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Immune checkpoint inhibitor (ICI)-induced thrombocytopenias are rare immune-related adverse events (irAE), but ICI-related thrombotic thrombocytopenic purpura (TTP) is extremely rare. A 79-year-old woman with non-small cell lung cancer received maintenance therapy with the anti-human PD-L1 monoclonal antibody durvalumab. Four weeks after the last infusion, she developed overt TTP. Remission was achieved by plasma exchange and prednisolone, and the patient has now been recurrence-free for over 12 months. To our knowledge, this is the first report of TTP occurring as an irAE of durvalumab.

A 75-year-old man who had lymphadenopathy was admitted to our hospital. Histopathological examination of cervical lymph node biopsy specimens showed diffuse proliferation of lymphoma cells with large nuclei. In immunohistochemistry, the lymphoma cells were positive for CD5, CD10, CD20, BCL2, BCL6, and MYC. The patient was diagnosed with CD5- and CD10-positive diffuse large B-cell lymphoma (DLBCL). MYD88 L265P mutations have been detected in DLBCL. Partial response was achieved after six courses of R-THP-COP therapy. However, the patient died because of disease progression 18 months after the diagnosis. On autopsy, lymphoma cells were found in the lymph nodes throughout the body, central nervous system, adrenals, and skin. CD5- and CD10-positive DLBCL account for 0.5-1% of DLBCL cases and have a very poor disease prognosis. This is a rare case of CD5- and CD10-positive DLBCL with MYC and BCL2 expressions harboring MYD88 L265P mutation.

Anatomical knowledge of target structures is essential in stereotactic functional neurosurgery. Thus, we created a three-dimensional(3D)atlas comprising frozen sections and histologically stained slides prepared from cadaveric brains. Herein, we describe the anatomical information of stereotactic functional neurosurgery targets gained from our atlas. The subthalamic nucleus(STN)was found to be clearly enclosed by neural fibers with high neuronal density. Based on our 3D models, the mean penetration length of deep brain stimulation leading into the STN was 6.6 mm. The globus pallidus was found to be clearly divided into the grobus pallidus externus(GPe)and internus(GPi)by its neural fibers, and the optic tract was located below the GPi. Although the thalamic lateral nuclear group(ventrooralis, ventrontermedius, and ventrocaudalis)could not be identified from either macroscopic frozen sections or MR images, these structures were clearly discernible from each other based on cell architecture(cell size and cell density)when viewed under a microscope. In contrast, distinguishing ventral and dorsal nuclei in humans is difficult. In addition to the main targets of the basal ganglia, we also investigated the anatomy of other targets in detail(posterior subthalamic area, pedunclopontine nucleus, nucleus accumbens, and nucleus basalis of Meynert). Overall, this anatomical knowledge from the atlas helps functional neurosurgeons interpret intraoperative microelectrode recording and MRI more precisely, helping facilitate more accurate surgeries.

We describe a case involving subarachnoid and intraperitoneal hemorrhage due to segmental arterial mediolysis(SAM). A 77-year-old female patient with sudden subarachnoid hemorrhage was immediately transferred to our institution. The hemorrhage was classified as grade 2 according to the World Federation of Neurosurgical Societies system. The patient was a non-smoker and did not drink alcohol regularly. A right internal carotid aneurysm was detected using CT angiography and was clipped during frontotemporal craniotomy. Bleeding was observed from the anterior wall of the internal carotid artery, and the tear was clipped. The patient had an uneventful postoperative course until sudden cardiopulmonary arrest eight days after craniotomy. She died of massive intraperitoneal hemorrhage. Autopsy revealed that the hemorrhage was due to dissection of the celiac artery. Tunica media denaturation was observed not only in the celiac artery, but also in the splenic and internal carotid arteries, which exhibited ruptured aneurysms, and the patient was diagnosed with segmental arterial mediolysis(SAM). SAM is an arterial degenerative disease affecting the medial layer of the arterial and dissecting walls. Multiple lesions are sometimes found. Radiographic imaging findings of SAM are similar to those of dissecting aneurysms, which are characterized by a single continuous dissection of the medial layer. As observed in this case, abdominal bleeding caused by SAM can occur after intracranial bleeding. When surgeons encounter unusual intracranial dissecting aneurysms, SAM should be considered as a differential diagnosis.

Cardiac involvement during lymphoma often causes complications, including arrhythmia. A 68-year-old male with cardiac tamponade was diagnosed with diffuse large B-cell lymphoma with cardiac involvement based on the presence of the tumor mass in the myocardium and lymphoma cells in the pericardial effusion. He developed atrial fibrillation, ventricular tachycardia, and atrial flutter after initiating chemotherapy. Following chemotherapy, sinus rhythm was restored without invasive treatment for arrhythmia, while the cardiac mass disappeared. No recurrent arrhythmias were observed. In lymphoma with cardiac involvement, unexpected arrhythmias can emerge after initiation of chemotherapy, which could potentially be related to accelerated cardiac remodeling owing to the rapid relief of cardiac damage. Follow-up using electrocardiogram is thus necessary during chemotherapy for cardiac lymphoma, despite the absence of arrhythmia at the time of diagnosis.

