[Quality standards in treatment and rehabilitation of traumatic brain injuries]. / Qualitätsstandards in der Behandlung und Rehabilitation von Schädel-Hirn-Verletzungen.

The quality standards of the "Deutsche gesetzliche Unfallversicherung" (DGUV) on the treatment of traumatic brain injuries were first published in 2015. They describe the optimal conditions and requirements of acute treatment and in all phases of rehabilitation and aftercare, according to the current state of knowledge. The aim is to enable a life worth living in family, school, occupation and society for as many injuries as possible. The quality standards, as systematic orientation and decision-making aids, should promote the future development of the treatment and rehabilitation of traumatic brain injuries of all grades of severity and guarantee a uniformly high quality of treatment. A special and comprehensive rehabilitative alignment as well as a close networking of medical and occupation-promoting services will be of particular importance for the institutions participating in the rehabilitation of patients with traumatic brain injuries.

Guidelines for the Treatment of Head Injury in Adults.

The workshop of scientific medical faculties (Arbeitsgemeinschaft wissenschaftlicher medizinischer Fakultäten [AWMF]) of Germany has asked societies of specific medical disciplines to jointly publish guidelines on the treatment of diseases and injuries. On behalf of the Deutsche Gesellschaft für Neurochirurgie, its commission on guidelines initiated an interdisciplinary approach to publish guidelines on the treatment of head injury in adults. These guidelines were published in German by the AWMF in late 2015. Because these guidelines have received widespread attention in Germany and became fundamental for research in head injuries, we have translated the German version into English to make it accessible to the international scientific community.

[Mental disorders after mild traumatic brain injury]. / Psychische Störungen nach leichtem Schädel-Hirn-Trauma.

Mild traumatic brain injury (mTBI) is a frequent neurological disorder following a closed head injury. It is often accompanied by temporary changes of consciousness as well as cognitive, emotional and physical symptoms. These symptoms subside in the vast majority of affected persons within a few weeks; however, in recent years it has become increasingly more apparent that functionally significant long-term effects can remain after an initially diagnosed mTBI. In these cases mental disorders, such as impairment of cognitive and emotional functions as well as somatic disorders play an important role. This article presents the frequency, diagnosis, therapy and possible mechanisms of cognitive and emotional dysfunction after mTBI, including medicolegal aspects.

Behavioural and neurophysiological markers reveal differential sensitivity to homeostatic interactions between centrally and peripherally applied passive stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is an effective tool for inducing functional plastic changes in the brain. rTMS can also potentiate the effects of other interventions such as tactile coactivation, a form of repetitive stimulation, when both are applied simultaneously. In this study, we investigated the interaction of these techniques in affecting tactile acuity and cortical excitability, measured with somatosensory evoked potentials after paired median nerve stimulation. We first applied a session of 5-Hz rTMS, followed by a session of tactile repetitive stimulation, consisting of intermittent high-frequency tactile stimulation (iHFS) to a group of 15 healthy volunteers ("rTMS + iHFS" group). In a second group ("rTMS w/o iHFS"), rTMS was applied without iHFS, with a third assessment performed after a similar wait period. In the rTMS w/o iHFS group, the 5-Hz rTMS induced an increase in cortical excitability that continued to build for at least 25 min after stimulation, with the effect on excitability after the wait period being inversely correlated to the baseline state. In the rTMS + iHFS group, the second intervention prevented the continued increase in excitability after rTMS. In contrast to the effect on cortical excitability, rTMS produced an improvement in tactile acuity that remained stable until the last assessment, independent of the presence or absence of iHFS. Our results show that these methods can interact homeostatically when used consecutively, and suggest that different measures of cortical plasticity are differentially susceptible to homeostatic interactions.

Bilateral somatosensory cortex disinhibition in complex regional pain syndrome type I.

OBJECTIVE: In a previous study, we found bilateral disinhibition in the motor cortex of patients with complex regional pain syndrome (CRPS). This finding suggests a complex dysfunction of central motor-sensory circuits. The aim of our present study was to assess possible bilateral excitability changes in the somatosensory system of patients with CRPS. METHODS: We measured paired-pulse suppression of somatosensory evoked potentials in 21 patients with unilateral CRPS I involving the hand. Eleven patients with upper limb pain of non-neuropathic origin and 21 healthy subjects served as controls. Innocuous paired-pulse stimulation of the median nerve was either performed at the affected and the unaffected hand, or at the dominant hand of healthy controls, respectively. RESULTS: We found a significant reduction of paired-pulse suppression in both sides of patients with CRPS, compared with control patients and healthy control subjects. CONCLUSION: These findings resemble our findings in the motor system and strongly support the hypothesis of a bilateral complex impairment of central motor-sensory circuits in CRPS I.

