Diffuse Axonal Damage Research Articles

Loss of microRNA-15a/16-1 function promotes neuropathological and functional recovery in experimental traumatic brain injury.

The diffuse axonal damage in white matter and neuronal loss, along with excessive neuroinflammation, hinder long-term functional recovery after traumatic brain injury (TBI). MicroRNAs (miRs) are small noncoding RNAs that negatively regulate protein-coding target genes in a posttranscriptional manner. Recent studies have shown that loss of function of the miR-15a/16-1 cluster reduced neurovascular damage and improved functional recovery in ischemic stroke and vascular dementia. However, the role of the miR-15a/16-1 cluster in neurotrauma is poorly explored. Here, we report that genetic deletion of the miR-15a/16-1 cluster facilitated the recovery of sensorimotor and cognitive functions, alleviated white matter/gray matter lesions, reduced cerebral glial cell activation, and inhibited infiltration of peripheral blood immune cells to brain parenchyma in a murine model of TBI when compared with WT controls. Moreover, intranasal delivery of the miR-15a/16-1 antagomir provided similar brain-protective effects conferred by genetic deletion of the miR-15a/16-1 cluster after experimental TBI, as evidenced by showing improved sensorimotor and cognitive outcomes, better white/gray matter integrity, and less inflammatory responses than the control antagomir-treated mice after brain trauma. miR-15a/16-1 genetic deficiency and miR-15a/16-1 antagomir also significantly suppressed inflammatory mediators in posttrauma brains. These results suggest miR-15a/16-1 as a potential therapeutic target for TBI.

Ionized hypocalcemia as a prognostic factor of early mortality in traumatic brain injury

ABSTRACT Traumatic brain injury (TBI) is a common neurological condition. It can affect mental, physical, and cognitive functions and is a common cause of mortality. Electrolytes imbalance is common in those patients. Effective therapy of electrolytes abnormalities improves neurological outcome and reduces mortality. Therefore, we studied the predictive significance of ionized hypocalcemia for early mortality in TBI patients. Patients and method This observational study in the intensive care units of the Ain Shams University hospitals was done on sixty adult patients with TBI of both sexes, divided into two groups: group A (ionized hypocalcemic patients), and group B (normocalcemic patients). On admission, medical history, physical examination including neurological evaluation, and appropriate investigations were performed. Ionized calcium was measured at the start of the 28-day study and then every five days after that. Results There was no statistically significant difference between the two groups for demographic data, brain injury type, or the number of intubated patients (p > 0.05). There was a statistically significant difference for diffuse axonal damage, subdural hemorrhage, cerebral edema, GCS, and mean blood pressure (p < 0.001). Serum ionized calcium in group A was significantly lower than in group B on the day of admission and day five (p < 0.001). On the day of admission, there was a significant difference in serum sodium (p < 0.05). In both groups, there was a significant difference in the ICU stay as regards survivors (p < 0.001). There was a statistically significant difference in 28-day mortality between the two groups (p = 0.001). Conclusion In TBI patients, ionized hypocalcemia on admission and on day five, hypernatremia and disturbed conscious level are strongly linked to greater fatality rates.

Traumatic Brain Injury and Neuromodulation Techniques in Rehabilitation: A Scoping Review.

Traumatic Brain Injury (TBI) is a condition in which an external force, usually a violent blow to the head, causes functional impairment in the brain. Neuromodulation techniques are thought to restore altered function in the brain, resulting in improved function and reduced symptoms. Brain stimulation can alter the firing of neurons, boost synaptic strength, alter neurotransmitters and excitotoxicity, and modify the connections in their neural networks. All these are potential effects on brain activity. Accordingly, this is a promising therapy for TBI. These techniques are flexible because they can target different brain areas and vary in frequency and amplitude. This review aims to investigate the recent literature about neuromodulation techniques used in the rehabilitation of TBI patients. The identification of studies was made possible by conducting online searches on PubMed, Web of Science, Cochrane, Embase, and Scopus databases. Studies published between 2013 and 2023 were selected. This review has been registered on OSF (JEP3S). We have found that neuromodulation techniques can improve the rehabilitation process for TBI patients in several ways. Transcranial Magnetic Stimulation (TMS) can improve cognitive functions such as recall ability, neural substrates, and overall improved performance on neuropsychological tests. Repetitive TMS has the potential to increase neural connections in many TBI patients but not in all patients, such as those with chronic diffuse axonal damage. This review has demonstrated that neuromodulation techniques are promising instruments in the rehabilitation field, including those affected by TBI. The efficacy of neuromodulation can have a significant impact on their lives and improve functional outcomes for TBI patients.

