Nagoya Journal of Medical Science

The pathological spectrum of nonalcoholic fatty liver disease includes simple steatosis and nonalcoholic steatohepatitis (NASH), the latter of which is the leading cause of cirrhosis and hepatocellular carcinoma. The available evidence shows that parenchymal cell injury and death trigger inflammation and tissue fibrosis. During the development of liver fibrosis, stromal cells dramatically changes in their cellular component and activation status responding to hepatocyte injury due to various etiologies. It is important to understand how cell death induces chronic inflammation and fibrosis, and the disease-specific macrophages and fibroblasts responsible for NASH development under metabolic stress. This review discusses recent progress in the understanding the pathogenesis of NASH, focusing on disease-specific macrophages and fibroblasts.

This study developed a chronic disease nursing educational program to enhance clinical reasoning in nursing students and then tested it for effectiveness. Before and after completing the program’s five 90-minute sessions, 54 second-year students in a four-year nursing degree program at a university completed a self-administered survey to evaluate their clinical reasoning ability. The measure used was the Scale to assess the Critical Thinking of Clinical Nurses. Results showed significant improvement in total scores and in the reasoning subscale scores, indicating the overall effectiveness of the program. However, no significant improvement was found in any of the measure’s subscales other than reasoning. Those skills could, potentially, be enhanced through clinical practicum.

Prolonged treatment with linezolid (LZD) is known to cause thrombocytopenia. However, some patients do not develop thrombocytopenia despite long-term administration of LZD. To determine the risk factors for LZD-associated thrombocytopenia in patients undergoing long-term LZD therapy, we conducted a retrospective cohort study among 212 patients receiving LZD treatment between December 2011 and June 2014 at a tertiary referral university hospital in Nagoya, Japan. Of the 217 patients who received LZD, 37 were treated with LZD for more than 14 days and were enrolled in the study. We compared data on demographic characteristics, underlying disease, microbiology, concomitant drugs, and laboratory tests between the thrombocytopenia group and the non-thrombocytopenia group. Thrombocytopenia was defined as having a platelet count < 100 × 103/μL or a ≥ 50% reduction in platelet count compared to baseline. Among the 37 patients who received LZD for more than 14 days, 17 (45.9%) developed thrombocytopenia. Multivariate logistic regression revealed that both the number of concomitant drugs with thrombocytopenic adverse effects (DTADE) (OR = 1.690; 95% CI = 1.037–2.754; P = 0.035) and a small decrease in the level of C-reactive protein (CRP) 14 days post-administration (OR = 0.965; 95% CI = 0.939–0.993; P = 0.013) were associated with thrombocytopenia during long-term LZD therapy. Therefore, the number of concomitant DTADE and a small decrease in CRP on the 14th day of treatment were key factors for the appearance of LZD-associated thrombocytopenia in patients with long-term LZD therapy. Our findings may be useful for preventing thrombocytopenia in patients treated with LZD for longer than 14 days.

Aging of society has increased the incidence of physical disability. The goal of this study was to examine the physical ability of elderly people classified as having sarcopenia, presarcopenia, or dynapenia (a low muscle function without low muscle mass) in a community in Japan. The subjects were volunteers aged >60 years who were participants in a health checkup in Yakumo, Hokkaido and were in good general health. Demographic data were collected and physical performance tests were performed to measure grip strength, walking speed, back muscle strength, maximum stride length, and 3-m timed-up-and-go (3m TUG) time. A measurement of skeletal muscle mass was used as a basis for calculating the appendicular skeletal muscle index (aSMI). The rates of sarcopenia, presarcopenia, and dynapenia were 10%, 22%, and 8% in males (n=101, age 69.7±5.4 years), and 19%, 23%, and 13% in females (n=112, 68.5±5.9 years). Body mass index in subjects with dynapenia was significantly higher compared to that in subjects with sarcopenia and presarcopenia (p<0.01). Back muscle strength, maximum stride length and 3m TUG were similar in dynapenia and sarcopenia, but differed significantly with those in presarcopenia in both males and females without the influence of age (p<0.05). Further studies are needed to evaluate the benefits of dynapenia intervention programs and to explore the underlying pathophysiology of dynapenia.

