The diagnosis of diffuse axonal injury: implications for forensic practice

Geddes, J. F.; Vowles, G. H.; Beer, Trevor W.; Ellison, D. W.

doi:10.1046/j.1365-2990.1997.4498044.x

Cited by 38 publications

(63 citation statements)

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“…␤-APP rapidly accumulates at sites of injury, stains damaged axons within 2 hours after injury, and remains detectable in axons and bulbs for more than 2 weeks. 9,17,20 In this study, all fatal malaria cases died within 2 weeks of admission to hospital. Therefore all damaged axons should remain visibly labeled using this method.…”

Section: Discussionmentioning

confidence: 81%

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Axonal Injury in Cerebral Malaria

Medana¹,

Day²,

Hien³

et al. 2002

The American Journal of Pathology

157

130

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Impairment of consciousness and other signs of cerebral dysfunction are common complications of severe Plasmodium falciparum malaria. Although the majority of patients make a complete recovery a significant minority, particularly children, have sequelae. The pathological process by which P. falciparum malaria induces severe but usually reversible neurological complications has not been elucidated. Impairment of transport within nerve fibers could induce neurological dysfunction and may have the potential either to resolve or to progress to irreversible damage. ␤-amyloid precursor protein (␤-APP) immunocytochemistry, quantified using digital image analysis, was used to detect defects in axonal transport in brain sections from 54 Vietnamese cases with P. falciparum malaria. The frequency and extent of ␤-APP staining were more severe in patients with cerebral malaria than in those with no clinical cerebral involvement. ␤-APP staining was often associated with hemorrhages and areas of demyelination, suggesting that multiple processes may be involved in neuronal injury. The age of focal axonal damage, as determined by the extent of the associated microglial response, varied considerably within tissue sections from individual patients. These findings suggest that axons are vulnerable to a broad range of cerebral insults that occur during P. falciparum malaria infection. Disruption in axonal transport may represent a final common pathway leading to neurological dysfunction in cerebral malaria. Cerebral malaria (CM) is a diffuse, potentially reversible, encephalopathy, caused by infection with the protozoan parasite Plasmodium falciparum. CM presents clinically with convulsions and coma, and carries 15 to 20% mortality. The malaria parasite invades and develops within erythrocytes that sequester in the cerebral microvasculature and other vital organs by adhesion to specific endothelial receptors. 1,2 The pathophysiological consequences of severe malaria infection have not been satisfactorily resolved. In particular it is not known how parasitized red blood cells, which remain within the vascular space, influence parenchymal brain function to induce coma and death. Histopathological studies reveal a variety of neurological abnormalities including chromatolysis, neuronophagia, and decreased glial cell numbers. [2][3][4][5]

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Section: Discussionmentioning

confidence: 81%

“…In addition, an approximate time scale of microglial responses to AI was used to estimate the timing of injury in individual lesions. 17,18 Slides were read blind to the clinical details of the patient by two independent observers (IM and GT).…”

Section: Other Neuropathological Featuresmentioning

confidence: 99%

Axonal Injury in Cerebral Malaria

Medana¹,

Day²,

Hien³

et al. 2002

The American Journal of Pathology

157

130

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“…In humans, axonal injury with similar histological features has been reported days to months after trauma, with the highest prevalence around 24 h after injury (Adams et al, 1977(Adams et al, , 1982(Adams et al, , 1989Vanezis et al, 1987;Christman et al, 1994;Graham et al, 1995;Geddes et al, 1997Geddes et al, , 2000Oehmichen et al, 1999). Reactive astrocytes can be seen as early as 1 d after TBI, but their numbers and GFAP immunoreactivity increase markedly during the first week (Vanezis et al, 1987;Geddes et al, 1997;Geddes et al, 2000;. Infiltration of macrophages occurs at 3-5 d after trauma and is most marked 1-2 weeks after injury (Adams et al, 1977;Geddes et al, 1997;Oehmichen et al, 1999).…”

Section: Discussionmentioning

confidence: 92%

“…(Strich, 1956(Strich, , 1961Nevin, 1967;Oehmichen et al, 2003). Another issue is whether pericontusional axonal injury (Strich, 1961;Cervos-Navarro and Lafuente, 1991; differs fundamentally from diffuse axonal injury not associated with contusion (Adams et al, 1977(Adams et al, , 1982Vanezis et al, 1987;Graham et al, 1995;Geddes et al, 1997). The controlled cortical impact model used in this study produces a central contusion and surrounding pericontusional axonal injury.…”

