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.

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.

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.

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.

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.

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.

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.

Feasible and promising modified trans-subxiphoid thoracoscopic extended thymectomy for patients with myasthenia gravis.

BACKGROUND: We have used a promising, minimally invasive thoracoscopic technique of extended thymectomy for patients with myasthenia gravis (MG). The aim of this study was to report our promising technique, a modified single-port trans-subxiphoid approach (MTXA) and to compare perioperative outcomes and effects on MG between our approach and sternotomy. METHODS: We retrospectively reviewed records of all patients undergoing extended thymectomy for MG and/or thymoma between January 1, 2010 and December 31, 2016. The patients were divided into the MTXA group and Sternotomy group. RESULTS: Of the 50 consecutive patients undergoing extended thymectomy for MG, finally, 13 patients undergoing our MTXA extended thymectomy technique were compared with 20 patients undergoing extended thymectomy via sternotomy. Intraoperative blood loss, postoperative length of stay, and C-reactive protein value on postoperative day 1 were significantly more favorable in the MTXA group than the Sternotomy group (P<0.0001, P=0.0040 and P=0.0073, respectively). Furthermore, no significant differences in the frequency of patients with improvement of their Quantitative Myasthenia Gravis score and/or MG-Activities of Daily Living scale, decrease in the serum level of acetylcholine receptor antibody, and dose reduction of oral prednisone were seen between the two groups. CONCLUSIONS: Our approach to extended thymectomy might be more favorable than sternotomy in patients with MG.

Practical issues in measuring autoantibodies to neuronal cell-surface antigens in autoimmune neurological disorders: 190 cases.

OBJECTIVES: To address practical issues in measuring autoantibodies to neuronal cell-surface antigens (NSAs) in various autoimmune neurological disorders (ANDs). METHODS: We retrospectively reviewed the clinical information of 221 patients with clinically suspected ANDs who underwent antibody testing for NSAs between January 2007 and September 2017. 31 were excluded. In 190 patients, antibody-detection rate (ADR) and antibody-phenotype association were assessed. RESULTS: Fifty-four patients had NSA-antibodies: NMDA receptor (NMDAR) (n = 39), AMPA receptor (n = 3), leucine-rich glioma inactivated 1 (LGI1) (n = 3), glycine receptor (GlyR) (n = 3), GABA(A) receptor (n = 2), GABA(B) receptor (n = 1), metabotrophic glutamate receptor 5 (n = 1), or unknown (n = 6); 3 had multiple NSA-antibodies. ADR in patients with diagnostic criteria for "possible autoimmune encephalitis (AE)", "probable anti-NMDAR encephalitis", "definite autoimmune limbic encephalitis (ALE)", and "stiff-person spectrum disorder (SPSD)", was 34% (46/134), 85% (34/40), 46% (11/24), and 22% (4/18), respectively, but NSA-antibodies were not identified in 11 patients with systemic autoimmune disorders (SADs). Among 134 patients with "possible AE" criteria, NMDAR-antibodies were more frequently identified in patients with typical anti-NMDAR encephalitis than those without (34/40 [85%] vs. 4/94 [4%], p < 0.0001). LGI1-antibodies were identified in patients with ALE but not in the others (3/24 [13%] vs. 0/110 [0%], p = 0.005). GlyR-antibodies were identified in those with stiff-person syndrome plus (2/8, 25%) or stiff-limb syndrome (1/6, 17%). CONCLUSIONS: NSA-antibodies were most frequently identified in "probable anti-NMDAR encephalitis", followed by "definite ALE", "possible AE", and "SPSD", but not identified in SADs. NMDAR, LGI1 and GlyR were associated with clinical phenotype. Cell-surface antigens should be determined based on individual phenotype.

Pitfalls in clinical diagnosis of anti-NMDA receptor encephalitis.

