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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.To discuss the value of inflow occlusion during LRH and provide tips for its performance.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'sNineteen 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 (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 Pringle maneuver is currently used in most institutions to prevent intraoperative hemorrhage during hepatectomy by occluding the blood flow to the liver. We investigated the postoperative effects of hepatic inflow occlusion time during hepatectomy. The surgical outcomes of 831 patients who underwent hepatic resection for liver tumors were retrospectively reviewed, including the association of hepatic inflow occlusion time with surgical outcomes and remnant liver regeneration. The Student’s t and χ2 tests, Mann–Whitney’s U test, Wilcoxon’s signed-rank test, or Fisher’s exact test were used. Patients were divided into two groups: the normal liver group (fibrosis stage 0–1; n = 560) and diseased liver group (fibrosis stage 2–4; n = 271). The Pringle maneuver was performed in 522 (62.8%) patients. The median occlusion time was 45 (9–167) min. There was an association between extended ischemia time and unfavorable blood test results in the early postoperative period. However, regardless of the ischemia time, the patients recovered by the 14th postoperative day. There were no correlations between total ischemia time and the frequency of postoperative complications in either the normal or diseased liver groups (p = 0.262 and 0.099, respectively). There were no correlations between ischemia time and remnant liver regeneration at 7 days, and 1, 2, 5, and 12 months, postoperatively, in either the normal or diseased liver groups. The intermittent Pringles maneuver over shorter periods was associated with favorable postoperative outcomes and complications, and had no significant effect on remnant liver regeneration.

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. 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. 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

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.

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, and 28 controls 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 and control 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.

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

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.

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.

We herein report the case of a 53-year-old man with cerebellar ataxia with anti-glutamic acid decarboxylase antibody (GAD-Ab) who mimicked Miller Fisher syndrome (MFS). He developed ophthalmoplegia, diplopia, and gait ataxia for one week. The serum and cerebrospinal fluid GAD-Ab titers were greatly increased, and the GAD-Ab index suggesting intrathecal antibody synthesis was elevated, while GQ1b-Ab was negative. After steroid pulse therapy and following prednisolone, his symptoms dramatically improved over the course of 11 months with the simultaneous decline of GAD-Ab titers. This case indicates that cerebellar ataxia with GAD-Ab can present with acute neurological findings mimicking MFS, and that steroid therapy has an excellent therapeutic effect.

Background Invasive and/or non-invasive mechanical ventilation are most important options of respiratory management in amyotrophic lateral sclerosis. Methods We evaluated the frequency, clinical characteristics, decision-making factors about ventilation and survival analysis of 190 people with amyotrophic lateral sclerosis patients from 1990 until 2013. Results Thirty-one percentage of patients underwent tracheostomy invasive ventilation with the rate increasing more than the past 20 years. The ratio of tracheostomy invasive ventilation in patients >65 years old was significantly increased after 2000 (25%) as compared to before (10%). After 2010, the standard use of non-invasive ventilation showed a tendency to reduce the frequency of tracheostomy invasive ventilation. Mechanical ventilation prolonged median survival (75 months in tracheostomy invasive ventilation, 43 months in non-invasive ventilation vs natural course, 32 months). The life-extending effects by tracheostomy invasive ventilation were longer in younger patients ≤65 years old at the time of ventilation support than in older patients. Presence of partners and care at home were associated with better survival. Following factors related to the decision to perform tracheostomy invasive ventilation: patients ≤65 years old: greater use of non-invasive ventilation: presence of a spouse: faster tracheostomy: higher progression rate; and preserved motor functions. No patients who underwent tracheostomy invasive ventilation died from a decision to withdraw mechanical ventilation. Conclusion The present study provides factors related to decision-making process and survival after tracheostomy and help clinicians and family members to expand the knowledge about ventilation.

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.

