Implementation of the "No ICU - Unless" approach in postoperative neurosurgical management in times of COVID-19.

Following elective craniotomy, patients routinely receive 24-h monitoring in an intensive care unit (ICU). However, the benefit of intensive care monitoring and treatment in these patients is discussed controversially. This study aimed to evaluate the complication profile of a "No ICU - Unless" strategy and to compare this strategy with the standardized management of post-craniotomy patients in the ICU. Two postoperative management strategies were compared in a matched-pair analysis: The first cohort included patients who were managed in the normal ward postoperatively ("No ICU - Unless" group). The second cohort contained patients routinely admitted to the ICU (control group). Outcome parameters contained detailed complication profile, length of hospital and ICU stay, duration to first postoperative mobilization, number of unplanned imaging before scheduled postoperative imaging, number and type of intensive care interventions, as well as pre- and postoperative modified Rankin scale (mRS). Patient characteristics and clinical course were analyzed using electronic medical records. The No ICU - Unless (NIU) group consisted of 96 patients, and the control group consisted of 75 patients. Complication rates were comparable in both cohorts (16% in the NIU group vs. 17% in the control group; p = 0.123). Groups did not differ significantly in any of the outcome parameters examined. The length of hospital stay was shorter in the NIU group but did not reach statistical significance (average 5.8 vs. 6.8 days; p = 0.481). There was no significant change in the distribution of preoperative (p = 0.960) and postoperative (p = 0.425) mRS scores in the NIU and control groups. Routine postoperative ICU management does not reduce postoperative complications and does not affect the surgical outcome of patients after elective craniotomies. Most postoperative complications are detected after a 24-h observation period. This approach may represent a potential strategy to prevent the overutilization of ICU capacities while maintaining sufficient postoperative care for neurosurgical patients.

Comparing Programming Sessions of Vim-DBS.

Background: Essential Tremor (ET) is a progressive neurological disorder characterized by postural and kinetic tremor most commonly affecting the hands and arms. Medically intractable ET can be treated by deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM). We investigated whether the location of the effective contact (most tremor suppression with at least side effects) in VIM-DBS for ET changes over time, indicating a distinct mechanism of loss of efficacy that goes beyond progression of tremor severity, or a mere reduction of DBS efficacy. Methods: We performed programming sessions in 10 patients who underwent bilateral vim-DBS surgery between 2009 and 2017 at our department. In addition to the intraoperative (T1) and first clinical programming session (T2) a third programming session (T3) was performed to assess the effect- and side effect threshold (minimum voltage at which a tremor suppression or side effects occurred). Additionally, we compared the choice of the effective contact between T1 and T2 which might be affected by a surgical induced "brain shift." Discussion: Over a time span of about 4 years VIM-DBS in ET showed continuous efficacy in tremor suppression during stim-ON compared to stim-OFF. Compared to immediate postoperative programming sessions in ET-patients with DBS, long-term evaluation showed no relevant change in the choice of contact with respect to side effects and efficacy. In the majority of the cases the active contact at T2 did not correspond to the most effective intraoperative stimulation site T1, which might be explained by a brain-shift due to cerebral spinal fluid loss after neurosurgical procedure.

Effect of thalamic deep brain stimulation on swallowing in patients with essential tremor.

OBJECTIVE: Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is a mainstay treatment for severe and drug-refractory essential tremor (ET). Although stimulation-induced dysarthria has been extensively described, possible impairment of swallowing has not been systematically investigated yet. METHODS: Twelve patients with ET and bilateral VIM-DBS with self-reported dysphagia after VIM-DBS were included. Swallowing function was assessed clinically and using by flexible endoscopic evaluation of swallowing in the stim-ON and in the stim-OFF condition. Presence, severity, and improvement of dysphagia were recorded. RESULTS: During stim-ON, the presence of dysphagia could be objectified in all patients, 42% showing mild, 42% moderate, and 16 % severe dysphagia. During stim-OFF, all patients experienced a statistically significant improvement of swallowing function. INTERPRETATION: VIM-DBS may have an impact on swallowing physiology in ET-patients. Further studies to elucidate the prevalence and underlying pathophysiological mechanisms are warranted.

Long term seizure freedom on perampanel in highly drug-resistant epilepsy caused by bilateral periventricular nodular heterotopia: A case report.

•NMDA-receptor subunit expression of NR2A and NR2B is downregulated in heterotopias.•Glutamatergic transmission in the hyperexcitability of nodular heterotopias is implicated.•Mechanisms in PVNH to establish etiology specific therapies are still to be defined.

