A review of published reports on neuroprotection in spinal cord injury.

STUDY DESIGN: Literature review. OBJECTIVES: To review the main published current neuroprotection research trends and results in spinal cord injury (SCI). SETTING: This paper is the result of a collaboration between a group of European scientists. METHODS: Recent studies, especially in genetic, immune, histochemical and bio (nano)-technological fields, have provided new insight into the cellular and molecular mechanisms occurring within the central nervous system (NS), including SCIs. As a consequence, a new spectrum of therapies aiming to antagonize the 'secondary injury' pathways (that is, to provide neuroprotection) and also to repair such classically irreparable structures is emerging. We reviewed the most significant published works related to such novel, but not yet entirely validated, clinical practice therapies. RESULTS: There have been identified many molecules, primarily expressed by heterogenous glial and neural subpopulations of cells, which are directly or indirectly critical for tissue damaging/sparing/re-growth inhibiting, angiogenesis and neural plasticity, and also various substances/energy vectors with regenerative properties, such as MAG (myelin-associated glycoprotein), Omgp (oligodendrocyte myelin glycoprotein), KDI (synthetic: Lysine-Asparagine-Isoleucine 'gamma-1 of Laminin Kainat Domain'), Nogo (Neurite outgrowth inhibitor), NgR (Nogo protein Receptor), the Rho signaling pathway (superfamily of 'Rho-dopsin gene-including neurotransmitter-receptors'), EphA4 (Ephrine), GFAP (Glial Fibrillary Acidic Protein), different subtypes of serotonergic and glutamatergic receptors, antigens, antibodies, immune modulators, adhesion molecules, scavengers, neurotrophic factors, enzymes, hormones, collagen scar inhibitors, remyelinating agents and neurogenetic/plasticity inducers, all aiming to preserve/re-establish the morphology and functional connections across the lesion site. Accordingly, modern research and experimental SCI therapies focus on several intricate, rather overlapping, therapeutic objectives and means, such as neuroprotective, neurotrophic, neurorestorative, neuroreparative, neuroregenerative, neuro(re)constructive and neurogenetic interventions. CONCLUSION: The first three of these therapeutical directions are generically assimilated as neuroprotective, and are synthetically presented and commented in this paper in an attempt to conceptually systematize them; thus, the aim of this article is, by emphasizing the state-of-the art in the domain, to optimize theoretical support in selecting the most effective pharmacological and physical interventions for preventing, as much as possible, paralysis, and for maximizing recovery chances after SCI.

Restoration of locomotion in posttraumatic paraplegics: the multidisciplinary approach and unexpected plasticity of single neurons--facts and fantasy.

In Europe there are about 300,000 paraplegics and in every country approximately 1000 new cases per year. Treatment requires a multidisciplinary approach with scientific cooperation targeted to exchange personal knowledge and expertise. At present a completely disrupted spinal cord cannot heal for recovery of motor and/or sensory functioning, although some promising treatment modalities in laboratory animal experiments have been reported. No interventional stem cell procedure so far has shown evidence to restore impaired functioning in human paraplegics. However, functional electrical stimulation (FES) via an implanted neuroprosthesis (SUAW concept) and central nervous system-peripheral nervous system (CNS-PNS) connection have successfully been used for alternative compensatory strategies for voluntary locomotion. This report is to analyse the authors' experience from two European projects in paraplegic. Factors will be identified that might have caused the one or other pitfall since so far both surgical reconstructive procedures have not been adopted by rehabilitation physicians and/or restorative (neuro-)surgeons despite the promising functional results we have achieved. Unexpected plasticity of single neurons following CNS-PNS by-pass procedures is discussed. Future interventions, for example the present phase 1 prospective multiple centre study on the side effects, effectiveness, and reliability of intrathecal treatment of anti-Nogo-A antibodies, are presented and the Chinese stem cell implantation is critically reviewed.

Posttraumatic rehabilitation and one year outcome following acute traumatic brain injury (TBI): data from the well defined population based German Prospective Study 2000-2002.

