Hyperbaric oxygen treatment in delayed post-hypoxic encephalopathy following inhalation of liquefied petroleum gas: a case report.

Delayed post-hypoxic encephalopathy can occur after an episode of anoxia or hypoxia. Symptoms include apathy, confusion, and neurological deficits. We describe a 47-year-old male patient who inhaled gas from a kitchen stove liquid petroleum gas cylinder. He was diagnosed with hypoxic ischaemic encephalopathy 12 hours after his emergency department admission. He received six sessions of hyperbaric oxygen treatment (HBOT) and was discharged in a healthy state after six days. Fifteen days later, he experienced weakness, loss of appetite, forgetfulness, depression, balance problems, and inability to perform self-care. One week later, he developed urinary and fecal incontinence and was diagnosed with post-hypoxic encephalopathy. After 45 days from the onset of symptoms, he was referred to the Underwater and Hyperbaric Medicine Department for HBOT. The patient exhibited poor self-care and slow speech rate, as well as ataxic gait and dysdiadochokinesia. Hyperbaric oxygen was administered for twenty-four sessions, which significantly improved the patient's neurological status with only hypoesthesia in the left hand remaining at the end of treatment. Hyperbaric oxygen has been reported as successful in treating some cases of delayed neurological sequelae following CO intoxication. It is possible that HBO therapy may also be effective in delayed post-hypoxic encephalopathy from other causes. This may be achieved through mechanisms such as transfer of functional mitochondria to the injury site, remyelination of damaged neurons, angiogenesis and neurogenesis, production of anti-inflammatory cytokines, and balancing of inflammatory and anti-inflammatory cytokines.

Hyperbaric oxygen therapy in acute stroke: is it time for Justitia to open her eyes?

Hypoxia is a critical component of neuronal death in patients with stroke. Therefore increasing oxygenation of brain tissue seems to be a logical therapy against cerebral ischemia. Oxygen therapy exists in two modalities: normobaric hyperoxia therapy and hyperbaric oxygen therapy (HBO). HBO is a therapeutic procedure in which pure (100%) oxygen is administered at greater than atmospheric pressure in HBO therapy chambers. In this review article, we aimed to summarize the current knowledge regarding the therapeutic use of HBO in acute stroke patients. Literature review and electronic search were performed using PubMed, Medscape, and UpToDate with the keywords stroke, acute stroke, hyperbaric oxygen therapy, and hyperoxia. According to the reviewed literature, the use of HBO as routine stroke therapy cannot be justified in acute stage of stroke. More randomized, controlled studies are needed regarding safety and especially effectives of HBO in stroke patients. Also, standardized definitionof HBO should be proposed and used in all future studies.

Methods for Defining the Neuroprotective Properties of Xenon.

Xenon has features that make it an ideal general anesthetic agent; cost and scarcity mitigate xenon's widespread use in the operating room. Discovery of xenon's cytoprotective properties resulted in its application to thwart ongoing acute neurologic injury, an unmet clinical need. The discovery that xenon's neuroprotective effect interacts synergistically with targeted temperature management (TTM) led to its investigation in clinical settings, including in the management of the postcardiac arrest syndrome, in which TTM is indicated. Following successful demonstration of xenon's efficacy in combination with TTM in a preclinical model of porcine cardiac arrest, xenon plus TTM was shown to significantly decrease an imaging biomarker of brain injury for out of hospital cardiac arrest victims that had been successfully resuscitated. With the development of an efficient delivery system the stage is now set to investigate whether xenon improves survival, with good clinical outcome, for successfully resuscitated victims of a cardiac arrest.

Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: a "two-hit" model.