We examined the effect of adipose-derived regenerative cells (ADRC) on bladder functions in a rat model of detrusor underactivity (DU) induced by bladder over-distention.
Adult female Sprague Dawley rats were divided into 3 groups: sham group (control); over-distention group; and over-distention with ADRC treatment group. Bladder was over-distended with saline (2.7mL) on day 1, 8, 15 and 22 of the study. ADRCs, which were harvested from male F344 rats, expanded via culture, were injected into the bladder wall at day 15. Cystometry and in vitro organ bath functional studies were performed on day 28. Moreover, histological assessment of the bladder was performed.
In cystometry, significant prolongation of the inter-contraction interval (ICI) and decrease of voiding ef-ficiency (VE) were observed in the over-distention group, compared to that in the control group. Significant improvement in ICI and VE was seen in the ADRC treatment group in comparison with the over-distention group. The over-distention group showed significantly weaker bladder contractile responses to carbachol and electrical field stimulation than the control group, while bladder contractile responses were significantly stronger in the ADRC treatment group than that in the over-distention group. The over-distention group showed substantial fibrosis of the bladder compared to the control group, whereas bladder fibrosis was alleviated in the ADRC treatment group.
In conclusion, the injection of ADRC into bladder wall improved bladder dysfunction and histological changes induced by bladder over-distention. ADRCs-based regenerative therapy could be novel treatment for DU.

Mongolia had an epidemic of measles in 2015–2016, even though more than 90% of the population have been vaccinated since 1997. This study aimed to examine the associations between unvaccinated proportion and measles incidence according to aimag. Mongolia has 21 provinces (aimag) with Ulaanbaatar as the capital city. Vaccination coverage between 1991 and 2014 and measles incidence according to aimag were obtained from the National Center for Communicable Diseases of Mongolia database. Accumulated unvac-cinated proportion (AUP) among those aged 1 to 24 years in 2015 was estimated from the unvaccinated at the 1st dose of 1991 to 2014. From 1991 to 2014, unvaccinated proportion among those aged 1 to 24 years in the whole country has been reducing from 28.0% in 1991 to 1.8% in 2014. The AUP in 2015 varied from 2.7% (Selenge) to 21.8% (Govisumber). The incidence was remarkably higher in only two aimags with a large density of the unvaccinated aged 1 to 24 years (Ulaanbaatar and Darkhan-Uul) than in the other aimags. The incidence had no significant correlation with the AUP, although the correlation between the incidence and the density of unvaccinated aged 1 to 24 years was significant when the two aimags were included. In conclusion, the AUP between 2.7% and 21.8% had no correlation with the incidence according to aimags in Mongolia measles epidemic 2015–2016.

Cell salvage is frequently used to avoid unnecessary allogeneic blood transfusions, which results in a reduction in blood transfusion volume and cost. The aspirated blood is washed with normal saline and centrifuged to recover only blood cells, salvaged blood is then made. In cardiovascular surgery, heparin is used to maintain activated clotting time over 400 seconds. Some practitioners believe that heparin remains in the salvaged blood. Therefore, we hypothesized that salvaged blood during cardiovascular surgery includes heparin. A pilot study was conducted to evaluate our hypothesis using three different salvage systems. This study was a prospective, observational, pilot study, with patients aged 20–85 years old who were scheduled for cardiovascular surgery from May 2018 to October 2018. The intent of this study was to evaluate whether salvaged blood with three different devices includes large enough quantities of heparin to influence activated clotting time in cardiovascular surgery. Between May and October 2018, 12 samples during heparinization were collected, and 12 samples of salvaged blood from 3 devices were collected after administrating protamine. The heparin concentration of the 24 samples was measured. All heparin concentrations in salvage blood sample from two devices was below the limit of measurement (0.10 IU/mL). Slightly measurable heparin was detected in salvaged blood sample from one device (mean 0.15 IU/mL). Salvaged blood during cardiovascular surgery intervention does not contain enough heparin to influence activated clotting time.