Longitudinal fibre-specific white matter damage predicts cognitive decline in multiple sclerosis.

During the course of multiple sclerosis, many patients experience cognitive deficits which are not simply driven by lesion number or location. By considering the full complexity of white matter structure at macro- and microstructural levels, our understanding of cognitive impairment in multiple sclerosis may increase substantially. Accordingly, this study aimed to investigate specific patterns of white matter degeneration, the evolution over time, the manifestation across different stages of the disease and their role in cognitive impairment using a novel fixel-based approach. Neuropsychological test scores and MRI scans including 30-direction diffusion-weighted images were collected from 327 multiple sclerosis patients (mean age = 48.34 years, 221 female) and 95 healthy controls (mean age = 45.70 years, 55 female). Of those, 233 patients and 61 healthy controls had similar follow-up assessments 5 years after. Patients scoring 1.5 or 2 standard deviations below healthy controls on at least two out of seven cognitive domains (from the Brief Repeatable Battery of Neuropsychological Tests, BRB-N) were classified as mildly cognitively impaired or cognitively impaired, respectively, or otherwise cognitively preserved. Fixel-based analysis of diffusion data was used to calculate fibre-specific measures (fibre density, reflecting microstructural diffuse axonal damage; fibre cross-section, reflecting macrostructural tract atrophy) within atlas-based white matter tracts at each visit. At baseline, all fixel-based measures were significantly worse in multiple sclerosis compared with healthy controls (P < 0.05). For both fibre density and fibre cross-section, a similar pattern was observed, with secondary progressive multiple sclerosis patients having the most severe damage, followed by primary progressive and relapsing-remitting multiple sclerosis. Similarly, damage was least severe in cognitively preserved (n = 177), more severe in mildly cognitively impaired (n = 63) and worst in cognitively impaired (n = 87; P < 0.05). Microstructural damage was most pronounced in the cingulum, while macrostructural alterations were most pronounced in the corticospinal tract, cingulum and superior longitudinal fasciculus. Over time, white matter alterations worsened most severely in progressive multiple sclerosis (P < 0.05), with white matter atrophy progression mainly seen in the corticospinal tract and microstructural axonal damage worsening in cingulum and superior longitudinal fasciculus. Cognitive decline at follow-up could be predicted by baseline fixel-based measures (R2 = 0.45, P < 0.001). Fixel-based approaches are sensitive to white matter degeneration patterns in multiple sclerosis and can have strong predictive value for cognitive impairment. Longitudinal deterioration was most marked in progressive multiple sclerosis, indicating that degeneration in white matter remains important to characterize further in this phenotype.

Significance of Corticospinal, Associative and Inter-Hemispheric Tracts for the Development of Posttraumatic Hemiparesis