A 55-year-old woman was diagnosed with aseptic meningitis at the age of 43 and 44. She developed sudden fever and headache, and she showed nuchal rigidity. Cerebrospinal fluid examination revealed pleocytosis (cell count 208/mm3) and was positive for herpes simplex virus type 2 (HSV-2) DNA by PCR. Acyclovir was started on the first day of admission, and she was complete recovery. Preserved cerebrospinal fluid specimen from aseptic meningitis at the age of 44 was also positive for HSV-2 DNA by PCR. She was diagnosed with HSV-2 associated recurrent aseptic meningitis (Mollaret's meningitis) with a recurrence after 11-year interval. She repeatedly relapsed genital herpes after 44 years old and she was treated with valacyclovir whenever genital herpes relapses. But she showed no genital herpes at the onset of meningitis. Because HSV-2 is one of the most significant causes of recurrent meningitis, we would like to stress that HSV-2 infection and antiviral therapy should always be kept in mind for a recurrent meningitis case.

To determine clinical features of neurologic disorders associated with anti-glutamic acid decarboxylase antibodies (anti-GAD-Ab), we examined titers and time-dependent changes of anti-GAD-Ab. Six patients, stiff person syndrome (2), cerebellar ataxia (1), limbic encephalitis (1), epilepsy (1), brainstem encephalitis (1), were compared with 87 type I diabetes mellitus (T1DM) patients without neurologic disorders. Anti-GAD-Ab titers and index were higher in neurologic disorders than in T1DM, suggesting intrathecal antibody synthesis. Anti-GAD-Ab titers in T1DM decreased over time, whereas they remained high in neurologic disorders. Immunotherapy improved neurological disorders and anti-GAD-Ab titers and index provide clinically meaningful information about their diagnostic accuracy.

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.

Objective To evaluate the factors related to the choice of a tracheostomy and invasive ventilation in amyotrophic lateral sclerosis patients and to determine survival time after a tracheostomy at a single institute in Japan between 1990 and 2010. Methods Data for survival time until death or tracheostomy were obtained from 160 patients. Fifty-two patients (33%) underwent tracheostomy/mechanical ventilation. Results Tracheostomy and invasive ventilation prolonged median survival time (74 months), as did non-invasive ventilation (48 months) when compared to a non-ventilation-supported control group (32 months; p 65 years old significantly increased after 1999 (27%) compared to earlier years (10%, p = 0.002). Cox proportional modeling confirmed an age of ≤ 65 years as advantageous for long-term survival after a tracheostomy. In univariate logistic regression analysis, factors related to the decision to perform a tracheostomy included an age of ≤ 65 years, greater use of non-invasive ventilation, the presence of a spouse, interval and speed from disease onset to diagnosis/tracheostomy and preservation of motor function. In multivariate logistic regression analysis, age, shorter duration from disease onset until tracheostomy and the presence of a spouse were independently associated with the decision to perform a tracheostomy. Kaplan–Meier plots revealed longer survival times in patients who resided at home after a tracheostomy compared to patients who stayed at a hospital (p = 0.007). Conclusions Tracheostomy and invasive ventilation are frequently used in Japan. Various factors impact patients' decisions to have these procedures. This study identified factors related to the decision-making process and post-tracheostomy survival.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system inflammatory disease characterized by the punctate gadolinium enhancement peppering the pons and the cerebellar peduncles as neuroimaging. We report the case of a 66-year-old woman who presented with CLIPPERS associated with swelling in the brainstem. She was hospitalized because of gait ataxia and consciousness disturbance. MRI of the brain showed FLAIR hyperintense lesions in the pons, cerebellar peduncles, cerebellum and the subcortical white matter lesion in the right occipital lobe with significant swelling in the brainstem. Diffusion-weighted MRI did not show an abnormal signal, indicating vasogenic edema. Post-contrast T1-weighted MRI showed enhanced area in the right occipital lobe and panctate gadolinium enhancement peppering brainstem. Treatment with steroids led to rapid improvement. However, she showed exacerbation of clinical and radiological findings during the tapering schedule of steroid. The biopsy from the occipital lobe revealed intense perivascular and parenchymal lymphocytic infiltrates composed of primarily T cells, B cells and macrophages. The patient was diagnosed with CLIPPERS, and treatment with increased dose of corticosteroid induced a clinical improvement. Previous reports well described a characteristic MRI finding of punctate enhancement peppering the pons. In addition, the pons and cerebellar peduncles swelling can occur in this disorder.

