bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life after multiple trauma -- summary and	recommendations of the consensus conference
Authors: Neugebauer E. , Bouillon B. , Bullinger M. , Wood-Dauphinée S.
Published: December 2024

In October 1999, an international and interdisciplinary consensus conference was held about the assessment and application of quality of life (QoL) measures after multiple trauma. Four working groups represented the following patients: children with traumatic brain injury (TBI); adults with TBI, adults with multiple injuries (but without TBI), and adults with spinal cord injury. According to predefined questions, the groups tried to identify the relevant problems of the patients, at different time points after the traumatic event. A review of the existing instruments for quality of life assessment and the evidence of their application in trauma patients in the scientific literature was performed by each group. Based on the results of these literature reviews it was concluded that there are not enough data to establish "evidence-based" guidelines for QoL assessments in these patients. Nevertheless, the groups comprised of experts clinicians and methodologists, agreed on the Glasgow Outcome Scale and the SF-36 as generic tools for QoL assessment across all trauma patients. It was further recommended to use these generic tools in combination with condition-specific instruments to better reflect the specific problems of the patients. Finally, the whole group suggested that it was not appropriate to view this conference as a "final report" about QoL assessment in trauma patients, but rather it should be seen as a starting point for increased efforts to initiate clinical research projects using QoL as an outcome, to develop better instruments, and to include QoL assessments into daily routines.
Quality of life in patients with multiple injuries -- basic	issues, assessment, and recommendations
Authors: Bouillon B. , Kreder H.J. , the MI Consensus Group
Published: December 2024

Background: While the primary goal of trauma care continues to be the preservation of life, interest has begun to focus on disability and quality of life of those who survive. Numerous instruments have been developed to measure personal well-being, impairment, or subjective life-satisfaction. But there is no consensus regarding which instruments are most appropriate to use in multiply injured patients, and comparison of results are difficult.

Objective: The objective of this multinational conference was to arrive at a consensus regarding the measurement of quality of life in survivors of multiple trauma. Specifically we sought to identify the best time intervals for measurement and a minimum set of instruments.

Method: The group reviewed instruments currently in use for quality of life measurement in multiply injured patients. A structured discussion covered the following topics: definition of the population, the concept of quality of life, the importance of different domains of quality of life at different time points, the type of measures and their validity, consistency, and practicability, the mode of administration, subject burden, and availability of population norms.

Results: The group suggested three time points, after 3, 12 and 24 months, for the assessment of quality of life after multiple injury. The Glasgow Outcome Scale (GOS) was suggested as an overall global outcome measure including death and vegetative state. The EuroQol was proposed to permit economic analysis, and the SF-36 as a validated global quality of life measure.

Conclusion: While most selected measures are psychometrically sound, many have had limited use in the setting of multiple injuries. Researchers and clinicians may use these suggestions as a source of information when developing a measurement strategy.
Altered sensory input improves the accuracy of muscle	reinnervation
Authors: Skouras Emmanouil , Popratiloff Anastas , Guntinas-Lichius Orlando , Streppel Michael , Rehm Klaus E. , Neiss Wolfram F. , Angelov Doychin N.
Published: December 2024

{\it Purpose:} To improve functional recovery after peripheral nerve suture, we characterized the quality of target reinnervation in rats in which the afferent trigeminal connection to facial motoneurons had been altered.

{\it Methods:} Employing an improved lesion model and a refined mode of retrograde tracer application, we studied the accuracy of reinnervation in rats which underwent buccal-buccal nerve anastomosis (BBA) alone (group 1), BBA plus excision of the ipsilateral infraorbital nerve (ION; group 2), and BBA plus excision of the contralateral ION (group 3). This was done by comparison between the number of double-labeled motoneurons after pre-operative injection of Fluoro-Gold (FG) and post-operative injection of Fast Blue (FB) into the whisker pad muscles.

{\it Results:} In the first group we counted 398 ± 80 FG+FB double labeled cells (mean ± SD; n=9 rats), i.e., only 27% of all motoneurons that grew axons into the whisker pad had projected to these muscles before surgery. In group 2, this value was increased marginally to 436 ± 68 (32%). In group 3,. we counted 580 ± 63 double-labeled neurons. This is the first morphological report demonstrating significantly improved specificity of reinnervation. Indeed, 41% of the motoneurons innervating the target in group 3 belonged to the original neuron pool. These morphological findings are supported by evidence obtained from electrophysiological recordings and behavioural studies.

{\it Conclusions:} The principle finding of the present study is that a peripheral lesion to the contralateral trigeminal nerve improves the quality of reinnervation of the whisker pad musculature by its original nerve. The contralateral trigeminal lesion may trigger behavioural demand and forced overuse of the axotomized facial nerve, which may be a key issue for recovery of vibrissae rhythmical whisking after facial nerve surgery.
Brain activation pattern as assessed with multi-modal EEG analysis	predict motor recovery among stroke patients with mild arm paresis who receive	the Arm Ability Training
Authors: Platz T. , Kim I.-H. , Engel U. , Kieselbach A. , Mauritz K.-H.
Published: December 2024

{\it Purpose:} Receiving the Arm Ability Training for three weeks improves motor function among stroke patients with mild arm paresis. There is, however, a considerable variability in recovery among patients receiving the Arm Ability Training. The study investigated whether intersubject differences in movement-related electric brain activity explain the variability in motor recovery.

