Case report: Consecutive hyperbaric oxygen therapy for delayed post-hypoxic leukoencephalopathy resulting from CHANTER syndrome caused by opioid intoxication

Delayed post-hypoxic leukoencephalopathy (DPHL) is a poorly recognized syndrome characterized by neuropsychiatric symptoms following recovery from an acute hypoxic episode. Although most cases are related to carbon monoxide poisoning, some have been linked to excessive opioid use. Opioid intoxication has recently become known for manifesting the characteristic imaging findings involving cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) syndrome. Herein, we present a patient with severe disturbances in consciousness who was initially diagnosed with CO poisoning but was later found to have taken excessive tramadol. Magnetic resonance imaging (MRI) in the acute phase revealed abnormal intensities in the bilateral globus pallidus and the cerebellum, indicative of CHANTER syndrome. After intensive care, his level of consciousness was restored. However, around the 3rd week after hospitalization, his consciousness gradually deteriorated and he developed severe neurological symptoms. Another MRI on day 25 revealed a new diffuse white matter abnormality; DPHL was suspected. Cerebrospinal fluid collected on day 28 revealed significantly elevated myelin basic protein levels. Although it was challenging to decide on a treatment plan, hyperbaric oxygen (HBO) therapy trials were initiated on day 58; the patient's condition improved after a series of HBO sessions. MRI revealed gradual shrinkage of the white matter abnormality. A total of 63 consecutive HBO sessions were performed, leading to the successful resolution of the serious neurological symptoms. While the effectiveness of HBO therapy for DPHL remains inconclusive, especially in opioid-related cases, this patient made a remarkable recovery, likely due to the therapeutic effect of improved cerebral blood flow and oxygenation

Facial trauma with life-threatening bleeding treated by andexanet alfa administration: A case report

Recently, anticoagulant reversal has become a treatment option for life-threatening bleeding, especially in intracranial hemorrhage. Although evidence of the beneficial efficacy of andexanet alfa accumulates in cases of intracranial hemorrhage, little is known about its effectiveness in head injuries without intracranial hemorrhage. We present the case of an 87-year-old man who suffered a stroke 1 year previously and had been taking apixaban since then, who was brought to the emergency department with facial trauma due to a fall. Upon arrival at the hospital, the patient was conscious, and his vital signs were normal; however, physical examination revealed epistaxis, and plain head computed tomography (CT) showed multiple facial fractures without intracranial hemorrhage. As epistaxis was challenging to control, upper airway obstruction developed. His percutaneous oxygen saturation (SpO₂) decreased rapidly, and he underwent tracheal intubation. Contrast-enhanced head CT revealed at least two extravasations, near the anterior wall of the right maxillary sinus and from the nasal canal to the nasopharynx area. However, embolization using interventional radiology was deemed difficult. Because the bleeding did not stop, we determined the bleeding was life-threatening and uncontrollable. Therefore, we infused andexanet alfa to stop the bleeding. After infusion, hemostasis was confirmed. This case suggests the effectiveness of andexanet alfa in cases of facial trauma and extracranial bleeding difficult to stop, resulting in favorable outcomes and hemostatic effects

Lipocalin-type prostaglandin D synthase: a glymphopathy marker in idiopathic hydrocephalus

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

特発性正常圧水頭症におけるアルツハイマー病脳脊髄液バイオマーカーの動的モニタリング

京都大学0048新制・課程博士博士(医学)甲第22636号医博第4619号新制||医||1044(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 高橋 淳, 教授 古川 壽亮, 教授 村井 俊哉学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Anterior Choroidal Artery Infarction Evaluated with ¹²³I-Imp Single-Photon Emission Computed Tomography and 7 Tesla Magnetic Resonance Imaging

Anterior choroidal artery (AchA) infarction remains a challenging diagnosis although it was first described almost 100 years prior. N-isopropyl-p-[¹²³I]-iodoamphetamine single-photon emission computed tomography (¹²³I-IMP SPECT) and 7 Tesla magnetic resonance angiography (7T-MRA) are not routinely performed in cases of AchA infarction. Therefore, the application of ¹²³I-IMP SPECT and 7T-MRA for AchA infarction has not been reported previously. A 67-year-old man presented with disturbed consciousness, gaze preference to the left, aphasia, right homonymous hemianopia, and right hemiparesis. Brain magnetic resonance imaging revealed infarction of the left posterior limb of the internal capsule. Left middle cerebral artery was clearly seen on MRA. However, ¹²³I-IMP SPECT on day 13 showed cortical hypoperfusion which indicated thalamus involvement with neural deactivation. Additionally, 7T-MRA on day 15 revealed an intact left AchA suggesting reperfusion. The neurological deficits improved gradually after treatment and rehabilitation. This case demonstrates AchA infarction with cortical hypoperfusion associated with thalamus involvement, which was clarified by performing ¹²³I-IMP SPECT and 7T-MRA. Perfusion analysis and evaluation of detailed vascular anatomy in stroke can be expected to elucidate pathological conditions