Neoadjuvant chemotherapy (NAC) using the combination of anthracycline and taxanes is the standard regimen for patients with primary breast cancer. Among the taxanes, conventional paclitaxel (PTX) and docetaxel have usually been adopted in the neoadjuvant or adjuvant setting. Nanoparticle albumin-bound paclitaxel (nab-PTX) is a solvent-free formulation that can be delivered to cancer cells at higher doses than conventional PTX. This study is a retrospective observational study in a single institution. We evaluated the efficacy and safety of nab-PTX followed by 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) in the neoadjuvant setting. In this study, 50 patients with primary breast cancer received nab-PTX (q3w, 260 mg/m² ± trastuzumab 6 mg/kg) followed by FEC (q3w, 5-fluorouracil 500 mg/m², epirubicin 100 mg/m², and cyclophosphamide 500 mg/m²) prior to surgery. The efficacy was evaluated using the clinical response rate (CRR), pathological complete response (pCR) rate, and Ki67 labeling index. Safety was evaluated using the frequency of treatment-related adverse events and relative dose intensity (RDI). All patients received at least one course of chemotherapy. The CRR and pCR rate were 88.0% and 40.0%, respectively. The mean Ki67 labeling index was significantly decreased from 47.7% to 24.6% after NAC. The safety profiles were comparable with previously reported regimens, and high RDIs were obtained (97.2% for nab-PTX and 95.5% for FEC). This study illustrated the efficacy and tolerability of a neoadjuvant regimen of nab-PTX followed by FEC.

Streptococcus pneumoniae is the most common pathogen for community-acquired pneumonia and is also common in nursing and healthcare-associated pneumonia. Pneumococcal vaccine shows clinical benefit and 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been introduced in a routine immunization program in Japan. However, uptake of PPSV23 remains low, at 40%. One opportunity for capturing unvaccinated subjects is hospital referrals. Identifying factors associated with pneumococcal vaccination among referred subjects is thus important so that pulmonologists can maximize the capture of unvaccinated subjects. We retrospectively reviewed the records of subjects with a first referral to the Department of Respiratory Medicine at Hiratsuka City Hospital from September 2017 to March 2018. Subjects who were ≥65 years old and lived in Hiratsuka were included in this study. We compared the backgrounds of subjects and investigated factors associated with pneumococcal vaccination. A total of 142 individuals were included in this study and the pneumococcal vaccination rate was 44.4% (95% confidence interval (CI), 36.0–52.9%). Of these, 127 subjects regularly visited clinics and/or hospitals for any diseases and their pneumococcal vaccine rate was 44.1% (95%CI, 35.3–53.2%). In multivariate analysis, chronic respiratory diseases (odds ratio 5.7; 95%CI, 2.2–14.9, P<0.001) and receipt of PPSV23 notification (odds ratio 8.5; 95%CI, 2.5–29.0, P<0.001) were positively associated with pneumococcal vaccination. In conclusion, chronic respiratory diseases and receipt of PPSV23 notification were positively associated with pneumococcal vaccination. However, pneumococcal vaccination rates remain relatively low, even in subjects regularly visiting clinics and/or hospitals.

We assessed the contribution of microsurgical seminal reconstruction to achieving natural conception in conjunction with advanced assisted reproductive technologies. Ninety obstructive azoospermic subjects who underwent microsurgical seminal reconstruction were evaluated. Vasovasostomy (VV) was undertaken in 45 subjects whereas vasoepididymostomy (VE) in 45, respectively. VV was performed by employing a two microlayer anastomotic technique, whilst VE was undertaken using double needle longitudinal vaspepididymostomy (LIVE). Patency was achieved in 41 VV (91.1%), and 25 VE (55.6%) cases. In cases where patency was achieved, pregnancy and healthy delivery were recorded following natural intercourse in 7/41 (17.0%) VV, and in 7/25 (28.0%) VE cases. Where patency was not achieved, the use of cryopreserved sperm for intracytoplasmic sperm injection (ICSI), resulted in a healthy delivery in 4/4 (100%) VV and 14/21 (66.6%) in VE subjects. Although natural pregnancy was achieved only in a limited number of subjects treated (14/90; 15.6%), sperm harvested during surgery and cryopreserved for future ICSI use proved valuable, doubling the overall delivery rate (32/90; 36.6%). Surgical intervention is considered to be a useful technique in order to allow the possibility of a natural conception and by harvesting sperm at the same time contributes to the cost-effectiveness.

