Hypophysitis that develops in cancer patients treated with monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4; an inhibitory molecule classically expressed on T cells) is now reported at an incidence of approximately 10%. Its pathogenesis is unknown, in part because no pathologic examination of the pituitary gland has been reported to date. We analyzed at autopsy the pituitary glands of six cancer patients treated with CTLA-4 blockade, one with clinical and pathologic evidence of hypophysitis, one with mild lymphocytic infiltration in the pituitary gland but no clinical signs of hypophysitis, and four with normal pituitary structure and function. CTLA-4 antigen was expressed by pituitary endocrine cells in all patients but at different levels. The highest levels were found in the patient who had clinical and pathologic evidence of severe hypophysitis. This high pituitary CTLA-4 expression was associated with T-cell infiltration and IgG-dependent complement fixation and phagocytosis, immune reactions that induced an extensive destruction of the adenohypophyseal architecture. Pituitary CTLA-4 expression was confirmed in a validation group of 37 surgical pituitary adenomas and 11 normal pituitary glands. The study suggests that administration of CTLA-4 blocking antibodies to patients who express high levels of CTLA-4 antigen in the pituitary can cause an aggressive (necrotizing) form of hypophysitis through type IV (T-cell dependent) and type II (IgG dependent) immune mechanisms.

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Radiation necrosis (RN) of brain tissue is a serious late complication of brain irradiation and recently bevacizumab has been suggested as treatment option of RN. There is a lack of data in the literature regarding the effectiveness of bevacizumab for the treatment of RN. The purpose of this review was to perform a comprehensive analysis of all reported cases using bevacizumab for the treatment of brain RN. In September 2016, we performed a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane Library. The research for the review was conducted using a combination of the keywords “radiation necrosis”, “radiotherapy” and “bevacizumab” alongside the fields comprising article title, abstract and keywords. Randomized trials, non-randomized trials, prospective studies, retrospective studies and single case reports were included in the review. Our research generated 21 studies and 125 cases where bevacizumab had been used for the treatment of RN. The median follow-up was 8 months and the most frequent bevacizumab dose used was 7.5 mg/kg for 2 weeks with a median of four cycles. Low-dose bevacizumab resulted in effectiveness with improvement in both clinical and radiographic response. The median decrease in T1 contrast enhancement and in T2/FLAIR signal abnormality was 64% and 60%, respectively. A reduction in steroidal therapy was observed in majority of patients treated. Based on the data of our review, bevacizumab appears to be a promising agent for the treatment of brain RN. Future prospective studies are required to evaluate the role of bevacizumab in RN and to define the optimal scheduling, dosage and duration of therapy.

Morphological indexes indicate midbrain atrophy in PSP patients The combination of the A(ms) and A(ms)/A(pn) ratio measurements allows to discriminate between PSP and other conditions.

ObjectivesTo explore the role of the available midbrain-based MRI morphometric assessments in (1) differentiating among progressive supranuclear palsy (PSP) subtypes (PSP Richardson’s syndrome (PSP-RS), PSP with predominant parkinsonism (PSP-P) and the other variant syndromes of PSP (vPSP)), and (2) supporting the diagnosis of PSP subtypes compared with Parkinson’s disease (PD) and healthy controls (HC).MethodsSeventy-eight patients with PSP (38 PSP-RS, 21 PSP-P and 19 vPSP), 35 PD and 38 HC were included in the present analysis. Available midbrain-based MRI morphometric assessments were calculated for all participants.ResultsCurrent MRI midbrain-based assessments do not display an adequate sensitivity and specificity profile in differentiating PSP subtypes. On the other hand, we confirmed MR Parkinsonism Index (MRPI) and pons area to midbrain area ratio (P/M) have adequate diagnostic value to support PSP-RS clinical diagnosis compared with both PD and HC, but low sensitivity and specificity profile in differentiating PSP-P from PD as well as from HC. The same measures show acceptable sensitivity and specificity profile in supporting clinical diagnosis of vPSP versus HC but not versus PD. Similar findings were detected for the newer MRPI and P/M versions.ConclusionsFurther studies are warranted to identify neuroimaging biomarkers supporting the clinical phenotypic categorisation of patients with PSP. MRPI and P/M have diagnostic value in supporting the clinical diagnosis of PSP-RS.Classification of evidenceThis study provides class III evidence that available MRI midbrain-based assessments do not have diagnostic value in differentiating the Movement Disorder Society PSP subtypes.