Functional imaging of central nervous system involvement in complex regional pain syndrome.

SUMMARY: In complex regional pain syndrome (CRPS), functional imaging studies gave evidence for an important role of the central nervous system (CNS) in the pathogenesis of the disease. Especially, reorganization in central somatosensory and motor networks was demonstrated, leading to an altered central processing of tactile and nociceptive stimuli, as well as to an altered cerebral organization of movement. These findings may explain a number of clinical signs and symptoms occurring in the course of the disease and seem to be closely related to chronic pain in CRPS. Neurorehabilitative strategies, which target cortical areas and aim to restore impaired sensorimotor function in patients with CRPS, therefore, may be effective not only in restoring impaired function but also in pain reduction. This article reviews findings of functional imaging studies, which have been conducted to clarify CNS involvement in the course of CRPS.

Transcallosal inhibition across the menstrual cycle: a TMS study.

OBJECTIVE: To determine if there are steroid-dependent changes in transcallosal transfer during the menstrual cycle in normal women. METHODS: We tested 13 normally cycling women during the menstrual, follicular and midluteal phases. Blood levels of estradiol (E) and progesterone (P) were determined by radioimmunoassay. Ipsilateral tonic voluntary muscle activity suppression, called ipsilateral silent period (iSP), was evoked by applying transcranial magnetic stimulation (TMS) over the left motor cortex and by measuring the EMG of the ipsilateral first dorsal interosseus (FDI) muscle. Both iSP-duration and transcallosal conduction times were measured and related to cycle phase and steroid levels. RESULTS: Duration of iSPs varied over the cycle with largest differences between follicular and midluteal phases. During the midluteal phase high levels of P were significantly related to short iSPs. This relation also applied to E levels and iSPs during the follicular phase. CONCLUSIONS: Our study shows for the first time that the transcallosal transfer is modulated by E and P and changes over the menstrual cycle. SIGNIFICANCE: It is suggested that gonadal steroid hormones affect the interhemispheric interaction and change the functional cerebral organization sex dependently via its neuromodulatory properties on GABAergic and glutamatergic neurons.

[Visual cortex in the Tolosa-Hunt syndrome. Functional imaging for the detection of a psychogenic disorder--a case report]. / Visusstörungen beim Tolosa-Hunt-Syndrom. Untersuchung mit der funktionellen Magnetresonanztomographie zur Abgrenzung psychogener Störungen--Ein Fallbericht.

Besides painful ophthalmoplegia, patients suffering from Tolosa-Hunt syndrome often present increasing loss of visual perception. The impairment of the optic nerve leads to a delay of the VEP (visual evoked potentials) responses. Using the method of magnetic resonance imaging (MRI), some patients present unspecific alterations in the vicinity of the optic nerve. However, both methods (VEP and MRI) are unsuitable to assess the effect of an impaired optic nerve function on neuronal processing in the visual cortex. We report one patient suffering from Tolosa-Hunt syndrome affecting the optic nerve. We used fMRI (functional magnetic resonance imaging) to show how this impairment of the optic nerve alters cortical processing of visual information. The activity of the unaffected visual cortex was bilaterally reduced when compared to healthy volunteers but greater that obtained from patients suffering from bilateral occipital infarction. Our results offer new opportunities to assess the efficiency of therapy in patients with increasing loss of visual perception due to the Tolosa-Hunt syndrome. Further studies are necessary to investigate, whether fMRI also provides the possibility to assess the efficiency of drug therapy on optic nerve function.

Amphetamine enhances training-induced motor cortex plasticity.

OBJECTIVES: Repetitive synchronized movements lead to short-term plastic changes in the primary motor cortex, which can be assessed by transcranial magnetic stimulation (TMS). Drugs which enhance such plastic changes could be of therapeutical interest, e.g. in patients with cerebral lesions. MATERIAL AND METHODS: We studied the effect of amphetamine on motor performance and plastic changes in the motor cortex as revealed by TMS mapping in healthy humans, who had to train a repetitive synchronized movement over 1 h. RESULTS: Cortical plastic changes observed after 1 h of training were more pronounced with amphetamine, whereas motor performance did not differ between training sessions with and without amphetamine. CONCLUSION: We conclude that amphetamine is able to enhance training-induced motor cortex plasticity. This effect could be due to its known influence on the GABAergic and glutamatergic system, but might also result from its role as an indirect catecholaminergic agonist.

[Therapeutic use of cannabinoids in neurology]. / Therapeutischer Einsatz von Cannabinoiden bei neurologischen Erkrankungen.

