The value of EEG attenuation in the prediction of outcome in COVID-19 patients.

INTRODUCTION: During the COVID-19 pandemic, electroencephalography (EEG) proved to be a useful tool to demonstrate brain involvement. Many studies reported non-reactive generalized slowing as the most frequent pattern and epileptiform activity in a minority of patients. OBJECTIVE: To investigate the prevalence of diffuse unreactive background attenuation or suppression and its correlation with outcome in a cohort of COVID-19 patients. METHODS: The EEGs recorded during the first year of the COVID-19 pandemic were retrospectively evaluated to identify the main pattern and focus on the occurrence of a low-voltage background, either attenuated (10-20 µV) or suppressed (< 10 µV). We sought a correlation between in-hospital mortality and low-voltage EEG. In a subsample of patients, biomarkers of inflammation, hypoxemia and organ failure were collected. Brain imaging was also evaluated. RESULTS: Among 98 EEG performed in 50 consecutive patients, diffuse unreactive slowing was the most prevalent pattern (54%), followed by unreactive attenuation or suppression pattern (26%), being the latter significantly correlated with an unfavourable outcome (p = 0.0004). Survivors showed significantly lower interleukine-6 values compared to non-survivors. Patients with attenuated EEG and non-survivors also showed lower PaO2/FiO2 values. Neuroradiological findings were very heterogeneous with a prevalence of lesions suggestive of a microangiopathic substrate. CONCLUSIONS: EEG attenuation or suppression may be more frequent than previously reported and significantly associated with a poor outcome. SARS-CoV-2 infection may result in encephalopathy and reduced EEG voltage through mechanisms that are still unknown but deserve attention given its negative impact on prognosis.

An eleven-year history of Vanishing White Matter Disease in an adult patient with no cognitive decline and EIF2B5 mutations. A case report.

Vanishing White Matter Disease (VWMD) is a rare autosomal recessive leukoencephalopathy . The classical presentation is characterized by a severe cerebellar ataxia, spasticity, neurological deterioration with a chronic progressive course and episodes of acute neurological deterioration after stress conditions.We report a 52-year-old man with VWMD and atypical features who manifested two major events of transient aphasia eleven years apart with complete recovery in 48 hours. No cognitive decline was present. Brain MRI revealed typical aspects of VWMD including diffuse leukoencephalopathy with relative sparing of U-fibers. We identified the presence of c.592G>A (p.Glu198Lys) and c.1360 C>T (p.Pro454Ser) mutations in EIF2B5.

Calcified brain metastases may be more frequent than normally considered.

OBJECTIVES: To verify the incidence of calcified brain metastases (CBM), illustrating the different presentation patterns and histology of primary tumor. METHODS: A series of 1002 consecutive brain computed tomography (CT) scans of patients with known primary tumors was retrospectively assessed. CBM were defined by the presence of calcification within intra-axial-enhancing lesions; identification of CBM was based on visual examination and ROI analysis (> 85 Hounsfield units). Also, calcifications in the primary tumor of all patients with brain metastases were evaluated. In CBM patients, we investigated the type of calcifications (punctate, nodular, cluster, ring, coarse), the histology of primary tumor, and if a previous RT was performed. RESULTS: Among 190 (18.9%) patients with brain metastatic disease, 34 presented with CBM (17.9%). Sixteen patients were previously treated with RT, while 18 presented calcifications ab initio (9.5% of all brain metastases). The majority of patients with CBM had a primitive lung adenocarcinoma (56%), followed by breast ductal invasive carcinoma (20%) and small cell lung carcinoma (11.8%). CBM were single in 44.1% of patients and multiple in 55.9%. With regard to the type of calcifications, the majority of CBM were punctate, without specific correlations between calcification type and histology of primary tumor. No patients with ab initio CBM had calcifications in primary tumor. CONCLUSION: In conclusion, our data show that CBM are more common than usually thought, showing an incidence of 9.5% ab initio in patients with brain metastases. This study underlines that neuroradiologists should not overlook intraparenchymal brain calcifications, especially in oncologic patients. KEY POINTS: • Among the differential diagnosis of brain intraparenchymal calcifications, metastases are considered uncommon and found predominantly in patients treated with radiotherapy (RT). • Our data show that CBM are more common than usually thought, showing an incidence of 9.5% ab initio in patients with brain metastases. • A proportion of intraparenchymal brain calcifications, especially in oncologic patients, might represent evolving lesions and neuroradiologists should not overlook them to avoid a delay in diagnosis and treatment.

