Advanced magnetic resonance imaging and neuropsychological assessment for detecting brain injury in a prospective cohort of university amateur boxers.

BACKGROUND/AIM: The safety of amateur and professional boxing is a contentious issue. We hypothesised that advanced magnetic resonance imaging and neuropsychological testing could provide evidence of acute and early brain injury in amateur boxers. METHODS: We recruited 30 participants from a university amateur boxing club in a prospective cohort study. Magnetic resonance imaging (MRI) and neuropsychological testing was performed at three time points: prior to starting training; within 48 h following a first major competition to detect acute brain injury; and one year follow-up. A single MRI acquisition was made from control participants. Imaging analysis included cortical thickness measurements with Advanced Normalization Tools (ANTS) and FreeSurfer, voxel based morphometry (VBM), and Tract Based Spatial Statistics (TBSS). A computerized battery of neuropsychological tests was performed assessing attention, learning, memory and impulsivity. RESULTS: During the study period, one boxer developed seizures controlled with medication while another developed a chronic subdural hematoma requiring neurosurgical drainage. A total of 10 boxers contributed data at to the longitudinal assessment protocol. Reasons for withdrawal were: logistics (10), stopping boxing (7), withdrawal of consent (2), and development of a chronic subdural hematoma (1). No significant changes were detected using VBM, TBSS, cortical thickness measured with FreeSurfer or ANTS, either cross-sectionally at baseline, or longitudinally. Neuropsychological assessment of boxers found attention/concentration improved over time while planning and problem solving ability latency decreased after a bout but recovered after one year. CONCLUSION: While this neuroimaging and neuropsychological assessment protocol could not detect any evidence of brain injury, one boxer developed seizures and another developed a chronic sub-dural haematoma.

Principles of intracranial pressure monitoring and treatment.

Intracranial pressure (ICP) is governed by volumes of intracranial blood, cerebrospinal fluid, and brain tissue. Expansion of any of these volumes will trigger compensatory changes in the other compartments, resulting in initially limited change in ICP. Due to the rigid skull, once compensatory mechanisms are exhausted, ICP rises very rapidly. Intracranial hypertension is associated with unfavorable outcome in brain-injured patients. This chapter discusses the pathophysiology of raised ICP, as well as typical waveforms, monitoring techniques, and clinical management. The dynamics of ICP are more important than the absolute value at any given time point, but mean ICP exceeding 20-25mmHg is usually treated aggressively. Algorithms based on data from patients with traumatic brain injury are applied also in other conditions. However, an understanding of the underlying pathophysiology allows adaptation of therapies to other pathologies. Typically, a three-staged approach is used, starting with restoration of systemic physiology, sedation, and analgesia. If these measures are insufficient, surgical options, such as drainage of cerebrospinal fluid or evacuation of mass lesions, are considered. In the absence of surgical options, stage 2 treatments are initiated, consisting of either mannitol or hypertonic saline. If these measures are insufficient, stage 3 therapies include hypothermia, metabolic suppression, or craniectomy.

Comparison of ventricular drain location and infusion test in hydrocephalus.

OBJECTIVES: Suspected cerebrospinal fluid shunt (CSF) dysfunction in hydrocephalic patients poses a diagnostic uncertainty. The clinical picture can be non-specific and CT imaging alone is not always pathognomonic. Infusion tests are an increasingly used investigation for real-time hydrodynamic assessment of shunt patency. We report the correlation between infusion test results with the quality of ventricular drain placement on CT scans in a large retrospective group of hydrocephalic patients. MATERIALS & METHODS: Three hundred and six infusion test results performed in 200 patients were correlated with 306 corresponding CT head scans. Nominal logistic regression was used to correlate shunt catheter position on CT imaging to patency of ventricular drain as determined by infusion tests. RESULTS: Infusion test results of shunt patency are statistically congruent with the analysis of shunt catheter position on CT head scans. Catheter tips completely surrounded by either parenchyma or CSF on CT imaging are strongly associated with evidence of occlusion or patency from infusion tests, respectively (χ² = 51.68, P < 0.0001, n = 306 and χ² = 31.04, P < 0.0001, n = 306). CONCLUSIONS: The most important anatomical factor for shunt patency is the catheter tip being completely surrounded by CSF. Infusion tests provide functional and reliable assessment of shunt patency in vivo and are strongly correlated with the position of the ventricular catheter on CT imaging.

