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Due to the forensic aspects of drinking and exposure to toxic substances, more sophisticated quantitative technology is needed to quantify the concentration of ethyl alcohol and acetaldehyde in the blood. In this study, we developed a headspace gas chromatography tandem mass spectrometry method that could simultaneously detect ethyl alcohol and acetaldehyde in human plasma. Through a simple preparation process, ethyl alcohol and acetaldehyde were quickly detected within 4 min, and a lower limit of quantification (LLOQ) (20 and 0.2 µg/mL) was obtained; these results confirmed the suitability of the system. According to Food and Drug Administration guidelines, the linearity (correlation coefficient > 0.9996), intraday and intraday accuracy, precision, and both short- and long-term stability and freeze-thaw stability satisfied the evaluation criteria (within 100.0 ± 15.0% and 20.0% of the LLOQ). Carryover and batch size assessment for the evaluation of the sample influence during analysis also satisfied the evaluation criteria. A valid method was applied to the pharmacokinetics study, and the plasma from 43 subjects after oral administration of the placebo or HK-GCM-H01 was analyzed. The developed analysis method for ethyl alcohol and acetaldehyde in blood could be used in various fields, such as forensics and those requiring precise quantification. [ABSTRACT FROM AUTHOR]

The principles of cerebrospinal fluid (CSF) production, circulation and outflow and regulation of fluid volumes and pressures in the normal brain are summarised. Abnormalities in these aspects in intracranial hypertension, ventriculomegaly and hydrocephalus are discussed. The brain parenchyma has a cellular framework with interstitial fluid (ISF) in the intervening spaces. Framework stress and interstitial fluid pressure (ISFP) combined provide the total stress which, after allowing for gravity, normally equals intracerebral pressure (ICP) with gradients of total stress too small to measure. Fluid pressure may differ from ICP in the parenchyma and collapsed subarachnoid spaces when the parenchyma presses against the meninges. Fluid pressure gradients determine fluid movements. In adults, restricting CSF outflow from subarachnoid spaces produces intracranial hypertension which, when CSF volumes change very little, is called idiopathic intracranial hypertension (iIH). Raised ICP in iIH is accompanied by increased venous sinus pressure, though which is cause and which effect is unclear. In infants with growing skulls, restriction in outflow leads to increased head and CSF volumes. In adults, ventriculomegaly can arise due to cerebral atrophy or, in hydrocephalus, to obstructions to intracranial CSF flow. In non-communicating hydrocephalus, flow through or out of the ventricles is somehow obstructed, whereas in communicating hydrocephalus, the obstruction is somewhere between the cisterna magna and cranial sites of outflow. When normal outflow routes are obstructed, continued CSF production in the ventricles may be partially balanced by outflow through the parenchyma via an oedematous periventricular layer and perivascular spaces. In adults, secondary hydrocephalus with raised ICP results from obvious obstructions to flow. By contrast, with the more subtly obstructed flow seen in normal pressure hydrocephalus (NPH), fluid pressure must be reduced elsewhere, e.g. in some subarachnoid spaces. In idiopathic NPH, where ventriculomegaly is accompanied by gait disturbance, dementia and/or urinary incontinence, the functional deficits can sometimes be reversed by shunting or third ventriculostomy. Parenchymal shrinkage is irreversible in late stage hydrocephalus with cellular framework loss but may not occur in early stages, whether by exclusion of fluid or otherwise. Further studies that are needed to explain the development of hydrocephalus are outlined. [ABSTRACT FROM AUTHOR]