Hypoxic ischemic brain injury (HIBI) after cardiac arrest (CA) is a leading cause of mortality and long-term neurologic disability in survivors. The pathophysiology of HIBI encompasses a heterogeneous cascade that culminates in secondary brain injury and neuronal cell death. This begins with primary injury to the brain caused by the immediate cessation of cerebral blood flow following CA. Thereafter, the secondary injury of HIBI takes place in the hours and days following the initial CA and reperfusion. Among factors that may be implicated in this secondary injury include reperfusion injury, microcirculatory dysfunction, impaired cerebral autoregulation, hypoxemia, hyperoxia, hyperthermia, fluctuations in arterial carbon dioxide, and concomitant anemia.Clarifying the underlying pathophysiology of HIBI is imperative and has been the focus of considerable research to identify therapeutic targets. Most notably, targeted temperature management has been studied rigorously in preventing secondary injury after HIBI and is associated with improved outcome compared with hyperthermia. Recent advances point to important roles of anemia, carbon dioxide perturbations, hypoxemia, hyperoxia, and cerebral edema as contributing to secondary injury after HIBI and adverse outcomes. Furthermore, breakthroughs in the individualization of perfusion targets for patients with HIBI using cerebral autoregulation monitoring represent an attractive area of future work with therapeutic implications.We provide an in-depth review of the pathophysiology of HIBI to critically evaluate current approaches for the early treatment of HIBI secondary to CA. Potential therapeutic targets and future research directions are summarized.

Hyperbaric oxygen can induce neuroplasticity and improve cognitive functions of patients suffering from anoxic brain damage.

PURPOSE: Cognitive impairment may occur in 42-50% of cardiac arrest survivors. Hyperbaric oxygen therapy (HBO2) has recently been shown to have neurotherapeutic effects in patients suffering from chronic cognitive impairments (CCI) consequent to stroke and mild traumatic brain injury.The objective of this study was to assess the neurotherapeutic effect of HBO2 in patients suffering from CCI due to cardiac arrest. METHODS: Retrospective analysis of patients with CCI caused by cardiac arrest, treated with 60 daily sessions of HBO2. Evaluation included objective computerized cognitive tests (NeuroTrax), Activity of Daily Living (ADL) and Quality of life questionnaires. The results of these tests were compared with changes in brain activity as assessed by single photon emission computed tomography (SPECT) brain imaging. RESULTS: The study included 11 cases of CCI patients. Patients were treated with HBO2, 0.5-7.5 years (mean 2.6 ± 0.6 years) after the cardiac arrest. HBO2 was found to induce modest, but statistically significant improvement in memory, attention and executive function (mean scores) of 12% , 20% and 24% respectively. The clinical improvements were found to be well correlated with increased brain activity in relevant brain areas as assessed by computerized analysis of the SPECT imaging. CONCLUSIONS: Although further research is needed, the results demonstrate the beneficial effects of HBO2 on CCI in patients after cardiac arrest, even months to years after the acute event.

Coming back to oneself: a case of anoxic brain damage from a phenomenological perspective.

Struck by a cardiac arrest that lasted 3/4 of an hour, a 53-year-old man suddenly collapsed one day at work. The result was a serious anoxic brain damage that developed into dementia. This essay presents the process of 'coming back to himself' while it questions what this concept might imply. The descriptions and analyses rest upon an ethnographic study of his life, at hospitals and then at home, assisted by his wife, who is also the author of this article. Theoretically, the analysis depends on Merleau-Ponty's phenomenology of perception and is also based on the therapeutic use of music in treating people with dementia championed by Oliver Sachs. It is argued that the field of medicine has much to learn from the anthropological method of long-term observation, as well as theories of embodiment that see the body as simultaneously being an object and a subject.

Protective effect of Dl-3n-butylphthalide on learning and memory impairment induced by chronic intermittent hypoxia-hypercapnia exposure.