Aim: As the number of aged stroke patients increases in Japan, the proportion of older patients who receive recombinant tissue plasminogen activator (rt-PA, 0.6 mg/kg) is also rising. However, the Japanese stroke guideline indicates that rt-PA therapy must be administered very carefully in older patients (i.e. ≥81 years of age) because of serious complications after the therapy. We retrospectively assessed the clinical outcomes of rt-PA therapy in older patients., Methods: This study included 321 patients who received rt-PA therapy for acute cerebral infarction at our hospital between April 2007 and April 2017. The outcomes (modified Rankin Scale [mRS] score at 3 months after treatment) and symptomatic intracerebral hemorrhaging (sICH) were compared and analyzed between patients ≥81 years of age (group A) and those <81 years of age (group B). In addition, propensity score matching was performed for the factors shown to have significant differences by a univariate analysis in order to adjust for confounding factors, and the outcomes were compared., Results: There were 58 patients in group A (18.1%) and 263 patients in group B (81.9%). The rate of favorable outcomes (mRS 0-1) was lower in group A (12.1%) than in group B (44.1%) (P<0.01). The mortality rate was higher in group A (17.2%) than in group B (4.6%) (P=0.002). No marked differences were observed between the 2 groups regarding the rate of sICH (group A, 3.4%; group B, 3.0%; P=1.00). After propensity score matching, the proportion of patients with favorable outcomes was significantly lower in group A (13.2%) than in group B (36.8%) (P=0.032). There were no marked differences in the mortality rates between the groups (group A, 17.2%; group B, 4.6%) (P=0.200), and no patients in either group had sICH., Conclusion: No marked differences in the incidence of ICH were observed between the older and younger groups receiving intravenous rt-PA therapy. However, in terms of efficacy, the proportion of patients with favorable outcomes was significantly lower in the older group than in the younger group.

Hyponatremia occurs while receiving bortezomib-containing combination therapy in multiple myeloma (MM) ; however, the mechanism of hyponatremia remains unclear. A 65-year-old female with MM was treated with bortezomib, lenalidomide, and dexamethasone. Fourteen days after chemotherapy initiation, she developed hyponatremia (serum sodium, 127 mEq/l, compared with 136 mEq/l before chemotherapy) with plasma hypo-osmolality and urine hyper-osmolality. She exhibited neither dehydration nor adrenal insufficiency. Her serum arginine vasopressin peptide (AVP) level was 1.5 pg/ml. She was diagnosed with syndrome of inappropriate secretion of antidiuretic hormone (SIADH), wherein causative roles of inflammatory cytokines were strongly suggested in the development because (1) SIADH was triggered by the cessation of the dexamethasone treatment and (2) hyponatremia was successfully treated with prednisolone, which was administered for the complication of drug eruption. Perhaps, bortezomib-induced immune reactions could be involved in a subset of hyponatremia during bortezomib-containing antimyeloma chemotherapy.

Among 238 patients with bilateral trigeminal neuralgia(TN)who visited our hospital between April 2007 and June 2014, 5(2%)were surgically treated by microvascular decompression(MVD). The initial symptom was on the right side in four and on both sides in one patient. Intervals between the initial and second onset on the other side(left)were two months, and four, six, and eight years. None of the patients showed involvement of the first branch of the trigeminal nerve. The patients with bilateral TN were younger than the 154 patients with unilateral TN who were treated surgically by MVD in this period(45 vs. 65 years), and the bilateral TN patients predominantly were women(4/5 vs. 99/154). In the surgical field, the trigeminal nerve and root entry zone were compressed more by veins in the bi lateral TN patients than in the unilateral TN(4/5 vs. 60/154, respectively)patients. We could not identify any differences in MRI CISS before versus after the onset of left trigeminal neuralgia, suggesting that compression is not the sole cause of the symptom.

Cancer patients often report a decreased quality of life due to cancer-related pain, especially neuropathic pain, which is difficult to manage and often develops resistance to morphine. Thus a supplementary analgesic can play an important role in the treatment of cancer-related pain. Carbamazepine (CBZ), for example, can be effective, but only if the patient can take medication orally because it is limited to oral administration. In this study we investigated the efficacy of a suppository containing CBZ tablet in hospital preparations. We selected a base for the suppository of either polyethylene glycol (P), Witepsol VOSCO(®) H-15 (H), or Witepsol VOSCO(®) S-55 (S). Six to eight in vitro and in vivo groups were divided randomly based on route of administration and treatment: intravenous (i.v.), per os (p.o.), and intrarectal administration (i.r.) (composed of CBZ powder and tablet formulations, CBZp and CBZt) prepared in either a base of P, H, or S (CBZp/P, CBZp/H, CBZp/S, CBZt/P, CBZt/H, and CBZt/S). The hardness levels of the CBZt suppository group were significantly lower than the CBZp suppository group. The drug release profiles of the CBZt suppository group were high in order of P, H, and S; there were no significant differences between these groups and the CBZp suppository group. The maximum drug concentration time levels of the CBZt suppository group significantly increased compared with the p.o. group. These two groups had equivalent maximum drug concentration and bioavailability levels. These results suggest that a suppository containing CBZ tablet can be useful for hospital preparations.

