Post-acute Stage Research Articles

Magnetisation transfer ratio in optic neuritis is associated with axonal loss, but not with demyelination

Background Pathophysiological basis of Magnetisation Transfer Ratio (MTR) reduction in multiple sclerosis still remains a matter of controversy. Optic nerve represents an ideal model to study the consequences of axonal loss and demyelination on MTR since effects of disease on the optic nerve are clinically apparent and potentially quantifiable by objective means. By measuring the latency of multifocal visual evoked potentials (mfVEP) (measure of optic nerve conduction) and Retinal Nerve Fiber Layer (RNFL) thickness (measure of axonal damage) we investigated the effect of neurodegeneration and demyelination on MTR after an episode of optic neuritis (ON). Methods 23 patients with a single unilateral episode of ON and 10 healthy volunteers were enrolled. Orbital MRI including MTR protocol, Optical Coherence Tomography and Multifocal VEP were performed at post-acute stage of ON. Results Average MTR of affected eye was significantly reduced as compared to the fellow eye and normal controls. There was a highly significant correlation between MTR and measures of axonal loss (RNFL thickness and mfVEP amplitude), which was independent on the level of demyelination. While latency delay also correlated significantly with MTR, correlation became non-significant when adjusted for the degree of axonal loss. There was a significant reduction of MTR in a group of patients with extensive axonal damage, while MTR remained normal in a group of patients with extensive demyelination, but little or no axonal loss. Conclusion Results of this study indicate that reduction of optic nerve MTR after an episode of ON has a strong association with the degree of axonal damage, but not with demyelination.

Crossover Trial of Subacute Computerized Aphasia Therapy for Anomia With the Addition of Either Levodopa or Placebo

Background. The effect of levodopa on recovery from aphasia is controversial. Objective. To determine whether levodopa enhances the effect of intensive computer-assisted therapy (CAT) of anomia in the postacute stage of aphasia. Methods. Double-blind multiple case study with intrasubject crossover design comparing the effect of levodopa (100 mg) versus placebo, each given for 2 weeks. Subjects. Twelve patients with onset of aphasia from 2 to 9 weeks after stroke or traumatic brain injury were compared on naming performance on items trained and not trained with CAT. Subjects were randomized to either levodopa or placebo first, separated by a 1-week washout, and then switched to the other drug intervention for the second 2-week CAT intervention. The subjects also received routine aphasia therapies during these periods. Results. All patients improved their naming performance for items trained by CAT in both periods (P = .001). No significant difference was found between the placebo and levodopa phases. Conclusion. Administration of levodopa for 2 weeks during the postacute stage of aphasia did not augment the positive effects of subacute intensive language treatment with CAT for a spoken naming task.

How Mild Traumatic Brain Injury May Affect Declarative Memory Performance in the Post-Acute Stage

Memory deficits are among the most frequently reported sequelae of mild traumatic brain injury (MTBI), especially early after injury. To date, these cognitive deficits remain poorly understood, as in most patients the brain is macroscopically intact. To identify the mechanism by which MTBI causes declarative memory impairments, we probed the functionality of the medial temporal lobe (MTL) and the prefrontal cortex (PFC), within 6 weeks after injury in 43 patients from a consecutive cohort, and matched healthy controls. In addition to neuropsychological measures of declarative memory and other cognitive domains, all subjects underwent functional magnetic resonance imaging (fMRI). Behavioral results showed poorer declarative memory performance in patients than controls, and decreasing performance with increasing duration of post-traumatic amnesia (a measure of injury severity). Task performance in the scanner was, as intended by the task and design, similar in patients and controls, and did not relate to injury severity. The task used reliably activated the MTL and PFC. Although we did not find significant differences in brain activity when comparing patients and controls, we revealed, in agreement with our neuropsychological findings, an inverse correlation between MTL activity and injury severity. In contrast, no difference in prefrontal activation was found between patients and controls, nor was there a relation with injury severity. On a behavioral level, injury severity was inversely related to declarative memory performance. In all, these findings suggest that reduced medial temporal functionality may contribute to poorer declarative memory performance in the post-acute stage of MTBI, especially in patients with longer post-traumatic amnesia.

