Background
Patients entering neurological and neurosurgical early rehabilitation are severely impaired. Morbidity is high [
1] and they are suffering from disorders of consciousness [
2,
3]. Early rehabilitation patients are dependent on nursing and may be colonized with multi-drug resistant germs [
4,
5]. Frequently, their outcome is poor, but it is quite difficult to predict outcome accurately [
3].
The role of clinical neurophysiology, in particular electroencephalography (EEG) and evoked potentials (EP) in predicting outcome of these patients is still unclear. Only a few studies are available on long-term rehabilitation results and clinical neurophysiology. The question is whether clinical neurophysiological techniques may help to distinguish between patients who benefit from neurological early rehabilitation and such who don’t. In contrast to imaging techniques, neurophysiological measurements are easy to perform, cheap, safe and available in most rehabilitation facilities.
Most studies focus on rehabilitation outcome of stroke patients (Table
1) [
6‐
16]. With respect to SEP, an absence or amplitude reduction of cortical responses seems to be associated with a poor long-term outcome after stroke [
6,
7,
10]. Like with SEP, absence of MEP may indicate poor recovery from stroke [
10,
16]. VEP have also been studied, suggesting that left-right asymmetry may be associated with functional outcome [
9]. Presence of delta and theta activity in EEG predicted unfavorable outcome one year after stroke [
8].
Table 1
Studies on long-term outcome of stroke patients involving clinical neurophysiological data
Zeman & Yiannikas 1989 [ 6] | 35 | Median SEP | Abnormal SEP (absence or amplitude reduction or prolonged latency N20) were associated with poor outcome (lower BI) after a mean LOS of 51 days |
| 35 | Median and tibial SEP | Tibial SEP: correlation between amplitude abnormalities (absence or attenuation) and occupational outcome after 1 y |
Median SEP: absence of N60 predicted poor outcome |
Cillessen et al. 1994 [ 8] | 55 | EEG in the acute stage | EEG (presence of delta and theta activity) predicted poor outcome after 1 year |
Ring, Bar & Abboud, 1999 [ 9] | 4 | VEP | Correlation between left-right asymmetry of VEP and functional outcome after a mean of 137 days inpatient rehabilitation |
| 64 | Median SEP and upper limb MEP | Absence of SEP and MEP indicated poor outcome 2 months after stroke |
Steube, Wiethölter & Correll 2001 [ 11] | 100 | Lower limb MEP more than 4 weeks after stroke | Preserved MEP predicted good outcome (independence in walking) after 8 weeks of inpatient rehabilitation |
Tzvetanov & Rousseff 2003 [ 12]; | 94 | Median and tibial SEP | N20-P25 amplitude is of some predictive value (1 y outcome), but MRC is stronger predictor of functional outcome, P40 amplitude correlated with BI (r = 0.63) after 3 months |
Tzvetanov, Rousseff, & Milanov 2003 [ 13]; |
Tsetanov, Rousseff & Atanassova 2005 [ 14] |
Al-Rawi, Hamdan & Abdul-Muttalib 2009 [ 15] | 22 | Median SEP | Correlation between SEP (N20 latency and amplitude) and 3-month outcome (BI, MRC) |
| 52 | Upper limb MEP | In patients with severe paresis (MRC <2), absence of MEP were predictive of poor recovery |
Some studies on long-term outcome of traumatic brain injury (TBI) patients are available (Table
2) [
17‐
23]. While AEP may be of some prognostic value in this group of patients [
17,
18], most studies focus on SEP. Like with stroke, TBI patients with a loss of cortical SEP-responses seem to have a poor outcome [
22].
Table 2
Studies on long-term outcome of traumatic brain injury (TBI) patients involving clinical neurophysiological data
Mackey-Hargadine & Hall 1985 [ 17] | 114 | AEP | Significant correlation between AEP, pupil reactivity and outcome in a 24 month period |
| 29 | AEP and SEP | SEP helped to improve prediction of outcome 12 months after TBI |
Thatcher et al. 1991 [ 19] | 162 | EEG and AEP | Combination of EEG and GCS bet predicted outcome 12 months after TBI |
| 27 | SEP and MEP from upper and lower limbs | Clinical and functional outcome was strongly correlated with abnormalities from tibial SEP, 6 and 12 months after TBI |
Özbudak-Demir et al. 1999 [ 21] | 26 | Median and tibial SEP | Normal SEP latencies were associated with better outcome, more than 8 months after TBI |
| 22 | Median SEP | Bilateral absence of SEP was strongly predictive of worst outcome (death or vegetative state), 6 months after TBI |
| 81 | Median SEP | SEP within 7 days after TBI correlate with 1 y outcome |
There are also studies on long-term outcome of disorders of consciousness (DOC) patients, in particular after hypoxic brain damage (Table
3) [
3,
24‐
28]. Results on the question whether SEP or AEP may be used to predict recovery are controversial [
24‐
27]. EEG could be of some value [
28]. Latest results from our group suggest that prolongation of wave III in flash VEP, theta or delta rhythm in EEG, and N20/P25 amplitude reduction in median SEP may be associated with poor outcome of hypoxic brain damage patients undergoing neurological early rehabilitation [
3].
