Plateau Waves of Intracranial Pressure: Methods for Automatic Detection and Prediction.

Plateau waves are recurrent phenomena observed in traumatic brain injury (TBI) patients, characterised by an increase in intracranial pressure (ICP) above 40 mmHg combined with an almost zero arterial blood pressure (ABP) variation and, hence, a decrease in cerebral perfusion pressure (CPP). A raised ICP for a long period of time, namely plateau waves, can lead to a secondary brain injury. Due to the impaired cerebral autoregulation mechanism these TBI patients present, they are admitted to neurocritical care units (NCCUs) to be under continuous multimodal monitoring, which allows a correct diagnosis for each patient. Plateau waves can end naturally by activating a vasoconstriction mechanism which decreases the amount of blood available in the brain. Alternatively, the phenomenon can end with therapeutic treatment.In this sense, the present study consists in the development of an algorithm capable of automatically detecting plateau waves using offline data, i.e. data already collected from patients. This creates an extra tool which allows for faster detection of events to assist their identification and final diagnosis. Despite the additional steps that can be included to improve the algorithm, the results show good performance, and thus it may be applied in NCCUs.

Intracranial pulse pressure waveform analysis using the higher harmonics centroid.

BACKGROUND: The pulse waveform of intracranial pressure (ICP) is its distinctive feature almost always present in the clinical recordings. In most cases, it changes proportionally to rising ICP, and observation of these changes may be clinically useful. We introduce the higher harmonics centroid (HHC) which can be defined as the center of mass of harmonics of the ICP pulse waveform from the 2nd to 10th, where mass corresponds to amplitudes of these harmonics. We investigate the changes in HHC during ICP monitoring, including isolated episodes of ICP plateau waves. MATERIAL AND METHODS: Recordings from 325 patients treated between 2002 and 2010 were reviewed. Twenty-six patients with ICP plateau waves were identified. In the first step, the correlation between HHC and ICP was examined for the entire monitoring period. In the second step, the above relation was calculated separately for periods of elevated ICP during plateau wave and the baseline. RESULTS: For the values averaged over the whole monitoring period, ICP (22.3 ± 6.9 mm Hg) correlates significantly (R = 0.45, p = 0.022) with HHC (3.64 ± 0.46). During the ICP plateau waves (ICP increased from 20.9 ± 6.0 to 53.7 ± 9.7 mm Hg, p < 10-16), we found a significant decrease in HHC (from 3.65 ± 0.48 to 3.21 ± 0.33, p = 10-5). CONCLUSIONS: The good correlation between HHC and ICP supports the clinical application of pressure waveform analysis in addition to the recording of ICP number only. Mean ICP may be distorted by a zero drift, but HHC remains immune to this error. Further research is required to test whether a decline in HHC with elevated ICP can be an early warning sign of intracranial hypertension, whether individual breakpoints of correlation between ICP and its centroid are of clinical importance.

Transcranial Doppler Monitoring of Intracranial Pressure Plateau Waves.

BACKGROUND: Transcranial Doppler (TCD) has been used to estimate ICP noninvasively (nICP); however, its accuracy varies depending on different types of intracranial hypertension. Given the high specificity of TCD to detect cerebrovascular events, this study aimed to compare four TCD-based nICP methods during plateau waves of ICP. METHODS: A total of 36 plateau waves were identified in 27 patients (traumatic brain injury) with TCD, ICP, and ABP simultaneous recordings. The nICP methods were based on: (1) interaction between flow velocity (FV) and ABP using a "black-box" mathematical model (nICP_BB); (2) diastolic FV (nICP_FV d ); (3) critical closing pressure (nICP_CrCP), and (4) pulsatility index (nICP_PI). Analyses focused on relative changes in time domain between ICP and noninvasive estimators during plateau waves and the magnitude of changes (∆ between baseline and plateau) in real ICP and its estimators. A ROC analysis for an ICP threshold of 35 mmHg was performed. RESULTS: In time domain, nICP_PI, nICP_BB, and nICP_CrCP presented similar correlations: 0.80 ± 0.24, 0.78 ± 0.15, and 0.78 ± 0.30, respectively. nICP_FV d presented a weaker correlation (R = 0.62 ± 0.46). Correlations between ∆ICP and ∆nICP were better represented by nICP_CrCP and BB, R = 0.48, 0.44 (p < 0.05), respectively. nICP_FV d and PI presented nonsignificant ∆ correlations. ROC analysis showed moderate to good areas under the curve for all methods: nICP_BB, 0.82; nICP_FV d , 0.77; nICP_CrCP, 0.79; and nICP_PI, 0.81. CONCLUSIONS: Changes of ICP in time domain during plateau waves were replicated by nICP methods with strong correlations. In addition, the methods presented high performance for detection of intracranial hypertension. However, absolute accuracy for noninvasive ICP assessment using TCD is still low and requires further improvement.

