Thomas Cadoux-Hudson

Altered cellular metabolism following traumatic brain injury: a magnetic resonance spectroscopy study.

Experimental studies have reported early reductions in pH, phosphocreatine, and free intracellular magnesium following traumatic brain injury using phosphorus magnetic resonance spectroscopy. Paradoxically, in clinical studies there is some evidence for an increase in the pH in the subacute stage following traumatic brain injury. We therefore performed phosphorus magnetic resonance spectroscopy on seven patients in the subacute stage (mean 9 days postinjury) following traumatic brain injury to assess cellular metabolism. In areas of normal-appearing white matter, the pH was significantly alkaline (patients 7.09 +/- 0.04 [mean +/- SD], controls 7.01 +/- 0.04, p = 0.008), the phosphocreatine to inorganic phosphate ratio (PCr/Pi) was significantly increased (patients 4.03 +/- 1.18, controls 2.64 +/- 0.71, p = 0.03), the inorganic phosphate to adenosine triphosphate ratio (Pi/ATP) was significantly reduced (patients 0.37 +/- 0.10, controls 0.56 +/- 0.19, p = 0.04), and the PCr/ATP ratio was nonsignificantly increased (patients 1.53 +/- 0.29, controls 1.34 +/- 0.19, p = 0.14) in patients compared to controls. Furthermore, the calculated free intracellular magnesium was significantly increased in the patients compared to the controls (patients 0.33 +/- 0.09 mM, controls 0.22 +/- 0.09 mM, p = 0.03)). Proton spectra, acquired from similar regions showed a significant reduction in N-acetylaspartate (patients 9.64 +/- 2.49 units, controls 12.84 +/- 2.35 units, p = 0.03) and a significant increase in choline compounds (patients 7.96 +/- 1.02, controls 6.67 +/- 1.01 units, p = 0.03). No lactate was visible in any patient or control spectrum. The alterations in metabolism observed in these patients could not be explained by ongoing ischemia but might be secondary to a loss of normal cellular homeostasis or a relative alteration in the cellular population, in particular an increase in the glial cell density, in these regions.

How useful is magnetic resonance imaging in predicting severity and outcome in traumatic brain injury

Major advances have been made in the ever-expanding field of magnetic resonance imaging and related technologies, such as magnetic resonance spectroscopy, haemodynamic and functional imaging. Although these magnetic resonance modalities are of great research interest, it is still questionable as to how useful these investigations are in the clinical setting. All of these modalities strive to define a few variables that might dominate the heterogeneous but common aetiopathology of traumatic brain injury. Recent studies have found that the use of various magnetic resonance imaging techniques at early and delayed time points can provide useful information with regard to the severity and clinical outcome of patients following traumatic brain injury. These new observations offer opportunities for improved clinical management in such patients.

Abnormal cerebral blood volume in regions of contused and normal appearing brain following traumatic brain injury using perfusion magnetic resonance imaging.

Following traumatic brain injury, there may be secondary alterations in cerebrovascular parameters leading to ischemia and further cellular damage. To assess possible subacute hemodynamic disturbances following traumatic brain injury, we used conventional and perfusion magnetic resonance imaging (MRI) in 18 patients, on average 10 days following injury. Six of the 18 patients had focal contusions or edema visible on conventional MRI. These six patients had a significantly reduced normalized regional cerebral blood volume (rCBV) in the regions of focal pathology compared to equivalent areas in control subjects (patients 0.47 +/- 0.20 [means +/- SD], controls 1.02 +/- 0.11, p < 0.001). In addition, four of these six patients had an increased rCBV (outside control range) in the region of normal appearing brain immediately surrounding the contusion. These six patients were more significantly injured and had a worse clinical outcome compared to the remaining patients (p = 0.004,p = 0.03, respectively). There were five patients who had a region of reduced rCBV (outside control range) in a quadrant of normal appearing white matter, away from any visible abnormality, who were not more significantly injured than the remaining patients but went on to have a significantly poorer clinical outcome (p = 0.27, p = 0.01, respectively). Traumatic brain injury is a heterogeneous insult causing a variety of pathology, not all of which is visible using conventional imaging methods. The current study has shown that regions of both normal appearing and contused brain may have an abnormal rCBV and that alterations in rCBV may play a role in determining the clinical outcome of patients.