Brain microvascular occlusive disorder in COVID-19: a case report.

We describe the case of a COVID-19 patient with severely impaired consciousness after sedation hold, showing magnetic resonance imaging (MRI) findings of (i) acute bilateral supratentorial ischemic lesions involving the fronto-parietal white matter and the corpus callosum and (ii) multiple diffuse susceptibility weighted imaging (SWI) hypointense foci, infra and supratentorial, predominantly bithalamic, suggestive of microhemorrhage or alternatively microthrombi. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA was detected in the cerebrospinal fluid. Our findings suggest the occurrence of vascular damage, predominantly involving microvessels. The underlying mechanisms, which include direct and indirect penetration of the virus to the central nervous system and systemic cardiorespiratory complications, are yet to be elucidated, and a direct correlation with SARS-CoV-2 infection remains uncertain.

Degree of microstructural changes within T1-SE versus T1-GE hypointense lesions in multiple sclerosis: relevance for the definition of "black holes".

OBJECTIVES: To retrospectively evaluate the different performances of T1-SE and T1-GE sequences in detecting hypointense lesions in multiple sclerosis (MS), to quantify the degree of microstructural damage within lesions and to correlate them with patient clinical status. METHODS: Sixty clinically isolated syndrome (CIS) and MS patients underwent brain magnetic resonance imaging (MRI) on 1.5-T and 3-T scanners. We identified T2 fluid-attenuated inversion recovery hyperintense lesions with no hypointense signal on T1-SE/T1-GE (a), hypointense lesions only on T1-GE (b), and hypointense lesions on both T1-SE and T1-GE sequences (c). We compared mean lesion number (LN) and volume (LV) identified on T1-SE and T1-GE sequences, correlating them with Expanded Disability Status Scale (EDSS); fractional anisotropy (FA) and mean diffusivity (MD) values inside each lesion type were extracted and normal-appearing white matter (NAWM). RESULTS: Thirty-five patients were female. Mean age was 39.2 (± 7.8); median EDSS was 3 (± 2). There were 23 CIS, 21 relapsing-remitting (RR), and 16 progressive MS. T1-GE and T1-SE LN and LV were significantly different (p < 0.001), both correlating with EDSS. Both FA and MD metrics resulted significantly different among the three lesion groups and NAWM (p < 0.001). FA and MD values extracted from (b) and (c) showed statistically significant differences (p < 0.001), while for (a) and (b), the differences were not significant (p = 0.31 for FA and p = 0.62 for MD). CONCLUSION: T1-SE hypointense lesions demonstrated a more pronounced degree of microstructural damage. T1-weighted sequence type must be more carefully evaluated in clinical and research settings. KEY POINTS: • T1-weighted spin-echo (T1-SE) images detect chronic hypointense lesions (so called black holes) associated with more severe microstructural changes. • In the last years, three-dimensional (3D) T1-weighted gradient-echo (T1-GE) sequences are often utilized in lieu of T1-SE acquisition, more so at 3 T or higher fields. • T1-weighted sequence type must be more carefully evaluated in clinical and research settings in the definition of "black holes" in MS, in order to avoid the overestimation of the effective severe tissue damage.

How much do periventricular lesions assist in distinguishing migraine with aura from CIS?

OBJECTIVE: To evaluate in clinically isolated syndrome (CIS) and migraine with aura (MA) how the number of periventricular lesions (PVLs) detected at MRI influences diagnostic performance when the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) or the 2017 revised criteria are applied. METHODS: In this retrospective study, white matter hyperintensities (WMH) of 84 patients with MA and 79 patients with CIS were assessed using manual segmentation technique. Lesion probability maps (LPMs) and voxel-wise analysis of lesion distribution by diagnosis were obtained. Furthermore, we performed a logistic regression analysis based on lesion locations and volumes. RESULTS: Compared to patients with MA, patients with CIS showed a significant overall higher T2 WMH mean number and volume (17.9 ± 16.9 vs 6.2 ± 11.9 and 3.1 ± 4.2 vs 0.3 ± 0.6 mL; p < 0.0001) and a significantly higher T2 WMH mean number in infratentorial, periventricular, and juxtacortical areas (p < 0.0001). LPMs identified the periventricular regions as the sites with the highest probability of detecting T2 WMH in patients with CIS. Voxel-wise analysis of lesion distribution by diagnosis revealed a statistically significant association exclusively between the diagnosis of CIS and the PVLs. MAGNIMS criteria demonstrated the highest specificity in differentiating patients with CIS from patients with MA (100% vs 87%) against a predictable lower sensitivity (63% vs 72%). CONCLUSIONS: PVLs play a key role in the differential diagnosis between MA and CIS, particularly when there are more than 3. Future studies on multiple sclerosis criteria might reconsider the 3 PVLs to minimize the risk of misdiagnosis. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the presence at least 3 PVLs increases the specificity in distinguishing MA from CIS.