Table 3
Studies on long-term outcome of DOC (disorders of consciousness) patients due to hypoxic or severe brain damage of different origin involving clinical neurophysiological data
Zeitlhofer et al. 1991 [ 24] | 22 | AEP and SEP | Evoked potentials had no value for the prognosis of “apallic” patients |
Goldberg & Karazim 1998 [ 25] | 33 | AEP and SEP | AEP and SEP predicted outcome of MCS patients |
| 113 | SEP | SEP did not predict outcome of hypoxic brain damage survivors |
Schorl, Valerius-Kukula & Kemmer 2014 [ 27] | 28 | Median SEP | Bliateral loss of SEP did not exclude recovery from severe brain damage |
| 101 | EEG | Reduced EEG amplitudes and delta frequencies were associated with bad clinical outcome (UWS, MCS) |
| 93 | EEG, flash VEP, median SEP | Prolongation of wave III (flash VEP), theta or delta EEG rhythm and N20/P25-amplitude reduction (SEP) predicted poor outcome (BI <50) |
The present study tried to figure out whether clinical neurophysiology may help to improve outcome prediction of a large cohort of neurological and neurosurgical early rehabilitation patients.
Methods
Patients
Medical records of 803 patients (376 female, 436 male) of the BDH-Clinic Hessisch Oldendorf, a large neurological and neurosurgical early rehabilitation facility located in Northern Germany, have been analyzed. Patients were admitted in 2010. Main diagnoses are presented in Table
4. The main diagnosis was defined according to the G-DRG- (German Diagnosis Related Groups) system as the disease justifying referral for early rehabilitation. When stroke patients also suffered from a peripheral disorder like diabetic polyneuropathy, for instance, stroke was defined as main diagnosis because it necessitated rehabilitation treatment.
Stroke | 349 | 43.5 |
Intracerebral bleeding | 107 | 13.3 |
Subarachnoidal bleeding | 65 | 8.1 |
Hypoxic brain damage | 37 | 3.4 |
Polyneuropathy, GBS | 24 | 3.0 |
Brain tumor | 23 | 2.9 |
Traumatic brain injury | 21 | 2.6 |
Spinal trauma | 13 | 1.6 |
Meningitis, encephalitis | 10 | 1.2 |
Other main diagnosis | 154 | 19.2 |
Sum | 803 | 100 |
Most patients underwent early rehabilitation after stroke (n = 349, 43.5 %), 34.0 (208.6) days after disease onset. Mean age was 66.6 (15.5) years. Length of stay (LOS) in early rehabilitation was 38.3 (37.2) days, LOS of the whole rehabilitation 58.5 (52.4) days. Discharge placement: 52.2 % (419/803) underwent subsequent rehabilitation or went home, 31.5 % (253/803) were discharged to a nursing home, 11.3 % (91/803) needed acute-care hospital treatment and 4.7 % (38/803) died. One patient was discharged against medical advice and another one was transferred to a hospice.
Clinical scales and assessments
On admission and at discharge, Barthel index (BI) [
29] and Early Rehabilitation Index (ERI) [
30] have been obtained. In line with previous studies, poor outcome was defined as a BI <50 points [
3]. In addition, CRS [
31], GCS [
32] and Early Functional Abilities scale [
33] have been analyzed.
Clinical neurophysiology
Electroencephalography (EEG), auditory evoked potentials (AEP), visual evoked potentials (VEP), somatosensory evoked potentials (SEP) of the median nerve were recorded usually within the first two weeks after admission. EEG was done using the international 10/20 system (Neurofax EEG 9000, Nihon Kohden Europe, Rosbach, Germany). Surface electrodes were used for evoked potentials (Nicolet Viking Select, Natus Medical, Middleton, WI, USA). VEPs were recorded with flashing light-emitting diodes (flash VEP, stimulation frequency 1.3Hz). Latencies and amplitudes of wave I-III were examined according to the guidelines of the American Clinical Neurophysiology Society [
34]. Further, AEP latencies I-V and N20/P25 latencies and amplitudes of median nerve SEPs were analyzed. Neurophysiological examinations were performed by an experienced team of only four paramedics working in this field for many years.