Assessment of non-invasive ICP during CSF infusion test: an approach with transcranial Doppler.

BACKGROUND: This study aimed to compare four non-invasive intracranial pressure (nICP) methods in a prospective cohort of hydrocephalus patients whose cerebrospinal fluid dynamics was investigated using infusion tests involving controllable test-rise of ICP. METHOD: Cerebral blood flow velocity (FV), ICP and non-invasive arterial blood pressure (ABP) were recorded in 53 patients diagnosed for hydrocephalus. Non-invasive ICP methods were based on: (1) interaction between FV and ABP using black-box model (nICP_BB); (2) diastolic FV (nICP_FVd); (3) critical closing pressure (nICP_CrCP); (4) transcranial Doppler-derived pulsatility index (nICP_PI). Correlation between rise in ICP (∆ICP) and ∆nICP and averaged correlations for changes in time between ICP and nICP during infusion test were investigated. RESULTS: From baseline to plateau, all nICP estimators increased significantly. Correlations between ∆ICP and ∆nICP were better represented by nICP_PI and nICP_BB: 0.45 and 0.30 (p < 0.05). nICP_FVd and nICP_CrCP presented non-significant correlations: -0.17 (p = 0.21), 0.21 (p = 0.13). For changes in ICP during individual infusion test nICP_PI, nICP_BB and nICP_FVd presented similar correlations with ICP: 0.39 ± 0.40, 0.39 ± 0.43 and 0.35 ± 0.41 respectively. However, nICP_CrCP presented a weaker correlation (R = 0.29 ± 0.24). CONCLUSIONS: Out of the four methods, nICP_PI was the one with best performance for predicting changes in ∆ICP during infusion test, followed by nICP_BB. Unreliable correlations were shown by nICP_FVd and nICP_CrCP. Changes of ICP observed during the test were expressed by nICP values with only moderate correlations.

Repeatability of cerebrospinal fluid constant rate infusion study.

OBJECTIVE: Infusion tests are important tools to assess cerebrospinal fluid (CSF)dynamics used in the preoperative selection of patients for shunt surgery, or to predict the scope of improvement from shunt revision. The aim of this study was to assess the repeatability of the key quantitative parameters describing CSF dynamics that are determined with infusion testing. MATERIALS AND METHODS: Eighteen patients in whom a constant infusion test was repeated within 102 days, without any intermediate surgical intervention, were studied. From each test baseline ICP, baseline pulse amplitude, outflow resistance, elastance coefficient and slope of the amplitude-pressure line were calculated and investigated with a regression and Bland-Altman analysis. RESULTS: Significant correlations (P < 0.01) were found for the outflow resistance (R = 0.96), the elastance coefficient (R = 0.778) and the slope of the amplitude-pressure line (R = 0.876). The estimated 95% confidence level for outflow resistance was 3 mmHg/ml min. Likewise, the elastance coefficient lay within a range of 0.16/ml and the slope of the amplitude-pressure line within 0.25. The most inconsistent parameter found were baseline ICP (R = 0.272) and baseline pulse amplitude (R = 0.171). CONCLUSION: The results of this study imply that the parameters resulting from an infusion study have to be considered within a range rather than as an absolute value.

Relationship between etiology and covert cognition in the minimally conscious state.

OBJECTIVES: Functional neuroimaging has shown that the absence of externally observable signs of consciousness and cognition in severely brain-injured patients does not necessarily indicate the true absence of such abilities. However, relative to traumatic brain injury, nontraumatic injury is known to be associated with a reduced likelihood of regaining overtly measurable levels of consciousness. We investigated the relationships between etiology and both overt and covert cognitive abilities in a group of patients in the minimally conscious state (MCS). METHODS: Twenty-three MCS patients (15 traumatic and 8 nontraumatic) completed a motor imagery EEG task in which they were required to imagine movements of their right-hand and toes to command. When successfully performed, these imagined movements appear as distinct sensorimotor modulations, which can be used to determine the presence of reliable command-following. The utility of this task has been demonstrated previously in a group of vegetative state patients. RESULTS: Consistent and robust responses to command were observed in the EEG of 22% of the MCS patients (5 of 23). Etiology had a significant impact on the ability to successfully complete this task, with 33% of traumatic patients (5 of 15) returning positive EEG outcomes compared with none of the nontraumatic patients (0 of 8). CONCLUSIONS: The overt behavioral signs of awareness (measured with the Coma Recovery Scale-Revised) exhibited by nontraumatic MCS patients appear to be an accurate reflection of their covert cognitive abilities. In contrast, one-third of a group of traumatically injured patients in the MCS possess a range of high-level cognitive faculties that are not evident from their overt behavior.

