Appendix e-1. CASE REPORTS

Subject 1. A 24 year-old woman suffered a basilar artery occlusion and a resulting brainstem infarct in May 2006. She was in her usual state of good health studying for final exams, when she complained of an unusual headache, had a generalized seizure and fell unconscious. She was taken to the hospital and found to have a basilar artery occlusion and a brainstem infarct. She was transferred to another hospital where a stent was placed. She remained ventilated for 2-3 weeks post-operatively. Her workup revealed a patent foramen ovale. Her only other known stroke risk factor was the use of oral contraceptives at the time. After her hospital stay, she spent 2 months in an acute rehabilitation program for MCS patients, then was transferred to a skilled nursing facility.

Since the brain injury, she has been in a minimally conscious state, with occasional periods of eye opening. She was started on amantadine in December 2007, which her mother reported to increase the frequency of her spontaneous eye opening. She also had been observed to communicate via purposeful movements of her left eye. Her speech therapist observed that she was more accurate in answering questions about the distant past than in those that required short term memory. Her Coma Recovery Scale- Revised (CRS-R) score during the initial evaluation varied during the day. Her first score was 9 (auditory 3, visual 3, motor 2, verbal 0, communication 0, and arousal 1), while her second score in the following days was 14 (auditory 4, visual 5, motor 2, verbal 0, communication 1, arousal 2).

Subject 2. A 27 year-old woman suffered diffuse axonal injury during a motor vehicle accident. In July 2004, the patient was driving to school when her car had a mechanical failure, causing her car to hit a tree. When found, the patient was unconscious. Upon arrival to the hospital, she was intubated. A shunt was placed for concerns of increased intracranial pressure (neurosurgical evaluation declined a hemicraniectomy at the time). Her initial hospital course was notable for thermodysregulation which resolved. She was hospitalized for 1 month, then transferred to a rehabilitation facility. After 4 months in rehabilitation, she spent one year in a nursing home before returning to her parents’ home in May 2006. Additional notable events since her brain injury included a generalized seizure in December 2004 and February 2005 after tapering of levetiracetam, amantadine, and dextroamphetamine.

Since her initial injury, the patient's level of consciousness and responsiveness had fluctuated. At five months, she occasionally spoke in simple sentences such as "why are you doing this" and identified family members when prompted. However, after her seizures, she stopped speaking. Her family reports that she could still occasionally vocalize, laugh, cry, curse, and direct her wheelchair. She could respond to simple commands such as giving a thumbs-up sign. Her CRS-R score on initial evaluation was 15 (auditory 3, visual 4, motor 5, verbal 1, communication 0, arousal 2).

Subject 3. A 58-year-old woman suffered diffuse strokes and a possible cardiac arrest following knee replacement surgery in September of 2007 at another hospital. Forty-five minutes after the surgery, she became suddenly unresponsive, had a generalized seizure, and was intubated. Head imaging revealed diffuse injury attributed to multiple fat emboli. Patient remained in the intensive care unit for three weeks, was later transferred to a neuro-rehabilitation unit for 6 weeks, then to a skilled nursing facility.

After about four months, she began to intermittently exhibit increased awareness and communication. She could reach for the spoon during pauses in feeding, mouth words, and cry when visited by a close friend. By the time of the first ASL measurement, 13 months after injury, she was alert, nodded appropriately to yes/no questions, tracked objects, but did not follow commands. Her Coma Recovery Score Revised total score (CRS-R) was 14 (auditory 2, visual 3, motor 5, verbal 2, communication 0, arousal 2). . By the time of the second ASL measurement, 20 months after injury. the patient had regained some intermittent speech function. On examination, she more reliably produced simple verbal responses to prompts, nodded appropriately to yes/no questions, but did not follow commands. She tracked objects and could reach with her right hand toward presented objects. The CRS-R total score increased to 16 at this time (auditory 3, visual 3, motor 5, verbal 3, communication 0, arousal 2). .

Since the second ASL evaluation, the patient has continued to improve in cognition and communication. She now responds accurately to most simple questions and reliably communicates with spoken language. She has been able to form new short term memories. She clearly recognizes family members. However, she is still occasionally confused and lacks insight into her deficits.

Subject 4. A 19-year-old female suffered traumatic brain injury after a motor vehicle accident in August 2008. The patient was riding on the hood of a car when the vehicle made a sudden stop. She fell off the hood of the vehicle, struck her head, and lost consciousness. Imaging showed multiple minimally displaced fractures and a left middle cranial fossa 2cm epidural hemorrhage. An emergent craniectomy was performed and the hemorrhage was evacuated. Several weeks later, she underwent a right-sided craniectomy for worsening tonsillar and subfalcine herniation. She received a feeding tube and a ventriculo-peritoneal shunt and was later discharged to a neuro-rehabilitation unit. She returned five months after her injury for a left sided cranioplasty. Three months later, she returned for a right-sided cranioplasty.

At the time of the ASL evaluation, approximately 10 months after the initial injury, the patient was noted to be intermittently responsive and able to communicate via gesture. The patient did not appear tracks objects, but could respond appropriately to questions by closing her eyes, moving her right arm, and sticking out her tongue. She had a left and upward gaze preference, but otherwise cranial nerves were intact. She was exquisitely sensitive to pain in her left arm and would reliably grimace and cry to passive movement. She had a right greater than left spastic hemiparesis and was diffusely hyperreflexic. Her CRS-R Score at the time of the study was 19 (auditory 4, visual 4, motor 6, verbal 2, communication 2, and arousal 2).