Forensic pathologists often encounter cases of acute subdural hematoma (SDH) due to trauma, whereas those attributable to endogenous causes are rare. Here, we report a case of the latter type in a 42-year-old man who was found dead at home after several months of fever and malaise. Postmortem computed tomography (PMCT) and autopsy were undertaken to clarify the cause of death. PMCT images revealed a fatal SDH and a localized hyper-density area in the right parietal lobe; macroscopic and microscopic examinations revealed SDH due to rupture of a mycotic aneurysm (MA) associated with meningitis. The PMCT images also indicated thickening and calcification of the mitral valve, while autopsy demonstrated infective endocarditis (IE). In addition, PMCT demonstrated a low-density area in the spleen, which was shown to be a splenic abscess at autopsy. PMCT also demonstrated tooth cavities. Based on the findings of autopsy, the cause of death was considered to be SDH due to rupture of the MA resulting from meningitis with IE and splenic abscess. Although PMCT was unable to clarify the significance of any individual feature, a retrospective review of the PMCT images might have suggested IE, bacteremia, or ruptured MA leading to SDH. This case suggests that, instead of interpreting individual features demonstrated on PMCT images, integrated interpretation of overall PMCT findings might provide clues for identifying causes of death, despite the fact that PMCT lacks diagnostic accuracy for infectious diseases such as IE and meningitis. [ABSTRACT FROM AUTHOR]

Background: Bidirectional reciprocal motion of cerebrospinal fluid (CSF) was quantified using four-dimensional (4D) flow magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) MRI. To estimate various CSF motions in the entire intracranial region, we attempted to integrate the flow parameters calculated using the two MRI sequences. To elucidate how CSF dynamics deteriorate in Hakim's disease, an age-dependent chronic hydrocephalus, flow parameters were estimated from the two MRI sequences to assess CSF motion in the entire intracranial region. Methods: This study included 127 healthy volunteers aged ≥ 20 years and 44 patients with Hakim's disease. On 4D flow MRI for measuring CSF motion, velocity encoding was set at 5 cm/s. For the IVIM MRI analysis, the diffusion-weighted sequence was set at six b-values (i.e., 0, 50, 100, 250, 500, and 1000 s/mm2), and the biexponential IVIM fitting method was adapted. The relationships between the fraction of incoherent perfusion (f) on IVIM MRI and 4D flow MRI parameters including velocity amplitude (VA), absolute maximum velocity, stroke volume, net flow volume, and reverse flow rate were comprehensively evaluated in seven locations in the ventricles and subarachnoid spaces. Furthermore, we developed a new parameter for fluid oscillation, the Fluid Oscillation Index (FOI), by integrating these two measurements. In addition, we investigated the relationship between the measurements and indices specific to Hakim's disease and the FOIs in the entire intracranial space. Results: The VA on 4D flow MRI was significantly associated with the mean f-values on IVIM MRI. Therefore, we estimated VA that could not be directly measured on 4D flow MRI from the mean f-values on IVIM MRI in the intracranial CSF space, using the following formula; e0.2(f−85) + 0.25. To quantify fluid oscillation using one integrated parameter with weighting, FOI was calculated as VA × 10 + f × 0.02. In addition, the FOIs at the left foramen of Luschka had the strongest correlations with the Evans index (Pearson's correlation coefficient: 0.78). The other indices related with Hakim's disease were significantly associated with the FOIs at the cerebral aqueduct and bilateral foramina of Luschka. FOI at the cerebral aqueduct was also elevated in healthy controls aged ≥ 60 years. Conclusions: We estimated pulsatile CSF movements in the entire intracranial CSF space in healthy individuals and patients with Hakim's disease using FOI integrating VA from 4D flow MRI and f-values from IVIM MRI. FOI is useful for quantifying the CSF oscillation. [ABSTRACT FROM AUTHOR]

