Middle meningeal artery embolization for chronic subdural hematoma with cerebrospinal fluid hypovolemia: A report of 2 cases.

BACKGROUND: Chronic subdural hematoma (CSDH) with cerebrospinal fluid hypovolemia syndrome (CHS) remains refractory to standard treatment with hematoma drainage by burr hole and irrigation and/or epidural blood patch. Previously, we reported the utility of middle meningeal artery (MMA) embolization for intractable CSDH. In this study, we present the usefulness of MMA embolization as a treatment for CSDHs with CHSs. CASES: We present two cases of CSDHs with CHSs occurring in patients, 1 treated with burr hole craniotomy and irrigation, and the other treated with the epidural blood patch. Both patients exhibited similar-appearing bilateral relatively-thin hematomas, hyperplasia, and enhanced contrast effects in the dura mater, and extradural hygroma in the cervical portion on enhanced magnetic resonance imaging scans. Also, to reviewing prior literature and imaging findings, they had already undergone conventional treatment. We added MMA embolization treatment and they followed a good course. RESULTS: Despite the known intractable outcomes of patients with CSDHs with CHSs, MMA embolization worked well in the current case series. CONCLUSION: MMA embolization might be considered as a preferred therapeutic option for CSDHs with CHSs in order to buy time before the epidural blood patch starts working.

Antimicrobial activity of the volatile compound 3,5-dichloro-4-methoxybenzaldehyde, produced by the mushroom Porostereum spadiceum, against plant-pathogenic bacteria and fungi.

AIMS: In this study, volatile compounds released from mycelia of some aromatic mushrooms were investigated for their inhibitory activity against plant-pathogenic bacteria and fungi. METHODS AND RESULTS: A screening revealed that volatile compounds from mycelia of Porostereum spadiceum remarkably inhibited the colony formation of plant-pathogenic bacteria, including Clavibacter michiganensis subsp. michiganensis and Ralstonia solanacearum while also inhibiting the conidial germination of plant-pathogenic fungi including Alternaria brassicicola and Colletotrichum orbiculare. The volatile compounds were isolated from the culture filtrate of P. spadiceum, and 3,4-dichloro-4-methoxybenzaldehyde (DCMB) was identified as a major compound. DCMB significantly inhibited bacterial colonization at 10 µg ml-1 and fungal conidial germination at 0·1-1 µg ml-1 as a vapour. CONCLUSIONS: This is the first report on the production of the volatile compound DCMB by P. spadiceum and on the antimicrobial activity of DCMB against plant-pathogenic bacteria and fungi at low concentrations. It may be possible to use the compound as an agent for protecting crops from bacterial and fungal diseases during cultivation and storage. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides an understanding of antimicrobial activity of the mushroom volatile compound that may be useful as a novel biological control agent for protecting various plant diseases.

Analysis of the Beaufort Gyre Freshwater Content in 2003-2018.

Hydrographic data collected from research cruises, bottom-anchored moorings, drifting Ice-Tethered Profilers, and satellite altimetry in the Beaufort Gyre region of the Arctic Ocean document an increase of more than 6,400 km3 of liquid freshwater content from 2003 to 2018: a 40% growth relative to the climatology of the 1970s. This fresh water accumulation is shown to result from persistent anticyclonic atmospheric wind forcing (1997-2018) accompanied by sea ice melt, a wind-forced redirection of Mackenzie River discharge from predominantly eastward to westward flow, and a contribution of low salinity waters of Pacific Ocean origin via Bering Strait. Despite significant uncertainties in the different observations, this study has demonstrated the synergistic value of having multiple diverse datasets to obtain a more comprehensive understanding of Beaufort Gyre freshwater content variability. For example, Beaufort Gyre Observational System (BGOS) surveys clearly show the interannual increase in freshwater content, but without satellite or Ice-Tethered Profiler measurements, it is not possible to resolve the seasonal cycle of freshwater content, which in fact is larger than the year-to-year variability, or the more subtle interannual variations.

CHARACTERIZATION OF AN IN-HOUSE DEVELOPED MULTI-CYLINDRICAL MODERATOR NEUTRON SPECTROMETER.

This article describes the characterization of an in-house developed multi-cylindrical moderator neutron spectrometer, which consists of a cylindrical 3He proportional counter and cylindrical moderator shells of different sizes. The response matrix of the spectrometer was calculated by Monte Carlo simulations for neutron energies from 1 × 10-8 to 10 MeV and verified with measurements in 0.144 MeV, 1.2 MeV and 241AmBe neutron standard fields. Influence of scattered neutrons was properly eliminated from the measured response using the shadow cone technique. The calculated and measured responses were in good agreement in most cases. Differences were <10% for all moderated counter configurations, while larger deviations were observed for the bare counter configuration. The performance of the neutron spectrometer in terms of spectrum unfolding was verified in the 241AmBe neutron standard field, showing reliable neutron spectrum and fluence rate in the energy range up to 10 MeV as investigated in this work.