This review gives insight into the potential therapeutical role of cannabinoids in neurology. Preclinical data are presented which could give a rationale for the clinical use of cannabinoids in the fields of multiple sclerosis, spasticity, epilepsy, movement disorders, and neuroprotection after traumatic head injury or ischemic stroke. Besides, clinical data (case reports, open-label and randomised controlled studies) dealing with the therapeutical use of cannabinoids in these fields are reported and discussed. At present, clinical data are insufficient to recommend the use of cannabinoids in any neurological disease as standard therapy. Several questions still have to be answered (which cannabinoid? which way of administration? stimulation of endogenous cannabinoids? separation between desired and undesired effects?), and controlled studies are still needed to clarify the potential therapeutical role of cannabinoids in neurology.

Bilateral motor cortex disinhibition in complex regional pain syndrome (CRPS) type I of the hand.

BACKGROUND: Complex regional pain syndrome type I (CRPS I) develops as a consequence of trauma affecting the limbs, without obvious nerve lesion. Its features include pain, edema, autonomic dysfunction, movement disorder, and trophic changes. CNS involvement is suggested by the symptoms, but the pathophysiology of CRPS I is unknown. OBJECTIVE: To assess excitability changes in the motor cortex in patients with CRPS I. METHODS: The authors studied 25 patients with unilateral CRPS I involving the hand by means of transcranial magnetic stimulation using a paired-pulse paradigm. Motor threshold (MT) and intracortical inhibition and facilitation were determined on the affected and the clinically unaffected side. A control group of 20 healthy subjects was studied. RESULTS: The authors found a significant reduction of intracortical inhibition on both sides of patients with CRPS compared with control subjects, whereas intracortical facilitation and MT did not differ significantly. However, in the patients' group, the presence of allodynia significantly decreased MT. CONCLUSIONS: The authors showed a bilateral disinhibition of the motor cortex in patients with complex regional pain syndrome.

NMDA-mediated mechanisms in cortical excitability changes after limb amputation.

OBJECTIVES: The aim of our study was to determine the role of N-methyl-d-aspartate (NMDA)-mediated mechanisms in cortical excitability changes after limb amputation, and their possible relationship to phantom pain. MATERIALS AND METHODS: Sixteen upper limb amputees who were suffering from chronic phantom pain received the NMDA-antagonist memantine or placebo for 3 weeks. Intracortical inhibition (ICI) and intracortical facilitation (ICF) were determined at baseline and on day 21 using transcranial magnetic stimulation. Simultaneously, phantom pain intensity was assessed. RESULTS: Memantine reduced ICF and enhanced ICI to roughly the same extent as seen in healthy subjects in a previous study. These changes were not correlated to the reduction of phantom pain. CONCLUSION: We therefore conclude that NMDA-mediated mechanisms influence changes of ICI and ICF occurring after limb amputation. However, our results suggest that these cortical excitability changes and phantom pain are independent of each other.

Repetitive training of a synchronised movement induces short-term plastic changes in the human primary somatosensory cortex.

The aim of our study was to assess possible short-term plastic changes in the human primary somatosensory cortex (S1) induced by a repetitive synchronised movement of the right thumb and shoulder. We therefore performed a source localisation of somatosensory evoked potentials after median nerve stimulation in twelve healthy subjects before and after 1 h of motor training. We found a significant medial shift of the N20 dipole on the left hemisphere after training, whereas the dipole location on the right hemisphere remained unchanged. However, no significant correlation was seen between the dipole shift and the improvement in motor performance. We conclude that repetitive synchronised movements are able to induce plastic changes in the contralateral S1, which might be mainly due to the synchronised proprioceptive input.

Shifts in cortical representations predict human discrimination improvement.

We report experiments combining assessment of spatial tactile discrimination behavior and measurements of somatosensory-evoked potentials in human subjects before and after short-term plastic changes to demonstrate a causal link between the degree of altered performance and reorganization. Plastic changes were induced by a Hebbian coactivation protocol of simultaneous pairing of tactile stimuli. As a result of coactivation, spatial discrimination thresholds were lowered; however, the amount of discrimination improvement was variable across subjects. Analysis of somatosensory-evoked potentials revealed a significant, but also variable shift in the localization of the N20-dipole of the index finger that was coactivated. The Euclidean distance between the dipole pre- and post-coactivation was significantly larger on the coactivated side (mean 9.13 +/- 3.4 mm) than on the control side (mean 4.90 +/- 2.7 mm, P = 0.008). Changes of polar angles indicated a lateral and inferior shift on the postcentral gyrus of the left hemisphere representing the coactivated index finger. To explore how far the variability of improvement was reflected in the degree of reorganization, we correlated the perceptual changes with the N20-dipole shifts. We found that the changes in discrimination abilities could be predicted from the changes in dipole localization. Little gain in spatial discrimination was associated with small changes in dipole shifts. In contrast, subjects who showed a large cortical reorganization also had lowest thresholds. All changes were highly selective as no transfer to the index finger of the opposite, non-coactivated hand was found. Our results indicate that human spatial discrimination performance is subject to improvement on a short time scale by a Hebbian stimulation protocol without invoking training, attention, or reinforcement. Plastic processes related to the improvement were localized in primary somatosensory cortex and were scaled with the degree of the individual perceptual improvement.