Intra-operative vertebroplasty combined with posterior cord decompression. A report of twelve cases.

Percutaneous vertebroplasty (VP) is a minimally invasive technique for the treatment of vertebral pathology providing early vertebral stabilization and pain relief. In cases of vertebral pathology complicated by spinal cord compression with associated neurological deficits, VP alone cannot be performed free of risks. We describe a combined approach in which decompressive laminectomy and intra-operative vertebroplasty (IVP) are performed during a single session. Among the 252 VP performed in our centre in the past three years, 12 patients (12 vertebral levels) with different pathologies (six symptomatic haemangiomas, two metastatic fractures, four osteoporotic fractures) were treated with an open procedure combined with surgery. All cases were treated with decompressive laminectomy and IVP (mono/bipeduncular or median-posterior trans-somatic access). Five patients with symptomatic haemangiomas were treated with endovascular embolization prior to the combined approach. A visual analogue scale (VAS) was applied to assess pain intensity before and after surgery. The neurological deficits were evaluated with an ASIA impairment scale. In all cases benefit from pain and neurological deficits was observed. The mean VAS score decreased from 7.8 to 2.5 after surgery. The ASIA score improved in all cases (five cases from D to E and five cases from C to D). No clinical complications were observed. In one case a CT scan performed after the procedure showed a foraminal accumulation of PMMA, but the patient referred no symptoms. IVP can be successfully applied in different pathologies affecting the vertebrae. In our limited series this approach proved safe and efficient to provide decompression of spinal cord and dural sac and vertebral body stabilization in a single session.

Evaluation of IAUGC indices and two DCE-MRI pharmacokinetic parameters assessed by two different theoretical algorithms in patients with brain tumors.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) quantifies blood-brain barrier (BBB) microvascular permeability in brain tumors where it is structurally and functionally abnormal. Twenty-five patients with glioblastomas (105 regions of interest) were compared using DCE-MRI metrics obtained with Tofts-Kety (TK) and extended TK (ETK) models using different arterial input function assessments and different initial area under the gadolinium curve (IAUGC) indices. Strong correlations between ve and IAUGC90 were found (EKT model: R=0.75 and R=0.69), while correlations of K(trans) with both IAUGC80/90 indices were weak. Differences in the permeability parameters, calculated by these two models, were found. While the IAUGC method can be implemented more easily than pharmacokinetic models, at this time, the IAUGC approach alone does not substitute pharmacokinetic models in BBB permeability characterization.

Measurement of blood-brain barrier permeability with t1-weighted dynamic contrast-enhanced MRI in brain tumors: a comparative study with two different algorithms.

The purpose of this study was to assess the feasibility of measuring different permeability parameters with T1-weighted dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in order to investigate the blood brain-barrier permeability associated with different brain tumors. The Patlak algorithm and the extended Tofts-Kety model were used to this aim. Twenty-five adult patients with tumors of different histological grades were enrolled in this study. MRI examinations were performed at 1.5 T. Multiflip angle, fast low-angle shot, and axial 3D T1-weighted images were acquired to calculate T1 maps, followed by a DCE acquisition. A region of interest was placed within the tumor of each patient to calculate the mean value of different permeability parameters. Differences in permeability measurements were found between different tumor grades, with higher histological grades characterized by higher permeability values. A significant difference in transfer constant (K (trans)) values was found between the two methods on high-grade tumors; however, both techniques revealed a significant correlation between the histological grade of tumors and their K (trans) values. Our results suggest that DCE acquisition is feasible in patients with brain tumors and that K (trans) maps can be easily obtained by these two algorithms, even if the theoretical model adopted could affect the final results.

Basal ganglia are active during motor performance recovery after a demanding motor task.