Cognitive impairment is a common finding in patients with chronic obstructive pulmonary disease (COPD), but little attention has been focused on therapeutic intervention for this complication. Chronic intermittent hypoxia hypercapnia (CIHH) exposure is considered to be responsible for the pathogenesis of COPD. Dl-3n-Butylphthalide (NBP), extracted from Apium graveolens Linn, has displayed a broad spectrum of neuroprotective properties. Our study aimed to investigate the potential of NBP on CIHH-induced cognitive deficits. The cognitive function of rats after CIHH exposure was evaluated by the Morris water maze, which showed that the NBP treated group performed better in the navigation test. NBP activated BDNF and phosphorylated CREB, the both are responsible for neuroprotection. Additionally, NBP decreased CIHH induced apoptosis. Moreover, NBP further induced the expression of HIF-1α, accompanied by the up-regulation of the autophagy proteins Bnip3, Beclin-1 and LC3-II. Finally, NBP also reversed the decreased expression of SIRT1 and PGC-1α, but the expression of Tfam, Cox II and mtDNA remained unchanged. These results suggested that the neuroprotective effects of NBP under CIHH condition possibly occurred through the inhibition of apoptosis, promotion of hypoxia-induced autophagy, and activation of the SIRT1/PGC-1α signalling pathway, while stimulation of mitochondrial biogenesis may not be a characteristic response.

Impact of acellular hemoglobin-based oxygen carriers on brain apoptosis in rats.

BACKGROUND: Extracellular hemoglobin (Hb)-based oxygen carriers (HBOCs) are under extensive consideration as oxygen therapeutics. Their effects on cellular mechanisms related to apoptosis are of particular interest, because the onset of proapoptotic pathways may give rise to tissue damage. STUDY DESIGN AND METHODS: The objective was to assess whether the properties of the Hb that replaces blood during an isovolemic hemodilution would modulate apoptotic-response mechanisms in rat brain and whether such signaling favors cytoprotection or damage. We exposed rats to exchange transfusion (ET; 50% blood volume and isovolemic replacement with Hextend [negative colloid control], MP4OX [PEGylated HBOC with high oxygen affinity], and ααHb [αα-cross-linked HBOC with low oxygen affinity; n=4-6/group]). Sham rats acted as control. Animals were euthanized at 2, 6, and 12 hours after ET; brain tissue was harvested and processed for analysis. RESULTS: In MP4OX animals, the number of neurons that overexpressed the hypoxia-inducible factor (HIF)-1α was higher than in ααHb, particularly at the early time points. In addition, MP4OX was associated with greater phosphorylation of protein kinase B (Akt), a well-known cytoprotective factor. Indeed, the degree of apoptosis, measured as terminal deoxynucleotidyl transferase-positive neurons and caspase-3 cleavage, ranked in order of MP4OX < Hextend < ααHb. CONCLUSION: Even though both HBOCs showed increased levels of HIF-1α compared to shams or Hextend-treated animals, differences in signaling events resulted in very different outcomes for the two HBOCs. ααHb-treated brain tissue showed significant neuronal damage, measured as apoptosis. This was in stark contrast to the protection seen with MP4OX, apparently due to recruitment of Akt and neuronal specific HIF-1α pathways.

Secondary mania in a patient with delayed anoxic encephalopathy after carbon monoxide intoxication caused by a suicide attempt.

We report herein a female patient presenting with delayed anoxic encephalopathy after carbon monoxide (CO) intoxication. Five months after she attempted suicide in her car using burning charcoal, she showed manic symptoms including aggressive behaviors, irritability, decreased total sleep time, increased energy and sexual interest, and hyperactivity, as well as illusions and visual hallucinations related to bugs, certain animals, monsters and her ex-husband. Fluid-attenuated inversion recovery and T2-weighted images in brain magnetic resonance imaging showed white-matter hyperintensity in the frontal lobe and periventricular area. Her manic symptoms and psychotic features improved following daily administration of valproate (600 mg) and olanzapine (10 mg). These observations indicate that clinicians should monitor for delayed neuropsychiatric symptoms in patients with CO intoxication.

[Case of carbon monoxide poisoning with delayed encephalopathy assessed by magnetic resonance imaging].