A 59-year-old man presented with right trigeminal neuralgia of the second branch, which had been treated with carbamazepine. The pain could not be controlled adequately because of side effects. CT and MRI revealed a 2-cm lesion in the right cerebellopontine angle. Retrosigmoid lateral suboccipital craniectomy was performed, and a soft yellowish mass was found to be associated with the 5th, 7th, and 8th cranial nerves, anterior inferior cerebellar artery, and small vessels. The lipoma was partially resected from around the root entry zone(REZ)of the 5th nerve and small vessels were coagulated around the REZ. After surgery, there was no trigeminal neuralgia, but facial numbness and cerebellar signs were noted. Postoperative MRI showed decompression of the trigeminal nerve and venous infarction in the middle cerebellar peduncle. Reviewing similar cases, we found 19 lipoma patients presenting with trigeminal neuralgia. Symptoms of involvement of other cranial nerves were also present in 11 patients, and 14 were younger than 30 years old. Of 17 surgical cases, total resection was not attempted apart from one case. Although pain relief was achieved in all surgical cases, complications developed in 11. Surgery should be performed only in patients with disabling and uncontrolled symptoms.

Ocular ischemic syndrome occurs when ocular circulation becomes impaired owing to various causes, leading to disturbances in the visual function. It ultimately progresses to neovascular glaucoma and loss of sight. Therefore, the early diagnosis and treatment of patients with ocular ischemic syndrome has a major effect on their visual prognosis. Herein, we describe a patient who complained of decreased vision in one eye. The patient was subsequently diagnosed with internal carotid artery stenosis because of neovascularity (rubeosis iridis) around the iris in the anterior eye. The vision of the patient improved immediately after carotid artery stenting. A review of the literature indicated that the visual improvement could be attributed to the reversal of retrograde blood flow, caused by internal carotid artery stenosis, to normal levels; the resolution of rubeosis in the anterior eye; and improvement in the visual field constriction.

A 76-year-old woman presented at our hospital complaining of loss of consciousness, dysarthria, and upper extremity paresis. Head CT showed no remarkable findings. 3D CT angiography (CTA) and CT perfusion (CTP) revealed acute aortic dissection (AAD) involving the innominate artery and decreased cerebral blood flow in the right cerebral hemisphere, although there were no clinical signs of AAD. The patient underwent emergency allograft replacement performed by cardiovascular surgeons. The symptoms disappeared within several days and no cerebral infarction developed. Although patients with AAD and neurological symptoms can show a fatal course when they receive tissue plasminogen activator (tPA), it is difficult to exclude patient with AAD as candidates for tPA treatment. Routine use of 3D CTA and CTP in the diagnosis of acute stroke may help overcome the above problem.

Epidermoid rarely appears in the cavernous sinus. We encountered a 41-year-old man with left abducens nerve palsy. A round-shaped, low-density lesion on CT was located lateral to the left cavernous sinus with a compressed and thinned lateral wall of the sphenoid sinus. We could not identify cranial nerves in the cavernous sinus, which was found to be packed with a non-enhanced, high-intensity tumor on both T1 and T2 MRI. Part of the tumor capsule and its pearly contents were removed with an intradural subtemporal approach, and an inner membranous layer with cranial nerves and a tumor capsule were seen at the bottom of the tumor cavity. Postoperatively, complete cure was achieved. Reviewing similar cases, we found 18 cavernous sinus epidermoids:extracavernous type in 5;interdural in 10;and intracavernous in 3. The interdural type could be further divided into two subtypes:superficial cavernous sinus and inner membranous types. The present case belongs to the former. Frontotemporal and subtemporal procedures via both intra- and extradural approaches are relatively safe for lesions except for the intracavernous type, because cranial nerves are not located in the lateral wall of the tumor. MRI provides more useful information on cranial nerves and aid in choosing a better treatment strategy.

For dozens of years, a variety of pathological findings have been revealed through previous observations on surgically resected lesions from patients with intractable epilepsy, including excessive number of neurons in the molecular layer of cortices, unexpected existence of white matter neurons, and persistent columnar structure. These findings have sometimes been referred to as microdysgenesis (MD) or mild malformation of cortical development (mMCD), which is defined as microscopic abnormalities of brain formations with no macroscopical and neuroradiological findings. Taylor et al. (1971) described surgical cases with giant neurons and bizarre, grotesque cells as "focal dysplasia of the cerebral cortices with epilepsy." Since 1997, such malformations have subsequently been referred to as focal cortical dysplasia (FCD), in Greenfield's Neuropathology. Since early 2000, the definition of FCD has gradually been given a broader interpretation than the case described by Taylor et al., as shown in Palmini's classification (2004) or the newest classification (2011) proposed by the Neuropathology Task Force of the International League Against Epilepsy (ILAE). The ILAE classification describes 3 types of disease: Type I, Type II, and Type III. Type I is equivalent to some, but not all, pathological phenotypes of MD or mMCD. Type II is Taylor's FCD alone. Type III, which was not included in Palmini's classification, merges brain malformation and other pathological findings. However, the reproducibility of pathological diagnosis by using the ILAE classification was low, except for Type IIb. Hence, future studies are necessary to provide further reliable criteria for the pathological diagnosis of epilepsy patients.