Critical thresholds for cerebrovascular reactivity after traumatic brain injury.

INTRODUCTION: Pressure-reactivity index (PRx) is a useful tool in brain monitoring of trauma patients, but the question remains about its critical values. Using our TBI database, we identified the thresholds for PRx and other monitored parameters that maximize the statistical difference between death/survival and favorable/unfavorable outcomes. We also investigated how these thresholds depend on clinical factors such as age, gender and initial GCS. METHODS: A total of 459 patients from our database were eligible. Tables of 2 × 2 format were created grouping patients according to survival/death or favorable/unfavorable outcomes and varying thresholds for PRx, ICP and CPP. Pearson's chi square was calculated, and the thresholds returning the highest score were assumed to have the best discriminative value. The same procedure was repeated after division according to clinical factors. RESULTS: In all patients, we found that PRx had different thresholds for survival (0.25) and for favorable outcome (0.05). Thresholds of 70 mmHg for CPP and 22 mmHg for ICP were identified for both survival and favorable outcomes. The ICP threshold for favorable outcome was lower (18 mmHg) in females and patients older than 55 years. In logistic regression models, independent variables associating with mortality and unfavorable outcome were age, GCS, ICP and PRx. CONCLUSION: The prognostic role of PRx is confirmed but with a lower threshold of 0.05 for favorable outcome than for survival (0.25). Results for ICP are in line with current guidelines. However, the lower value in elderly and in females suggests increased vulnerability to intracranial hypertension in these groups.

What comes first? The dynamics of cerebral oxygenation and blood flow in response to changes in arterial pressure and intracranial pressure after head injury.

BACKGROUND: Brain tissue partial oxygen pressure (Pbt(O(2))) and near-infrared spectroscopy (NIRS) are novel methods to evaluate cerebral oxygenation. We studied the response patterns of Pbt(O(2)), NIRS, and cerebral blood flow velocity (CBFV) to changes in arterial pressure (AP) and intracranial pressure (ICP). METHODS: Digital recordings of multimodal brain monitoring from 42 head-injured patients were retrospectively analysed. Response latencies and patterns of Pbt(O(2)), NIRS-derived parameters [tissue oxygenation index (TOI) and total haemoglobin index (THI)], and CBFV reactions to fluctuations of AP and ICP were studied. RESULTS: One hundred and twenty-one events were identified. In reaction to alterations of AP, ICP reacted first [4.3 s; inter-quartile range (IQR) -4.9 to 22.0 s, followed by NIRS-derived parameters and CBFV (10.9 s; IQR: -5.9 to 39.6 s, 12.1 s; IQR: -3.0 to 49.1 s, 14.7 s; IQR: -8.8 to 52.3 s for THI, CBFV, and TOI, respectively), with Pbt(O(2)) reacting last (39.6 s; IQR: 16.4 to 66.0 s). The differences in reaction time between NIRS parameters and Pbt(O(2)) were significant (P<0.001). Similarly when reactions to ICP changes were analysed, NIRS parameters preceded Pbt(O(2)) (7.1 s; IQR: -8.8 to 195.0 s, 18.1 s; IQR: -20.6 to 80.7 s, 22.9 s; IQR: 11.0 to 53.0 s for THI, TOI, and Pbt(O(2)), respectively). Two main patterns of responses to AP changes were identified. With preserved cerebrovascular reactivity, TOI and Pbt(O(2)) followed the direction of AP. With impaired cerebrovascular reactivity, TOI and Pbt(O(2)) decreased while AP and ICP increased. In 77% of events, the direction of TOI changes was concordant with Pbt(O(2)). CONCLUSIONS: NIRS and transcranial Doppler signals reacted first to AP and ICP changes. The reaction of Pbt(O(2)) is delayed. The results imply that the analysed modalities monitor different stages of cerebral oxygenation.