Impaired wound healing is one of the most common complications of diabetes, and is known to be caused by multiple complicated factors. For instance, impaired angiogenesis, neuropathy, and hyperglycemia all function to delay subsequent wound closure. Alternatively, moist wound healing, which provides an appropriate environment for wounds, was reported to permit rapid healing by managing wound exudate. Accordingly, wound dressing materials that facilitate moist healing have been developed. The present study sought to clarify the effects of wound dressing material for moist healing of diabetic wounds, in terms of the dynamics of angiogenic factors and macrophages, using a mouse model of naturally occurring diabetes. Wounds with full-thickness skin defects were inflicted on the backs of mice and covered with dressing materials of hydrogel or gauze (control), which were retained for 3, 5, 7, 10, or 14 days following wound generation. During this time, the localization of neutrophils, fibroblasts and macrophages as well as the expression of vascular endothelial growth factor (VEGF) in the wounds and surrounding areas was observed each day. Healing clearly occurred in the hydrogel group with an increase in neutrophils and the angiogenic factor, VEGF. Moreover, the use of hydrogel resulted in a rapid rise in M1 macrophages, which appeared in the early stage of the injury, as well as rapid subsequent appearance of M2 macrophages. Thus, herein, we demonstrate that the formation of a moist environment via wound dressing material effectively improves diabetic wound healing.

The mechanisms underlying interstitial lung disease (ILD) are characterized by variable inflammation or fibrosis of the pulmonary interstitium. A negative heart sign (NHS) on ⁶⁷Ga scintigrams of patients with ILD is due to considerably increased inflammatory activity in the lungs. We retrospectively analyzed relationships between NHS and established biomarkers of disease severity in patients with ILD. Among 81 consecutive non-smoking patients with ILD (mean age, 63 years) who had been hospitalized between April 2009 and October 2011, we selected 52 who had been assessed by ⁶⁷Ga scintigraphy. We then evaluated relationships between NHS and blood biomarkers, pulmonary function and high-resolution computed tomography (HRCT). Among these 52 patients, 10 showed idiopathic pulmonary fibrosis and 42 had other ILD. Multivariate analysis with stepwise variable selection, serum surfactant protein (SP)-A (OR (odds ratio), 1.026; 95%CI (confidence interval), 1.003–1.050; P = 0.024) and inflammation index calculated from HRCT findings (OR, 1.358; 95%CI, 1.079–1.709; P = 0.009) were significant predictors of an NHS. Serum SP-A offered 85% sensitivity and 75% specificity for predicting NHS at an optimal cut-off of 45.8 ng/mL. Serum SP-A concentrations correlated positively with inflammation index (r = 0.344, P = 0.015). In conclusion, serum SP-A might serve as a surrogate biomarker for predicting an NHS in patients with ILD.

Sasa veitchii and other Sasa species are traditional medicinal herbs belonging to a group of Japanese bamboos collectively called Kumazasa, and these species possess the potential for a wide variety of uses. The present study aimed to elucidate the anticancer mechanisms exerted by S. veitchii extract (SE) against a human breast cancer cell line, MCF-7 cells. Freeze-dried Sunchlon^® was used as the SE, and cell proliferation activity was measured using the [³H]-thymidine incorporation assay. Induction of apoptosis was assessed via Annexin V and caspase-3 fluorescent staining, the induction of necrosis was measured via propidium iodide staining, and cell cycle-related protein expression was determined using western blot-ting. The IC₅₀ value of the SE was 7.7 μg/mL in MCF-7 cells. Although the primary active ingredient in Sunchlon^® is sodium copper chlorophyllin (0.25%), the present results indicated that ingredients other than SCC exert anti-cancer activities (the IC50 value of SCC was 715 μg/mL), and late apoptosis or necrosis was induced in an SE dose-dependent manner. The expression levels of cyclin D1 and Cdk6 were decreased after SE treatment, and there was no change in the Cdk1/2 expression levels. Additionally, the expression of the necrosis-related cell death indicators RIP1 and RIP3 was increased in response to high-dose SE treatments, and this was indicative of cells preparing for programmed cell death. SE induces cell death in MCF-7 cells via the inhibition of cyclin D1 expression at low concentrations, and this extract induces programmed necrosis (necroptosis) by potentiating RIP1/RIP3 expression.