Derangement of Cerebral Blood Flow Autoregulation During Intracranial Pressure Plateau Waves as Detected by Time and Frequency-Based Methods.

Plateau waves are sudden elevations of intracranial pressure (ICP) above 40 mmHg, lasting at least 5 min, and are associated with cerebral vasodilatation. We studied the performance of several parameters for cerebral autoregulation assessment during 30 plateau waves of 24 patients with traumatic brain injury. Continuous signals were collected for ICP, arterial blood pressure (ABP) and transcranial Doppler flow velocity (FV). Parameters both in the time domain (autoregulation index, ARI and mean flow index, Mx) and the frequency domain (transfer function gain, phase and coherence) were analysed. The role of different inputs, using either ABP or cerebral perfusion pressure (CPP) as input, was also tested.Autoregulation deteriorated from baseline to plateau, which could be demonstrated by a significant decrease in both ARI between ABP and FV (p = 0.013) and ARI between CPP and FV (p = 0.014). There was also a significant increase in Mx between CPP and FV (p = 0.004), but not in Mx between ABP and FV (p = 0.472). From the baseline to plateau, there was a significant increase in coherence between the ABP and FV at the very low frequency (p = 0.004). The transfer function phase and gain, on the other hand, revealed inconsistent performance.

Plateau Waves of Intracranial Pressure and Multimodal Brain Monitoring.

The aim of this study was to describe multimodal brain monitoring characteristics during plateau waves of intracranial pressure (ICP) in patients with head injury, using ICM+ software for continuous recording. Plateau waves consist of an abrupt elevation of ICP above 40 mmHg for 5-20 min. This is a prospective observational study of patients with head injury who were admitted to a neurocritical care unit and who developed plateau waves. We analyzed 59 plateau waves that occurred in 8 of 18 patients (44 %). At the top of plateau waves arterial blood pressure remained almost constant, but cerebral perfusion pressure, cerebral blood flow, brain tissue oxygenation, and cerebral oximetry decreased. After plateau waves, patients with a previously better autoregulation status developed hyperemia, demonstrated by an increase in cerebral blood flow and brain oxygenation. Pressure and oxygen cerebrovascular reactivity indexes (pressure reactivity index and ORxshort) increased significantly during the plateau wave as a sign of disruption of autoregulation. Bedside multimodal brain monitoring is important to characterize increases in ICP and give differential diagnoses of plateau waves, as management of this phenomenon differs from that of regular ICP.

A clinical evaluation of variation in paediatric intracranial pressure waveforms.

Introduction: Intracranial pressure (ICP) monitoring is commonly used in investigating the aetiology of chronic paediatric neurological conditions. A series of high-amplitude spikes has been observed in overnight ICP recordings of some children, many of whom have hydrocephalus or craniosynostosis. Research question: This clinical evaluation aimed to define the spike pattern, describe the patient group in which it is most likely to occur, and conduct high-resolution waveform analysis. Material and methods: ICP waveforms from 40 patients aged 0-5 years (inclusive), recorded between 2017 and 2021 at the Royal Hospital for Children Glasgow, were retrospectively analysed. The pattern was defined through visual inspection of regions of interest by two reviewers. Patients were stratified using demographic and clinical data. R software was used to perform regression and high-resolution waveform analyses. Results: The spike pattern was defined as the presence of 2 consecutive spikes with an amplitude of at least 8 mmHg, with a gap of at least 30 min between spikes. In the adjusted Poisson regression, age was significantly associated with the number of spikes (IRR 0.8, 95% CI 0.70 to 0.92, p-value 0.001). Discussion and conclusion: Younger age was significantly associated with an increased number of spikes in this cohort. Investigation of clinical consequences of the spikes is warranted.

Leptomeningeal Disease Secondary to Thr60Ala Transthyretin Amyloidosis: Case Report and Review of the Literature.