Longitudinal quantitative MRI assessment of cortical damage in multiple sclerosis: A pilot study.

PURPOSE: Quantitative MRI (qMRI) allows assessing cortical pathology in multiple sclerosis (MS) on a microstructural level, where cortical damage has been shown to prolong T1 -relaxation time and increase proton density (PD) compared to controls. However, the evolution of these changes in MS over time has not been investigated so far. In this pilot study we used an advanced method for the longitudinal assessment of cortical tissue change in MS patients with qMRI in comparison to cortical atrophy, as derived from conventional MRI. MATERIALS AND METHODS: Twelve patients with relapsing-remitting MS underwent 3T T1 /PD-mapping at two timepoints with a mean interval of 12 months. The respective cortical T1 /PD-values were extracted from the middle of the cortical layer and the cortical thickness was measured for surface-based identification of clusters with increasing/decreasing values. RESULTS: Statistical analysis showed clusters with increasing PD- and T1 -values over time (annualized rate for T1 /PD increase in these clusters: 3.4 ± 2.56% for T1 , P = 0.0007; 2.3 ± 2.59% for PD, P = 0.01). Changes are heterogeneous across the cortex and different patterns of longitudinal PD and T1 increase emerged. Analysis of the cortical thickness yielded only one small cluster indicating a decrease of cortical thickness. CONCLUSION: Changes of cortical tissue composition in MS seem to be reflected by a spatially inhomogeneous, multifocal increase of the PD values, indicating replacement of neural tissue by water, and of the T1 -relaxation time, a surrogate of demyelination, axonal loss, and gliosis. qMRI changes were more prominent than cortical atrophy, showing the potential of qMRI techniques to quantify microstructural alterations that remain undetected by conventional MRI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1485-1490.

Evaluation of brain ageing: a quantitative longitudinal MRI study over 7 years.

OBJECTIVES: T1 relaxometry is a promising tool for the assessment of microstructural changes during brain ageing. Previous cross-sectional studies demonstrated increasing T1 values in white and decreasing T1 values in grey matter over the lifetime. However, these findings have not yet been confirmed on the basis of a longitudinal study. In this longitudinal study over 7 years, T1 relaxometry was used to investigate the dynamics of age-related microstructural changes in older healthy subjects. METHODS: T1 mapping was performed in 17 healthy subjects (range 51-77 years) at baseline and after 7 years. Advanced cortical and white matter segmentation was used to determine mean T1 values in the cortex and white matter. RESULTS: The analysis revealed a decrease of mean cortical T1 values over 7 years, the rate of T1 reduction being more prominent in subjects with higher age. T1 decreases were predominantly localized in the lateral frontal, parietal and temporal cortex. In contrast, mean white matter T1 values remained stable. CONCLUSIONS: T1 mapping is shown to be sensitive to age-related microstructural changes in healthy ageing subjects in a longitudinal setting. Data of a cohort in late adulthood and the senescence period demonstrate a decrease of cortical T1 values over 7 years, most likely reflecting decreasing water content and increased iron concentrations. KEY POINTS: • T1 mapping is sensitive to age-related microstructural changes in a longitudinal setting. • T1 decreases were predominantly localized in the lateral frontal, parietal and temporal cortex. • The rate of T1 reduction was more prominent in subjects with higher age. • These changes most likely reflect decreasing cortical water and increasing iron concentrations.

Comparison of two quantitative proton density mapping methods in multiple sclerosis.

OBJECTIVE: Proton density (PD) mapping requires correction for the receive profile (RP), which is frequently performed via bias-field correction. An alternative RP-mapping method utilizes a comparison of uncorrected PD-maps and a value ρ(T1) directly derived from T1-maps via the Fatouros equation. This may be problematic in multiple sclerosis (MS), if respective parameters are only valid for healthy brain tissue. We aimed to investigate whether the alternative method yields correct PD values in MS patients. MATERIALS/METHODS: PD mapping was performed on 27 patients with relapsing-remitting MS and 27 healthy controls, utilizing both methods, yielding reference PD values (PDref, bias-field method) and PDalt (alternative method). RESULTS: PDalt-values closely matched PDref, both for patients and controls. In contrast, ρ(T1) differed by up to 3 % from PDref, and the voxel-wise correlation between PDref and ρ(T1) was reduced in a patient subgroup with a higher degree of disability. Still, discrepancies between ρ(T1) and PDref were almost identical across different tissue types, thus translating into a scaling factor, which cancelled out during normalization to 100 % in CSF, yielding a good agreement between PDalt and PDref. CONCLUSION: RP correction utilizing the auxiliary parameter ρ(T1) derived via the Fatouros equation provides accurate PD results in MS patients, in spite of discrepancies between ρ(T1) and actual PD values.

