973, 0.120, and not applicable, respectively). However, the rate of conversion to open repeat hepatectomy (ORH) was significantly lower in the Pringle manoeuvre group (p = 0.034). In many cases, the cause of conversion to ORH was the non-use of inflow occlusion and the resulting inability to control intraoperative haemorrhage. Laboratory data collected after surgery showed no significant difference between the 2 groups regardless of whether blood flow was occluded or not. Conclusions: LRH with the Pringle manoeuvre can be performed safely using various surgical devices. However, it is often challenging to perform the Pringle manoeuvre in patients with a history of cholecystectomy or segment 5 resection of the liver, and caution is required.

The Management of Recurrence of Hepatocellular Carcinoma Occurring Within 6 Months After Hepatic Resection: A Comparative Study Using a Propensity Score Matching Analysis.

BACKGROUND: Hepatectomy is currently recommended as the most reliable treatment for hepatocellular carcinoma. However, the association between the choice of treatment for recurrence and the timing of recurrence remains controversial. METHODS: Three-hundred thirty-nine patients who underwent hepatectomy were retrospectively analyzed using a propensity score matching analysis for the risk factors and outcomes for early recurrences within 6 months. The remnant liver volumes and laboratory data were measured postoperatively using multidetector computed tomography on days 7 and months 1, 2, and 5 after surgery. The Student's t test and chi-square test, the likelihood-ratio test, Fisher's exact test, Mann-Whitney U test, or Wilcoxon signed-rank test were used in the statistical analyses. RESULTS: Early recurrence developed in 41/312 patients (13.1%). Vascular invasion and non-curative resection were independent risk factors for the occurrence of early recurrence (P < 0.001 and < 0.001, respectively). Patients with early recurrence had a poorer prognosis than patients who developed later recurrences (P < 0.001). Patients who underwent surgery or other local treatments had better outcomes (P < 0.001). The changes in remnant liver volumes and laboratory data after postoperative month 2 were not significantly different between the two groups. CONCLUSION: Patients with early recurrence within 6 months had a poorer prognosis than patients who developed a later recurrence. However, patients who underwent repeat hepatectomy for recurrences had a better prognosis than did those who underwent other treatments, with good prospects for long-term survival.

Onset and spreading patterns of lower motor neuron involvements predict survival in sporadic amyotrophic lateral sclerosis.

OBJECTIVE: To define patterns of spread through the order of lower motor neuron involvement (first, second or third order), relationships between interval or sites of affected areas from onset to involvement of a second region, and prognosis, including 5 year survival, normal preservation of motor function at onset of respiratory symptoms and cumulative occurrence of each region and direction of spread. METHOD: 150 patients with sporadic amyotrophic lateral sclerosis (ALS) underwent follow-up at 3 month intervals until the appearance of respiratory symptoms. Symptom appearances were determined using the revised version of the ALS Functional Rating Scale. RESULT: Median survival with combined type onset (two regions simultaneously) was shorter (18 months) than with bulbar onset (26 months, p=0.01). The interval from onset to involvement of the second region correlated significantly with survival, independent of particular combinations. 5 year survival rate was 21% for lower limb onset, 18% for upper limb onset and 16% for bulbar onset. No patient with a rapid spread pattern (two regions within 3 months from onset) survived >5 years. Early manifestations of bulbar symptoms within 1 year were associated with worse survival (p<0.001) although no significant difference in survival was seen between groups with and without bulbar symptoms (p=0.51). In terms of cumulative occurrence, symptoms spread longitudinally to adjacent regions. Bulbar function remained preserved in 27%, lower limb function in 10% and upper limb function in 2.7%. CONCLUSION: The interval between onset and involvement of the second region is an important predictor of survival. The data support the contiguous anatomical propagation of lower motor neuron involvement in sporadic ALS.

Recurrent high-dose intravenous methylprednisolone succinate pulse therapy-induced hepatopathy in a patient with multiple sclerosis.

OBJECTIVE: We describe recurrent and reversible hepatopathy in a girl with multiple sclerosis (MS) after glucocorticoid pulse therapy, to point out the possibility that glucocorticoid may harm the liver. CLINICAL PRESENTATION AND INTERVENTION: An 11-year-old girl with MS, who was treated with high-dose methylprednisolone succinate pulse therapy, developed elevation of liver enzymes. The episodes of hepatopathy occurred 1-5 weeks after the therapy and disappeared within several weeks. The examination for antinuclear antibody and viruses which can cause hepatitis produced negative results. CONCLUSION: The present case emphasizes the possible effects of high-dose glucocorticoids in the induction of liver enzymes and the importance of follow-up liver tests after pulse therapy.

Neuron-specific enolase level is a useful biomarker for distinguishing amyotrophic lateral sclerosis from cervical spondylotic myelopathy.

The current study aimed to evaluate whether cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels are elevated in amyotrophic lateral sclerosis (ALS) and are effective in distinguishing ALS from cervical spondylotic myelopathy (CSM). We retrospectively evaluated 45 patients with ALS, 23 with CSM, 28 controls, and 10 with Parkinson's disease (PD) who underwent analysis of CSF NSE levels. The control group comprised patients aged above 45 years who underwent lumbar puncture because of suspected neurological disorders that were ruled out after extensive investigations. CSF NSE levels were evaluated using the electro-chemiluminescent immunoassay. The ALS group had significantly higher CSF NSE levels than the CSM and control groups (P < 0.001 for both comparisons). The CSM, control, and PD groups did not significantly differ in terms of CSF NSE levels. A receiver-operating characteristic curve analysis was performed to assess the diagnostic value of CSF NSE levels in distinguishing ALS from CSM. The area under the curve for CSF NSE levels was 0.86. The optimal cutoff value was 17.7 ng/mL, with a specificity of 87% and a sensitivity of 80%. Hence, CSF NSE levels are elevated in ALS and are effective in distinguishing ALS from CSM.

