Functional and Structural Integrity of Frontoparietal Connectivity in Traumatic and Anoxic Coma.

OBJECTIVES: Recovery from coma might critically depend on the structural and functional integrity of frontoparietal networks. We aimed to measure this integrity in traumatic brain injury and anoxo-ischemic (cardiac arrest) coma patients by using an original multimodal MRI protocol. DESIGN: Prospective cohort study. SETTING: Three Intensive Critical Care Units affiliated to the University in Toulouse (France). PATIENTS: We longitudinally recruited 43 coma patients (Glasgow Coma Scale at the admission < 8; 29 cardiac arrest and 14 traumatic brain injury) and 34 age-matched healthy volunteers. Exclusion criteria were disorders of consciousness lasting more than 30 days and focal brain damage within the explored brain regions. Patient assessments were conducted at least 2 days (5 ± 2 d) after complete withdrawal of sedation. All patients were followed up (Coma Recovery Scale-Revised) 3 months after acute brain injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional and structural MRI data were recorded, and the analysis was targeted on the posteromedial cortex, the medial prefrontal cortex, and the cingulum. Univariate analyses and machine learning techniques were used to assess diagnostic and predictive values. Coma patients displayed significantly lower medial prefrontal cortex-posteromedial cortex functional connectivity (area under the curve, 0.94; 95% CI, 0.93-0.95). Cardiac arrest patients showed specific structural disturbances within posteromedial cortex. Significant cingulum architectural disturbances were observed in traumatic brain injury patients. The machine learning medial prefrontal cortex-posteromedial cortex multimodal classifier had a significant predictive value (area under the curve, 0.96; 95% CI, 0.95-0.97), best combination of subregions that discriminates a binary outcome based on Coma Recovery Scale-Revised). CONCLUSIONS: This exploratory study suggests that frontoparietal functional disconnections are specifically observed in coma and their structural counterpart provides information about brain injury mechanisms. Multimodal MRI biomarkers of frontoparietal disconnection predict 3-month outcome in our sample. These findings suggest that fronto-parietal disconnection might be particularly relevant for coma outcome prediction and could inspire innovative precision medicine approaches.

Minor head trauma-induced sporadic hemiplegic migraine coma.

Familial hemiplegic migraine is a severe, rare subtype of migraine. Gene mutations on chromosome 19 have been identified in the calcium channel, voltage-dependent, P/Q type, alpha-1A subunit gene (chromosome 19p13) for familial hemiplegic migraine. Recently a gene mutation (Serine-218-Leucine) for a dramatic syndrome associated with familial hemiplegic migraine, commonly named "migraine coma", has implicated exon 5 of this gene. The occurrence of trivial head trauma, in such familial hemiplegic migraine patients, may also be complicated by severe, sometimes even fatal, cerebral edema and coma occurring after a lucid interval. Sporadic hemiplegic migraine shares a similar spectrum of clinical presentation and genetic heterogeneity. The case report presented in this article implicates the involvement of the Serine-218-Leucine mutation in the extremely rare disorder of minor head trauma-induced migraine coma. We conclude that the Serine-218-Leucine mutation in the calcium channel, voltage-dependent, P/Q type, alpha-1A subunit gene is involved in sporadic hemiplegic migraine, delayed cerebral edema and coma after minor head trauma.

Recovery process of immediate prolonged posttraumatic coma following severe head injury without mass lesions.

The recovery process of immediate posttraumatic coma was investigated in 24 patients with severe head injury. The correlation between poor outcome in the recovery process and magnetic resonance (MR) imaging findings was analyzed. MR imaging was performed within the first 7 days for all patients. The recovery process was classified into phase 1 for recovery to moderately disabled and phase 2 to good recovery (GR) according to the Glasgow Outcome Scale. The median of phase 1 was 21.0 days. Four patients did not recover to GR and had poor outcome. Twenty patients recovered to GR. Thirteen patients had short phase 2 of under 10 days and seven patients had long phase 2 of over 60 days. All patients had abnormal lesions on MR imaging considered to be diffuse axonal injury. The number of lesions ranged from two to 10, with a mean of five. Lesions in the dorsal upper brainstem were significantly associated with poor outcome (p < 0.05). The combination of focal lesions in the callosal splenium and dorsal upper brainstem was most common in patients with poor outcome. Patients with long phase 2 had significantly more lesions than patients with short phase 2.

Changes in white matter in long-term survivors of severe non-missile traumatic brain injury: a computational analysis of magnetic resonance images.

The aim of this study was to investigate long-term consequences of severe non-missile traumatic brain injury (nmTBI) in patients without macroscopic focal brain lesions (>1.6 cm(3)) on regional white-matter density (WMd), and possible correlations with days of coma and memory performances. T1-weighted magnetic-resonance images (MRI) were acquired in 19 nmTBI patients, 3-113 months following the injury, and in 19 control subjects matched for age and gender. In addition, nmTBI patients underwent a battery of standardised memory tests. The MRIs were processed in a fully automatic system using voxel-by-voxel methods. Corpus callosum, fornix, anterior limb of the internal capsule, superior frontal gyrus, para-hippocampal gyrus, optic radiation and chiasma showed significant WMd reduction in nmTBI when compared to control subjects. None of the correlations between days of coma and memory performance scores with nmTBI voxels value that showed WMd reduction reached significance, with the exception of a significant negative correlation between WMd in the mid body of corpus callosum and short-story delayed recall. We detected reductions in WM density in several brain locations similar to those described in previous post mortem investigations. In addition, we observed WMd reduction in the optic chiasma and in the optic radiations; this finding may reflect transneural degeneration along the visual pathway. The weak correlations between specific anatomical sites of the reduced WMd and behavior may reflect the diffuse nature of the brain damage and/or the different time of onset between behavioral manifestations and neuropathological modifications occurring in nmTBI.