We report a 53-year-old male with Cogan's syndrome. He was admitted to our hospital because of a fever of 2-weeks duration, blurred vision for 10 days, hypoacusis, and numbness of the left hand for 3 days. In addition to uveitis, hypoacusis, and aseptic meningitis, multiple mononeuropathy was diagnosed based on a nerve conduction study. Furthermore, positron emission tomography/computed tomography (PET/CT) revealed diffuse aortitis. Accordingly, the patient was diagnosed with Cogan's syndrome. After starting steroid-pulse therapy followed by 1 mg oral prednisolone/kg/day, the uveitis and hypoacusis improved immediately, while the peripheral neuropathy persisted until effectively treated with intravenous gamma globulin therapy. Prompt steroid therapy for Cogan's syndrome based on a diagnosis made using PET/CT prevented progression of the hypoacusis.

We have reported that the apparent diffusion coefficient (ADC) was correlated with bone mineral density, but the relation between the restricted diffusion of the water molecules and the trabecular bone structure was unclear. The purpose of our study is to clarify this relationship using two component analyses with an original phantom. With an increase in the interspace area of the simulated trabecular bone, the ADC of the fast component was increased, and the fraction of the fast component was also increased. On the other hand, with an increase in the interspace area of the simulated trabecular bone, the ADC of the slow component was decreased, and the fraction of the slow component was increased. Moreover, the ADC and fraction of the dry vertebral bone agreed with those of the simulated trabecular bone. This result means that our phantoms can reproduce the actual trabecular bone structure, which induces the restricted diffusion. The diffusion of the water molecules was separated into fast and slow components because of the restricted diffusion of the trabecular bone structure. Our original phantom enables analyzing restricted diffusion, and this analytical method obtains more detailed information on trabecular bone structure.

Pulmonary involvement is a serious complication in Gaucher disease, as is neuronopathic involvement. Few reports are available, however, on the frequency, clinical course and therapy for pulmonary involvement in patients with Gaucher disease. We report a case of type 2 Gaucher disease with severe hepatosplenomegaly, anemia, hypertonia, and psychomotor retardation. The diagnosis of Gaucher disease was confirmed by the presence of Gaucher cells in bone marrow and low serum beta-glucocerebrosidase activity (patient, 0.8; control, 4.1-9.7 nmol/mg.protein/hr) at the age of 1 year. The patient's genotype is L444P/unknown. Enzyme replacement therapy (ERT) with intravenous imiglucerase at 78 U/kg/2weeks was started, and hepatosplenomegaly and laboratory abnormalities were markedly improved after 6 months of therapy. After 8 months of therapy, respiratory impairment appeared together with a decrease of tidal volume and low SpO2 during sleep. Serum acid phosphatase and angiotensin converting enzyme levels mildly increased, and radiological findings showed bilateral ground-glass appearance without signs of respiratory infection. With the diagnosis of progressive pulmonary involvement in Gaucher disease, we increased the dosage of imiglucerase from 50 to 75 U/kg/2 weeks. After a month, respiratory symptoms and CT findings of ground-glass appearance remarkably improved, but interlobular septal and intralobular interstitial thickening persisted. The maximum permitted dosage of imiglucerase in Japan is 60 U/kg/2 weeks. Based on our experience with this case, we propose that a higher ERT dosage would be uselul for serious pulmonary involvement.

We reported two patients with unilateral lateral medullary infarction involving severe, long-term respiratory failure. The first patient is an 86-year-old man presenting with gait disturbance, hoarseness and dysphagia. A right lateral medullary infarction was revealed by brain MRI. On the fifth hospitalized day, acute respiratory failure occurred. His condition failed to recover, and he was still attached to a ventilator 10 months after the onset. The second patient is an 83-year-old woman mainly presenting with dysphagia. A tiny infarction in the right lateral medulla was revealed by brain MRI. On the third day after the onset, acute respiratory failure occurred, which was not changed even at 8 months later. Although the symptoms and the lesion in the medulla were quite different between two patients, dysphagia and respiratory failure occurred in both patients. Therefore, it is postulated that the lesion that causes dyspnea may be approximate to the lesion that causes dysphagia. Many previously reported cases presenting respiratory failure seemed to suffer swallowing difficulty as well. We conclude that elderly patients suffering from unilateral lateral medullary infarction with dysphagia can present respiratory failure a few days after the onset, demonstrating the need to observe them under intensive attention.