Follow-up examination to review the one-year outcome of patients after craniocerebral trauma with respect to health related quality of life (QoL) and social reintegration. The data are derived from the prospective controlled, well defined population based, multiple centre study that was performed in Germany for the first time in the years 2000-2001 with emphasis on quality management (structural, process, outcome) and regarding the patient's age, physical troubles, and impaired mental-cognitive, neurobehavioral functioning. TBI severity assessment is according to the Glasgow Coma Scale (GCS) score. Early outcome after rehabilitation is assessed by the Glasgow Outcome Scale (GOS) score of patients following rehabilitation and of 63% of all TBI with the aid of follow-up examination (simplified questionnaire) after one year. Catchment areas are Hanover (industrial) and Münster (more rural) with 2,114 million inhabitants. TBI is diagnosed according to ICD 10 S-02, S-04, S-06, S-07, S-09 with at least two of the following symptoms: dizziness or vomiting; retrograde or anterograde amnesia, impaired consciousness, skull fracture, and/or focal neurological impairment. Within one year 6.783 patients (58% male) were examined in the regional hospitals after acute TBI. The regional TBI incidence regarding hospital admission was 321/100.000 TBI. 28% of patients were < 1 to 15 years, 18% > 65 years of age. GCS was only assessed in 55% of patients. They were 90.9% mild, 3.9% moderate, and 5.2% severe TBI. A total of 5.221 TBI (= 77%) was hospitalised; 1.4% of them died. Only 258 patients (= 4.9%) of the hospitalized TBI received in-hospital neurorehabilitation (73% male), 68% within one month after injury. They were 10.9% severe, 23.4% moderate, and 65.7 mild TBI. 5% were < 16 years, 25% > 65 years. One-year follow-up examinations of 4307 individuals (= 63.5% of all TBI) are discussed. A total of 883 patients (= 20.6%) reported posttraumatic troubles, one half were > 64 years. One hundred and sixty patients (= 3.8%) could manage their daily life only partly; 75 TBI (= 87.2%) following mild, 5.8% moderate, and 7% severe TBI. One hundred and sixteen patients could not at all manage their activities in training, at school, or in their jobs (N = 33 MTBI respectively 54%), 6 (= 10%) moderate, and 22 (= 36%) severe TBI. 2.8% of individuals failed when compared with their pre-traumatic situation. TBI severity, patient's age, concomitant organ lesions, and complications influence health related QoL and early social reintegration.

Early rehabilitation of higher cortical brain functioning in neurosurgery, humanizing the restoration of human skills after acute brain lesions.

OBJECTIVE: Increasingly more patients after brain damage survive, however, suffering from severe impairments of higher cerebral functioning. METHODS: Patients after acute brain damage, mainly secondary to TBI, are referred for early neurosurgical rehabilitation. Our concept follows the German Guidelines. It is based on a multidisciplinary team approach. Next-of kin are included in the treatment and caring. RESULTS: The essential aspect of early neurosurgical rehabilitation is the integration of disciplines and consistent goal setting to regard individual patients' needs. Good structural organization of the team, notice of basic communication rules, conflict management and a definite decision making increase productive interdisciplinary working. The film (shown at the symposium) shows how to humanize human skills after brain damage. DISCUSSION: Obviously the impairment of mental-cognitive and neurobehavioral functioning and not the loss of physical skills cause the patients' loss of life transactions and final outcome after brain damage. Our concept supports and fosters the individuals' neural plasticity and final social reintegration. CONCLUSION: Functional rehabilitation is a process whereby patients regain their former abilities or, if full recovery is not possible, achieve their optimum physical, mental, social and vocational capacity. Neurosurgeons will have to work in close collaboration with the neuropsychologist and all other members of the interdisciplinary team day by day.

Functional neurorehabilitation in locked-in syndrome following C0-C1 decompression.

Today, thanks to intensive care treatment and modern diagnostic tools, increasingly more patients with severe brain and spinal cord lesions, mainly secondary to accidents, stroke, tumours, and congenital malformations survive the acute impact on the central nervous system (CNS). Complicated operative procedures and concomitant complication may also lead to severe impairment of the sensory motor and cognitive behavioural functioning as it can be described according to the WHO-ICF criteria. New developments of functional neurorehabilitation in neurosurgery can significantly improve patients' quality of life (QoL) in terms of both brain and body functioning and certain health-related components of well-being (such as social activities and leisure). Rehabilitation starts with assessment of the functional impairment and the underlying pathophysiology by using all modern diagnostic tools. Our concept of postoperative neurorehabilitation is exemplarily demonstrated in one patient who suffered from acute postoperative locked-in syndrome. Surgical decompression and fusion were required for post traumatic and recurrent congenital craniovertebral instability at C0-C1. Subsequent functional neurorehabilitation is based on careful planning in accordance with our concept of a holistic Spectrum of functional early Neurorehabilitation.

Quality management in traumatic brain injury (TBI) lessons from the prospective study in 6.800 patients after acute TBI in respect of neurorehabilitation.

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.

Quality of life in patients with traumatic brain injury-basic issues, assessment and recommendations.

