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An 82-year-old man presented with subacute bilateral lower limb paralysis, deep sensory disturbance, and vesico-rectal disturbance. MRI of the spinal cord revealed a large gray matter-dominant lesion extending from the medulla oblongata to the lower thoracic spinal cord. The patient was treated with steroid-pulse therapy for myelitis, but without symptomatic improvement. A spinal cord biopsy was performed for treatment-resistant myelopathy, and histopathology revealed a diffuse large B-cell lymphoma, that was diagnosed as a primary intramedullary spinal cord lymphoma because systemic examination didn't show any other findings suggestive of malignant lymphoma. A spinal cord biopsy is necessary for the definitive diagnosis of this disease, but in the case of poor response to treatment and a progressive course, intramedullary malignant lymphoma should be considered if there is a persistent elevation of CSF IL-10 or a prolonged contrast effect.

Objective To clarify the detailed pharmacokinetics (PK) of orally administered voriconazole in tear fluid (TF) of horses for evaluating the efficacy of voriconazole secreted into TF against equine keratomycosis. Animals studied Five healthy Thoroughbred horses. Procedures Voriconazole was administrated through a nasogastric tube to each horse at a single dose of 4.0 mg/kg. TF and blood samples were collected before and periodically throughout the 24 hours after administration. Voriconazole concentrations in plasma and TF samples were analyzed using liquid chromatography‐electrospray tandem‐mass spectrometry. The predicted voriconazole concentration in both samples following multiple dosing every 24 hours was simulated by the superposition principle. Results The mean maximum voriconazole concentrations in plasma and TF were 3.3 μg/mL at 1.5 h and 1.9 μg/mL at 1.6 h, respectively. Mean half‐life in both samples were 16.4 and 25.2 h, respectively. The ratio of predicted AUC0–24 at steady state in TF (51.3 μg∙h/mL) to previously published minimum inhibitory concentration (MIC) of Aspergillus and Fusarium species was >100 and 25.7, respectively. Conclusions This study demonstrated the detailed single‐dose PK of voriconazole in TF after oral administration and simulated the predicted concentration curves in a multiple oral dosing. Based on the analyses of PK‐PD, the simulation results indicated that repeated oral administration of voriconazole at 4.0 mg/kg/d achieves the ratio of AUC to MIC associated with treatment efficacy against Aspergillus species. The detailed PK‐PD analyses against pathogenic fungi in TF can be used to provide evidence‐based medicine for equine keratomycosis.

OBJECTIVEShunt surgery is the most common treatment for hydrocephalus, but it is associated with several long-term complications. Endoscopic choroid plexus coagulation (CPC) and endoscopic third ventriculostomy (ETV) are alternative surgeries that may avoid the need for shunt surgery. Although the short-term efficacy and safety of CPC have been reported in previous studies, long-term outcome, including not only avoiding shunt placement but also intellectual development, remains to be elucidated. The purpose of the present study was to investigate the long-term outcome of CPC.METHODSThe study population comprised patients who had infantile hydrocephalus treated by endoscopic CPC before the age of 24 months and who were followed until at least 5 years of age. Retrospective review was performed using the medical charts. The authors assessed educational status and the full-scale intelligence quotient (FSIQ) using the Wechsler Intelligence Scale for Children (WISC) IV as the means to evaluate the intellectual development.RESULTSFourteen patients with infantile hydrocephalus underwent CPC with or without ETV as a primary surgery. There were no intraoperative complications. In 7 patients (50%), hydrocephalus was successfully controlled without shunt placement. Six patients (43%) eventually required shunt placement. In one patient hydrocephalus was controlled by additional ETV. In the shunt-independent group, 4 patients went to age-appropriate school or achieved age-appropriate development according to intelligence quotient (IQ), 1 patient went to specialized school, and 2 patients had disabilities. In the shunt-dependent group, 4 patients went to an age-appropriate school or achieved age-appropriate development by IQ, 1 patient went to specialized school, and 1 patient had disabilities. The mean FSIQ score in 3 patients without shunts was 90 (range 89–91) and the mean FSIQ score in 4 patients with shunts was 80 (range 48–107). There was no significant difference in the rate of normal development between the shunt-independent group and the shunt-dependent group (p = 0.72).CONCLUSIONSThe CPC with or without ETV can be a safe and effective treatment in children with infantile hydrocephalus. Long-term control of hydrocephalus and normal intellectual development can be achieved in successful cases. Further prospective studies should be required to elucidate appropriate indications.