Motor disorders are among the most common consequences of severe craniocerebral injury (traumatic brain injury — TBI). Deeper insights into pathophysiological mechanisms of these disorders is important both from a theoretical point of view and in terms of improving neurorehabilitation approaches.The aim of the study was to investigate the correlation of right–sided posttraumatic hemiparesis severity with composite characteristics of fractional anisotropy (FA) in the segments of the corpus callosum (CC), corticospinal tract (CST) and the inferior fronto-occipital fasciculus (IFO) at different stages of traumatic disease (acute, subacute and long-term periods).Material and methods. Cases of 43 patients with TBI were analyzed (28 men and 15 women aged 13 to 59 years, mean age 28±9 years). Forty patients were diagnosed with severe TBI with diffuse axonal damage, three patients had moderate severity TBI. Long-term follow up included continuous clinical and neurological examination with evaluation of patient’s level of consciousness using the CRS-R scale, and the degree of motor deficits in right-sided hemiparesis using a five-point scale. During three post-TBI periods (up to 1 month, from 1 to 6 months, and from 6 to 12 months), patients were examined using diffusion tensor MRI (DTI), tractography and FA. Motor, cortico-spinal tracts and IFO were divided by measurement grid, correlations between FA and scores of right-sided hemiparesis were calculated for each segment.Results. FA correlations (P0.05) with the severity of hemiparesis were established not only for CST motor-specific segments, but also for some CC and IFO segments. In the early period of TBI significant correlations with hemiparesis severity were found not only in the contralateral CST segments, but also in the ipsilateral ones. Significant differences in FA in the related CC and CST segments were found between the groups with good and limited motor recovery: at all stages after TBI, FA was higher in patients with successful recovery.Conclusion. The results of the study provide better insight into pathophysiological mechanisms of post-traumatic motor disorders development, therefore favoring optimization of therapeutic strategies.

Altered brain connectivity, neuroinflammation and AD‐related markers following 7 days after repetitive mild traumatic brain injury in young wild‐type mice

AbstractBackgroundTraumatic brain injuries (TBI) substantially increase the risk for neurodegenerative disorders including tauopathies and synucleinopathies. Repetitive mild TBI (rmTBI) exacerbate damage in brain impacting cognitive and emotional processes through lifetime. Therefore, there is a critical need to identify the molecular mechanisms underlying TBI‐mediated brain dysfunction. In doing so, we can develop effective therapies as the etiology for dementia remain poorly understood. Our goal is to identify early, unbiased, and novel biomarkers of brain dysfunction following rmTBI. These include defects in the brain connectome and protein expression in the areas most functionally susceptible to damage following rmTBI.MethodTo do this, we exposed young male and female C57BL/6J wild‐type mice to two rmTBI (2 × 0.6 J impacts/24 h apart) using the closed head injury model of engineered rotational acceleration (CHIMERA) or sham procedures. We measured changes in brain functional connectivity (FC) using resting state functional MRI (rsfMRI) and graph theory, examined microstructural differences in white and grey matter regions through diffusion tensor imaging (DTI) analyses, surveyed neuropathological proteins using NanoString‐GeoMx Digital spatial protein profiling spatial profiling (DSP).ResultThe rsfMRI data revealed that rmTBI induces aberrant changes in the graph metrics such as node clustering coefficient, global and local efficiency, participation coefficient, eigenvector centrality, and betweenness centrality in brain regions processing visual, auditory, and somatosensory information. The optic tract and thalamus were the most affected regions showing significant differences in phospho‐tau (S199), neuroinflammatory markers (GFAP, Iba‐1, GPNMB), and other proteolytic (cathepsin‐D) and proliferation (ki‐67) cell markers. We identified extensive white matter damage, defects in brain FC, and exacerbated anatomically distinct protein profiles.ConclusionThese findings align with results reported in individuals with TBI such as diffuse axonal damage, glial activation, and functional network disruption in the visual tract and specific thalamic regions. Upcoming studies will evaluate the potential use of using brain imaging along with molecular markers to predict longitudinal damage after rmTBI.

Repeated blast-induced neurotrauma (systematic review)

