H-intensity scale score to estimate CSF GluN1 antibody titers with one-time immunostaining using a commercial assay.

Introduction: Anti-NMDA receptor encephalitis is an autoimmune disorder caused by autoantibodies (abs) against the conformational epitope on GluN1 subunits. GluN1-abs have been determined with cell-based assay (CBA) co-expressing GluN1/GluN2 subunits. However, commercial fixed CBA expressing only GluN1 subunit has increasingly been used in clinical practice. The ab titers can be determined with serial dilutions, but its clinical significance remains unclear. We aimed to develop an H-intensity scale (HIS) score to estimate GluN1-ab titers in cerebrospinal fluid (CSF) with one-time immunostaining using both commercial CBA and immunohistochemistry and report its usefulness. "H" is the initial of a patient with high CSF GluN1-ab titers (1:2,048). Methods: We first determined the reliability of CBA in 370 patients with suspected autoimmune encephalitis by comparing the results between commercial CBA and established assay in Dalmau's Lab. Then, we made positive control panels using the patient H's CSF diluted in a fourfold serial dilution method (1:2, 1:8, 1:32, 1:128, 1:512, and 1:2,048). Based on the panels, we scored the intensity of ab reactivity of 79 GluN1-ab-positive patients' CSF (diluted at 1:2) on a scale from 0 to 6 (with ≥1 considered positive). To assess inter-assay reliability, we performed immunostaining twice in 21 patients' CSF. We investigated an association between the score of CSF obtained at diagnosis and the clinical/paraclinical features. Results: The sensitivity and specificity of CBA were 93.7% (95% CI: 86.0-97.3) and 98.6% (95% CI: 96.5-99.5), respectively. Linear regression analysis showed a good agreement between the scores of the first and second assays. Patients with a typical spectrum, need for mechanical ventilation support, autonomic symptoms/central hypoventilation, dyskinesias, speech dysfunction, decreased level of consciousness, preceding headache, ovarian teratoma, and CSF leukocyte count >20 cells/µL had a higher median HIS score than those without, but HIS score was not associated with sex, age at onset, or seizure. HIS score at diagnosis had a significant effect on 1-year functional status. Discussion: The severity of disease and four of the six core symptoms were associated with higher GluN1-ab titers in CSF at diagnosis, which may play a role in poor 1-year functional status. An incomplete phenotype can be attributed to low CSF GluN1-ab titers.

Elevation in body temperature may increase susceptibility to cortical spreading depression in a rat model.

One characteristic of migraine is recurrent headache attacks, which are known to be induced by changes in climatic variables such as atmospheric pressure, humidity, and outside temperature. However, the relationship between temperature changes and migraine remains unclear. Therefore, we investigated the relationship between body temperature changes and cortical spreading depression (CSD) using KCl-induced rat models of CSD. We initially induced CSD under controlled conditions at a room temperature of 28°C on an operating table maintained at 37°C. Subsequently, we controlled the operating table temperature to induce a second round of CSD under conditions of either a 10 ± 1% increase or decrease in body temperature. We ensured 1 h rest period between the first and second inductions of CSD. The results indicated that the number of CSDs significantly increased after body temperature elevation (before, 8.8 ± 1.2 times vs. after, 13.4 ± 1.3 times; p = 0.0003). The mean percentage change in cerebral blood flow decreased after body temperature increased (before, 33.1 ± 2.4% vs. after, 18.2 ± 1.4%; p = 0.006). There were no significant changes in CSD after body temperature decreased. The susceptibility of the cortex to CSD may increase under conditions of elevated body temperature.

Classification of odors associated with migraine attacks: a cross-sectional study.

Migraine, a common primary headache disorder, is associated with various factors such as stress, hormones in women, fasting, weather, and sleep disturbance as well as odors. We aimed to categorize odors associated with migraine and explore their relationships with clinical characteristics. A total of 101 migraineurs answered a questionnaire to determine the odors associated with migraine attacks. We performed factor analysis to explore the common factors of the odors and the relationship between these factors and the clinical characteristics. The factor analysis estimated six common factors: factor 1, fetid odor; factor 2, cooking products; factor 3, oil derivatives and others; factor 4, shampoo and conditioner; factor 5, cleaning products; factor 6, perfumes, insecticides, and rose. Factor 5 also included hair styling preparations, laundry detergent, and fabric softener, usually those with floral fragrances, and factor 5 was more likely to be associated with migraine attacks in patients with chronic migraine than in those with episodic migraine (P = 0.037). Our study showed that odors associated with migraine attacks could be categorized into six groups and suggested that some chemicals were more likely associated with migraine attacks in patients with chronic migraine than in those with episodic migraine.