We report a case of intractable epilepsy caused by tuberous sclerosis with multiple tubers that was treated successfully by single resection of a tuber A 2-year-old boy developed tonic spasm-like seizures at the age of 4 months and the frequency of the seizures increased despite therapy with various anticonvulsants. He had no neurological deficits, and his intelligence was normal. MRI showed lesions in the left frontal and the right parietal lobe, and EEG (electroencephalogram) demonstrated sharp waves and spike-and-wave complex bursts over the right parietal region. Subdural electrodes were implanted over these lesions, and ictal low-voltage fast waves were demonstrated on the right parietal lesion. Therefore the right cortical lesion and the epileptogenic cortex were resected. Multiple subpial transaction was also added in the irritative cortex. Histological examination proved that the lesion was a tuberous sclerosis complex (TSC) tuber. Since surgery, the patient has remained seizure-free for 2 years. In patients with multiple TSC tubers in the cortex, we suggest that seizures can be suppressed by single resection of a tuber if the tuber can be identified as epileptogenic before surgery.

We evaluated the effectiveness of the "Picolumi ucOC" kit for measuring the serum level of ucOC. When used with an autoanalyzer, the kit achieved highly sensitive and rapid measurement over a range of 0.39 to 50 ng/mL. Assessment of reproducibility testing showed good results, since the coefficient of variation was

We devised a method of analyzing a regional fat fraction using a modulus and real multiple gradient-echo (MRM-GRE) 4-7 echo Dixon sequence. The regional fat fraction was calculated with a theoretically fitted signal-intensity curve for multiple GRE images at each echo time (i.e., 4-7 echoes.) on a 1.5 Tesla MRI to correct T2* decay and phase cycling. Then the real image of the first echo was used to differentiate between the areas above and below the 50 percent fat fraction. To eliminate the T1-effect, the flip angle was set at 12 degrees. Fat fractions of the phantom with MRM-GRE were compared with those using conventional double-GRE and other MRI techniques. Fat fractions of liver and spinal bone marrow in healthy volunteers were determined during a breath-hold. The fat fraction of the phantom obtained by the MRM-GRE method tended to agree with the actual fat fraction. On the other hand, in both the phantom and in healthy volunteers, the double-GRE was underestimated owing to T2* decay. The MRM-GRE method enables simple, accurate analysis of the regional fat fraction.

We report a case of Sturge-Weber syndrome with intractable epilepsy presenting complex partial seizures(CPSs) and severe temper tantrum successfully treated with anterior temporal lobectomy. A 23-month-old girl without facial angioma presented with seizures from 8 months after birth. Neuroradiological examination demonstrated angioma in the left temporooccipital lobes and calcification in the left occipital lobe. Thus she was diagnosed as having Sturge-Weber syndrome. Her parents sought medical advice because of intractable and more frequent CPSs and a change in temperament manifesting as severe temper tantrums. Interictal electroencephalogram (EEG) showed relatively mild abnormal slow wave discharges in the left temporal region. The patient underwent left anterior temporal lobectomy based on intraoperative electrocorticography (ECoG) findings. Histopathological examination demonstrated gliotic change in the amygdala. After the surgery, she has remained seizure-free for 14 months while taking anticonvulsants and temper tantrums ultimately showed remission 10 months following surgery. This case may indicate that severe temper tantrum was associated with a change in amygdala structures.

We experienced 8 cases of progressive multifocal leukoencephalopathy (PML) complicated by human immunodeficiency virus (HIV) type-1 infection from 1985 to 1999. These cases showed dementia, bradykinesia, dysarthria, hemiparesis, and so on. All of the cases were severely immunocompromised hosts, because none had more than 150/mm3 CD4 + lymphocytes; indeed, 5 of the cases were below 20/mm3. Other neurological complications except PML were primary CNS lymphoma, HIV encephalitis, and CMV encephalitis. The mean life durations was 7.6 months after the first symptom appeared, for all but one of the patients; the exceptional patient lived for 24 months after. Autopsy studies of the central nervous systems were performed for 7 cases, all of which showed extensive demyelinating lesions of the white matter, and in some cases these extended into the spinal cord. In contrast to Western countries, in Japan there have been few reports of AIDS-associated PML. Thus, this report was thought to be important here.

In 2002, the Dental Hospital of Tokyo Medical and Dental University set up a working group for risk management. This working group analyzed 225 incident and accident reports submitted to the hospital in 2001 and 2002. Each report was analyzed with regard to "type," "place," "reporter," "severity," and "cause" in order to diagnose hospital safety and prevent future incidents and accidents. The cause of incidents and accidents was analyzed using the SHEL model, where S stands for Software, H for Hardware, E for Environment, and L for Liveware. The severity of the consequence was classified into 6 levels, where level 0 = "error not applied," level 1 = "not affected," level 2 = "watch and see or additional test," level 3 = "treatment," level 4 = "aftereffect," and level 5 = "death." The incidents and accidents judged to have potentially high risk were given a score of "+H," irrespective of the level. The results of the analyses revealed that most of the incidents and accidents happened in "wards," "operation rooms," and "oral surgery clinics." This is probably because the incident and accident reporting system is well established by nurses working in these clinics. Additional analysis revealed that most of the reports were written and submitted by nurses. The frequencies of "treatment procedure," "misuse of dental instruments," "mis-prescription," "falling down" and "needlestick" related incidents and accidents were the highest and were caused mainly by L and S. There were only 3 accidents above level 4, however, less severe cases were given a score of +H due to the high potential risk involved.

