Mark H. Wilson

The cerebral effects of ascent to high altitudes

Cellular hypoxia is the common final pathway of brain injury that occurs not just after asphyxia, but also when cerebral perfusion is impaired directly (eg, embolic stroke) or indirectly (eg, raised intracranial pressure after head injury). We Review recent advances in the understanding of neurological clinical syndromes that occur on exposure to high altitudes, including high altitude headache (HAH), acute mountain sickness (AMS), and high altitude cerebral oedema (HACE), and the genetics, molecular mechanisms, and physiology that underpin them. We also present the vasogenic and cytotoxic bases for HACE and explore venous hypertension as a possible contributory factor. Although the factors that control susceptibility to HACE are poorly understood, the effects of exposure to altitude (and thus hypobaric hypoxia) might provide a reproducible model for the study of cerebral cellular hypoxia in healthy individuals. The effects of hypobaric hypoxia might also provide new insights into the understanding of hypoxia in the clinical setting.

Cerebral artery dilatation maintains cerebral oxygenation at extreme altitude and in acute hypoxia—an ultrasound and MRI study

Transcranial Doppler is a widely used noninvasive technique for assessing cerebral artery blood flow. All previous high altitude studies assessing cerebral blood flow (CBF) in the field that have used Doppler to measure arterial blood velocity have assumed vessel diameter to not alter. Here, we report two studies that demonstrate this is not the case. First, we report the highest recorded study of CBF (7,950 m on Everest) and demonstrate that above 5,300 m, middle cerebral artery (MCA) diameter increases (n = 24 at 5,300 m, 14 at 6,400 m, and 5 at 7,950 m). Mean MCA diameter at sea level was 5.30 mm, at 5,300 m was 5.23 mm, at 6,400 m was 6.66 mm, and at 7,950 m was 9.34 mm (P<0.001 for change between 5,300 and 7,950 m). The dilatation at 7,950 m reversed with oxygen. Second, we confirm this dilatation by demonstrating the same effect (and correlating it with ultrasound) during hypoxia (FiO2 = 12% for 3 hours) in a 3-T magnetic resonance imaging study at sea level (n = 7). From these results, we conclude that it cannot be assumed that cerebral artery diameter is constant, especially during alterations of inspired oxygen partial pressure, and that transcranial 2D ultrasound is a technique that can be used at the bedside or in the remote setting to assess MCA caliber.

Direct measurement of intracranial pressure at high altitude and correlation of ventricular size with acute mountain sickness: Brian Cummins' results from the 1985 Kishtwar expedition.

OBJECTIVE AND IMPORTANCEThe “tight-fit” hypothesis and subsequent current understanding of acute mountain sickness (AMS) is that individuals with less compliant cerebrospinal fluid systems (smaller ventricles and cerebrospinal fluid spaces) have a greater increase in intracranial pressure (ICP) for a given increase in brain volume as a result of hypoxic cerebral edema. There has only been 1 study of direct (telemetric) ICP measurement at high altitude. This was performed in 1985 on 3 subjects by Brian Cummins up to a maximum height of 16 500 ft (5030 m). The group also investigated the “tight-fit” hypothesis by correlating computed tomographic scans that measured ventricular size (read blindly) with headache score and AMS symptomatology in 10 subjects. Unfortunately, the data were thought to have been destroyed by fire, and, hence, the findings were not published. The data have now been rediscovered, and this article reviews the methodology and findings of this unique piece of work. RESULTSThe ICP monitoring study demonstrated that ICP remained normal at rest at all altitudes; however, in the single subject with AMS, there was a dramatic increase in ICP even on minimal exertion. The computed tomographic scan analysis of brain compliance demonstrated an inverse correlation between ventricular size and headache score. CONCLUSIONThis unique research, which is unlikely to ever be repeated, is the only report of direct ICP measurement at high altitude. This and the computed tomographic study provide the first objective evidence supporting the “tight-fit” hypothesis of AMS.

Cerebral venous system and anatomical predisposition to high-altitude headache

As inspired oxygen availability falls with ascent to altitude, some individuals develop high‐altitude headache (HAH). We postulated that HAH results when hypoxia‐associated increases in cerebral blood flow occur in the context of restricted venous drainage, and is worsened when cerebral compliance is reduced. We explored this hypothesis in 3 studies.