An alternative option of the retroperitoneal laparoscopic approach for limited hepatectomy for recurrent hepatocellular carcinoma at the transected edge after previous hepatectomy.

Laparoscopic hepatectomy is safely performed with minimal invasiveness on patients with recurrent liver tumors after previous hepatectomy. However, it is still difficult to dissect and expose the operative field at the transected edge or plane after open right hepatectomy, even for limited resection by a laparoscopic approach, due to severe adhesion to the surrounding peritoneum or organs. We herein applied the retroperitoneal laparoscopic approach to limited resection of the dorsal surface at the transected edge of Couinaud's segment 6 after previous repeated hepatectomies in a patient with recurrent hepatocellular carcinoma (HCC) by avoiding severe intra-abdominal adhesion. We safely resected recurrent HCC via the retroperitoneal space. This approach is a useful and alternative option for laparoscopy which minimizes the dissecting time and avoids organ injury on the right side of the transected area of the liver after hepatectomy in patients with liver malignancies.

Retroperitoneal-first dissection approach at the dorsal space for a huge serous cystic neoplasm of the pancreatic tail: a case report.

BACKGROUND: Large tumors of serous cystic adenomas in the pancreatic body-to-tail severely compress the surrounding organs and retroperitoneal space. CASE PRESENTATION: We present a unique surgical challenge for distal pancreatectomy (DP). We present the case of a patient who had a massive mass lesion measuring more than 20 cm in size that had been misdiagnosed as a retroperitoneal tumor by the previous hospital. However, an expert radiologist at our institute diagnosed serous cystadenoma of the pancreas based on imaging characteristics. We decided to perform retroperitoneal space first dissection using a small incision because we were concerned about tumor infiltration or compressive adhesions in important retroperitoneal vessels. We safely attempted distal pancreatectomy by limiting the laparotomy incision step-by-step while securing the main vascular injury of the retroperitoneum. In addition to the ordinary cooperation with urological surgeons, this technique is referred to by the concept of retroperitoneal procedures for minimally invasive surgery in urology. CONCLUSIONS: This approach is useful for lifting resected specimens by prior and wide retroperitoneal dissection, which may lead to safety and the prevention of unexpected vascular injury.

Prognostic Value of Repeat Hepatectomy for Hepatocellular Carcinoma Patients.

BACKGROUND/AIM: The potential for repeat hepatectomy has been increasing in hepatocellular carcinoma (HCC) patients. PATIENTS AND METHODS: To assess its significance, we examined the clinical features, surgical records, and survival of 279 HCC patients who underwent hepatectomy as primary treatment. Patients were divided into three groups: single hepatectomy without HCC relapse in 97 patients (Group 1), single hepatectomy with HCC relapse in 133 patients (Group 2) and repeat hepatectomy for HCC relapse in 49 patients (Group 3). Group 3 was divided into three subgroups. Multiple, larger size (>5 cm), and confluent nodular HCC. RESULTS: Child-Pugh B patients were significantly higher in Group 2 (p<0.01). The prevalence of histological vascular involvement was significantly higher in Group 2 than in the other groups (p<0.01). Although Group 2 showed significantly poorer survival (p<0.01), the 10-year overall survival in Groups 1 and 3 was over 70% but not different between groups. The relapse-free survival period was significantly correlated with overall survival, and patients with a cancer-free period of over 36 months showed significantly better 10-year survival rates than those with a period of less than 36 months (p<0.01). Patients undergoing 3 or more repeat hepatectomies also showed good survival periods. CONCLUSION: Careful follow-up and proper decision-making in terms of repeat hepatectomy with multimodal treatments including novel chemotherapies upon assessment of postoperative tumor relapse are important in HCC patients to prolong survival.

