Anoxic brain injury (ABI) is a decline in brain function due to a disruption of the oxygen supply to the brain. This can occur in the presence or absence of adequate blood supply and can be caused by any event interfering with the brain’s ability to receive or utilize oxygen such as drowning, suffocation, cardiac or respiratory arrest, cerebrovascular accident, or carbon monoxide poisoning.1
Hypoxic ischemic encephalopathy (HIE) is a condition that occurs in infants and is characterized by inadequate oxygenation to the brain either prenatally, intrapartum, or postnatally, that results in abnormal neurologic function. 2,3 Neurologic abnormalities resulting from hypoxia and anoxia vary in severity and include seizures, cognitive deficits, and motor impairments.2
Anoxia can be defined as total absence of oxygen; therefore, anoxic brain injury (ABI) can be considered a total absence of oxygen to the brain resulting in injury. This term, ABI, is frequently exchangeable in literature as hypoxic ischemic injury (HIE) as well as anoxic ischemic, hypoxic, or cerebral anoxia. 31 A variety in nomenclature fits appropriately as there is often a variety, or continuum, of injury severity following an event.
Anoxic brain injury is alternatively described as any event that deprives the brain of sufficient oxygenation.31 Hypoxemia is defined as severe disruption in perfusing blood flow (cardiac arrest/hypovolemic shock). Brain tissue hypoxia can result from hypoxemia in the setting of normal brain perfusion, as seen with carbon monoxide poisoning or suffocation.
Hypoxic Ischemic Brain Injury (HIBI) is collectively defined as complete, global, temporary loss of blood supply and oxygen to the brain.32 HIE can cause extensive neurologic impairment. The brain is extremely sensitive to oxygen deprivation, regardless of duration.
Anoxic/Hypoxic brain injury (ABI/HBI) can be defined as a global disturbance related to brain function with resultant loss (Anoxic) or decrease (Hypoxic) in oxygen supply to the brain. The term anoxia is used to refer to a complete loss of tissue oxygenation.33
Tissue oxygenation is affected by deliverable blood oxygen content and blood flow. When these factors are altered, hypoxemia and ischemia can result. Prolonged hypoxia induces neuronal cell death that results in irreversible brain injury.33 The severity of these events affects anoxic and hypoxic injury levels.
Etiologies of Hypoxia
Cardiac arrest and respiratory failure are common causes of anoxic brain injury. Other causes include carbon monoxide poisoning, asphyxiation due to hanging, and near drowning.31
Common causes of pediatric anoxic brain injury and primary prevention4-6
Primary anoxic brain injury consists of ischemia (anoxic depolarization, ATP depletion, and glutamate release with free radical formation and nitric oxide production) and reperfusion (creates cerebral edema and death).31,34
Secondary injury is seen with return of spontaneous circulation. Failure of auto-regulation, ongoing ischemia, cerebral hypoperfusion, seizures, as well as the breakdown of the blood brain barrier are seen as cumulative events.31
Impaired cell membrane function causes decreased extracellular sodium, chloride, and calcium and efflux of potassium out of cells into extracellular space. Calcium influx triggers apoptosis causing cell death. Deep gray matter nuclei, cortices, hippocampi, basal ganglia, white matter and cerebellum are all vulnerable.7
ATP depletion at cellular level creates Sodium/Potassium ATP pump failure, causing Sodium influx into cells. Loss of transmembrane gradients leads to anoxic depolarization. Calcium influx into cell, Neuro-glial swelling occurs. N-methyl-D aspartate glutamate receptor activation causes intracellular calcium accumulation, causing impaired cellular stability and activated Calpain system, leading to death.32
During reperfusion phase, formation of free radicals (oxygen and nitrogen) cause neuronal injury, and release of excitotoxic glutamate. Hypoperfusion can also manifest in smaller vessels even as larger vessels are reperfused following injury.32
Most sensitive areas of brain susceptible to global hypoxia are the basal ganglia, layers 3, 5 & 6 of the cerebral cortex, and the deep cerebellar folia. In ABI, brainstem nuclei are most resistant.32
Common outcomes include cerebral edema, elevated intracranial pressure, and cerebral autoregulation dysfunction.32
Brain death and disorders of consciousness8,9
Patients with ABI have variable outcomes depending on length of time of hypoxia, degree of hypoxic injury, duration of impaired consciousness, and duration of post-injury confusion.10
Specific secondary complications in anoxic brain injury as opposed to traumatic brain injury
Patients with anoxic brain injury have differences in neuropathology than those with traumatic brain injury, which may contribute to differences in recovery. Some proposed reasons for recovery difference include more global injury (as opposed to focal injury), more neuronal apoptosis (as opposed to axonal injury) that decreases opportunity for plasticity, and overall different mechanisms of competition for neural responses between cognitive and motor recovery.