Temozolomide responsiveness in aggressive corticotroph tumours: a case report and review of the literature.

Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard chemotherapy regimens showing limited efficacy. Recent evidence suggests that temozolomide (TMZ), an orally-active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. A low level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) predicts TMZ responsiveness in glioblastomas, and a similar correlation has been observed in the majority of aggressive pituitary adenomas/carcinomas reported to date. Here, we report a case of a silent pituitary corticotroph adenoma, which subsequently re-presented with Cushing's syndrome due to functioning hepatic metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ therapy (200 mg/m² for 5 days every 28 days-seven cycles) resulted in marked clinical, biochemical [>50% fall in adrenocorticotrophic hormone (ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral adrenalectomy. However, despite reintroduction of TMZ therapy (further eight cycles) ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ therapy in glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of pituitary adenomas/carcinomas are also considered.

Pulsatile intracranial pressure and cerebral autoregulation after traumatic brain injury.

BACKGROUND: Strong correlation between mean intracranial pressure (ICP) and its pulse wave amplitude (AMP) has been demonstrated in different clinical scenarios. We investigated the relationship between invasive mean arterial blood pressure (ABP) and AMP to explore its potential role as a descriptor of cerebrovascular pressure reactivity after traumatic brain injury (TBI). METHODS: We retrospectively analyzed data of patients suffering from TBI with brain monitoring. Transcranial Doppler blood flow velocity, ABP, ICP were recorded digitally. Cerebral perfusion pressure (CPP) and AMP were derived. A new index-pressure-amplitude index (PAx)-was calculated as the Pearson correlation between (averaged over 10 s intervals) ABP and AMP with a 5 min long moving average window. The previously introduced transcranial Doppler-based autoregulation index Mx was evaluated in a similar way, as the moving correlation between blood flow velocity and CPP. The clinical outcome was assessed after 6 months using the Glasgow outcome score. RESULTS: 293 patients were studied. The mean PAx was -0.09 (standard deviation 0.21). This negative value indicates that, on average, an increase in ABP causes a decrease in AMP and vice versa. PAx correlated strong with Mx (R (2) = 0.46, P < 0.0002). PAx also correlated with age (R (2) = 0.18, P < 0.05). PAx was found to have as good predictive outcome value (area under curve 0.71, P < 0.001) as Mx (area under curve 0.69, P < 0.001). CONCLUSIONS: We demonstrated significant correlation between the known cerebral autoregulation index Mx and PAx. This new index of cerebrovascular pressure reactivity using ICP pulse wave information showed to have a strong association with outcome in TBI patients.

Clinical assessment of cerebrospinal fluid dynamics in hydrocephalus. Guide to interpretation based on observational study.

OBJECTIVES: The term hydrocephalus encompasses a range of disorders characterised by clinical symptoms, abnormal brain imaging and derangement of cerebrospinal fluid (CSF) dynamics. The ability to elucidate which patients would benefit from CSF diversion (a shunt or third ventriculostomy) is often unclear. Similar difficulties are often encountered in shunted patients to predict the scope for improvement by shunt re-adjustment or revision. In this study we aimed to update our knowledge of how key quantitative parameters describing CSF dynamics may be used in diagnosis of shunt-responsive hydrocephalus and in the assessment of shunt function. METHODS: A number of quantitative parameters [including resistance to CSF outflow (Rcsf), pulse amplitude of intracranial pressure waveform (AMP), RAP index and slow vasogenic waves] were studies in 1423 patients with 2665 CSF infusion tests and 305 overnight intracranial pressure (ICP)-monitoring sessions over a 17 year period. OBSERVATIONS: We demonstrate our observations for typical values of Pb, Rcsf, AMP, slow vasogenic waves derived from infusion studies or overnight ICP monitoring in differentiating atrophy from shunt-responsive normal pressure hydrocephalus or acute hydrocephalus. From the same variables tested on shunted patients we demonstrate a standardised approach to help differentiate a properly-functioning shunt from underdrainage or overdrainage. CONCLUSIONS: Quantitative variables derived from CSF dynamics allow differentiation between clinically overlapping entities such as shunt-responsive normal pressure hydrocephalus and brain atrophy (not shunt responsive) as well as allowing the detection of shunt malfunction (partial or complete blockage) or overdrainage. This observational study is intended to serve as an update for our understanding of quantitative testing of CSF dynamics.