During military conflicts, explosive injuries are observed, in particular, explosion-induced neurotrauma, which leads to significant impairment of brain functions and deterioration of the quality of life of the victims. Therefore, the study of the pathogenesis of such injuries is definitely relevant. Attention is drawn to repetitive blast-induced neurotrauma, because gunners and tankers, as well as civilians living in areas where such weapons are used, are most often exposed to it. In order to establish the already investigated features of the clinical and experimental course of mild repetitive blast-induced trauma, the aim of the work was to conduct a retrospective and prospective analysis of literary sources dedicated to the study of the features of the mechanisms of damage to the central nervous system after repeated blast wave action. To achieve the goal, a retro- and prospective analysis of literature and patents for the period 2003–2023 was conducted. As a result of the analysis, it was established that the action of the blast wave can cause a mild brain injury and that its repeated exposure leads to more serious consequences. These consequences include: diffuse axonal damage, oxidative stress, tissue damage, hemorrhage, vasoconstriction, edema, pseudoaneurysm formation, and induction of apoptosis. It can also be said that, in contrast to a single exposure, repeated exposure to a blast wave has a cumulative effect on different areas of the brain and causes chronic neuropathological changes. Dissociation of cerebral blood flow and metabolism, excitotoxicity, oxidative stress, cell death, astrocyte reactivity, blood-brain barrier dysfunction, microglia activation, dysmyelination, diffuse axon damage play a leading role in the pathogenesis of repeated blast-induced neurotrauma. Keywords: central nervous system, blast wave, brain, trauma.

A-35 Difficulty Speaking, Stuttering, and Missing Words Post-Concussion: Findings from Two Independent Studies

Abstract Purpose The current investigation examined the potential consequences of concussion on speech-language abilities by analyzing quantitative and qualitative data from two independent studies. Methods Study 1: 185 rugby, soccer, football, rowing, and hockey athletes (M=17.42 years, SD=3.80; 44% female) completed the Rosenbaum Concussion Attitude and Knowledge Survey (RoCKAS). Study 2: 19 varsity soccer, rugby, volleyball, and basketball athletes (M=21.74 years, SD=2.13; 37% female) with history of at least one concussion completed individual one-hour semi-structured interviews, and thematic analysis was used to identify patterns across athletes’ experiences of concussion. Results Study 1: Quantitative analysis of athletes’ endorsements of distractor and legitimate post-concussive symptoms on the RoCKAS yielded a relatively low rate of endorsement across all distractor symptoms (1–29%, M=11%), with the exception of ‘difficulty speaking’, which was endorsed by majority (70%) of the sample. Study 2: Thematic analysis of interview content identified long-term difficulties with speech articulation (i.e., stuttering and word-finding) as a post-concussive symptom for 42% of the sample. Conclusions While speech abilities are largely thought to remain intact following concussion, quantitative and qualitative findings from these two independent studies suggest that speech difficulties may be an overlooked outcome of concussion. Several neuropsychological (e.g., attention, memory, executive function, or processing speed) and neuropathophysiological (e.g., diffuse axonal damage to cortico-subcortical pathways) processes may be underlying this relationship. Exploratory studies and longitudinal data are needed to elucidate the potential consequences of concussion on speech-language abilities.

Expert errors in formulating a forensic diagnosis and conclusions in cases of diffuse axonal brain damage

The study objective is to review expert errors in the wording of a post-mortem diagnosis and expert conclusions in cases of traumatic brain injury with diffuse axonal brain damage. We reviewed 50 corpse examinations of those who died from a traumatic brain injury with diffuse axonal brain damage. A retrospective analysis of the results of expert examinations, the structure of the post-mortem forensic diagnosis, and the validity of expert conclusions showed that expert errors were made in 30% of cases. In 93% of cases, the errors were epistemological due to the lack of a scientifically based methodological approach to the expert opinion on a particular mechanism for the development of traumatic brain injury with diffuse axonal brain damage; and lack of professional expertise. A case is provided demonstrating the most common expert errors in the examination of this type of traumatic brain injury.

Mechanisms of Neurodegeneration in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which results in the formation of primary demyelinating lesions in the white and gray matter, as well as diffuse axonal and neuronal damage. Although there has been substantial progress in drug research in relapsing-remitting MS, treatment of progressive forms of the disease, can be challenging. Diffuse and compartmentalized lymphocyte and macrophage infiltration of the CNS tissue inhibits the differentiation of myelinating mature oligodendrocytes, disrupting the process of remyelination. Chronic inflammation that occurs behind a closed blood-brain barrier (BBB) leads to microglia activation, which increases mitochondrial damage to axons and neurons, and therefore triggers chronic oxidative stress and histotoxic hypoxia. Thus, raising awareness about the mechanisms of neurodegeneration appears relevant. In the late stages of MS, it is caused by chronic neuroaxonal damage, disruption of the regenerative ability of the CNS, and to a great extent determines the disease outcome.

