Medical aspects of the minimally conscious state in children

Brain & Development 25 (2003) 535–545 www.elsevier.com/locate/braindev

Review article

Medical aspects of the minimally conscious state in children Stephen Ashwal* Department of Pediatrics, Coleman Pavilion, Loma Linda University School of Medicine, 11175 Campus Street, Loma Linda, CA 92350, USA Received 18 December 2002; received in revised form 30 January 2003; accepted 18 April 2003

Abstract The minimally conscious state is a condition of severely altered consciousness in which minimal but definite behavioral evidence of self or environmental awareness is demonstrated. This must be established on a reproducible or sustained basis by one or more of four types of behaviors including simple command-following, gestural or verbal ‘yes/no’ responses, intelligible verbalizations, or purposeful behaviors. The minimally conscious state can occur in children and usually is due to acquired brain injuries (traumatic and non-traumatic), central nervous system degenerative and neurometabolic disorders or congenital or developmental disorders. It is assumed that the lower limit of the minimally conscious state occurs when patients emerge from a vegetative state. What remains uncertain is how we can assess the upper limits, that is the degree of improvement that indicates that an individual is no longer minimally conscious. It also is unknown if, when and to what extent children can emerge from a minimally conscious state and whether their prognosis is better than children who are vegetative. It is assumed that the minimally conscious state may become ‘permanent’ 12 months after traumatic brain injury and 3 months after nontraumatic injury although there have been no studies that have examined this issue. Medical and rehabilitative treatment of children in a minimally conscious state should be provided to maintain comfort, reduce complications, and optimize functional recovery. q 2003 Elsevier B.V. All rights reserved.

1. Introduction

2. Consciousness

In 2002, a case definition of the minimally conscious state (MCS) was published based on consensus recommendations from several neurological and rehabilitation medicine professional organizations [1]. Recommended in this document were specific criteria to help clinicians establish a diagnosis of MCS and distinguish this condition from the vegetative state (VS). This prompted some individuals to question whether there is such an entity as MCS [2,3] and others to address some of the ethical and legal issues related to the care of children in MCS [4]. Publication of this case definition of MCS also will likely stimulate future research concerning the evaluation, treatment and prognosis of children suffering from this condition. This review will concentrate on the medical aspects of MCS in children and is based on earlier work on this topic [4]. Table 1 summarizes selective clinical aspects of the disorders of consciousness, other conditions in which consciousness is severely impaired and brain death [5].

‘Consciousness’ is a spontaneously occurring state of awareness of self and environment. Consciousness has two dimensions: wakefulness and awareness [6 – 8]. Normal consciousness requires arousal, an independent, autonomicvegetative brain function subserved by ascending stimuli, emanating from the pontine tegmentum, posterior hypothalamus, and thalamus that activate mechanisms inducing wakefulness. Cerebral cortical neurons and their reciprocal projections to and from the major subcortical nuclei subserve awareness. Awareness requires wakefulness but wakefulness can be present without awareness. In the past decade, new insights into the physiology of consciousness and disorders of consciousness have been made and several theories have been proposed to explain its biological basis and importance [9].

* Tel.: þ1-909-558-8242; fax: þ 1-909-558-4184. E-mail address: [email protected] (S. Ashwal). 0387-7604/03/$ - see front matter q 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0387-7604(03)00095-0

3. Disorders of consciousness Disorders of consciousness in children include coma and the VS and are due to a wide variety of acquired, degenerative, and congenital conditions [7]. ‘Coma’ is a state of deep, unarousable sustained pathologic unconsciousness

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Table 1 Severe disorders of consciousness and related conditions Condition

Self awareness

Pain and Sleep–wake Motor function suffering cycles

Respiratory function Outcome

Brain death

Absent

No

Absent

Coma

Absent

No

Vegetative state Absent Minimally conscious Very limited state Akinetic mutism Limited Locked-in syndrome