Compared to traumatic brain injury, anoxic brain injury is associated with a higher incidence and frequency of seizures, as well as increased pneumonia, gastrointestinal, and heterotopic ossification issues.35
The increased severity of complications in anoxic brain injury are associated with the following rehabilitation and prognostic outcomes:
- Longer rehabilitation stays
- More severe impairments
- Slower rate of recovery as measured by FIM score, with physical recovery slowed than cognitive recovery
- For those in vegetative states, anoxic brain injury patients improved to minimally conscious states (or better) at a lower rate than traumatic brain injury.
- Higher mortality
Essentials of Assessment
Historical Evaluation should include onset of injury, mechanism, duration of ischemia and time of reperfusion (if known). Medication use and abuse should also be researched, to include prescription medications, over the medications, and any illegal substance use/abuse. Prior psychiatric history, educational history, and functional history will also provide key details in relation to prognosis and functional recovery. Social support should also be documented at this time.31
- History of present illness: Detailed history of event leading up to anoxia; duration of anoxia; details of immediate resuscitation, including effectiveness; use of any medications/drugs- prescribed (antiepileptics or antidepressants) or recreational (alcohol, heroin); history of trauma; allergies to medications.
- Birth and developmental history, including gestational age; type of delivery: Vaginal vs Cesarean section; any anoxia at birth; baseline developmental history information
- Past medical/surgical history: Specifically include cardiac history, respiratory history, seizure history, or history related to another specific known cause of anoxia for specific patients.
- Family history: Specifically include cardiac history (sudden death suggesting Wolff Parkinson White syndrome, prolonged QT syndrome); history of epilepsy, or history related to another specific known cause of anoxia for specific patient
- Social history: Type of house family lives in, any steps in, who will help care for the child, adults involved in child’s care at this time, educational stage
Examination following anoxic brain injury may vary based on severity. In severe injuries (to include children without consciousness), the child may be evaluated for brainstem reflexes, generalized myoclonus, and motor responses to stimuli. In any child, it is important to assess motor movements, range of motion, skin integrity, and muscle tone.
In a conscious child, it is important to assess cognitive impairment. Areas of evaluation should include attention, processing speed, memory, executive dysfunction, language, calculation, apraxia, agnosia, and visuospatial impairments. Specific motor impairment should be identified during the musculoskeletal (MSK) exam as well as the neurological exam. These can include Parkinsonism, dystonia, spasticity, chorea, tremor, tics, athetosis, seizures, or myoclonic syndromes.31
- Level of arousal / consciousness
- Circulatory status:
- Vital Signs
- Capillary refill
- Respiratory status:
- Regular vs. irregular spontaneous breathing
- Intubation: Breathing over vent, at vent rate or apneic?
- For infants: anterior fontanelle exam for fullness, assess sutures for separation
History, physical examination, and imaging need to be interpreted together to further guide management. For this reason, it is important that the neurologic exam is not altered by medications, fluctuations in temperature, or metabolic abnormalities that could contribute to an altered neurologic examination. Sedatives, analgesics, and paralytics may alter the ability of a patient in assessment of neurologic capability.
