Inherited Multisystem Disorders Causing Cerebral Ischemia Inherited Metabolic Disorders and Stroke Part 1 : Fabry Disease and Mitochondrial Myopathy , Encephalopathy , Lactic Acidosis , and Strokelike Episodes

Background: The vegetative state describes patients who emerge from coma with normal wakefulness, but show no awareness of self or surroundings. Meaningful neurological recovery is rare. In 2006, however, Owen and Coleman described a vegetative woman who exhibited volitional brain activity on functional MRI (fMRI). When she was asked to imagine playing tennis, her supplementary motor area (SMA) demonstrated cortical activation similar to controls. When asked to imagine walking through her home, activation occurred in the parahippocampal gyrus, posterior parietal and lateral premotor cortex, indistinguishable from controls. This suggested the vegetative state could be misdiagnosed if based exclusively on clinical criteria. Impaired motor function could prevent an aware individual from responding to commands. This caveat also applies to the minimally conscious state (MCS) where some cognitive behavior is preserved in a severely fragmented form. How often this occurs is unknown. Objective: To determine incidence of undetected awareness in survivors of severe brain injury. Methods: Investigators examined 23 vegetative and 31 MCS patients with fMRI using blood-oxygen-leveldependent (BOLD) responses to the 2 mental-imagery tasks described above. In 1 vegetative patient, the unique cortical activation by the 2 mental tasks allowed a yes-no response to simple autobiographical questions. Imagining playing tennis meant "yes", moving room-to-room meant "no." Results: Of 54 patients, 33 had traumatic brain injury (TBI), 16 anoxic brain injury, and 6 stroke or meningitis. Of patients, 5 (4 vegetative, 1 MCS) modulated their brain activity on fMRI when asked to imagine playing tennis or roaming their home. All had suffered head trauma at 1, 2, 6, 30, or 61 months earlier. In 3 of these patients, further bedside testing revealed signs of awareness not previously detected, upgrading the diagnosis to MCS. In the other 2 patients, no voluntary behavior could be detected by clinical testing. One male patient, aged 22 years and in a vegetative state, 5 years after head trauma, used fMRI to answer accurately 5 yes-orno questions about family members; immediate bedside retesting to establish communication was unsuccessful. fMRI disclosed evidence of cognitive awareness in 2 vegetative (18%) and 3 MCS (14%) TBI patients. Conclusions: fMRI can detect clinically unrecognized cognitive awareness in roughly 15% of vegetative or MCS patients due to TBI. When re-examined clinically, many of these "covertly aware" patients are reclassified to MCS. Similar evidence of awareness is not observed in patients with non-traumatic brain damage. Reviewer's Comments: fMRI was used for "mind-reading" by employing a binary yes-no system linked to mental imagery. This presents a remarkable tool for probing the limits of sentience in the mind of a person who can hear, but is unable to respond motorically. (Reviewer-Michael Jacewicz, MD).