Present

Absent

No recovery

Absent

None or only reflex spinal movements No purposeful movement

Variably depressed

No Yes

Intact Intact

No purposeful movement Severe limitation of movement

Normal Variably depressed

Evolves to PVS, death, or recovery, in 2–4 weeks Depends on etiology Recovery unknown

Yes

Intact

Moderate limitation of movement

Yes

Intact

Normal to variably depressed Quadriplegia; pseudobulbar palsy; Normal to variably eye movements preserved depressed

Recovery unlikely or limited Recovery unlikely; remain quadriplegic

Based in part on The Multi-Society Task Force Report on PVS [6] and the report of the Aspen working group [1].

with the eyes closed that results from dysfunction of the ascending reticular activating system either in the brainstem or in both cerebral hemispheres [8]. Coma usually requires the period of unconsciousness to persist for at least 1 h to distinguish coma from syncope, concussion, or other states of transient unconsciousness. The term ‘unconsciousness’ implies global or total unawareness and applies equally to patients in either coma or a VS. Patients in coma are unconscious because they lack both wakefulness and awareness. The depth of coma may be further specified by assessment of brainstem reflexes, breathing pattern, change of pulse or respiratory rate to stimulation, or stimulus induced non-specific movement. The ‘vegetative state’ is a condition of complete unawareness of the self and the environment accompanied by sleep – wake cycles with either complete or partial preservation of hypothalamic and brain stem autonomic functions. Criteria to diagnose the VS have been recommended for adults and children by The Multi-Society Task Force on PVS [6]. Children in a VS lack evidence of selfawareness or recognition of external stimuli. Rather than being in a state of ‘eyes-closed’ coma, they remain unconscious but have irregular periods of wakefulness alternating with periods of sleeping. Vegetative patients have inconsistent head and eye turning movements to sounds and inconsistent non-purposeful trunk and limb movements. Perhaps, of most importance and most easy to objectively examine is the fact that they do not have evidence of sustained visual fixation nor do they demonstrate sustained visual tracking. The clinical course of evolution to a VS after an acute injury usually begins with eyes-closed coma for several days to weeks followed by the appearance of sleep/wake cycles [10]. Other responses such as decorticate and decerebrate posturing, roving eye movements, and eye blinking appear earlier than sleep – wake cycles. Diagnosis of the VS is made clinically. There are no confirmatory laboratory tests. However, absence of somatosensory evoked responses to

median nerve stimulation has been associated with the VS [11]. Neuroimaging usually demonstrates diffuse or multifocal cerebral disease involving the gray and white matter. In children with traumatic and non-traumatic brain injury, serial imaging studies usually demonstrate progressive atrophy. It is important to correctly identify children in a VS because of the implications for continued care, family expectations, and the need for rehabilitation. Children in a VS have been reported to have considerably shorter than normal life expectancy [12]. Several national and international groups have addressed aspects of the VS related to diagnosis and prognosis [13 –17]. It is now generally agreed that it is preferable to describe the duration and etiology of the VS rather than use the term ‘persistent’. There is also consensus that the term ‘permanent VS’ describes patients who remain vegetative for 12 months after traumatic brain injury or 3 months after non-traumatic (e.g. anoxic –ischemic) brain injury [1]. In rare instances, late recoveries may occur and false positive and negative errors in diagnosis of the VS are made more frequently than previously suspected [18,19]. The term MCS was introduced to better describe patients who are emerging from a VS. This term and its definition and criteria evolved after a series of meetings of the Aspen Neurobehavioral Work Group that had used as its starting point, the concept of the ‘minimally responsive state’ as proposed by the Brain Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine [14]. At a recent meeting of the Aspen group, a consensus-based definition of MCS and criteria delineating the entry into and emergence from MCS were proposed and subsequently published [1].