Section: Discussionmentioning

confidence: 97%

“…Reactive astrocytes can be seen as early as 1 d after TBI, but their numbers and GFAP immunoreactivity increase markedly during the first week (Vanezis et al, 1987;Geddes et al, 1997;Geddes et al, 2000;. Infiltration of macrophages occurs at 3-5 d after trauma and is most marked 1-2 weeks after injury (Adams et al, 1977;Geddes et al, 1997;Oehmichen et al, 1999). Other strengths and limitations of this mouse model and the specific histological techniques used have previously been addressed (Mac Donald et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

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Diffusion Tensor Imaging Reliably Detects Experimental Traumatic Axonal Injury and Indicates Approximate Time of Injury

Donald¹,

Dikranian²,

Bayly³

et al. 2007

J. Neurosci.

395

337

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Traumatic axonal injury (TAI) may contribute greatly to neurological impairments after traumatic brain injury, but it is difficult to assess with conventional imaging. We quantitatively compared diffusion tensor imaging (DTI) signal abnormalities with histological and electron microscopic characteristics of pericontusional TAI in a mouse model. Two DTI parameters, relative anisotropy and axial diffusivity, were significantly reduced 6 h to 4 d after trauma, corresponding to relatively isolated axonal injury. One to 4 weeks after trauma, relative anisotropy remained decreased, whereas axial diffusivity "pseudo-normalized" and radial diffusivity increased. These changes corresponded to demyelination, edema, and persistent axonal injury. At every time point, DTI was more sensitive to injury than conventional magnetic resonance imaging, and relative anisotropy distinguished injured from control mice with no overlap between groups. Remarkably, DTI changes strongly predicted the approximate time since trauma. These results provide an important validation of DTI for pericontusional TAI and suggest novel clinical and forensic applications.

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Diffusely Abnormal White Matter in Chronic Multiple Sclerosis

Seewann¹,

Vrenken²,

Valk³

et al. 2009

Arch Neurol

156

171

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Background: Diffuse abnormalities in the white matter (WM), ie, the so-called diffusely abnormal WM (DAWM), as observed on magnetic resonance imaging (MRI), may contribute to the development of clinical disability in multiple sclerosis (MS). Underlying pathologic and MRI characteristics of DAWM are largely unknown.Objectives: To explore and describe the histopathologic and radiologic characteristics of DAWM in chronic MS.Design: An MRI and histopathologic postmortem correlative study. Methods:We analyzed 17 formalin-fixed hemispheric brain slices from 10 patients with chronic MS using histopathologic analysis and qualitative and quantitative MRI. A region-of-interest approach was applied to compare radiologically defined DAWM, normal-appearing WM, and focal WM lesions and to correlate quantitative MRI measures with histopathologic findings. Main Outcome Measures:The DAWM consisted of extensive axonal loss, decreased myelin density, and chronic fibrillary gliosis, all of which were substantially abnormal compared with normal-appearing WM and significantly different from focal WM lesion pathology. Increased T1-and T2-relaxation times and decreased fractional anisotropy values were found in DAWM regions of interest, in association with extensive axonal loss and reduced myelin density. Increased T1-and T2relaxation times were associated with chronic gliosis.Conclusions: This study classifies DAWM in chronic MS as an abnormality that is different from normalappearing WM and focal WM lesions, most likely resulting from the cumulative effects of ongoing inflammation and axonal pathology. As such, DAWM is likely to substantially contribute to disease progression and may prove to be an important new disease marker in clinical trials focusing on the neurodegenerative aspects of MS.

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The diagnosis of diffuse axonal injury: implications for forensic practice

Cited by 38 publications

References 0 publications

Axonal Injury in Cerebral Malaria

Axonal Injury in Cerebral Malaria

Diffusion Tensor Imaging Reliably Detects Experimental Traumatic Axonal Injury and Indicates Approximate Time of Injury

Diffusely Abnormal White Matter in Chronic Multiple Sclerosis

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