Cisplatin is an important drug for the treatment of head and neck squamous cell carcinoma (HNSCC). Determining chemoresistant factors prior to treatment will lead to great benefits for clinicians and patients. Here, we evaluated chemoresistant factors by integrating proteomic and transcriptomic data using HNSCC cell lines to identify a more precise chemoresistant factor in HNSCC. We used four HNSCC cell lines: cisplatin-sensitive, acquired cisplatin resistance, naturally cisplatin-resistant, and acquired 5-FU resistance. Proteomic analysis was performed using iTRAQ, tandem mass spectrometry, and liquid chromatography-electrospray ionization-tandem mass spectrometry. Transcriptomic analysis was performed using microarrays. By integrating these independent data, common factors were addressed and functional analysis was performed using small interfering RNAs (siRNAs) to change the chemosensitivity. Using iTRAQ analysis, 7 proteins were identified as specific for cisplatin chemoresistance factors. Transcriptomic analysis revealed hundreds of potential candidate factors. By combining and integrating these data, S100A2 was identified as a potential cisplatin-specific chemoresistance factor. Functional analysis with siRNA revealed that the expression of S100A2 was reduced and cisplatin sensitivity recovered in the acquired and naturally cisplatin-resistant cell lines, but not in the cisplatin-sensitive cell lines. S100A2 was identified as a cisplatin-specific chemoresistance factor by integrating the transcriptomic and proteomic results obtained using HNSCC cell lines. This is a novel technique that allows for a precise identification, also known as a comprehensive analysis. Our findings indicate that these proteins could be used as biomarkers of HNSCC treatments, providing physicians with new treatment strategies for patients with HNSCC, showing chemoresistance.

This study aimed to identify the elderly generation with the worst prognoses for high-grade astrocytoma and find independent predictors of good outcomes. We conducted a retrospective analysis of 91 patients, ≥65 years old, with anaplastic astrocytoma or glioblastoma. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method and compared using log-rank test or multivariate Cox regression analysis. We included 21 (23%) and 70 (77%) patients aged 65–69 years and ≥70 years. In the two generations, significant differences were found in the Charlson comorbidity index, extent of resection, chemoradiotherapy (CRT) as adjuvant therapy, and radiation dose (all P < 0.05). The median PFS was 9.9 and 6.9 months in patients aged 65–69 and ≥70 years (P = 0.10). The median OS was 22.8 and 11.6 months in patients aged 65–69 and ≥70 years (P = 0.009). In the multivariate analyzes in patients ≥70 years, only postoperative Karnofsky performance status (KPS) scores ≥70 were significantly related to prolonged PFS (hazard ratio [HR]: 0.48, P = 0.04), and postoperative KPS, CRT as adjuvant therapy, and salvage therapy were significantly related to prolonged OS (HR: 0.45, P = 0.03, HR: 0.38, P = 0.002, and HR: 0.43, P = 0.01, respectively). In conclusion, in patients ≥70 with high-grade astrocytoma, OS was significantly shorter compared to those aged 65–69. Postoperative KPS score was significantly related to prolonged PFS and OS. Postoperative CRT and salvage therapy at recurrence may be effective in the selected elderly.

Diarrhea is the second leading cause of under-five mortality and globally accounts for 526,000 child deaths every year. Afghanistan, with 33,000 child deaths in 2012, was ranked 8^th among nations, with the highest under-five deaths being from pneumonia and diarrhea. This study aimed to identify the determinants of diarrhea in children under the age of five in Afghanistan. A secondary data analysis of the Afghanistan Demographic and Health Survey (AfDHS) 2015 was focused on diarrhea in children under the age of five. The dataset of the AfDHS 2015 was used for the analysis. The subjects for this study were 30,238 under-five children. A logistic regression model was applied to examine the determinants of childhood diarrhea. This study found that 7,921 (26.2%) out of 30,238 under-five children had diarrhea within the two weeks preceding the survey. Higher maternal education accompanied a lower risk of childhood diarrhea with an adjusted odds ratio (AOR) of 0.70 (P<0.01) than did no education. Flush toilets (AOR=0.84, P<0.01) and traditional dry vaults (AOR=0.83, P<0.001) were less likely associated with diarrhea compared with pit latrines. Tube wells, public taps, and unprotected wells and springs were sources of drinking water with a higher risk of diarrhea than piped water. This study identified that the type of toilet facility, source of drinking water, age of the child, and maternal education were important determinants of under-five diarrhea. Intervention programs concerning improved sanitation facilities, sources of drinking water, and raising women’s level of education and health awareness are important.