Detecting residual cognitive function in disorders of consciousness.

Clinical audits have suggested up to 40% of patients with disorders of consciousness may be misdiagnosed, in part, due to the highly subjective process of determining, from a patient's behaviour, whether they retain awareness of self or environment. To address this problem, objective neuroimaging methods, such as positron emission tomography and functional magnetic resonance imaging have been explored. Using these techniques, paradigms, which do not require the patient to move or speak, can be used to determine a patient's level of residual cognitive function. Indeed, visual discrimination, speech comprehension and even the ability to respond to command have been demonstrated in some patients who are assumed to be vegetative on the basis of standard behavioural assessments. Functional neuroimaging is now increasingly considered to be a very useful and necessary addition to the clinical assessment process, where there is concern about the accuracy of the diagnosis and the possibility that residual cognitive function has remained undetected. In this essay, the latest neuroimaging findings are reviewed, the limitations and caveats pertaining to interpretation are outlined and the necessary developments, before neuroimaging becomes a standard component of the clinical assessment are discussed.

Impact of duration of symptoms on CSF dynamics in idiopathic normal pressure hydrocephalus.

OBJECTIVE: Cerebrospinal fluid (CSF) pressure-volume compensation may change over time as part of normal ageing, where the resistance to CSF outflow increases and the formation of CSF decreases with age. Is CSF compensation dependent on duration of symptoms in idiopathic normal pressure hydrocephalus (iNPH)? METHODS: We investigated 92 patients presenting with iNPH. Mean age was 73 (range 47-86). There were 60 men and 32 women. They all presented with gait disturbance and ventricular dilatation. Memory deficit occurred in 72% and urinary incontinence in 52% of patients. All patients underwent computerized CSF infusion tests. Sixty-four shunted patients were available for follow-up, and their improvement was expressed using the NPH score. RESULTS: Mean intracranial pressure (ICP) was 10.1±5.1 mmHg, and mean resistance to CSF outflow was 17.3±5.2 mmHg/(ml/min). Mean duration of symptoms was 24±19 months (range from 2 weeks to 86 months). Baseline ICP, magnitude of ICP pulse waveform, brain compliance and improvement after shunting (72% of patients improved) did not exhibit any dependency on the duration of symptoms. The resistance to CSF outflow showed a strong tendency to decrease in time with the duration of symptoms beyond 2 years (R= -0.702; P<0.005). CONCLUSION: This is a preliminary observation, and it suggests that for patients with duration of symptoms longer than 2-3 years, the threshold for normal resistance to CSF outflow should be duration-adjusted.

Cerebral arterial compliance in patients with internal carotid artery disease.

BACKGROUND: A decrease in arterial compliance of the internal carotid artery has been associated with an increased risk in ipsilateral ischaemic stroke. However, so far, no technique has been validated to monitor the compliance of intracerebral arteries (Ca) in patients with carotid artery disease. In this study, we sought to monitor Ca in patients with unilateral symptomatic disease and to determine its variations during changes in PaCO(2). METHODS: We studied 18 patients with unilateral symptomatic internal carotid artery stenosis >50% or occlusion. Patients underwent monitoring of arterial blood pressure (ABP) and middle cerebral artery cerebral blood flow velocities (CBFV) during baseline, hyperventilation and 5%CO(2) inhalation. Ca was calculated from pulsatile amplitudes of ABP and Cerebral arterial blood volume, extracted from the CBFV waveform using a new mathematical model. RESULTS: At baseline, the decrease in Ca on the diseased side was correlated with the degree of stenosis (r = -0.35; P = 0.01). During hypocapnia, Ca was lower compared to baseline on the normal side (P = 0.004) and on the diseased side (P = 0.04). Ca reactivity, reflecting the changes in Ca per changes in 1 mmHg PaCO(2), was lower on the diseased side between baseline and hypocapnia (3.4 vs. 2.6%; P = 0.04). During hypercapnia, no changes in Ca on the diseased (P = 0.8) nor on the normal sides (P = 0.2) were observed. CONCLUSIONS: The decrease in cerebral arterial compliance the side of stenosis/occlusion was correlated with the severity of the internal carotid artery disease. Further studies are needed to determine whether Ca may improve the prediction of ischaemic events in symptomatic and asymptomatic patients.