Idiopathic normal pressure hydrocephalus in elderly people is considered a form of glymphopathy caused by malfunction of the waste clearance pathway, called the glymphatic system. Tau is a representative waste material similar to amyloid-β. During neurodegeneration, lipocalin-type prostaglandin D synthase (L-PGDS), a major cerebrospinal fluid (CSF) protein, is reported to act as a chaperone that prevents the neurotoxic aggregation of amyloid-β. L-PGDS is also a CSF biomarker in idiopathic normal pressure hydrocephalus and significantly correlates with tau concentration, age, and age-related brain white matter changes detected by magnetic resonance imaging. To investigate this glymphopathy, we aimed to analyze white matter changes and contributing factors in vivo and their interactions ex vivo. Cerebrospinal tap tests were performed in 60 patients referred for symptomatic ventriculomegaly. Patients were evaluated using an idiopathic normal pressure hydrocephalus grading scale, mini-mental state examination, frontal assessment battery, and timed up-and-go test. The typical morphological features of high convexity tightness and ventriculomegaly were measured using the callosal angle and Evans index, and parenchymal white matter properties were evaluated with diffusion tensor imaging followed by tract-based spatial statistics. Levels of CSF biomarkers, including tau, amyloid-β, and L-PGDS, were determined by ELISA, and their interaction, and localization were determined using immunoprecipitation and immunohistochemical analyses. Tract-based spatial statistics for fractional anisotropy revealed clusters that positively correlated with mini-mental state examination, frontal assessment battery, and callosal angle, and clusters that negatively correlated with age, disease duration, idiopathic normal pressure hydrocephalus grading scale, Evans index, and L-PGDS. Other parameters also indicated clusters that correlated with symptoms, microstructural white matter changes, and L-PGDS. Tau co-precipitated with L-PGDS, and colocalization was confirmed in postmortem specimens of neurodegenerative disease obtained from the human Brain Bank. Our study supports the diagnostic value of L-PGDS as a surrogate marker for white matter integrity in idiopathic normal pressure hydrocephalus. These results increase our understanding of the molecular players in the glymphatic system. Moreover, this study indicates the potential utility of enhancing endogenous protective factors to maintain brain homeostasis. [ABSTRACT FROM AUTHOR]

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Background: Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a key feature for Hakim disease (idiopathic normal pressure hydrocephalus: iNPH), but subjectively evaluated. To develop automatic quantitative assessment of DESH with automatic segmentation using combined deep learning models. Methods: This study included 180 participants (42 Hakim patients, 138 healthy volunteers; 78 males, 102 females). Overall, 159 three-dimensional (3D) T1- weighted and 180 T2-weighted MRIs were included. As a semantic segmentation, 3D MRIs were automatically segmented in the total ventricles, total subarachnoid space (SAS), high-convexity SAS, and Sylvian fissure and basal cistern on the 3D U-Net model. As an image classification, DESH, ventricular dilatation (VD), tightened sulci in the high convexities (THC), and Sylvian fissure dilatation (SFD) were automatically assessed on the multimodal convolutional neural network (CNN) model. For both deep learning models, 110 T1- and 130 T2-weighted MRIs were used for training, 30 T1- and 30 T2-weighted MRIs for internal validation, and the remaining 19 T1- and 20 T2-weighted MRIs for external validation. Dice score was calculated as (overlapping area) × 2/total area. Results: Automatic region extraction from 3D T1- and T2-weighted MRI was accurate for the total ventricles (mean Dice scores: 0.85 and 0.83), Sylvian fissure and basal cistern (0.70 and 0.69), and high-convexity SAS (0.68 and 0.60), respectively. Automatic determination of DESH, VD, THC, and SFD from the segmented regions on the multimodal CNN model was sufficiently reliable; all of the mean softmax probability scores were exceeded by 0.95. All of the areas under the receiver-operating characteristic curves of the DESH, Venthi, and Sylhi indexes calculated by the segmented regions for detecting DESH were exceeded by 0.97. Conclusion: Using 3D U-Net and a multimodal CNN, DESH was automatically detected with automatically segmented regions from 3D MRIs. Our developed diagnostic support tool can improve the precision of Hakim disease (iNPH) diagnosis. [ABSTRACT FROM AUTHOR]

