Early Effect of Calcitonin Gene-related Peptide Monoclonal Antibodies in Migraine with Medication Overuse: A Single-center Retrospective Study.

Objective Calcitonin gene-related peptide (CGRP)-(receptor) monoclonal antibody (mAb) has been reported to reduce the frequency of medication overuse in patients with migraine. The present study investigated whether or not CGRP-mAb treatment shows early effectiveness for medication overuse headache (MOH) in Japan. Methods We retrospectively reviewed 34 patients with MOH who received preventive treatment with CGRP-mAb from June 2021 to October 2022. The International Classification of Headache Disorders, 3rd edition was used to diagnose MOH. This study was conducted at the Department of Neurology, Saitama Medical University. Patients were recruited from this specialized headache outpatient center. Results In total, 69 patients with migraine had newly introduced CGRP-mAb, and 34 patients had MOH (49.3%). The mean±standard deviation patient age was 44±15.5 years old. The study population included 24 women (70.6%). The types of CGRP-mAb used were galcanezumab in 16 patients (47.0%), fremanezumab in 10 (29.4%), and erenumab in 8 (23.5%). The mean disease duration was 19.6±13.1 years. The types of migraine diagnosis were chronic migraine in 28 patients (82.4%) and migraine with aura in 11 patients (32.4%). The mean number of headache days in the month before administration of CGRP-mAb was 22±7.7 days; 1 month after administration, the MHD was 16.9±9.1 days. The change in MHD was -5.7 days (22.7%), indicating significant improvement (p<0.05). Conclusion CGRP-mAb has been suggested as a preventive treatment for patients with MOH. Further investigation of the long-term efficacy of CGRP-mAb for MOH is needed.

The Sudden Onset of Pure Parkinsonism Caused by Intracranial Dural Arteriovenous Fistulas.

We herein report a case of sudden-onset parkinsonism, with no other symptoms, caused by intracranial dural arteriovenous fistulas (DAVFs). Diffusion-weighted magnetic resonance imaging (MRI) revealed an increased signal intensity in the bilateral lenticular nucleus. Endovascular embolization improved the patient's parkinsonism and MRI findings. DAVF should be suspected in cases of sudden-onset parkinsonism.

Polycystic subdural hygroma associated with immunoglobulin G4-related intracranial hypertrophic pachymeningitis: a case report.

BACKGROUND: Recent studies have examined hypertrophic pachymeningitis as an IgG4-RD. However, there are no reports of immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis with polycystic subdural hygroma. CASE PRESENTATION: A 56-year-old man presented to the hospital with complaints of a persistent, pulsatile, occipital headache and general malaise. Magnetic resonance imaging of the brain revealed hypertrophic pachymeningitis with polycystic subdural hygroma and hematoma. Based on the dural biopsy findings and exclusion of other diseases, the patient was diagnosed with immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis. IgG4-related diseases may cause subdural hygroma more commonly than other diseases that cause hypertrophic pachymeningitis. CONCLUSIONS: This is the first case report discussing polycystic subdural hygroma and hematoma with IgG4-related hypertrophic pachymeningitis.

Effects of Edaravone on Nitric Oxide, Hydroxyl Radicals and Neuronal Nitric Oxide Synthase During Cerebral Ischemia and Reperfusion in Mice.

BACKGROUND: The purpose of this study was to investigate the effects of edaravone on nitric oxide (NO) production, hydroxyl radical (OH-) metabolism, and neuronal nitric oxide synthase (nNOS) expression during cerebral ischemia and reperfusion. METHODS: Edaravone (3 mg/kg) was administered intravenously to 14 C57BL/6 mice just before reperfusion. Eleven additional mice received saline (controls). NO production and OH- metabolism were continuously monitored using bilateral striatal in vivo microdialysis. OH- formation was monitored using the salicylate trapping method. Forebrain ischemia was produced in all mice by bilateral occlusion of the common carotid artery for 10 minutes. Levels of NO metabolites, nitrite (NO2-) and nitrate (NO3-), were determined using the Griess reaction. Brain sections were immunostained with an anti-nNOS antibody and the fractional area density of nNOS-immunoreactive pixels to total pixels determined. RESULTS: Blood pressure and regional cerebral blood flow were not significantly different between the edaravone and control groups. The levels of NO2- did not differ significantly between the 2 groups. The level of NO3- was significantly higher in the edaravone group compared with the control group after reperfusion. 2,3-dihydroxybenzoic acid levels were lower in the edaravone group compared with those in the control group after reperfusion. Immunohistochemistry showed nNOS expression in the edaravone group to be significantly lower than that in the control group 96 hours after reperfusion. CONCLUSIONS: These in vivo data indicate that edaravone may have a neuroprotective effect by reducing levels of OH- metabolites, increasing NO production and decreasing nNOS expression in brain cells.