{\it Methods:} In a sample of 9 patients receiving the Arm Ability Training both motor performance using a standardised arm function test (TEMPA) and movement-related electric brain activity, i.e. slow cortical potentials (DC) as well as event-related desynchronisation of alpha (alpha-ERD) and beta activity (beta-ERD), were assessed before the Arm Ability Training was started. Stepwise multiple regression was used to establish the best predictive model for motor improvement scores (TEMPA difference from pre to post test three weeks later).

{\it Results:} Stepwise multiple regression indicated that electric brain activity during movement preparation explained the variance of motor improvement scores completely. Further, electric brain activity during movement as well as baseline motor performance accounted each for 50% of the variance of motor improvement scores.

{\it Conclusions:} Activation of sensorimotor areas during movement preparation and deactivation of other cortical areas during movement execution seem to be factors that predict a favourable outcome after training.
Experimental hyperthyroidism increases the effectiveness of	predegenerated peripheral nerve graft implantation into hippocampus of adult	rats
Authors: Lewin-Kowalik Joanna , Gołka Beata , Larysz-Brysz Magdalena , Świech-Sabuda Ewa , Granek Arkadiusz
Published: December 2024

Purpose: The aim of the study was to ascertain whether experimental hyperthyroidism changes the neurotrophic activity of 14- and 21-day-predegenerated peripheral nerve grafts towards CNS neurites. Methods: Hyperthyroidism was induced by subcutaneous injections of T $_4$ . Autologous peripheral nerve grafts were implanted into the hippocampus of both euthyrotic and hyperthyrotic animals 14 or 21 days after sciatic nerve transection (groups ET14, Et21, Ht14 and Ht21, respectively). Non-predegenerated grafts were used as a control group (groups EtN adn HtN). Cells extending their neurites into the grafts were traced with FITC-HRP. Results: The number of traced cells in individual groups was as follows: EtN -- 39.4 ± 9.46, Et14 -- 1 ± 0.94, Et21 - 0.6 ± 0.69; HtN -- 95 ± 19.46; Ht14 -- 95.94 ± 16.3, Ht21 -- 99.94 ± 7.26. Conclusions: We found that experimentally induced hyperthyroidism strongly enhanced the regeneration of injured hippocampal neurites after implantation of peripheral nerve grafts that were practically inactive in euthyrotic animals.
S100B and cardiac surgery: Possibilities and limitations
Authors: Jönsson Henrik
Published: December 2024

Serum determinations of the glial protein S100B has been found to correlate with brain damage after cardiac surgery. Forty-eight hours and later after surgery, increased S100B levels correlates with the presence of brain infarction, and the extent of infracted brain tissue. S100B at this time-point has been shown to predict long-term outcome, higher S100B levels correlated with decreased survival. Early levels (2–8 hours after surgery) of S100B have shown disparate results when trying to correlate it with postoperative cognitive decline. One reason for the lack of strong correlation could be the contamination of S100B from shed blood the first hours after surgery.
Brain derived proteins as markers of acute stroke: Their relation	to pathophysiology, outcome prediction and neuroprotective drug	monitoring
Authors: Herrmann Manfred , Ehrenreich Hannelore
Published: December 2024

Purpose: Ischemic stroke is associated with a variety pathophysiological changes affecting both glial and neuronal brain tissue. These changes are mirrored in the release of specific proteins into peripheral blood. Neurone-specific enolase (NSE), protein S100B and glial fibrillary acidic protein (GFAP) are those proteins investigated most often as peripheral surrogate markers of brain damage after stroke in humans.

Methods and results: In the present article we present data which show that the release patterns of neuronal and glial tissue derived proteins after acute stroke are associated with the neuroradiological and neurobehavioral consequences of ischemic brain lesions and, additionally, may be useful in short-term outcome prediction. Kinetics of protein serum concentrations, however, are highly dependent on subtype of stroke lesions and do not merely reflect the degree of brain damage. They rather express complex neuronal-glial interactions as a (patho-)physiological consequence of ischemic brain lesions. We further demonstrate that S100B release patterns do reflect successful neuroprotective drug treatment with recombinant human erythropoietin (EPO) in acute stroke patients.

Conclusions: The analysis of poststroke serum concentrations of glial tissue derived proteins might be a promising strategy to monitor and evaluate neuroprotective approaches in stroke treatment.
Differential diagnosis of neurodegenerative diseases with special	emphasis on Creutzfeldt-Jakob disease
Authors: Otto Markus , Wiltfang Jens
Published: December 2024

In principle, two research approaches can be considered for the laboratory diagnosis of transmissible spongiform encephalopathies (TSE): (i) the direct detection of PrP $^{Sc}$ and (ii) the detection of surrogate markers in biological materials that show an altered pattern of expression in early stages of the disease or are used in the differential diagnosis of other dementias and thus enable an exclusion diagnosis. This review concentrates on the second approach.

