Persistent Vegetative State & Minimally Conscious State:
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1 Persistent Vegetative State & Minimally Conscious State: Audrius V. Plioplys MD, FRCPC, FAAP, CMD AMDA s 29 th Annual Symposium Dallas, Texas, March 17, 2006 International Conference on Life Care Planning Atlanta, Georgia, October 15, 2006 Disclosures: No financial interests
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3 Relevance & Importance Definition of terms PVS & MCS in the severely disabled Limitations of the definitions Recent research in cognitive awareness in PVS Therapies to stimulate cognitive awareness Possibility of emergence from PVS Providing for optimal medical care in the LCP will maximize life expectancy
4 Terry Schiavo
5 Brain Death Brain damage vs. brain death Mechanical ventilation, life support Organ transplantation 1959, Mollaret and Goulon, coma depasse (irreversible coma): no cortical or brain stem functions, no respirations and flat EEG 1968, ad hoc committee, Harvard Medical School, similar definition
6 Brain Death 1971, Mohandas and Chou: damage to brain stem is a critical component 1976, Conference of Medical Royal Colleges, UK, complete and irreversible loss of brain stem function 1981, President s Commission guidelines: use of confirmatory tests to reduce duration of observation; 24 hour wait for anoxic damage
7 Brain Death 1995, American Academy of Neurology, practice parameters The Diagnosis of Brain Death, Wijdicks, New England Journal of Medicine, 344: , 2001
8 Brain Death Precise clinical examination Establishment of the cause of the coma Ascertainment of irreversibility Resolving any misleading clinical neurologic signs Recognition of possible confounding factors Confirmatory laboratory tests
9 Coma and absence of motor response
10 Pain response, corneal reflex, pupillary response, caloric testing, gag/cough reflex
11 Apnea Testing: temp 36.5, BP 90 mm Hg, + fluid balance 6 hours, O2 ventilation to reach 200 mm Hg, 8-10 min observe and rise in PCO2 of 20 mm Hg
12 Interval between 2 evaluations / Need for confirmatory tests Term to 2 m old: 48 hrs 2 tests 2 m to 1 year old: 24 hrs 1 test 1 to 18 years: 12 hrs optional Over 18 years: optional optional
13 Confirmatory Tests Cerebral angiography Transcranial Doppler ultrasonography Electroencephalogram Cerebral Scintigraphy (technetium)
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16 Persistent Vegetative State Jennett and Plum, Persistent vegetative state after brain damage, Lancet, 1: , 1972 Medical aspects of the persistent vegetative state, Multi-Society Task Force on PVS, New England Journal of Medicine, 330: , , 1994 Practice Parameters, American Academy of Neurology, Neurology, 45: , 1995
17 Persistent Vegetative State No evidence of awareness of self or environment, and an inability to interact with others No evidence of sustained, reproducible, purposeful, or voluntary behavioral responses to visual, auditory, tactile, or noxious stimuli No evidence of language comprehension or expression
18 Persistent Vegetative State Intermittent wakefulness manifested by the presence of sleep-wake cycles Sufficiently preserved hypothalamic and brain stem autonomic functions to permit survival with medical and nursing care Bowel and bladder incontinence Variably preserved cranial nerve and spinal reflexes (pupillary, oculocephalic, corneal, gag, spinal withdrawal)
19 Persistent Vegetative State PVS can be diagnosed 1 month after acute brain injury PVS can be judged to be permanent 12 months after traumatic brain injury in children and adults PVS can be judged to be permanent for nontraumatic brain injury in children and adults after 3 months
20 Persistent Vegetative State: Degenerative / Metabolic Degenerative and metabolic disorders of the brain: as the disease progresses, impairment of consciousness takes place Intercurrent illnesses and medication effects can produce temporary PVS. If the vegetative state persists for several months, then can be considered PVS.