The headache of high altitude and microgravity—similarities with clinical syndromes of cerebral venous hypertension

Syndromes thought to have cerebral venous hypertension as their core, such as idiopathic intracranial hypertension and jugular foramen outlet obstruction, classically result in headaches. Do they provide an insight into the cause of the headache that commonly occurs at altitude? The classic theory of the pathogenesis of high altitude headache has been that it results from increased intracranial pressure (ICP) secondary to hypoxemia in people who have less compliant intracranial volumes (Roach and Hackett, 2001). However, there does not appear to be a correlation between the headache of acute mountain sickness (AMS) and the presence of cerebral edema (Bailey et al, 2006; Wilson et al, 2009). Research has concentrated on arterial perfusion to the brain in hypoxia, but there has been little study of venous drainage. Hypoxia results in markedly increased cerebral blood flow; however, if it has been considered at all, venous outflow has to date been assumed to be of little consequence. Retinal venous distension and the increased venous blood demonstrated by near infra-red spectroscopy and more recently by MRI imply that, in hypoxia, a relative venous insufficiency may exist. Similarly, there is increasing evidence that manifestations of the fluid shift during microgravity is of similar nature to idiopathic intracranial hypertension, which is thought to be primarily a venous insufficiency condition. The unique anthropomorphic adaptations of large brained biped humans with cerebral venous systems that have to cope with large changes in hydrostatic pressure may predispose us to conditions of inflow/outflow mismatch. In addition, slight increases in central venous pressures (e.g., from hypoxia-induced pulmonary vasoconstriction) may further compromise venous outflow at altitude. A better understanding of cerebral venous physiology may enlighten us with regards the pathogenesis of headaches currently considered idiopathic. It may also enable us to trigger headaches for study and hence enable us to develop new treatment strategies.

Surgical management of acute subdural haematomas: current practice patterns in the United Kingdom and the Republic of Ireland.

Abstract Introduction. Uncertainty remains as to the role of decompressive craniectomy (DC) for primary evacuation of acute subdural haematomas (ASDH). In 2011, a collaborative group was formed in the UK with the aim of answering the following question: “What is the clinical- and cost-effectiveness of decompressive craniectomy, in comparison with craniotomy for adult patients undergoing primary evacuation of an ASDH?” The proposed RESCUE-ASDH trial (Randomised Evaluation of Surgery with Craniectomy for patients Undergoing Evacuation of Acute Subdural Haematoma) is a multicentre, pragmatic, parallel group randomised trial of DC versus craniotomy for adult head-injured patients with an ASDH. In this study, we used an online questionnaire to assess the current practice patterns in the management of ASDH in the UK and the Republic of Ireland, and to gauge neurosurgical opinion regarding the proposed RESCUE-ASDH trial. Materials and methods. A questionnaire survey of full members of the Society of British Neurological Surgeons and members of the British Neurosurgical Trainees Association was undertaken between the beginning of May and the end of July 2012. Results. The online questionnaire was answered by 95 neurosurgeons representing 31 of the 32 neurosurgical units managing adult head-injured patients in the UK and the Republic of Ireland. Forty-five percent of the respondents use primary DC in at least 25% of patients with ASDH. In addition, of the 22 neurosurgical units with at least two Consultant respondents, only three units (14%) showed intradepartmental agreement regarding the proportion of their patients receiving a primary DC for ASDH. Conclusion. The survey results demonstrate that there is significant uncertainty as to the optimal surgical technique for primary evacuation of ASDH. The fact that the majority of the respondents are willing to become collaborators in the planned RESCUE-ASDH trial highlights the relevance of this important subject to the neurosurgical community in the UK and Ireland.

Magnetic Resonance investigation into the mechanisms involved in the development of high-altitude cerebral edema