A Delayed Presentation of Diffuse Axonal Injury

Diffuse axonal injury is one of the most common and debilitating pathologies resulting from mechanical deformation of the brain. The current case involves a 19-year-old female involved in a high velocity ski crash. The accident resulted in a right lower leg fracture, with no loss of consciousness or evidence of head trauma. Approximately 6.5 hours after her admission, the neurological status of the patient deteriorated markedly, and magnetic resonance imaging findings were consistent with diffuse axonal injury. This presentation illustrates a case of delayed diffuse axonal injury, a phenomenon not commonly described. Diffuse axonal injury involves rapid inertial forces causing strain to brain tissue. This strain results in various stages of diffuse axonal damage and inflammation. This article highlights a case of delayed onset diffuse axonal injury, describes the progression of neural sequelae post-injury resulting in axonal damage and explores proposed therapeutic targets.

Traumatic brain injury: Estimate of the age of the injury based on neuroinflammation, endothelial activation markers and adhesion molecules.

Studies on traumatic brain injury (TBI) are applicable not only in the clinical context, but also in the forensic field. Over time, the literature has accumulated scientific evidence supporting the use of specific histopathological tests in dating traumatic brain injuries. In primary damage, cell death occurs by necrosis/apoptosis. In secondary injury, the underlying mechanisms are inflammation and ischemia. The inflammatory response of the central nervous system (CNS) follows the common steps of the innate response. In head injury, the blood brain barrier (BBB) undergoes both functional damage and, subsequently, finer structural changes. Scientific evidence has shown modifications of the junctional-endothelial system that favors the extravasation of immunocompetent cells. The histological evaluation of the subdural hematoma, of the cerebral contusions, of the diffuse axonal damage can certainly bring useful elements, with limitations, to the chronological evaluation of the lesions. Many markers have been used to better define the dating of the head injury. Several authors also analyzed the usefulness of secondary damage markers in brain tissue. The progress achieved with immunohistochemistry is significant compared to the use of routine staining. With immunohistochemistry it is possible to identify much narrower and more precise time intervals and, above all, with greater probative reliability. Recently attention has been paid to the modification of structural proteins and miRNAs. Future research is already started and entrusted to multidisciplinary teams that know how to combine their specific skills in search of a reproducible standard of known and sufficient accuracy.

Forensic criteria for determining the time of diffuse axonal damage in the event of traumatic brain injury

Establishing the diagnostic criteria for diagnosing of brain diffuse axonal injury duration as a separate form of traumatic brain injury. The dynamics of structural and functional changes in the neuron-gliovascular module and neuroinflammatory response revealed at the light-optical level and their diagnostically significant morphological signs established as a result of a comprehensive study that can be considered as evidence-based criteria for the diffuse axonal brain damage duration.

Axotomy in the postmortem diagnosis of diffuse axonal brain injury

The results of the study of the significance of axotomy in the postmortem diagnosis of diffuse axonal brain damage are presented. In the corpus callosum, two main types of changes in the processes of neurons were found: damage to the processes without mechanical rupture and axotomy. The revealed polymorphism of damage to the processes of neurons indicates the heterogeneity and staging of pathological processes caused both by the trauma itself and by developing reactive post-traumatic changes. Severe damage to the processes is secondary and not earlier than 2 days after the injury lead to axotomy, the morphological manifestation of which is retraction balls with a diameter of 15.5±6.33 μm, detected by staining with hematoxylin and eosin. Research results indicate that axotomy should not be differentiated into primary and secondary.