Hypertrophic pachymeningitis is an inflammatory disease that causes various neural symptoms, including headache and cranial neuropathy, presenting as pachymeningeal hypertrophy with contrast enhancement on imaging. The cause of this disease is classified as idiopathic, in which the underlying disease is unknown, and is associated with autoimmunity, such as antineutrophil cytoplasmic autoantibody (ANCA)-related vasculitis, IgG4-related disease and infections [1]. Here, we describe a patient with ANCArelated hypertrophic pachymeningitis that developed with visual impairment caused by optic perineuritis. Although optic perineuritis closely resembles optic neuritis, it is a different condition. Thus, it is important to ascertain the condition after hypertrophic pachymeningitis diagnosis and to provide appropriate treatment. An 87-year-old woman underwent surgery for a cataract of the left eye; however, immediately after the surgery, blurred vision occurred in the eye. Thereafter, she developed headaches and loss of vision. Visual acuity of the left eye was 0.4, and 3 days later, only light perception was possible, and she was admitted to our hospital. However, on identifying a high inflammatory response and abnormal findings through magnetic resonance imaging (MRI) of the head, she was admitted to our department. On admission, she had right visual acuity of 0.8 with left light perception, no difference in left–right pupil size, normal eye movement. She was negative for neck stiffness, and no other neurological deficit suggesting neuromyelitis optica spectrum disorders was detected. Blood tests revealed a high inflammatory response with white blood cell counts of 10,970/mm, C-reactive protein (CRP) levels of 9.25 mg/ dL, anti-nuclear antibodies 1:640, proteinase 3 (PR3)ANCA levels of 7.1 U/mL, and high myeloperoxidase (MPO)-ANCA levels of 5.1 U/mL. However, IgG4 level was normal at 108 mg/dL. Anti-aquaporin 4 antibody was negative. Examination of the cerebrospinal fluid revealed a cell count of 13/mm and protein and glucose levels of 107.3 and 54 mg/dL, respectively. PCR revealed the absence of herpes simplex virus, varicella zoster virus, and tuberculosis bacterial DNA in cerebrospinal fluid. There were no abnormalities on fundoscopy, and no papilledema was observed; however, visual field test on the Goldmann perimeter revealed central scotoma with concentric narrowing of the visual field in the left eye. MRI of the optic nerve on T2-weighted fat-suppressed imaging revealed linear high signal intensity and tram-track signs [2] that were believed to be an enlargement of the cerebrospinal fluid cavity surrounding the left and right optic nerves (Fig. 1a). The left optic nerve showed increased enhancement of the gadolinium contrast medium surrounding the optic nerve (Fig. 1b, c). These visual field test and MRI findings were believed to be signs of left optic perineuritis. Cerebral MRI revealed increased enhancement of the pachymeninx extending to the entire cerebral hemisphere with left-side predominance (Fig. 1d–f), and positive results for PR3-ANCA and MPO-ANCA on blood testing led to the consideration of ANCA-related hypertrophic pachymeningitis. Furthermore, diffusion-weighted imaging & Hideto Nakajima in1045@poh.osaka-med.ac.jp

Eicosapentaenoic acid (EPA), one of the n-3 polyunsaturated fatty acids, is a neuroprotective lipid with anti-inflammatory properties. We investigated the possible therapeutic effect of EPA on experimental autoimmune encephalomyelitis (EAE). EAE mice were fed a diet with or without EPA. The clinical EAE scores of the EPA-fed mice were significantly lower than those of the non-EPA mice. In the EPA-treated mice, IFN-γ and IL-17 productions were remarkably inhibited and the expression levels of peroxisome proliferator-activated receptors were significantly enhanced in the CNS-infiltrating CD4T cells. Thus EPA shows promise as a potential new therapeutic agent against multiple sclerosis.