21 Persistent Vegetative State: Infants Severe developmental malformations of the nervous system PVS can be diagnosed at birth only in infants with anencephaly Other severe malformations: must wait for 3 to 6 months before diagnosing PVS
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23 Persistent Vegetative State: Emergence Wilson and Gill-Thwaites, Early indication of emergence from vegetative state. Brain Injury, 14: , 2000, UK 13 out of 30 emerged from PVS Time from injury to improvement: 4 to 60 months
24 Persistent Vegetative State Pediatric / Young Adult Long-Term Care Years of 24-7 attending physician care Peds / Young Adult: 3,813 Adult: 1,320 Total: 5,133 Many referred cases diagnosed PVS No actual cases of PVS
25 Persistent Vegetative State The PVS means an irreversible state, a definition, as with all clinical diagnoses in medicine, based on probabilities, not absolutes. A PVS patient becomes permanently vegetative when the diagnosis of irreversibility can be established with a high degree of clinical certainty, ie, when the chance of regaining consciousness is exceedingly rare.
26 PVS: Donald Herbert Buffalo, NY firefighter Dec. 1995, trapped under a collapsed roof during a fire Anoxia for several minutes PVS, Dr. Ahmed, PMR
27 PVS: Donald Herbert April 30, 2005, started talking, responding
28 PVS: Donald Herbert April 30, 2005, started talking 3 months after starting a combination of a stimulant, a SSRI and a dopamine agonist Unknown which medicines were used No neurology involvement for many years Multifactorial injury: anoxia, carbon monoxide, traumatic brain injury 1996 was communicative, responsive, 1997 lapsed into an unresponsive state 2005 improvement lasted only 14 hours
29 Minimally Conscious State The minimally conscious state: Definition and diagnostic criteria. Giacino et al. Aspen Neurobehavioral Consensus Conference, Neurology, 58: , 2002 American Academy of Neurology recommends this report as an educational tool Endorsed by the AAPMR, AANS, ACRM, BIA and CNS
30 Minimally Conscious State Severe alteration in consciousness, but do not meet criteria for PVS Behavioral evidence of consciousness but remain unable to reproduce this behavior consistently Partial preservation of conscious awareness Prevalence estimate, adult and pediatric: 112,000 to 280,000 in US
31 Minimally Conscious State Diagnostic Criteria For MCS, limited but clearly discernible evidence of self or environmental awareness must be demonstrated on a reproducible or sustained basis, by one or more of the 4 behaviors: 1 Following simple commands 2 Gestural or verbal yes / no responses (regardless of accuracy)
32 Minimally Conscious State Diagnostic Criteria 3 Intelligible verbalization 4 Purposeful behavior, including movements or affective behaviors that occur in contingent relation to relevant environmental stimuli, and are not due to reflex activity, such as: appropriate smiling or crying vocalizations or gestures in response to language
33 Minimally Conscious State Diagnostic Criteria 4 Purposeful behavior (continued): reaching for objects, relation between object and direction of reach touching or holding objects that accommodates the size and shape of the object pursuit eye movement or sustained fixation in response to moving or salient stimuli
34 Emergence from the Minimally Conscious State: 1 FUNCTIONAL INTERACTIVE COMMUNICATION Accurate yes / no answers to 6 of 6 basic questions on two consecutive evaluations Examples: Are you sitting down?, Am I pointing to the ceiling? Speech, writing, yes / no signals, augmentative communucation devices
35 Emergence from the Minimally Conscious State: 2 FUNCTIONAL USE OF TWO DIFF OBJECTS Demonstrates behavioral evidence of object discrimination Appropriate use of 2 different objects on 2 consecutive occasions Examples: bringing a comb to the head, putting a pencil to a sheet of paper
36 Emergence from the Minimally Conscious State: 3 QUESTIONS / CONCERNS Severe physical impairment Severe cerebral palsy Even MCS diagnostic criteria are of uncertain applicability
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38 Minimally Conscious State fmri scans, verbal and tactile fmri reveals large-scale network activation in minimally conscious patients. Schiff, et al. Neurology, 64: , 2005 Columbia, Cornell, Georgetown Univ. 2 patients with MCS, 7 more since then Patient A, MCS 18 m, left temporal spontaneous intracerebral hemorrhage Patient B, MCS 24 m, TBI and SDH
39 fmri scans controls, passive listening: forward-yellow, reverse-blue, overlap-red
40 Composite fmri scans controls passive listening: forward-yellow, reverse-blue, overlap-red
41 Minimally Conscious State fmri scan patient A
42 Minimally Conscious State fmri scan patient B
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44 Minimally Conscious State fmri scans patient A and B
45 Minimally Conscious State fmri; tactile stimulation; Pt A, Pt B, Control
46 Persistent Vegetative State Auditory brain stem response: P300 Fabien Perrin PhD, et al., Lyon, France, Archives of Neurology, 63: , 2006 Own first name / mixed with 7 equiprobable names PVS: 3 / 5 MCS: 6 / 6
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48 Persistent Vegetative State / Minimally Conscious State Many other techniques: PET, SPECT, EEG, Event Related Potentials (ERP s) Kotchoubey, et al., Tubingen, Germany, Clinical Neurophysiology, 2005, patients, 50 PVS, 38 MCS Complex verbal tasks for late ERP s
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51 Persistent Vegetative State Adrian Owen, et al., U of Cambridge, UK, Science, September 8, 2006 fmri July 2005, 23 year old female, MVA, TBI 5 months later in a vegetative state There was milk and sugar in the coffee vs. acoustically matched noise sequences The creak came from a beam in the ceiling ambiguous words, more response
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53 Persistent Vegetative State Imagine playing a game of tennis Imagine walking through all of the rooms in your house
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55 PVS & MCS: Medications Levodopa Matsuda, et al., Neuropsychol Rehabil, 15: , 2005, Kyoto, Japan 4 with PVS, 1 with MCS Parkinsonian symptoms MRI changes in the dopaminergic pathway What percentage PVS & MCS is levodopa effective?
