Anti-vascular endothelial growth factor biosimilars for neovascular age-related macular degeneration.

RATIONALE: Neovascular age-related macular degeneration (AMD) is a progressive eye disease characterized by choroidal neovascularization (CNV) and is a leading cause of vision loss and disability worldwide. Although intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is an effective treatment option that helps to prevent vision loss or to improve visual acuity in people with neovascular AMD, treatment imposes a significant financial burden on patients and healthcare systems. A biosimilar is a biological product that has been developed to be nearly identical to a previously approved biological product. The use of biosimilars may help reduce costs and so may increase patient access to effective biologic medicines with similar levels of safety to the drugs on which they are based. OBJECTIVES: To assess the benefits and harms of anti-VEGF biosimilar agents compared with their corresponding anti-VEGF agents (i.e. the reference products) that have obtained regulatory approval for intravitreal injections in people with neovascular AMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registries together with reference checking and contact with study authors to identify studies that are included in the review. The latest search date was 2 June 2023. ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) that compared approved anti-VEGF biosimilars with their reference products for treating the eyes of adult participants (≥ 50 years) who had an active primary or recurrent choroidal neovascularization lesion secondary to neovascular AMD. OUTCOMES: Our outcomes were: best-corrected visual acuity (BCVA), central subfield thickness (CST), vision-related quality of life, serious ocular and non-ocular adverse events (AE), treatment-emergent adverse events (TEAEs), anti-drug antibodies (ADAs), and serum concentrations of biosimilars and reference drugs. RISK OF BIAS: We assessed the risk of bias (RoB) for seven outcomes reported in a summary of findings table by using the Cochrane RoB 2 tool. SYNTHESIS METHODS: We synthesized results for each outcome using meta-analysis, where possible, by calculating risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for dichotomous outcomes and continuous outcomes, respectively. Where this was not possible due to the nature of the data, we summarized the results narratively. We used GRADE to assess the certainty of evidence for prespecified outcomes. INCLUDED STUDIES: We included nine parallel-group multi-center RCTs that enrolled a total of 3814 participants (3814 participating eyes), with sample sizes that ranged from 160 to 705 participants per study. The mean age of the participants in these studies ranged from 67 to 76 years, and the proportion of women ranged from 26.5% to 58.7%. Ranibizumab (Lucentis) was the reference product in seven studies, and aflibercept (Eyelea) was the reference product in two others. All the included studies had been supported by industry. The follow-up periods ranged from 12 to 52 weeks (median 48 weeks). Five studies (56%) were conducted in multi-country settings across Europe, North America and Asia, two studies in India, and one each in Japan and the Republic of Korea. We judged all the included studies to have met high methodological standards. SYNTHESIS OF RESULTS: With regard to efficacy, our meta-analyses demonstrated that anti-VEGF biosimilars for neovascular AMD resulted in little to no difference compared with the reference products for BCVA change at 8 to 12 weeks (MD -0.55 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% CI -1.17 to 0.07; 8 studies, 3603 participants; high-certainty evidence) and the proportion of participants who lost fewer than 15 letters in BCVA at 24 to 48 weeks (RR 0.99, 95% CI 0.98 to 1.01; 7 studies, 2658 participants; moderate-certainty evidence). Almost all participants (96.6% in the biosimilar group and 97.0% in the reference product group) lost fewer than 15 letters in BCVA. The evidence from two studies suggested that there was no evidence of difference between biosimilars and reference products in vision-related quality of life measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) summary scores at 24 to 48 weeks (MD 0.82, 95% CI -0.70 to 2.35; 2 studies, 894 participants; moderate-certainty evidence). With regard to the safety profile, meta-analyses also revealed little to no difference between anti-VEGF biosimilars and the reference products for the proportion of participants who experienced serious ocular AEs (RR 1.24, 95% CI 0.68 to 2.26; 7 studies, 3292 participants; moderate-certainty evidence), and for TEAEs leading to investigational product discontinuation or death (RR 0.96, 95% CI 0.63 to 1.46; 8 studies, 3497 participants; moderate-certainty evidence). Overall, 1.4% of participants in the biosimilar group and 1.2% in the reference product group experienced serious ocular adverse events. The most frequently documented serious ocular AEs were retinal hemorrhage and endophthalmitis. Although the evidence is of low certainty due to imprecision, meta-analysis suggested that anti-VEGF biosimilars led to no difference compared with the reference products for cumulative incidence of ADAs (RR 0.84, 95% CI 0.58 to 1.22; 8 studies, 3066 participants; low-certainty evidence) or mean maximum serum concentrations (MD 0.42 ng/mL, 95% CI -0.22 to 1.05; subgroup of 3 studies, 100 participants; low-certainty evidence). We judged the overall risk of bias to be low for all studies. AUTHORS' CONCLUSIONS: In our review, low to high certainty evidence suggests that there is little to no difference, to date, between the anti-VEGF biosimilars approved for treating neovascular AMD and their reference products in terms of benefits and harms. While anti-VEGF biosimilars may be a viable alternative to reference products, current evidence for their use is based on a limited number of studies - particularly for comparison with aflibercept - with sparse long-term safety data, and infrequent assessment of quality of life outcomes. Our effect estimates and conclusions may be modified once findings have been reported from studies that are currently ongoing, and studies of biosimilar agents that are currently in development. FUNDING: Cochrane Eyes and Vision US Project is supported by grant UG1EY020522, National Eye Institute, National Institutes of Health. Takeshi Hasegawa and Hisashi Noma were supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant numbers: 22H03554, 19K03092, 24K06239). REGISTRATION: Protocol available via doi.org/10.1002/14651858.CD015804.

