Diffusion tensor imaging helps identify shunt-responsive normal pressure hydrocephalus patients among probable iNPH cohort.

The aim of this study was to investigate whether white matter changes as measured by diffusion tensor imaging (DTI) can help differentiate shunt-responsive idiopathic normal pressure hydrocephalus (iNPH) patients from patients with other causes of gait disturbances and/or cognitive decline with ventriculomegaly whose clinical symptoms do not improve significantly after cerebrospinal fluid derivation (non-iNPH). Between 2017 and 2022, 85 patients with probable iNPH underwent prospective preoperative magnetic resonance imaging (MRI) and comprehensive clinical workup. Patients with clinical symptoms of iNPH, positive result on lumbar infusion test, and gait improvement after 120-h lumbar drainage were diagnosed with iNPH and underwent shunt-placement surgery. Fractional anisotropy (FA) and mean diffusivity (MD) values for individual regions of interest were extracted from preoperative MRI, using the TBSS pipeline of FSL toolkit. These FA and MD values were then compared to results of clinical workup and established diagnosis of iNPH. An identical MRI protocol was performed on 13 age- and sex-matched healthy volunteers. Statistically significant differences in FA values of several white matter structures were found not only between iNPH patients and healthy controls but also between iNPH and non-iNPH patients. ROI that showed best diagnostic ability when differentiating iNPH among probable iNPH cohort was uncinate fasciculus, with AUC of 0.74 (p < 0.001). DTI methods of white matter analysis using standardised methods of ROI extraction can help in differentiation of iNPH patients not only from healthy patients but also from patients with other causes of gait disturbances with cognitive decline and ventriculomegaly.

Congenital internal carotid artery hypoplasia: A systematic review.

This review evaluates the current evidence for the clinical management of congenital internal carotid artery hypoplasia (CICAH). We summarise clinical presentations diagnostic standards, imaging recommendations, treatment and follow-up. The review was prompted by a case of CICAH in a 50-year-old female who presented to our neurosurgery clinic with an acute episode of vertigo. The patient underwent CT angiogram, which showed an unusually low right carotid bifurcation. The right internal carotid artery (ICA) was hypoplastic, and the A1 segment of the anterior cerebral artery (ACA) was absent. Skull base CT showed an ipsilateral hypoplastic carotid canal. To summarise current evidence for clinical management of CICAH we followed PRISMA guidelines to identify papers meeting our predefined inclusion criteria. We searched three databases using the terms 'ICA' and 'Hypoplasia'. We reviewed 41 papers meeting our criteria. 34 were clinical reports. We performed a data extraction and quality appraisal on these reports. We found that CICAH may be less rare than previously described. Blood pressure control in CICAH is crucial due to the increased risk of stroke and aneurysm formation. Follow-up imaging is strongly recommended. Carotid doppler sonography is a powerful and underutilised diagnostic tool, and carotid canal hypoplasia is not a pathognomic sign. In conclusion, clinicians should be alert to anatomic variations such as CICAH because these produce haemodynamic changes that may have serious clinical consequences. We recommend a central registry of patients with CICAH in order to understand the longer-term natural history of the condition.

Boosting phase-contrast MRI performance in idiopathic normal pressure hydrocephalus diagnostics by means of machine learning approach.

OBJECTIVE: Phase-contrast MRI allows detailed measurements of various parameters of CSF motion. This examination is technically demanding and machine dependent. The literature on this topic is ambiguous. Machine learning (ML) approaches have already been successfully utilized in medical research, but none have yet been applied to enhance the results of CSF flowmetry. The aim of this study was to evaluate the possible contribution of ML algorithms in enhancing the utilization and results of MRI flowmetry in idiopathic normal pressure hydrocephalus (iNPH) diagnostics. METHODS: The study cohort consisted of 30 iNPH patients and 15 healthy controls examined on one MRI machine. All major phase-contrast parameters were inspected: peak positive, peak negative, and average velocities; peak amplitude; positive, negative, and average flow rates; and aqueductal area. The authors applied ML algorithms to 85 complex features calculated from a phase-contrast study. RESULTS: The most distinctive parameters with p < 0.005 were the peak negative velocity, peak amplitude, and negative flow. From the ML algorithms, the Adaptive Boosting classifier showed the highest specificity and best discrimination potential overall, with 80.4% ± 2.9% accuracy, 72.0% ± 5.6% sensitivity, 84.7% ± 3.8% specificity, and 0.812 ± 0.047 area under the receiver operating characteristic curve (AUC). The highest sensitivity was 85.7% ± 5.6%, reached by the Gaussian Naive Bayes model, and the best AUC was 0.854 ± 0.028 by the Extra Trees classifier. CONCLUSIONS: Feature extraction algorithms combined with ML approaches simplify the utilization of phase-contrast MRI. The highest-performing ML algorithm was Adaptive Boosting, which showed good calibration and discrimination on the testing data, with 80.4% accuracy, 72.0% sensitivity, 84.7% specificity, and 0.812 AUC. Phase-contrast MRI boosted by the ML approach can help to determine shunt-responsive iNPH patients.