It was shown that a single determination of just a few markers (tau-protein, S-100B, 14-3-3-protein) was already sufficient to achieve a high degree of diagnostic certainty in the diagnosis of CJD. On the basis of the available data, it is to be expected that a combination of these markers will bring improved diagnostic strength with regard to the differential diagnosis of dementias as a whole. This especially applies to some of the subtypes of CJD and Alzheimer's dementia (AD).
A temporal study of axonal degeneration and glial scar formation	following a standardized crush injury of the optic nerve in the adult rat
Authors: Ohlsson Marcus , Mattsson Per , Svensson Mikael
Published: December 2024

Purpose: In this methodological study, we describe a standardized optic nerve injury model in adult rats. The temporal pattern of the glial response is mapped in relation to axonal regeneration and degeneration.

Methods: A standardized optic nerve crush injury was made in adult rats, using a fine pair of forceps with a preset pressure of 0.6~N during 10 seconds.

Results: This crush injury resulted in a pronounced astroglial and microglial proliferation 2–7 dpi. Degenerative axons distal to the lesion presented a gradual decrease in neurofilament immunoreactivity. In contrast, Fluoro-Jade staining was gradually increased in these degenerative axons from 2–7 dpi. Regeneration was observed proximal to the lesion in sprouts double labeled with the tracer Fluoro-Gold and anti-GAP43.

Conclusion: The standardized optic nerve crush injury model used in the present study resulted in a reproducible degenerative pattern including a pronounced astroglial and microglial proliferation. The gradual decrease in Neurofilament immunoreactivity in degenerative axons, and a gradual increase in Fluoro-Jade staining was paralleled with a spontaneous regeneration proximal to the lesion, shown with tracing and GAP43-immunoreactivity. The combination of these markers and this experimental setup thus allows analysis of the entire degenerative/regenerative process in a standardized CNS axotomy model.
Do peripheral nerve extracts protect retinal ganglion cells from	axotomy-induced death?
Authors: Świ�ch-Sabuda Ewa , Gołka Beata , Kotulska Katarzyna , Larysz-Brysz Magdalena , Górka Dariusz , Gołka Dariusz , Marcol Wiesław , Lewin-Kowalik Joanna
Published: December 2024

Purpose: Study the effect of peripheral nerve extracts and BDNF on retinal ganglion cell (RGC) regeneration in adult rats.

Methods: Postmicrosomal fractions were obtained from 7-day, predegenerated, as well as non-predegenerated peripheral adult rats nerves. Autologous connective tissue chambers filled with fibrin were implanted into a gap-injury site in the optic nerve. Chambers contained either fibrin, the fractions, or BDNF. RGCs retrogradely labeled with DiI were counted, the distance covered by regrowing fibers traced with rhodamine B was measured, and number of myelinated fibers in the middle part of the chambers was estimated.

Results: BDNF and predegenerated nerve extracts enhanced RGC fiber outgrowth. The regeneration was significantly weaker in the groups with non-predegenerated nerve extracts, as well as fibrin, and was absent in the control group.

Conclusion: Predegenerated nerve extracts, as well as BDNF, applied to injured optic nerves by means of connective tissue chambers, are able to induce retinal ganglion cell regeneration.
Non-invasive mapping of brain functions and brain recovery:	Applying lessons from cognitive neuroscience to neurorehabilitation
Authors: Matthews P.M. , Johansen-Berg H. , Reddy H.
Published: December 2024

Modern cognitive neuroscience provides a powerful framework in which biological models of recovery and neurorehabilitation can be constructed and tested. The widespread availability, relatively low cost and informativeness of functional magnetic resonance imaging (fMRI) has made it the most popular of the techniques available to help with this task. Here, on the basis of functional imaging studies of stroke, diffuse microvascular disease and multiple sclerosis, we argue that processes of motor control and learning in the healthy brain share common mechanisms with those for adaptive functional reorganisation during spontaneous recovery after brain injury or with neurorehabilitation. Relatively stringent criteria can be met to confirm that adaptive functional reorganisation limits disability even in the adult brain: functional brain changes are related to disease burden, can be found in patients with demonstrable pathology but no clinical deficits and can be defined (in motor cortex) even in the absence of volitional recruitment. Initial studies of neurorehabilitation responses using fMRI and transcranial magnetic stimulation demonstrate that adaptive reorganisation can be manipulated directly with both pharmacological and behavioural interventions. The combination of strategies based on a strong biological rational with monitoring their effects using highly informative functional brain imaging methods heralds a new era of scientifically-founded neurorehabilitation.
Noradrenergic modulation of hemiplegia: Facilitation and	maintenance of recovery
Authors: Feeney Dennis M. , De Smet Ayshea M. , Rai Seema
Published: December 2024