We report here a 14-year-old boy suffering from intractable epilepsy since the age of 2. Neuroimaging showed a lesion in the left temporal lobe. He underwent resection of the left temporal lobe and multiple subpial transection of the left frontal lobe at the age of 8. Histopathological findings of surgical specimens were similar to those of tubers of tuberous sclerosis (TSC), although he had no other TSC stigmata. To discriminate from cortical dysplasia grade III, we examined the immunohistochemical expression of hamartin and tuberin, the TSC1 and TSC2 gene products. Based on results, we diagnosed this case as having TSC. He has been seizure free since the operation. Although lower than preoperatively, his intelligence quotient has not been declining progressively.

To evaluate clinical significance of measurement of urinary leukotriene E4 (LTE4) in asthmatic patients without attack, we measured urinary LTE4 in 68 asthmatic patients without attack and investigated its correlation with severity of asthma, % FEV1, bronchial hyperresponsiveness and peripheral eosinophil counts. Values of urinary LTE4 were significantly higher in the asthmatic patients (113.6 +/- 9.7 pg/mg.cr) than in healthy control subjects (67.8 +/- 4.7, n = 31), and the level of urinary LTE4 was in proportion to the severity of disease. Urinary LTE4 showed significant negative correlation with % FEV1 in atopic patients (Rs = -0.43, p = 0.025, n = 28), which was not recognized in non-atopic patients. Urinary LTE4 showed no significant correlation with bronchial hyperresponsiveness and peripheral eosinophil counts. Our findings suggested that basal LTE4 in urine reflected chronic airway inflammation of asthma.

A 30-year-old man with multiple emphysematous bullae and bronchiectasis was admitted to Toyama Medical and Pharmaceutical University Hospital because of exertional dyspnea and fever. His chest radiograph and CT scan revealed multiple large bullae in the right lung and infiltrative shadows in the left middle lung field. Pseudomonas aeruginosa was isolated from his sputum culture. Although standard therapies including various antibiotics were administered, his respiratory condition was exacerbated, accompanied with the enlargement of bullae in the right lung and the consequent shift of the mediastinum to the left. The patient and his family proposed lung transplantation, and we concluded that lung transplantation would be an appropriate treatment for his disease. We transported the patient to Osaka University Hospital. Living-donor lung transplantation from the patient's identical twin brothers was successfully performed.

Purpose: To examine the factors which affect changes in the position of the eyes following the strabismus surgery., Methods: The postoperative position of 240 eyes with concomitant strabismus was examined. The factors which seemed to have an effect on the position of the eyes were enumerated, and a logistic regression analysis of the results was done., Results: In comparison with esotropia, in exotropia the eyes showed a tendency to return gradually to a normal position. There was no remarkable improvement in stereoscopic vision following strabismus surgery. Based on the standards of the Japanese Association of Strabismus and Amblyopia [the cure standard for strabismus], the results of strabismus surgery were as follows: Grade 1(cosmetically satisfactory) was mainly observed for esotropia, and Grade 3(good) for exotropia. The factors which had a significant effect on the postoperative position of the eyes were as follows: esotropia amblyopia, muscle movement, and operative methods; exotropia: retinal correspondence, operative methods, and the necessity of inferior oblique muscle surgery., Conclusions: There was little correction of the position of the eyes. In individual cases, the factors which affect position of eyes were examined, and it was considered necessary to increase the amount of correction. Age is a factor which has an effect, but the effect on esotropia and exotropia is small.

A 26-year-old woman was admitted because of a 12-year history of intractable epileptic seizures. Every seizure began with an upper abdominal discomfort, and often followed by massive salivation. Whenever the epileptic salivation happened, the patient lost consciousness, and sometimes she developed generalized convulsions. In terictal sphenoidal EEG recordings revealed abnormal discharges in the left mesial temporal region. MRI demonstrated left hippocampal atrophy. Since her seizures were medically intractable, left temporal lobectomy was performed. Neuropathologic examination revealed hippocampal sclerosis. After the operation, she became completely seizure-free with no episode of massive salivation. From the literature, epileptic salivation can originates from the rolandic area; fronto-orbital cortex & cingulate gyrus; insula & operculum; and mesial temporal structures. The abnormal massive salivation in our patient might be attributable to the activation of frontal limbic system triggered by hippocampal abnormal firing during the ictal period of TLE.

There have recently been a number of new pathological findings of specimens from epileptic foci that have increasingly been highlighted as opportunities for surgical treatment. These findings include a wide range from hippocampal sclerosis-related lesions of temporal lobe epilepsy to newly established malformative lesions. As to the former, special interest has been paid to additional knowledge regarding the pathology inside and outside the medial temporal regions, such as the significance of 1) accumulation of corpora amylacea in hippocampal sclerotic lesions, 2) dispersion of the granular layer of the dentate gyrus, 3) various pathologic features in the lateral temporal lobe, and 4) dual pathology in extratemporal areas. As increasing opportunities for surgical treatment of intractable epilepsy, new categories of malformative lesions are being established, including focal cortical dysplasia and microdysgenesis, the latter of which can be diagnosed only by pathological examination after surgery. In the field of surgical pathology of epilepsy patients, further clues to clarify the pathomechanism of epilepsy remain to be discovered.