Pulvinar quantitative susceptibility mapping predicts visual hallucinations post-deep brain stimulation in Parkinson's disease.

PURPOSE: We have reported the relationship between low pulvinar nuclei (PN) intensity in susceptibility-weighted imaging and the appearance of visual hallucinations and cognitive function. The aim of the study was to examine the changes in the quantitative susceptibility mapping (QSM) in patients with Parkinson's disease (PD) who underwent deep brain stimulation (DBS) and verify whether the PN susceptibility value (SV) on QSM can predict visual hallucination and cognitive changes after DBS. METHODS: This study examined 24 patients with PD who underwent DBS along with QSM imaging on magnetic resonance imaging (MRI). All MRIs were performed within 3 months before surgery. The PN SV was further assessed based on the QSM. Then, associations were examined among cognitive changes, hallucination, and PN SV. The cognitive function of the patient was compared immediately before surgery and at 1 year postoperatively. RESULTS: Visual hallucinations were observed in seven patients during the follow-up period. The PN SV was ≥0.045 ppm in nine patients with PD, and six of them had visual hallucinations, whereas only one of 15 patients with PD with SV of <0.045 ppm had visual hallucinations (Fisher's exact test, p = .0037). CONCLUSIONS: The SV of >0.045 ppm at the PN in QSM in patients with PD may provide useful information suggesting visual hallucination and cognitive deterioration after DBS treatment.

Advanced multiparametric MRI and FDG-PET/CT in multinodular and vacuolating neuronal tumor: A pathologically confirmed case.

Multinodular and vacuolating neuronal tumor (MVNT) is a relatively new disease concept proposed in 2013 and was classified as a separate tumor type in 2021 by the World Health Organization (WHO) classification. MVNT can cause seizures but is a benign disease, with no cases of enlargement or postoperative recurrence reported. Recent reports described advanced MRI features in MVNT cases, but the diagnosis of MVNT is usually based on characteristic MRI findings of clusters of nodules. Here, we report advanced multiparametric MRI and FDG-PET/CT findings in a case of MVNT with epileptiform symptoms that was pathologically confirmed by surgery.

Antimicrobial Stewardship Program for Patients in the Hematological Department Receiving Carbapenem Therapy: A Single-Center and Interrupted Time Series Analysis.

As antibiotic resistance has become a global problem, the intervention of an antimicrobial stewardship team (AST) is warranted. In hematological disorders, infectious complications are crucial owing to abnormal neutrophil function and decreased cell-mediated immunity. Despite the widespread implementation of AST intervention, the effectiveness of stewardship practices for immunocompromised patients remains uncertain. We determined the effect of AST interventions on carbapenem therapy in the department of hematology. Patients admitted to the department and undergoing carbapenem therapy were enrolled. We compared carbapenem use between the pre-AST (April 2016-March 2018) and post-AST (April 2018-March 2021) periods. Factors associated with long-term carbapenem therapy were investigated. Overall, 515 episodes of carbapenem therapy in 264 patients in the department were evaluated. According to the interrupted time series analysis, the number of days of therapy decreased with AST intervention (ß = -0.263, p = 0.011). In multivariate analysis, predictive factors associated with long-term carbapenem therapy (>8 days) were outpatient onset, chronic obstructive pulmonary disease, acute myeloid leukemia, multiple myeloma, and infection with resistant bacteria (such as extended spectrum ß-lactamases and AmpC) (95% confidence interval, 1.030-2.818, 1.067-66.667, 1.057-2.782, 0.168-0.742, and 1.382-5.750, respectively). The AST intervention reduced carbapenem use in patients with hematological disorders.