This review presents data from laboratory studies and clinical trials indicating the efficacy of the "Noradrenergic Strategy" for enhancing recovery after cortical injury. Short-term acute treatment combining Physical Therapy (PT) with drugs increasing noradrenaline (NA) levels enhances recovery of hemiplegia in both laboratory studies and clinical trials which also report improved aphasia recovery. Importantly these effects endure even when treatment is initiated months after stroke onset. The hypothesized mechanisms included modulation of neuronal processes underlying "spontaneous" recovery since drugs reducing NA levels slow spontaneous recovery. The effect of some drugs change with time after sensorimotor cortex (SMCx) injury. Drugs reducing NA levels, including clonidine and prazosin, and GABA receptor agonists at doses having little effect early after injury, when administered to animals or stroke patients after "complete recovery" transiently reinstate the original symptoms. Reinstatement by prazosin remains unchanged after repeated testing for over six months in rat, and the deficits can be as severe as the first days after injury. This suggests "completed" recovery is an inaccurate label for an enduring "fragile" state. This transient reinstatement of symptoms may be useful for distinguishing causal from corollary relationships between symptoms and physiological processes proposed as mechanisms for recovery of function.
Word learning can be achieved without feedback: Implications for	aphasia therapy
Authors: Breitenstein Caterina , Kamping Sandra , Jansen Andreas , Schomacher Marion , Knecht Stefan
Published: December 2024

Purpose. Children acquire new words through exposure, without the necessity for explicit feedback by caregivers. In aphasia therapy, feedback to the patient is considered an important asset even though the empirical base demonstrating superior learning with online feedback is lacking. The present study examined if healthy adults and patients with chronic aphasia can acquire a new lexicon by intense frequency of exposure alone.

Methods. We compared learning rates with "frequency of exposure alone" (no-feedback condition: n = 19 healthy adults; two patients with chronic Broca's and Wernicke's aphasia, respectively) with a condition where subjects additionally received online feedback (feedback condition; n = 19). The learning principle was higher statistical co-occurrences of "correct" picture-pseudoword pairings as compared to "incorrect" pairings. In the feedback condition, immediate online feedback on the correctness of respective choices was additionally provided.

Results. Both healthy groups successfully acquired the vocabulary. Feedback led to a slight initial acceleration of learning but did not improve latency to peak performance or long-term retention of lexical knowledge. These findings show that high frequency interactive exposure is a potent word learning mechanism in adults and that feedback is not crucial. This is further corroborated by our successful training of two patients with chronic aphasia without online feedback.

Conclusions. Our findings demonstrate that word re-learning in aphasia could benefit from maximizing on the frequency of exposure and exploiting the therapeutic principle of "massed practice", which has been successful in physical rehabilitation after stroke. Additionally, economizing on feedback may prevent patients becoming discouraged by continuous confrontation with their deficits.
Development and application of virtual reality technology to	improve hand use and gait of individuals post-stroke
Authors: Deutsch Judith E. , Merians Alma S. , Adamovich Serge , Poizner Howard , Burdea Grigore C.
Published: December 2024

Development and application of virtual reality (VR) systems for rehabilitation is an iterative process produced by collaboration of an inter-disciplinary team of engineers, neuroscientists and clinician-scientists. In this paper the use of virtual reality technology for the rehabilitation of individuals post-stroke is described. The development of the hardware is based on principles of motor control. Development of the software uses findings from the enrichment and motor plasticity and training literatures as well as principles of motor learning. Virtual environments are created to afford individuals post-stroke opportunities to practice tasks for which they require rehabilitation. These tasks, related to hand function and gait, are trained both at the impairment and functional level. The training engages users to allow for the repetitive intensive practice required for behavioral motor plasticity. Results from a series of upper and lower extremity studies indicate that use of VR technology to augment rehabilitation of individuals post-stroke merits further study.
The interplay between behavior and neurodegeneration in rat models	of Parkinson's disease and stroke
Authors: Woodlee Martin T. , Schallert Timothy
Published: December 2024

The effects of extreme disuse or overuse of the limbs in rat models of Parkinson's disease and stroke are discussed. In unilaterally lesioned rats, immobilizing one forelimb in a cast forces complete disuse of this limb and extreme overuse of the uncasted limb. This procedure has diverse effects on histological and behavioral outcomes in these models, depending upon how and when it is applied relative to the lesion. Effects on behavioral outcome, post-lesion plasticity events, and expression of trophic factors are discussed. The effects of forced disuse or overuse vary among lesion types and can include neuroprotection, changes in synaptogenesis, or even exaggeration of tissue loss. The diversity of behavior-driven structural changes in the brain underscores the potential importance of carefully tailoring physical restorative therapy to specific neurological problems in order to optimize outcomes. In addition, we stress the need to recognize the reciprocal influence that behavior and the brain can have upon each other.
Compensatory changes in cortical cholinergic innervation in the	rat following an immunotoxic lesion
Authors: Hartonian Ivet , de Lacalle Sonsoles
Published: December 2024

Purpose: To investigate the plastic capacity of the cholinergic system in a partial animal model of Alzheimer's disease.

Methods: Rats received unilateral lesions of the horizontal diagonal band of Broca (HDB) using a cholinergic-specific toxin, 192 IgG-saporin. After the appropriate survival time (2, 4, 8, 12 and 24 weeks post-lesion) rats were sacrificed and the brains were prepared for histology. Immunocytochemical and morphometric techniques were employed to quantify the cholinergic neurons surviving the lesion and to measure the density of cortical cholinergic fibers.