Background: Intracranial infectious aneurysms (IIAs) are very rare, and fungal aneurysms are infrequently reported. We report a case of an unruptured IIA caused by fungal rhinosinusitis and treated with a flow-diverting stent Case Description: An 81-year-old woman visited the ophthalmology department with impaired eye movement and ptosis and was placed under follow-up. A week later, she also developed a headache; magnetic resonance angiography revealed an aneurysm measuring 2 mm in the C4 portion of the right internal carotid artery. A 3-week follow-up with contrast-enhanced magnetic resonance imaging showed an increase in its size to 10 mm, and a contrast lesion was observed surrounding the right cavernous sinus. The patient started treatment with voriconazole and steroids on the same day. Ten weeks later, despite improvements in inflammation, the size of the aneurysm was unchanged; we, therefore, treated the aneurysm with a flow-diverting stent. Oculomotor nerve palsy improved, and the patient was discharged to a rehabilitation hospital 28 days after the placement, with a modified Rankin Scale of 4. A 1-year follow-up angiogram showed a partial decrease in the size of the aneurysm, with an O'Kelly-Marotta grading scale of B3. Conclusion: IIAs grow rapidly, and the risk of rupture is high due to the weakening of the aneurysmal wall. To reduce the risks of rupture and recurrence after treatment, the infection should be treated before inserting a flowdiverting stent. Flow-diverting stent placement may be an effective treatment for IIA once the original infection has been cured. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoids, a type of new psychoactive substances, are likely to be rapidly metabolized; thus, the detection of their metabolites, rather than the parent compound, is a common method used to prove drug consumption. Although the analysis of metabolites is generally performed by mass spectrometry, it is limited to structural estimation because of few commercially available standards. In particular, distinguishing between positional isomers is difficult. Synthetic cannabinoids with a cumyl moiety can be hydroxylated at the cumyl moiety during metabolism, but it remains unclear whether the hydroxylation occurs at the ortho, meta, or para position. This study determined the structures of a metabolite formed by mono-hydroxylation at the cumyl moiety of the synthetic cannabinoid CUMYL-THPINACA, used as a model compound. Chemical synthesis was performed to create possible metabolites with one hydroxyl group at the ortho, meta, or para positions of the cumyl moiety. Using the synthesized metabolites and liquid chromatography-quadrupole time-of-flight mass spectrometry, the metabolite detected in the microsomal reaction of CUMYL-THPINACA was identified as a compound mono-hydroxylated at the para position based on retention time and product ion spectra. Moreover, the rapid metabolism of CUMYL-THPINACA was demonstrated with an in vitro half-life of 4.9 min and the identified metabolite could be detected for a relatively long time in vitro. The synthesized metabolite may be utilized as a good reference standard for proof of CUMYL-THPINACA consumption. These findings have potential applications in the synthesis of metabolites of other synthetic cannabinoids bearing a cumyl moiety., (© 2023 John Wiley & Sons, Ltd.)

Purpose: Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was performed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) of cyst fluid in cystic brain tumors., Methods: Cyst fluid was obtained from 22 patients undergoing surgery for a cystic brain tumor with confirmed genetic alterations in tumor DNA. Pathological diagnoses based on WHO 2021 classification and diagnostic alterations in the tumor DNA, such as IDH1 R132H and TERT promoter mutation for oligodendrogliomas, were detected by Sanger sequencing. The same alterations were analyzed by both droplet digital PCR (ddPCR) and Sanger sequencing in cyst fluid cfDNA. Additionally, multiplex ligation-dependent probe amplification (MLPA) assays were performed to assess 1p/19q status, presence of CDKN2A loss, PTEN loss and EGFR amplification, to assess whether differentiating between astrocytomas and oligodendrogliomas and grading is possible from cyst fluid cfDNA., Results: Twenty-five genetic alterations were found in 22 tumor samples. All (100%) alterations were detected in cyst fluid cfDNA by ddPCR. Twenty of the 25 (80%) alterations were also detected by Sanger sequencing of cyst fluid cfDNA. Variant allele frequency (VAF) in cyst fluid cfDNA was comparable to that of tumor DNA (R = 0.62, Pearson's correlation). MLPA was feasible in 11 out of 17 (65%) diffuse gliomas, with close correlation of results between tumor DNA and cyst fluid cfDNA., Conclusion: Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diagnosing brain tumors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)