4. Definition The ‘minimally conscious state’ is a condition of severely altered consciousness in which minimal but

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Table 2 Diagnostic criteria for the MCS

Table 3 Recommendations to facilitate detection of MCS

1. Simple command-following 2. Gestural or verbal ‘yes/no’ responses (regardless of accuracy) 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 reflexive activity. Some behavioral examples of qualifying purposeful behaviors include (a) Appropriate smiling or crying in response to the linguistic or visual content of emotional but not to neutral topics or stimuli (b) Vocalizations or gestures that occur in direct response to the linguistic content of questions (c) Reaching for objects in a manner that demonstrates a clear relationship between object location and direction of reach (d) Touching or holding objects in a manner that accommodates the size and shape of the object (e) Pursuit eye movement or sustained fixation that occurs in direct response to moving or salient stimuli

1. Adequate stimulation should be administered to assure that arousal is maximized 2. Factors adversely affecting arousal should be addressed (e.g. sedating medications, seizures) 3. Attempts to elicit behavioral responses through verbal instruction should not involve behaviors that frequently occur on a reflexive basis 4. Command-following trials should incorporate motor behaviors expected to be within the person’s capability 5. A variety of different behavioral responses should be investigated using a broad range of eliciting stimuli 6. Examination procedures should be conducted in a distraction-free environment 7. Serial reassessment incorporating systematic observation and measurement strategies should be employed to confirm the validity of the initial assessment. Specialized tools and procedures designed for quantitative assessment may be useful 8. Observations of family members, caregivers, and professional staff participating in the care of the person should be considered in designing assessment procedures

Ref. [1].

definite behavioral evidence of self or environmental awareness is demonstrated.

5. Diagnostic criteria To make the diagnosis of the MCS, evidence of limited but ‘clearly discernible’ self or environmental awareness must be demonstrated on a reproducible or sustained basis by one or more of the four types of behaviors listed in Table 2. In order to better assess equivocal behavioral responses of patients suspected of being in a MCS, the Aspen Group developed specific recommendations to facilitate detection of conscious awareness as outlined in Table 3.

Ref. [1].

variably preserved cranial nerve and spinal reflexes and (6) severe impairment of motor function. 6.1. Epidemiology There have been few published case reports or series that meet the recently published diagnostic criteria of MCS and those reported primarily concern adult patients. However, it has been estimated that there are between 112,000 and 180,000 adult and pediatric patients in the MCS compared with current estimates of 14,000– 35,000 adult and pediatric VS patients [12]. Based on United States census data from the year 2000 (http://www.census.gov/) in which there were 72,293,812 children under age of 18 years, the prevalence of MCS is between 44 and 110 per 100,000 children.

6. Characteristics of MCS in children 6.2. Etiology MCS is characterized by behaviors associated with conscious awareness that occur inconsistently but are reproducible or sustained long enough to be discerned. MCS differs from the VS in several ways (Table 4). Children in a VS have no awareness of self or environment whereas children in MCS have definite although limited awareness of the self or environment. Children in a VS have no evidence of language comprehension or expression using verbal or non-verbal signals. MCS children may show a limited but reproducible form of simple communication. MCS children are also more likely to experience pain and suffering in contrast to VS children who by definition are unable to do so. VS and MCS children share in common: (1) sufficiently preserved hypothalamic and brain stem autonomic functions to permit prolonged survival with medical and nursing care; (2) some degree of preserved respiratory function; (3) intermittent wakefulness manifested by the preservation of sleep –wake cycles; (4) bowel and bladder incontinence; (5)

It is presumed that MCS can occur in the same general groups of conditions that cause the VS. For convenience, this has been grouped into three general categories: (1) acquired brain injuries (traumatic and non-traumatic); (2) central nervous system (CNS) degenerative and neurometabolic disorders and (3) congenital or developmental disorders [6]. In the same study that provided prevalence estimates of MCS in children, data on etiology were also reported [12]. Of the 4511 children in MCS, 13% were due to acquired brain injuries, 44% to perinatal or genetic conditions, and 2% to degenerative disorders. In 41%, the etiology was unknown or not reported. 6.3. Neuropathology and neuroimaging The neuropathologic substrate of MCS is unknown but is thought to require bilateral multi-focal or diffuse injury to