Altered functional connectivity in the motor network after traumatic brain injury.

BACKGROUND: A large proportion of survivors of traumatic brain injury (TBI) have persistent cognitive impairments, the profile of which does not always correspond to the size and location of injuries. One possible explanation could be that TBI-induced damage extends beyond obvious lesion sites to affect remote brain networks. We explored this hypothesis in the context of a simple and well-characterized network, the motor network. The aim of this cross-sectional study was to establish the residual integrity of the motor network as an important proof of principle of abnormal connectivity in TBI. METHODS: fMRI data were obtained from 12 right-handed patients and 9 healthy controls while they performed the finger-thumb opposition task with the right hand. We used both conventional and psychophysiologic interaction (PPI) analyses to examine the integrity of functional connections from brain regions we found to be activated in the paradigm we used. RESULTS: As expected, the analysis showed significant activations of the left primary motor cortex (M1), right cerebellum (Ce), and bilateral supplementary motor area (SMA) in controls. However, only the activation of M1 survived robust statistical thresholding in patients. In controls, the PPI analysis revealed that left M1, SMA, and right Ce positively interacted with the left frontal cortex and negatively interacted with the right supramarginal gyrus. In patients, we observed no negative interaction and reduced interhemispheric interactions from these seed regions. CONCLUSIONS: These observations suggest that patients display compromised activation and connectivity patterns during the finger-thumb opposition task, which may imply functional reorganization of motor networks following TBI.

Head injury rehabilitation: the role of a neurotrauma clinic.

Survivors of head injury are often left with varying degrees of disability and complex and varied needs, necessitating prolonged periods of rehabilitation and continuing care. Advances have been made in the acute management of these patients, but continuing management in terms of rehabilitation remains deficient with lack of specialist resources and a fragmented service. For head-injured patients, lack of access to appropriate ongoing rehabilitation may have profound effects on outcome and social re-integration. There are also considerable economic implications for planning and provision of services. The aims of this paper are to describe, review and evaluate the role of a Neurotrauma clinic within the Head Injury Service at Addenbrooke's Hospital, Cambridge. The multidisciplinary Neurotrauma clinic commenced in June 2003 following an extensive collaborative research programme to assess current regional head injury service provision and address deficiencies and management issues. Patients of all ages with ongoing problems following varying severity of head injury are followed up at 2 months + post-injury for as long as appropriate. Patients complete an SF-36 and GOSE questionnaire at each clinic appointment and this self-reported data is complemented by neuropsychological assessments, and demographic data entered on a database. The clinic acts as a 'gateway' to access appropriate ongoing rehabilitation and a source of information and support. The routine collection of outcome data enables tracking of individual patient progress and outcome and provides an information resource for further research. The findings highlight deficiencies in rehabilitation both in general service provision and specific patient need. Evidence in support of demand, need and effectiveness of rehabilitation for head injury is particularly relevant within the limited resources of the NHS. Early indications show that a specialist clinic can assist in providing continuity of patient care, in improving coordination of services, and act as a resource for further research on epidemiology, outcome and impact of rehabilitation.

A multimodal approach to the assessment of patients with disorders of consciousness.