Pseudocontinuous Arterial Spin Labeling: Clinical Applications and Usefulness in Head and Neck Entities.

As functional magnetic resonance imaging, arterial spin labeling (ASL) techniques have been developed to provide quantitative tissue blood flow measurements, which can improve the performance of lesion diagnosis. ASL does not require contrast agents, thus, it can be applied to a variety of patients regardless of renal impairments and contrast agent allergic reactions. The clinical implementation of head and neck lesions is limited, although, in recent years, ASL has been increasingly utilized in brain lesions. Here, we review the development of the ASL techniques, including pseudocontinuous ASL (pCASL). We compare readout methods between three-dimensional (3D) turbo spin-echo and 2D echo planar pCASL for the clinical applications of pCASL to head and neck lesions. We demonstrate the clinical usefulness of 3D pCASL for diagnosing various entities, including inflammatory lesions, hypervascular lesions, and neoplasms; for evaluating squamous cell carcinoma (SCC) treatment responses, and for predicting SCC prognosis.

Tumor blood flow and apparent diffusion coefficient histogram analysis for differentiating malignant salivary tumors from pleomorphic adenomas and Warthin's tumors.

We aimed to assess the combined diagnostic value of apparent diffusion coefficient (ADC) and tumor blood flow (TBF) obtained by pseudocontinuous arterial spin labeling (pCASL) for differentiating malignant tumors (MTs) in salivary glands from pleomorphic adenomas (PAs) and Warthin's tumors (WTs). We used pCASL imaging and ADC map to evaluate 65 patients, including 16 with MT, 30 with PA, and 19 with WT. We evaluated all tumors by histogram analyses and compared various characteristics by one-way analysis of variance followed by Tukey post-hoc tests. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis. There were significant differences in the mean, 50th, 75th, and 90th percentiles of TBF among the tumor types, in the mean TBFs (mL/100 g/min) between MTs (57.47 ± 35.14) and PAs (29.88 ± 22.53, p = 0.039) and between MTs and WTs (119.31 ± 50.11, p < 0.001), as well as in the mean ADCs (× 10-3 mm2/s) between MTs (1.08 ± 0.28) and PAs (1.60 ± 0.34, p < 0.001), but not in the mean ADCs between MTs and WTs (0.87 ± 0.23, p = 0.117). In the ROC curve analysis, the highest areas under the curves (AUCs) were achieved by the 10th and 25th percentiles of ADC (AUC = 0.885) for differentiating MTs from PAs and the 50th percentile of TBF (AUC = 0.855) for differentiating MTs from WTs. The AUCs of TBF, ADC, and combination of TBF and ADC were 0.850, 0.885, and 0.950 for MTs and PAs differentiation and 0.855, 0.814, and 0.905 for MTs and WTs differentiation, respectively. The combination of TBF and ADC evaluated by histogram analysis may help differentiate salivary gland MTs from PAs and WTs.

Long-term MRI changes in a patient with Kelch-like protein 11-associated paraneoplastic neurological syndrome.

BACKGROUND AND PURPOSE: The aim of this study was to identify the long-term radiological changes, autoantibody specificities, and clinical course in a patient with kelch-like protein 11 (KLHL11)-associated paraneoplastic neurological syndrome (PNS). METHODS: Serial brain magnetic resonance images were retrospectively assessed. To test for KLHL11 autoantibodies, longitudinal cerebrospinal fluid (CSF) and serum samples were screened by Phage-display ImmunoPrecipitation and Sequencing (PhIP-Seq). Immunohistochemistry was also performed to assess for the presence of KLHL11 in the patient's seminoma tissue. RESULTS: A 42-year-old man presented with progressive ataxia and sensorineural hearing loss. Metastatic seminoma was detected 11 months after the onset of the neurological symptoms. Although immunotherapy was partially effective, his cerebellar ataxia gradually worsened over the next 8 years. Brain magnetic resonance imaging revealed progressive brainstem and cerebellar atrophy with a "hot-cross-bun sign", and low-signal intensity on susceptibility-weighted imaging (SWI) in the substantia nigra, red nucleus and dentate nuclei. PhIP-Seq enriched for KLHL11-derived peptides in all samples. Immunohistochemical staining of mouse brain with the patient CSF showed co-localization with a KLHL11 commercial antibody in the medulla and dentate nucleus. Immunohistochemical analysis of seminoma tissue showed anti-KLHL11 antibody-positive particles in cytoplasm. CONCLUSIONS: This study suggests that KLHL11-PNS should be included in the differential diagnosis for patients with brainstem and cerebellar atrophy and signal changes not only on T2-FLAIR but also on SWI, which might otherwise be interpreted as secondary to a neurodegenerative disease such as multiple system atrophy.