Traumatic Axonal Injury

A 17-year-old prisoner was found unconscious during a morning check. The previous night, he had been struck on the chin multiple times by one of the other inmates. The patient remained unconscious and eventually died after nearly 1.5 months of care. The primary task of the forensic pathological examination was to investigate the events leading to his death; therefore, it was necessary to examine whether there was a connection between the abuse and eventual death. In our case, the key element was the repetitive, mild-to-moderate force in abuse, resulting in grade I traumatic diffuse axonal damage. Due to progressive brain edema, aspiration subsequently developed, which eventually resulted in irreversible hypoxic damage of the brain.

Emerging Diagnosis Improvements and Treatments of Mild to Traumatic Brain Injuries

This review paper evaluates the current clinical and research practices for diagonising and treating TBI and mTBI. It provides an overview of the new emerging treatments for mTBI and TBI that are in varying stages of research. The paper analyzes the shortcomings and practices of diagnosing mTBI and TBI and also evaluates new and potentially break-through mTBI and TBI treatments such as Iron Chelators, Cellular Therapy, Cannabinoid Receptor Treatment, Electroaccupuncture, and Transcanial Magnetic Stimulation. While the current method of diagnosis for severe TBI is sound, mTBIs remain largely undiagnosed or misdiagnosed. This paper identifies the limitations of current neuroimaging and diagnostic techniques for mTBI and TBI. There are many current treatments for the primary symptoms/damage of TBI and mTBI (severe swelling, trauma, neuroinflammation, edema, diffuse axonal damage, and loss of consciousness). However, there is little or no treatment for secondary injuries (personality shifts, free iron collection, cognitive deficits in short-term memory, abstract reasoning, and many unique deficits dependent on the site of injury). This review paper seeeks to evaluate emerging research and diagnostic methods and explores possible new directions for diagnosis and conceivable conjunction therapies to treat multiple aspects and deficits of mTBI and TBI.

Dissociation between declarative and procedural memory in patients following head injury – Evidence from finger opposition sequence paradigm

Many patients surviving traumatic brain injury (TBI) are left with significant disabilities, including memory impairment which can be declarative, procedural, or context-dependent. Dissociation between procedural and declarative learning has been described in a number of patients following focal brain injuries. Described below are two such cases involving diffuse axonal damage that demonstrated such dissociation. Description of two patients (out of ten) who participated in a study aimed to characterize procedural learning after TBI and presented with implicit–explicit memory dissociation. Subjects were tested using a series of finger opposition movements which they had to perform as rapidly and accurately as possible through several training session over two weeks and one month afterwards. The subjects underwent evaluation to characterize their cognitive impairments and subsequent impacts on learning ability. Both subjects demonstrated severe declarative memory deficits as demonstrated in the Rivermead Battery Memory Test (RBMT) but showed effective procedural learning of finger movement sequence as defined by improved performance speed across the training period without speed-accuracy trade-off. In addition, these findings were retained at the one month follow-up. The findings from the examination of these two subjects coincide with the current paradigm that declarative and procedural memory are two separate processes that appear to occur in spatially segregated brain regions that utilize functionally distinct pathways and demonstrate that such dissociation might be evident in damage to white matter tracts. Consequently, severe injury to one may present in parallel with preservation of the other domain. The ability to maintain the ability for procedural learning after severe head injuries, even in the presence of a severe impairment of declarative memory, can be exploited in therapeutic strategies aimed at increasing the patient's daily functioning.

The detection of the biomolecular markers of the axonal damage resulting from the craniocerebral injury by the immunohistological methods

The objective of the present study was to define and evaluate the parameters of validity of the diagnostic signs of the diffuse axonal damage resulting from the craniocerebral injury with the use of the immunohistological reaction for the presence of amyloid precursor protein (beta-APP) in the brain tissue associated with the craniocerebral injury. Both histological and immunological methods were used. The positive beta-APP reaction was documented in 2 of the six cases. It is concluded that the positive results of the immunohistological reaction for the presence of beta-APP protein provide an additional information about the mechanism behind the damage and confirm the diagnosis of the craniocerebral injury in the cases when its macroscopic signs are either absent or unapparent.