Interrelationship of Optical Coherence Tomography and Multifocal Visual-Evoked Potentials after Optic Neuritis

Acute optic neuritis (ON) is often followed by recovery of visual function. Although this recovery is mainly attributable to resolution of the acute inflammation, the redistribution of ion channels along the demyelinated membrane, and subsequent remyelination, part of it may be the result of neural plasticity. In the present study, the interrelationship was examined between structural (retinal nerve fiber layer [RNFL] thickness) and functional (amplitude of multifocal visual evoked potentials [mfVEPs]) measures of the integrity of the visual pathway in the postacute stage of ON, to determine whether there was any evidence of ongoing neural reorganization. Twenty-five subjects with acute unilateral ON underwent serial RNFL thickness measurement and mfVEP recording. The inter-eye asymmetry of both measures was analyzed. In the period between 6 and 12 months, the subjects were considered free of optic disc edema, and that period was used to analyze the structure-function relationship. Twenty control subjects were also examined. There were significant but opposite changes in RNFL thickness and mfVEP amplitude. The average asymmetry of RNFL thickness between affected and fellow eyes increased from 17.5 +/- 11.5 to 21.1 +/- 12.8 microm (P = 0.0003), indicating progressive axonal loss, whereas mfVEP amplitude asymmetry decreased from 46.6 +/- 32.4 to 38.3 +/- 31.1 nV (P = 0.0015), indicating continuous functional recovery. In comparison to the 6-month results, the mfVEP amplitude in the ON eye improved by 17.8%, whereas RNFL thickness decreased by 20.8%. The result remained unchanged regardless of the degree of optic nerve remyelination. The finding of structural-functional discrepancy at the postinflammatory stage may support the concept that neural plasticity contributes to functional recovery after acute ON.

Frequency and Prognostic Value of Cognitive Disorders in Stroke Patients

Background: Stroke is one of the most common diseases to cause cognitive disorders in adults. Aims: To assess the frequency of cognitive deficits in stroke patients and to evaluate the prognostic value of cognitive syndromes for functional recovery. Methods: 200 consecutive patients were examined using a clinical screening battery for cognitive assessment in the second week after their first-ever stroke. 80 were re-examined after a 1-year follow-up. Results: In the post-acute stage, 78% patients were impaired in one or more cognitive domains. The most frequently affected cognitive abilities were attention (48.5%), language (27%), short-term memory (24.5%) and executive functions (18.5%). At the 1-year follow-up, attention deficits were still the most frequent symptom. In contrast, executive dysfunction, aphasia, and long-term memory disorder were significantly less frequent than in the post-acute period. Logistic regression analysis showed that older age, lower score on the Barthel Index, and the presence of executive dysfunction on initial examination were significant predictors of a poor functional outcome at the 1-year follow-up examination. Conclusions: Cognitive-behavioral syndromes are frequent and often chronic consequences of stroke. Executive deficits proved to be the most robust cognitive predictor of poor functional recovery after stroke.