A 46-year-old woman with a 2-year history of xerostomia, who had had an episode of suspected Sjögren's syndrome in 1995, was admitted to our hospital because of a dry cough. Chest radiography on admission showed ground-glass infiltrates and reticular shadows in both lower lung fields. Primary Sjögren's syndrome was diagnosed by lip biopsy. Video-assisted thoracoscopic lung biopsies revealed the co-existence of interstitial pneumonia with the BOOP pattern and follicular bronchiolitis. Treatment with oral prednisolone improved the symptoms, and reduced the abnormal chest shadows. This was an interesting case of the BOOP pattern in a lung lesion associated with primary Sjögren's syndrome.

A 21-year-old man was admitted to our hospital with high fever, general fatigue and dyspnea. Chest radiography on admission showed diffuse bilateral infiltrate shadows with Kerley's B lines, and a CT scan showed patches of infiltrates with thickened interlobular septa in both lungs. Examination of the bronchoalveolar lavage fluid and the clinical course led to a diagnosis of acute eosinophilic pneumonia. The patient improved without steroid therapy. We suspected that the disease was related to smoking because the patient had started smoking seven days before the onset of the symptoms. Because a lymphocyte stimulation test gave a positive reaction to a cigarette extract, a challenge test was done. After this, the patient had fever and hypoxemia. These findings suggest that cigarette smoking induces acute eosinophilic pneumonia.

To clarify the prognosis of asthmatics treated with low-dose of inhaled beclomethasone dipropionate (BDP), we retrospectively assessed 43 patients treated with initial dose of 200 or 400 micrograms/day for 5 years, and obtained the following results. 1) 15 patients achieved step-down therapy (group A), 17 patients maintained initial dose of BDP (group B), and 11 patients required step-up therapy of BDP or daily use of oral prednisolone (group C). 2) There was no significant difference in age, sex, duration of disease, severity of disease, peripheral eosinophil counts, %FEV1 and histamine PC20 before BDP treatment among three groups. The percentage of atopic asthmatics was significantly higher in group C than in group A. 3) There was no significant difference in symptom and histamine PC20 between after 1 year state and after 5 years state in three groups. 4) After 1 year from the start of BDP treatment, only 18% patients got symptom free and neither patients exceeded 20,000 micrograms/ml of histamine PC20 in group C. Long-term treatment of low-dose BDP inhalation was effective on mild/moderate asthmatics. Patients requiring step-up therapy had not got sufficient improvement in bronchial hyperresponsiveness after one-year treatment.

A 52-year-old man with a 4-year history of rheumatoid arthritis, and who had an episode of suspected BOOP in early 1994, was admitted to our hospital because of cough and fever. A chest X-ray film on admission showed small patchy infiltrates, and a computed tomographic (CT) scan showed centrilobular nodules and patchy infiltrates with thickened broncho-vascular bundles in both lungs. Transbronchial and thoracoscopic lung biopsies disclosed the coexistence of interstitial pneumonia with BOOP pattern, follicular bronchiolitis, and diffuse panbronchiolitis-like purulent and obliterative bronchiolitis. Due to findings of chronic sinusitis, the patient was treated with erythromycin for 8 weeks, and the abnormal CT shadows regressed. This was an interesting case of various pulmonary lesions associated with rheumatoid arthritis, and successfully treated with erythromycin.

We have previously obtained evidence that DOPA is probably involved in an upstream process of mechanisms for in vivo neuronal cell death in striatum. We attempted to clarify whether or not this is also the case in hippocampal region of conscious Wistar rats. Four vessels were occluded for 5 min during microdialysis of hippocampus. DOPA, dopamine and glutamate (Glu) in perfusates collected every 10 min were measured by HPLC-ECD and spectrophotometer. Delayed neuronal cell death in hippocampus was evaluated 96 hr after ischemia. Five-min transient brain ischemia induced Glu release, with the peak being 2.5-fold of a basal release at the fraction immediately after ischemia. The release of DOPA and dopamine was not consistently detectable, but an increase was sometimes observed during and after ischemia. Delayed neuronal cell death was slight to moderate with 5-min ischemia. Intrastriatal perfusion of DOPA cyclohexyl ester (DOPA CHE) at 100 nM, a novel stable potent competitive DOPA antagonist, almost completely inhibited the ischemia-induced glutamate release, and protected hippocampal neurons from delayed cell death. Endogenously released DOPA itself seems to act on its recognition site and to behave as a causal and/or deteriorating factor on glutamate release and resultant delayed neuronal cell death by transient ischemia in rats.

