Intravenous immunoglobulin treatment for steroid-resistant optic neuritis: a multicenter, double-blind, randomized, controlled phase III study.

PURPOSE: To evaluate the efficacy and safety of intravenous "freeze-dried sulfonated human normal immunoglobulin (GGS)" in patients with steroid-resistant optic neuritis (ON). STUDY DESIGN: Multicenter, prospective, double-blind, parallel-group, randomized controlled trial. METHODS: Patients with steroid-resistant acute ON were randomly assigned to receive either intravenous GGS (GGS group) or intravenous methylprednisolone (steroid pulse [SP] group). Visual acuity (logarithm of the minimum angle of resolution [logMAR]), mean deviation (MD) value of the Humphrey Field Analyzer, and critical flicker fusion frequency were measured as efficacy endpoints; adverse events (AEs) were assessed as the safety endpoint. RESULTS: Thirty-two patients (16 patients/group) received the study drugs. The primary endpoint, change in logMAR at week 2 compared to baseline, showed no statistically significant intergroup difference. However, compared with the SP group, change in the GGS group was increasingly indicative of visual improvement, with least squares mean difference of > 0.3 logMAR. On post-hoc analyses, the percentage of patients in the GGS and SP groups with improvement by ≥ 0.3 logMAR at week 2 were 75.0% and 31.3%, respectively. Changes in MD values at week 2 compared to baseline were 9.258  ±  8.296 (mean ± standard deviation) dB and 3.175  ±  6.167 dB in the GGS and SP groups, respectively. These results showed statistically significant intergroup differences (visual acuity improvement, P = 0.032; change in MD values, P = 0.030). No clinically significant AEs were observed. CONCLUSION: Our results suggest that intravenous immunoglobulin could be a safe and efficacious therapeutic option for prompt treatment of steroid-resistant acute ON. TRIAL REGISTRATION: JapicCTI-132080.

Extended transsphenoidal approach for surgical management of pituitary adenomas invading the cavernous sinus.

OBJECTIVES: The authors devised an extended transsphenoidal approach involving a submucosal posterior ethmoidectomy that allows for adequate exposure of the cavernous sinus. To evaluate the adequacy of this approach for removal of adenomas invading the cavernous sinus, the authors retrospectively analyzed the surgical outcomes obtained in treated patients. METHODS: During a 9-year period, 36 patients with pituitary adenomas extending into the cavernous sinus underwent tumor removal at Kinki University Hospital. In the authors' technique of extended transsphenoidal surgery, the inferior wall of the affected cavernous sinus was entirely exposed, not only to permit safe removal of the tumor but also to secure the petrous portion of the internal carotid artery (ICA). For prevention of intraoperative injury to the cranial nerves, a low-profile pressure sensor was attached on the eyelid to detect eye movements in response to electrical stimulation of the cranial nerves. RESULTS: Total or subtotal tumor removal was achieved in 72% of 36 patients. In eight (67%) of 12 patients with growth hormone-secreting adenomas, hormonal remission was achieved postoperatively. Postoperative transient double vision was observed in 27% of the patients, but no serious complications, such as permanent cranial nerve palsy or ICA injury, occurred. CONCLUSIONS: These reasonable surgical results obtained in the present series of patients suggest that the extended transsphenoidal approach is safe and effective for removal of adenomas within the cavernous sinus. These preliminary results may lead to a reevaluation of the role of surgery as the therapeutic strategy for invasive pituitary adenomas.

Postoperative improvement in visual function in patients with tuberculum sellae meningiomas: results of the extended transsphenoidal and transcranial approaches.

OBJECT: Recently, extended transsphenoidal surgery (ETSS) has become an alternative to transcranial surgery (TCS) for suprasellar meningiomas, although the relative benefits of ETSS have yet to be established. To evaluate the effectiveness of ETSS, the authors analyzed surgical outcomes of TCS and ETSS. METHODS: During a 12-year period, 28 patients with meningiomas arising from the tuberculum sellae underwent tumor removal at Kinki University Hospital. The first 12 patients underwent TCS, and the remaining 16 underwent ETSS. In the TCS group, the optic canal on the approach side was unroofed in all cases. In the ETSS group bilateral optic canals were opened, and the dural and bone defects of the skull base were repaired using abdominal fascia and hydroxyapatite cement. In half of the cases, lumbar drainage of cerebrospinal fluid (CSF) was also performed. RESULTS: In a retrospective analysis of this consecutive series of patients, improvement in visual acuity and intraoperative blood loss were significantly better in the ETSS group (p = 0.010 and p = 0.011, respectively), whereas improvement in visual field defects, operative times, and the tumor removal rate were not significantly different between the two groups. Nonvisual surgical complications such as CSF leakage (one patient) and infarction of a perforating artery (three patients) were observed in the TCS group. In the ETSS group, CSF leakage (two patients), anosmia (two patients), and infarction of a perforating artery (two patients) were observed. CONCLUSIONS: Given the encouraging results in improvement in visual acuity, ETSS may be acceptable for the treatment of tuberculum sellae meningiomas.

