Traumatic microbleeds suggest vascular injury and predict disability in traumatic brain injury

Griffin, Allison; Turtzo, L. Christine; Parikh, Gunjan; Tolpygo, Alexander; Lodato, Zachary; Moses, Anita D; Nair, Govind; Perl, Daniel P.; Edwards, Nancy A.; Dardzinski, Bernard J.; Armstrong, Regina C.; Ray‐Chaudhury, Abhik; Mitra, Partha P.; Latour, Lawrence L.

doi:10.1093/brain/awz290

Cited by 107 publications

(101 citation statements)

References 49 publications

(66 reference statements)

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“…36,37 APP that is strongly expressed acutely after TBI in injured axons also shows decreased expression with time. 40 Indeed, blood brain barrier disruption and microvascular pathology has been found to be widespread even in less severe head injury and partially overlap with regions of axonal injury. 41 Postmortem MRI has been proposed as an adjuvant to standard neuropathological assessment, 42 as ex vivo MRI measures of white matter integrity may help to elucidate the neuroanatomic basis of altered consciousness and cognitive deficits observed antemortem.…”

Section: Discussionmentioning

confidence: 99%

Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study

Nolan

Petersen²,

Iacono

et al. 2020

Preprint

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Diffusion tractography MRI can infer changes in network connectivity in patients with traumatic brain injury (TBI), but pathological substrates of disconnected tracts have not been well-defined due to a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750 μm resolution, followed by histopathologic evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. Analysis of 74 cerebral hemispheric white matter regions revealed a heterogeneous distribution of tract disruptions. Associated histopathology identified variable white matter injury with patchy deposition of amyloid precursor protein and loss of neurofilament-positive axonal processes, myelin dissolution, astrogliosis, microgliosis, and perivascular hemosiderin-laden macrophages. Multiple linear regression revealed that tract disruption strongly correlated with neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.

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Section: Discussionmentioning

confidence: 99%

Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study

Nolan

Petersen²,

Iacono

et al. 2020

Preprint

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“…Cerebral edema and contusion expansion are key secondary injury contributors to post-traumatic morbidity and mortality and for decades have commanded a significant proportion of neurosurgical and neurocritical care resources . There is also evidence that traumatic microbleeds (previously considered markers of axonal injury) may represent vascular injury with perivascular iron laden macrophages tracking a network of injured vessels [29]-yet another permutation of vascular secondary injury that has unfavorable functional consequences and that may respond to targeted therapy [29][30][31][32]. Cerebral edema has been noted to occur in up to 60% of TBI patients with mass lesions and~15% with initially 'negative' CT scans [13,[33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence

Jha

Bell

Citerio

et al. 2020

IJMS

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Cerebral edema and contusion expansion are major determinants of morbidity and mortality after TBI. Current treatment options are reactive, suboptimal and associated with significant side effects. First discovered in models of focal cerebral ischemia, there is increasing evidence that the sulfonylurea receptor 1 (SUR1)—Transient receptor potential melastatin 4 (TRPM4) channel plays a key role in these critical secondary injury processes after TBI. Targeted SUR1-TRPM4 channel inhibition with glibenclamide has been shown to reduce edema and progression of hemorrhage, particularly in preclinical models of contusional TBI. Results from small clinical trials evaluating glibenclamide in TBI have been encouraging. A Phase-2 study evaluating the safety and efficacy of intravenous glibenclamide (BIIB093) in brain contusion is actively enrolling subjects. In this comprehensive narrative review, we summarize the molecular basis of SUR1-TRPM4 related pathology and discuss TBI-specific expression patterns, biomarker potential, genetic variation, preclinical experiments, and clinical studies evaluating the utility of treatment with glibenclamide in this disease.

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“…[33][34][35] In contrast, in adult patients and especially in studies focusing strictly on TMBs the results are at best mixed. 29,30,32,[52][53][54] Van der Horn and colleagues 30 could not find any differences in terms of number, depth, and anatomical location of TMBs in patients after CHI with or without posttraumatic complaints. Furthermore, a substantial relationship between the initial GCS score and trauma-associated microbleeds emerged in the present study.…”

Section: Generalmentioning

confidence: 88%

Higher sensitivity for traumatic cerebral microbleeds at 7 T ultra-high field MRI: is it clinically significant for the acute state of the patients and later quality of life?

Hütter

Altmeppen

Kraff

et al. 2020

Ther Adv Neurol Disord

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Background: The present study evaluates the possible prognostic benefits of 7 T susceptibility weighted imaging (SWI) of traumatic cerebral microbleeds (TMBs) over 3 T SWI to predict the acute clinical state and subjective impairments, including health-related quality of life (HRQOL), after closed head injury (CHI). Methods: The study group comprised 10 participants with known TMBs All subjects underwent 3 T magnetic resonance imaging (MRI) and 7 T MRI, respectively. Location and count of TMBs were independently evaluated by two neuroradiologists. The initial Glasgow Coma Scale (GCS), the duration of coma and further clinical data were taken from the patients records. HRQOL was assessed by means of a questionnaire. Memory complaints and neurological symptoms were inquired at the time of the MRI examinations. Results: SWI revealed a total of 485 TMBs at 3 T, 584 TMBs at 7 T with similar spatial resolution, and 684 TMBs at 7 T with a factor of 10 higher spatial resolution. The TMBs depicted by 7 T high-resolution SWI were correlated with the duration of coma (Spearman’s rho of 0.77). The corresponding association with TMBs in 3 T MRI SWI showed a Spearman’s rho of 0.71. The initial GCS score and TMBs correlated with a Spearman’s rho of −0.35 at 3 T SWI MRI and a rho of −0.33 at 7 T high-resolution SWI, respectively. The physical aspect of HRQOL correlated substantially with the count of TMBs (rho = 0.44 for 3 T SWI and rho = 0.35 for both 7 T SWI sequences, respectively). Conclusions: The number of TMBs showed a substantial association with indicators of the acute clinical state and chronic neurobehavioral parameters after CHI, but there was no additional advantage of 7 T MRI. These preliminary findings warrant a larger prospective study for the future.

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Traumatic microbleeds suggest vascular injury and predict disability in traumatic brain injury

Cited by 107 publications

References 49 publications

Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study

Tractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study

Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence

Higher sensitivity for traumatic cerebral microbleeds at 7 T ultra-high field MRI: is it clinically significant for the acute state of the patients and later quality of life?

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