A 21-year-old man attempted suicide by burning charcoal in a car for more than one day and was admitted to a regional hospital. On admission, his blood carboxyhemoglobin concentration was 4.4%. The patient was transferred to our emergency department because of suspected carbon monoxide poisoning. Hyperbaric oxygen therapy (HBO) was performed 5 times over 3 days. Fluid-attenuation inversion recovery (FLAIR) and diffusion-weighted (DWI) magnetic resonance imaging (MRI) performed on day 3 showed high signal-intensity lesions in the cerebral white matter. Additional HBO was performed once per day until day 16. Wecheler Memory Scale-Reviced (WMS-R) and Mini-Mental State Examination (MMSE) performed on day 17 showed his cognitive impairment. He gradually recovered the cognitive function and was discharged from the hospital without neurological sequelae on day 49. Delayed encephalopathy after acute carbon monoxide poisoning with dementia, mental impairment, and psychosis is a serious complication. Hyperintensity in FLAIR and DWI MRI predicts delayed encephalopathy and indicates cellular edema and demyelination of the white matter. One of the risk factors is prolonged carbon monoxide exposure. This case suggests that the patient, who was exposed to carbon monoxide for many hours, was at a high risk of delayed encephalopathy despite the low blood carboxyhemoglobin concentration and therefore must be monitored using MRI.

Reduced regional gray matter volume in patients with chronic obstructive pulmonary disease: a voxel-based morphometry study.

BACKGROUND AND PURPOSE: Decreased oxygen supply may cause neuronal damage in the brains of patients with COPD, which is manifested by clinical symptoms such as neuropsychological deficits and mood disorders. The aim of the present study was to investigate brain gray matter change in COPD. MATERIALS AND METHODS: Using voxel-based morphometry based on the high-resolution 3D T1-weighted MR images of GM volume, we investigated 25 stable patients with COPD and 25 matching healthy volunteers. A battery of neuropsychological tests was also performed. RESULTS: Patients with COPD (versus controls) showed reduced GM volume in the frontal cortex (bilateral gyrus rectus, bilateral orbital and inferior triangular gyri, and left medial superior gyrus), right anterior insula, cingulate cortex (left anterior and middle gyri, right middle gyrus), right thalamus/pulvinar, right caudate, right putamen, right parahippocampus, and left amygdala. In COPD, in some of these regions, regional GM volume had positive correlations with arterial blood po(2), while in some regions, regional GM volume had negative correlations with disease duration. Patients with COPD (versus controls) had poorer performance in the Mini-Mental State Examination, Visual Reproduction, and Figure Memory tests. Moreover, the GM volume in the inferior triangular frontal cortex in patients with COPD was significantly correlated with the Picture Memory score. CONCLUSIONS: Our findings suggest GM reductions in a number of brain regions in COPD, which were associated with disease severity and may underlie the pathophysiologic and psychological changes in patients with COPD.

Bilateral supratentorial epidural hematomas: a rare complication in adolescent spine surgery.

A 14-year-old girl presented with a rare case of spontaneous bilateral supratentorial epidural hematomas which developed rapidly following cervical surgery. The hematomas presumably resulted from dural dynamics changes secondary to cerebrospinal fluid loss and intracranial hypotension. Intracranial epidural hemorrhage after spinal surgery is extremely uncommon with only one previous case report. Spontaneous intracranial epidural hematoma is an extremely rare complication, but should be considered as a possible complication of spine surgery, especially in adolescents complicated by delayed consciousness and breathing restoration from anesthesia. This case report expands the presently known clinical spectrum of this uncommon complication.

A maternal diet supplemented with creatine from mid-pregnancy protects the newborn spiny mouse brain from birth hypoxia.