Background and purposeDifferential diagnosis between Parkinson's disease (PD) and Atypical Parkinsonisms, mainly Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA), remains challenging. The low sensitivity of macroscopic findings at imaging might limit early diagnosis. The availability of iron-sensitive MR techniques and high magnetic field MR scanners provides new insights in evaluating brain structures in degenerative parkinsonisms. Quantitative Susceptibility Mapping (QSM) allows quantifying tissue iron content and could be sensitive to microstructural abnormalities which precede the appearence of regional atrophy. We measured the magnetic susceptibility (χ) of nigral and extranigral regions in patients with PD, PSP and MSA to evaluate the potential utility of the QSM technique for differential diagnosis.Materials and methods65 patients (36 PD, 14 MSA, 15 PSP) underwent clinical and radiological evaluation with 3 T MRI. QSM maps were obtained from GRE sequences. ROI were drawn on substantia nigra (SN), red nucleus (RN), subthalamic nucleus (STN), putamen, globus pallidus and caudate. χ values were compared to detect inter-group differences.ResultsThe highest diagnostic accuracy for PSP (area under the ROC curve, AUC, range 0.9–0.7) was observed for increased χ values in RN, STN and medial part of SN whereas in MSA (AUC range 0.8–0.7) iron deposition was significantly higher in the putamen, according to the patterns of pathological involvement that characterize the different diseases.ConclusionQSM could be used for iron quantification of nigral and extranigral structures in all degenerative parkinsonisms and should be tested longitudinally in order to identify early microscopical changes.

BackgroundMyotonic dystrophy type 1 (Steinert’s disease or DM1), the most common form of autosomal dominant muscular dystrophy in adults, is a multisystem disorder, affecting skeletal muscle as well as eyes, heart, gastrointestinal tract, endocrine system, and central nervous system, finally responsible of increasing disabilities and secondary social consequences. To date, DM1-related brain involvement represents a challenging field of research. It is well known that DM1 patients frequently present neuropsychological disturbances and psychiatric comorbidities among which reduced awareness of disease burden and its progression, also defined as anosognosia, is common in clinical practice, this leading to secondary misattribution of symptoms, delay in timely diagnostic procedures and low compliance to treatment.MethodsHere we present an observational cross sectional study in which disease-related cognitive dysfunctions and quality of life were assessed by a protocol finally designed to estimate the prevalence of disease awareness in a sample of 65 adult-onset DM1 patients.ResultsOur analysis showed that in DM1 patients several cognitive functions, including executive and mnesic domains with visuo-spatial involvement, were affected. The assessment of anosognosia revealed that a high percentage (51.6 %) of DM1 subjects was disease unaware. The reduced illness awareness occurs across different physical and life domains, and it appears more prominent in Activities and Independence domains investigated by the Individualized Neuromuscular Quality Of Life (INQoL) questionnaire. Moreover, the unawareness resulted significantly related (at p <0.05 and p < 0.01) to the performance failure in cognitive tests, specifically in the domains of visuo-spatial memory, cognitive flexibility and conceptualization.ConclusionsThe obtained data confirm, by a systematic analysis, what’s the common clinical perceiving of disease unawareness in Steinert’s disease, this related to the already known cognitive-behavioural impairment of frontal type in affected patients. We believe that a deep knowledge of this aspect will be useful for medical practice in the management of patients with DM1, also for guidance in occupational and social interventions, definition of outcome measures and in preparation of trial readiness.

The rotational variance dependence of diffusion tensor imaging (DTI) derived parameters on the number of diffusion weighting directions (N) has been investigated by several Monte Carlo simulation studies. However, the dependence of fractional anisotropy (FA) and mean diffusivity (MD) maps on N, in terms of accuracy and contrast between different anatomical structures, has not been assessed in detail. This experimental study further investigated in vivo the effect of the number of diffusion weighting directions on DTI maps of FA and MD. Human brain FA and MD maps of six healthy subjects were acquired at 1.5T with varying N (6, 11, 19, 27, 55). Then, FA and MD mean values in high false(FAH,.2emMDHfalse) and low false(FAL,.2emMDLfalse) anisotropy segmented brain regions were measured. Moreover, the contrast‐to‐signal variance ratio false(CVRFA,.2emCVRMDfalse) between the main white matter and the surrounding regions was calculated. Analysis of variance showed that FAL,.2emFAH and CVRFA significantly false(p<0.05false) depend on N. In particular, FAL decreased (6%–11%) with N, whereas FAH (1.6%–2.5%) and CVRFA (4%–6.5%) increased with normalN..2emMDL,.2emMDH and CVRMD did not significantly false(p>0.05false) depend on N. Unlike MD values, FA values significantly vary with N. It is noteworthy that the observed variation is opposite in low and high anisotropic regions. In clinical studies, the effect of N may represent a confounding variable for anisotropy measurements and the employment of DTI acquisition schemes with high normalN.2emfalse(>.2em20false) allows an increased CVR and a better visualization of white matter structures in FA maps.PACS number: 87.61.Tg, 82.56.Lz