DISORDERS OF CONSCIOUSNESS AFTER ACQUIRED BRAIN INJURY
DISORDERS OF CONSCIOUSNESSAFTER ACQUIRED BRAIN INJURYA REVIEW OF POSSIBILITIES WITHDEEP BRAIN STIMULATION METHODKlemen GRABLJEVEC, MD MScUniversity Rehabilitation InstituteLjubljana, Slovenia
VEGETATIVE STATE (VS)Some patients after anoxic or traumatic brain injury (1-3): Demonstrate preserved normal cirrcadian rhythmAbsence of self-awareness AND absent response fromenvironmentRemain with completelly / partially preserved autonomic functionsof hypothalamus and brainstemDue to: Focal (billateral) injury of thalamic and subthalamic – as wellrostrocaudal regionsNeurons of those structures: role in maintaining and regulation ofsleep - wake mechanism and awarenessNeurons in centro-thalamic region are extremelly sensitive tomechanism of diffuse axonal injury and hypoxic / anoxic injuryGrosseries O, et al. NeuroRehabilitation 2011; 28: 3-14.Adams JH, Graham DI, Jennet B. Brain 2000; 123: 1327-38.Jennet B, Adams JH, Murray LS, Graham DI. Neurology 2001; 56: 486-90.
CRITERIA / WHEN TO DECLARE VS (I)American Academy for Neurology, 1994 No evidence of awareness of self or environment and an inabilityto interact with others No evidence of sustained, reproducible, purposeful, or voluntarybehavioral responses to visual, auditory, tactile, or noxious stimuli No evidence of language comprehension or expression; Intermittent wakefulness manifested by the presence of sleepwake cyclesAssesment and management of patients in the persistent vegetative state(summary statement). Neurology 1995; 45: 1015-8.
CRITERIA / WHEN TO DECLARE VS (II)American Academy for Neurology, 1994 (4) Sufficiently preserved hypothalamic and brainstem autonomicfunctions to permit survival with medical and nursing care; Bowel and bladder incontinence Variablypreservedcranialnerve(pupillary, oculocephalic, corneal, vestibulo-ocular, gag) andspinal reflexes.
COMMON & FREQUENT MISLEADING After a period of coma the patient opens his/her eyes, at first topain and then to less arousing stimuli. This is then followed byperiods with the eyes open (5). Some authorities do not like to talk in terms of ‘sleep–awake’since this implies a higher cortical function. They prefer to use thesimple terms of eye opening and closing (6-9). It is very difficult, however, to persuade caring staff and relativesnot to talk in terms of a sleep and awake.Andrews K. T Postgrad Med J 1999: 75: 321-4.von Wild K, Gerstenbrand F, et al. s Eur J Trauma Emerg Surg 2007; 3: 268-92.Andrews K, Murphy L, Munday R, Littlewood C. BMJ 1996; 313: 13-6.Strens LHA, Mazibrada G, Duncan JS, Greenwood J. Brain Inj 2004. 18: 213-8.Childs N. BMJ 1996; 313: 944.
COMMON & FREQUENT MISLEADING There may be roving eye movements and the patient’s eyesmay seem to briefly follow moving objects. The movement is usually inconsistent and never sustained. The main early sign that the patient is emerging from thevegetative state is that he begins to focus on and/or tracks amoving object or person . Andrews et al found that 60% of patients who weremisdiagnosed as being vegetative were blind or had severevisual impairments which would make focussing an impossibility.
COMMON & FREQUENT MISLEADING A non-volitional grasp reflex may be present. This can causeconsiderable concern to relatives who feel that the patientrecognises them when they hold his hand .Chewing movements or grinding of teeth, sometimesaccompanied by constant movement of the tongue. Theseagain cause concern to relatives who may feel that the patientis indicating that he is thirsty or hungry .Grunting and groaning may be provoked by noxious stimuli butno speech occurs. These sounds are often interpreted byrelatives as indicating an attempt to communicate.This can cause disagreement between family and clinicianswhen some relatives claim to be able to ‘understand’ the wordsspoken when others only hear sounds.Strens LHA, Mazibrada G, Duncan JS, Greenwood J. Brain Inj 2004. 18: 2138
PERSISTIVE / PERMANENT VS DEFINITIONThe persistent vegetative state can be defined as a vegetative statepresent at 1 month after acute traumatic or nontraumatic braininjury, and present for at least 1 month in degenerative/metabolicdisorders or developmental malformations.The permanent vegetative state means an irreversible state, adefinition, as with all clinical diagnoses in medicine, based onprobabilities, not absolutes.VS can be judged to be permanent 12 months after traumatic injury inadults and children. Special attention to signs of awareness shouldbe devoted to children during the first year after traumatic injury.PVS can be judged to be permanent for nontraumatic injury in adultsand children after 3 months .Jennet B, Adams JH, Murray LS, Graham DI.Neuropathology in vegetative and severely disabled patients after head injury. Neurology 2001; 56: 486-90.