Effect of Yokukansan on Nitric Oxide Production and Hydroxyl Radical Metabolism During Cerebral Ischemia and Reperfusion in Mice.

BACKGROUND: The purpose of this study was to investigate the effects of yokukansan on forebrain ischemia. Because we can measure nitric oxide production and hydroxyl radical metabolism continuously, we investigated the effect of yokukansan on nitric oxide production and hydroxyl radical metabolism in cerebral ischemia and reperfusion. METHODS: Yokukansan (300 mg per kg per day) was mixed into feed and given to 16 mice for 10days. Sixteen additional mice received normal feed (control). Nitric oxide production and hydroxyl radical metabolism were continuously monitored using the salicylate trapping method. Forebrain ischemia was producedin all mice by occluding the common carotid artery bilaterally for 10minutes. Levels of the nitric oxide metabolites nitrite and nitrate were determined using the Griess reaction. Survival rates of hippocampal CA1 neurons were calculated and 8-hydroxydeoxyguanosine-immunopositive cells were counted to evaluate the oxidative stress in hippocampal CA1 neurons 72hours after the start of reperfusion. RESULTS: Arterial blood pressure and regional cerebral blood flow were not significantly different between the 2 groups. The level of nitrate was significantly higher in the yokukansan group than in the control group during ischemia and reperfusion. Levels of 2,3- and 2,5-dihydroxybenzoic acid were significantly lower in the yokukansan group than in the control group during ischemia and reperfusion. Although survival rates in the CA1 did not differ significantly, there were fewer 8-hydroxydeoxyguanosine-immunopositive cells in animals that had received yokukansan than in control animals. CONCLUSIONS: These data suggest that yokukansan exerts reducing hydroxyl radicals in cerebral ischemic injury.

The Clinical Features of Ischemic Stroke Patients for Whom Smoking Was Considered the Sole Risk Factor for Ischemic Stroke.

Objective The purpose of this study was to clarify the clinical features of ischemic patients for whom cigarette smoking was the sole risk factor for ischemic stroke. Methods Among the 1,329 patients (male, n=833; female, n=496) with acute ischemic stroke who were admitted to our hospital between April 2005 and September 2016, 346 (26%) were smokers [male, n=308 (36.9%); female, 38 (7.6%)]. In 42 (3.1%; male, n=41; female, n=1) cases, cigarette smoking was considered to be the sole risk factor for ischemic stroke. Data regarding gender, age, the clinical type of ischemic stroke, the National Institutes of Health Stroke Scale (NIHSS) score at the admission, the modified Rankin scale (mRS) scores before the onset and at discharge, the progression of symptoms, and the recurrence of infarction were investigated. Results The mean age of the 42 patients was 63.2±12.4 years (range, 26-86 years). The clinical types of ischemic stroke included atherothrombosis (n=19), lacunar (n=17), other type (n=2) and undetermined type (n=4). The median NIHSS score at the time of admission for ischemic stroke was 2 (interquartile range: IQR 1-4.25). The median mRS scores before the onset and at the discharge were 0 (IQR 0-0) and 1 (IQR 0-2), respectively. One patient had symptoms of progression; no patients had recurrence of infarction. Conclusion Our findings suggest that cigarette smoking alone may induce ischemic stroke; moreover, patients for whom smoking was the sole risk factor for ischemic stroke showed milder symptoms in comparison to patients with other risk factors; however, ischemic stroke was induced from youth. Since cigarette smoking has detrimental effects on the central nervous system, we suggest that people be encouraged to quit smoking in order to maintain good health.

Effects of Memantine on Nitric Oxide Production and Hydroxyl Radical Metabolism during Cerebral Ischemia and Reperfusion in Mice.