Axonal loss and myelin in early ON loss in postacute optic neuritis

To investigate the relation between retinal nerve fiber layer (RNFL) thickness and latency and amplitude of multifocal visual-evoked potentials (mfVEPs) in the postacute stage of optic neuritis in patients with early or possible multiple sclerosis. Thirty-two patients with clinical diagnosis of unilateral optic neuritis and magnetic resonance imaging lesions typical of demyelination and 25 control subjects underwent mfVEP and optical coherence tomography imaging. Although there was significant reduction of RNFL thickness in the affected eyes (18.7%), a considerably larger decrease was observed for the amplitude of the mfVEPs (39.8%). Latency of the mfVEPs was also significantly delayed in optic neuritis eyes. In fellow eyes, the amplitude of mfVEPs was significantly reduced and the latency prolonged, but RNFL thickness remained unaltered. RNFL thickness correlated highly with the mfVEP amplitude (r = 0.90). There was also strong correlation between optical coherence tomography measure of axonal loss and mfVEP latency (r = -0.66). Although our findings demonstrate strong associations between structural and functional measures of optic nerve integrity, the functional loss was more marked. This fact, together with amplitude and latency changes of the mfVEPs observed in clinically normal fellow eyes, may indicate greater sensitivity of mfVEPs in detecting optic nerve abnormality or the presence of widespread inflammation in the central nervous system, or both. The significant correlation of the mfVEP latency with RNFL thickness suggests a role for demyelination in promoting axonal loss.

Cortical and subcortical anatomy of chronic spatial neglect following vascular damage

BackgroundThe role of the inferior parietal lobule (IPL) and superior temporal gyrus (STG) or subcortical pathways as possible anatomical correlates of spatial neglect is currently intensely discussed. Some of the conflicting results might have arisen because patients were examined in the acute stage of disease.MethodsWe examined the anatomical basis of spatial neglect in a sample of patients examined in the post-acute stage following right-hemispheric vascular brain damage. Lesions of 28 patients with chronic spatial neglect were contrasted to lesions of 22 control patients without neglect using lesion subtraction techniques and voxel-wise comparisons.ResultsThe comparisons identified the temporo-parietal junction (TPJ) with underlying white matter, the supramarginal gyrus, the posterior STG, and the insula as brain regions damaged significantly more often in neglect compared to non-neglect patients. In a subgroup of neglect patients showing particularly large cancellation bias together with small errors on line bisection damage was prevalent deep in the frontal lobe while damage of patients with the reverse pattern was located in the white matter of the TPJ.ConclusionConsidering our results and the findings of previous studies, spatial neglect appears to be associated with a network of regions involving the TPJ, inferior IPL, posterior STG, the insular cortex, and posterior-frontal projections. Frontal structures or projections may be of particular relevance for spatial exploration, while the IPL may be important for object-based attention as required for line bisection.

Hämorrhagisch-nekrotisierende Pankreatitis und bildgebende Verfahren

Ultrasound and computed tomography have been used routinely over the last five years in the diagnosis of acute pancreatitis. This has made classification as to degrees of severity easier. In addition to the direct imaging of destruction of pancreatic parenchyma, these imaging methods also (preoperatively) make an exact assessment of the extension of peripancreatic necrosis and necrosis paths possible, as well as the presence of any gallstone disease or pancreatic abscess. Under the influence of these imaging procedures the indications for operation and the extent of surgical intervention has become more limited. High-risk "early operation" has been drastically reduced in number and is indicated only in very severe disease with organ complications. The "delayed operation" in the postacute stage of disease is largely restricted to local septic complications. Here excision of necrotic tissue and drainage is now largely preferred to resection, previously practised more frequently. Extensive necrotising processes with only minor clinical symptoms have now been observed as a result of early employment of ultrasound and computed tomography. The successful conservative treatment of these uncomplicated disease processes has contributed to an overall reduction in the mortality of postacute pancreatitis.

Normalisation and increase of abnormal ERP patterns accompany recovery from aphasia in the post-acute stage