Relationship of immunonutritional factor with changes in liver volume after portal vein embolization.

Background: To identify predictors of changes in hepatic volumes after portal vein embolization, we examined the relationship with preoperative nutritional and immunological parameters. Patients and Methods: Ninety-three patients who underwent portal vein embolization were included. The control group comprised 13 patients who underwent right hepatectomy without portal vein embolization. Computed tomographic volumetric parameter was measured for changes in embolized and nonembolized liver. Correlation with various candidates of immunonutritional parameters was examined. Results: Difference in increased liver ratio was 9.1%. C-reactive protein levels significantly increased after portal vein embolization (P < .01), whereas albumin and total cholesterol levels significantly decreased, respectively (P < .01). The C-reactive protein/albumin ratio, prognostic nutritional index, Controlling Nutritional Status score, and modified Glasgow Prognostic Score were significantly different, respectively (P < .01). Prothrombin activity and total cholesterol level significantly correlated with the increased change in nonembolized liver (P < .05). The C-reactive protein and C-reactive protein/albumin ratio after portal vein embolization negatively correlated with hypertrophic ratio (P < .05). By comparing posthepatectomy outcomes between 64 patients undergoing portal vein embolization and 13 who did not, the prevalence of severe complications and mortality in the portal vein embolization group was not different from that in the non-portal vein embolization group. Liver activity at 15 minutes > 0.92 and increased liver volume ≥ 10% tended to correlate with lower prevalence of severe complications. Only increased intraoperative blood loss ≥ 1,500 mL was significantly associated with morbidity and mortality (P < .05). Conclusion: Contrary to our hypothesis, immunonutritional parameters, except C-reactive protein and C-reactive protein/albumin ratio, did not reflect hypertrophy after portal vein embolization. Although it is difficult to predict the hypertrophic degree, the strategy of scheduled hepatectomy should be switched in case of impaired inflammatory status after portal vein embolization.

Liver hanging maneuver is suitable in major hepatectomy for liver malignancies over 5 cm.

Objectives: Hepatic transection through an anterior approach is required to successfully complete anatomical hepatectomy for large liver malignancies. The liver hanging maneuver (LHM) is an alternative procedure for transection on an adequate cut plane and may reduce intraoperative bleeding and transection times. Material and Methods: We examined the medical records of 24 patients with large liver malignancies (>5 cm) who had undergone anatomical hepatic resection with LHM (n= 9) or without LHM (n= 15) between 2015 and 2020. Patient demographics, preoperative hepatic function, surgical records, and post-hepatectomy outcomes were retrospectively compared between the LHM and non-LHM groups. Results: The prevalence of tumors >10 cm was significantly higher in the LHM group than in the non-LHM group (p <0.05). Furthermore, LHM was significantly performed to right and extended right hepatectomies in the background normal liver (p <0.05). Although transection times did not significantly differ between the two groups, the amount of intraoperative blood loss was slightly lower in the LHM group than in the non-LHM group (1.566 mL vs. 2.017 mL), and blood transfusion was not needed for patients in the LHM group. Post-hepatectomy liver failure and bile leakage were not observed in LHM. However, the length of hospitalization was slightly shorter in the LHM group than in the non-LHM group. Conclusion: LHM is useful for transecting an adequately cut plane in hepatectomy for liver tumors over 5 cm-in-size located on the right side and achieves better outcomes.

Neuronal surface antigen-specific immunostaining pattern on a rat brain immunohistochemistry in autoimmune encephalitis.