BACKGROUND: The purpose of this study was to investigate the effects of memantine on brain ischemia. Because we can measure nitric oxide (NO) production and hydroxyl radical metabolism continuously, we investigated the effect of memantine on NO production and hydroxyl radical metabolism in cerebral ischemia and reperfusion. METHODS: Memantine (25 µmol/kg) was administered intraperitoneally to 6 C57BL/6 mice 30 minutes before ischemia. Seven additional mice received no injection (controls). NO production and hydroxyl radical metabolism were continuously monitored using bilateral striatal microdialysis in vivo. Hydroxyl radical formation was monitored using the salicylate trapping method. Forebrain ischemia was produced in all mice by occluding the common carotid artery bilaterally for 10 minutes. Levels of the NO metabolites nitrite (NO2-) and nitrate (NO3-) were determined using the Griess reaction. Survival rates of hippocampal CA1 neurons were calculated and 8-hydroxydeoxyguanosine (8-OHdG)-immunopositive cells were counted to evaluate the oxidative stress in hippocampal CA1 neurons 72 hours after the start of reperfusion. RESULTS: The regional cerebral blood flow was significantly higher in the memantine group than in the control group after reperfusion. Furthermore, the level of 2,3-dihydroxybenzoic acid was significantly lower in the memantine group than in the control group during ischemia and reperfusion. Levels of NO2- and NO3- did not differ significantly between the 2 groups. Although survival rates in the CA1 did not differ significantly, there were fewer 8-OHdG-immunopositive cells in animals that had received memantine than in control animals. CONCLUSIONS: These data suggest that memantine exerts partially neuroprotective effects against cerebral ischemic injury.

[A Case of Disseminated Peritoneal Leiomyomatosis with Several Recurrences].

A 60's woman had undergone abdominal total hysterectomy due to uterine leiomyoma 17 years previously. She underwent resection of multiple intra-abdominal tumors 9 years previously, and was diagnosed with disseminated peritoneal leiomyomatosis. Because of several recurrences, she was referred to our hospital and treated with GnRH agonist therapy. However, the tumors enlarged gradually and she underwent further resection for multiple intra-abdominal tumors. After surgery, we performed several operations. This is an extremely rare disease and we present this case with a discussion of the literature.

[A case of syndrome of inappropriate antidiuretic hormone secretion in a patient with esophageal carcinoma possibly induced by cisplatin in neoadjuvant chemotherapy].

A 60 -year-old man complained of dysphagia and was admitted to our hospital for adjuvant chemotherapy under a diagnosis of esophageal carcinoma(squamous cell carcinoma[SCC], Stage II ). He was treated with cisplatin(CDDP)and 5- fluorouracil(5-FU). On the fifth day after administration, he experienced mild disorientation, and early morning on the sixth day, he showed impaired consciousness. Laboratory studies revealed a serum sodium level of 111mEq/L and a serum chloride level of 73mEq/L. The findings of computed tomography and magnetic resonance imaging of the head were unremarkable. Other laboratory studies revealed a plasma vasopressin level of 19.2 pg/mL, a plasma osmolality of 219mOsm/kg, a serum creatinine level of 0.61mg/dL, a serum cortisol level of 27.1 mg/dL, a urine osmolality of 665mOsm/kg, and a urine sodium level of 157.1mEq/L. There were no signs of dehydration, and so the patient was diagnosed with syndrome of inappropriate antidiuretic hormone secretion(SIADH). We discontinued chemotherapy and initiated fluid restriction and sodium supplementation. After this treatment, the patient's consciousness progressively improved. On the fifth day of treatment, laboratory studies revealed a serum sodium level of 138mEq/L and a serum chloride level of 98mEq/L, indicating recovery from hyponatremia.

[A case of cancer in the dilated jejunal pouch after total gastrectomy].

We report a case of cancer in the dilated jejunal pouch after total gastrectomy, in which we resected the jejunal pouch. The patient was a man in his 60s and had a history of total gastrectomy with jejunal pouch ρ-interposition for mucosa-associated lymphoid tissue (MALT) lymphoma in 1994. In late July 2012, he presented to the emergency department with a protracted ileus-like symptom and was admitted to the gastroenterological department after the diagnosis of a dilated jejunal pouch. He was managed conservatively; however, the same symptom recurred. Examinations showed a duodenal carcinoma and cancer in the jejunal pouch; therefore, he was referred for digestive surgery in early August. Endoscopic mucosal resection( EMR) was performed on the duodenal carcinoma, and we resected the jejunal pouch with Roux-en-Y reconstruction for the jejunal cancer. He recovered from postoperative wound infection and was discharged 15 days after the second operation.

[Two cases of bleeding from locally advanced esophageal cancer successfully treated by transcatheter arterial embolization].