Rapid ascent to high altitude commonly results in acute mountain sickness, and on occasion potentially fatal high-altitude cerebral edema. The exact pathophysiological mechanisms behind these syndromes remain to be determined. We report a study in which 12 subjects were exposed to a FiO2 = 0.12 for 22 h and underwent serial magnetic resonance imaging sequences to enable measurement of middle cerebral artery velocity, flow and diameter, and brain parenchymal, cerebrospinal fluid and cerebral venous volumes. Ten subjects completed 22 h and most developed symptoms of acute mountain sickness (mean Lake Louise Score 5.4; p < 0.001 vs. baseline). Cerebral oxygen delivery was maintained by an increase in middle cerebral artery velocity and diameter (first 6 h). There appeared to be venocompression at the level of the small, deep cerebral veins (116 cm3 at 2 h to 97 cm3 at 22 h; p < 0.05). Brain white matter volume increased over the 22-h period (574 ml to 587 ml; p < 0.001) and correlated with cumulative Lake Louise scores at 22 h (p < 0.05). We conclude that cerebral oxygen delivery was maintained by increased arterial inflow and this preceded the development of cerebral edema. Venous outflow restriction appeared to play a contributory role in the formation of cerebral edema, a novel feature that has not been observed previously.

Caudwell Xtreme Everest expedition

The Caudwell Xtreme Everest (CXE) expedition involved the detailed study of 222 subjects ascending to 5300 m or higher during the first half of 2007. Following baseline measurements at sea level, 198 trekker-subjects trekked to Everest Base Camp (EBC) following an identical ascent profile. An additional group of 24 investigator-subjects followed a similar ascent to EBC and remained there for the duration of the expedition, with a subgroup of 14 collecting data higher on Everest. This article focuses on published data obtained by the investigator-subjects at extreme altitude (>5500 m). Unique measurements of peak oxygen consumption, middle cerebral artery diameter and blood velocity, and microcirculatory blood flow were made on the South Col (7950 m). Unique arterial blood gas values were obtained from 4 subjects at 8400 m during descent from the summit of Everest. Arterial blood gas and microcirculatory blood flow data are discussed in detail.

Can contrast-enhanced ultrasonography improve Zone III REBOA placement for prehospital care?

BACKGROUND Torso hemorrhage is the primary cause of potentially preventable mortality in trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been advocated as an adjunct to bridge patients to definitive hemorrhage control. The primary aim of this study was to assess whether contrast-enhanced ultrasonography can improve the accuracy of REBOA placement in the infrarenal aorta (Zone III). METHODS A fluoroscopy-free “enhanced” Zone III REBOA technique was developed using a porcine cadaver model. A “standard” over-the-wire Seldinger technique was used, which was enhanced with the addition of a microbubble contrast medium to inflate the balloon, observed with ultrasonography. Following this, attending- and resident-level physicians were randomized into two groups. They were taught either the enhanced with ultrasonography guidance (Group A) or the standard measuring length of catheter insertion (Group B) technique as part of a human cadaver trauma skills course. Outcomes assessed included time (seconds) from insertion to inflation, accuracy, and missed targets. All results were benchmarked against three endovascular experts. RESULTS There were 20 participants who performed REBOA with Group A (51 [31]) being significantly faster than Group B (90 [63]) (p = 0.003) and more accurate (p = 0.023) with no missed targets. Group B had five missed targets, the most common error being inflation within Zone II. CONCLUSION For Zone III REBOA, contrast-enhanced ultrasonography technique is faster and more accurate than the standard technique. This may have value in time-critical and austere environments. Clinical studies are now required to evaluate this approach further.

Monro-Kellie 2.0: The dynamic vascular and venous pathophysiological components of intracranial pressure

For 200 years, the ‘closed box’ analogy of intracranial pressure (ICP) has underpinned neurosurgery and neuro-critical care. Cushing conceptualised the Monro-Kellie doctrine stating that a change in blood, brain or CSF volume resulted in reciprocal changes in one or both of the other two. When not possible, attempts to increase a volume further increase ICP. On this doctrine’s “truth or relative untruth” depends many of the critical procedures in the surgery of the central nervous system. However, each volume component may not deserve the equal weighting this static concept implies. The slow production of CSF (0.35 ml/min) is dwarfed by the dynamic blood in and outflow (∼700 ml/min). Neuro-critical care practice focusing on arterial and ICP regulation has been questioned. Failure of venous efferent flow to precisely match arterial afferent flow will yield immediate and dramatic changes in intracranial blood volume and pressure. Interpreting ICP without interrogating its core drivers may be misleading. Multiple clinical conditions and the cerebral effects of altitude and microgravity relate to imbalances in this dynamic rather than ICP per se. This article reviews the Monro-Kellie doctrine, categorises venous outflow limitation conditions, relates physiological mechanisms to clinical conditions and suggests specific management options.