First experiences with Miethke M.blue® valve in iNPH patients.

The literature on hydrocephalus treatment shows support for adjustable valves and devices which prevent the so-called "siphon effect". In our study, 21 probable iNPH patients were indicated to shunt surgery with the Miethke M.blue® adjustable gravitational valve. Outcomes at three months were measured using the following tests: Dutch Gait Scale, International Consortium on Incontinence Questionnaire (ICIQ-UI SF), SF12V2-Health Survey, Kiefer Scale, 3T MRI, and a neuropsychological testing battery. Preoperative parameters were studied for any signs of overdrainage risk. Valves were set according to the manufacturer's recommendations. Significant improvement at three months was seen in the Dutch Gait Scale, ICIQ-UI SF, Kiefer Scale, Mental Health Component of the SF12V2-Health Survey (MCS-12) and three neuropsychological tests: Rey-Osterrieth complex figure test (ROCFT 30 min), auditory verbal learning test (AVLT I-V) and the NKP version of verbal fluency test. Seven patients needed more than one adjustment of the valve. This subgroup significantly improved only in Walking Score and Step Score but the trend was toward significant improvement in other variables. Eight patients had subdural effusions that were completely managed with adjustments until the 3-month control. BMI was significantly lower in patients with ≥2 adjustments compared to those with a maximum of one adjustment. Implantation had low complication rates and no mortality. Initial results are promising however more studies are needed to provide rationale for gravitational valves in iNPH. We recommend increasing the initial valve setting by 2-4 cm H2O above manufacturer's recommendation, especially in lean patients.

From head micro-motions towards CSF dynamics and non-invasive intracranial pressure monitoring.

Continuous monitoring of the intracranial pressure (ICP) is essential in neurocritical care. There are a variety of ICP monitoring systems currently available, with the intraventricular fluid filled catheter transducer currently representing the "gold standard". As the placement of catheters is associated with the attendant risk of infection, hematoma formation, and seizures, there is a need for a reliable, non-invasive alternative. In the present study we suggest a unique theoretical framework based on differential geometry invariants of cranial micro-motions with the potential for continuous non-invasive ICP monitoring in conservative traumatic brain injury (TBI) treatment. As a proof of this concept, we have developed a pillow with embedded mechanical sensors and collected an extensive dataset (> 550 h on 24 TBI coma patients) of cranial micro-motions and the reference intraparenchymal ICP. From the multidimensional pulsatile curve we calculated the first Cartan curvature and constructed a "fingerprint" image (Cartan map) associated with the cerebrospinal fluid (CSF) dynamics. The Cartan map features maxima bands corresponding to a pressure wave reflection corresponding to a detectable skull tremble. We give evidence for a statistically significant and patient-independent correlation between skull micro-motions and ICP time derivative. Our unique differential geometry-based method yields a broader and global perspective on intracranial CSF dynamics compared to rather local catheter-based measurement and has the potential for wider applications.

Identifying Factors Associated with the Growth of Vestibular Schwannomas: A Systematic Review.

BACKGROUND: Surveillance imaging is a valid management option for selected vestibular schwannomas (VS). An ideal protocol for radiologic monitoring would highlight growth-related risk factors and tailor management accordingly. This study aims to identify variables associated with the growth of sporadic VS to enhance surveillance imaging, enable early intervention, and optimize outcomes. METHODS: The review was conducted according to the PRISMA guidelines. A systematic review of 5 databases (PubMed, Ovid, Cochrane Library, Web of Science, and Google Scholar) was performed to identify negative and positive growth predictors of sporadic vestibular schwannomas. The search was limited to studies reported between January 2015 and January 2020. We conducted an individual patient data meta-analysis using a 1-stage multivariate mixed-effect logistic regression model. RESULTS: A total of 437 studies were identified, of which 25 met our criteria for full-text analysis. Articles that measured VS with comparable methods were determined eligible for meta-analysis inclusion. The selected articles were highly heterogeneous in their use of grading scales and assessment of tumor size. Our review showed that size at diagnosis (odds ratio, 1.15; 95% confidence interval, 1.11-1.18; P < 0.0001) and intracanalicular localization (odds ratio, 0.49; 95% confidence interval, 0.26-0.90; P = 0.023) were associated with VS growth. CONCLUSIONS: The factors most frequently reported as being associated with growth within the literature were size of VS at diagnosis and localization of an intracanalicular component. Greater attention should be placed on these criteria within the surveillance imaging algorithm for VS.

