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.

Diverse effects of hypothermia therapy in patients with severe traumatic brain injury based on the computed tomography classification of the traumatic coma data bank.

A multicenter randomized controlled trial of patients with severe traumatic brain injury who received therapeutic hypothermia or fever control was performed from 2002 to 2008 in Japan (BHYPO). There was no difference in the therapeutic effect on traumatic brain injury between the two groups. The efficacy of hypothermia treatment and the objective of the treatment were reexamined based on a secondary analysis of the BHYPO trial in 135 patients (88 treated with therapeutic hypothermia and 47 with fever control). This analysis was performed to examine clinical outcomes according to the CT classification of the Traumatic Coma Data Bank on admission. Clinical outcomes were evaluated with the Glasgow Outcome Scale and mortality at 6 months after injury. Good recovery and moderate disability were defined as favorable outcomes. Favorable outcomes in young patients (≤50 years old) with evacuated mass lesions significantly increased from 33.3% with fever control to 77.8% with therapeutic hypothermia. Patients with diffuse injury III who were treated with therapeutic hypothermia, however, had significantly higher mortality than patients treated with fever control. It was difficult to control intracranial pressure with hypothermia for patients with diffuse injury III, but hypothermia was effective for young patients with an evacuated mass lesion.

Search for clinical and neurophysiological prognostic patterns of brain coma outcomes in children.

OBJECTIVE: The aim of the study was to evaluate the possible predictive values of clinical examinations combined with the recordings of electroencephalography and brainstem auditory-evoked potentials in traumatic coma of pediatric patients. MATERIAL AND METHODS: A total of 43 children in coma with severe acute head trauma were included in the study. They were investigated and treated in pediatric intensive care unit using standard evaluation and treatment protocol. Evaluation of coma was performed using Glasgow Coma Scale. Electroencephalography for 35 patients and brainstem auditory-evoked potentials for 24 patients were recorded. RESULTS: Glasgow coma scale statistic pool median was equal to 4 points as measured in presence of brain edema, meanwhile it was 6 as measured in absence of edema. In case of supratentorial damage, median duration of consciousness recovery was 10 days. In absence of above-mentioned supratentorial damage, recovery of the consciousness was earlier - median was 5 days. Determined duration of artificial lung ventilation was statistically significantly shorter for those who had edema (P=0.048). In 20 patients (57% of all cases), constant or alternating slow wave activity was observed during the first electroencephalographic recording. In other cases, "alpha coma" or low amplitude of arrhythmic activity and local slowing activity corresponding to brain damage seen on computerized tomography were recorded. For 24 patients, brainstem auditory-evoked potentials were recorded. In 9 cases, they were abnormal; in these cases, the consciousness of the patients recovered after 44 days or did not recover. CONCLUSIONS: Glasgow coma scale results alone may have limited prognostic value in absence of other objective neurophysiologic investigation data concerning the coma outcome in children. Prognosis may be worse if pathological brainstem auditory-evoked potentials correlate with pathological dynamic changes in electroencephalography and brain lesions, diagnosed during computerized tomography scan.

[Cerebral circulatory autoregulation as a guide for controlling the parameters of assisted ventilation in acute severe brain injury].

The paper presents the results of cerebral circulation (CC) in 17 ventilated patients with severe brain injury in its acute phase. All the patients developed traumatic subarachnoidal hemorrhage, which was accompanied with angiospasm in the majority of cases. Doppler transcranial study (DTCS) was performed, by using the carotid compression test; the findings correlated with paCO2 and CV parameters. A dynamic study was performed every two days starting from their admission to an intensive care unit to the recovery from coma or normalization of CC parameters. The dilation and constriction components of the CC reserve were assessed from the results of this test and continued to be controlled during therapy. Thus, this paper shows the possibility of goal-oriented correction of CC autoregulation and optimization by selecting the parameters of assisted ventilation and by changing paCO2 under the guidance of Doppler transcranial study.

Epidemiology of traumatic comas: a prospective population-based study.

OBJECTIVE: Most studies on patients with severe brain injury (SBI) are based on data from specialized centres. This prospective epidemiologic study included all patients in a defined region with a coma lasting more than 24 hours or leading to a death. METHODS: All patients with a SBI admitted to an emergency department in the region were included during a 1-year period. A data form was completed with initial neurological state, CT scan lesions and associated injuries. Outcome at the end of acute hospitalization was assessed from medical notes. RESULTS: Two hundred and forty-eight patients were registered. Annual incidence was 8.5/100 000 population. Median age was 41 years. Traffic crashes were the most frequent cause (59%). Falls occurred in 30% (16% from a high level, 14% from one level). Initial GCS was above 8 in 31%, and patients with a neurological deterioration were older (52 vs 32 years). Death occurred in 52% of the cohort. Outcome was related to CT scan diagnosis, delay before eye opening and delay before obeying commands. CONCLUSION. This population-based cohort of patients with SBI was different from patients selected in trauma centres. The patients were older, more often injured in falls and their mortality rate remained very high.

Extraordinary arousal from semi-comatose state on zolpidem. A case report.

A young semi-comatose male patient was investigated using 99mTc hexamethyl-propylene amine oxime (99mTc HMPAO) brain single photon emission computed tomography (SPECT) before and after administration of the gamma-aminobutyric acid (GABA) agonist zolpidem. It was observed that 15 minutes after application of the drug the patient awoke from his semi-comatose condition and remained awake for the next 3-4 hours. When drug action subsided he returned to his semi-comatose state. Brain SPECT before drug application showed large hypo-active areas in certain parts of the brain. Brain SPECT after drug application showed a generalised cortical activation relative to the cerebellum and a marked and amplified activation of the areas that were hypo-active before drug application.