INTRODUCTION: Traumatic brain injuries (TBI) are one of the most common consequences of traffic accidents. Patients with mild, moderate or severe brain injuries suffer from physical, cognitive, behavioral, emotional and social problems. Most of these problems have been a long standing focus amongst practitioners and researchers. Only recently a development has started that took interest in the quality of life outcome of TBI patients. The international members of this consensus meeting reviewed the literature on Quality of Life assessment after TBI and discussed the applicability of different measurements to this specific patient group. TIME POINTS: During the acute phase (T1; < 3 month after trauma) QoL it is difficult to assess due to the reduced consciousness of TBI patients. In the phase of rehabilitation (T2; < one year after trauma) and in the post-rehabilitation phase (T3) repeated assessment of QoL is recommended. INSTRUMENTS: Several generic and disease-specific instruments possibly relevant to TBI patients or specifically developed for this group were assessed according to the existing evidence in the literature. Criteria for the evaluation of these instruments were: feasibility, specificity, validity, comprehensiveness, international availability, existence of norms, and psychometric quality. The cognitive impairment and the existential dimension were not sufficiently considered in most of the reviewed instruments. GROUP CONSENSUS: The family's and relatives' view of the patient's QoL should not be used as a proxy but provides an additional source of information in the acute phase. At T2 and T3, assessment of the patient's quality of life should include a generic as well as a disease specific instrument. Among the generic instruments the SF-36, the EuroQol and the WHO-QoL should be considered. The literature about specific instruments for patients with TBI like the EBIC is scarce. Therefore, the group could hardly give an empirically based recommendation. The need for further investigation on QoL instruments in TBI patients is strongly emphasized.

New development of functional neurorehabilitation in neurosurgery.

OBJECTIVES: Today, increasingly more patients with severe brain and spinal cord lesions mainly secondary to accidents, violence, stroke, and tumours survive their injuries, in many cases, however, suffering from severe functional impairments of functioning as described by the WHO-ICF criteria. New developments of functional neurorehabilitation in neurosurgery could significantly improve the patients' quality of life (QoL) in terms of brain and body functioning and certain health-related components of well-being (such as social activities and leisure). METHODS: Functional rehabilitation is an original task of neurosurgery from the very outset. Advances in biotechnology regarding both basic research and clinical application have opened up a new and very promising field to restore or compensate impaired or definitively lost organic functions in addition to the conservative rehabilitation methods. RESULTS: Along with the scientific progress in biotechnology and functional MRI and PET, neurosurgeons have become increasingly interested and actively involved in rehabilitation science and neurosurgical re-engineering of the damaged brain and spinal cord. Some of them have developed new specially designed institutions for early (acute) and subacute neurorehabilitation. Attached to the acute services, neurosurgeons thus become responsible for neurorehabilitation and at the same time for the management of all kinds of complications, which significantly improves the early and late functional outcome. At the same time microelectronics, biotechnology, and genetic engineering are being introduced into the field of neurosurgical rehabilitation in a step-by-step manner. DISCUSSION: Progress in the fields of microelectronics, computer technology, and genetic engineering along with rehabilitation science is opening up a new field of unknown chances to partially restore lost body functions and to help improve the quality of life of disabled patients in the sense of ICF. Functional neurosurgery plays a major role in neurosurgical rehabilitation. e.g. functional electrostimulation, brain-stem implants, pain and epilepsy control, restoration of locomotion and grasp faculties, and the use of potent substances such as botulinum toxin (Btx). This demands the capacity of time work and the realization of the necessity to draw up a detailed plan for the restoration of impaired functions prior to enacting a neurosurgical intervention in the sense of a complex neurorehabilitation, and consequently to assume the responsibility for the patient's outcome. From the beginning of neurological surgery, the preservation and restoration of impaired brain and spinal-cord functions as an original task for neurosurgeons demand their involvement with issues of functional neurorehabilitation including neurosurgical re-engineering of the damaged brain and spinal cord. In this connection the close and trusting cooperation with the clinical neuropsychologist from the very outset is an indispensible factor.

Restoration of locomotion in paraplegics with aid of autologous bypass grafts for direct neurotisation of muscles by upper motor neurons--the future: surgery of the spinal cord?