Electrophysiological correlates of recovery from anomia were analysed in four aphasic patients in the post-acute stage. Event-related potentials (ERPs) were recorded during picture naming at baseline and after a period of therapy for anomia. All patients had severe anomia at baseline assessment and improved significantly in naming during the study period. Waveform analyses and temporal segmentation were carried out on the ERPs of each patient in comparison with 15 healthy control subjects. Normalisation as well as an increase of abnormal electrophysiological correlates accompanied recovery. An increase of abnormal amplitudes appeared in a patient with semantic impairment during the first 300 ms after picture onset, while only normalisation of amplitudes and topographic maps accompanied recovery in the three patients with lexical–phonological impairment in this early time-window. Abnormal amplitudes and topographic maps emerged during recovery in the patients with lexical–phonological impairment in later time-windows, starting between 250 and 300 ms. Follow-up ERP recordings carried out 6 months later in two of them showed normalisation of amplitudes and persistence of abnormal maps. The results suggest that electrophysiological changes accompanying recovery from anomia in the post-acute stage are observed in specific time-windows, probably corresponding to different encoding processes and that recovery correlates with normalisation of EEG patterns as well as with the emergence of abnormalities, which presumably indicates compensation mechanisms of specific encoding processes.

Cognitive-behavioural stimulation protocol for severely brain-damaged patients in the post-acute stage in developmental age

Purpose. To present a cognitive-behavioural stimulation (CBS) protocol designed to help severely damaged patients in the early post-acute stage by describing the underlying methodology and assessing its efficacy compared to traditional rehabilitation methods. This protocol combines multisensory stimulation and cognitive-behavioural techniques to elicit and intensify the occurrence of adaptive responses and reduce maladaptive behavioural patterns.Methods. A control group and an experimental group – both evaluated with the Levels of Cognitive Functioning Assessment Scale (LOCFAS) – were compared at the beginning of the rehabilitation programme and at the end of it. The control group consisting of patients assessed and treated before receiving the CBS protocol was enrolled in a traditional rehabilitation programme (only physical therapy and speech therapy). Besides the traditional therapy, the experimental group also received the CBS protocol.Results. Patients on the CBS protocol show a greater improvement and are therefore more responsive than the control group after the 16-week remediation programme. The mean LOCFAS improvement of the experimental group is more marked during the first month of rehabilitation and is associated to the entry LOCFAS level, while in the control group the improvement on LOCFAS is considered to be ‘spontaneous’ and is associated to the aetiology of the brain damage.Conclusions. Our results show a better initial outcome for patients receiving the CBS protocol.

COILING VERSUS CLIPPING FOR THE TREATMENT OF ANEURYSMAL SUBARACHNOID HEMORRHAGE

Endovascular coiling has been used increasingly as an alternative to neurosurgical clipping for treating subarachnoid hemorrhage secondary to aneurysm rupture. The aim of the present study was to provide a prospective, longitudinal investigation into cognitive function in patients with aneurysmal subarachnoid hemorrhage treated with either neurosurgical clipping or endovascular coiling. Twenty-three patients who were treated for aneurysmal subarachnoid hemorrhage at the National Hospital for Neurology and Neurosurgery in London, England, were recruited prospectively. Twelve patients who underwent surgical clipping were compared with a group of 11 patients who underwent endovascular coiling. All patients underwent a comprehensive, standardized neuropsychological assessment using the same battery of tests at the acute stage (within 2 wk after treatment). All patients who underwent coiling and 11 of the 12 patients who underwent clipping were reassessed at the post-acute long-term follow-up (6 mo) stage. Group comparisons at the acute assessment revealed a significant difference favoring coiling patients on only one measure of verbal recall. However, there were no other significant differences between the groups at this stage. At the post-acute assessment, the clipped group performed better than the coiled group on measures of intellectual functioning (P < 0.05), although no other differences were found on a range of cognitive tests. Intragroup comparisons between the acute and post-acute assessments found equivocal, significant improvements in measures of intellectual functioning, memory, executive functions, and speed of information processing in both groups of patients. We argue that there are minimal differences in the long-term cognitive outcome between endovascular coiling and surgical clipping. In the acute phase after treatment, we suggest that coiled patients, having been spared neurosurgical intervention, may have a slightly better cognitive outcome than clipped patients. However, these differences level off and both groups of patients ultimately experience widespread improvement in cognitive functioning by the post-acute stage of recovery.