Discrepancies between cerebral perfusion and metabolism after subarachnoid haemorrhage: a magnetic resonance approach

INTRODUCTION There is a variable relation between angiographic vasospasm and delayed ischaemic neurological deficit (DIND). Magnetic resonance (MR) techniques have the potential to investigate the haemodynamic, metabolic, and structural changes occurring with these complications. These techniques have been applied to study DIND in patients recovering from subarachnoid haemorrhage. METHODS Fifteen studies were performed on 11 patients, 10 with DIND. Vasospasm was diagnosed angiographically or with transcranial Doppler. The MR protocol consisted of T2 weighted imaging, contrast enhanced dynamic perfusion scanning, TI weighted imaging, and two dimensional localised proton spectroscopy. Relative cerebral blood volume maps were generated from perfusion scans. Metabolite ratios were calculated from proton spectra. RESULTS All patients had cortical oedema on T2 weighted images, significantly more pronounced in patients of poor clinical grade (p<0.01). Spectra were normal in good grade patients. Lactate was increased and N-acetyl aspartate decreased in the poor grades, significantly worse in grade 4 compared with grade 3 patients (p<0.05). Spectral changes also correlated with the severity of oedema (p<0.05). Relative blood volumes were significantly higher in oedematous regions of poor compared with good grade patients (p<0.05). Lactate was seen in regions of the brain with increased relative blood volume. CONCLUSIONS Despite the paramagnetic effects of haemorrhage, or of the coils and clips used to treat aneurysms, this study demonstrates that patients recovering from subarachnoid haemorrhage can undergo complex MR studies. Oedema, lactate, and increased relative blood volume correlate well with each other and with DIND and poor clinical grade.

The presence of an extractable substance in the CSF of humans with cerebral vasospasm after subarachnoid haemorrhage that correlates with phosphatase inhibition.

The cellular events leading to cerebral vasospasm after subarachnoid haemorrhage are poorly understood, although an increase in smooth muscle myosin light chain phosphorylation has been observed. This study set out to determine if phosphatase inhibition may be involved in the pathological maintenance of tension observed during vasospasm. We found that 1 nM okadaic acid, a type 2A protein phosphatase inhibitor, elicited an increase in rate of O(2) consumption in the porcine carotid artery similar to that by cerebrospinal fluid (CSF) from vasospastic patients (CSF(V), n=5) (control 0.23+/-0.03, CSF(V) 0.84+/-0.16 and okadaic acid 0.85+/-0.02 micromol min(-1) g dwt(-1)). It was also observed that phosphatase inhibition with 1 nM okadaic acid significantly slowed relaxation after a stretch in a similar fashion to CSF(V) haemorrhage. CSF from vasospastic subarachnoid haemorrhage patients, but not from those without vasospasm, contains an extractable substance which modulates myosin light chain phosphorylation in vitro. A phosphatase preparation obtained from the porcine carotid artery dephosphorylated 63+/-2% of the phosphorylated (MLC(20)) substrate in vitro, and non-vasospastic CSF treated enzyme dephosphorylated 60+/-2.6%. Okadaic acid inhibited phosphatase dephosphorylated only 7.5+/-1% of the substrate where CSF(V) treated enzyme dephosphorylated 22+/-2.8% of the substrate. We conclude that inhibition of smooth muscle phosphatase may be involved in the mechanisms associated with cerebral vasospasm after subarachnoid haemorrhage.

Platelets play an essential role in the aetiology of cerebral vasospasm after subarachnoid haemorrhage

Platelets have long been implicated in the aetiology of cerebral vasospasm (CV) after subarachnoid haemorrhage (SAH). It was noticed that vasospastic CSF (CSF(V)) could be formed in vitro by the mixing of control blood (with platelets) and non-SAH CSF. We also propose a hypothesis for the aetiology of CV after SAH based on this and previous research. This study also aims to determine which blood fraction is responsible for the stimulation of O(2) consumption and vasospasm of blood vessels. Control blood was separated into various fractions and mixed with non-SAH CSF. The activity of the resulting mixture and the blood fraction alone were assessed. Only the fractions containing platelets mixed with CSF showed vasoactivity. These data suggest that platelets plus some component in the CSF produce vasoactive factors with actions similar to CSF(V). This study may help to elucidate the aetiology of CV after SAH.