Myositis-specific autoantibodies (MSAs) are associated with myositis. Anti-nuclear matrix protein 2 (NXP-2) antibody was recently identified as a major MSA and was observed mostly in juvenile dermatomyositis. We report the case of a 44-year-old man who presented with myopathy with anti-NXP-2 antibody and large cell carcinoma of the lung. He was hospitalized because of myalgia and edema of limbs. Neurological examination revealed mild proximal-dominant weakness in all four extremities, and laboratory studies showed elevated creatine kinase level (6,432 IU/l). Needle electromyography showed myogenic patterns. MRI of the lower limbs demonstrated inflammatory lesions in the thighs. Biopsied specimen from the left quadriceps femoris muscle showed mild mononuclear inflammatory infiltrate surrounding muscle fibres but no fiber necrosis. He was diagnosed with myopathy based on neurological examinations and clinical symptoms. His chest X-ray and CT showed tumor shadow on the right upper lung field, but CT didn't indicate the findings of interstitial lung disease. This was surgically removed, and a histological diagnosis of non-small cell lung cancer was suspected. He was also treated with definitive chemoradiotherapy before and after operation. His symptoms of myopathy promptly remitted with the preoperative chemotherapy. His serum analysis was positive for the anti-NXP-2. Further investigation and experience of MSAs are necessary to evaluate the therapeutic strategy against cancer-associated myopathy/myositis.

A 78-year-old woman was diagnosed with bullous pemphigoid 2 months ago, and she had been treated with steroid and plasmapheresis. She developed sudden fever, vomiting, disorientation, and abnormal behavior. Diffusion weighted images and fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images showed high-intensity signals in the right temporal lobe hippocampus and right insular cortex. Cerebrospinal fluid (CSF) examination showed normal cell count (4/mm(3)), but was positive for HSV1-DNA by PCR. She was diagnosed with herpes simplex encephalitis (HSE), and acyclovir was started on the first day of admission. She had complete recovery, and was discharged. She didn't show CSF pleocytosis throughout her course of HSE. No CSF pleocytosis could be due probably to her immunosuppressed state under the steroid therapy for bullous pemphigoid. Because the morbidity and mortality of HSE is drastically reduced by early antiviral treatment, it is important to accelerate the diagnosis and treatment of HSE, especially in immunosuppressed or immunocompromised hosts.

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.

Mutation in the transthyretin (TTR) gene may clinically manifest as cardiomyopathy. Here, we describe 69-year-old and 72-year-old brothers who were diagnosed as having TTR-related familial amyloid cardiomyopathy by endomyocardial biopsy at different hospitals at around the same time. They were not from an endemic area of familial amyloid polyneuropathy. Genetic analysis showed a base change in the TTR gene leading to a p.Val30Met mutation in both patients. Screening of family members, as well as detailed family history taking, is important for the diagnosis of cardiomyopathy of unknown etiology.

A misfolding pathology has been suggested to spread from onset site to neighbouring areas in a prion-like manner. We examined the pattern of spread and direction of clinical lower motor neuron involvement over time until the appearance of respiratory symptom. A total of 150 patients with sporadic ALS underwent follow-up until respiratory symptoms. Symptom appearances were determined using ALSFRS-R. The interval from onset to involvement of the second region correlated significantly with survival, independent of particular combinations. No patient with a rapid spread pattern (two regions within 3 months from onset) survived >5 years. Time from onset to spread to the second site, suggesting propagation speed, is a strong predictor for survival. In terms of cumulative occurrence, symptoms spread longitudinally to adjacent regions. In most of ALS patients, the spread appears to have a contiguous pattern rather than a random pattern of progression, although the spread to non-contiguous regions was observed in 13%. This finding supports the notion that the ALS pathology gradually spreads to adjacent regions in a longitudinal manner. Although precise mechanism of symptom spread in ALS is not understood, knowledge about the pattern of onset and the anatomical direction of spread may provide valuable prognostic insights.