OBJECTIVES: To report pitfalls in the clinical diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: We retrospectively reviewed the clinical information of 221 patients with clinically suspected autoimmune neurological disorders who underwent testing for autoantibodies against neuronal cell-surface antigens between January 1, 2007 and September 10, 2017. Forty-one patients met the diagnostic criteria for probable anti-NMDAR encephalitis (probable criteria), but one was excluded because neither serum nor CSF was examined at the active stage. Thus, in 220 patients, sensitivity and specificity of the probable criteria were assessed. RESULTS: NMDAR-antibodies were detected in 34 of 40 patients (85%) with the probable criteria; however, 2 of the 6 antibody-negative patients had ovarian teratoma. The median age at onset was higher in antibody-negative patients than those with antibodies (49 vs. 27 years, p = 0.015). The age at onset was associated with the probability of antibody detection (p = 0.014); the probability was less than 50% in patients aged 50 years or older. NMDAR-antibodies were also detected in 5 of 180 patients who did not fulfill the probable criteria; these patients presented with isolated epileptic syndrome (n = 2), atypical demyelinating syndrome (n = 2; one with aquaporin 4 antibodies), and autoimmune post-herpes simplex encephalitis (post-HSE) (n = 1). Sensitivity and specificity of the probable criteria was 87.2 and 96.7%, respectively. CONCLUSION: The probable criteria are valid, but the diversity of clinical phenotype should be taken into account in diagnosing anti-NMDAR encephalitis particularly in patients aged 50 years or older, or with isolated epileptic syndrome, atypical demyelinating syndrome, or post-HSE.

Cryptogenic NORSE: Its distinctive clinical features and response to immunotherapy.

OBJECTIVE: To report the distinctive clinical features of cryptogenic new-onset refractory status epilepticus (C-NORSE) and the C-NORSE score based on initial clinical assessments. METHODS: A retrospective study was conducted for 136 patients with clinically suspected autoimmune encephalitis who underwent testing for autoantibodies to neuronal surface antigens between January 1, 2007, and August 31, 2016. Eleven patients with C-NORSE were identified. Their clinical features were compared with those of 32 patients with anti-NMDA receptor encephalitis (NMDARE). RESULTS: The clinical outcome of 11 patients (median age, 27 years; 7 [64%] women) with C-NORSE was evaluated after a median follow-up of 11 months (range, 6-111 months). Status epilepticus was frequently preceded by fever (10/11 [91%]). Brain MRIs showed symmetric T2/fluid-attenuated inversion recovery hyperintensities (8/11 [73%]) and brain atrophy (9/11 [82%]). Only 2 of the 10 treated patients responded to the first-line immunotherapy, and 4 of the 5 patients treated with IV cyclophosphamide responded to the therapy. The long-term outcome was poor in 8 patients (73%). Compared with 32 patients with NMDARE (median age, 27 years; 24 [75%] women), those with C-NORSE had more frequent prodromal fever, status epilepticus, ventilatory support, and symmetric brain MRI abnormalities, had less frequent involuntary movements, absent psychobehavioral symptoms, CSF oligoclonal bands, or tumor association, and had a worse outcome. The C-NORSE score was higher in patients with C-NORSE than those with NMDARE. CONCLUSIONS: Patients with C-NORSE have a spectrum of clinical-immunological features different from those with NMDARE. The C-NORSE score may be useful for discrimination between them. Some patients could respond to immunotherapy.

Tafamidis for the Treatment of Hereditary Transthyretin Amyloid Cardiomyopathy: A Case Report.

Tafamidis meglumine is a novel medicine that has been shown to slow the progression of peripheral neurological impairment in patients with hereditary transthyretin amyloidosis (ATTR). However, the efficacy of tafamidis against ATTR-related cardiac amyloidosis remains unclear. A 72-year-old woman had cardiac hypertrophy and axonopathy in her lower legs. Endomyocardial biopsy revealed an infiltrative cardiomyopathy consistent with amyloidosis. Immunostaining and genetic studies confirmed the diagnosis of ATTR, and tafamidis was started subsequently. Two years after the initiation of tafamidis treatment, electromyography demonstrated no change in the axonopathy in her lower legs; however, electrocardiography displayed QRS prolongation, and echocardiography disclosed an increase in interventricular septal thickness. Endomyocardial biopsy indicated that transthyretin amyloid infiltration of the myocardium was not reduced. In this case, there was no apparent progression of axonopathy, although there were signs of worsening amyloid cardiomyopathy during the treatment with tafamidis.