Subarachnoid haemorrhage-induced cerebral vasospasm: a subcellular perspective on the control of tension

Vasospasm occurs in many human pathologies often resulting in tissue infarction and increasing morbidity and mortality. Cerebral vasospasm following subarachnoid haemorrhage, whilst a relatively rare condition, has a well described time course with clear neurological end-points and remains largely unresponsive to current therapies. The mechanisms underlying cerebral vasospasm have been investigated but are still poorly understood. The relationship between oxidative metabolism and force generation has not been extensively investigated, with much of the work done dependent upon force measurements to investigate the vascular changes. We propose that the relationship between force generation, relaxation, intracellular signalling and control of the contractile apparatus via protein phosphatases may be an important mechanism of disease and a therapeutic target. This is a potential new therapeutic avenue applicable to cerebral vasospasm and vasospasm affecting other organs.

High field structural MRI in the management of degenerative cervical myelopathy

Abstract Introduction: This is a narrative overview of the pathophysiology, investigation and management of Degenerative Cervical Myelopathy (DCM). This review article also takes a look ahead to the impact high resolution MRI may have on treatment. Background: DCM is the most common cause of spinal dysfunction and yet it remains poorly understood. It is becoming increasingly common in our ageing population. Disc and facet joint abnormalities, osteophytes, spondylothisthesis and ligamentous hypertrophy all act together to produce spinal canal and neuronal foramina stenosis which in turn causes neural compromise. Its impact on the quality of life of this patient group and the wider economy is vast. Some patients with overt cord compression and MRI signal change in their cervical cord may only have subtle clinical signs whilst others with less striking imaging may be profoundly myelopathic. Who to operate on and when remains a neurosurgical dilemma in this group of patients. Methods: A number of articles with a broad variation in methodology were reviewed and referenced during the production of this paper. Results: This paper is a narrative review. The results presented in all the referenced articles were considered. Conclusion: The process of developing new imaging techniques will give a greater understanding of the causes of the symptoms of DCM and in a wider context facilitate further surgical and medical strategies that are more cost effective and beneficial to patients. The advent of 7T MRI or further optimisation of safer 3T MRI sequences may soon provide this opportunity and the diagnostic gap in spinal cord imaging can begin to close.

Routine radiographs one day after anterior cervical discectomy and fusion are neither necessary nor cost-effective

Abstract Objectives: Anterior cervical discectomy and fusion (ACDF) is a common operative treatment of compressive pathology of the cervical spinal cord, when caused by one or more degenerated intervertebral discs or related osteophytes. In addition to intra-operative radiographs to confirm spinal level before discectomy and implant position after insertion, traditional practice is to obtain post-operative antero–posterior and lateral plain radiographs (XR) before hospital discharge, despite a paucity of evidence supporting their benefit to patient care. Minimising unnecessary radiation to radiosensitive neck structures is desirable, and furthermore, with increasing financial pressure on healthcare resources, routine investigations should be clinically justified and evidence-based. We aim to compare the utility of routine post-operative cervical spine X-rays following ACDF. Methods: We compare two groups of consecutive patients undergoing ACDF in a single UK neurosurgical centre. The first group (n = 109) received routine post-operative XR imaging, and the second group (n = 113) received radiographs only when clinically indicated. Results: There were no differences in post-operative complication rates (4.6% vs. 5.3%), or requirement for further imaging or of further operative intervention (1.8% vs. 0.9%). The group that did not have routine post-operative radiographs had a significantly shorter stay in hospital (median two days vs. three days). There were no patients in either group where post-operative XR changed clinical management and mandated revision surgery or further imaging. All cases requiring surgery or further imaging were identified by clinical deterioration. Conclusions: We suggest that the practice of obtaining routine radiographs of the cervical spine following ACDF should be abandoned, unless there is a clear clinical indication.

Screening for intracranial aneurysms. Short natural course makes screening impracticable.

EDITOR,--Since migraine without aura aggregates in families of probands with migraine without aura, it is expected that migraine without aura is less common in families of probands who have never had migraine. We calculated the population relative risk, adjusting for sex and age, since migraine without aura depends on these factors. If the population relative risk significantly exceeds one an increased family aggregation is implied, whereas a result significantly below one implies a decreased family aggregation. W E Waters states that the risk of migraine without aura among the first degree relatives …