Functional Neural Changes after Low-Frequency Bilateral Globus Pallidus Internus Deep Brain Stimulation for Post-Hypoxic Cortical Myoclonus: Voxel-Based Subtraction Analysis of Serial Positron Emission

Post-hypoxic myoclonus (PHM) and Lance–Adams syndrome (LAS) are rare conditions following cardiopulmonary resuscitation. The aim of this study was to identify functional activity in the cerebral cortex after a hypoxic event and to investigate alterations that could be modulated by deep brain stimulation (DBS). A voxel-based subtraction analysis of serial positron emission tomography (PET) scans was performed in a 34-year-old woman with chronic medically refractory PHM that improved with bilateral globus pallidus internus (Gpi) DBS implanted three years after the hypoxic event. The patient required low-frequency stimulation to show myoclonus improvement. Using voxel-based statistical parametric mapping, we identified a decrease in glucose metabolism in the prefrontal lobe including the dorsolateral, orbito-, and inferior prefrontal cortex, which was suspected to be the origin of the myoclonus from postoperative PET/magnetic resonance imaging (MRI) after DBS. Based on the present study results, voxel-based subtraction of PET appears to be a useful approach for monitoring patients with PHM treated with DBS. Further investigation and continuous follow-up on the use of PET analysis and DBS treatment for patients with PHM are necessary to help understanding the pathophysiology of PHM, or LAS.

098 A case of delayed post-hypoxic leukoencephalopathy complicating drug overdose

IntroductionDelayed post-hypoxic leukoencephalopathy (DPHL) is a syndrome characterised by neurological deterioration following a period of recovery after an initial hypoxic event with striking white-matter change on magnetic resonance imaging. We present a case characterised by insidious onset and a fluctuating course of cognitive and neuropsychiatric symptoms.MethodsSingle case report.ResultsA 61 year old lady, with a background history of previously well managed bipolar affective disorder, was found unresponsive following an intentional overdose of temazepam and tramadol. She was hypotensive, hypoxic and required ventilatory and inotropic support. Following extubation, the patient had residual left-sided weakness and MRI confirmed a right frontal watershed infarction. A three week period of clinical improvement was followed by marked deterioration firstly with fluctuating mood and other neuropsychiatric symptoms which progressed to severe impairment of cognition and alertness. There was generalised slowing on the EEG and the CSF was unremarkable. Repeat neuroimaging undertaken on day 41 of the admission, revealed new symmetric and confluent cerebral white matter changes with high signal on the Diffusion Weighted Images (DWI) and Fluid Attenuated Inversion Recovery (FLAIR) images. The patient was managed with supportive care and sustained a clinically significant recovery (MOCA 26/30), despite ongoing cognitive impairments including working memory and deficits in social cognition including mood instability and disinhibition. Repeat neuroimaging 3 months after initial presentation revealed partial resolution of the white matter changes.ConclusionA diagnosis of DPHL should be considered in patients with variable mood and cognition following initial improvement after a hypoxic event.

Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent

Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO2 < 10 mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these targets we separated the seizure from the resulting severe hypoxia and show that structure specific postictal memory and behavioral impairments are the consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much more than a disease hallmarked by seizures, since the occurrence of postictal hypoperfusion/hypoxia results in a separate set of neurological consequences that are currently not being treated and are preventable.

Sperm motility and fertilisation success in an acidified and hypoxic environment

The distribution and function of many marine species is largely determined by the effect of abiotic drivers on their reproduction and early development, including those drivers associated with elevated CO2 and global climate change. A number of studies have therefore investigated the effects of elevated pCO2 on a range of reproductive parameters, including sperm motility and fertilisation success. To date, most of these studies have not examined the possible synergistic effects of other abiotic drivers, such as the increased frequency of hypoxic events that are also associated with climate change. The present study is therefore novel in assessing the impact that an hypoxic event could have on reproduction in a future high CO2 ocean. Specifically, this study assesses sperm motility and fertilisation success in the sea urchin Paracentrotus lividus exposed to elevated pCO2 for 6 months. Gametes extracted from these pre-acclimated individuals were subjected to hypoxic conditions simulating an hypoxic event in a future high CO2 ocean. Sperm swimming speed increased under elevated pCO2 and decreased under hypoxic conditions resulting in the elevated pCO2 and hypoxic treatment being approximately equivalent to the control. There was also a combined negative effect of increased pCO2 and hypoxia on the percentage of motile sperm. There was a significant negative effect of elevated pCO2 on fertilisation success, and when combined with a simulated hypoxic event there was an even greater effect. This could affect cohort recruitment and in turn reduce the density of this ecologically and economically important ecosystem engineer therefore potentially effecting biodiversity and ecosystem services.