DOPA itself is a neuromodulator in striata. In rat striata, DOPA by itself released neuronal glutamate in slices and caused cell death via glutamate release in cultured fetal neurons, suggesting involvement of DOPA in an upstream process of mechanisms for in vivo neuronal cell death. We attempted to clarify whether or not this idea is truly the case in conscious Wistar rats. Four vessels were occluded for 10 min during microdialysis of striata. DOPA, dopamine and glutamate in perfusates collected every 10 min were measured by HPLC-ECD and spectrophotometer. Delayed neuronal cell death in striata and hippocampus was evaluated 96 hr after ischemia. DOPA was indeed evoked with dopamine and glutamate during and after ischemia, and peak increases by respective 6-, 210- and 8-fold of a basal level were seen at the fraction immediately after ischemia. Delayed neuronal cell death was slight to moderate in striata and severe in hippocampus. Intrastriatal perfusion of NSD-1015, a central DOPA decarboxylase inhibitor, at 30 microM 10 min before ischemia, markedly increased DOPA and glutamate release by ischemia with slight inhibition of dopamine release and exaggerated delayed neuronal cell death in striata. Meanwhile, intrastriatal perfusion of DOPA cyclohexyl ester (DOPA CHE) at 10-100 nM, a novel stable potent competitive DOPA antagonist, antagonized dose-dependently increases in glutamate release by ischemia without modification of dopamine release. DOPA CHE at 100 nM protected striatal neurons from delayed cell death. Hippocampal neuronal cell death was neither affected by NSD-1015 nor by DOPA CHE. Endogenously released DOPA itself seems to act on its recognition site and to be a causal factor for increase in glutamate release and resultant delayed neuronal cell death by transient ischemia in rats.

A 46-year-old man with a history of left upper lobectomy for pulmonary tuberculosis was admitted to our hospital because of dilated cardiomyopathy. During hospitalization, fever and weight loss developed. The cause was suspected to be a round mass inside a cavity and a neighboring infiltrative shadow in the left upper lung field as seen on chest radiography. A percutaneous needle biopsy was done, and examination of the specimen showed an aggregate of Aspergillus fumigatus hyphae. Fluconazole (FCZ) was injected through an intracavitary catheter every day, and was then given by mouth. Treatment with FCZ was effective temporarily. However, he was again admitted to our hospital because of lower extension of the cavity and deteriorated inflammatory findings. From the clinical course, chronic necrotizing pulmonary aspergillosis was diagnosed. Treatment with all available antifungal agents did not improve his condition. Although he had decreased cardiac function due to dilated cardiomyopathy, partial pulmonary resection was done. The cavity with the fungus ball was resected completely. As of the time of this writing, he remains free of aspergillosis.

The relationships between imaging, pathology and presumed causes in surgical cases of temporal lobe epilepsy (TLE) was studied. The subject was 62 patients (33 males and 29 females) who had had no attacks for more than one year after surgery. Average age at surgery was 28.2 +/- 9.9 years. Obvious neurological abnormalities were not found in these cases. MRI, PET and SPECT were performed. Hematoxylin and eosin was used for pathological judgement. Their medical charts were used to investigate their clinical factors. Although patients suspected of having encephalitis/meningitis had been hospitalized for 2 days to three months during childhood due to disturbance of consciousness with high fever and convulsion for several days; they were not diagnosed with encephalitis/meningitis at that time, and they suffered almost no handicaps other than epilepsy for several years following their comatose episodes. [Result] (1) On MRI, mesial temporal sclerosis (MTS) was detected in 48 of 52 patients (92%); 32 (62%) had high-signal intensity on T 2-weighted images; 31 (60%) had atrophy ¿23 (44%) had high-signal intensity on T 2 + atrophy¿; 5 (10%) had calcified lesions; and 2 (4%) had cystic lesions. On PET and SPECT, abnormal cerebral blood flow was noted in 33 of 36 (92%). (2) On pathological findings (61 cases), Ammon's horn sclerosis (AHS), tumors, gliosis in lateral temporal and meningeal inflammatory finding were detected in 42 (69%), 10 (23%) and 8 (13%) cases, respectively, whereas 2 showed no abnormalities. The 2 patients with normal pathology showed both high-signal intensity and atrophy on MRI. (3) The presumed causes of TLE were encephalitis/meningitis and/or suspected of these diseases in 15 patients (24%), injuries at birth in 5 (8%), and none in 42 (68%). The presumed causes in the 43 patients with AHS were encephalitis/meningitis in 11, injuries at birth in 3, and none in 29. Of the 15 patients in whom encephalitis/meningitis was estimated as the causes of TLE, only 6 (40%) had pathological evidence of meningeal inflammatory finding. Of the 42 patients in whom cause could not be determined, 2 had pathological evidence of meningeal inflammatory finding.

A 64-year-old man was admitted to our hospital with multiple brain abscesses accompanied by pulmonary arteriovenous fistula (PAVF). He had been diagnosed with PAVF eight years previously, but had refused any treatment despite a developing exertional dyspnea. Rendu-Osler-Weber disease was diagnosed as well because the patient exhibited teleangiectasis of the nasopharyngeal mucosa and persistent gastro-intestinal bleeding. Despite administration of antibiotics and corticosteroids the abscesses perforated into the lateral ventricle. The natural history of this rare disease is still incompletely understood. Thus, the time at which treatment should be commenced remains unclear. However the natural course of PAVF is unsatisfactory, and it appears that treatment by surgery and/or embolization should be considered in all cases.