A variety of neuronal surface (NS) antibodies (NS-Ab) have been identified in autoimmune encephalitis (AE). Tissue-based assay (TBA) using a rodent brain immunohistochemistry (IHC) is used to screen NS-Ab, while cell-based assay (CBA) to determine NS antigens. Commercial rat brain IHC is currently available but its clinical relevance remains unclear. Immunostaining patterns of NS antigens have not been extensively studied yet. To address these issues, we assessed a predictive value of "neuropil pattern" and "GFAP pattern" on commercial IHC in 261 patients, and characterized an immunostaining pattern of 7 NS antigens (NMDAR, LGI1, GABAaR, GABAbR, AMPAR, Caspr2, GluK2). Sensitivity and specificity of "neuropil pattern" for predicting NS-Ab were 66.0% (95% CI 55.7-75.3), and 98.2% (95% CI 94.8-99.6), respectively. False-positive rate was 1.8% (3/164) while false-negative rate was 34.0% (33/97). In all 3 false-positive patients, neuropil-like staining was attributed to high titers of GAD65-Ab. In 33 false-negative patients, NMDAR was most frequently identified (n=18 [54.5%], 16/18 [88.9%] had low titers [< 1:32]), followed by GABAaR (n=5). Of 261 patients, 25 (9.6%) had either GFAP (n=21) or GFAP-mimicking pattern (n=4). GFAP-Ab were identified in 21 of 31 patients examined with CBA (20 with GFAP pattern, 1 with GFAP-mimicking pattern). Immunostaining pattern of each NS antigen was as follows: 1) NMDAR revealed homogenous reactivity in the dentate gyrus molecular layer (DG-ML) with less intense dot-like reactivity in the cerebellar granular layer (CB-GL); 2) both GABAaR and GluK2 revealed intense dot-like reactivity in the CB-GL, but GABAaR revealed homogenous reactivity in the DG-ML while GluK2 revealed intense reactivity along the inner layer of the DG-ML; and 3) LGI1, Caspr2, GABAbR, and AMPAR revealed intense reactivity in the cerebellar ML (CB-ML) but LGI1 revealed intense reactivity along the middle layer of the DG-ML. Whereas, Caspr2, GABAbR, and AMPAR revealed similar reactivity in the DG-ML but some difference in other regions. TBA is useful not only for screening NS- or GFAP-Ab but also for estimating NS antigens; however, negative results should be interpreted cautiously because "neuropil pattern" may be missed on commercial IHC when antibody titers are low. Antigen-specific immunoreactivity is a useful biomarker of AE.

Status epilepticus suspected autoimmune: Neuronal surface antibodies and main clinical features.

OBJECTIVES: Status epilepticus (SE) can be associated with neuronal surface antibodies (NS-Abs) but NS-Ab detection rate remains unknown in patients with SE of unclear etiology at symptom presentation but suspected of having an autoimmune etiology (SE suspected autoimmune). We aimed to determine the NS-Ab detection rate and the clinical features that predict the presence of NS-Abs in patients with SE suspected autoimmune. METHODS: We retrospectively reviewed the clinical information of 137 patients with SE suspected autoimmune who underwent testing for NS-Abs between January 2007 and September 2020. NS-Abs were examined in both serum and cerebrospinal fluid (CSF) obtained at symptom onset with established assays. We classified brain magnetic resonance imaging (MRI) findings into unremarkable, autoimmune limbic encephalitis (ALE) (bilateral abnormalities highly restricted to the medial temporal lobes), ALE-Plus (ALE pattern and additional extramedial temporal lobe abnormalities), multifocal cortico-subcortical (MCS), or other pattern. We compared the clinical features between patients with and without NS-Abs. RESULTS: Forty-four patients (32.1%) had NS-Abs, including 35 N-methyl-d-aspartate receptor (NMDAR) (one with concurrent γ-aminobutyric acid B receptor [GABAbR] and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor [AMPAR]), 5 γ-aminobutyric acid A receptor (GABAaR), 2 leucine-rich glioma-inactivated 1(LGI1), 1 GABAbR, and 1 unknown antigens. Compared with NS-Ab-negative patients, NS-Ab-positive patients were more likely to have a preceding headache (56.8% vs 26.7%), preceding psychobehavioral or memory alterations (65.9% vs 20.4%), involuntary movements (79.5% vs 16.1%), CSF pleocytosis (81.8% vs 62.0%), elevated immunoglobulin G (IgG) index (45.2% vs 15.6%), oligoclonal bands (51.5% vs 9.5%), tumor (47.7% vs 8.6%), and higher APE2 score (median of 9 vs 7), and they were less likely to have an ALE-Plus pattern (2.3% vs 23.7%). However, preceding fever and ALE or MCS pattern were not different between the two groups of patients. SIGNIFICANCE: When an autoimmune etiology was suspected, there was a relatively high likelihood (one of three patients) of identifying NS-Abs. Some clinical features (preceding symptoms, inflammatory CSF) predict a higher likelihood of finding NS-Ab positivity, but the ALE-Plus MRI pattern is more likely suggestive of NS-Ab negativity.

