IMproving diagnosis and PRediction of Outcome in patients with seVEre Disorders Of Consciousness (IMPROVE-DOC)

It remains difficult to assess the level of consciousness in patients with
severe brain injury and disturbed consciousness. Since signs of behaviour may
be minimal or inconsistently present in these patients, standard behavioural
assessments remain subject to errors. Therefore, the rate of misdiagnosis of
patients with disorders of consciousness (DOC) remains high. This forms a large
problem for clinicians, since consciousness is an important parameter for
clinical decision-making in both the early as late phase after severe brain
injury. Life-or-death decisions are made with the use of fairly limited bedside
tests and conventional brain imaging. In addition, there is only limited
evidence of outcome in specific subgroups of DOC patients. There is still no
standard diagnostic protocol for patients with persistent DOC in the
Netherlands. Families are often told that recovery of consciousness is
uncertain, and prognosis remains unknown. However, it has recently been shown
that multidimensional testing with the use of electroencephalography (EEG) and
additional neuroimaging, such as FDG-PET might provide valuable diagnostic and
prognostic information in DOC patients. In this study, a specific diagnostic
protocol will be implemented for patients with DOC after severe brain injury in
the Amsterdam University Medical Centers, location Academic Medical Center
(AMC), in order to complement standard behavioural assessments of
consciousness. A multimodal diagnostic approach with specific EEG tests and
structural and functional neuroimaging may provide objective information
regarding the integrity of residual cognitive functions, and remove the
dependency of the patient to move or speak in order to reveal awareness of self
or environment. Moreover, more stringent follow-up with repeated behavioral
measurements, EEG*s, and neuroimaging will provide valuable data of outcome
after DOC and the first opportunity to relate early-phase findings to late
clinical outcome. This approach may resolve many of the dilemmas faced by
clinicians interpreting solely behavioural indices, and might inform the
clinical decision process, lead to more adequate prognostication, and provide
families with tailor-made information of the condition of their loved ones.

To provide more objective information regarding the integrity of residual
cognitive functions in patients with DOC after severe brain injury, and to
relate early-phase behavioural, EEG, and neuroimaging findings to late clinical
outcome. This might eventually lead to improvements in diagnosis, estimation of
prognosis and clinical decision-making in patients with severe brain injury.

A prospective study.

The differential diagnosis between coma, unresponsive wakefulness syndrome
(UWS, formerly known as the vegetative state) and minimally conscious state
(MCS) is often challenging, as these states occupy a border zone between
unconsciousness and awareness. At present, the clinical standard for detecting
signs of consciousness is based on bedside behavioural examination. The
frequency of misdiagnoses by clinical consensus methods is, however,
disturbingly high: around 40%. Motor deficits (paralysis, spasticity), impaired
cognition (aphasia, apraxia), sensory impairment (blindness, deafness), pain
and fatigability of patients with DOC are some of the factors that account for
misdiagnosis. The differential diagnosis between patients in coma, UWS and MCS
has important implications regarding prognosis and treatment. Moreover, it is
an important factor in clinical decision-making. There is an increasingly body
of evidence from EEG techniques and neuroimaging studies that highlights the
necessity for using multimodal and multidimensional diagnostic procedures to
measure residual cognitive capacity. However, these techniques have not been
implicated in standard clinical care, and there is no standard diagnostic
protocol for patients with DOC in the Netherlands. In this study, a multimodal
and multidimensional approach with specific EEG tests and structural and
functional neuroimaging will be performed in order to obtain objective
information regarding the integrity of residual cognitive functions in DOC
patients. Moreover, a stringent follow-up protocol with repeated longitudinal
behavioural, EEG and neuroimaging measurements will provide valuable data of
outcome after DOC and the first opportunity to relate early-phase findings in
DOC patients to late clinical outcome. There is only a small risk involved with
participation, since EEGs and (functional) neuroimaging are minimal-invasive
techniques that are frequently used in normal hospital care. Usually, DOC
patients have a long length of hospital stay, since there is a waiting list for
rehabilitation and nursing homes. In this time-frame, families often express
their need for more objective information on the condition of their
beloved-ones. It is therefore expected that there will be willingness for
participation. This approach might resolve many of the dilemmas faced by
clinicians currently interpreting solely behavioural indices, might inform the
clinical decision process, and may lead to more adequate estimation of
prognosis. Eventually, it might benefit the whole circle of care after severe
brain injury, including the patient, family, and clinicians.