Rehabilitation for Traumatic Brain Injury in Children and Adolescents

Children and adolescents who have sustained a traumatic brain injury (TBI) may be left with multiple deficits and impairments that can impact adversely their abilities to return to premorbid functioning in the home, school and community. Early rehabilitation has been shown to improve functional outcome; the rehabilitation programme itself has to be based on real-world demands and experiences. Rehabilitation has to be continued beyond the post-acute stage in order to promote neuronal re-organisation, monitor the child's development as well as identify and manage new issues that may appear with growth, development and maturation. The availability of relevant research data and findings for children is much less than those for adults. It is not always appropriate to apply data for adults to the younger persons due to important differences in the 2 groups and these are discussed in more detail in the article. Multiple factors have been found to affect recovery and functional outcome. Apart from age and developmental stage at injury, other variables can be grouped as injury-related, patient-related and treatment-related factors. The goals and components of the rehabilitation process are examined for the various stages of recovery and the last section of the article describes the paediatric rehabilitation scene in Singapore.

The testis and epididymis are productively infected by SIV and SHIV in juvenile macaques during the post-acute stage of infection

BackgroundLittle is known about the progression and pathogenesis of HIV-1 infection within the male genital tract (MGT), particularly during the early stages of infection.ResultsTo study HIV pathogenesis in the testis and epididymis, 12 juvenile monkeys (Macacca nemestrina, 4–4.5 years old) were infected with Simian Immunodeficiency Virus mac 251 (SIVmac251) (n = 6) or Simian/Human Immunodeficiency Virus (SHIVmn229) (n = 6). Testes and epididymides were collected and examined by light microscopy and electron microscopy, at weeks 11–13 (SHIV) and 23 (SIV) following infection. Differences were found in the maturation status of the MGT of the monkeys, ranging from prepubertal (lacking post-meiotic germ cells) to post-pubertal (having mature sperm in the epididymal duct). Variable levels of viral RNA were identified in the lymph node, epididymis and testis following infection with both SHIVmn229 and SIVmac251. Viral protein was detected via immunofluorescence histochemistry using specific antibodies to SIV (anti-gp41) and HIV-1 (capsid/p24) protein. SIV and SHIV infected macrophages, potentially dendritic cells and T cells in the testicular interstitial tissue were identified by co-localisation studies using antibodies to CD68, DC-SIGN, αβTCR. Infection of spermatogonia, but not more mature spermatogenic cells, was also observed. Leukocytic infiltrates were observed within the epididymal stroma of the infected animals.ConclusionThese data show that the testis and epididymis of juvenile macaques are a target for SIV and SHIV during the post-acute stage of infection and represent a potential model for studying HIV-1 pathogenesis and its effect on spermatogenesis and the MGT in general.

Functional and cognitive progress in aphasic patients with traumatic brain injury during post-acute phase

Objectives: To investigate the relationship between language functions and cognitive and functional outcome and to evaluate the effects of a conventional language rehabilitation programme on aphasic adult patients in the post-acute stage of traumatic brain injury (TBI).Design: Non-concurrent prospective study. Patients were assessed pre-treatment and post-treatment with standardized assessment tools.Subjects: Sixty-one aphasic patients with TBI who were admitted to a rehabilitation centre in the post-acute phase for a late inpatient rehabilitation programme.Methods: The motor sub-scales of the Functional Independence Measures and Disability Rating Scale were used to assess functional status and disability. Cognitive status was evaluated with the Mini-Mental Status Examination and the Functional Independence Measure cognitive sub-scale. The language function was evaluated with the Gülhane Aphasia Test.Results: All functional, cognitive and language scores increased significantly during the rehabilitation programme. Language functions at admission were correlated with the Functional Independence Measure motor change scores and the Mini-Mental Status Examination change scores. Regression analyses revealed that auditory comprehension at admission was the most important independent determinant of functional and cognitive gain during rehabilitation.Conclusion: Post-acute language functions after late admission to a rehabilitation centre appear to be related to measures of cognitive and functional progress in patients with TBI. Functional and cognitive outcome is mainly affected by auditory comprehension. Results also showed the effectiveness of post-acute conventional rehabilitation in improving language functions.