Rapidly Progressive Cognitive Disturbances Due to Nonconvulsive Status Epilepticus Associated with a Cerebral Microbleed: Clinical Application of FDG-PET

Cerebral microbleeds (CMBs) usually produce no symptoms. We encountered a patient who developed cognitive decline and psychotic symptoms associated with nonconvulsive status epilepticus (NCSE), with presumptive epileptogenic focus possibly caused by a CMB. A 70-year-old man developed progressive cognitive disturbances including disorientation and hallucinations two months after a mild head injury. He was admitted to our hospital three months after the trauma, because of progression of symptoms. The first positron emission tomography (PET) with [18F]fluoro-2-deoxy-d-glucose (FDG) demonstrated intense FDG uptake in the left occipitoparietal region, in which a CMB was detected by T2∗-weighted magnetic resonance imaging (MRI). Electroencephalography showed continuous slow waves in the left occipital and parietal areas. After anticonvulsive therapy, his symptoms completely disappeared, accompanied by change in FDG uptake. Our case suggests that CMBs may be an epileptogenic focus of NCSE, and that FDG-PET is useful for the diagnosis of NCSE and assessment of therapeutic efficacy

Idiopathic Normal Pressure Hydrocephalus has a Different Cerebrospinal Fluid Biomarker Profile from Alzheimer's Disease.

The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is sometimes complicated by concomitant Alzheimer's disease (AD) pathology. The purpose of the present study is to identify an iNPH-specific cerebrospinal fluid (CSF) biomarker dynamics and to assess its ability to differentiate iNPH from AD. Total tau (t-tau), tau phosphorylated at threonine 181 (p-tau), amyloid-β (Aβ) 42 and 40, and leucine-rich α-2-glycoprotein (LRG) were measured in 93 consecutive CSF samples consisting of 55 iNPH (46 tap test responders), 20 AD, 11 corticobasal syndrome, and 7 spinocerebeller disease. Levels of t-tau and p-tau were significantly decreased in iNPH patients especially in tap test responders compared to AD. Correlation was observed between Mini-Mental State Examination scores and Aβ42 in AD (R = 0.44) and mildly in iNPH (R = 0.28). Although Aβ42/40 ratio showed no significant difference between iNPH and AD (p = 0.08), the levels of Aβ40 and Aβ42 correlated positively with each other in iNPH (R = 0.73) but much less in AD (R = 0.26), suggesting that they have discrete amyloid clearance and pathology. LRG levels did not differ between the two. Thus, our study shows that although CSF biomarkers of iNPH patients can be affected by concomitant tau and/or amyloid pathology, CSF t-tau and p-tau are highly useful for differentiation of iNPH and AD

Two-Point Dynamic Observation of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus

Background: Extensive research into cerebrospinal fluid (CSF) biomarkers was performed in patients with idiopathic normal pressure hydrocephalus (iNPH). Most prior research into CSF biomarkers has been one-point observation. Objective: To investigate dynamic changes in CSF biomarkers during routine tap test in iNPH patients. Methods: We analyzed CSF concentrations of tau, amyloid-β (Aβ) 42 and 40, and leucine rich α-2-glycoprotein (LRG) in 88 consecutive potential iNPH patients who received a tap test. We collected two-point lumbar CSF separately at the first 1 ml (First Drip (FD)) and at the last 1 ml (Last Drip (LD)) during the tap test and 9 patients who went on to receive ventriculo-peritoneal shunt surgery each provided 1 ml of ventricular CSF (VCSF). Results: Tau concentrations were significantly elevated in LD and VCSF compared to FD (LD/FD = 1.22, p = 0.003, VCSF/FD = 2.76, p = 0.02). Conversely, Aβ₄₂ (LD/FD = 0.80, p <  0.001, VCSF/FD = 0.38, p = 0.03) and LRG (LD/FD = 0.74, p <  0.001, VCSF/FD = 0.09, p = 0.002) concentrations were significantly reduced in LD and VCSF compared to FD. Gait responses to the tap test and changes in cognitive function in response to shunt were closely associated with concentrations of tau (p = 0.02) and LRG (p = 0.04), respectively. Conclusions: Dynamic changes were different among the measured CSF biomarkers, suggesting that LD of CSF as sampled during the tap test reflects an aspect of VCSF contributing to the pathophysiology of iNPH and could be used to predict shunt effectiveness