Results: Cell counts revealed on average a 60% reduction in cholinergic neurons on the lesioned side, compared to the spared side. This cell loss was permanent, that is, there was no significant change in the amount of cell loss over time. In correlation with this cell loss, cholinergic fibers in the target area, the entorhinal cortex (EC), were also reduced such that the density of acetylcholinesterase (AChE)-stained fibers on the lesioned side was 44% of the spared side. The density of cholinergic fibers in the EC increased significantly between 2 and 12 weeks post-lesion (p = 0.0216) but remained stable at that level by 24 weeks after the lesion.

Conclusions: Following a cholinergic-specific lesion, a compensatory mechanism is activated in the basal forebrain cholinergic system, such that surviving neurons, projecting to the same target, extend their terminals to occupy the denervated area. It remains to be investigated whether these sprouts are able to establish proper synaptic connections and make a functional recovery in this particular system.
Adult neurogenesis and neuroplasticity
Authors: Taupin Philippe
Published: December 2024

After cerebral strokes and traumatic brain injuries (TBIs), there is a striking amount of neurological recovery in the following months and years, despite often-permanent structural damage. Though the mechanisms underlying such recovery are not fully understood, properties of plasticity of the central nervous system (CNS), such as the reorganization of the pre-existing network and axonal sprouting have been implicated in the recovery. With the recent evidences that neurogenesis occurs in the adult brain, and neural stem cells (NSCs) reside in the adult CNS, the involvement of newly generated neuronal cells in the recovery following injury to the CNS remains to be established. Neurogenesis is increased bilaterally in the dentate gyrus (DG) and the subventicular zone (SVZ) after cerebral strokes and TBIs, and new neuronal cells are generated at the sites of injury, where they replace some of the degenerated nerve cells. Newly generated neuronal cells at the sites of injury may represent an attempt by the CNS to regenerate itself after injury, whereas the increased neurogenesis in the DG and SVZ would also contribute to the CNS plasticity. Thus, injury-induced neurogenesis may contribute to the recovery and plasticity of the CNS.
Recovery of a partially damaged corticospinal tract in a patient	with intracerebral hemorrhage: A diffusion tensor image study
Authors: Jang Sung Ho , Byun Woo Mok , Han Bong Soo , Park Hae-Jeong , Bai Daiseg , Ahn Young Hwan , Kwon Yong-Hyun , Lee Mi Young
Published: December 2024

Purpose: We hypothesized that diffusion tensor imaging (DTI) could be useful for exploring corticospinal tract (CST) regeneration if longitudinal changes of diffusion anisotropy can be detected. In this study, we explored the recovery of a CST partially damaged by intracerebral hematoma in a patient by DTI.

Methods: A 61-year-old female patient and six age-matched control subjects were evaluated. The patient presented with complete paralysis of the left extremities, which occurred at the onset of a spontaneous intracerebral hemorrhage (ICH) in the right corona radiata and internal capsule. Over the five-month period following onset, motor function of the affected extremities slowly recovered to the normal range. Two longitudinal DTIs were acquired from the patient (at 3 weeks and 5 months from onset) and one DTI from the control subjects. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured using a region of interest (ROI) method.

Results: On the 3-week DTI, FA values of ROIs in the ICH regions in the affected hemisphere were significantly lower, and ADC values of ROIs in the same areas were significantly higher than those of the control subjects (p<0.002). However, both mean FA and ADC values of the affected hemisphere in the 5-month DTI showed no significant differences versus those of the control.
Spinal reflex control of micturition after spinal cord	injury
Authors: Tai Changfeng , Roppolo James R. , de Groat William C.
Published: December 2024

Purpose: This review summarizes possible spinal reflexes involved in micturition control as well as current treatments for lower urinary tract dysfunction after spinal cord injury (SCI) in an effort to further promote the development of new treatments for people with SCI.

Methods: A systematic literature search was conducted on the Medline database, and on the Web of Science.

Results: After SCI normal functions of the lower urinary tract are lost. The detrusor contracts frequently even at a small bladder volume, which results in urinary incontinence. In addition, the hyperactive bladder can not empty well because the urethral sphincter contracts simultaneously with the bladder (detrusor sphincter dyssynergia), which results in a large residual volume of urine. The malfunction of the lower urinary tract after SCI is caused by remaining and newly emerged bladder and urethral sphincter spinal reflexes. Current treatments have either limited success or troublesome side effects, and many new treatments are under development.

Conclusions: In order to restore the functions of the lower urinary tract after SCI, efforts should be directed at re-establishing the coordination between the spinal reflex control of bladder and urethral sphincter using either pharmacological or neurophysiological approaches.
Motor enrichment sustains hindlimb movement recovered after spinal	cord injury and glial transplantation
Authors: Moon L.D.F. , Leasure J.L. , Gage F.H. , Bunge M.B.
Published: December 2024

Purpose: This study investigated whether enrichment improves hindlimb movement following complete spinal cord transection and transplantation of olfactory ensheathing glia (OEG), with or without a Schwann cell (SC) bridge.