Aim: Anhedonia has been proposed as a specific mood disorder related to the dopaminergic nerve dysfunction seen in Parkinson's disease (PD). This study examined hedonic tone in patients with PD using the Snaith–Hamilton Pleasure Scale (SHAPS) and investigated the associations with depressive mood by the Self-Rating Questionnaire for Depression (SRQ-D). Methods: This study examined 100 patients with PD and 111 age-matched controls (C2) recruited from 300 healthy subjects (C1) to compare the frequency of anhedonia and to clarify whether anhedonia in PD is associated with depression and anti-Parkinson medication. Results: Forty-six percent of PD patients revealed possible/probable depression and 10 patients (10%) with PD showed anhedonia as compared to 3.3% in C1 and 2.7% in C2. The reduction in hedonic tone was related to depression in PD. Among 10 PD patients with anhedonia, seven were in anhedonia with depression and three were in anhedonia without depression. There was no sex difference in anhedonia and depression. No patients treated with pramipexole showed anhedonia but also the highest proportion of normal hedonic tone was found in patients treated with pramipexole among PD patients. In analysis of each SHAPS item, no significant difference was seen on social interaction scores in contrast to the significant reduction of interest/pastimes and sensory experience and food/drink scores between PD patients and C1/C2. Conclusion: Anhedonia may overlap depressive syndrome but some PD patients without depression presented anhedonia. Pramipexole could maintain hedonic tone. The PD patients could enjoy attracting attention and wish to do things helpful for others. Geriatr Gerontol Int 2011; 11: 275–281.

We report the case of a 62-year-old man who presented with malignant lymphoma as recurrent multiple cranial nerve palsy after spontaneous regression of oculomotor nerve palsy. He developed ptosis and diplopia due to right oculomotor nerve palsy. Brain MRI/MRA showed no abnormality, and he recovered with conservative medical management. Three months later, he showed diplopia due to right abducens nerve palsy and facial pain and trigeminal sensory loss. Neurological examination revealed multiple cranial nerve palsy involved cranial nerve III, V, IX, and X of the right side. Serum soluble interleukin-2 receptor levels were normal, and cerebrospinal fluid examination was unremarkable. Steroid and subsequent intravenous immunoglobulin therapy didn't improve his symptoms. Six weeks after his admission, he showed rapid enlargement of the cervical lymph node and the right tonsil, and post-contrast T1-weighted MRI showed enlargement and enhancement of the left infraorbital nerve, the bilateral cavernous sinus, the bilateral facial nerves, and the left trigeminal nerve. The histopathologic examination of the tonsil biopsy revealed diffuse large B cell lymphoma. The cause of these symptoms was thought to be infiltrating the cavernous sinus, and adjacent nerves. Spontaneous regression of malignant lymphoma is an exceptional event, but this possibility should be considered so as to the correct diagnosis and proper treatment.

Two patients presented with malignant hypertension associated with encephalopathy predominantly manifesting as brainstem lesion. T(2)-weighted and fluid-attenuated inversion recovery magnetic resonance (MR) imaging revealed diffuse hyperintense areas in the pons and scattered lesions in the cerebellum, basal ganglia, and cerebral subcortex without parieto-occipital lesions. Diffusion-weighted MR imaging demonstrated these lesions as normal intensity, indicating vasogenic edema. These lesions resolved rapidly once hypertension was controlled. Review of clinical findings for 14 other patients with hypertensive brainstem encephalopathy without parieto-occipital lesions suggested that anterior circulation structures supplied by the carotid artery are frequently involved in such patients.