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Table 4 Clinical differences between VS and MCSs

Awareness of self or environment Evidence of sustained, reproducible, purposeful or voluntary behavioral responses to visual, auditory, tactile, or noxious stimuli Evidence of language comprehension or expression Intermittent wakefulness manifested by the preservation of sleep–wake cycles Sufficiently preserved hypothalamic and brainstem autonomic functions to permit survival with medical and nursing care Bowel and bladder incontinence Variably preserved cranial nerve and spinal reflexes Simple command-following Gestural or verbal ‘yes/no’ responses (regardless of accuracy) Intelligible verbalization Movements or affective behaviors that occur in contingent relation to relevant environmental stimuli not attributable to reflexive activity Able to experience pain and suffering Able to express preferences regarding self-care or quality of life decisions

cortical or subcortical structures similar to patients in a VS. This would include subcortical white matter injury, diffuse axonal injury particularly in the thalamus, ischemic injury in the neocortex, and focal injury to brain stem or diencephalic structures [20]. Little is known about neuroimaging in children or adults with MCS. In one study of six patients, bilateral cortical lesions were seen with computed axial tomography [21]. No reports of case series of magnetic resonance imaging (MRI) in MCS patients have been published. The following five case histories provide some clinical MRI and MR spectroscopy examples of MCS in the pediatric age group. 6.3.1. Patient #1. Adolescent with severe traumatic brain injury who emerged from VS to MCS This 16-year-old girl had suffered a severe traumatic brain injury after a motor vehicle accident at the age of 14 years. At the time of injury, she immediately lost consciousness and during transport to hospital required a needle cricothyrotomy because she could not be ventilated. Her admission Glasgow Coma Scale score was 3 and her head computed tomography scan showed diffuse edema and punctate parenchymal hemorrhages in the internal capsule and thalamus that suggested diffuse axonal injury. A repeat scan done 4 days later showed additional punctate hemorrhages in the basal ganglia and corpus callosum as well as a contusion of the left temporal lobe. She required intracranial pressure monitoring, evacuation of a subdural fluid collection, tracheostomy, treatment of diabetes insipidus and casting of several fractures. Her MRI scan done 16 days after injury (Fig. 1A) showed a right frontotemporal subdural hematoma and multiple small and moderate sized intraparenchymal hemorrhagic lesions consistent with diffuse axonal injury with moderate ventricular dilatation. MR spectroscopy (Fig. 1B) showed

Vegetative state

Minimally conscious state

No No

Yes Yes

No Yes

Yes Yes

Yes

Yes

Yes Yes No No No No

Yes Yes Yes Yes Yes Yes

No No

Yes No

marked reductions in N-acetyl aspartate (NAA) derived ratios and a small lactate peak. She was discharged 42 days after admission in a VS with a tracheostomy, nasojejunal tube feedings, and with diphenylhydantoin and carbamazepine for control of seizures and desmopressin acetate (DDAVP) for treatment of her diabetes insipidus. She was transferred to a rehabilitation facility. At age of 16 years, she was seen for neurological evaluation. She was thought to be in a MCS because she had visual tracking that appeared consistent and responded to her mother by head turning and smiling that appeared purposeful. She had no functional object use, moderate to severe flaccid quadriplegia, and intermittently had nystagmoid jerking movements of her eyes and rhythmic jerking movements of her orofacial muscles. 6.3.2. Patient #2. Infant with severe ischemic brain injury who evolved from VS to MCS This 6-week-old boy, presented with cyanosis and respiratory distress, was diagnosed with transposition of the great arteries and had an atrial balloon septostomy. The following day, he became hypotensive and had partial complex seizures manifested by lip-smacking. His electroencephalogram (EEG) demonstrated left frontal spike discharges with secondary generalization. On examination, he was alert without focal findings. At 8 weeks of age, a complete arterial switch procedure was performed. The following day, he suffered a cardiac arrest and required 1 h of cardiopulmonary resuscitation after which he was unresponsive. He has had three MR imaging and spectroscopy studies performed (10 days before and 13 days and 6 weeks after the arterial switch procedure). The first MRI demonstrated diffuse T2 lengthening throughout the brain consistent with cytotoxic edema (Fig. 2A). This was felt to be due to previous ischemia due to his heart disease.