Micro-MRI improves the accuracy of clinical diagnosis in cerebral small vessel disease.

Even with postmortem pathological examination, only limited information is provided of the foci of in vivo clinical information. Cerebral small vessel disease, which is associated with ageing, dementia and stroke, highlights the difficulty in arriving at a definitive diagnosis of the lesions detected on in vivo radiological examination. We performed a radiological-pathological comparative study using ex vivo MRI to examine small cerebral lesions. Four patients with small vessel disease lesions detected on in vivo MRI were studied. Exact pathological findings of in vivo MRI-detected lesions were revealed. The ischaemic lesion after 17 days from onset showed positivity for peroxiredoxin, cluster of differentiation 204 and glial fibrillary acidic protein, indicating sterile inflammation and neuroprotective reaction. Cortical microinfarcts beneath the cortical superficial siderosis were associated with inflammation from the superficial layer in a patient with cerebral amyloid angiopathy; in this patient, a bilinear track-like appearance of the cortical superficial siderosis on the ex vivo MRI was compatible with iron deposition on the pia matter and within cortical layers II-III. An in vivo MRI-detected cerebral microbleed was revealed to be heterogeneous. An in vivo MRI-detected cerebral microbleed was revealed to be a venous angioma. Furthermore, a neuropathologically confirmed embolic cerebral microbleed was firstly detected using this method. Our results suggest that in vivo MRI-detected lobar cerebral microbleeds can be caused by non-cerebral amyloid angiopathy aetiologies, such as microembolism and venous angioma. Venous angioma and embolic microbleeds may mimic cerebral amyloid angiopathy markers on in vivo MRI. To clarify the clinical importance of these lesions, we should investigate their rate and frequency in a large cohort of healthy individuals and patients with cardiac risk factors. Thus, we provide evidence that ex vivo micro-MRI improves the clinical diagnosis of small vessel diseases.

Hemangioblastoma of the Cerebellopontine Angle Evaluated with Pseudocontinuous Arterial Spin Labeling.

Hemangioblastomas of the cerebellopontine angle (CPA) that emerge extra-axially from the peripheral nervous system are extremely rare. We report a case of hemangioblastoma of the CPA evaluated by pseudocontinuous arterial spin labeling (pCASL). The high rate of tumor blood flow determined using pCASL provided additional useful information for the differential diagnosis of the CPA tumors in this patient.

A Case of Miyazaki Syndrome Caused by Arachnoid Cyst-Peritoneal Shunt.

BACKGROUND: Miyazaki syndrome is overshunting-associated myelopathy, which is a rare complication of ventriculoperitoneal shunt. We present the first case of Miyazaki syndrome caused by cystoperitoneal (CP) shunt for an arachnoid cyst (AC) in this report. CASE DESCRIPTION: We report a case of a 42-year-old man with 12-year progressive spastic paraplegia, who underwent CP shunt for an AC at the age of 15 years. Although few findings suggested overshunting on symptoms and head computed tomography, contrast-enhanced magnetic resonance imaging revealed the engorgement of the cervical spinal epidural venous plexus compressing the spinal cord. Shunt valve replacement with a pressure-adjustable valve was performed. Postoperatively, the cervical cord compression by the enlarged spinal epidural venous plexus was completely improved, but, possibly due to delayed diagnosis and treatment, the patient's symptoms only partially improved. CONCLUSIONS: When patients with a history of any kind of shunt surgery develop myelopathy, Miyazaki syndrome should be suspected and, for early diagnosis, cervical and/or contrast-enhanced magnetic resonance imaging should be performed.

Evaluation of Intradural Ecchordosis Physaliphora With Three-Dimensional Fluid-Attenuated Inversion Recovery.