Methods: Motor activity was encouraged through provision of motor enrichment housing (MEH); a multi-level cage containing ramps, textured surfaces and rewards. Hindlimb joint movement was assessed weekly for 22 weeks starting one week post-surgery, comparing rats housed in MEH to those in basic housing (BH). Transganglionic tracer was injected into the crushed right sciatic nerve three days prior to sacrifice, allowing sensory axons in the dorsal columns to be visualized by immunolabeling. Serotonergic axons and glial cells expressing low affinity nerve growth factor receptor were identified by immunolabeling.

Results: All rats, having received transplants, recovered some hindlimb movement. Rats housed in BH progressively lost recovered hindlimb function whereas recovered hindlimb movements were sustained in most rats in MEH. In rats transplanted with SCs and OEG, effects of MEH were first significant 14 weeks after injury. In rats transplanted with OEG, a trend was seen from 14 weeks after injury, but this did not reach significance. In all rats, traced sensory axons died back from sites of transplantation and did not regenerate rostrally. Further, in no rat were serotonergic axons observed regenerating into, around or beyond transplants.

Conclusions: Transection and transplantation of SC/OEG or OEG induced recovery of hindlimb function. This recovered hindlimb movement was sustained in rats housed in MEH but was progressively lost in rats housed in BH. Because benefits of MEH were not observed until 14 weeks after injury, long-term assessment of behavior is recommended. BH conditions are not conducive to maintenance of recovered hindlimb function, and MEH should be used in studies of recovery of function following spinal cord injury.
Impact of neglect on functional outcome after stroke – a	review of methodological issues and recent research findings
Authors: Jehkonen M. , Laihosalo M. , Kettunen J.E.
Published: December 2024

Purpose: This study provides an update on recent research findings concerning neglect and its impact on functional outcome. The review covers studies published during the past ten years.

Methods: A systematic review was carried out on reports drawn from electronic databases (MEDLINE and PSYCHLIT, January 1996 – August 2005) and identified from the lists of references in these reports. Unpublished reports, articles in other than the English language, and studies with non-human and non-adult subjects were excluded. The selection criteria were met by 26 articles.

Results: 15 of the 26 studies recruited heterogeneous patient groups (patients with right and left and/or unspecified lesions). The results from homogeneous groups (right hemisphere patients) were more consistent, emphasizing neglect as an independent predictor of functional outcome. Studies with homogeneous patient groups used consecutive series of patients, standardized measures of neglect, and a broader concept of functional outcome (both motor and cognitive items) than those with heterogeneous patient groups. Follow-ups longer than one year were very rare.

Conclusions: Neglect has a significant negative impact on functional outcome, either as an independent predictive factor or in connection with other variables. The results, however, are inevitably affected by differences in patient samples and in the methods used in assessing neglect and functional outcome. Research focusing on homogeneous patient groups and especially on left hemisphere patients is needed. Neglect should be assessed with a standardized test battery rather than a single test, and functional outcome should be measured with scales consisting of cognitive, social and motor items. Also longer follow-ups are needed to verify the long-term functional outcome of neglect patients.
Impact of creatine kinase correction on the predictive value of	S-100B after mild traumatic brain injury
Authors: Bazarian Jeffrey J. , Beck Christopher , Blyth Brian , von Ahsen Nicolas , Hasselblatt Martin
Published: December 2024

Purpose: To validate a correction factor for the extracranial release of the astroglial protein, S-100B, based on concomitant creatine kinase (CK) levels.

Methods: The CK- S-100B relationship in non-head injured marathon runners was used to derive a correction factor for the extracranial release of S-100B. This factor was then applied to a separate cohort of 96 mild traumatic brain injury (TBI) patients in whom both CK and S-100B levels were measured. Corrected S-100B was compared to uncorrected S-100B for the prediction of initial head CT, three-month headache and three-month post concussive syndrome (PCS).

Results: Corrected S-100B resulted in a statistically significant improvement in the prediction of 3-month headache (area under curve [AUC] 0.46 vs 0.52, p=0.02), but not PCS or initial head CT. Using a cutoff that maximizes sensitivity (⩾90%), corrected S-100B improved the prediction of initial head CT scan (negative predictive value from 75% [95% CI, 2.6%, 67.0%] to 96% [95% CI: 83.5%, 99.8%]).

Conclusions: Although S-100B is overall poorly predictive of outcome, a correction factor using CK is a valid means of accounting for extracranial release. By increasing the proportion of mild TBI patients correctly categorized as low risk for abnormal head CT, CK-corrected S100-B can further reduce the number of unnecessary brain CT scans performed after this injury.
A battery of tests for the quantitative assessment of unilateral	neglect
Authors: Azouvi Philippe , Bartolomeo Paolo , Beis Jean-Marie , Perennou Dominic , Pradat-Diehl Pascale , Rousseaux Marc
Published: December 2024

Purpose: The lack of agreement regarding assessment methods is responsible for the variability in the reported rate of occurrence of unilateral neglect (UN) after stroke. In addition, dissociations have been reported between performance on traditional paper-and-pencil tests and UN in everyday life situations.

Methods: In this paper, we present the validation studies of a quantitative test battery for UN, including paper-and-pencil tests, an assessment of personal neglect, extinction, and anosognosia, and a behavioural assessment, the Catherine Bergego Scale (CBS). The battery was given to healthy subjects (n=456–476) and to patients with subacute stroke, either of the right or the left hemisphere.