PROGNOSIS Expected life-span time of persons in VS is 2 – 5 years Survival for more than 10 years is very unlikely Survival for more than 15 years is anecdotical Recovery of consciousness after TBI – PVS is 46 % after 6months and 52 % after 12 months, most of those patients areseverely disabled Recovery of consciousness after nonTBI – PVS is 15 % after 6and 12 months (6).Andrews K. The vegetative state – clinical diagnosis (editorials). Postgrad Med J 1999: 75: 321-4.
INCIDENCE & PREVALENCE OF VS (5) UK:Incidence 14 / million pop. (overall, after 1 month) ISR: Incidence: 4.5 / million pop. (TBI, after 1 month) DK: FRA: Incidence: 67 / million pop. (overall, after 1 month) AUT: Prevalence: 19 / million pop. (overall) N.IRL: Prevalence of VS MCS: 19 / million pop.(overall) USA: Incidence: 46 / million pop. (overall, after 1month)Prevalence: 40 – 168 / milion pop. (overall)Prevalence: 1.3 / milion pop. (TBI, after 5 years)
MINIMAL CONSCIOUSS STATE - MCSDEFINITION & CRITERIAMCS is distinguished from VS by the presence of behaviors associatedwith conscious awareness.In MCS, cognitively mediated behavior occurs inconsistently, but isreproducible or sustained long enough to be differentiated fromreflexive behavior.The reproducibility of such evidence is affected by the consistency andcomplexity of the behavioral response.Extended assessment may be required to determine whether a simpleresponse (e.g., a finger movement or eye blink) that is observedinfrequently is occurring in response to a specific environmentalevent (e.g., command to move fingers or blink eyes) or on acoincidental basis (11).Fins JJ, The Minimally conscious state. Arch Neurol 2007; 64: 1400-5.Giacino JT,The MCS – Definition and diagnostic criteria. Neurology 2002; 58: 349-53.
Comparison of clinical features associated with coma, vegetativestate and minimally conscious UNCTIONReflex entStartleVSNONE Postures orwithdraws tonoxiousstimuliStartleBriefOccasionalorienting tononpurposefu soundlmovementMCSPARTIAL LocalizesnoxiousStimuliReaches forobjectsHolds stainedvisualpursuitReflexivecrying orsmilingContingentVocalizationInconsistent butintelligibleverbalization orgestureContingentsmilingor crying
Future questions / directions for research. Incidence and prevalence of MCS Natural history, recovery course and outcome. Interrater and test–retest reliability of the diagnostic criteria forMCS. Validation of diagnostic criteria for MCS with respect topathophysiologic mechanisms and outcome. Differences in rate of recovery and outcome between adults andchildren. Interactions among cause of the injury (e.g., trauma vs anoxia vs.dementia), length of time after onset, and recovery ofconsciousness.
Future questions / directions for research. Predictors and patterns of emergence from VS and MCS. Utility of existing assessment methods and scales for monitoringrecovery and predicting outcome. Treatment efficacy. Efficacy and cost analysis of different care settings. Issues related to family beliefs and their relation to functionaloutcome, service use, and evaluative decisions regarding quality oflife. Cross-cultural differences in evaluation and management practices.
New perspectives in Neurorehabilitation: incoming experiences, PAVIA; May 24th 2013
DEEP BRAIN STIMULATION METHODCurrent use: neurology, psychiatry, neurosurgerySuccesfull: extrapiramidal movement disorders, obsesive-compulsivedisordersUnconfirmed: MCS and VSFirst trials - Hassler (1969) in Moruzzi (1995) : increase of arousal andawareness with stimulation of subthalamic regions and RF.Kinamura (1996): importance of intralaminar nuclei for sustainedawareness and short memory formationV d Werf (2002): relevance of thalamo-cortical connections andthalamic centro-lateral nuclei for sustained wakefullness andawareness
IMPLANTABLE DBS SYSTEMRoutine clinical practice from 1970'sNeurosurgical procedure under 3D stereotactic guidanceImplantation of two wired electrodes w/ four stimulation electrodeseach in the region of subthalamic nucleiWired electrodes are subcutaneously connected with the stimulatorplaced infraclavicullary.
DBS – literature overviewHassler, 1969: 19 days of stimulation of R pallidum and L lateropolar thalamic nuclei in male patient 5 months after TBIRaised wakefulness, spontaneous left limbs movement, turning toobjects and subjects as well beginning of non-functionalvocalisation.Additionally: EEG changes in term of decreased delta activity Ltemporal, asimetry reduction and partial restorement of alpharhytmMajority of effects diminished soon after the stimulation wasswitched off.