Recanalisation of the internal carotid artery via the vasa vasorum after coil occlusion.

Antegrade recanalisation of a completely occluded internal carotid artery (ICA) via the vasa vasorum is extremely rare. Here, we report such a case after proximal endovascular coiling in a case of dissected (i.e. non-atherosclerotic) ICA. A 42-year-old man presented with thromboembolic stroke of the left frontal lobe owing to pseudo-occlusion of the left ICA manifesting as motor aphasia and right hemiparesis. There were abundant floating thrombi in the petrous portion of the left ICA. Because of good collateral flow in the left middle cerebral artery territory through the anterior communicating artery and external carotid artery system, endovascular coil embolisation of the left ICA was performed for prevention of further thromboembolic stroke. The patient showed progressive recovery following endovascular treatment, and was discharged with mild right hemiparesis 1 month later. He maintained a regimen of aspirin and physical rehabilitation. At follow-up, 38 months later, the patient was asymptomatic. Angiography demonstrated occlusion of the left ICA and multiple serpiginous vessels originating from the proximal internal and external carotid arteries and which filled the ICA distal to the occlusion. This case suggests that an ICA occluded by proximal coil embolisation-even in a non-atherosclerotic case-might be recanalised via the vasa vasorum.

Effects of sleep on the cardiovascular and thermoregulatory systems: a possible role for hypocretins.

Sleep influences the cardiovascular, endocrine, and thermoregulatory systems. Each of these systems may be affected by the activity of hypocretin (orexin)-producing neurons, which are involved in the etiology of narcolepsy. We examined sleep in male rats, either hypocretin neuron-ablated orexin/ataxin-3 transgenic (narcoleptic) rats or their wild-type littermates. We simultaneously monitored electroencephalographic and electromyographic activity, core body temperature, tail temperature, blood pressure, electrocardiographic activity, and locomotion. We analyzed the daily patterns of these variables, parsing sleep and circadian components and changes between states of sleep. We also analyzed the baroreceptor reflex. Our results show that while core temperature and heart rate are affected by both sleep and time of day, blood pressure is mostly affected by sleep. As expected, we found that both blood pressure and heart rate were acutely affected by sleep state transitions in both genotypes. Interestingly, hypocretin neuron-ablated rats have significantly lower systolic and diastolic blood pressure during all sleep stages (non-rapid eye movement, rapid eye movement) and while awake (quiet, active). Thus, while hypocretins are critical for the normal temporal structure of sleep and wakefulness, they also appear to be important in regulating baseline blood pressure and possibly in modulating the effects of sleep on blood pressure.

Loss of polyubiquitin gene Ubb leads to metabolic and sleep abnormalities in mice.

AIMS: Ubiquitin performs essential roles in a myriad of signalling pathways required for cellular function and survival. Recently, we reported that disruption of the stress-inducible ubiquitin-encoding gene Ubb reduces ubiquitin content in the hypothalamus and leads to adult-onset obesity coupled with a loss of arcuate nucleus neurones and disrupted energy homeostasis in mice. Neuropeptides expressed in the hypothalamus control both metabolic and sleep behaviours. In order to demonstrate that the loss of Ubb results in broad hypothalamic abnormalities, we attempted to determine whether metabolic and sleep behaviours were altered in Ubb knockout mice. METHODS: Metabolic rate and energy expenditure were measured in a metabolic chamber, and sleep stage was monitored via electroencephalographic/electromyographic recording. The presence of neurodegeneration and increased reactive gliosis in the hypothalamus were also evaluated. RESULTS: We found that Ubb disruption leads to early-onset reduced activity and metabolic rate. Additionally, we have demonstrated that sleep behaviour is altered and sleep homeostasis is disrupted in Ubb knockout mice. These early metabolic and sleep abnormalities are accompanied by persistent reactive gliosis and the loss of arcuate nucleus neurones, but are independent of neurodegeneration in the lateral hypothalamus. CONCLUSIONS: Ubb knockout mice exhibit phenotypes consistent with hypothalamic dysfunction. Our data also indicate that Ubb is essential for the maintenance of the ubiquitin levels required for proper regulation of metabolic and sleep behaviours in mice.

Hypocretin/orexin and narcolepsy: new basic and clinical insights.

Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain-Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for 'narcolepsy with cataplexy' and 'narcolepsy due to medical condition'). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress.

Endovascular treatment of aneurysmal subarachnoid hemorrhage associated with bilateral common carotid artery occlusion.

SUMMARY: Cases of aneurysm associated with the occlusion of both common carotid arteries are very rare.We present a case of ruptured aneurysms of the basilar bifurcation and posterior cerebral artery coexisting with bilateral common carotid artery occlusion, successfully treated by endovascular coil embolization with a double-balloon remodeling technique. Finally, we review the literature. A 62-year-old woman presented with severe headache; a computed tomography scan demonstrated subarachnoid hemorrhage. Angiography revealed that the bilateral common carotid arteries were occluded. The muscle branches of the vertebral arteries had anastomosed to the bilateral external carotid arteries. Bilateral posterior communicating arteries had developed and supplied the bilateral internal carotid arteries. Two aneurysms (a saccular aneurysm of the P1 portion of the left posterior cerebral artery and a wide-necked aneurysm of the basilar bifurcation) were also observed. Endovascular embolization of the aneurysms was successfully performed using a double-balloon remodeling technique. The patient made a full recovery after treatment, and the aneurysms remained obliterated 12 months after embolization. We believe that this is the first report of ruptured aneurysms associated with bilateral common carotid artery occlusion successfully treated by endovascular coiling. The double-balloon remodeling technique was useful for treatment of wide-necked basilar bifurcation aneurysm.

Unusual variant of persistent primitive hypoglossal artery.

Here, we present a case of an unusual variant of a persistent primitive hypoglossal artery, which was found incidentally during an examination for a hypertensive thalamic haemorrhage. The anastomotic vessel arose from the external carotid artery and joined the vertebral artery through the hypoglossal canal. The embryology of the anomaly is briefly discussed.

Review of pathophysiology and clinical management of narcolepsy in dogs.

Narcolepsy is a chronic sleep disorder that affects human beings and animals. Up to 17 breeds of dogs are affected sporadically, and familial forms occur in dobermanns, labrador retrievers and dachshunds. These dogs display characteristics strikingly similar to those of human narcolepsy, including cataplexy (a sudden loss of muscle tone in response to emotional stimulation) and a shorter sleep latency. It has recently been shown that the aetiology of both the familial form (receptor null mutation) and the sporadic form (loss of ligand production) of canine narcolepsy is associated with a deficit in hypocretin/orexin neurotransmission. Hypocretin deficiency can be detected by the measurement of hypocretin-1 in cerebrospinal fluid, and this could be used to diagnose hypocretin ligand deficient cases in clinical practice. Narcolepsy is neither progressive nor life-threatening, but the clinical signs persist throughout life, and lifelong treatment and care are required. This article reviews the recent progress in narcolepsy research in dogs, and describes the diagnosis and treatment of the disease.

Early embolization for ruptured aneurysm in acute stage of subarachnoid hemorrhage with neurogenic pulmonary edema.

SUMMARY: Four cases of ruptured aneurysmal subarachnoid hemorrhage (SAH) presented with severe neurogenic pulmonary edema (NPE). On admission, two patients were grade IV and two were grade V according to Hunt and Hess grading. All patients needed respiratory management with the assistance of a ventilator. Three of them underwent endovascular treatment for the ruptured aneurysms within three days from onset after ensuring hemodynamic stability. Immediately after the endovascular treatment, lumbar spinal drainage was inserted in all the patients. The pulmonary edema findings disappeared rapidly after the respiratory management. The results were good recovery in two, and moderate disability in two. We concluded that early embolization of ruptured aneurysm and placement of spinal drainage is a satisfactory option for severe SAH with NPE.

Histamine H3 receptor antagonists: from target identification to drug leads.

The successful cloning and functional expression of the histamine H(3) receptor in the late 1990 s has greatly facilitated our efforts to identify small molecule, non-imidazole based compounds to permit the evaluation of H(3) antagonists in models of CNS disorders. High-throughput screening identified several series of lead compounds, including a series of imidazopyridines, which led to JNJ-6379490, a compound with high affinity for the human H(3) receptor. Analysis of structural features common to several series of non-imidazole H(3) receptor ligands resulted in a pharmacophore model. This model led to the design of JNJ-5207852, a diamine-based H(3) antagonist with good in vitro and in vivo efficacy but with an undesirable long half-life. However, further modifications of the template provided an understanding of the effect of structural modifications on pharmacokinetic properties, ultimately affording several additional series of compounds including JNJ-10181457, a compound with an improved pharmacokinetic profile. These compounds allowed in vivo pharmacological evaluation to show that H(3) antagonists promote wakefulness, but unlike modafinil and classical psychostimultants, they do not increase locomotor activity or produce any alteration of the EEG power spectral activity in rats. H(3) antagonists also increase extracellular acetylcholine and norepinephrine but not dopamine in rat frontal cortex and show efficacy in various models of learning-memory deficit. In addition, cFos immunoreactivity studies show H(3) antagonists activate neuronal cells in restricted rat brain regions in contrast to widespread activation after modafinil or amphetamine treatment. Therefore, H(3) antagonists are promising clinical candidates for the treatment of excessive day time sleepiness and/or cognitive disorders.