Results: In healthy subjects, a significant effect of age, education duration and acting hand was found in several tasks. In patients with right hemisphere stroke, the most sensitive paper and pencil measure was the starting point in the cancellation task. The whole battery was more sensitive than any single test alone. An important finding was that behavioural assessment was more sensitive than any other single test. Neglect was two to four times less frequent, but also less severe and less consistent after left hemisphere stroke.

Conclusion: Assessment of UN should rely on a battery of quantitative and standardised tests. Some patients may show clinically significant UN in everyday life while obtaining a normal performance on paper-and-pencil measures. This underlines the necessity to use a behavioural assessment of UN.
Simulating unilateral neglect in normals: Myth or reality?
Authors: Michel Carine
Published: December 2024

Hemispatial neglect is a neurological deficit of perception, attention, representation, and/or performing actions within the left-sided space. The condition also produces many functional debilitating effects on everyday life, and is associated with poor functional recovery and inability to benefit from treatment. Numerous methods of rehabilitation (sensory stimulations or active training) have been proposed to alleviate neglect condition. It has been recently shown that visuo-manual adaptation to rightward optical shift leads to profound and enduring improvements of neglect symptoms. Based on the different methods commonly used in the rehabilitation of neglect, several techniques have been employed to simulate neglect symptoms in healthy subjects with a view to better understand the physiopathology of neglect. The present paper reviews studies of neglect-like behaviour in healthy individuals and in particular the use of prism adaptation as a procedure for simulating various symptoms of clinical neglect in normals. Neglect-like symptoms following prism adaptation offer insights as to the mechanisms of spatial neglect and provide an understanding of the interaction between low level sensorimotor processes and spatial cognition. Implications for the functional mechanisms and the anatomical substrates of prism adaptation are discussed in terms of inter-sensory plasticity and sensorimotor coordination and the way these may affect higher-level representations of space.
Spatial and non-spatial attention deficits in neurodegenerative	diseases: Assessment based on Bundesen's theory of visual attention (TVA)
Authors: Bublak Peter , Redel Petra , Finke Kathrin
Published: December 2024

Purpose: The aim was to present evidence that, similarly as in neglect, a combined pattern of spatial and non-spatial deficits of visual attention can also be typically observed in patients suffering from neurodegenerative disorders.

Method: Whole and partial report of brief letter arrays, based on Bundesen's 'theory of visual attention' (TVA), was applied in patients suffering from Huntington's disease (HD), mild cognitive impairment (MCI), or Alzheimer's disease (AD). TVA-based parameter estimates were derived reflecting (a) perceptual processing speed and visual working memory storage capacity as non-spatial aspects of visual attention (determined by whole report performance), and (b) spatial attentional weighting (determined by partial report performance).

Results: Processing speed was severely slowed in HD, and also reduced, although to a lesser degree, in MCI and AD patients. In HD and AD patients, but not in MCI patients, a strong leftward bias of spatial attention was observed.

Conclusion: Neglect and neurodegenerative diseases both involve a similar constellation of non-spatial and spatial deficits of visual attention. Therefore, by using TVA-based measurement, results from both fields of research may fruitfully inform each other in future studies, thus improving our understanding of the interaction of spatial and non-spatial attention deficits and its behavioral consequences.
Development of a rehabilitative program for unilateral	neglect
Authors: Pizzamiglio Luigi , Guariglia Cecilia , Antonucci Gabriella , Zoccolotti Pierluigi
Published: December 2024

Purpose: The aim of the present paper is to review several studies which assessed the validity of a visuo-spatial training for the rehabilitation of neglect patients. In addition two peripheral stimulations (TENS and Optokinetic Stimulation) have been studied to assess the improvements of neglect disorders when used in combination with the visuo-spatial training. Also we analyzed the potential effect of training for attention on neglect and, viceversa, the effect of visuo-spatial training on attentional impairments.

Methods: the goals have been investigated by both group studies and descriptions of single cases.

Results: The visuo-spatial training produced significant improvements on the performance of neglect patients which generalized to every day living situations: the results showed to be stable over time and had positive effects on a variety of other neurological impairments. It was also shown that the improvements are confined to tasks involving spatial exploration of extrapersonal space, but did not extend to other neglect disorders, such as representational and personal neglect. The use of peripheral stimulations, at variance with other studies in the literature, did not add any advantage as compared to the improvements produced by the visuo-spatial training. No transfer between training for neglect and attention was observed.

Conclusions: the present review pointed out that neglect disorders can be improved in a clinically meaningful way: the studies described also showed some limitations and proposed the need of further researches in order to extend the improvements to several other aspects of the neglect syndrome.
Construction and psychometric properties of a novel test for body	representational neglect (Vest Test)
Authors: Glocker D. , Bittl P. , Kerkhoff G.
Published: December 2024

Purpose: Multimodal spatial neglect manifests itself also in nonvisual modalities such as audition, touch and body representation. Yet, quantitative tests for the diagnosis of nonvisual neglect are still quite rare. The purpose of the present paper was to develop and evaluate a novel, simple and sensitive test for the assessment of body representational neglect (BRN) in patients with left or right cerebral hemispheric lesions.