DBS – literature overviewSturm, 1971: Stimulation of polar reticular subtalamic nuclei inmale patient after stroke in mesencephalic region – withsubsequent condition described as “intermediate between comaand apalic syndrome”.More reliable folowing to comands, longer awakenessperiods, improved oral communication, more efficient oralintake.Patient died two months after permanent DBS system implantation
DBS – literature overviewTsubokawa, 1990: Eight patients in VS of at least six monthsduration.Three patients after TBI, two after anoxic injury and three afterspontaneous CVI (ICH and / or SAH).System for permanent stimulation of RF and non-specificsubthalamic nuclei was implanted in all patients.Previous neurophysiological assesment: EEG, SEP, SSEP, APBSNeuro assesment: response to painful stimuli, spontaneous eyeopening, spontaneous limb movement, eye movement, emotionalresponse, oral intake, vocalisation, verbal response and followingto commands
DBS – literature overviewTsubokawa (1990) - RESULTS:Six months after DBS:Two patients after CVI regained effective oralcommunication, following of comands, proper emotionalresponse and oral intake.One patient after CVI showed partial and inconsistent following ofcommands, full object eye-tracking and spontaneous limbmovement.In five patients (including all after TBI), there was no improvement inneurological condition or level of awareness.
DBS – literature overviewTsubokawa (1990) - CONCLUSIONS:It is reccomended to wait up to three months to asses the effect ofDBSEffect of DBS is not only early activation of ascendent RAS butpredominantly increase of brain circulation and glucosemetabolism in cortex and thalamusLater might induce neuroplasticity in those regions as wellsurrounding tissue and so a basis of improved awareness andconsciousness.
DBS – literature overviewSchiff et al. , 2007:Intervention:Implantation of permanent DBS of subthalamic pf nuclei in a patientsix months after TBIObservation:Primary parameter: „JFK – Coma recovery scale – revised“ duringdouble blind “on” and “off“ stimulation for period of six months.Secondary parameter: object naming, following motoricalcommands, oral intake.Conclusion:Significant correlation between „on“ period and qualitative changesin patient s behaviour – prolonged eye opening periods, followingcommands, trying of functional use of objects and verbalisation
DBS – literature overviewYamamoto et al., 2010 (18)Study group: 21 patients in VS (AAN criteria), four to eight monthsafter TBI or stroke (9 stroke, 9 TBI, 3 anoxic BI)Average age 44 yrs (range 19-72)Control group consisted of 86 patients in VS (AAN criteria) ofvarious aetiologiesMethods: In two patients DBS electrodes were implanted in theregion of mesencephalo-RF and 19 patients in the subthalamicCM-pf nuclei of dominant haemisphere
DBS – literature overviewYamamoto et al. (2010)Prior to DBS implantation:- ABsR for assesment of brainstem function- SEP over primary somatosensory cortex to asses cortico-thalamicconnections- Pain related P250 to asses higher neural activity- Continuous EEGAfter DBS implantation:DBS „on“ for 30 minutes every 2 – 3 hours during day.Follow up in study group for 10 years after implantation or untildeathFollow up in control group for two years.
DBS – literature overviewYamamoto et al. (2010) - RESULTSAll 86 patients in control group remained in VS.21/21 patients in study group showed early arousal immediately afterswitching the system „on“ in term of:eye opening with dilated pupils, raise of heart frequency and arterialpressure as well mouth opening.8/21 patients emerged from VS, and could communicate withsome speech or other responses, but needed some assistance withtheir everyday life in bed.Even after long-term rehabilitation, their state of being bedriddenremained unchanged in seven of these eight cases. The other casebecame able to live in a wheelchair.The remaining 13 cases were unable to communicate at all and failedto emerge from the VS.
DBS – literature overviewYamamoto et al. (2010) – RESULTS in MCS GROUPAll of the 5 cases of MCS displayed inconsistent behavioural evidenceof consciousness before DBS therapy, and they became able tocommunicate withdefinite behavioural responses after the DBS.Four cases emerged from the bedridden state, and were able to enjoylife in their own home.The other case still remained in a bedridden state.
DBS – literature overviewDISCUSSIONDBS seems to be promising in patients, that show preservedconnectivity among the brainstem and cortex as well withpreserved cortico-thalamic connectivity. Immediate response in term of eye-opening, arterial pressureelevation and heart rate dynamics is a favourable prognosticfactor for long term positive effect of DBS All patients in Yamamoto et al „large“ study group who improvedawareness had electrodes implanted in CM-pf complex No „spontaneous“ improvement in a control group
DBS – literature overviewDISCUSSIONDBS seems to be far from reccomended for general use in patients inVS or / and MCS. Even when clinical status in different patientsseem to be similar, their basal brain activity is undoubtfullydifferent. Prior to consideration about the DBS, assesment of corticothalamic and cortico – mesencephalic connectivity withneurophysiology diagnostic and neuro imaging is reccomnded(SSEP, ABR, EEG, PET, f-MRI) We are not aware of any reliable prognostic factors that couldpredict the outcome with DBS therapy.
present at 1 month after acute traumatic or nontraumatic brain injury, and present for at least 1 month in degenerative/metabolic disorders or developmental malformations. The permanent vegetativestate means an irreversible state, a definition, as with all clinical diagnoses in medicine, based on probabilities, not absolutes.
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