Transient intracranial pressure elevations (B waves) are associated with sleep apnea.

BACKGROUND: Repetitive transient intracranial pressure waveform elevations up to 50 mmHg (ICP B-waves) are often used to define pathological conditions and determine indications for ICP-reducing treatment. We recently showed that nocturnal transient ICP elevations are present in patients without structural brain lesions or hydrocephalus in whom they are associated with sleep apnea. However, whether this signifies a general association between ICP macropatterns and sleep apnea remains unknown. METHODS: We included 34 patients with hydrocephalus, or idiopathic intracranial hypertension (IIH), who were referred to the Neurosurgical Department, Copenhagen, Denmark, from 2017 to 2021. Every patient underwent diagnostic overnight ICP monitoring for clinical indications, with simultaneous polysomnography (PSG) sleep studies. All transient ICP elevations were objectively quantified in all patients. Three patients were monitored with continuous positive airway pressure (CPAP) treatment for an additional night. RESULTS: All patients had transient ICP elevations associated with sleep apnea. The mean temporal delay from sleep apnea to transient ICP elevations for all patients was 3.6 s (SEM 0.2 s). Ramp-type transient ICP elevations with a large increase in ICP were associated with rapid eye movement (REM) sleep and sinusoidal-type elevations with non-REM (NREM) sleep. In three patients treated with CPAP, the treatment reduced the number of transient ICP elevations with a mean of 37%. CPAP treatment resulted in insignificant changes in the average ICP in two patients but elevated the average ICP during sleep in one patient by 5.6 mmHg. CONCLUSION: The findings suggest that sleep apnea causes a significant proportion of transient ICP elevations, such as B-waves, and sleep apnea should be considered in ICP evaluation. Treatment of sleep apnea with CPAP can reduce the occurrence of transient ICP elevations. More research is needed on the impact of slow oscillating mechanisms on transient ICP elevations during high ICP and REM sleep.

Remission, response, retention and persistence to treatment with disease-modifying agents in patients with rheumatoid arthritis: a study of harmonised Swedish, Danish and Norwegian cohorts.

OBJECTIVE: Precision medicine in rheumatoid arthritis (RA) requires a good understanding of treatment outcomes and often collaborative efforts that call for data harmonisation. We aimed to describe how harmonisation across study cohorts can be achieved and investigate how the observed proportions reaching remission vary across remission criteria, study types, disease-modifying antirheumatic drugs (DMARDs) and countries, and how they relate to other treatment outcomes. METHODS: We used data from eight existing large-scale, clinical RA registers and a pragmatic trial from Sweden, Denmark and Norway. In these, we defined three types of treatment cohorts; methotrexate monotherapy (as first DMARD), tumour necrosis factor inhibitors (TNFi) (as first biological DMARD) and rituximab. We developed a harmonised study protocol defining time points during 36 months of follow-up, collected clinical visit data on treatment response, retention, persistence and six alternative definitions of remission, and investigated how these outcomes differed within and between cohorts, by treatment. RESULTS: Cohort sizes ranged from ~50 to 22 000 patients with RA. The proportions reaching each outcome varied across outcome metric, but with small to modest variations within and between cohorts, countries and treatment. Retention and persistence rates were high (>50% at 1 year), yet <33% of patients starting methotrexate or TNFi, and only 10% starting rituximab, remained on drug without other DMARDs added and achieved American Congress of Rheumatology/European Alliance of Associations for Rheumatology or Simplified Disease Activity Index remission at 1 year. CONCLUSION: Harmonisation of data from different RA data sources can be achieved without compromising internal validity or generalisability. The low proportions reaching remission, point to an unmet need for treatment optimisation in RA.

k-Shape clustering for extracting macro-patterns in intracranial pressure signals.

BACKGROUND: Intracranial pressure (ICP) monitoring is a core component of neurosurgical diagnostics. With the introduction of telemetric monitoring devices in the last years, ICP monitoring has become feasible in a broader clinical setting including monitoring during full mobilization and at home, where a greater diversity of ICP waveforms are present. The need for identification of these variations, the so-called macro-patterns lasting seconds to minutes-emerges as a potential tool for better understanding the physiological underpinnings of patient symptoms. METHODS: We introduce a new methodology that serves as a foundation for future automatic macro-pattern identification in the ICP signal to comprehensively understand the appearance and distribution of these macro-patterns in the ICP signal and their clinical significance. Specifically, we describe an algorithm based on k-Shape clustering to build a standard library of such macro-patterns. RESULTS: In total, seven macro-patterns were extracted from the ICP signals. This macro-pattern library may be used as a basis for the classification of new ICP variation distributions based on clinical disease entities. CONCLUSIONS: We provide the starting point for future researchers to use a computational approach to characterize ICP recordings from a wide cohort of disorders.

Dorsal striatal dopamine induces fronto-cortical hypoactivity and attenuates anxiety and compulsive behaviors in rats.