Background and Purpose— Fibroblast growth factor-2 (FGF-2) administration and bone marrow stromal cell (MSC) transplantation could improve neurological deficits after occlusive cerebrovascular disease. In the present study, we examined the effects of neurological improvement after transient middle cerebral artery occlusion (MCAO) in rats by a novel therapeutic strategy with FGF-2 gene–transferred MSCs by the herpes simplex virus type 1 (HSV-1) vector. Methods— Adult Wistar rats were anesthetized. Nonmodified MSCs, FGF-2–modified MSCs with HSV-1 1764/-4/pR19/ssIL2-FGF-2, or PBS was administered intracerebrally 24 hours after transient right MCAO. All animals underwent behavioral tests for 21 days, and the infarction volume with 2-3-5-triphenylterazolium was detected 3 days and 14 days after the MCAO. Three days and 7 days after the MCAO, the FGF-2 production in the ipsilateral hemisphere of the MCAO was measured with ELISA. Seven and 14 days after the MCAO, immunohistochemical staining for FGF-2 was applied. Results— The stroke animals receiving FGF-2–modified MSCs demonstrated significant functional recovery compared with the other groups. Fourteen days after the MCAO, there was a significant reduction in infarction volume only in FGF-2–modified MSC-treated group. FGF-2 production in the FGF-2–modified MSC-treated brain was significantly higher compared with the other groups at 3 and 7 days after MCAO. Administrated FGF-2–modified MSCs strongly expressed the FGF-2 protein, which was proven by ELISA. Conclusions— Our data suggest that the FGF-2 gene–modified MSCs with the HSV-1 vector can contribute to remarkable functional recovery after stroke compared with MSCs transplantation alone.

Guillain–Barre syndrome (GBS) is an acute, post-infectious, inflammatory, autoimmune peripheral neuropathy with a highly diverse clinical course and outcome. We classified GBS on the basis of patients’ first nerve conduction and validated this system to be associated with outcome on the basis of electrophysiological characteristics during the acute phase of GBS. We retrospectively evaluated 40 GBS patients who underwent their first electrophysiological study within 14 days of onset and classified GBS into four patterns: (1) acute inflammatory demyelinating polyneuropathy (AIDP) pattern with sensory nerve conduction abnormalities (motor–sensory AIDP: MS-AIDP), (2) AIDP pattern without sensory nerve conduction abnormalities (motor AIDP: M-AIDP), (3) acute motor axonal neuropathy (AMAN) pattern, and (4) minor abnormalities pattern. We compared the clinical, electrophysiological, and laboratory findings between groups and determined subgroups associated with poor outcome. The MS-AIDP and AMAN patterns more frequently exhibited prolonged recovery compared with the M-AIDP and minor abnormalities patterns and were associated with prolonged recovery (specificity, 100 %; sensitivity, 73 %; P < 0.001). The period of inability to walk independently was significantly longer in the MS-AIDP and AMAN patterns than in the M-AIDP and minor abnormalities patterns (median 85 vs. 10 days; P < 0.001). In conclusion, our classification of GBS using a single nerve conduction study in the early phase of disease is associated with outcomes. This classification can be used to counsel individual patients and guide decision-making with respect to treatment.

Ceftriaxone is known to induce gallstones and intrabiliary debris as the adverse effects. Ceftriaxone-related cholelithiasis occurs mainly in children treated with a high dosage of ceftriaxone for severe infections and has been rarely reported in adults. Here we report two cases of bacterial meningitis, with cholelithiasis complication developed during ceftriaxone treatment. A 65 year old man and a 66 year old man were treated with long-term (3 weeks) administration of high-dose ceftriaxone (4 g/day) for bacterial meningitis. Both patients had renal dysfunction, which may have affected gallstone formation. In one patient, gallstones spontaneously disappeared after discontinuing ceftriaxone treatment. However, the other patient needed the drainage by endoscopic retrograde cholangiopancreatography. These events are associated with elevated doses of ceftriaxone and require particular attention in the elderly and patients with renal dysfunction.

We report on a case of intracerebral hemorrhage associated with livedo racemosa in a 13-year-old girl. A skin biopsy specimen showed endothelitis and mixed inflammatory cellular infiltrate around the small arteries. We believe that the cerebral hemorrhage might have been caused by fragility of the intracranial small arteries and that this case could be an example of an early stage of Sneddon's syndrome.

