Introduction Assessing the treatment response of glioblastoma multiforme during immunotherapy (IT) is an open issue. Treatment response assessment maps (TRAMs) might help distinguish true tumor progression (TTP) and pseudoprogression (PsP) in this setting. Methods We recruited 16 naïve glioblastoma patients enrolled in a phase II trial consisting of the Stupp protocol (a standardized treatment for glioblastoma involving combined radiotherapy and chemotherapy with temozolomide, followed by adjuvant temozolomide) plus IT with dendritic cells. Patients were followed up till progression or death; seven underwent a second surgery for suspected progression. Clinical, immunological, and MRI data were collected from all patients and histology in case of second surgery. Patients were classified as responders (progression-free survival, PFS > 12 months), and non-responders (PFS ≤ 12), HIGH-NK (natural killer cells, i.e., immunological responders), and LOW-NK (immunological non-responders) based on immune cell counts in peripheral blood. TRAMs differentiate contrast-enhancing lesions with different washout dynamics into hypothesized tumoral (conventionally blue-colored) vs. treatment-related (red-colored). Results Using receiver operating characteristic (ROC) curves, a threshold of −0.066 in V Blue/ V CE (volume of the blue portion of tumoral area/volume of contrast enhancement) variation between values obtained in the MRI performed before PsP/TTP and at TTP/PSP allowed to discriminate TTP from PsP with a sensitivity of 71.4% and a specificity of 100%. Among HIGH-NK patients, at month 6 there was a significant reduction compared to baseline and month 2 in median “blue” volumes. Discussion In conclusion, in our pilot study TRAMs support the discrimination between tumoral and treatment-related enhancing features in immunological responders vs. non-responders, the distinction between PsP and TTP, and might provide surrogate markers of immunological response.
Spontaneous intracranial hypotension (SIH) is characterised by orthostatic headache, low cerebrospinal fluid pressure and diffuse pachymeningeal enhancement after intravenous gadolinium contrast administration. Magnetic resonance imaging (MRI) often plays a crucial role for correct diagnosis.We described two similar cases of SIH, whose clinical and imaging features are typical for this pathology. At MRI brain scan, both patients showed diffuse and intense pachymeningeal enhancement and moderate venous distension and epidural vein engorgement. The two patients were treated with bed rest and oral steroid therapy, with complete and long-lasting symptomatic relief.Orthostatic nature of headache is the most indicative clinical feature suggesting SIH; contrast-enhanced MRI provides definite imaging diagnostic findings. Conservative treatment coupled to steroid therapy is often sufficient to obtain complete disappearance of symptoms.
Introduction: Lysosomal storage disorders (LSD) are often characterized by abnormal brain development, reflected by a reduction of intracranial volume (ICV). The aim of our study was to perform a volumetric analysis of intracranial tissues in Fabry Disease (FD), investigating possible reductions of ICV as a potential expression of abnormal brain development in this condition. Materials and Methods: Forty-two FD patients (15 males, mean age 43.3 ± 13.0 years) were enrolled along with 38 healthy controls (HC) of comparable age and sex. Volumetric MRI data were segmented using SPM12 to obtain intracranial tissue volumes, from which ICV values were derived. Results: Mean ICV of FD patients was 8.1% smaller compared to the control group (p < 5·10-5). Unlike what typically happens in neurodegenerative disorders, no significant differences emerged when comparing between the two groups the fractional volumes of gray matter, white matter and CSF (i.e., normalized by ICV), consistent with a harmonious volumetric reduction of intracranial structures. Discussion: The present results suggest that in FD patients an abnormality of brain development is present, expanding the current knowledge about central nervous system involvement in FD, further emphasizing the importance of an early diagnosis.
ABSTRACT Background and Methods Mutations in WDR45 cause β‐propeller protein‐associated neurodegeneration (BPAN), a type of neurodegeneration with brain iron accumulation (NBIA). We reviewed clinical and MRI findings in 4 patients with de novo WDR45 mutations. Results Psychomotor delay and movement disorders were present in all cases; early‐onset epileptic encephalopathy was present in 3. In all cases, first MRI showed: prominent bilateral SN enlargement, bilateral dentate nuclei T2‐hyperintensity, and corpus callosum thinning. Iron deposition in the SN and globus pallidus (GP) only became evident later. Diffuse cerebral atrophy was present in 3 cases. Conclusions In this series, SN swelling and dentate nucleus T2 hyperintensity were early signs of BPAN, later followed by progressive iron deposition in the SN and GP. When clinical suspicion is raised, MRI is crucial for identifying early features suggesting this type of NBIA.
The aim of this study was to perform the first resting-state functional MRI (RS-fMRI) analysis in Friedreich's ataxia (FRDA) patients to assess possible brain functional connectivity (FC) differences in these patients, and test their correlations with neuropsychological performances.In total, 24 FRDA patients (M/F: 15/9, mean age 31.3 ± 15.0) and 24 healthy controls (HC; M/F: 15/9, mean age 30.7 ± 15.5) were enrolled in this cross-sectional study. All patients underwent a thorough neuropsychological battery, investigating different cognitive domains. RS-fMRI data were analyzed using a seed-based approach, probing the FC of cortical areas potentially referable to specific executive and cognitive functions compromised in FRDA.Compared to HC, FRDA patients showed overall worse neuropsychological scores in several domains, including global cognitive assessment, spatial memory, visuoperception and visuospatial functions, and executive functions. Analysis of RS-fMRI data showed a higher FC in FRDA patients compared to HC between paracingulate gyri and the medial frontal gryrus, between the superior frontal gyrus and bilateral angular gyri, and between the middle temporal gyrus and the cingulate gyrus, with a reduced FC between the medial frontal gryrus and the cerebellum.We found a reduction in FC between frontal areas and the contralateral cerebellar cortex in FRDA, in line with the known alteration in cerebello-cortical pathway in this condition. On the other hand, a higher FC between different cortical areas was shown, possibly reflecting a compensatory phenomenon. These results, in conjunction with clinical findings, may shed new light on the pattern of supratentorial and infratentorial involvement, and on dynamics of brain plasticity in this disease.