UNLABELLED: Case 1: A man in his 60s presented with a type 1 tumor of the middle thoracic esophagus that almost blocked the esophageal lumen. On the day of tumor biopsy, the patient developed massive melena and hemorrhagic shock. Hemostasis could not be achieved endoscopically, and therefore, transcatheter arterial embolization( TAE) was performed. Shock was resolved in the patient, thus avoiding the need for emergent surgery. The patient was diagnosed as having esophageal cancer, and standard elective surgery was performed. Case 2: A man in his 50s with cancer of the middle and lower thoracic esophagus underwent surgery after neoadjuvant chemotherapy. However, we were unable to resect the tumor because it had invaded the left main bronchus and the lower lobe of the right lung. We initiated chemoradiotherapy on postoperative day 42; however, the patient developed massive hematemesis. We could not achieve hemostasis endoscopically and therefore performed TAE. The hematemesis stopped following TAE, and the patient was able to undergo chemoradiotherapy. CONCLUSION: We successfully treated 2 cases of bleeding associated with locally advanced esophageal cancer by TAE. Our experience suggests that TAE is effective for controlling bleeding associated with locally advanced esophageal cancer.

[Two cases of stage IV gastric cancer treated by resection of the primary tumor after chemotherapy combined with trastuzumab].

We report 2 cases of stage IV gastric cancer in which the primary tumor was resected after chemotherapy combined with trastuzumab was administered. Case 1: A 57-year-old man who reported epigastric discomfort was diagnosed as having gastric cancer with Virchow's lymph node metastasis. Because his gastric cancer was human epidermal growth factor receptor( HER)-2-positive, he was treated with trastuzumab+capecitabine and CDDP( XP therapy). After 2 courses of this treatment, he underwent distal gastrectomy because of advanced pyloric stenosis. He was treated postoperatively with capecitabine+trastuzumab, and the residual lymph node shrank. Case 2: A 62-year-old man examined for weight loss was diagnosed as having gastric cancer with peritoneal metastases. Because his gastric cancer was HER2-positive, he was treated with trastuzumab+S-1 and CDDP( SP therapy). After 5 courses of this treatment, he underwent total gastrectomy because of advanced pyloric stenosis. He was treated postoperatively with trastuzumab+SP therapy, and his condition remained stable. Chemotherapy combined with trastuzumab could allow resection of the primary tumor and thereby improve the prognosis.

[A case of mixed adenoneuroendocrine carcinoma of the esophagogastric junction treated with neoadjuvant chemotherapy].

We present a case of a 63-year-old man who was admitted to another hospital because of abdominal distension and body weight loss. Gastric endoscopy revealed a type III tumor at the posterior wall of the upper gastric body. The tumor had invaded into the esophagogastric junction. On the basis of the pathology of the biopsy specimen, the tumor was diagnosed as neuroendocrine carcinoma of the esophagogastric junction. Computed tomography (CT) scans showed regional lymph node swelling. Cisplatin( CDDP) +irinotecan( CPT-11) therapy was selected and administered to the patient. After 2 courses, the patient received S-1+CDDP. He was considered to have stable disease. We performed partial resection of the lower esophagus, total gastrectomy, splenectomy, and cholecystectomy. On pathology, the tumor was immunohistochemically positive for chromogranin A, AE1/AE3, neural cell adhesion molecule (NCAM), neuron-specific enolase (NSE), and p53. The Ki-67 index was 80%. The tumor was diagnosed as a mixed adenoneuroendocrine carcinoma (MANEC) of the esophagogastric junction. The patient was treated with S-1 and CDDP. Neuroendocrine cell carcinoma of the esophagogastric junction is rare and usually has a very poor prognosis. We herein report a case of mixed adenoneuroendocrine carcinoma of the esophagogastric junction that was curatively resected and resulted in patient survival without recurrence.

[A case of rapidly fatal gastric cancer with disseminated carcinomatosis of the bone marrow].