The Ball Technique for Peri-implant Soft Tissue Augmentation Using a Xenogeneic Collagen Matrix: A Technical Report.

In the maxillary anterior region, augmentation to correct a soft tissue deficiency is often required for an esthetic outcome and long-term implant therapy success. This case series of three patients presents a novel approach for soft tissue augmentation using xenogeneic collagen matrix balls in the esthetic zone around the implants. This technique avoids a secondary donor site compared to autogenous connective tissue graft. With this technique, a horizontal soft tissue volume increase (range: 3 to 5 mm) was observed postsurgically and maintained at later follow-ups. The described ball technique offers a viable method for peri-implant mucosal augmentation in the maxillary anterior region.

Asymptomatic acute ischemic lesions in intracerebral hemorrhage: Its frequency, MRI features, and risk factors.

BACKGROUND: Asymptomatic acute ischemic lesions (AIL) may be coincidentally found on brain magnetic resonance imaging (MRI) obtained during the acute phase of intracerebral hemorrhage, but its clinical significance has yet to be determined. The objective of this study is to determine the frequency of asymptomatic AIL, its characteristic features of brain MRI and risk factors in patients with acute intracerebral hemorrhage. METHODS: We retrospectively reviewed the clinical information of 108 patients with intracerebral hemorrhage who underwent brain MRIs within 30 days of hospitalization between April 2013 and January 2018. We determined the frequency of asymptomatic AIL, its brain MRI features, and risk factors. RESULTS: AIL was found in 26 of 108 patients; symptomatic in 2 and asymptomatic in 24 (22.2%). Asymptomatic AIL were small, multiple, mainly distributed to the white matter in the anterior circulation (22/24, 91.7%), and occasionally seen in deep watershed areas (15/24, 62.5%). Only 2 patients had severe major vessel stenosis. Asymptomatic AIL was associated with high mean blood pressure (BP) on admission (> 145 mmHg), excessive drug-induced reduction in mean BP (≥ 55 mmHg), and large hemorrhage (> 31 mL in volume). CONCLUSIONS: Asymptomatic AIL were found in 22.2% of patients with intracerebral hemorrhage within 30 days of hospitalization. Asymptomatic AIL were often small, multiple and occasionally developed in deep watershed areas despite the absence of major vessel stenosis. High mean BP on admission, excessive drug-induced BP reduction, and larger hemorrhage may be a risk factor for development of asymptomatic AIL.

Endoscopic filling with polyglycolic acid sheets and fibrin glue of persistent fistula after esophagectomy.

BACKGROUND: Treatment of anastomotic leakage in reconstruction after esophagectomy remains challenging. This report presents a new endoscopic filling method for persistent fistula after failure of conservative treatment of leakage caused by anastomotic insufficiency. METHODS: 10 of 14 patients, in whom post-esophagectomy leakage had failed to resolve after 2 weeks of conservative treatment, underwent endoscopic filling with polyglycolic acid (PGA) sheet and fibrin glue into the anastomotic leakage site, using a delivery tube and endoscopic catheter, respectively. RESULTS: Each patient underwent jejunostomy, to secure nutrition. The leakage was resolved in all 10 patients. The mean number of PGA - fibrin glue procedures was 1.7. The mean period from the first application to the resumption of oral intake was 31.6 days, from the final application it was 14.7 days. CONCLUSIONS: The reported filling method offers a new endoscopic approach for persistent fistula after esophagectomy when conservative treatment of leakage has failed.

Clinically based score predicting cryptogenic NORSE at the early stage of status epilepticus.