CSF hypocretin-1/orexin-A concentrations in patients with subarachnoid hemorrhage (SAH).

The aim of this study was to examine the role of the hypothalamic hypocretin/orexin system in complications of delayed ischemic neuronal deficit (DIND) resulting from symptomatic vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). CSF hypocretin-1/orexin-A levels were measured in 15 SAH patients. DIND complications occurred in seven patients with symptomatic vasospasm. Hypocretin-1/orexin-A levels were low in SAH patients during the 10 days following the SAH event. CSF hypocretin-1/orexin-A levels were lower in patients with DIND complications than in those who did not develop DIND. A significant transient decline in CSF hypocretin-1/orexin-A levels was also observed at the onset of DIND in all patients with symptomatic vasospasm. The reduced hypocretin/orexin production observed in SAH patients may reflect reduced brain function due to the decrease in cerebral blood flow. These results, taken together with recent experimental findings in rats that indicate hypocretin receptor 1 (orexin 1 receptor) mRNA and protein are elevated following middle cerebral artery occlusion, suggest that a reduction in hypocretin/orexin production in SAH and DIND patients is associated with alterations in brain hypocretin/orexin signaling in response to ischemia.

Hypocretin deficiency in Prader-Willi syndrome.

Four patients with clinically and genetically confirmed Prader-Willi syndrome (PWS) underwent nocturnal polysomnograpy (PSG), multiple sleep latency test (MSLT), human leukocyte antigens (HLA) typing and estimation of cerebrospinal fluid (CSF) hypocretin-1 (Hcrt-1) level to investigate if a role of hypothalamic dysfunction and sleep disturbance might be functionally connected through the hypocretin (orexin) system. In all four patients physical examination confirmed extreme obesity (increasing with age) with dysmorphogenetic features. Excessive daytime sleepiness (EDS) was manifested in only two subjects without any imperative feature. None of the patients under study suffered from cataplexy. Nocturnal PSG revealed fragmented sleep with low efficiency, the hypopnea and apnea indexes increasing from borderline up to very high values in direct proportion to the patients' age. MSLT latency was shortened in two patients with clinically expressed EDS, only one sleep onset rapid eye movements (REM) period (SOREM) was found. HLA typing showed DQB1*0602 positivity in two patients; the further two were negative. Mean value of CSF Hcrt-1 in the patients group was down to 164 +/- 46.8 pg/ml (in comparison with 265.8 +/- 48.8 pg/ml in 10 young healthy subjects, P=0.02). The deficiency of CSF Hcrt-1 level correlated in PWS patients with their EDS severity.

Hypocretin-1 CSF levels in anti-Ma2 associated encephalitis.

Idiopathic narcolepsy is associated with deficient hypocretin transmission. Narcoleptic symptoms have recently been described in paraneoplastic encephalitis with anti-Ma2 antibodies. The authors measured CSF hypocretin-1 levels in six patients with anti-Ma2 encephalitis, and screened for anti-Ma antibodies in patients with idiopathic narcolepsy. Anti-Ma autoantibodies were not detected in patients with idiopathic narcolepsy. Four patients with anti-Ma2 encephalitis had excessive daytime sleepiness; hypocretin-1 was not detectable in their cerebrospinal fluid, suggesting an immune-mediated hypocretin dysfunction.

CSF hypocretin levels in Guillain-Barré syndrome and other inflammatory neuropathies.

CSF hypocretin-1 was measured in 28 Guillain-Barré syndrome (GBS), 12 Miller-Fisher syndrome, 12 chronic inflammatory demyelinating polyneuropathy (CIDP), and 48 control subjects. Seven GBS subjects had undetectably low hypocretin-1 levels (<100 pg/mL). Hypocretin-1 levels were moderately reduced in an additional 11 GBS, 5 Miller-Fisher syndrome, and 1 CIDP subject. Low levels in GBS occurred early in the disease and were associated with upper CNS level abnormalities.