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Fig. 1. Adolescent with severe traumatic brain injury who emerged from VS to MCS. (A) Axial T2-weighted MR image 16 days after injury demonstrates a right frontotemporal subdural hematoma and multiple small and moderate sized intraparenchymal hemorrhagic lesions consistent with diffuse axonal injury with moderate ventricular dilatation. (B) Single voxel proton MRS (STEAM acquisition, TR ¼ 3000 ms/TE ¼ 20 ms) of an 8-cm cube volume in the occipital gray matter of the same patient shows reductions in NAA/creatine (NAA/Cre, 0.94) and NAA/choline (NAA/Cho, 1.16) ratios to more than two standard deviations below normal for age as well as the presence of a small lactate peak, both indicating a poor prognosis (Courtesy of Dr Barbara Holshouser, Department of Radiology, Loma Linda University Medical Center).

Spectroscopy showed very low NAA derived metabolite ratios that were indicative of severe neuronal injury (Fig. 2B). The second MRI scan demonstrated mild to moderately severe generalized cerebral atrophy as well as diffuse T2 hyperintensity consistent with edema (Fig. 2C). Spectroscopy again showed severe reductions in NAA derived ratios (not shown). The third MRI scan showed diffuse atrophy with bilateral subdural hygromas (Fig. 2D). MR spectroscopy findings were similar to his previous studies (not shown). At the time of hospital discharge (age of 5 months), he was in a VS with severe generalized spasticity. At age of 9 months, he was visually tracking, appeared interactive, and was considered to be in a MCS. He was also having intermittent clonus of his extremities and had spastic quadriplegic cerebral palsy with truncal ataxia. No language was present. At age 17 months, he was visually tracking, intermittently reached appropriately for objects, and consistently responded to his name. His cerebral palsy was slightly improved. 6.3.3. Patient #3. Child with a CNS degenerative disease with progression from MCS to VS This 3-year-old girl with genetically confirmed Huntington disease presented with moderate developmental delay, marked ataxia, choreoathetosis, and increasing rigidity. Her development had been normal until the age of 18 months when she began to plateau and then regressed. Her mother, sister, and numerous other family members have been

diagnosed with this disorder. She was able to follow commands, crawl, and had a 3 –10 word vocabulary at the time of examination. Her MRI scan showed severe cerebellar atrophy but no evidence of ventriculomegaly or basal ganglia atrophy (Fig. 3A). Spectroscopy showed that the metabolite peaks and their ratios were within normal limits (Fig. 3B). At the age of 4 years, she began to have generalized seizures; her EEG showed a low amplitude fast activity with generalized 4 Hz spike and slow wave discharges most prominent in the occipital regions. She was placed on Depakote. By the age of 5 years, she had deteriorated into a MCS with limited awareness of the environment. She could follow some simple commands, visually track and intermittently reach for objects. She had lost all language function. Over the next year, she descended into a VS and had increasing generalized seizures, severe weight loss, and worsening spasticity and rigidity. She was hospitalized several times for treatment of uncontrolled seizures and failure to gain weight. She died at the age of 9 years after a cardiorespiratory arrest. 6.3.4. Patient #4. Child with inborn error of metabolism, who emerged from VS to MCS and then from MCS to severe developmental delay This child presented in the newborn period with poor feeding and seizures. His MRI scan showed diffuse T2 lengthening in the cerebral white matter and was felt to be consistent with a diffuse demyelinating disorder (Fig. 4A).