We describe a case of internal trapping including the vasa vasorum for a thrombosed giant rapidly growing posterior cerebral artery aneurysm and performing a detailed analysis. A 48-year-old woman was followed up in our hospital for a thrombosed large posterior cerebral artery aneurysm located in the P2 segment. She initially presented after experiencing a sudden headache on two occasions. Head computed tomography and magnetic resonance imaging indicated a larger aneurysm than before. Digital subtraction angiography with balloon occlusion test was assessed, and internal trapping was sequentially conducted. We detected that the vasa vasorum originated from the posterior temporal artery. Therefore, we embolized the posterior temporal artery including the vasa vasorum using N-butyl-2-cyanoacrylate and Lipiodol. Next, the anterior temporal artery was embolized with N-butyl-2-cyanoacrylate and Lipiodol, posterior temporal artery P3 segment and the aneurysm and finally the proximal P2 segment were embolized with coils. Final vertebral and internal carotid angiography showed complete obliteration of the aneurysm. On the day after the procedure her paresis worsened and she developed left upper quadrantanopia, however was finally discharged with no hemiparesis. We reported a case of a rapidly growing thrombosed giant posterior cerebral artery aneurysm treated by parent artery occlusion including the vasa vasorum with detailed image analysis.

Dermal sinus tracts (DSTs) of the cervical and thoracic spine are extremely rare, particularly in adult patients because diagnosis is typically made in the early stage after birth by pediatricians. These cases should be treated surgically as soon as possible to prevent neurological sequelae. This report describes two rare adult cases with cervical and thoracic spine DSTs. The first patient presented with back pain and headache, whose skin lesion had been long known, but disregarded since birth. The second patient had long suffered from residual cervical myelopathy from the prior incomplete surgical treatment. Both cases had these sinus tracts excised completely and had spinal cord untethered successfully without any neurological deterioration. There has been a trend toward earlier diagnosis of these entities, but still some cases that were diagnosed in a delayed fashion or underwent incomplete treatment are reported. Improper management during childhood could lead to irreversible neurological deficit caused by spinal cord tethering and/or direct compression due to DSTs-associated tumors. The early detection and prompt surgical intervention improve the chance of a good surgical outcome. Furthermore, complete excision of the sinus tracts and associated tumors could help prevent future bacterial contamination and recurrence.

A 65-year-old woman died of congestive heart failure and diabetes mellitus. She had a history of mild anemia since adolescence, but received neither iron supplementation nor transfusion. The cirrhotic liver obtained at autopsy contained a large amount of iron. The heart and pancreas also had excess iron. Her iron overload may be due to excess iron absorption in the gut because of the absence of an iatrogenic background such as transfusion or iron supplementation.

A 46-year-old Japanese woman visited a nearby hospital because of diplopia after flu-like symptoms. One month later, she presented with blepharoptosis and external ophthalmoplegia. Laboratory tests showed a high creatine kinase concentration (3146 U/L). She underwent intravenous immunoglobulin therapy; however, her symptoms did not improve, prompting transfer to our institute. On admission, transthoracic echocardiography revealed 30% of left ventricular ejection fraction and edema of the left ventricular wall. Coronary angiography showed no significant coronary stenosis. An endomyocardial biopsy resulted in a diagnosis of acute myocarditis. On the following day, she needed a temporary pacemaker because she had complete atrioventricular block and intra-aortic balloon pump because of cardiogenic shock. Intravenous immunoglobulin therapy was again administered and her cardiac function gradually recovered. She was successfully weaned off her temporary pacemaker and intra-aortic balloon pump on Day 5 after improvement in her complete atrioventricular block. Steroid therapy administered from Day 9 was effective in reducing her creatine kinase concentrations. However, contrast-enhanced magnetic resonance imaging revealed inflammation of the scalene, semispinalis cervicis, sternocleidomastoid, and intercostal muscles. On Day 25, her cardiac function had recovered to a left ventricular ejection fraction of 59%. Finally, she was successfully discharged on Day 45 after undergoing rehabilitation.

Sjögren syndrome (SS) is one of several collagen vascular diseases that occasionally involve the central nervous system. We report two cases of SS involving young patients who initially presented with aseptic meningitis. A male with recurrent AM was found to have anti-Ro/SSA and La/SSB antibodies in a screening test for autoimmune process. A minor salivary gland biopsy revealed lymphocytic infiltrations compatible with SS, although the patient did not exhibit sicca symptoms. A female presenting with AM and polyarthritis also reported xerophthalmia. Anti-Ro/SSA antibody testing and a positive result in a minor salivary gland biopsy led to the diagnosis of SS. In the literature review, we found that AM or aseptic meningoencephalitis (AME) preceded or had a concomitant onset with SS in approximately 70% of cases. Screening for anti-Ro/SSA antibody, as well as systemic assessment for rheumatic symptoms, may be useful for diagnosing AM/AME of unknown etiology.