Sirs: Bone lesions are frequently present in patients with POEMS syndrome [1, 2]. Since solitary bone lesions are often plasmacytomas, they must be aggressively treated with surgery or radiotherapy. We report a case of POEMS syndrome with a solitary bone lesion. In this patient, plasma cells in the osteosclerotic lesion were the source of vascular endothelial growth factor (VEGF). A 42–year-old man developed distal dominant polyneuropathy two months after myocardial infarction. Following the onset of neurological symptoms, he exhibited edema, bristly skin, and swelling of the liver in the abdominal CT. Platelet counts were 822,000/mm, and immunoelectrophoresis demonstrated Mprotein of IgA k. Serum IL-6 and VEGF were measured using standardized ELISA (SRL, Inc., Tokyo, Japan). Although the IL-6 level was normal (2.1 pg/ml. Normal value

(mononuclear), pro-tein concentration 54 mg/dl and glucose 63 mg/dl. PCR for herpes simplex virus (HSV) DNA was negative. He was treated with acyclovir (30 mg/kg/day for 14 days) and betamethasone (16 mg/day for 7 days) based on the diagnosis of limbic encepha-litis. His symptoms and MRI abnormali-ties gradually disappeared by the second hospital month, and he was discharged without any sequelae. In November 1995, the patient again experienced a week of fever, headache and disorientation. At second admission, the patient was disoriented with memory im-pairment, including anterograde and ret-rograde amnesia. His Mini-Mental State Examination score was 17/30. FLAIR MRI again revealed hyperintense lesions in the bilateral hippocampal structures (f ig. 1B ). CSF examination showed 6 cells/mm

We studied the effect of IV administration of a dehydroepiandrosterone sulfate (DHEAS) preparation (200 mg/day for 8 weeks) in 11 patients with myotonic dystrophy (MyD). After DHEAS, activities of daily living improved, muscle strength increased, and myotonia decreased. Conduction block and premature beats also improved in the four patients with cardiac involvement. This pilot study may provide a rationale for a controlled study of DHEAS in MyD.

Primary leptomeningeal lymphoma (PLML) is a rare disorder, and the pathogenesis of it has not been well described [1,2]. We report herein a case of B-cell PLML associated with Epstein–Barr virus (EBV) infection in an old patient. A 73-year-old HIV negative woman experienced a 3-month history of progression of bilateral leg weakness and paresthesias of the bilateral planta pedis. Gadolinium (Gd)-enhanced magnetic resonance imaging showed diffuse thickening of the nerve roots of the cauda equina and enhancement of the dorsal surface of the cervical cord and the root of the right oculomotor nerve (Fig. 1). A cerebrospinal fluid (CSF) examination revealed elevation of the protein concentration (292 mg/dl) and soluble interleukin-2 receptor concentration (3910 U/ml) and of the white blood cell count (224/mm). Polymerase chain reaction (PCR) studies of CSF were negative for cytomegaly

Expansion of the polyglutamine tracts in the androgen receptor (AR) has been recognized as a cause of X-linked spinal and bulbar muscular atrophy (SBMA). In the present study, NG108–15 cells were stably transfected with expression vectors coding for either the wild type (WT) AR gene (CAG repeat number=22) or a mutated (MT) AR gene (CAG repeat number=52). Cells proliferation and cell cycle parameters were evaluated for NG108–15-WT and NG108–15-MT cells in the presence or absence of androgen. NG108–15-WT cells demonstrated an androgen-dependent increase in cell number, while NG108–15-MT cells did not. Our results demonstrate that expansion of polyglutamine tracts in the AR may affect the proliferation and differentiation of nerve cells.

Polyglutamine tracts encoded by trinucleotide CAG repeats have been found in some transcription factors. Expansion of the polyglutamine tracts in the androgen receptor (AR) has been recognized as a cause of X-linked spinal and bulbar muscular atrophy (SBMA). To study the role of AR as a transcription factor in SBMA, we constructed AR genes encoding expanded polyglutamine tracts (repeat numbers = 52, 92, 132, and 212), and analyzed AR-induced transcriptional activation in NG108-15 cells. We found that AR-induced transcriptional activation gradually decreased with increasing glutamine repeat numbers, and polyglutamine expansion caused a specific reduction in transcription activity in motor neurons. However, the degree of reduction was slight in comparison with the normal AR gene and that of SBMA. Thus, subtle disorders of transcriptional control may occur in SBMA.