Background The aim of the present study was to evaluate clinical efficacy of constant rate infusions (CRIs) of medetomidine–propofol combined with sevoflurane anesthesia in Thoroughbred racehorses undergoing arthroscopic surgery. Thirty horses were sedated intravenously (IV) with medetomidine (6.0 μg/kg) and midazolam (0.02 mg/kg) and induced IV with ketamine (1.0 mg/kg) and propofol (1.0 mg/kg). These horses were randomly allocated to three groups and maintained with sevoflurane and CRI of either medetomidine (3.0 μg/kg/h) (Group M; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (3.0 mg/kg/h) (Group MP3; n = 10); or medetomidine (3.0 μg/kg/h) and propofol (6.0 mg/kg/h) (Group MP6; n = 10). End-tidal sevoflurane concentration (ETSEVO), cardiovascular parameters, plasma propofol concentration, and recovery time and quality were compared among groups. Data were analyzed by using ANOVA with Tukey’s multiple comparison test, considering P

Intracranial artery stenosis (ICAS) is the most common cause of ischemic stroke worldwide. RNF213 single nucleotide variant c.14429G > A (p.Arg4810Lys, rs112735431) was recently reported to be associated with ICAS in East Asians. However, the disease susceptibility of other RNF213 variants has not been clarified. This study comprehensively investigated ICAS-associated RNF213 variants in a pool of 168 Japanese ICAS patients and 1,194 control subjects. We found 138 nonsynonymous germline variants by target resequencing of all coding exons in RNF213. Association study between ICAS patients and control subjects revealed that only p.Arg4810Lys had significant association with ICAS (P = 1.5 × 10–28, odds ratio = 29.3, 95% confidence interval 15.31–56.2 [dominant model]). Fourteen of 138 variants were rare variants detected in ICAS patients not harboring p.Arg4810Lys variant. Two of these rare variants (p.Cys118Arg and p.Leu2356Phe) consistent with variants previously reported in moyamoya disease patients characterized by stenosis of intracranial artery and association with RNF213, and three rare variants (p.Ser193Gly, p.Val1817Leu, and p.Asp3329Tyr) were found neither in control subjects and Single Nucleotide Polymorphism Database. The present findings may improve our understanding of the genetic background of intracranial artery stenosis.

Certain driver mutations and pathological diagnoses are associated with the anatomical site of meningioma, based on which the meninges have different embryological origins. We hypothesized that mutations and pathological diagnoses of meningiomas are associated with different embryological origins. We comprehensively evaluated associations among tumor location, pathological diagnosis (histological type), and genetic alterations including AKT1, KLF4, SMO, POLR2A, and NF2 mutations and 22q deletion in 269 meningioma cases. Based on the embryological origin of meninges, the tumor locations were as follows: neural crest, paraxial mesodermal, and dorsal mesodermal origins. Tumors originating from the dura of certain embryologic origin displayed a significantly different pathological diagnoses and genetic abnormality ratio. For instance, driver genetic mutations with AKT1, KLF4, SMO, and POLR2A, were significantly associated with the paraxial mesodermal origin (p = 1.7 × 10−10). However, meningiomas with NF2-associated mutations were significantly associated with neural crest origin (p = 3.9 × 10–12). On analysis of recurrence, no difference was observed in embryological origin. However, POLR2A mutation was a risk factor for the tumor recurrence (p = 1.7 × 10−2, Hazard Ratio 4.08, 95% Confidence Interval 1.28–13.0). Assessment of the embryological origin of the meninges may provide novel insights into the pathomechanism of meningiomas.

Although middle fossa arachnoid cysts (MFACs) are common, the optimal surgical treatment for these lesions remains controversial. In this study, we present our experiences of treating MFACs by microsurgical fenestration and evaluate its effectiveness.We performed retrospective review of 28 patients who underwent microsurgical fenestration for MFACs between May 2003 and December 2014. We reviewed patient characteristics and treatment outcomes including age, sex, symptoms, complicating hydrocephalus, Gallasi classification, change in cyst size after surgery, complicating subdural hygroma, symptom resolution, regrowth of the cyst, and reoperation (including additional CSF diversion).Twenty-eight MFACs in 28 patients were investigated. The average age at the time of surgery was 61.6 months. The average follow-up duration was 53.5 months. After surgery, 19 (90.5 %) of 21 patients with symptomatic MFACs experienced improvements. The cysts decreased in size in all cases (100 %, 28/28) and disappeared in three cases (11 %, 3/28). None of the cases experienced regrowth of the cyst. Subdural hygroma was identified in 23 cases (82.1 %) at the immediate postoperative period. Hygroma was asymptomatic in all cases but one. Hygroma disappeared in 19 cases (83 %) and decreased in size in three cases (13 %) in the long term. Only one case (4 %) required an additional subdural-peritoneal shunt. The rate of CSF diversion after the fenestration was significantly higher in patients with preoperative ventricular dilation (p = 0.0002).Microsurgical fenestration for pediatric MFACs was considered to be safe and effective. Although subdural hygroma developed in significant number of patients at the immediate postoperative period, it was mostly asymptomatic and disappeared or decreased in size in the long term.