Role of DESH, callosal angle and cingulate sulcus sign in prediction of gait responsiveness after shunting in iNPH patients.

Primary endpoint of this single-centre, prospective consecutive cohort study was to evaluate DESH score, CA, CSS and Evans index of suspected iNPH patients against the reference standard of lumbar infusion test (LIT) and external lumbar drainage (ELD) in prediction of gait response after VP shunt implantation in patients with idiopathic normal pressure hydrocephalus (iNPH). Patients were assigned to NPH and non-NPH groups based on LIT and ELD results. Age-matched controls were added for group comparison. 32 NPH, 46 non-NPH and 15 control subjects were enrolled in the study. There were significant differences in mean preoperative DESH scores of NPH, non-NPH and control groups (6.3 ± 2.3 ([±SD]) (range 2-10) vs 4.5 ± 2.4 (range 0-10) vs 1.0 ± 1.2 (range 0-4)). Differences in mean CA and Evans index were not significant between NPH and non-NPH groups. CSS showed 62.5% sensitivity, 60.87% specificity, 52.63% PPV and 70% NPV for differentiation of NPH and non-NPH groups. A CA of 68 degrees had 48.49% sensitivity, 76.09% specificity, 59.26% PPV 67.31% NPV and DESH score of 4 had 93.75% sensitivity, 41.30% specificity, 52.63% PPV and 90.48% NPV for differentiation between NPH and non-NPH groups. The groups of probable iNPH patients with gait impairment diagnosed by high DESH score or positive functional testing did not overlap and DESH score did not correlate with gait improvement after ELD. DESH score should not be used as a simple diagnostic or prognostic marker of iNPH and we could not confirm the benefit of measurement of callosal angle and cingulate sulcus sign.

Large-scale neuroanatomical study uncovers 198 gene associations in mouse brain morphogenesis.

Brain morphogenesis is an important process contributing to higher-order cognition, however our knowledge about its biological basis is largely incomplete. Here we analyze 118 neuroanatomical parameters in 1,566 mutant mouse lines and identify 198 genes whose disruptions yield NeuroAnatomical Phenotypes (NAPs), mostly affecting structures implicated in brain connectivity. Groups of functionally similar NAP genes participate in pathways involving the cytoskeleton, the cell cycle and the synapse, display distinct fetal and postnatal brain expression dynamics and importantly, their disruption can yield convergent phenotypic patterns. 17% of human unique orthologues of mouse NAP genes are known loci for cognitive dysfunction. The remaining 83% constitute a vast pool of genes newly implicated in brain architecture, providing the largest study of mouse NAP genes and pathways. This offers a complementary resource to human genetic studies and predict that many more genes could be involved in mammalian brain morphogenesis.

Mouse genomic variation and its effect on phenotypes and gene regulation.

We report genome sequences of 17 inbred strains of laboratory mice and identify almost ten times more variants than previously known. We use these genomes to explore the phylogenetic history of the laboratory mouse and to examine the functional consequences of allele-specific variation on transcript abundance, revealing that at least 12% of transcripts show a significant tissue-specific expression bias. By identifying candidate functional variants at 718 quantitative trait loci we show that the molecular nature of functional variants and their position relative to genes vary according to the effect size of the locus. These sequences provide a starting point for a new era in the functional analysis of a key model organism.

Sequence-based characterization of structural variation in the mouse genome.

Structural variation is widespread in mammalian genomes and is an important cause of disease, but just how abundant and important structural variants (SVs) are in shaping phenotypic variation remains unclear. Without knowing how many SVs there are, and how they arise, it is difficult to discover what they do. Combining experimental with automated analyses, we identified 711,920 SVs at 281,243 sites in the genomes of thirteen classical and four wild-derived inbred mouse strains. The majority of SVs are less than 1 kilobase in size and 98% are deletions or insertions. The breakpoints of 160,000 SVs were mapped to base pair resolution, allowing us to infer that insertion of retrotransposons causes more than half of SVs. Yet, despite their prevalence, SVs are less likely than other sequence variants to cause gene expression or quantitative phenotypic variation. We identified 24 SVs that disrupt coding exons, acting as rare variants of large effect on gene function. One-third of the genes so affected have immunological functions.