The document discusses three studies that examined the effects of multimodal early onset stimulation (MEOS) therapy in patients and rats with severe brain injuries. The studies found that MEOS therapy combined with an enriched environment: 1) Led to improvements in vegetative parameters and motor functions in some comatose patients. 2) Resulted in reduced brain lesion volumes and enhanced recovery of motor functions in rats. 3) Provided additional benefits over enriched environment alone, including better reversal of motor and cognitive dysfunction in rats.

1. Brain Inj. 2000 Jun;14(6):585-94.
Multimodal early onset stimulation (MEOS) in rehabilitation
after brain injury.
Grüner ML, Terhaag D.
Source
Klinik für Allgemeine Neurochirurgie, Universität zu Köln, Germany. dsg@dr-gruner.de
Abstract
An early and consistent administration of the correct rehabilitation programme is of crucial importance
for the restoration and improvement of cerebral function, as well as social reintegration. This has led
to the development of a multimodal onset stimulation therapy (MEOS), which the neurosurgical
intensive care unit administers during an early phase of rehabilitation to patients who have been in a
coma for more than 48 hours after trauma. This study, which was carried out over a period of 2 years,
focuses on 89 patients aged 16-65 years suffering from severe brain injury. Sixteen of these (age
mean: 43.6 years) fulfil the criteria required to start the MEOS. The authors were able to identify
significant changes in two of the patients' vegetative parameters (viz. heart and respiratory
frequencies), even in cases of deep coma (GCS 3-4). The most significant changes were caused by
tactile and acoustic stimulation. Standardized behavioural assessment turned out to be particularly
advisable in cases of medium coma. Here, too, a stimulation of the tactile and acoustic senses
resulted mainly in head and eye movements.
PMID:
10887891
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/10887891
Eur J Neurosci. 2005 May;21(9):2406-18.
Multimodal early onset stimulation combined with enriched
environment is associated with reduced CNS lesion volume
and enhanced reversal of neuromotor dysfunction after
traumatic brain injury in rats.
Maegele M, Lippert-Gruener M, Ester-Bode T, Garbe J, Bouillon B, Neugebauer E, Klug N, Lefering R, Neiss
WF, Angelov DN.
Source

2. Biochemical and Experimental Division, Faculty of Medicine, University of Cologne, Germany.
Abstract
This study was designed to determine whether exposure to multimodal early onset stimulation
(MEOS) combined with environmental enrichment (EE) after traumatic brain injury (TBI) would
improve neurological recovery and to elucidate its morphological correlates. Male Sprague-Dawley
rats were subjected to lateral fluid percussion (LFP) brain injury or to sham operation. After LFP, one-
third of the animals (injured and sham) were placed under conditions of standard housing (SH), one-
third were kept in EE only, and one-third received EE + MEOS. Assessment of neuromotor function
24 h post-injury using a standardized composite neuroscore test revealed an identical pattern of
neurological impairment in all animals subjected to LFP. Neuromotor dysfunction in SH animals
remained on a similar level throughout the experiment, while improvements were noted in both other
groups 7 days post-injury (dpi). On 15 dpi, reversal of neuromotor dysfunction was significantly better
in EE + MEOS animals vs. SH- and EE-only groups. In parallel, the comparison of lesion volume in
EE + MEOS- vs. EE-only vs. SH rats revealed that animals exposed to EE + MEOS had consistently
the lowest values (mm3, mean +/- SD; n = 6 rats in each group) as measured in serial brain sections
immunostained for neuron-specific enolase (5.2 +/- 3.4 < or = 5.5 +/- 4.1 < 9.5 +/- 1.9), caspase 3-
active/C3A (5.9 +/- 4.0 < or = 6.4 +/- 3.9 < 10.3 +/- 1.8) and glial fibrillary acidic protein (6.0 +/- 3.4 <
or = 6.5 +/- 4.3 < 10.7 +/- 1.2). This first report on the effect of EE + MEOS treatment strongly
indicates that the combined exposure reduces CNS scar formation and reverses neuromotor deficits
after TBI in rats.
PMID:
15932599
[PubMed - indexed for MEDLINE
ww.ncbi.nlm.nih.gov/pubmed/15932599
J Neurotrauma. 2005 Jul;22(7):772-82.
Reversal of neuromotor and cognitive dysfunction in an enriched
environment combined with multimodal early onset stimulation after
traumatic brain injury in rats.
Maegele M, Lippert-Gruener M, Ester-Bode T, Sauerland S, Schäfer U, Molcanyi M, Lefering R, Bouillon B, Neiss
WF, Angelov DN, Klug N, McIntosh TK,Neugebauer EA.
Source
Biochemische und Experimentelle Abteilung, Medizinische Fakultät der Universität zu Köln, Chirurgische Klinik der Universität Witten-
Herdecke, Klinikum Köln-Merheim, Germany. Marc.Maegele@t-online.de
Erratum in
J Neurotrauma. 2007 Dec;24(12):1889. Molcany, Marek [corrected to Molcanyi, Marek].
Abstract
This study was designed to investigate the additional benefits of a multimodal early onset stimulation (MEOS)
paradigm when combined with enriched environment (EE) versus EE only and standard housing (SH) on the
recovery after experimental traumatic brain injury (TBI). Male Sprague- Dawley rats were subjected to moderate
lateral fluid percussion (LFP) brain injury (n = 40) or sham operation (n = 6). Thereafter, the injured and sham/EE +

3. MEOS and EE only groups were placed into a complex EE consisting of tunnel-connected wide-bodied cages with
various beddings, inclining platforms, and toys. Along with group living and environmental complexity, injured and
sham/EE + MEOS animals were additionally exposed to a standardized paradigm of multimodal stimulation
including auditory, visual, olfactory, and motor stimuli. In contrast, injured and sham/SH groups were housed
individually without stimulation. A standardized composite neuroscore (NS) test was used to assess acute post-
traumatic neuromotor deficits (24 h after injury) and recovery on days 7 and 15; recovery of cognitive function was
assessed on days 11-15 using the Barnes maze. Neuromotor impairment was comparable in all injured animals at
24 h post-injury, but braininjured EE + MEOS rats performed significantly better than both brain-injured SH and EE
groups when tested on post-injury days 7 and 15 (p = 0.004). Similarly, latencies to locate the hidden box under the
Barnes maze platform were significantly shortened in EE + MEOS animals at day 15 (p = 0.003). These results
indicate that the reversal of neuromotor and cognitive dysfunction after TBI can be substantially enhanced when
MEOS is added to EE.
PMID:
16004580
[PubMed - indexed for MEDLINE
http://www.ncbi.nlm.nih.gov/pubmed/16004580.