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Preliminary results on epidemiology, acute hospital care, and neurorehabilitation of TBI are presented of the first ever prospective controlled German study to analyse the use of regional structures and quality management as provided by the German social healthcare system. The sum of inhabitants in Hannover and Münster area was 2,114 million. Within an area of 100 kilometres diameter each. 6.783 acute TBI (58% male) were admitted for acute treatment from March 2000 to 2001. Definition of acute TBI was according to the ICD 10 S-02, S-04, S-06, S-07, S-09 in combination with dizziness or vomiting; retrograde or anterograde amnesia, impaired consciousness, skull fracture, and/or focal neurological impairment. The incidence was 321/100.000 population. Cause of TBI was traffic accident in 26%, during leisure time 35%, at home 30% and at work 15%. Initial GCS (emergency room) was only assessed in 3.731 TBI (=55%). Out of those 3.395 = 90,9% were mild, 145 = 3,9% were moderate, and 191 = 5,2% severe TBI. 28% of 6.783 patients were <1 to 15 years, 18% > 65 years of age. The number admitted to hospital treatment is 5.221 = 77%, of whom 72 patients (=1,4%) died caused by TBI. One year follow-up in 4.307 TBI patients (=63.5%) revealed that only 258 patients (=3,8%) received neurorehabilitation (73% male), but 68% within one month of injury. Five percent of these patients were <16 years of age, 25% > 65 years. Early rehabilitation “B” was performed in 100 patients (=39%), 19% within one week following TBI. The management of frequent complications in 148 patients (=57%) and the high number of one or more different consultations (n = 196) confirmed the author’s concept for early neurosurgical rehabilitation in TBI when rehabilitation centres were compared regarding GCS and GOS: Early GOS 1 = 4%; GOS 2 = 2,7%, GOS 3 = 37,3%, GOS 4 = 26,7%, GOS 5 = 29,3%, final GOS scores were 1 = 1,2%, 2 = 1,7%, 3 = 21,8%, 4 = 36,2%, and 5 = 39,1% of all patients at the end of rehabilitation. Mean duration for both “B” and “C” was 41 days compared to 80 days for “D” and “E”. An assessment of both GCS and GOS was insufficient (Fig. 1).

Posttraumatic epileptic seizures have an incidence of about 10% in series of severe head injuries. Control of “early seizures”, i.e. those occurring in the first week after injury, is mandatory. Attacks, especially if recurrent, may add secondary damage to the injured brain: intravenous phenythoin with therapeutic plasma level allows control of the attacks. Seizures occurring months or years after injury are called “late seizures”: recurring “late seizures” make up the clinical syndrome of “posttraumatic epilepsy”. “Prophylaxis” should mean that drug treatment, given for a more or less prolonged period of time, blocks permanently the ripening of the epileptogenic foci avoiding the occurrence of seizures. In animal “prophylaxis” by antiepileptic drugs seems efficacious in many experimental models including iron induced epilepsy which is considered a model of posttraumatic epilepsy and vice versa. In the human being “prophylaxis” has been attempted with: phenytoin, phenobarbital, carbamazepine, valproate but without success. During treatment period the occurrence of seizures is prevented but, after discontinuation of the drug, seizures occur just as in non treated patients. The ripening of the epileptic focus in posttraumatic epilepsy, as in iron induced epilepsy, seems to be due to a cascade of events beginning with haemorrhage, haemolysis, iron or heme compound liberation, free radical formation, peroxidation and cell death. Experimentally free radical scavengers and antiperoxidants have marked prophylactic effect. Some of them (phosphate diester of vitamin E and C, melatonin, vanillyl alcohol) may be employed in clinical practice, but up to date there is no controlled study in human beings.