Pupillary and corneal reflexes, motor response to pain, and myoclonus status epilepticus have prognostic potential. For example, a bilaterally absent pupillary light response as well as a bilaterally absent corneal reflex on day 3 is a strong predictor of poor prognosis.32
- Fundoscopic exam: multilayered retinal hemorrhage suggestive of non-accidental head injury
- Extraocular assessment including brainstem function:
- Ocular movements
- Sustained down/up-gaze, irregular upward nystagmus, ping-pong gaze, periodic lateral gaze associated with poor outcome
- Corneal reflexes
- Pupillary light reflex16
- Unilateral fixed dilated pupil suggestive of transtentorial herniation
- Acute bilateral fixed dilated pupils (concern for central herniation)
- Oculocephalic reflexes
- Ocular movements
- Motor exam
- Muscle Tone
- Motor response to pain
- Decorticate and decerebrate posturing
- Ability to follow motor commands
- Sensory exam
- Reflex exam
- Coordination exam
- Abnormal Movement
- Rigidity, dystonia, chorea, action myoclonus more common in ABI
- Muscle Bulk
- Muscle Tone
- Spasticity, rigidity and dystonia often more severe and generalized in children with ABI compared to TBI
- Range of Motion
- Common contractures include equinus deformity, hip flexion contracture, and knee flexion contracture.
- Hip subluxation/dislocation
- Found in 34% of near-drowning children with ABI as early as 1 month after injury
- Found in 18% of children with ABI
- 70% children with ABI from near-drowning non-ambulatory
Note: Neurologic exam is often limited in acute phase of anoxic brain injury due to severe cognitive compromise. PICU clinical assessment is often compromised by sedation, neuromuscular blockade, ventilation, hypothermia, inotropic management etc.
Early prognostic indicators31
Circumstances of Event & Patient Factors
- Non-Modifiable: Age, Gender, Pre-existing Conditions
- Modifiable: Time to Resuscitation, Medication Administration
- Comorbid conditions and circumstances of initial resuscitation (duration of CPR, no-flow time, initial rhythm, lactate levels) are strong predictors of short term survival
- Good functional status prior to the event, as well as absence of mechanical ventilation, is associated with a positive neurologic outcome.
Common prognostic scales
- Modified Pediatric Glasgow Coma Scale
- Full Outline of Unresponsiveness (FOUR) Scores10
- Eye responses
- Motor responses
- Brainstem reflexes
- Respiration pattern
Intracranial Pressure (ICP) Monitoring
- Ventricular catheter placement provides most accurate assessment of ICP, as well as allows for therapeutic CSF drainage
- ICP > 20mmHg in comatose patients associated with poor outcome
- Look out for increased ICP / herniation syndromes16
- Decerebration pattern
- Abrupt pupillary change
- Impaired upward gaze
- Sudden deterioration of respiration and apnea
- Sustained late intracranial hypertension more likely a sign of irreversible brain damage
Electroencephalography (EEG) Monitoring
EEG is one of the most widely used tests for early prognostication after Hypoxic Ischemic Brain Injury (HIBI). EEG provides information about brain activity in Real-Time. It assesses the efferent functions of pyramidal cells in the cortex.32
EEG waveforms are associated with degree of injury. Three features play a role in evaluation: background activity, reactivity, epileptiform changes. Background activity represents overall function as well as associated outcome.32
- Continuous or repetitive EEG monitoring most helpful for evaluation of encephalopathy (EEG background) and seizure detection (HIBI results in decreased amplitude and slowing of background activity)
- Good outcome predictors:
- Moderate background activity, sleep patterns, response to auditory and painful stimulations, numerous beta rhythms
- Early recovery of continuous background
- Late appearance of epileptiform activity
- Poor outcome predictors: Low Voltage or isoelectric EEG
- High voltage, rhythmic delta waves, biphasic sharp waves, “burst suppression” pattern (Use with caution as burst suppression can be induced by midazolam or propofol), absence of beta rhythms, generalized suppression, status epilepticus, nonreactivity
- Persistently abnormal EEG at 48 hours or more associated with adverse neurodevelopmental outcome
- Epileptiform Features (sharp waves, polyspikes, spikes, wave patterns) 32
Somatosensory Evoked Potential (SSEP) Monitoring
Somatosensory Evoked Potentials (SSEPs) assess afferent thalamocortical integrity. 32
- SSEP is used as a neurophysiologic test for assessing integrity of neuronal pathways from the peripheral nerves, spinal cord, brainstem and cerebral cortex.