Multi-parametric quantitative MRI of normal appearing white matter in multiple sclerosis, and the effect of disease activity on T2.

White matter (WM) lesions with a distinct lesion-tissue contrast are the main radiological hallmark of multiple sclerosis (MS) in standard magnetic resonance imaging (MRI). Pathological WM changes beyond lesion development lack suitable contrasts, rendering the investigation of normal appearing WM (NAWM) more challenging. In this study, repeat quantitative MRI (qMRI) was collected in 9 relapsing remitting MS patients with mild disease over nine months. The relaxation times T1 and T2, the proton density (PD), and the magnetization transfer ratio (MTR) were analysed in the NAWM. For each parameter, both the mean value and the standard deviation were determined across large NAWM regions. The resulting 8-dimensional multi-parameter space includes parameter non-uniformities as additional descriptors of NAWM inhomogeneity. The goals of the study were to investigate (1) which of the eight parameters differ significantly between NAWM and normal WM, (2) if parameter time courses differ between patients with and without radiological disease activity, and (3) if a suitable biomarker can be derived from the multi-parameter space, allowing for NAWM characterization and differentiation from controls. On a group level, all parameters investigated except mean T1 values were significantly affected in MS NAWM. Group classification accuracy using a multi-parametric support vector machine approach in NAWM was 66.7 %. In addition, mean T2 values increased significantly with time for patients with radiological disease activity, but not for patients without radiological activity. In conclusion, our data demonstrate the potential of qMRI for investigating MS pathology in NAWM. T2 measurements in NAWM may enable monitoring of disease activity outside of overt lesions.

The Relationship between Gray Matter Quantitative MRI and Disability in Secondary Progressive Multiple Sclerosis.

PURPOSE: In secondary progressive Multiple Sclerosis (SPMS), global neurodegeneration as a driver of disability gains importance in comparison to focal inflammatory processes. However, clinical MRI does not visualize changes of tissue composition outside MS lesions. This quantitative MRI (qMRI) study investigated cortical and deep gray matter (GM) proton density (PD) values and T1 relaxation times to explore their potential to assess neuronal damage and its relationship to clinical disability in SPMS. MATERIALS AND METHODS: 11 SPMS patients underwent quantitative T1 and PD mapping. Parameter values across the cerebral cortex and deep GM structures were compared with 11 healthy controls, and correlation with disability was investigated for regions exhibiting significant group differences. RESULTS: PD was increased in the whole GM, cerebral cortex, thalamus, putamen and pallidum. PD correlated with disability in the whole GM, cerebral cortex, putamen and pallidum. T1 relaxation time was prolonged and correlated with disability in the whole GM and cerebral cortex. CONCLUSION: Our study suggests that the qMRI parameters GM PD (which likely indicates replacement of neural tissue with water) and cortical T1 (which reflects cortical damage including and beyond increased water content) are promising qMRI candidates for the assessment of disease status, and are related to disability in SPMS.

Multimodal quantitative MRI assessment of cortical damage in relapsing-remitting multiple sclerosis.

PURPOSE: To investigate magnetization transfer ratio (MTR), T1 relaxation time, and proton density (PD) as indicators of gray matter damage in relapsing-remitting multiple sclerosis (RRMS), reflecting different aspects of microstructural damage and as imaging correlates of clinical disability. We aimed to determine which of these parameters may optimally quantify cortical damage, and serve as an imaging surrogate of clinical disability. In this study, cortical values of MTR, a surrogate for demyelination in MS, of PD, reflecting replacement of neural tissue by water, and of T1 , indicating a complex array of microstructural changes, were assessed in a group of RRMS patients in comparison to healthy controls (HC). MATERIALS AND METHODS: 22 RRMS patients with varying disease duration (4.0 ± 6.54 years) and 10 HC received quantitative 3T magnetic resonance imaging (MRI) with MTR, T1 , and PD mapping. We tested for differences in cortical measurements between patients and HC. Additionally, correlation with disability as quantified by the Expanded Disability Status Scale was investigated. RESULTS: Cortical parameter values were significantly altered in the RRMS group, with increased values of T1 (P = 0.008) and PD (P = 0.028) and reduced values of MTR (P = 0.043). Only cortical T1 was correlated with clinical disability measurements (P = 0.001, r = 0.65). Receiver operating characteristic analysis demonstrated the best discriminatory power for T1 (area under the curve 0.79, PD: 0.75, MTR 0.73). CONCLUSION: Out of the parameters studied, cortical T1 is best suited to detect cortical damage as an imaging surrogate of clinical disability in RRMS. J. Magn. Reson. Imaging 2016;44:1600-1607.

