Prediction of Neurological Outcome After Cardiac Arrest: Is Serum Procalcitonin the Future?

Neurocritical Care -     

Chasing Certainty After Cardiac Arrest: Can a Technological Innovation Solve a Moral Dilemma?

When information on a coma patient’s expected outcome is uncertain, a moral dilemma arises in clinical practice: if life-sustaining treatment is continued, the patient may survive with unacceptably poor neurological prospects, but if withdrawn a patient who could have recovered may die. Continuous electroencephalogram-monitoring (cEEG) is expected to substantially improve neuroprognostication for patients in coma after cardiac arrest. This raises expectations that decisions whether or not to withdraw will become easier. This paper investigates that expectation, exploring cEEG’s impacts when it becomes part of a socio-technical network in an Intensive Care Unit (ICU). Based on observations in two ICUs in the Netherlands and one in the USA that had cEEG implemented for research, we interviewed 25 family members, healthcare professionals, and surviving patients. The analysis focuses on (a) the way patient outcomes are constructed, (b) the kind of decision support these outcomes provide, and (c) how cEEG affects communication between professionals and relatives. We argue that cEEG can take away or decrease the intensity of the dilemma in some cases, while increasing uncertainty for others. It also raises new concerns. Since its actual impacts furthermore hinge on how cEEG is designed and implemented, we end with recommendations for ensuring responsible development and implementation.

     

Multimodal Outcome Prognostication After Cardiac Arrest and Targeted Temperature Management: Analysis at 36 °C

Background

Targeted temperature management (TTM) represents the standard of care in comatose survivors after cardiac arrest (CA) and may be applied targeting 33° or 36 °C. While multimodal prognostication has been extensively tested for 33 °C, scarce information exists for 36 °C.

Methods

In this cohort study, consecutive comatose adults after CA treated with TTM at 36 °C between July 2014 and October 2016 were included. A combination of neurological examination, electrophysiological features, and serum neuron-specific enolase (NSE) was evaluated for outcome prediction at 3 months (mortality; good outcome defined as cerebral performance categories (CPC) score of 1–2, poor outcome defined as CPC 3–5).

Results

We analyzed 61 patients. The presence of two or more predictors out of, unreactive electroencephalogram (EEG) background, epileptiform EEG, absent pupillary and/or corneal reflex, early myoclonus, bilaterally absent cortical somatosensory evoked potentials, and serum NSE >75 μg/l, had a high specificity for predicting mortality (positive predictive value [PPV] = 1.00, 95% CI 0.87–1.00) and poor outcome (PPV = 1.00, 95% CI 0.80–1.00). Reactive EEG background was highly sensitive for predicting good outcome (0.95, 95% CI 0.74–0.99).

Conclusions

Prediction of outcome after CA and TTM targeting 36 °C seems valid in adults using the same features tested at 33 °C. A reactive EEG under TTM appears highly sensitive for good outcome.

     

TREM1: A Potential Therapeutic Target For Alzheimer’s Disease

Immunity has been suggested to play crucial roles in the pathogenesis of Alzheimer’s disease (AD). The triggering receptor expressed on myeloid cells-1 (TREM1), a member of the immunoglobulin superfamily of receptors, is widely expressed in monocytes and microglia. On the other hand, TREM1 variant, rs6910730^G, is reported to associate with AD pathology; however, the exact mechanism is not yet clear. Since phagocytosis of Aβ by monocytes enhances Aβ clearance and attenuates AD pathogenesis, Jiang et al. has investigated if TREM1 can modulate Aβ phagocytosis and degradation by monocytes in the central nervous system (CNS). They found that TREM1 facilitates microglial Aβ phagocytosis while rs6910730^G impairs this function and exacerbates AD pathogenesis. These findings suggest that TREM1 can be implemented investigated as a potential therapeutic target in AD.     