Unlike other neurological conditions, the heterogeneous pathology linked to disorders of consciousness currently excludes a distinction between the vegetative and minimally conscious states based upon pathological presentation. The clinical assessment is therefore made on the basis of the patient's clinical history and exhibited behaviour. This creates a particular challenge for the clinician who has to decide whether a certain behaviour, which might be inconsistent or incomplete, reflects a conscious or an unconscious process. In an alarmingly high number of cases, identified during clinical audit, this decision process has been shown to be particularly fallible. The behavioural assessment is not only highly subjective, but also dependent upon the ability of the patient to move or speak; it is the only way someone can demonstrate they are aware. To address this problem we propose a multimodal approach, which integrates objective tools, such as electrophysiology and functional brain imaging, with traditional behavioural scales. Together this approach informs the clinical decision process and resolves many of the dilemmas faced by clinicians interpreting solely behavioural indices. This approach not only provides objective information regarding the integrity of residual cognitive function, but also removes the dependency on the patient to move or speak by using specially designed paradigms that do not require a motor output in order to reveal awareness of self or environment. To demonstrate this approach we describe the case of BW, who sustained a traumatic brain injury seven months prior to investigation. BW was admitted to a five-day assessment programme, which implemented our multimodal approach. On behavioural assessment BW demonstrated evidence of orientation and visual pursuit. However, he showed no response to written or verbal command, despite holding command cards and scanning text. Electrophysiology confirmed that he retained a preserved neural axis supporting vision and hearing, and suggested some evidence that he was able to create a basic memory trace. A hierarchical fMRI auditory paradigm suggested he was able to perceive sound and speech, but revealed no evidence of speech comprehension or ability to respond to command. This was corroborated in the visual modality using a hierarchical paradigm demonstrating that he was able to perceive motion, objects and faces, but retained no evidence of being able to respond to command. We briefly review work by other teams advocating the use of brain imaging and electrophysiology and discuss the steps that are now required in order to create an international standard for the assessment of persons with impaired consciousness after brain injury.

Towards the routine use of brain imaging to aid the clinical diagnosis of disorders of consciousness.

Clinical audits have highlighted the many challenges and dilemmas faced by clinicians assessing persons with disorders of consciousness (vegetative state and minimally conscious state). The diagnostic decision-making process is highly subjective, dependent upon the skills of the examiner and invariably dictated by the patients' ability to move or speak. Whilst a considerable amount has been learnt since Jennett and Plum coined the term 'vegetative state', the assessment process remains largely unchanged; conducted at the bedside, using behavioural assessment tools, which are susceptible to environmental and physiological factors. This has created a situation where the rate of misdiagnosis is unacceptably high (up to 43%). In order to address these problems, various functional brain imaging paradigms, which do not rely upon the patient's ability to move or speak, have been proposed as a source of additional information to inform the diagnostic decision making process. Although accumulated evidence from brain imaging, particularly functional magnetic resonance imaging (fMRI), has been encouraging, the empirical evidence is still based on relatively small numbers of patients. It remains unclear whether brain imaging is capable of informing the diagnosis beyond the behavioural assessment and whether brain imaging has any prognostic utility. In this study, we describe the functional brain imaging findings from a group of 41 patients with disorders of consciousness, who undertook a hierarchical speech processing task. We found, contrary to the clinical impression of a specialist team using behavioural assessment tools, that two patients referred to the study with a diagnosis of vegetative state did in fact demonstrate neural correlates of speech comprehension when assessed using functional brain imaging. These fMRI findings were found to have no association with the patient's behavioural presentation at the time of investigation and thus provided additional diagnostic information beyond the traditional clinical assessment. Notably, the utility of brain imaging was further underlined by the finding that the level of auditory processing revealed by functional brain imaging, correlated strongly (rs = 0.81, P < 0.001) with the patient's subsequent behavioural recovery, 6 months after the scan, suggesting that brain imaging may also provide valuable prognostic information. Although further evidence is required before consensus statements can be made regarding the use of brain imaging in clinical decision making for disorders of consciousness, the results from this study clearly highlight the potential of imaging to inform the diagnostic decision-making process for persons with disorders of consciousness.

In vivo assessment of hydrocephalus shunt.

OBJECTIVES: Over a 3-year period, we have performed 312 tests in 197 shunted patients. The data have been analyzed retrospectively to: (1) investigate the parameters describing CSF dynamics that correlate with shunt under-drainage and (2) estimate accuracy of this method. METHODS: Constant rate infusion tests into shunt prechamber were performed. RESULTS: In 161 of the 312 infusion tests, results indicated under-draining shunts. Patients in the under-draining group had higher baseline and plateau CSF pressures, higher resistance to CSF outflow and higher levels of baseline pulse amplitude waveform. During the test, a significantly greater vasogenic waves and lower compensatory reserve was noticed in patients with blocked shunts. In 21 patients with suggestion of shunt blockage and who subsequently underwent operative revision of the shunt, reports of intraoperative shunt patency were available. Shunt blockage was confirmed intra-operatively during surgery in 19 cases. CONCLUSIONS: In vivo shunt testing is easy, safe and clinically useful, aiding decision in difficult clinical situations, where shunt malfunction is suspected but not certain. It also has satisfactory positive predictive power.