Safety and Efficacy of Laparoscopic Liver Resection for Colorectal Liver Metastasis With Obesity.

INTRODUCTION: Laparoscopic liver resection (LLR) in obese patients has been reported to be particularly challenging owing to technical difficulties and various comorbidities. METHODS: The safety and efficacy outcomes in 314 patients who underwent laparoscopic or open nonanatomical liver resection for colorectal liver metastases (CRLM) were analyzed retrospectively with respect to the patients' body mass index (BMI) and visceral fat area (VFA). RESULTS: Two hundred and four patients underwent LLR, and 110 patients underwent open liver resection (OLR). The rate of conversion from LLR to OLR was 4.4%, with no significant difference between the BMI and VFA groups (P = .647 and .136, respectively). In addition, there were no significant differences in terms of operative time and estimated blood loss in LLR (P = .226 and .368; .772 and .489, respectively). The incidence of Clavien-Dindo grade IIIa or higher complications was not significantly different between the BMI and VFA groups of LLR (P = .877 and .726, respectively). In obese patients, the operative time and estimated blood loss were significantly shorter and lower, respectively, in LLR than in OLR (P = .003 and < .001; < .001 and < .001, respectively). There was a significant difference in the incidence of postoperative complications, organ/space surgical site infections, and postoperative bile leakage between the LLR and OLR groups (P = .017, < .001, and < .001, respectively). CONCLUSION: LLR for obese patients with CRLM can be performed safely using various surgical devices with no major difference in outcomes compared to those in nonobese patients. Moreover, LLR has better safety outcomes than OLR in obese patients.

Visual field defects of optic neuritis in neuromyelitis optica compared with multiple sclerosis.

BACKGROUND: Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that predominantly affects the optic nerves and the spinal cord, and is possibly mediated by an immune mechanism distinct from that of multiple sclerosis (MS). Central scotoma is recognized as a characteristic visual field defect pattern of optic neuritis (ON), however, the differing pathogenic mechanisms of NMO and MS may result in different patterns of visual field defects for ON. METHODS: Medical records of 15 patients with NMO and 20 patients with MS having ON were retrospectively analyzed. A thorough systemic and neurological examination was performed for evaluating ON. The total number of relapses of ON and visual fields was investigated. Visual fields were obtained by Goldmann perimeter with each ON relapse. RESULTS: All MS patients experienced central scotoma, with 90% of them showing central scotoma with every ON relapse. However, 53% of NMO patients showed central scotoma with every ON relapse (p = 0.022), and the remaining 47% of patients experienced non-central scotoma (altitudinal, quadrant, three quadrant, hemianopia, and bitemporal hemianopia). Thirteen percent of NMO patients did not experience central scotoma during their disease course. Altitudinal hemianopia was the most frequent non-central scotoma pattern in NMO. CONCLUSIONS: NMO patients showed higher incidence of non-central scotoma than MS, and altitudinal hemianopia may be characteristic of ON occurring in NMO. As altitudinal hemianopia is highly characteristic of ischemic optic neuropathy, we suggest that an ischemic mechanism mediated by anti-aquaporin-4 antibody may play a role in ON in NMO patients.

[National survey of radiation protection for workers in positron emission tomography facilities in Japan-1st report: occupational role assignment, radiation exposure to medical workers].

We have investigated the role assignment and radiation exposure of medical workers (including receptionists) in PET (positron emission tomography) facilities in Japan using a questionnaire. The survey period was from October 1st to November 15th 2006. The response rate for the questionnaire was 60.0% (72/120 facilities). Nurses were engaged in the intravenous administration of radioactive FDG in 66.9% of PET facilities. In 89.5% of PET facilities, radiological technologists mainly performed the PET examination. The average radiation exposure to medical workers was 0.13 mSv/month (n: 709, S.D.: 0.16) as the effective dose. It was shown that radiation exposure was significantly different depending on the occupation and content of work (p<0.01). The radiation exposure of cyclotron operators and radiological technologists was higher than that of the other occupations (p<0.01). The highest radiation dose to one worker per a PET facility was 0.60 [mSv month(-1)], which was 4.6 times higher than the average dose of 0.13 [mSv month(-1)]. We have clarified the actual conditions of radiation protection in PET facilities in Japan for the first time.

Biological roles of anti-GM1 antibodies in patients with Guillain-Barré syndrome for nerve growth factor signaling.

To reveal the biological and pathological roles of anti-GM1 antibody in Guillain-Barré syndrome (GBS), we examined its effects on nerve growth factor (NGF) induced TrkA autophosphorylation (NGF-TrkA signaling) in PC12 cells, a sympathetic nerve cell line. The NGF-TrkA signaling is enhanced by exogenous GM1 ganglioside and this phenomenon is regarded as one of the functional aspects of GM1. The IgGs purified from patients' sera inhibited the NGF-TrkA signaling in GM1 pre-incubated PC12 cells. The degrees of inhibition by IgGs from patients paralleled their immunological reactivity to GM1. In addition, the IgGs also inhibited the neurite outgrowth of NGF-treated PC12 cells. Immunoglobulins in the rabbit sera, which were immunized by GM1, also caused a similar suppressive phenomenon. These results suggested that the anti-GM1 antibody could play roles in pathophysiology in anti-GM1 antibody positive GBS through interfering with the neurotrophic action of NGF and GM1 mediated signal modulation including NGF-TrkA signaling. It is suggested that the modulation of GM1 function is one important action of antibodies and could be one of the important mechanisms in GBS.