- Most reliable evoked potential waveform as median N20 component of SSEP
- Median N20 SSEP: first cortical response of SSEP with median nerve stimulation
- Bilateral absence of median N20 response on days 1 and 3 or later following CPR accurately predicts poor outcome (reflects widespread cortical necrosis) Bilateral absence of N20 potentials is a reliable/strong predictor of poor outcome after cardiac arrest yet may be impacted by hypothermia.32
- Advantage: less susceptible to effects of sedative drugs, metabolic changes and artifact interference compared to EEG monitoring.
- Disadvantage: require advanced neurologic training, interpretation limited to specialized centers, low sensitivity
Serum Biomarkers for ABI Prognostication
- Serum NSE (neuron-specific enolase)
- Isomer of intracytoplasmic glycolytic enzyme enolase found in neuronal bodies, axons, neuroendocrine cells and tumors
- NSE peaks in serum and CSF at ours after injury
- Serum NSE > 33 microgram/L at days 1 and 3 associated with poor outcome
- Use limited by lack of laboratory standardization, long turn-around time
- Most widely investigated serum biomarker of neuronal damage 32
- S100 protein
- Calcium-binding protein highly concentrated in glial and Schwann cells
- Highest level in first 24 hours after anoxic injury; declines over next 48 hours
- Released from injured glial cells 32
- CKBB (creatine kinase brain isozyme)
- Present in neurons and astrocytes; leaks from cytoplasm of destroyed cells
- Peaks around 48-72 hours after injury
- Tau Protein
- Marker of axonal injury
- Released into serum and CSF
- Predicts poor outcome
- Neurofilament Light Chain
- Biomarker of axonal injury
- Currently under investigation for prognostication of TIBI
- Most accurate marker with poor predictive outcome in first 24 hours post event 32
Laboratory studies to monitor for complications
- Ideal for newborn/infants
- Suitable for screening and follow-up exam
- Generally performed using anterior fontanelle as acoustic window
- Posterior fontanelle and mastoid fontanelles can be used as acoustic windows to study posterior fossa and brainstem
- Noninvasive and low cost, can be done at bedside
- Cons: does not depict white matter signal abnormalities, does not give detailed information on myelination and detect lesions on posterior limb of internal capsule
- Very limited role in young infants due to high ionizing radiation
- Excellent for detecting hemorrhage
- Not great for detecting edema/infarction newborn with hypoxic-ischemic brain injury due to high water content in newborn brain
- Superb soft tissue contrast differentiation
- Diffusion-weighted imaging (DWI)—uses hydrogen molecules physical property of diffusion: sensitive for detecting cytotoxic edema; white matter lesions; ventricular enlargement vs loss of gyri and sulci causing an ex vacuo effect.
Neuropsychological deficits often pronounced in pediatric survivors of anoxic brain injury due to diffuse and often more severe nature of cerebral involvement.
Exact impairments depend on nature and duration of anoxic event, associated neuronal degeneration, age at injury, and selective vulnerability of different brain regions (e.g., hippocampus, globus pallidus, thalamus, putamen, caudate nucleus, parieto-occipital cortex, substantia nigra and cerebellum.)
Common neuropsychological impairments seen in anoxic brain injury
- Memory deficits
- Learning difficulties
- Attention deficits
- Decreased visuospatial abilities
- Generalized intellectual impairment
- Behavioral problems
- Dysexecutive syndromes
- Personality changes
Early predictions of outcomes
Indicators of recovery include presence or absence of spontaneous movements; response to voice, light touch, and painful stimuli; pupillary size, response to light; cranial nerve function: corneal and oculovestibular reflexes; respiratory pattern.
A Glasgow Coma Scale (GCS) score of ≤4 within the first 48 hours has been associated with poor outcomes, such as coma or death. Absent corneal or pupillary light reflexes at 24 hours, and absent motor responses at 24 or 72 hours, have been associated with severe disability/death.