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Fig. 2. Infant with severe ischemic brain injury who evolved from VS to MCS. (A) Axial T2-weighted MR image performed 10 days before the patient had a cardiac arrest shows diffuse T2 lengthening throughout the brain consistent with cytotoxic edema. (B) Single voxel proton MRS (STEAM acquisition, TR ¼ 3000 ms/TE ¼ 20 ms) of an 8-cm cube volume in the occipital gray matter of the same patient shows a reduction in the NAA peak and a significant lactate peak that together are indicative of a poor outcome. (C) A second MRI scan, 13 days after the cardiac arrest, shows increased T2 lengthening throughout both cerebral hemispheres consistent with vasogenic and cytotoxic edema with mild to moderate generalized atrophy. (D) A third MRI scan 6 weeks after the cardiac arrest, demonstrates marked central and peripheral atrophy with bilateral panhemispheric subdural fluid collections (Courtesy of Dr Barbara Holshouser, Department of Radiology, Loma Linda University Medical Center).

His MR spectroscopy showed near complete absence of NAA and marked reductions in creatine and choline (Fig. 4B). At the age of 3 months, he was readmitted with lethargy, vomiting, and hyperammonemia. Based on the results of a 24 h urine collection, he was diagnosed as having propionic acidemia and placed on a special formula (Priopiomex-1). His seizures were treated for several months with diphenylhydantoin, which was then discontinued. He was hospitalized numerous times in the first 3 years of life with gastrointestinal symptoms and eventually required placement of a gastrostomy tube. He appeared unaware of the environment and had no evidence of social interaction. Between 15 and 18 months, he began to show some purposeful activities with inconsistent but reproducible

attempts at using his hands and inconsistent visual tracking and was felt to be in a MCS. By the age of 2.5 years, he showed mild hyperreflexia with increased tone and severe developmental delay, functioning at a 4 –8-month level. At the age of 5 years, he is severely delayed. He is able to walk and stand with assistance, has a vocabulary of less than five single words, and communicates by making noises or by using other non-verbal behaviors. 6.3.5. Patient #5. Child with lissencephaly who was diagnosed to be in a MCS This 4-year-old girl was diagnosed at the age of 10 months with lissencephaly when she was being evaluated for developmental delay manifested by her

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Fig. 3. Child with a CNS degenerative disease with progression from MCS to VS. (A) Sagittal T1-weighted MR image of a 3-year-old child with Huntington disease shows cerebellar atrophy. There was no evidence of ventriculomegaly or basal ganglia atrophy on other views. (B) Single voxel proton MRS (STEAM acquisition, TR ¼ 3000 ms/TE ¼ 20 ms) of an 8-cm cube volume in the occipital gray matter of the same patient was slightly compromised because the patient was coughing. However, metabolite ratios were reduced suggesting some degree of neuronal loss (courtesy of Dr Barbara Holshouser, Department of Radiology, Loma Linda University Medical Center).

not rolling over and having no babbling or other evidence of language development. Her seizures began at the age of 2 years, initially with fever but then she began to have repeated generalized tonic clonic seizures without fever. She has been hospitalized several times because of recurrent seizures and has been on various

combinations of antiepileptic medications. During a recent hospitalization at the age of 4 years, her MRI scan (Fig. 5) was repeated and confirmed the findings noted on her earlier study. On examination, she had no language function, was able to visually track, had intermittent purposeful reaching for objects, and was

Fig. 4. Child with inborn error of metabolism, who emerged from VS to MCS and then from MCS to severe developmental delay. (A) Axial T2-weighted MR image of a 17-day-old newborn with poor feeding and seizures shows diffuse T2 lengthening in the cerebral white matter thought to be consistent with a diffuse demyelinating disorder. (B) Single voxel proton MRS (STEAM acquisition, TR ¼ 3000 ms/TE ¼ 20 ms) of an 8-cm cube volume in the occipital gray matter of the same patient shows near complete absence of the NAA and marked reductions in Cre and Cho. Possible elevation of the glutamate/glutamine peak is also noted (courtesy of Dr Barbara Holshouser, Department of Radiology, Loma Linda University Medical Center).