OBJECTIVE. Not much is known about surgical management of patients with chronic subdural haematoma (CSDH) treated with antiplatelet or anticoagulant therapy. The aims of this study were to review the surgical outcomes of patients with CSDH and assess the risks of antiplatelet in their surgical management. METHODS. We retrospectively analysed 448 consecutive patients with CSDH treated by one burr hole surgery at our institution. Among them, 58 patients had been on antiplatelet therapy. We discontinued the antiplatelet agents before surgery for all 58 patients. For 51 of these 58 patients (87.9%), early surgery was performed within 0-2 days from admission. We analysed the association between recurrence and patient characteristics, including history of antiplatelet or anticoagulant therapy; age (< 70 years or ≥ 70 years); side; history of angiotensin receptor II blocker, angiotensin converting enzyme blocker, or statin therapy; and previous medical history of head trauma, infarction, hypertension, diabetes mellitus, haemodialysis, seizure, cancer, or liver cirrhosis. RESULTS. Recurrence occurred in 40 patients (8.9%), which was one of the lowest rates in the literature. Univariate analysis showed that only the presence of bilateral haematomas was associated with increased recurrence rate while antiplatelet or anticoagulant therapy did not significantly increase recurrence risk. Also, the recurrence rate from early surgery (0-2 days from drug cessation) for patients on antiplatelet therapy was not significantly higher than that from elective surgery (5 days or more after drug cessation). However, multivariate analysis revealed that previous history of cerebral infarction was an independent risk factor for CSDH recurrence. CONCLUSIOns. Our overall data support the safety of early surgery for patients on the preoperative antiplatelet therapy without drug cessation or platelet infusion. Patients with a previous history of infarction may need to be closely followed regardless of antiplatelet or anticoagulant therapy.

Pilomyxoid astrocytoma (PMA) was recently classified as a variant of pilocytic astrocytoma (PA) with significantly more aggressive clinical features than those of PA. Like PAs, PMAs frequently arise in the chiasmatic/hypothalamic regions. The cerebellum is also a common site of occurrence for PAs but not for PMAs. We present the case of a 31-month-old boy with cerebellar PMA that showed rapid regrowth during the 3 months following the first subtotal resection. Gross total resection was achieved in the second surgery, followed by radiation to the tumor bed. During follow-up over the next 12 years, there has been no evidence of recurrence on magnetic resonance imaging. Although the prognosis of cerebellar PMAs remains unknown because of the paucity of cases, the relevant literature reports a more favorable outcome for cerebellar PMAs than for PMAs occurring at other locations. The results of this case study and a review of the relevant literature advocate radical resection, sometimes involving multiple surgeries, for cerebellar PMAs because gross total or near total resection is more feasible in the cerebellum than in other locations.

Destructive infiltration of invasive fungal sinusitis can easily occur into the central nervous system (CNS). Cerebral aneurysms associated with fungal infection are highly vulnerable to rupture, and can frequently and rapidly take a serious clinical course. We experienced a patient who twice developed cerebral aneurysm followed by rupture due to invasive fugal sinusitis. This 77-year-old man was admitted for progressive bilateral visual disturbance, which was initially treated as idiopathic hypertrophic pachymeningitis. The patient subsequently suffered subarachnoid hemorrhage (SAH) twice in only 12 days. Both SAH originated from different newly formed cerebral aneurysms. Trapping was performed for both ruptured aneurysms. Pathological examination of the resected aneurysms indicated the presence of fungi determined to be Aspergillus. This Aspergillus infection was also discovered inside the frontal sinus by endoscopic biopsy, so a regimen of antifungal agents was instituted. Prolonged antifungal therapy caused renal impairment, which ultimately led to the patient’s death. Autopsy detected no mycotic infiltration of the major cerebral arteries, except for the 2 ruptured cerebral aneurysms. However, prolonged mycosis of the CNS, such as in the deep part in the falx cerebri and in the small veins proximal to the tentorium cerebelli, was observed, indicating that mycosis invading the cranium is refractory even to long-term administration of antifungal agents. The present case strongly suggests that urgent and proactive definitive diagnosis is essential to successfully treat invasive paranasal sinus aspergillosis. If infiltration of the CNS is suspected, early surgical resection and antifungal therapy must be initiated immediately.

