Can median nerve stimulation restore consciousness following subarachnoid hemorrhage?

Stimulating Recovery of Consciousness Following Aneurysmal Subarachnoid Hemorrhage

Jan Claassen, M.D., Ph.D.

New York Presbyterian Hospital

Funded in December, 2016: $300000 for 3 years
LAY SUMMARY . ABSTRACT .

LAY SUMMARY

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Can median nerve stimulation restore consciousness following subarachnoid hemorrhage?

This study in patients who have lost consciousness following a subarachnoid hemorrhage will lay the foundation for undertaking larger-scale clinical trials to see whether stimulating patients’ median nerve helps them to regain consciousness. The study also will see whether EEG (electroencephalogram) changes can serve as a biomarker to predict outcomes.

A subarachnoid hemorrhage (SAH) is a bleed in the space between the brain’s surface and the tissues that cover it (called the subarachnoid space). One of the most common causes of SAH is a burst aneurysm in the brain. This occurs when a blood vessel wall weakens, bulges and then ruptures. With this type of stroke, patients experience a sudden “thunderous” headache. Consequences range from severe neck and shoulder pain, seizures, numbness, paralysis or other problems to loss of consciousness.

The investigators have identified impaired consciousness as an important outcome measure for SAH. This finding is part of their large study using invasive multi-modal monitoring (through a hole in the skull) of comatose patients in the ICU to identify metabolic and electrical brain changes that signal problems and require intervention. Surprisingly, though, their initial findings in comatose SAH patients is that non-invasive EEG (electroencephalogram), rather than multi-modal monitoring, provides the best prognosis of whether a patient is likely to recover consciousness.

EEG uses electrodes placed on the scalp that record electrical changes in the brain. Specifically, EEG findings of electrical changes in certain brain areas in comatose SAH patients correlate with behavioral assessments, such as recovery of consciousness. Their initial evidence in comatose SAH patients indicates that if they can restore the functional integrity of the anterior forebrain by stimulating the thalamus, they may increase the likelihood of promoting patients’ recovery of consciousness.

While stimulating the thalamus directly via implanted electrodes has shown promise in raising consciousness levels in some minimally conscious patients, this procedure cannot feasibly be used acutely following brain injury. That is an important constraint, since research indicates that interventions to restore consciousness that are undertaken following the acute injury have the most chance of working.  

An indirect method of stimulating the thalamus, though, is safe and may be effective in the immediate post-acute stroke phase. This method entails placing electrodes on the arm, just above the wrist to stimulate the median nerve that extends from the wrist up the arm. Early pilot studies suggest that stimulating the median nerve may then stimulate the thalamus, which then stimulates the frontal neuronal networks to promote recovery of consciousness.   

 The investigators will assess the feasibility of using median nerve stimulation to restore consciousness in comatose SAH patients. They also will gather initial evidence of whether EEG results can serve as a biomarker for predicting which patients are likely to return to consciousness.   

The researchers do not yet know what level of indirect electrical stimulation is optimal. One study by other scientists conducting direct thalamus stimulation in minimally conscious adults indicates that 100 Hz appears optimal, while a small pilot study of median nerve stimulation by another group of scientists suggests that 40 Hz provides benefit.

The investigators, therefore, will randomly assign 60 comatose SAH patients to receive either a control setting (using a single standard diagnostic assessment) or treatment consisting of 8 hours per day of median nerve stimulation at either 40Hz or 100Hz during the first two weeks post injury. Surrogates for all comatose participants will have given informed consent.

They will measure outcomes using EEG and behavioral results. EEG measures: They will see, after one week of treatment, whether median nerve stimulation-evoked EEG changes in neural connectivity predicts recovery of consciousness. Specifically, they will see whether there is propagation of activity between different brain areas, and whether cortical information transfer following simulation predicts recovery of consciousness.

Behavioral measures: these will be assessed after two weeks of treatment and will be based on the revised Coma Recovery Scale, along with standard neurological exam that assesses eye opening, obtained twice daily for two weeks. Outcome categories will be: 1) unconscious without eye opening; 2) unconscious with eye opening; and 3) conscious.

Investigators anticipate that the insights gained from this pilot study will be transferable to other acute brain injury pathologies associated with impaired consciousness such as cardiac arrest and intracerebral hemorrhage. They intend to utilize the results to design a large, multi-center randomized controlled trial using median nerve stimulation to support recovery of consciousness during the acute phase following brain injury.

Significance :  This pilot study and the anticipated large-scale research it is intended to inform may lead both to improved treatment for promoting recovery of consciousness and of more reliable measures for predicting the likelihood of recovery.      

ABSTRACT

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Stimulating Recovery of Consciousness Following Aneurysmal Subarachnoid Hemorrhage

Impaired consciousness is highly prevalent after acute brain injury and poorly understood. Consciousness heavily influences goals of care decisions and is one of the primary determinants of ICU and hospital length of stay. This proposal is intended establish the foundation for interventional trials enabling recovery of consciousness following acute brain injury. Our EEG and resting state MRI data implicate the functional integrity of anterior forebrain thalamo-cortical circuitry as promising targets for interventions to promote recovery of consciousness. Direct or indirect brain stimulation may facilitate evaluation and restoration of consciousness. Direct thalamic stimulation has been shown to improve level of consciousness but is invasive and likely not feasible acutely following brain injury. However, interventions during the early post injury phase may have the greatest impact and early pilot studies suggest that median nerve electrical stimulation may facilitate stimulation of frontal neuronal networks via the thalamus. We will study adult patients admitted with subarachnoid hemorrhage (SAH) that are unconscious and admitted to an intensive care unit. The goal of the proposed research is to establish the feasibility of indirectly stimulating frontal neuronal networks via the thalamus in an effort to assess and support recovery of consciousness in patients with SAH. We will utilize a median nerve stimulation paradigm to assess neuronal connectivity as a predictor for recovery of consciousness and explore the effect on behavioral measures. Short and long term outcomes will be assessed.

INVESTIGATOR BIOGRAPHIES

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Jan Claassen, M.D., Ph.D.

Dr. Jan Claassen is an Associate Professor in the Department of Neurology at Columbia University College of Physicians and Surgeons. He received a degree in medicine and a PhD in neurophysiology studying evoked potentials after traumatic brain injury from the University of Hamburg. He underwent post-doctoral research training and clinical training in neurology, electrophysiology, and neurocritical care at Columbia University, NY. He is the Head of Neurocritical Care and medical director of the Neuro ICU at Columbia University, and a board certified neurologist and neurointensivist.

His research characterizes physiologic changes following acute brain injury, focusing on novel treatment approaches to potentially improve patient outcomes. Dr Claassen’s group has focused on the use of innovative brain monitoring techniques including continuous EEG monitoring with a particular focus on studying recovery of consciousness. Dr Claassen has been intimately involved with national and international guideline development for patients with acute brain injury. He is on the Editorial board of Annals of Neurology and Neurocritical Care. He has published over 200 peer-reviewed articles and many book chapters. He is the co-editor of the 5th edition of Plum and Posner's Diagnosis and Treatment of Stupor and Coma and the 3rd Edition of Seizures in Critical Care - A Guide to Diagnosis and Therapeutics. His long-term goals are to develop interventions to promote recovery and diagnostics to assess consciousness during the acute stage following severe brain injuries. 

KEYWORDS


Anatomy: Central nervous system
Conditions: Brain injury
Stroke
Function: Consciousness
Sociology/Social Phenomena: Neuroethics
Technology: Neuromodulation and neural plasticity