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Fig. 5. Child with lissencephaly who was diagnosed in a MCS. Axial T2weighted MR image shows diffusely thickened cortex with bilateral posterior parietal and occipital agyria compatible with the agyria/pachgyria form of lissencephaly (courtesy of Dr Barbara Holshouser, Department of Radiology, Loma Linda University Medical Center).

considered to be in a MCS. She was non-ambulatory and had spastic quadriplegic cerebral palsy.

7. Management of children in MCS Medical and rehabilitative treatment of children in MCS should be provided to maintain comfort, reduce complications, and optimize functional recovery [1]. Discussions about the appropriate level of treatment should be initiated early in the course of the child’s illness and physicians must determine who is the responsible decision-maker acting on behalf of the child. Determination of the appropriate level of care will require periodic reassessment, particularly if there is no evidence of improvement and MCS is deemed permanent. The Aspen Work Group did not include specific recommendations for treatment of MCS patients as this report concentrated on defining and establishing criteria for MCS [1]. However, treatment of children with MCS should be based on standard neurorehabilitative measures used for children with severe brain injury [22 – 24]. As preliminary data in adults suggest that some subgoups of MCS patients might have a better outcome than VS patients, it is important to develop a comprehensive rehabilitation plan for the care and periodic evaluation of children in MCS, particularly if the etiology is due to traumatic brain injury [25,26]. At some point in an MCS child’s course, there may be a need to make end-of-life decisions regarding the level of care [27]. This may occur before or after it is known if MCS is considered permanent. For example, one might decide to withhold expensive, burdensome, or scarce treatments (e.g. transplant) from a severely compromised MCS patient who

is still improving. Likewise, it may be more humane to limit treatment rather than prolong life in a MCS patient who is suffering without relief from other conditions and has very little likelihood of significant recovery. In such cases, it is again important to identify the surrogate(s) of the child when considering decisions to withhold or withdraw lifesustaining treatments. Treatment decisions may be related to a range of interventions: (1) cardiopulmonary resuscitation, (2) intubation, (3) need for surgery, (4) admission to an intensive care unit, (5) complex organ sustaining treatments such as dialysis, (6) administration of blood products, (7) use of antibiotics, (8) use of medications other than antibiotics, (9) provision of supplemental oxygen, and (10) artificial nutrition and hydration. Specific treatment decisions should be made contingent upon: (a) the individual needs of the child; (b) the child’s prior course of treatment; (c) the potential for improvement and (d) whether the underlying condition is stable or characterized by progressive deterioration. In all circumstances, the child should be treated with dignity and caregivers should be cognizant of the child’s potential for understanding.

8. Diagnostic evaluation of children in whom MCS is suspected As shown in Fig. 6, the neurological examination can help determine whether a child has a disorder of consciousness and whether he/she can be diagnosed as being in a MCS. If the patient has no evidence of sustained or reproducible purposeful responses to external stimuli, then the patient is deemed unconscious. Further examination to determine if the patient is in coma, VS or brain dead is required. The diagnosis of brain death can be confirmed based on well established criteria in children that include unresponsiveness, absent brain stem reflexes, and apnea [28,29]. Depending on the age of the patient, supportive laboratory testing such as an EEG or cerebral blood flow determination might be indicated. If the patient has sleep – wake cycles and appears ‘awake but unaware’, the diagnosis of the VS can be made. If the patient does not have sleep – wake cycles, the patient is considered to be in coma. It should also be mentioned that children, like adults, might have severe motor disabilities and it is clear that it may be difficult to assess whether a child’s severe motor impairments might make it difficult to assess the cognitive function of a child. If the patient has evidence of sustained or reproducible purposeful responses to external stimuli, then the patient would be considered to be conscious and one must differentiate between the MCS, locked-in syndrome, some degree of disability, or normal. As the Aspen Group has suggested, there are four behavioral criteria that, if present, indicate that the patient is in a MCS. However, if the patient has functional interactive communication and/or functional use of the extremities, then, the patient has emerged from