Sirs: Patients with Down’s syndrome, the most common human chromosomal malformation, often suffer from a variety of concomitant disorders, such as congenital heart disease, leukemia, or malignancy [5]. Several cases of Down’s syndrome (DS) with stroke disorders and moyamoya-like vessels have been reported in the literature [2, 3, 10, 11]. We report here a case of recurrent embolic stroke in a young adult with DS. A 31-year-old right-handed female with DS developed a sudden onset of nuchal pain and vertigo. She could not stand because of weakness in her lower extremities. She was admitted to Osaka Medical College on September 6, 2003. A karyotype of trisomy 21 had been confirmed when the patient was 1 month old. Upon her admission now, the stigmata of DS were present: ocular hypertelorism; broad, flat facies; wide neck; low-set, posteriorly rotated ears; and short hands with clinodactylism. The rest of the physical examination, including her cardiovascular system, was unremarkable. She had entered into a confused state and her speech had become slow and slurred. A neurological examination showed hemiparesis with hyperreflexia and Babinski’s sign on the right side. Both eyes rested in an inward position, and there was paralysis of upward and downward gaze. Striking dysmetria was noted in the left upper and lower extremities. Her gait was very broad-based and she could not walk without support. Cranial MRI showed hypersignal intensity in the left cerebellar hemisphere on T2 and diffusionweighted images, and in the medial part of the left thalamus on diffusion-weighted images (Fig. 1a, b). MR angiography of the brain was normal. There were normal findings in several studies: complete blood count, sedimentation rate, prothrombin time, partial thromboplastin time, thrombin anti-thrombin III complex, fibrinogen, fasting plasma glucose, serum cholesterol, triglyceride, C-reactive protein, antinuclear antibody, rheumatoid factors, serology of syphilis, antiphospholipid antibodies, protein C, and urine homocystine levels. There were normal results in a cardiac evaluation that included electrocardiogram, echocardiogram, and 24-hour rhythm monitor. A spine roentgenogram revealed a dislocation of the C1 and C2 vertebrae (Fig. 2a). Color-coded Doppler ultrasonography showed anterograde and severely reduced flow in the left vertebral artery. She was treated with aspirin. On 13th day after admission, she suddenly developed memory disturbance. Neurologically, her hemiparesis and motor ataxia were not aggravated, and there was no evidence of other abnormalities. A follow-up MRI of the brain showed high signals in the pons as well as in the bilateral hippocampal and occipital regions on T2 and diffusion-weighted images (Fig. 1c, d). Three-dimensional helical CT (3D-CT) demonstrated hypoplasia of the left vertebral artery and local occlusion at the C2 level; this was the same portion where there was the atlantoaxial dislocation (Fig. 2b). After a relapse of the disease, she was treated with aspirin and ticlopidine hydrochloride. Her neurological signs, except for amnesia, then improved. The occurrence of stroke in DS has been rarely reported; and some of the cases that have been reported were secondary to cyanotic heart disease with paradoxical emboli or to meningitis [11]. Epidemiologic studies have found a higher incidence of moyamoya syndrome in patients with DS [6]. Patients with DS associated with cerebral amyloid angiopathy have been represented in few previous reports [4]. Our patient manifested a top-ofthe-basilar-artery syndrome without evidence of any congenital cardiac lesion, right-to-left shunts, or valvular endocarditis. These emboli usually present as cerebral infarcts in the carotid distribution. Moreover, there were no stenosed or occluded lesions of major arteries on cranial MR angiography. The findings of 3D-CT and Doppler ultrasonography suggested that posterior circulation stroke in our patient might result from kinking and occlusion of the vertebral artery at the level of an atlantoaxial dislocation. To our knowledge, there have been no previous reports of patients with DS associated with infarction caused by atlantoaxial dislocation. Stroke due to atlantoaxial dislocation has been observed in a few cases, most of which were caused by cervical spine trauma [8, 9] and rarely by ankylosing spondylitis [14] or cranio-cervical anomalies [1]. In a retrospective review of cineangiography of patients with DS, 40 % of LETTER TO THE EDITORS