Assessment of reorganization in the sensorimotor cortex after upper limb amputation.

OBJECTIVE: We wanted to investigate plastic changes occurring in the motor and somatosensory cortex after upper limb amputation, and their possible relationship to phantom pain. METHOD: To assess these plastic changes, we used transcranial magnetic stimulation (TMS) and source localization of somatosensory evoked potentials (SEP). Eleven patients with upper limb amputation were investigated. The phantom pain intensity was assessed by visual analogue scaling (VAS). RESULTS: Using TMS mapping, we found a significant lateralization of the amplitude-weighted centre of gravity (P<0.01) and an enlargement of the excitable area (P<0.05) on the hemisphere contralateral to the amputation. SEP mapping showed a significant medialization of the N20 dipole (P<0.05) on this side. None of these changes correlated with the phantom pain intensity. CONCLUSIONS: We conclude that after limb amputation, the relationship between plastic changes occurring in the sensorimotor cortex and phantom pain seems to be more complex than previously believed.

Changes of cortical excitability in patients with upper limb amputation.

In our study we wanted to assess motor excitability in patients with upper limb amputation by means of transcranial magnetic stimulation (TMS). In 12 patients, TMS was applied using a paired pulse paradigm in order to test cortico-cortical excitability. Additional parameters of motor excitability like motor threshold and cortical silent period were also measured. Recordings from the amputated side were compared to the contralateral side and to healthy controls. We found a significant reduction of intracortical inhibition in forearm amputees and an enhancement of intracortical facilitation in upper arm amputees on the affected side. We conclude that after upper limb amputation, changes in the activity of intracortical interneuronal circuits appear in the affected hemisphere. These changes may depend on the level of amputation, and be the base of cortical reorganization.

Riluzole suppresses motor cortex facilitation in correlation to its plasma level. A study using transcranial magnetic stimulation.

The aim of our study was to measure the effects of the glutamate antagonist riluzole on different parameters of motor excitability, using transcranial magnetic stimulation (TMS) during 7 days of riluzole administration, and to correlate these effects with riluzole plasma levels. Nine healthy volunteers received a dose of 100 mg riluzole from day 1 to 7 of the study period. Electrophysiological examinations were performed on day 1 before and 2 h, 5 h and 8 h after riluzole administration, on day 2, day 3 and day 5 before riluzole administration, and on day 8. Plasma samples were taken simultaneously. The excitability of the motor cortex, supraspinal and spinal motor pathways was tested by studying intracortical facilitation and inhibition, the cortical silent period and motor threshold after TMS, as well as the peripheral silent period and F-wave amplitudes after electrical peripheral nerve stimulation. We found a significant reduction of intracortical facilitation, which correlated significantly with riluzole plasma levels. To a lesser extent, intracortical inhibition was enhanced on day 1, motor threshold was increased on day 8 and F-wave amplitudes were reduced. These changes did not correlate with riluzole plasma levels. We conclude that the main effect of riluzole in vivo is a reduction of intracortical facilitation, which is closely related to the drug's level in the plasma. The most probable mechanism involves an effect on glutamatergic synaptic transmission.

Assessment of postexcitatory inhibition in patients with focal dystonia.

The aim of our present study was to detect whether a generalized disturbance of intracortical inhibitory mechanisms as assessed by transcranial magnetic stimulation (TMS) can be observed in a movement disorder with localized clinical expression, that is, in focal cervical dystonia. We measured motor threshold intensity, central motor conduction time and the duration of postexcitatory inhibition evoked by single and paired stimuli TMS from a small hand muscle in 20 patients with idiopathic cervical dystonia, and 21 healthy volunteers. A significant difference could not be found in any of the neurophysiological parameters between patients and controls. These findings are unlike the observations made in Parkinson's disease and Huntington's disease, where significant changes of postexcitatory inhibition after TMS can be observed. This suggests a lack of widespread change in activity of underlying cortical inhibitory mechanisms, as seen in other diseases of the extrapyramidal system with more generalized clinical involvement.