Background No studies exist dealing with the outcome of dysphagic patients with posterior fossa (IV. ventricle) tumours (PFT) or cerebellar hemorrhage (CH), and the outcome of patients with Wallenberg’s syndrome (WS) after functional swallowing therapy (FST) has so far not been studied in detail. Patients and methods 208 patients with neurogenic dysphagia (ND) who were consecutively admitted for functional swallowing therapy (FST) over a 3 year period to our hospital were examined clinically, by use of a videofluoroscopic swallowing study (VFSS) and/or fibreoptic evaluation of swallowing (FEES). The most frequent etiology was stroke (48%), followed by CNS tumours (13%). In the present study we defined three groups. Group 1 comprised 8 patients with PFT or CH. Group 2 consisted of 27 patients with WS, which was the leading cause among patients with non-hemispheric stroke. Since in WS a vagal nerve paresis due to affection of the Nucleus ambiguus occurs, 8 patients with Avellis’ syndrome or unilateral paresis of the vagal nerve served as controls and were defined as group 3. Findings In the three groups, functional feeding status showed significant improvement after FST comprising methods of restitution, compensation and adaptation, each of which were applied in more than 80% of patients. Outcome was, however, significantly worse in group 1 as compared to group 2 and in group 2 as compared to group 3. Dysfunction of the upper esophageal sphincter and reflex triggering were significantly more severely disturbed in groups 1 and 2 as compared to group 3. Group 1 showed significantly more severe disturbances of the oral phase as compared to groups 2 and 3. After FST, more than 50% (5/8) of group 1 and 30% (8/27) of WS patients (group 2) were dependent on tube feeding, whereas all patients of group 3 were full-oral feeders. Interpretation This is the first study dealing with the outcome of dysphagic patients with PFT or CH. Based on our results it can be assumed that in these patients pressure is exerted on both dorsomedial central pattern generators (DMCPGs) for swallowing in a posterior-anterior direction. Due to the importance of the DMCPGs for swallowing, bilateral (and often MRI-invisible) lesions seem to be very harmful. For a better understanding of the pathomechanism responsible for ND in patients with PFT or CH, modern imaging methods such as proton magnetic resonance spectroscopy should be used for studying metabolic changes in the dorsal medulla in the future. Since the outcome of patients with WS with regard to dependence of tube feeding was not associated with the site or size of the lesion, it may — due to the individual asymmetry of the swallowing-dominant forebrain hemisphere — depend on the side of the medullary infarction.

Patients with moderately severe to severe traumatic brain injury (TBI) can demonstrate disturbances in self-awareness several months or years after injury. Patients may underreport cognitive and behavioral difficulties, which are the true residuals of their brain injury. Increasingly, research indicates that the residuals of these disturbances in consciousness greatly affect the process and outcome of rehabilitation. A recent model for conceptualizing disturbances of self-awareness after various forms of brain injury is reviewed.

Background Health-related quality of life (HRQOL) associated or not with the measurement of neuropsychological functioning is a relatively new outcome variable in the field of traumatic brain injury (TBI). In both cases, accuracy and precision are increased in outcome estimation. Validation of generic, cross-culturally (cc) administered HRQOL measures in persons after TBI is not yet well established. Disease-specific HRQOL instruments do not exist in an international context. The objective here is to present the TBI consensus group’s (QOLIBRI-Group) approach in cc development of a specific HRQOL measure — the QOLIBRI (Quality of Life after Brain Injury). Methods Special issues of TBI-specific instrument creation will be highlighted as well as cc questionnaire construction, development, translation and psychometric testing. Results The validation process of the preliminary version of the disease-specific QOLIBRI in 15 countries and 13 languages will be described. The QOLIBRI assesses HRQOL within six domains (physical condition, thinking activities, feelings and emotions, functioning in daily life, relationships and social/leisure activities, current situation and future prospects). The QOLIBRI integrates disease-specific issues of TBI patients, i.e. cognition, existential aspects (as the sense of self ) etc., which are missing in generic tools. Conclusion In TBI patients, generic and disease-specific aspects of HRQOL need to be assessed with measures of adequate psychometric quality, applicable across different populations and cultural conditions. The QOLIBRI is a promising instrument for sensitive patient-centered specific outcome evaluation after TBI.