Association of Progressive Cerebellar Atrophy With Long-term Outcome in Patients With Anti-N-Methyl-d-Aspartate Receptor Encephalitis.

IMPORTANCE: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disorder that occurs with IgG antibodies against the GluN1 subunit of NMDAR. Some patients develop reversible diffuse cerebral atrophy (DCA), but the long-term clinical significance of progressive brain and cerebellar atrophy is unknown. OBJECTIVE: To report the long-term clinical implications of DCA and cerebellar atrophy in anti-NMDAR encephalitis. DESIGN, SETTING, AND PARTICIPANTS: A retrospective observational study and long-term imaging investigation was conducted in the Department of Neurology at Kitasato University. Fifteen patients with anti-NMDAR encephalitis admitted to Kitasato University Hospital between January 1, 1999, and December 31, 2014, were included; data analysis was conducted between July 15, 2015, and January 18, 2016. EXPOSURES: Neurologic examination, immunotherapy, and magnetic resonance imaging (MRI) studies were performed. MAIN OUTCOMES AND MEASURES: Long-term MRI changes in association with disease severity, serious complications (eg, pulmonary embolism, septic shock, and rhabdomyolysis), treatment, and outcome. RESULTS: The clinical outcome of 15 patients (median age, 21 years, [range, 14-46 years]; 10 [67%] female) was evaluated after a median follow-up of 68 months (range, 10-179 months). Thirteen patients (87%) received first-line immunotherapy (intravenous high-dose methylprednisolone, intravenous immunoglobulin, and plasma exchange alone or combined), and 4 individuals (27%) also received cyclophosphamide; 2 patients (13%) did not receive immunotherapy. In 5 patients (33%), ovarian teratoma was found and removed. Serious complications developed in 4 patients (27%). Follow-up MRI revealed DCA in 5 patients (33%) that, in 2 individuals (13%), was associated with progressive cerebellar atrophy. Long-term outcome was good in 13 patients (87%) and poor in the other 2 individuals (13%). Although cerebellar atrophy was associated with poor long-term outcome (2 of 2 vs 0 of 13 patients; P = .01), other features, such as DCA without cerebellar atrophy, serious complications, ventilatory support, or prolonged hospitalization, were not associated with a poor outcome. Five patients with DCA had longer hospitalizations (11.1 vs 2.4 months; P = .002), required ventilatory support more frequently (5 of 5 vs 4 of 10 patients; P = .04), and developed more serious complications (4 of 5 vs 0 of 10 patients; P = .004) compared with those without DCA. Although DCA was reversible, cerebellar atrophy was irreversible. CONCLUSIONS AND RELEVANCE: In anti-NMDAR encephalitis, DCA can be reversible and does not imply a poor clinical outcome. In contrast, cerebellar atrophy was irreversible and associated with a poor outcome. This observation deserves further study to confirm progressive cerebellar atrophy as a prognostic marker of poor outcome.

Efficacy of autologous peripheral blood stem cell transplantation in POEMS syndrome with polyneuropathy.

POEMS syndrome (POEMS) is a rare multi-system disease which is typically associated with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. We report herein a case of POEMS with progressive polyneuropathy resistant to high-dose intravenous immunoglobulin therapy who experienced improvement in polyneuropathy after the administration of high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. Improvements in polyneuropathy remain despite recognition of monoclonal gammopathy by immunofixation as of 1 year after treatment. We demonstrated that autologous peripheral blood stem cell transplantation can improve clinical symptoms and signs due to polyneuropathy in POEMS even without achieving complete remission.