Dorsal striatal dopamine transmission engages the cortico-striato-thalamo-cortical (CSTC) circuit, which is implicated in many neuropsychiatric diseases, including obsessive-compulsive disorder (OCD). Yet it is unknown if dorsal striatal dopamine hyperactivity is the cause or consequence of changes elsewhere in the CSTC circuit. Classical pharmacological and neurotoxic manipulations of the CSTC and other brain circuits suffer from various drawbacks related to off-target effects and adaptive changes. Chemogenetics, on the other hand, enables a highly selective targeting of specific neuronal populations within a given circuit. In this study, we developed a chemogenetic method for selective activation of dopamine neurons in the substantia nigra, which innervates the dorsal striatum in the rat. We used this model to investigate effects of targeted dopamine activation on CSTC circuit function, especially in fronto-cortical regions. We found that chemogenetic activation of these neurons increased movement (as expected with increased dopamine release), rearings and time spent in center, while also lower self-grooming. Furthermore, this activation increased prepulse inhibition of the startle response in females. Remarkably, we observed reduced [18F]FDG metabolism in the frontal cortex, following dopamine activation in the dorsal striatum, while total glutamate levels- in this region were increased. This result is in accord with clinical studies of increased [18F]FDG metabolism and lower glutamate levels in similar regions of the brain of people with OCD. Taken together, the present chemogenetic model adds a mechanistic basis with behavioral and translational relevance to prior clinical neuroimaging studies showing deficits in fronto-cortical glucose metabolism across a variety of clinical populations (e.g. addiction, risky decision-making, compulsivity or obesity).

Causal relationship between slow waves of arterial, intracranial pressures and blood velocity in brain.

PURPOSE: Slow vasogenic waves in arterial blood pressure (ABP), intracranial pressure (ICP) and cerebral blood flow velocity (FV) carry information on multiple brain homeostatic control mechanisms. This work presents an approach to evaluate causal relation between oscillatory modes of these signals as an alternative to time or frequency domain Granger analysis. METHODS: Forty-five patients with simultaneous recordings of ICP, ABP and FV during CSF infusion studies were examined retrospectively. Each time series was decomposed into ten intrinsic mode functions (IMFs) via Ensemble Empirical Mode Decomposition (EEMD) and, afterwards, Granger causality (GC) was computed. RESULTS: Slow waves of ICP, ABP and FV were reconstructed from mode functions IMF6-9 of each time series, covering a frequency range between 0.013 and 0.155 Hz. Most significant connections were from FV to ICP, being stronger during elevation of mean ICP during infusion study. No G-causality was found between any of the IMFs during the baseline phase. CONCLUSION: Nonlinearity and nonstationarity of the cerebral and systemic signals can be addressed using EEMD decomposition There is a causal influence of slow waves of FV on slow waves on ICP during the plateau phase of the infusion study for a frequency band between 0.095 and 0.155 Hz. This relationship is magnified during mild intracranial hypertension.

Empirical Mode Decomposition-Based Method for Artefact Removal in Raw Intracranial Pressure Signals.

Intracranial pressure (ICP) signals are often contaminated by artefacts and segments of missing values. Some of these artefacts can be observed as very high and short spikes with a physiologically impossible high slope. The presence of these spikes reduces the accuracy of pattern recognition techniques. Thus, we propose a modified empirical mode decomposition (EMD) method for spike removal in raw ICP signals. The EMD breaks down the signal into 16 intrinsic mode functions (IMFs), combines the first 4 to localize spikes using adaptive thresholding, and then either removes or imputes the identified ICP spikes.

B-waves are present in patients without intracranial pressure disturbances.

Intracranial pressure (ICP) B-waves are defined as short, repeating elevations of ICP of up to 50 mmHg with a frequency of 0.5-2 waves/min. The presence of B-waves in overnight recordings is regarded as a pathological phenomenon. However, the physiology of B-waves is still not fully understood and studies with transcranial Doppler, as a surrogate marker for ICP, have suggested that B-waves could be a normal physiological phenomenon. We present four patients without known structural neurological disease other than a coincidentally found unruptured intracranial aneurysm. One of the patients had experienced well-controlled epilepsy for several years, but was included because ICP under these conditions is unlikely to be abnormal. Following informed consent, all four patients had a telemetric ICP probe implanted during a prophylactic operation with closure of the aneurysm. They underwent overnight ICP monitoring with simultaneous polysomnography (PSG) sleep studies at 8 weeks after the operation. These patients exhibited nocturnal B-waves, but did not have major structural brain lesions. Their ICP values were within the normal range. Nocturnal B-waves occurred in close association with sleep-disordered breathing (SDB) in rapid eye movement (REM) and non-REM sleep stages. SDB during REM sleep was associated with ramp-type B-waves; SDB during non-REM sleep was associated with the sinusoidal type of B-wave. We propose that B-waves are a physiological phenomenon associated with SDB and that the mechanical changes during respiration could have an essential and previously unrecognised role in the generation of B-waves.

B waves: a systematic review of terminology, characteristics, and analysis methods.

BACKGROUND: Although B waves were introduced as a concept in the analysis of intracranial pressure (ICP) recordings nearly 60 years ago, there is still a lack consensus on precise definitions, terminology, amplitude, frequency or origin. Several competing terms exist, addressing either their probable physiological origin or their physical characteristics. To better understand B wave characteristics and ease their detection, a literature review was carried out. METHODS: A systematic review protocol including search strategy and eligibility criteria was prepared in advance. A literature search was carried out using PubMed/MEDLINE, with the following search terms: B waves + review filter, slow waves + review filter, ICP B waves, slow ICP waves, slow vasogenic waves, Lundberg B waves, MOCAIP. RESULTS: In total, 19 different terms were found, B waves being the most common. These terminologies appear to be interchangeable and seem to be used indiscriminately, with some papers using more than five different terms. Definitions and etiologies are still unclear, which makes systematic and standardized detection difficult. CONCLUSIONS: Two future lines of action are available for automating macro-pattern identification in ICP signals: achieving strict agreement on morphological characteristics of "traditional" B waveforms, or starting a new with a fresh computerized approach for recognition of new clinically relevant patterns.