A 31-year-old woman with transthyretin (TTR) amyloidosis secondary to a Thr60Ala mutation developed recurrent stroke-like episodes with fluctuating mental status. Evaluation for stroke and seizures was unrevealing. She was found to have leptomeningeal contrast enhancement on magnetic resonance imaging, which was confirmed to be CNS TTR amyloidosis on histopathology following brain and dura biopsy. While leptomeningeal disease has rarely been known to be associated with TTR amyloidosis, this is the first documented case of leptomeningeal disease secondary to a Thr60Ala mutation in the TTR gene. A literature review of TTR amyloidosis is presented with special focus on the treatment of leptomeningeal TTR amyloidosis.

Peak appearance time in pulse waveforms of intracranial pressure and cerebral blood flow velocity.

The shape of the pulse waveforms of intracranial pressure (ICP) and cerebral blood flow velocity (CBFV) typically contains three characteristic peaks. It was reported that alterations in cerebral hemodynamics may influence the shape of the pulse waveforms by changing peaks' configuration. However, the changes in peak appearance time (PAT) in ICP and CBFV pulses are only described superficially. We analyzed retrospectively ICP and CBFV signals recorded in traumatic brain injury patients during decrease in ICP induced by hypocapnia (n = 11) and rise in ICP during episodes of ICP plateau waves (n = 8). All three peaks were manually annotated in over 48 thousand individual pulses. The changes in PAT were compared between periods of vasoconstriction (expected during hypocapnia) and vasodilation (expected during ICP plateau waves) and their corresponding baselines. Correlation coefficient (rS) analysis between mean ICP and mean PATs was performed in each individual recording. Vasodilation prolonged PAT of the first peaks of ICP and CBFV pulses and the third peak of CBFV pulse. It also accelerated PAT of the third peak of ICP pulse. In contrast, vasoconstriction shortened appearance time of the first peaks of ICP and CBFV pulses and the second peak of ICP pulses. Analysis of individual recordings demonstrated positive association between changes in PAT of all three peaks in the CBFV pulse and mean ICP (rS range: 0.32-0.79 for significant correlations). Further study is needed to test whether PAT of the CBFV pulse may serve as an indicator of changes in ICP-this may open a perspective for non-invasive monitoring of alterations in mean ICP.

Change in Blood Flow Velocity Pulse Waveform during Plateau Waves of Intracranial Pressure.

A reliable method for non-invasive detection of dangerous intracranial pressure (ICP) elevations is still unavailable. In this preliminary study, we investigate quantitatively our observation that superimposing waveforms of transcranial Doppler blood flow velocity (FV) and arterial blood pressure (ABP) may help in non-invasive identification of ICP plateau waves. Recordings of FV, ABP and ICP in 160 patients with severe head injury (treated in the Neurocritical Care Unit at Addenbrookes Hospital, Cambridge, UK) were reviewed retrospectively. From that cohort, we identified 18 plateau waves registered in eight patients. A "measure of dissimilarity" (Dissimilarity/Difference Index, DI) between ABP and FV waveforms was calculated in three following steps: 1. fragmentation of ABP and FV signal according to cardiac cycle; 2. obtaining the normalised representative ABP and FV cycles; and finally; 3. assessing their difference, represented by the area between both curves. DI appeared to discriminate ICP plateau waves from baseline episodes slightly better than conventional pulsatility index did: area under ROC curve 0.92 vs. 0.90, sensitivity 0.81 vs. 0.69, accuracy 0.88 vs. 0.84, respectively. The concept of DI, if further tested and improved, might be used for non-invasive detection of ICP plateau waves.

Electrographic Correlates of Plateau Waves in Patients With Leptomeningeal Metastases.

We describe video electroencephalography (video-EEG) correlates of transient neurological attacks due to plateau waves-paroxysmal elevations in intracranial pressure-in patients with leptomeningeal metastases. We identified 3 patients with leptomeningeal metastases, intracranial hypertension, and transient neurological attacks captured on video-EEG without evidence of seizures or epileptiform activity. We identified all clinical events on video and reviewed the corresponding EEG data for evidence of abnormalities. All 3 patients had mild to moderate slowing and 2 had frontal intermittent rhythmic delta activity during background EEG recording. There were 33 clinical events recorded and stereotyped for each patient. All 33 events were associated with an increase in delta range slowing of ≥30% compared to the background. This abnormality started ≤2 minutes before the onset of clinical symptoms and persisted for minutes after clinical resolution. This study is the first to carefully describe the electrographic correlates of transient neurological attacks due to plateau waves in patients with leptomeningeal metastasis. Clinical attacks were consistently associated with a possible EEG signature of diffuse delta range slowing. Future studies can validate the sensitivity and specificity of these EEG changes as a prognostic and/or response biomarker in patients with leptomeningeal metastases with or without intracranial hypertension.