56 PVS & MCS: Medications Zolpidem (Ambien) Claus and Nel, NeuroRehabilitation, 21: 23-28, 2006, Surrey, UK 3 with PVS for more than 3 years 10 mg in AM, effect peaked min., lasted up to 4 hours Cases with marked functional improvement Continued response for 3 to 6 years? How many cases Zolpidem was tried
57 PVS & MCS: Medications Zolpidem (Ambien) effects: Meaningful conversation Telephone conversation Able to feed self and swallow Count to five Understand humor, laugh and make jokes Knows names of Rugby players Theory: omega-1 GABA receptor-based reactivation of dormant neural tissue
58 MCS: Terry Wallis
59 MCS: Terry Wallis 19 years old, 1984, truck roll-over, TBI and PVS for several months In nursing home MCS no improvement 19 years after accident, 38 years old, 2003, first word: Mom Recognized daughter Remembered use of cell phones Progressively more awareness and motor movement
60 MCS: Terry Wallis Voss, et al., Journal of Clinical Investigation, 116: , 2006 Possible axonal regrowth in late recovery from the minimally conscious state MRI Diffusion Tensor Imaging track flow of water along axons axonal regrowth FDG PET Scans radioactively labeled glucose uptake by neurons neuronal activity
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63 Minimally Conscious State: Serious Questions Misuse and / or misdiagnosis of MCS (Robert Wendland case--to the CA Supreme Court) Can consciousness be quantified? How much consciousness do you need to be human? Other measures of consciousness: IQ (MCS low IQ) and other distinctions MCS is not a useful diagnosis
64 Persistent Vegetative State / Minimally Conscious State Life expectancy / survival rates Most important factors: Degree of disability Ongoing and intercurrent medical / neurologic illnesses Access to optimal acute and ongoing medical / nursing care
65 PVS & MCS: Implications Recent research: majority PVS patients, all MCS patients have cognitive awareness Clinical improvement can occur, spontaneously or with medicines Reactivation of dormant neuronal systems; axonal regrowth neuronal interconnections Areas of awareness: Auditory, especially familiar words, sounds Somatosensory, visual Appropriate therapies may hasten recovery
66 PVS: Previous Studies Wilson, et al. Vegetative state and responses to sensory stimulation: an analysis of 24 cases. Brain Injury, 10: , 1996 Meta-analysis of 24 individual published cases: multimodal sensory stimulation was of benefit Lombardi, et al. Sensory stimulation of brain-injured individuals. Clinical Rehabilitation, 16: , 2002 Meta-analysis of reports Only 3 reports with total of 68 cases. Techniques extremely varied, comparative analysis could not be done. Summary: No good studies, but new information
67 PVS & MCS: Implications Speech & music therapy: familiar words, expressions, voices, stories, music, etc. Somatosensory stimulation: standard PT & OT, massage, other forms (Vestibular ABR data) With evidence of posterior cortical activity, visual stimulation programming: TV shows, especially familiar programs, photographs Providing for optimal medical care will maximize life expectancy
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69 Thank you
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