OBJECTIVE: To determine whether a clinically based score predicts cryptogenic new-onset refractory status epilepticus (C-NORSE) at the early stage of status epilepticus (SE) with prominent motor symptoms (SE-M) of unclear etiology. METHODS: The score (range 0-6) included 6 clinical features: highly refractoriness to antiseizure drugs, previously healthy individual, presence of prodromal fever, absence of prodromal psychobehavioral or memory alterations, absence of dyskinesias, and symmetric brain MRI abnormalities (the first 2 mandatory). We retrospectively assessed the usefulness of a high scale score (≥5) in predicting C-NORSE in 83 patients with SE-M of unclear etiology, who underwent testing for neuronal surface antibodies (NS-Abs) between January 2007, and December 2019. RESULTS: Thirty-one (37.3%) patients had a high score. Patients with a high score had more frequent prodromal fever (28/31 vs 24/52), mechanical ventilatory support (31/31 vs 36/52), and symmetric MRI abnormalities (26/31 vs 12/52), had less frequent involuntary movements (2/31 vs 30/52), and had absent prodromal psychobehavioral alterations (0/31 vs 27/52), CSF oligoclonal band detection (0/27 vs 11/38), tumor association (0/31 vs 13/52), or NS-Abs (0/31 vs 29/52) than those with a low score (<5). Thirty-three patients (median age, 27 years; 18 [54.5%] female) were finally regarded as C-NORSE. The sensitivity and specificity of a high score for predicting C-NORSE were 93.9% (95% CI 0.87-0.94) and 100% (95% CI 0.95-1.00), respectively. CONCLUSIONS: Patients with a high score in the indicated scale are more likely to have C-NORSE, making it a useful diagnostic tool at the early stage of SE-M before antibody test results become available.

Differences in clinical features of cluster headache between drinkers and nondrinkers in Japan.

OBJECTIVE: Alcohol has been recognized as the main trigger for a cluster headache attack, but clinical features to distinguish between cluster headache in drinkers and nondrinkers are unclear. Thus, the present study aimed to investigate the differences in clinical features of cluster headache between drinkers and nondrinkers. METHODS: This retrospective, observational study compared the clinical features of cluster headache between drinkers and nondrinkers among patients who were diagnosed with cluster headache between November 2004 and April 2018 at the Japanese Red Cross Shizuoka Hospital. Demographic and clinical data were collected from medical records and/or by patient interview. RESULTS: Of 131 patients, 98 (75%) were drinkers, and 33 (25%) were nondrinkers. Compared with nondrinkers, drinkers had significantly more frequent conjunctival injection (43% vs. 21%, p = 0.037) but significantly less frequent nasal congestion (31% vs. 52%, p = 0.0037), vomiting (11% vs. 30%, p = 0.014), and photophobia (29% vs. 45%, p = 0.008). CONCLUSION: Among individuals with cluster headache, the frequencies of conjunctival injection, nasal congestion, vomiting, and photophobia were different between drinkers and nondrinkers. These results suggested that drinking might influence the responses of the cranial autonomic reflex with respect to conjunctival injection or nasal congestion.

A rare case of rectal cancer with perianal metastasis: a case report.

BACKGROUND: Cancer metastasis from colon cancer to an anal fistula is very rare. We herein reported a rare case in which local excision was performed for metastatic anal fistula cancer originating from rectal cancer. CASE PRESENTATION: A 68-year-old man was referred to our institution with a diagnosis of rectal cancer. He had complained of anal fistula for 5 years. Based on a recent history of cerebral infarction, Hartmann's operation was performed to treat the rectal cancer after the administration of preoperative chemotherapy for 3 months. However, 1 month after Hartmann's operation, the anal fistula was found to have worsened. Pelvic magnetic resonance imaging (MRI) revealed tumor formation at the perianal lesion. Metastatic anal fistula cancer originating from the rectal cancer was diagnosed based on the examination of the biopsied tissue. We selected local excision because the anal tumor had not invaded the surrounding tissue. There has been no recurrence in the 31 months after the curative operation. CONCLUSION: Metastatic cancer should be ruled out when treating left-sided colon cancer with anal fistula. Local excision is one possible treatment for metastatic anal fistula cancer.

Correction to: A cluster of disseminated small cortical lesions in MELAS: its distinctive clinical and neuroimaging features.

The author would like to correct the errors in the publication of the original article. The corrected details are given below for your reading.

A cluster of disseminated small cortical lesions in MELAS: its distinctive clinical and neuroimaging features.