Background Immunoglobulin G (IgG)4-related disease is a syndrome that forms inflammatory pseudotumors with increasing IgG4-positive plasma cells and lymphocytes infiltrating the exocrine gland and other organs. The concept of this disease gradually has gained more recognition. However, reports of intracranial pseudotumors associated with IgG4-related disease are very rare. The purpose of this report is to provide further information helpful in distinguishing IgG4-related disease from multiple meningiomas. Case Description We report a case of a 62-year-old man who presented with visual disturbance and quadrantanopia of the right eye. Magnetic resonance imaging revealed uniformly enhancing masses located near the right paraclinoid at the right Meckel's cave and along the left foramen magnum. He had experienced autoimmune pancreatitis 7 years previously, and the condition had responded to steroid therapy. Laboratory data revealed elevation of IgG (1877 mg/dL) and IgG4 (405 ng/dL). The right paraclinoidal lesion causing visual disturbance was subtotally removed, which provided sufficient decompression of the right optic nerve. IgG4 was strongly positive on immunohistochemical staining, and we started oral corticosteroid medication. Consequently, all lesion masses shrank remarkably within 1 month. Conclusion There have been a growing number of reports of such multiple pseudotumors associated with IgG4-related disease. In differential diagnosis, this disease entity requires special attention when multiple dural-based tumors are observed. Preoperative presumption is very important because this disease is likely to respond to steroid therapy.

Growing teratoma syndrome (GTS) is a rare clinical phenomenon defined as the paradoxical growth of mature teratoma components during or after chemotherapy. The mechanism of this phenomenon is not well understood. We present two cases of pineal mixed germ cell tumors that exhibited the similar course to GTS and speculate its pathogenesis.The first case was accompanied by slightly elevated alpha-fetoprotein (8.8 ng/ml; normal6.6 ng/ml). The tumor rapidly grew from 1.5 to 2.7 cm in diameter within 4 weeks. Despite this rapid preoperative growth, thorough pathological investigation found only mature teratoma components along with multiple micro- and macro-cysts. The other case was diagnosed as a pure germinoma based on biopsy and serological examinations. During three courses of chemotherapy, this tumor presented a honeycomb-like appearance on magnetic resonance (MR) images and an exceptionally rapid enlargement. Second-look surgery confirmed the histological diagnosis of a mature teratoma. In both cases, meticulous pathological examination of all whole tumor sections revealed no malignant histological features, and the MIB-1 labeling indices were too low to account for the extremely rapid tumor growth. Instead, both MR images and histological findings demonstrated a predominant formation of multiple cysts.We speculate that this paradoxical growth might not be tumorous proliferation but instead the formation and expansion of multiple cysts inside mature teratoma components and that the presence or absence of growth might be a subsidiary phenomenon. Our hypothesis appears consistent with the characteristic radiological findings of GTS reported in the literature.

We envisage the efficacy and safety of intra-arterial infusion of fasudil hydrochloride (IAF) for symptomatic vasospasm (SVS) after subarachnoid hemorrhage (SAH). We compared results obtained from the groups that received selective IAF (a microcatheter inserted in intracranial arteries) and nonselective IAF (a microcatheter inserted in the cervical arteries). Glasgow Outcome Scale (GOS) value and computed tomographic (CT) score were used to evaluate clinical outcome and the extent of infarction due to delayed vasospasm.Over 2 years, 113 patients with SAH underwent clipping or coiling. Among them, 31 patients (27.4%) developed SVS. We performed nonselective IAF in 10 patients and selective IAF in 10 other patients. Eleven patients with SVS were treated without IAF. The data were statistically analyzed.By univariate linear regression analysis, IAF negatively correlated with CT score (p = 0.016), but IAF was significantly correlated with GOS (p = 0.035). By multiple regression analysis, Hunt and Kosnik grade and CT score significantly correlated with GOS.CT score significantly correlated with functional outcome. Although IAF, both selective and nonselective, was significantly effective for the treatment of delayed vasospasm, the former seemed to be more beneficial.