The term “RNA editing” is used to identify any mechanism responsible for producing mRNA molecules with sequence information not specifically encoded in the DNA. RNA editing is therefore an important event in gene modification, which takes place at a post-transcriptional level. The molecular mechanism of RNA editing involves site-selective deamination of adenosine to inosine in pre-mRNA, which leads to altering translation codons and splicing in nuclear transcripts, whereby functionally distinct proteins can be produced from a single gene. The mammalian editing enzymes ADARs (adenosine deaminases acting on RNA) are widely expressed in brain and other tissues: however, up until now their substrates have mainly been found in the Central Nervous System (CNS). Of particular relevance in the CNS is the editing occurring at the ionotropic glutamate receptors (GluRs) level. Three AMPA and two Kainate receptors are subject to RNA editing. The consequence of this process is the substitution of specific amino acids in functionally critical positions of the receptors. Depending on the GluR involved, the consequences of editing will involve: activation and/or inhibition of splicing sites; modulation of the trafficking of the receptor to the plasma membrane; the process of tetramerization of the receptor subunits; modification of the ions passage through the receptor channel; modulation of the desensitization and action potential recovery times. All these events are specific to the different GluRs and are genetically and developmentally controlled. RNA editing is therefore a crucial event involved in controlling transmission of the action potential at the postsynaptic level. This modulation involves the transmission of all sensory stimuli to the CNS and gives rise to the “Sensotype”. The Sensotype therefore defines the “way” in which the information acquired from the environment by the sensory systems is transmitted to the brain. The signals and inputs deriving from the Sensotype are transmitted to the brain, which processes and stores these signals thus generating the “Brainotype”. Brainotype and Sensotype are genetically and environmentally determined; they are individually unique and specific to every living organism with a nervous system. Their characteristics are, at least in part, dependent on the modulation of the “RNA editing” process since glutamate receptors represent the main neurotransmitter system in the CNS.

NF-κB is a nuclear transcription factor involved in the control of fundamental cellular functions including regulation of cell survival. We investigated NF-κB activation induced by two opposing modulators of cell viability: IL-1β and glutamate. We found that IL-1β activated p50, p65 and c-Rel subunits of NF-κB, while glutamate activated only p50 and p65 proteins. Cell stimulation by glutamate, correlated with expression of the pro-apoptotic genes Caspase-3, Caspase-2L and Bax. Conversely, IL-1β induced the expression of the short anti-apoptotic isoform of Caspase-2. Finally, we analysed the effect of the inhibition of IκBα degradation on glutamate-induced toxicity by using BAY 11-7082, a selective inhibitor of IκBα phosphorylation. Our results suggest that BAY 11-7082 preserves neuron viability from the glutamate-mediated injury.

Recovery after focal brain lesions is supposed to be mediated by cerebral reorganization. Stroke is a powerful model to study these processes in the human brain, since middle cerebral artery infarction is a common neurological disease with a clearly defined onset of a lateralized sensorimotor deficit syndrome. Brain tumours constitute a further model differing from stroke by their slow lesion dynamics. Evidence from functional neuroimaging and transcranial magnetic stimulation will be presented showing that recovery of hand function is related to reorganization of local perilesional and large-scale circuits involving the contralesional hemisphere.

In neurorehabilitation, transcranial magnetic stimulation (TMS) offers information regarding prognosis and pathophysiology and could also be useful for therapeutic purposes. Numerous studies have indicated that, after stroke, the absence of motor evoked potentials is associated with a poor motor recovery. In contrast, MEPs obtained in the paretic muscle with low stimulus intensities suggest a good restitution of motor function. TMS studies have shown that the location of a brain lesion determines motor cortex excitability changes: Patients with central somatosensory lesions show a disinhibition in the ipsilesional motor cortex. Lesions in the territory of the superior cerebellar artery are associated with a loss of motor cortex excitability. Stroke patients participating in a Constraint-induced movement therapy show an enlargement of the motor output area in the affected hemisphere after therapy. This enhancement of motor excitability is associated with an improvement of motor function. Some evidence is emerging that the application of low frequency repetitive TMS over the non-lesioned hemisphere improves neglect phenomena by down-regulation of the excitability of the non-lesioned hemisphere.