Methods: The vest test covers the front part of the trunk. The blindfolded subject wears the vest and is instructed to pick up all objects from the 24 pockets of the vest (12 on each side) as quickly as possible using the ipsilesional, nonparetic hand. Two samples of healthy control subjects (each N=25) using either their left or their right hand performed the test in identical way to obtain normative data for patients searching with their left hand (i.e. left hemisphere stroke patients) versus their right hand (i.e. right hemisphere stroke patients). The test can be performed within 5~minutes, even with aphasic or apractic stroke patients.

Results: Psychometric evaluations in a sample of 50 patients with unilateral stroke (25 leftsided, 25 rightsided) show high objectivity, high internal consistency (Cronbach's alpha=0.96), good retest-reliability (0.79 after 1 week in neglect patients) and good validity as compared with two other measures of BRN or multimodal neglect. Patient examples show that BRN as assessed with the vest test allows the detection of qualitatively and quantitatively different patterns of BRN, and shows double dissociations from visual neglect and from apraxia in left hemisphere stroke patients. Details of the test including instructions and cut-off values are given for users in the appendix of this article.

Conclusions: In conclusion, the vest test is a sensitive, quick and reliable test for BRN which complements the assessment of visuo- and audiospatial neglect and allows to measure recovery (spontaneous or treatment-induced) in patients with BRN. Furthermore, it can help to improve our knowledge about the multisensory coding of our body and the surrounding space in the human brain.
Combined transcranial direct current stimulation and	robot-assisted arm training in subacute stroke patients: A pilot study
Authors: Hesse S. , Werner C. , Schonhardt E.M. , Bardeleben A. , Jenrich W. , Kirker S.G.B.
Published: December 2024

Background and Purpose: Preliminary reports suggest that central stimulation may enhance the effect of conventional physical therapies after stroke. This pilot study examines the safety and methodology of using transcranial direct stimulation (tDCS) with robot-assisted arm training (AT), to inform planning a larger randomised controlled trial.

Subjects: Ten patients, after an ischaemic stroke 4–8 weeks before study onset, no history of epilepsy, participated. Eight had a cortical lesion and 2 had subcortical lesions: all had severe arm paresis and, co-incidentally, 5 had severe aphasia.

Methods: Over six weeks, they received thirty 20 min-sessions of AT. During the first 7 minutes, 1.5mA of tDCS was applied, with the anode over the lesioned hemisphere and the cathode above the contralateral orbit. Arm and language impairment were assessed with the Fugl-Meyer motor score (FM, full range 0–66) and the Aachener Aphasie Test.

Results: No major side effects occurred. Arm function of three patients (two with a subcortical lesion) improved significantly, with FM scores increasing from 6 to 28, 10 to 49 and 11 to 48. In the remaining seven patients, all with cortical lesions, arm function changed little, FM scores did not increase more than 5 points. Unexpectedly, aphasia improved in 4 patients.

Conclusions: These procedures are safe, and easy to use in a clinical setting. In future studies, patients should be stratified by degree of arm weakness and lesion site, also the unexpected aphasia improvement warrants following-up.
The novel antiepileptic agent RWJ-333369-A, but not its analog	RWJ-333369, reduces regional cerebral edema without affecting neurobehavioral	outcome or cell death following experimental traumatic brain injury
Authors: Keck Carrie A. , Thompson Hilaire J. , Pitkänen Asla , LeBold David G. , Morales Diego M. , Plevy Jamie B. , Puri Rishi , Zhao Boyu , Dichter Marc , McIntosh Tracy K.
Published: December 2024

Purpose: To evaluate the therapeutic efficacy of two antiepileptic compounds, RWJ-333369 and RWJ-333369-A in a well-established experimental model of lateral fluid percussion (FP) traumatic brain injury (TBI) in the rat.

Methods: Anethestized Male Sprague-Dawley rats (n=227) were subjected to lateral FP brain injury or sham-injury. Animals were randomized to receive treatment with RWJ-333369 (60 mg/kg, p.o.) or its analog RWJ-333369-A (60 mg/kg, p.o.), or vehicle (equal volume) at 15 minutes, 4, 8, and 24 hours post-injury. In Study I, animals were assessed at 48 hours for acute motor and cognitive function and then sacrificed to evaluate regional cerebral edema. In Study II, animals were evaluated post-injury for motor function at 48 hours and weekly thereafter from 1 to 4 weeks. Post-traumatic learning ability was assessed 4 weeks post-injury, followed by evaluation of hemispheric tissue loss.

Results: In Study I, no improvement in acute memory or motor function was observed following administration of either RWJ-333369 or RWJ-333369-A in brain-injured animals compared to vehicle-treated, brain-injured animals. However, brain-injured animals receiving treatment with RWJ-333369-A had a significant reduction in post-traumatic cerebral edema in both injured and contralateral hippocampus compared to brain-injured, vehicle-treated controls (p<0.05). In Study II, treatment with either compound did not result in any improvement of neuromotor function, learning ability or change in lesion volume following brain injury.