Potassium Channels: A Potential Therapeutic Target for Parkinson’s Disease

The pathogenesis of the second major neurodegenerative disorder, Parkinson’s disease (PD), is closely associated with the dysfunction of potassium (K⁺) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K⁺ channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K⁺ channels enhances the spontaneous firing frequency of nigral dopamine (DA) neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum. Recently, three K⁺ channels have been identified to protect DA neurons and to improve the motor and non-motor symptoms in PD animal models: small conductance (SK) channels, A-type K⁺ channels, and K_V7/KCNQ channels. In this review, we summarize the physiological and pharmacological effects of the three K⁺ channels. We also describe in detail the laboratory investigations regarding K⁺ channels as a potential therapeutic target for PD.     

A Precision Medicine Approach to Cerebral Edema and Intracranial Hypertension after Severe Traumatic Brain Injury: Quo Vadis?

Purpose of Review

Standard clinical protocols for treating cerebral edema and intracranial hypertension after severe TBI have remained remarkably similar over decades. Cerebral edema and intracranial hypertension are treated interchangeably when in fact intracranial pressure (ICP) is a proxy for cerebral edema but also other processes such as extent of mass lesions, hydrocephalus, or cerebral blood volume. A complex interplay of multiple molecular mechanisms results in cerebral edema after severe TBI, and these are not measured or targeted by current clinically available tools. Addressing these underpinnings may be key to preventing or treating cerebral edema and improving outcome after severe TBI.

Recent Findings

This review begins by outlining basic principles underlying the relationship between edema and ICP including the Monro-Kellie doctrine and concepts of intracranial compliance/elastance. There is a subsequent brief discussion of current guidelines for ICP monitoring/management. We then focus most of the review on an evolving precision medicine approach towards cerebral edema and intracranial hypertension after TBI. Personalization of invasive neuromonitoring parameters including ICP waveform analysis, pulse amplitude, pressure reactivity, and longitudinal trajectories are presented. This is followed by a discussion of cerebral edema subtypes (continuum of ionic/cytotoxic/vasogenic edema and progressive secondary hemorrhage). Mechanisms of potential molecular contributors to cerebral edema after TBI are reviewed. For each target, we present findings from preclinical models, and evaluate their clinical utility as biomarkers and therapeutic targets for cerebral edema reduction. This selection represents promising candidates with evidence from different research groups, overlap/inter-relatedness with other pathways, and clinical/translational potential.

Summary

We outline an evolving precision medicine and translational approach towards cerebral edema and intracranial hypertension after severe TBI.

     

Cerebral Dopamine Neurotrophic Factor: A Potential Therapeutic Agent for Parkinson’s Disease

The application of neurotrophic factors (NTFs) is a promising therapeutic strategy for neurodegenerative disorders such as Parkinson’s disease (PD). Many NTFs have been reported to enhance the survival, regeneration, and differentiation of neurons and to induce synaptic plasticity. However, because of their potential side-effects and low efficacy after clinical administration, more potent treatments for neurodegenerative disorders are being sought. Cerebral dopamine neurotrophic factor (CDNF), a newly-identified NTF homologous to mesencephalic astrocyte-derived NTF, is structurally and functionally different from other NTFs, providing new hope especially for PD patients. In various animal models of PD, CDNF is efficient in protecting and repairing dopaminergic neurons, and it inhibits endoplasmic reticulum stress, neuroinflammation, and apoptosis. Recent progress in all facets of CDNF research has enabled researchers to better understand its beneficial effects in the treatment of PD.     

Hypoxia Conditioning as a Promising Therapeutic Target in Parkinson's Disease?

Several lines of research point to a key role of low oxygen supply (hypoxia) in Parkinson's disease pathogenesis. Although severe hypoxia is detrimental for the brain, physiological adaptations to mild hypoxia are neuroprotective. Herein we discuss, how neuroprotective effects can be induced by hypoxia conditioning and how related approaches have the potential to be harnessed as therapeutic strategies in Parkinson's disease. © 2021 International Parkinson and Movement Disorder Society