Mild Fluid Percussion Injury Induces Diffuse Axonal Damage and Reactive Synaptic Plasticity in the Mouse Olfactory Bulb

Despite the regenerative capacity of the olfactory bulb (OB), head trauma causes olfactory disturbances in up to 30% of patients. While models of olfactory nerve transection, olfactory receptor neuron (ORN) ablation, or direct OB impact have been used to examine OB recovery, these models are severe and not ideal for study of OB synaptic repair. We posited that a mild fluid percussion brain injury (mFPI), delivered over mid-dorsal cortex, would produce diffuse OB deafferentation without confounding pathology. Wild type FVB/NJ mice were subjected to mFPI and OB probed for ORN axon degeneration and onset of reactive synaptogenesis. OB extracts revealed 3 d postinjury elevation of calpain-cleaved 150-kDa αII-spectrin, an indicator of axon damage, in tandem with reduced olfactory marker protein (OMP), a protein specific to intact ORN axons. Moreover, mFPI also produced a 3-d peak in GFAP+ astrocyte and IBA1+ microglial reactivity, consistent with postinjury inflammation. OB glomeruli showed disorganized ORN axons, presynaptic degeneration, and glial phagocytosis at 3 and 7 d postinjury, all indicative of deafferentation. At 21 d after mFPI, normal synaptic structure re-emerged along with OMP recovery, supporting ORN afferent reinnervation. Robust 21 d postinjury upregulation of GAP-43 was consistent with the time course of ORN axon sprouting and synapse regeneration reported after more severe olfactory insult. Together, these findings define a cycle of synaptic degeneration and recovery at a site remote to non-contusive brain injury. We show that mFPI models diffuse ORN axon damage, useful for the study of time-dependent reactive synaptogenesis in the deafferented OB.

14 Recovery of pre-morbid levels of functioning after grade ii diffuse axonal injury following severe tbi

<h3>Objective</h3> To present a case of complete functional recovery, achieving pre-morbid levels of functioning, after sustaining a severe v TBI (GCS: 8; PTA: 9 days) with neuro-radiological evidence of grade II diffuse axonal injury. <h3>Method</h3> A 32 year old, right handed manager of a shipping company was referred to our unit for neuro-rehabilitation following a severe TBI in a road traffic accident (RTA), 13 days previously. Within 24 hours post-TBI a brain CT Scan and a brain MRI T1, T2, FLAIR and DWI sequences) at 2 weeks were performed. The patient underwent full neuropsychological assessment, 14 weeks post-TBI, to evaluate his premorbid IQ using the Test of Word Accentuation (Spanish) and the Vocabulary subtest of the Wechsler Adult Intelligence Scale III version (WAIS III). His current IQ was assessed using the WAIS III full scale. The Barcelona Test – revised version assessed his language ability. Executive function was evaluated using the Stoop Test, Trail B and the Wisconsin Card Sorting Test (WCST). He was discharged with out-patient follow-up 3 weeks after the RTA. Out-patient neuropsychiatric review took place at 6, 20 weeks post-TBI and by telephone at 6 months. <h3>Results</h3> The patient made an excellent physical recovery with no neurological focal signs detected on discharge. The initial brain CT Scan was reported within normal range. Brain MRI (T2, FLAIR, DWI) revealed bilateral frontal hyperintensities in subcortical white matter, anterior splenium, posterior corpus callosum (CC), left internal capsule extending to the cerebral peduncle and left dorsolateral mescenphalon, compatible with non-haemorrhagic diffuse axonal damage (grade II).Pre- morbid IQ was estimated in the “above average” range. He scored in the “high or superior” range in all the rest of the tests of current cognitive performance (percentile range 77–96). Neuropsychiatric assessment found no evidence of neuropsychiatric or behavioural problems, only referring mild fatigue at 20 weeks follow-up. He gradually returned to work and was working full time at 6 months follow-up, referring improvement in his fatigue. <h3>Conclusions</h3> Complete recovery after grade II diffuse axonal damage is achievable.