A 50-year-old man underwent thorough examination for a chief complaint of melena. Gastric cancer and right kidney cancer were diagnosed. The gastric cancer was in the antrum, and poorly differentiated adenocarcinoma was diagnosed by biopsy. The right kidney cancer was diagnosed as clear cell carcinoma by computed tomography-guided biopsy. We performed right nephrectomy and distal gastrectomy. The final diagnosis of the gastric cancer was por2, pT3( ss), pN3b( 46/ 61), M0, pStage IIIB, R0, and that of the kidney cancer was clear cell carcinoma, pT3a, pN0, pM0. The patient reported lower back pain approximately 2 months after surgery. Several examinations revealed that the patient had multiple bone metastases, disseminated carcinomatosis of the bone marrow, and disseminated intravascular coagulation (DIC).We treated the bone metastasis with denosumab and palliative radiation therapy and the gastric cancer with weekly paclitaxel (PTX). The DIC subsided during the first course but recurred during the discontinuation period. We attempted additional trastuzumab treatment but did not achieve a curative effect, and the patient died. It is necessary to provide appropriate medical care while taking into consideration the possibility of disseminated carcinomatosis of the bone marrow in cases with a high likelihood of lymph node metastasis.

[Two cases of afferent loop obstruction associated with peritoneal dissemination after total gastrectomy].

We report 2 cases of afferent loop obstruction associated with peritoneal dissemination after total gastrectomy. Case 1: A 57-year-old man, who underwent total gastrectomy with Roux-en Y reconstruction for gastric cancer 5 years earlier, experienced lumbago. Computed tomography scans showed a fluid-filled dilated afferent loop. Bypass surgery was performed after inserting a drainage tube into the afferent loop. Case 2: A 61-year-old woman, who underwent total gastrectomy with Roux-en Y reconstruction for a gastric cancer 2 years earlier, experienced abdominal pain. CT and magnetic resonance imaging scans showed a fluid-filled dilated afferent loop and mass lesion near the Y anastomosis. After percutaneous transhepatic duodenal drainage, a duodenal stent was inserted. Here, we describe 2 cases of afferent loop obstruction, improved surgery, and non-surgical therapy.

[A case of gastric cancer treated with modified docetaxel, cisplatin and 5-fluorouracil(mDCF)with ingestion inability].

The standard regimen of S-1 and cisplatin is not adaptable for patients with gastric cancer with an ingestion inability. A 74- year-old man was revealed to have unresectable gastric cancer with severe pyloric stenosis(cT4, cN3, cH1, cP0, cStage IV). He was treated with systemic chemotherapy using modified docetaxel, cisplatin and 5-fluorouracil(mDCF). He had manageable neutropenia(grade 3 and 4)during his treatment. CT findings after 3 courses showed reduced primary tumor and metastatic lesions. A curative operation was performed based on the effective response with downstaging. Palliative surgery was considered before receiving chemotherapy. mDCF therapy is one of the recommended options for gastric cancer with an ingestion inability.

[Analysis of postoperative pulmonary complications after esophagectomy for esophageal cancer].

We examined factors contributing to an onset of postoperative pulmonary complications following esophagectomy for esophagus cancer. One hundred thirty-two cases of the resected esophageal cancer were studied. We considered the relationship between preoperative patient factors, operative factors, clinical stage factors and postoperative pulmonary complications. Postoperative pulmonary complication was observed in 27 cases (20%). The incidence of postoperative pulmonary complications was significantly higher in patients aged 70 and above and those with a preoperative serum albumin value of less than 4 .0 g/dL. Additionally, these two factors were correlated with an onset of postoperative pulmonary complications in multivariate analyses. A decrease of preoperative serum albumin value was reflecting the chronic poor nutritional condition. Moreover, it was possible that poor nutritional condition served as a prognostic factor of postoperative complications in relation to reduction of cellular immunity. The results indicated that there was a possibility of decreasing an onset of postoperative pulmonary complications using various nutrition managements before operations.

[A case of advanced esophageal cancer patient surviving more than 7 years treated with chemoradiotherapy].

We report here a long-term survival case of advanced esophageal cancer with distant lymph node metastases, treated with definitive chemoradiotherapy (CRT). A man in his 60s with disturbance of swallowing was diagnosed as middle esophageal cancer involving multiple metastases of distant lymph nodes. CRT (combination of 5-FU and nedaplatin every four weeks for four courses with 66 Gy of radiation) was administered. After a completion of CRT, CT scan revealed shrinking metastatic lymph nodes. No tumor but a scar at the site of cancer was observed by endoscopy, and histopathology of biopsy specimen detected no tumor cells. From these results, we diagnosed the curative effect of CRT as complete response. Five years after CRT, a swelling of left inguinal lymph node with uptake of fluorine-18-fluorodeoxyglucose appeared and was extirpated, and the swelling was diagnosed histopathologically as metastasis of esophageal cancer. The patient is surviving with no recurrence for 7 years and 8 months from the first diagnosis. In cases of highly advanced esophageal cancer, a long-term follow-up should be performed.