OBJECTIVES: Paraplegia means a lifelong sentence of sensory loss, paralysis and dependence. Complete spinal cord lesions cannot heal up to now despite intensive experimental research, remarkable efforts and recent achievements in bio-technology and re-engineering. Traumatic paraplegia due to spinal cord injury (SCI) is a quite frequent condition and related to the socio-economical situation of the population. It is experienced disproportionately by young people. The rise in gunshot wounds is dramatic. SCI has appeared refractory to treatment. PATIENTS AND METHODS: Since 1980 G.A.B. had tried surgical repair of the spinal cord (SC) after experimental bisection in rats, and since 1993 research was done on monkeys (macaca fascicularis) to be closer to human physiology. The sciatic nerve was removed and used as an autologous graft from the lateral bundle of the spinal cord (tractus corticospinalis ventro lateralis) to the three muscles of both legs being known to be most important for locomotion: M. gluteus maximus, M. gluteus medius and M. quadriceps femoris. The first fruitful transplantation in a human being was performed in July 2000. RESULTS: The results in rats were promising and fulfilled the requirements of the American Task Force of the National Institute of Neurological and Communicative Disorders and Stroke of the US. The results in monkeys confirmed the paradigm so that we performed the first operation in a young lady suffering for four months from complete SC lesion T9 after approval by the ethical committee. First voluntary movements of the connected muscles after 17 months. 27 months after op she was able to walk up to 60 steps with the help of a walker and to climb steps in the water. Improvement is still continuing. DISCUSSION: SCI has appeared refractory to any kind of treatment. Compensatory strategies are still experimental in human beings. Autologous nerve grafts from the spinal cord tissue (the lateral spinal bundle) connected to peripheral muscle nerves seem promising in paraplegics. But the physiology is still unclear when the glutamatergic upper motor neuron connected to motor end-plates (cholinergic) does work like in our patient. CONCLUSION: Further studies in primates and paraplegic patients are necessary to clarify the bypass grafting of the SC to muscle groups distal to the complete SCI to restore locomotion.

Standards of neurologic-neurosurgical early rehabilitation--a concept of the study group neurological-neurosurgical early rehabilitation.

Neurological neurosurgical early rehabilitation (NNER) is a new important therapeutic link within the spectrum of neurorehabilitation. This concept was formulated by expert opinion of the German Task Force on NNER to define both the structural and process quality of rehabilitation in patients who sustained brain damage with sensory motor, cognitive, and neurobehavioural impairment. NNER is focused on improving higher nervous functions, preventing or treating secondary and tertiary complications and thus to recuse disabilities. This concept is based on interdisciplinary teamwork and needs multidisciplinary cooperation with all specialists involved. The progress of recovery can be measured with the aid of the Coma Remission Scale.

Incidence and management of complications during posttraumatic early rehabilitation.

Early rehabilitation after traumatic brain injury has become a worldwide accepted interface between intensive care medicine and rehabilitation to aim for a better functional outcome of the surviving patients. So each chain can only be as strong as its weakest link, and there is still need for well defined quality standards depending on the medical demands during this period of treatment. Hence we were interested in quantifying the complications occurring until discharge to further rehabilitation with special regard on severe physical handicaps and organ failure necessitating surgical or intensive care therapy. Our results demonstrate that early rehabilitation is a part of intensive care medicine with enhanced approaches to preserve rehabilitation potential of the brain and for coma stimulation.

Neurological and social long-term outcome after early rehabilitation following traumatic brain injury. 5-year report on 240 TBI patients.

The long term courses of patients after traumatic brain injury (TBI) are particularly influenced by the quality of neuropsychological rehabilitation and social reintegration. Though we do have data from different European countries about the success of surgery and intensive care, we don't know much about the long term courses, mirrored by the patients, their relatives and local physicians in their domestic environment. Supported by a pilot project of the government of Nordrhein--Westfalia we reviewed 252 patients with different grades of TBI, which were treated in our department from emergency to the end of early rehabilitation. At least 240 files could be completed, including observations up to 5 years after trauma (mean 26 months). 66% of the patients suffered from severe TBI according to the initial Glasgow Coma Scale (GCS), 23% showed moderate and 11% mild TBI. After discharge from early rehabilitation and during further treatment in rehabilitation hospitals patients with persistent vegetative state (PVS) did not show a significant benefit from therapy: Only 1 patient improved to GOS 3, fatal courses were observed in 3 patients, 11 patients remained unchanged. Patients with GOS 3 at the end of early rehabilitation on the other hand could improve in 51 cases to GOS 4 and 5. At the time of the actual investigation 32% of the patients reached GOS 5, 27% GOS 4. Unfavourable courses showed 21% (GOS 3), 5% (GOS 2) and 15% (GOS 1). Referred to the initial GCS only 16% of the severe, 27% of the moderate and 33% of the mild TBI could return to their former social activities and profession without any cuts. 145 of the total of surviving patients could return to their families, in the group of vegetative patients all except 1 patient were submitted for nursing homes. Only 58% of the patients practiced any kind of outpatient rehabilitation, a specialized neuropsychological training has been restricted to 7% of the patients. So we observe a significant gap between a high impact clinical medicine on one side and a deficient outpatient treatment on the other. At least many patients are standing alone after discharge from rehabilitation hospitals, resulting in prolonged stationary treatment with extensive costs to minimize damage from this situation. Our consequence for a more efficient treatment is, that we substantially need better programs by local administrations, insurance companies and employers for better and earlier reintegration to avoid isolation and unnecessary invalidation, especially of those patients with the best medical prognosis.