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Fig. 6. An approach to evaluating the patient who might be unconscious to determine whether they are in a MCS or have some other disorder of consciousness. See text for details. Pt, patient.

a MCS. If the patient shows functional interactive communication but has quadriplegia and no functional use of the extremities, the patient may be in a locked-in state.

9. Controversies regarding MCS 9.1. What are the lower and upper limits of MCS? It is assumed that the lower limit of MCS occurs when patients emerge from the VS and show evidence of awareness. What remains uncertain is how we can best assess the upper limits of MCS, that is, the degree of improvement that indicates that an individual is no longer minimally conscious. This is particularly difficult in young children in whom cognitive and language skills are still in the process of development. At the present time, there are no data or consensus that address this issue in children. Valid and reliable bedside clinical methods that are age appropriate and easy to use are needed so that physicians, psychologists, and others caring for such patients can employ them in a timely and cost-effective manner. It is important to be able to better differentiate between being minimally conscious and minimally responsive. Patients can be minimally responsive (i.e. lack the ability to perform a motor act) yet be fully conscious; presumably,

such patients are able to express preferences and other complex behaviors. In contrast, MCS patients have such impaired degrees of consciousness that their motor responses are minimal. It is possible that new neuroimaging technologies (e.g. functional MRI) may help to evaluate such children. Age normative data will determine if these technologies have sufficient resolution to differentiate between these conditions [30 –33]. A recent study using positron emission tomographic scanning in five adult VS patients demonstrated residual cerebral activity and behavioral fragments but unique to each patient [34]. Thus, although functional studies may be sensitive enough to find that fragments of brain activity are present in severely cognitively impaired patients, there may not be a pattern that is specific for either MCS or VS. However, such studies may be able to determine the location and the minimal amount of viable tissue that is necessary to evolve from a MCS to a higher functional level. It is also essential that the definition of minimal consciousness be restrictive so that it is clear that such patients do not have the ability to express preferences, use judgment, or express choices about their care options or other quality of life issues. This is an important issue to resolve as others have suggested a broader concept of the term, implying the possibility that MCS patients may have higher than minimal cognition [35].

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9.2. When is MCS permanent? While it is unknown if and to what extent patients can emerge from MCS, 12 months after injury, participants in the Aspen Work Group observed that the majority of persons in MCS for 12 months remain severely disabled according to the Glasgow Outcome Scale [26]. However, this is clearly an area where further studies are needed. Effects on recovery that need to be examined include those of the patient’s age, etiology of injury, and medical and surgical treatments and complications. 9.3. When can children be diagnosed with MCS and how can this be assessed? The Aspen Work Group stated that “special care must be taken when evaluating infants and children under the age of 3 years who have sustained severe brain injury. In this age group, assessment of cognitive function is constrained by immature language and motor development. This limits the degree to which command-following, verbal expression, and purposeful movement can be relied upon to determine whether the diagnostic criteria for MCS have been met” [1]. Although it is likely that younger children could be diagnosed as being in MCS, the lower age limits when this would be appropriate remain uncertain. The MultiSociety Task Force on persistent VS, stated that except for anencephaly, the diagnosis of the VS may be difficult to make in children younger than 3 months of age [6]. A survey of child neurologists published in 1992 reported that 93% believed a diagnosis of the VS could be made in children [36]. However, only 70% believed that the diagnosis could be made in children under 2 years of age and 16% believed the diagnosis could be made in infants under 2 months of age. The same opinions are likely to apply to the diagnosis of MCS in children but this remains to be determined.

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