Poster 33: Blood Level of Insulin-Like Growth Factor-1/Insulin-Like Growth Factor–Binding Protein-3 and Functional Status in Postacute Stage Brain Diseases

Objectives: To evaluate insulin-like growth factor-1 (IGF-1)/binding protein-3 (/IGFBP-3) blood level in patients with postacute-stage brain disease insulin-like growth factor and to investigate the relation between IGF-1/IGFBP-3 blood level and functional status in patients with brain diseases after acute stage. Design: Cross-sectional study. Setting: Inpatient departments of rehabilitation medicine at a hospital in Korea. Participants: 32 patients with postacute-stage brain disease. Interventions: Not applicable. Main Outcome Measures: Initial IGF-1/IGFBP-3 blood levels were obtained and various functional indices, including the Modified Barthel Index (MBI), Functional Ambulatory Category, and Jebsen-Taylor Hand Function Test (JTHFT), were assessed initially and at discharge. Results: Initial IGF-1/IGFBP-3 levels were associated with a change of MBI score during admission (r2=.214, P<.05; r2=.213, P<.05). There was a correlation between IGF-1/IGFBP-3 levels and JTHFT score only on the healthy side at discharge (r2=.278, P<.05). There was no relation between IGF-1/IGFBP-3 levels and the change of JTHFT score on either side during admission. Conclusions: Initial IGF-1/IGFBP-3 blood level check can be a useful method to anticipate functional improvement of patients with postacute stage brain disease.

EFNS guidelines on cognitive rehabilitation: report of an EFNS task force

Disorders of language, spatial perception, attention, memory, calculation and praxis are a frequent consequence of acquired brain damage [in particular, stroke and traumatic brain injury (TBI)] and a major determinant of disability. The rehabilitation of aphasia and, more recently, of other cognitive disorders is an important area of neurological rehabilitation. We report here a review of the available evidence about effectiveness of cognitive rehabilitation. Given the limited number and generally low quality of randomized clinical trials (RCTs) in this area of therapeutic intervention, the Task Force considered, besides the available Cochrane reviews, evidence of lower classes which was critically analysed until a consensus was reached. In particular, we considered evidence from small group or single cases studies including an appropriate statistical evaluation of effect sizes. The general conclusion is that there is evidence to award a grade A, B or C recommendation to some forms of cognitive rehabilitation in patients with neuropsychological deficits in the post-acute stage after a focal brain lesion (stroke, TBI). These include aphasia therapy, rehabilitation of unilateral spatial neglect (ULN), attentional training in the post-acute stage after TBI, the use of electronic memory aids in memory disorders, and the treatment of apraxia with compensatory strategies. There is clearly a need for adequately designed studies in this area, which should take into account specific problems such as patient heterogeneity and treatment standardization.

Imagery-induced Cortical Excitability Changes in Stroke: A Transcranial Magnetic Stimulation Study

Focal transcranial magnetic stimulation (TMS) was employed in a population of hemiparetic stroke patients in a post-acute stage to map out the abductor digiti minimi (ADM) muscle cortical representation of the affected (AH) and unaffected (UH) hemisphere at rest, during motor imagery and during voluntary contraction. Imagery induced an enhancement of the ADM map area and volume in both hemispheres in a way which partly corrected the abnormal asymmetry between AH and UH motor output seen in rest condition. The voluntary contraction was the task provoking maximal facilitation in the UH, whereas a similar degree of facilitation was obtained during voluntary contraction and motor imagery in the AH. We argued that motor imagery could induce a pronounced motor output enhancement in the hemisphere affected by stroke. Further, we demonstrated that imagery-induced excitability changes were specific for the muscle 'prime mover' for the imagined movement, while no differences were observed with respect to the stroke lesion locations. Present findings demonstrated that motor imagery significantly enhanced the cortical excitability of the hemisphere affected by stroke in a post-acute stage. Further studies are needed to correlate these cortical excitability changes with short-term plasticity therefore prompting motor imagery as a 'cortical reservoir' in post-stroke motor rehabilitation.