OBJECTIVE: This study evaluated the efficacy of 3-dimensional fluid-attenuated inversion recovery (3D FLAIR) for detecting intradural ecchordosis physaliphora (EP). METHODS: We retrospectively determined the presence or absence of intradural EP on 3D FLAIR for 3888 consecutive patients, classifying the EP as "classical" or "possible" and analyzing the prevalence, size, and presence or absence of an intraosseous stalk. Where available, magnetic resonance cisternography images were compared with the 3D FLAIR images. RESULTS: Intradural EP was identified in 50 patients (1.3%): 36 (0.9%) classical and 14 (0.4%) possible. The classical EPs were significantly larger than the possible EPs (P < 0.01). Nine EPs (18.0%) showed an osseous stalk. Magnetic resonance cisternography was performed for 19 EPs (16 classical, 3 possible), detecting all 16 classical EPs but none of the possible EPs. CONCLUSIONS: Classical EPs were detected by 3D FLAIR as with magnetic resonance cisternography. The 3D FLAIR findings suggested a new type of possible EP variant previously unreported.

Low Pulvinar Intensity in Susceptibility-Weighted Imaging May Suggest Cognitive Worsening After Deep Brain Stimulation Therapy in Patients With Parkinson's Disease.

Purpose: Deep brain stimulation (DBS) is an established therapy for Parkinson's disease (PD). However, deteriorating cognitive function after DBS is a considerable problem for affected patients. This study was undertaken to assess whether pulvinar findings in susceptibility-weighted imaging (SWI) can suggest cognitive worsening. Methods: We examined 21 patients with PD who underwent DBS along with SWI and neuromelanin-sensitive MR imaging (NMI). We further assessed pulvinar hypointensity based on the SWI findings and also the area of the substantia nigra (SN) pars compacta in NMI. We then examined associations among cognitive changes, pulvinar hypointensity, and SN area. The cognitive function of the patient immediately before surgery was compared with function at 1 year postoperatively. Results: Pulvinar hypointensity in SWI was found in 11 of 21 patients with PD at baseline. One year postoperatively, six of the 21 patients demonstrated a Mini-Mental State Examination score that was ≥3 points lower than the baseline score. We observed pulvinar hypointensity in SWI before DBS surgery in five of these six patients (p = 0.072). During the first postoperative year, six of 21 patients reported both transient or permanent hallucinations; we observed pulvinar hypointensity in these six patients, while 10 patients without pulvinar hypointensity had no hallucinations. Conclusion: Pulvinar hypointensity in SWI in patients with PD may provide information that is useful for suggesting cognitive deterioration after DBS treatment.

Evaluation of a high-signal lesion posterior to the intracranial vertebral artery using 3D balanced fast-field echo imaging.

Previous reports have identified a small, benign, high-signal lesion (HSL) posterior to the intracranial vertebral artery and associated with the ipsilateral spinal accessory nerve (SAN) using 3D fluid-attenuated inversion recovery (3D FLAIR) imaging as an emerging new entity. To elucidate the relationship between HSLs and SAN, 76 patients with 86 HSLs were evaluated using 3D FLAIR and 3D balanced fast-field echo (3D bFFE imaging). All HSLs showed contact with ipsilateral SAN on both the sequences. 3D bFFE imaging clearly distinguished between the two structures unlike 3D FLAIR. Moreover, SAN was surrounded by HSLs on 3D bFFE images, which may be a characteristic of this entity.

A case of a rosette-forming glioneuronal tumor arising from the pons with disappearance of contrast enhancement.

A rosette-forming glioneuronal tumor (RGNT) is a rare and slow-growing central nervous system tumor. This tumor is usually assessed by MRI during the follow-up period. RGNT can show alteration of contrast enhancement regardless of tumor growth. Here, we report a case of RGNT arising from pons which shows partial enhancement on initial MRI, smaller enhancement on follow-up MRI at 10 months, and totally disappeared at 18 months without any therapy.

Vertebral artery dissection associated with familial Mediterranean fever and Behçet's disease.

Vertebral artery dissection and recurrent meningitis are rare complications in Behçet's disease. Behçet's disease may be associated with familial Mediterranean fever. Here, we describe a 52-year-old woman with severe headache who exhibited recurrent meningitis and vertebral artery dissection. Cerebrospinal fluid showed high levels of interleukin-6. Magnetic resonance imaging revealed right vertebral artery dissection. The patient had three heterozygous mutations in the familial Mediterranean fever gene (MEFV) gene. She fulfilled criteria for diagnosis of Behçet's disease and familial Mediterranean fever. In conclusion, mutations of the MEFV gene may cause neuro-inflammatory disorders and cerebrovascular disorders by reducing anti-inflammatory activity of pyrin.