The creatine-phosphocreatine shuttle is essential for the maintenance of cellular ATP, particularly under hypoxic conditions when respiration may become anaerobic. Using a model of intrapartum hypoxia in the precocial spiny mouse (Acomys cahirinus), the present study assessed the potential for maternal creatine supplementation during pregnancy to protect the developing brain from the effects of birth hypoxia. On day 38 of gestation (term is 39 days), the pregnant uterus was isolated and placed in a saline bath for 7.5 min, inducing global hypoxia. The pups were then removed, resuscitated, and cross-fostered to a nursing dam. Control offspring were delivered by caesarean section and recovered immediately after release from the uterus. At 24 h after birth hypoxia, the brains of offspring from dams fed a normal diet showed significant increases in lipid peroxidation as measured by the amount of malondialdehyde. In the cortical subplate, thalamus and piriform cortex there were significant increases in cellular expression of the pro-apoptotic protein BAX, cytoplasmic cytochrome c and caspase-3. When pregnant dams were fed the creatine supplemented diet, the increase in malondialdehyde, BAX, cytochrome c and caspase 3 were almost completely prevented, such that they were not different from control (caesarean-delivered) neonates. This study provides evidence that the neuroprotective capacity of creatine in the hypoxic perinatal brain involves abrogation of lipid peroxidation and apoptosis, possibly through the maintenance of mitochondrial function. Further investigation into these mechanisms of protection, and the long-term development and behavioural outcomes of such neonates is warranted.

Acupuncture as complementary therapy for hypoxic encephalopathy: a case study.

OBJECTIVE: In acute carbon monoxide intoxication, more serious neuronal damage may induce hypoxic encephalopathy with variable degrees of brain damage, ranging from confusion to deep coma. We report herein on a patient who developed hypoxic encephalopathy and acute respiratory failure after acute carbon monoxide intoxication. Acupuncture therapy has been applied along with prescription medication to restore consciousness. CLINICAL PRESENTATION: The patient had a 2-month history of consciousness disturbance and frequent generalised episodic clonic twitching with upward gazing, which was diagnosed as hypoxic encephalopathy. INTERVENTION: Acupuncture therapy has been applied to restore consciousness with routine treatment and medication prescription. The patient was treated 29 times by abdominal acupuncture in conjunction with scalp, body and foot acupuncture according to the 12 meridians' points as an assistant therapy. After 2 months of acupuncture treatment, the patient regained consciousness; the Glasgow Coma Scale (GCS) index increased from 7 to 15, before and after acupuncture therapy. CONCLUSION: This case report suggests that there may be a role for complementary treatment with acupuncture in such cases, and it would be more definitive, meaningful and a welcome addition to our database of knowledge if more case studies about the possibility of acupuncture use in these circumstances were done.

Effect of virgin olive oil plus acetylsalicylic acid on brain slices damage after hypoxia-reoxygenation in rats with type 1-like diabetes mellitus.

Aspirin is the most widely used drug for the secondary prevention of ischemic stroke in patients suffering from diabetes mellitus. Moreover virgin olive oil (VOO) administration exerts a neuroprotective effect in healthy rat brain slices. The aim of the present study was to determine the possible influence of VOO administration to streptozotocin-diabetic rats (DR) on the neuroprotective effect of aspirin in rat brain. DR were treated during 3 months with saline, aspirin (2mg/kg/day p.o.), VOO (0.5 mL/kg/day p.o.) or its association; a control normoglycemic group was treated with saline. Brain slices were subjected to oxygen-glucose deprivation before a reoxygenation period. All the treatments significantly reduced lactate dehydrogenase LDH efflux after reoxygenation (-54.1% for aspirin, -51.3% for VOO and -72.9% for aspirin plus VOO). Lipid peroxides in brain slices were also reduced after the treatment with aspirin (-17.90%), VOO (-37.3%) and aspirin plus VOO (-49.2%). Production of nitric oxide after reoxygenation was inhibited by all the treatments (-46.5% for ASA, -48.2% for VOO and -75.8% for ASA plus VOO). The activity of the inducible isoform (iNOS) was inhibited by the three types of treatment (-31.8% for ASA, -29.1% for VOO and -56.0% for ASA plus VOO). The main conclusion of our study is that daily oral administration of VOO to diabetic rats may be a natural way to increase the neuroprotective effect of aspirin in diabetic animals.