Ethics
This is a retrospective data analysis, only (no intervention). Local ethics committee of the BDH-Clinic Hessisch Oldendorf gave approval to use facility’s data. Patient records/information were anonymized and de-identified prior to analysis. No written informed consent for participation was obtained (retrospective data analysis, no intervention).
Statistics
For statistical analyses, SPSS™ 21.0 software package (SPSS Inc, Chicago, USA) was used. In the results section, mean values and standard deviations (in brackets) are displayed. In parametric (t-tests for independent samples and analysis of variance) as well as non-parametric tests (χ
2-tests), differences were regarded as significant with p < 0.05. In addition, bivariate Pearson correlations were computed.
Discussion
So far, reliable data on the usefulness of neurophysiological measurements in predicting the outcome from neurological and neurosurgical early rehabilitation is lacking. The present study analysed data of a large sample 803 patients. One would opt for clinical neurophysiology as a predictor because it is cheap, safe (no radiation), easy to perform and available in most rehabilitation facilities (in contrast to imaging like CT or MRI).
As with previous studies, present results suggest that outcome of neurological early rehabilitation patients mainly depends on age, morbidity and functional status on admission [
3]. However, neurophysiological data may be of some predictive value, in particular median SEP, AEP, flash VEP and EEG.
It turned out that patients with worse outcome had longer AEP III latencies. AEP wave III represents the cochlear nucleus which is located in the pontomedullary junction of the dorsolateral brainstem [
35]. It is well known that brainstem lesions are associated with poor neurological outcome and fatality [
36]. This finding could be reproduced in this study: Subjects with brain stem lesions on one or both sides showed a worse functional outcome from neurological early rehabilitation. As yet, a prolongation of AEP wave III latency has not been identified as a predictor of poor outcome and is a novel finding. Age, however, correlated significantly with wave III latency. Since age is a well-known predictor of poor outcome in neurological rehabilitation [
3], it may partially explain this finding. In addition, it has to be pointed out that even in the normal ageing brain, a delay of evoked potentials, in particular VEP and AEP, may be observed [
37,
38].
Another finding of this study was a prolongation of wave III in flash VEP in the poor outcome group. This finding is in line with a previous study from our group which focused on hypoxic brain damage patients [
3]. VEP wave III abnormalities might be a neurophysiological correlate of cortical dysfunction [
3]. As with AEP, VEP wave III latency also correlated with age. Thus, age might influence AEP wave III, too.
Another finding was that loss of cortical median SEP responses on one or both sides was associated with poor outcome. We know from literature that long-term outcome of stroke patients is also worse with absent SEP [
6,
10]. Thus, it may be hypothesized that absence of SEP indicates poor outcome in early rehabilitation patients.
There are a couple of studies focusing on EEG and outcome prediction. As with previous studies [
3,
8], theta and delta activity was associated with poor outcome.
There are some limitations to this study. First of all, this was a retrospective data analysis, only. This explains why only a proportion of the sample has been studied with all four neurophysiological examinations (EEG, SEP, AEP, VEP). Secondly, the patients showed a wide heterogeneity. This, however, is a common finding when examining neurological early rehabilitation patients [
1]. These patients suffer from a broad specter of neurological and neurosurgical disorders, central as well as peripheral disturbances. In addition, the study employed no control group and confounding medication (e.g. neuroleptics, benzodiazepines) has not been included in the analysis. Sedatives, however, are rarely used in our rehabilitation facility.
Results from this study defy ready summary, but EEG, median SEP, AEP and flash VEP may be of some predictive value in early rehabilitation patients. Further studies are strongly encouraged.
Conclusion
Results from this study suggest that loss of median nerve SEP, prolongation of wave III in early AEP and flash-VEP, as well as theta or delta rhythms in EEG are associated with poor outcome from neurological early rehabilitation. Clinical neurophysiology may help to improve outcome prediction of neurological and neurosurgical rehabilitation patients. EEG and evoked potentials are widely-used, cheap, easy to perform and non-invasive.
Competing interests
The author declares that he has no competing interests.