Neuropsychological outcome and community re-integration following traumatic brain injury: The impact of frontal and non-frontal lesions

Primary objective: To examine the relationship between cortical lesion location and brain injury outcome. It was hypothesized that focal frontal lesions after traumatic brain injury (TBI) would result in decreased executive and memory functioning and poor community participation outcome.Research design: Three quasi-experimental, prospective studies employed a total of 643 patients with focal frontal, fronto-temporal, non-frontal or no lesions in CT scans.Methods and procedures: CT scan analysis, neuropsychological assessment, the Neurobehavioural Functioning Inventory (NFI), the Community Integration Questionnaire (CIQ).Main results: In study 1, frontal and fronto-temporal groups performed worse in executive functioning and better in constructional ability. Study 2 found no differences in neuropsychological and community re-integration measures at 1-year follow-up. Study 3 found comparable neuropsychological test score improvement across groups over 1 year.Conclusions: Results are consistent with previous findings and document the potential for test score improvement with rehabilitation and suggest that lesion location needs to be considered when individual rehabilitation plans are being implemented in the post-acute stage of TBI.

Development of an Integrative Cognitive Rehabilitation Program for Brain Injured Patients in the Post-acute Stage

This study was conducted to develop a comprehensive cognitive rehabilitation program that can be easily applied to brain injured patients by family members or nurses in community or hospital settings. A Systemic literature review design was used. Thirty-three related studies were reviewed. Based on the results of the literature review, the training tasks for attention were designated to enhancing 4 hierarchical areas, i.e., focused, selective, alternating, and divided attention. On the other hand, the memory rehabilitation tasks mainly consisted of mnemonic skills, such as the association method which helps patients memorize given information by linking together common attributes, the visual imagery method, and self-instruction method. The problem solving rehabilitation program included a task of games or plays which stimulated the patients' curiosity and interest. The training tasks for problem solving were to encourage the process of deriving reasonable solutions for a problematic situation resembling real problems that the patients were faced with in their everyday life. It is expected that the cognitive rehabilitation program developed from this study could help patients having difficulty in their every day life, due to a reduced cognitive ability resulting from brain injury, to effectively adapt to every day life.

Review of subjectThe role of pharmacotherapy in the management of behaviour disorders in traumatic brain injury patients

The aim of this paper was to systematically review the research published in English language on the effectiveness of drugs for the treatment of neurobehavioural disorders in patients with traumatic brain injury (TBI). A literature search using Medline, Pre-Medline, Embase, Psychlit and Cochrane Library databases between 1990 and January 2003 as well as a hand search of Brain Injury since 1996 were carried out. Phrases such as ‘head injury’, ‘brain injury’, ‘drug treatment’, ‘drug trials’ and ‘randomized controlled trials’ were used. Sixty-three papers were selected for data synthesis. Of these, 13 were randomized controlled trials, eight were prospective observational studies, four were retrospective studies, 25 were case series and 13 were single case studies. There was a dearth of type I-III evidence. There was no strong evidence either way to suggest that drugs are effective in the treatment of behaviour disorders in patients with TBI. However, there was weak evidence, primarily based on case studies that psychostimulants are effective in the treatment of apathy, inattention and slowness; high dose beta-blockers in the treatment of agitation and aggression; anti-convulsants and anti-depressants (particularly SSRIs) in the treatment of agitation and aggression, particularly in the context of an affective disorder; and possibly a specific neuroleptic methotrimeprazine in the treatment of agitation in the post-acute stage of Acquired Brain Injury. Some drugs that are effective in some patients have been shown to be ineffective in others. Some drugs, particularly lithium and dopaminergic drugs could cause adverse effects and deterioration in some patients.