A numerical approach for a discrete Markov model for progressing drug resistance of cancer.

The presence of treatment-resistant cells is an important factor that limits the efficacy of cancer therapy, and the prospect of resistance is considered the major cause of the treatment strategy. Several recent studies have employed mathematical models to elucidate the dynamics of generating resistant cancer cells and attempted to predict the probability of emerging resistant cells. The purpose of this paper is to present numerical approach to compute the number of resistant cells and the emerging probability of resistance. Stochastic model was designed and developed a method to approximately but efficiently compute the number of resistant cells and the probability of resistance. To model the progression of cancer, a discrete-state, two-dimensional Markov process whose states are the total number of cells and the number of resistant cells was employed. Then exact analysis and approximate aggregation approaches were proposed to calculate the number of resistant cells and the probability of resistance when the cell population reaches detection size. To confirm the accuracy of computed results of approximation, relative errors between exact analysis and approximation were computed. The numerical values of our approximation method were very close to those of exact analysis calculated in the range of small detection size M = 500, 100, and 1500. Then computer simulation was performed to confirm the accuracy of computed results of approximation when the detection size was M = 10000,30000,50000,100000 and 1000000. All the numerical results of approximation fell between the upper level and the lower level of 95% confidential intervals and our method took less time to compute over a broad range of cell size. The effects of parameter change on emerging probabilities of resistance were also investigated by computed values using approximation method. The results showed that the number of divisions until the cell population reached the detection size is important for emerging the probability of resistance. The next step of numerical approach is to compute the emerging probabilities of resistance under drug administration and with multiple mutation. Another effective approximation would be necessary for the analysis of the latter case.

Comparison of Premortem Magnetic Resonance Imaging and Postmortem Autopsy Findings of a Cortical Microinfarct.

An 85-year-old woman diagnosed with amyotrophic lateral sclerosis died of pneumonia and was autopsied. Magnetic resonance imaging (MRI) performed 16 days before death revealed an intracortical high-intensity lesion in her right temporal cortex on three-dimensional (3D)-double inversion recovery (DIR) and 3D-fluid-attenuated inversion recovery (FLAIR) images. Histopathological examination indicated a cortical microinfarct (CMI) juxtaposed to cerebral amyloid angiopathy. Recently, in vivo detection of CMIs using 3D-DIR and 3D-FLAIR on 3-tesla MRI has been reported, and postmortem MRI study confirmed the presence of CMIs. This is the first case study to compare CMI findings detected upon premortem MRI to the CMI itself discovered upon postmortem neuropathological examination.

Ipilimumab-induced hypophysitis involving the optic tracts and tuber cinereum evaluated using 3D fluid-attenuated inversion recovery.

Ipilimumab, a human monoclonal antibody against cytotoxic T-lymphocyte antigen 4, was approved by the U.S. FDA (Food and Drug Administration) in 2011 for the treatment of unresectable or metastatic malignant melanoma. Occurrence of hypophysitis, an immune-related adverse event due to ipilimumab use, has been frequently reported. We report a case of ipilimumab-induced hypophysitis involving the optic tracts and tuber cinereum, identified using 3D fluid-attenuated inversion recovery.

Diffusion tensor imaging and magnetic resonance spectroscopy in a patient with adult onset tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) 1 or TSC2 is mutated in most TSC patients. TSC2 mutations are more frequently associated with worse outcomes, earlier age at seizure onset, more severe intellectual disability, and higher tuber load than TSC1. The degree of white matter involvement is thought to be associated with the severity of neurological impairment. At present, genotype-phenotype correlations and relationship between tuber burden and neurological disability in TSC are debatable. We presented a 43-year-old patient with TSC2 mutation, whose symptom was only incomplete quadrantic visual field deficit in spite of multiple brain tubers. The visual field deficit was thought to be due to a small lesion in the upper medial part of the optic radiation revealed by diffusion tensor imaging. Her brain tubers showed normal findings in magnetic resonance spectroscopy. Our case suggested that neurological and neuropsychiatric manifestations of TSC are affected by the quality rather than number of the lesions. In addition, MRS may be useful to identify the correlation between brain tubers and neurological disability in TSC patients.