Assessment of cortical damage in early multiple sclerosis with quantitative T2 relaxometry.

T2 relaxation time is a quantitative MRI in vivo surrogate of cerebral tissue damage in multiple sclerosis (MS) patients. Cortical T2 prolongation is a known feature in later disease stages, but has not been demonstrated in the cortical normal appearing gray matter (NAGM) in early MS. This study centers on the quantitative evaluation of the tissue parameter T2 in cortical NAGM in a collective of early MS and clinically isolated syndrome (CIS) patients, hypothesizing that T2 prolongation is already present at early disease stages and variable over space, in line with global and focal inflammatory processes in MS. Additionally, magnetization transfer ratio (MTR) mapping was performed for further characterization of the expected cortical T2 alteration. Quantitative T2 and MTR maps were acquired from 12 patients with CIS and early MS, and 12 matched healthy controls. The lesion-free part of the cortical volume was identified, and the mean T2 and MTR values and their standard deviations within the cortical volume were determined. For evaluation of spatial specificity, cortical lobar subregions were tested separately for differences of mean T2 and T2 standard deviation. We detected significantly prolonged T2 in cortical NAGM in patients. T2 prolongation was found across the whole cerebral cortex and in all individual lobar subregions. Significantly higher standard deviations across the respective region of interest were found for the whole cerebral cortex and all subregions, suggesting the occurrence of spatially inhomogeneous cortical damage in all regions studied. A trend was observed for MTR reduction and increased MTR variability across the whole cortex in the MS group, suggesting demyelination. In conclusion, our results suggest that cortical damage in early MS is evidenced by spatially inhomogeneous T2 prolongation which goes beyond demyelination. Iron deposition, which is known to decrease T2, seems less prominent.

Quantitative T1 and proton density mapping with direct calculation of radiofrequency coil transmit and receive profiles from two-point variable flip angle data.

Quantitative T1 mapping of brain tissue is frequently based on the variable flip angle (VFA) method, acquiring spoiled gradient echo (GE) datasets at different excitation angles. However, accurate T1 calculation requires a knowledge of the sensitivity profile B1 of the radiofrequency (RF) transmit coil. For an additional derivation of proton density (PD) maps, the receive coil sensitivity profile (RP) must also be known. Mapping of B1 and RP increases the experiment duration, which may be critical when investigating patients. In this work, a method is presented for the direct calculation of B1 and RP from VFA data. Thus, quantitative maps of T1 , PD, B1 and RP can be obtained from only two spoiled GE datasets. The method is based on: (1) the exploitation of the linear relationship between 1/PD and 1/T1 in brain tissue and (2) the assumption of smoothly varying B1 and RP, so that a large number of data points can be fitted across small volume elements where B1 and RP are approximately constant. The method is tested and optimized on healthy subjects. Copyright © 2016 John Wiley & Sons, Ltd.

Changes and variability of proton density and T1 relaxation times in early multiple sclerosis: MRI markers of neuronal damage in the cerebral cortex.

OBJECTIVES: Proton density (PD) and T1 relaxation time are promising quantitative MRI (qMRI) markers of neuronal damage in multiple sclerosis (MS). However, it is unknown whether cortical differences of these parameters between patients and controls exist in the early stages of disease. This study investigates cortical T1 and PD in early MS stages, hypothesizing that these are altered and display a high spatial variability. METHODS: Quantitative T1 and PD mapping was performed on 11 patients with clinically isolated syndrome (CIS)/early MS in remission and 11 healthy controls. The normal appearing cortical gray matter was extracted, lobar regions were identified, and mean values and standard deviations of both parameters were calculated within each region. RESULTS: Increased PD was detected in MS/CIS patients in the cerebral cortex as a whole and all subregions, indicating an increase of water content. Increase of PD variability reached significance in the whole cortex and in the frontal and parietal regions. Longer T1 relaxation times and increased variability were found in the cerebral cortex in all regions studied, indicating a change of microstructural tissue composition that is spatially heterogeneous. CONCLUSIONS: The data show spatially heterogeneous cortical involvement in early MS is reflected in T1 and PD qMRI. KEY POINTS: • Cortical involvement in early MS is reflected in T1/PD quantitative MRI. • The changes are spatially heterogeneous. • Cortical damage goes beyond increased water content.