OBJECTIVES: To investigate a diversity of stroke-like episodes (SLEs) in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and report a disseminated form of SLEs (D-SLEs) attributed to a cluster of disseminated small cortical lesions. METHODS: We retrospectively reviewed the clinical information of 27 MELAS patients seen at Kitasato University Hospital between January 1990 and April 2018. Among those, we selected 13 patients with m.3243A>G mutation [median age at onset, 35 years (11-68 years), two pediatric onset < 17 years] who had at least one SLE. SLEs were classified into classic or non-classic based on characteristic features of stroke-like lesions. RESULTS: 44 SLEs were identified during a median observational period of 119 months (3-240 months). Among those, 29 (65.9%) were classic SLEs (C-SLEs) mainly attributed to a single continuous lobular lesion incongruent to vascular territory and occasionally accompanied by a gradual spread associated with hyperperfusion and persistent seizure activity. The remaining 15 were non-classic attributed to sparsely distributed (n = 10), disseminated (n = 4) or cerebellar lesions (n = 1). C-SLEs developed in all patients but non-classic SLEs in 5; D-SLEs developed in 4 patients accounting for 4 of 44 SLEs (9.1%). Non-classic SLEs developed more frequently in pediatric-onset than in adult-onset patients (12/15 vs. 3/29, p < 0.0001). SLEs began with acute onset of symptoms in 42 SLEs (95.5%), but D-SLEs of 2 adult-onset patients began with ill-defined subacute-onset fluctuating encephalopathy. CONCLUSIONS: This study showed a diversity of SLEs in patients with m.3243A>G mutation. Further studies are required to elucidate the pathophysiological mechanisms of non-classic SLEs including D-SLEs.

Autoimmune Encephalitis as an Extra-articular Manifestation of Rheumatoid Arthritis.

Autoimmune encephalitis (AE) is an immune-mediated encephalitis characterized by the subacute onset of memory deficits, altered mental status, or psychiatric symptoms. Limbic encephalitis associated with rheumatoid arthritis (RA) has not been reported yet. A 57-year-old man presented with the subacute onset of headache, depression, and anorexia 7 months before the onset of RA. Brain magnetic resonance imaging showed symmetric parenchymal lesions involving the medial temporal lobes. He was diagnosed with RA and AE, but no autoantibodies to neuronal intracellular or cell-surface antigens were identified in either the serum or cerebrospinal fluid. His symptoms improved with immunotherapy. AE can develop as an extra-articular manifestation of RA.

Prodromal headache in anti-NMDAR encephalitis: An epiphenomenon of NMDAR autoimmunity.

OBJECTIVE: To investigate the nature of prodromal headache in anti-NMDA receptor (NMDAR) encephalitis. METHODS: Retrospective review of the clinical information of 39 patients with anti-NMDAR encephalitis admitted between January 1999 and September 2017. Five patients with an atypical presentation were excluded. Thus, in 34 patients (median 27 years [range, 12-47 years]; 28 [82%] female), the clinical features were compared between patients who initially reported headache and those who did not report. RESULTS: Twenty-two patients (65%) reported headache either transiently (n = 5) or continuously (n = 17). Encephalitic symptoms (psychobehavioral memory alterations, seizure, dyskinesias, or altered level of consciousness) developed in 20 patients with median 5.5 days (range, 1-29 days) after headache onset. In one patient, NMDAR antibodies were detected in CSF 3 days after headache onset. Patients with headache had more frequently fever (14/22 [64%] vs. 2/12 [17%] p = 0.013) and higher CSF pleocytosis (median white blood cells 79/µl [range, 6-311/µl] vs. 30/µl [range, 2-69/µl], p = 0.035) than those without headache, but there was no difference in gender, age at onset, seizure, migraine, CSF oligoclonal band detection, elevated IgG index, tumor association, or brain MRI abnormalities between them. CONCLUSIONS: Headache often developed with fever and pleocytosis, but it was rapidly replaced by psychiatric symptoms. Based on current knowledge on the antibody-mediated mechanisms that cause a decrease of synaptic NMDAR through crosslinking and internalization leading to a state mimicking "dissociative anesthesia," we speculated that prodromal headache is not likely caused by direct effect of the autoantibodies but rather meningeal inflammation (noninfectious aseptic meningitis) that occurs in parallel to intrathecal antibody synthesis as an epiphenomenon of NMDAR autoimmunity. Psychobehavioral alterations following headache is an important clue to the diagnosis.