Two types of acute zonal occult outer retinopathy differentiated by dark- and light-adapted perimetry.

PURPOSE: To assess the results of perimetry recorded under dark- and light-adapted (DA and LA) conditions in patients with acute zonal occult outer retinopathy (AZOOR) and to compare the results of electroretinography (ERG) and spectral-domain optical coherence tomography (SD-OCT) in two groups of AZOOR patients. METHODS: Twelve patients with AZOOR were studied. The diagnosis of AZOOR was based on the results of ophthalmoscopy, Goldmann kinetic perimetry, and multifocal ERGs. In addition, DA and LA perimetry, ERG, and SD-OCT were performed. The patients were followed for 1-9 years. RESULTS: The patients were classified into two types: type A patients (3) had a scotoma detected by both DA and LA perimetry, normal or equally abnormal cone and rod ERGs, atrophy of the outer nuclear layer (ONL), and disruption of the inner segment/outer segment (IS/OS) junction line in the OCT images. Type B patients (7) had a scotoma that was more prominent in LA than in DA perimetry and a continuous IS/OS junction line in the OCT images. Two patients had characteristics of both type A and type B AZOOR. CONCLUSIONS: Our findings suggest that eyes with type A AZOOR have focal and severe impairment of both the rods and cones, and eyes with type B AZOOR have focal and specific impairment of the cones.

Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features.

BACKGROUND: Wolfram syndrome (WFS) is a recessive neurologic and endocrinologic degenerative disorder, and is also known as DIDMOAD (Diabetes Insipidus, early-onset Diabetes Mellitus, progressive Optic Atrophy and Deafness) syndrome. Most affected individuals carry recessive mutations in the Wolfram syndrome 1 gene (WFS1). However, the phenotypic pleiomorphism, rarity and molecular complexity of this disease complicate our efforts to understand WFS. To address this limitation, we aimed to describe complications and to elucidate the contributions of WFS1 mutations to clinical manifestations in Japanese patients with WFS. METHODOLOGY: The minimal ascertainment criterion for diagnosing WFS was having both early onset diabetes mellitus and bilateral optic atrophy. Genetic analysis for WFS1 was performed by direct sequencing. PRINCIPAL FINDINGS: Sixty-seven patients were identified nationally for a prevalence of one per 710,000, with 33 patients (49%) having all 4 components of DIDMOAD. In 40 subjects who agreed to participate in this investigation from 30 unrelated families, the earliest manifestation was DM at a median age of 8.7 years, followed by OA at a median age of 15.8 years. However, either OA or DI was the first diagnosed feature in 6 subjects. In 10, features other than DM predated OA. Twenty-seven patients (67.5%) had a broad spectrum of recessive mutations in WFS1. Two patients had mutations in only one allele. Eleven patients (27.5%) had intact WFS1 alleles. Ages at onset of both DM and OA in patients with recessive WFS1 mutations were indistinguishable from those in patients without WFS1 mutations. In the patients with predicted complete loss-of-function mutations, ages at the onsets of both DM and OA were significantly earlier than those in patients with predicted partial-loss-of function mutations. CONCLUSION/SIGNIFICANCE: This study emphasizes the clinical and genetic heterogeneity in patients with WFS. Genotype-phenotype correlations may exist in patients with WFS1 mutations, as demonstrated by the disease onset.

Novel strategy for orbital tumor resection: surgical "displacement" into the maxillary cavity.

Surgical intervention consisting of lateral orbitotomy, the indication of which is extremely wide for orbital tumor surgery, has been applied in cases of large, retrobulbar cavernous hemangioma. However, no method exists involving displacement of the tumor from the crowded orbital contents, with the exception of tumor traction toward the outer side. The impact of traction force on the fragile hemangioma is extremely traumatic and dangerous. The authors examined how a tumor might be "displaced" in the absence of traction force effect, into an appropriate cavity neighboring the orbit. The maxillary sinus may afford the most suitable space to shift the laterally situated orbital tumor. Thus, the osteotomy level was extended to the lateral half of the inferior orbital floor and orbital rim in order to displace the tumor through an "escape window" of sufficient size between the orbit and maxilla. This report describes the treatment of two cases with long histories of progressive proptosis associated with retrobulbar large cavernous hemangiomas. This novel procedure resulted in a successful outcome. The current approach and management, which involves displacement of the tumor into the maxillary sinus through the orbital floor escape window, is a novel procedure for orbital tumor surgery.