Motor performance recovery after a demanding finger motor task does not follow the excitability dynamics of primary motor cortex (M1), which remains depressed also when performance is restored. Thus, other neural circuits are supposed to cope with central fatigue, re-establishing adequate motor performance levels. A hint that the basal ganglia (BG) can be involved in this process is provided by studies showing an association of central fatigue with the BG. To investigate this possibility, we conducted an fMRI study with simultaneous motor performance recording in 20 healthy volunteers at different stages of a demanding finger motor task: baseline, central fatigue induced by 5-min sequence repetition, performance recovery after a short rest period. When motor performance was recovered, we observed a significant activation with respect to baseline in subcortical structures belonging to different BG circuits (putamen and globus pallidus), involving the limbic system functionally interacting with the BG (amygdala). Then, to assess whether the BG activation was exclusively related to the fatigue and recovery processes or to increasing automatism in motor performance, a control fMRI experiment based on a shorter motor task duration was carried out on 14 healthy subjects. In this case, the task repetition did not induce decreased performance, and no significant effect on the BOLD signal change was found in BG regions of interest with respect to baseline. All these findings suggest that motor and non-motor BG circuits run parallel and converge in a common motor path to successfully compensate motor performance deterioration in a central fatigue condition.

White matter lesions progression in migraine with aura: a clinical and MRI longitudinal study.

OBJECTIVE: To prospectively evaluate longitudinal changes in white matter lesions (WMLs) in migraineurs with aura, by magnetic resonance imaging (MRI), and to correlate WMLs modifications with patients' clinical characteristics. METHODS: Forty-one consecutive migraineurs with aura were followed for a mean time of 33.2 months. Patients underwent MRI at baseline and follow-up and were evaluated for cerebrovascular risk factors. Presence of WMLs on MRI was assessed by two neuroradiologists. RESULTS: WMLs were present in 26 subjects (63.4%) at baseline MRI. At follow-up a total of 8 patients had new WMLs (19.5%). There was a significant correlation between aura duration and number of new WMLs, and between the number of migraine attacks with aura and new WMLs. CONCLUSIONS: Our study demonstrates that in migraine with aura WMLs number can progress over time and suggests an association between aura features and WMLs progression. Studies with a higher number of patients are required to confirm these findings.

Continuous involuntary hand movements and schizencephaly: epilepsia partialis continua or dystonia?

Schizencephaly is regarded as a malformation of cortical development (due to abnormal neuronal organization) and may be associated with continuous involuntary hand movements. The mechanisms underlying these movements are not clear and both dystonia and epilepsia partialis continua have been considered in previously reported cases. We describe a young patient affected by schizencephaly and continuous involuntary movements of the contralateral hand. Functional MRI showed bilateral cerebral activation, while the subject performed tapping movements with the affected hand and no significant difference in the activation pattern after diazepam infusion. Standard and back-averaged EEG showed no alterations. The results obtained from these investigations and the clinical features of the involuntary movements are not in favor of an epileptic genesis, while support the diagnosis of secondary dystonia.

Signal intensity in T2' magnetic resonance imaging is related to brain glioma grade.

OBJECTIVES: T2' values reflect the presence of deoxyhaemoglobin related to high local oxygen extraction. We assessed the feasibility of T2' imaging to display regions with high metabolic activity in brain gliomas. METHODS: MRI was performed in 25 patients (12 female; median age 46 years; range 2-69) with brain gliomas with additional T2 and T2* sequences. T2' maps were derived from T2 and T2*. Dynamic susceptibility weighted contrast (DSC) perfusion was performed in 12/25 patients. Images were visually assessed by two readers and five ROIs were evaluated for each patient. Pearson correlation, Mann-Whitney and Kruskal-Wallis tests were applied for statistical analysis. RESULTS: Three patients were not further evaluated because of artefacts. Mean values of high-grade (III-IV) gliomas showed significantly lower T2' values than low-grade (II) gliomas (p < 0.001). An inverse relationship was observed between rCBV and sqr (T2') (r = -0.463, p < 0.001). No correlation was observed between T2' and rCBV for grade II tumours (r = 0.038; p = 0.875). CONCLUSIONS: High-grade tumours revealed lower T2' values, presumably because of higher oxygen consumption in proliferating tissue. Our results indicate that T2' imaging can be used as an alternative to DSC perfusion in the detection of subtle deviations in tumour metabolism.