Based on clinical data, the typical outcome in ABI is recovery, chronic unresponsive wakefulness, or death. If a patient is in chronic unresponsive wakefulness at time of discharge, life expectancy is approximately two to five years. Absent motor responses, extensor motor responses, absent pupillary reflexes, or absent corneal reflexes on the third day after injury are associated with poor outcomes.
Children who sustain ABI demonstrate worse outcomes than children with traumatic brain injury (TBI), cognitively and motorically, especially if unconscious for more than 60 days.
Social role and social support system
The patient, family, and/or caregiver(s) should be asked about who lives at home; adults who can help with care; structure and accessibility of home, including bathroom setup, doorway sizes, stairs to enter and stairs inside home; transportation options for the patient, including vehicle(s), public transportation, and school transportation; and current school setting.
Rehabilitation Management and Treatments
Available or current treatment guidelines
In the early phases of anoxic brain injury, rehabilitation primarily focuses on increasing arousal and participation.39 This can be seen especially during Disorders of Consciousness. Pharmacologic management and non-pharmacologic modalities may be employed. These may include interventions such as sleep hygiene, as well as pharmacological approaches such as amantadine which has been shown in a pilot study to help recover consciousness.25 Other pharmacology, including stimulants such as methylphenidate, have been used in pediatric ABI to help improve attention, concentration, and memory, typically after emergence from MCS.41
Following emergence from a minimally conscious state (MCS), rehabilitation focus transitions to specific task based assistance and responsibility associated with functional movements and self-care. Therapy efforts tend to focus on spasticity management, fall prevention, and environmental navigation while encouraging independence. Pharmacologic efforts tend to be focused on improving agitation, attention, processing speed, memory deficits, sleep disturbances, depression, and headaches.31 Various treatment modalities can be further utilized through disease progression.
Spasticity management in anoxic brain injury is a rehabilitation focus of recovery. Adequate spasticity management may allow for decreased energy expenditure, improved ambulation, and increased range of motion (ROM).31,40
Patients with anoxic brain injury often initially have flaccid musculature. Initial flaccidity can change to hypertonicity with spasticity, rigidity, or dystonia.
Spasticity can be effectively treated using oral, intrathecal, or injectable pharmacologic agents. Oral medications commonly include, but are not limited to, baclofen, tizanidine, clonidine, diazepam, and dantrolene (all have been shown to reduce muscle spasms). There is limited evidence as to the effect on anoxic brain injury specifically in comparison to traumatic brain injury.31 Spasticity can also be treated with interventional chemodenervation using botulinum toxins in muscles and/or ethanol/phenol in muscles. It is important to begin treating early to prevent contracture development. Dystonia is difficult to treat pharmacologically; enteral carbidopa/levodopa, enteral bromocriptine, botulinum toxin injections, and intrathecal baclofen via pump have all shown promise.
Another complication, although less reported in the pediatric population, is post-anoxic myoclonus (PAM), a rare but significantly debilitating consequence of anoxic brain injury. PAM, usually a type of intention myoclonus (including response to stimuli), can be classified into acute and chronic (Lance-Adams type) forms.36 There are several forms of myoclonus which can be further classified via electrophysiological findings, which can help reveal sites of origin (cortical, subcortical, brainstem, segmental, peripheral), as well as potential seizure activity. In post-anoxic brain injury, cortical, exaggerated startle, and reticular reflex myoclonus types are predominant. Clinically, in cortical myoclonus, there can be focal, multifocal, bilateral or generalized movements, while in exaggerated startle and reticular reflex myoclonus there are more generalized movements. Classifying the types of myoclonus can guide treatment. Clonazepam, valproate, levetiracetam, and piracetam can be used to treat cortical myoclonus. Clonazepam has been used to treat exaggerated startle while Diazepam, clonazepam, while clonazepam, diazepam, 5-HTP, as well as DBS (deep-brain stimulation) can be used in reticular reflex myoclonus.37
Seizures are another known complication of both anoxic and traumatic brain injury, more commonly associated with penetrating trauma. Most seizure activity occurs in the acute post-injury time period (days to weeks), although some may occur even years after the injury. Post traumatic epilepsy may also develop. Common AEDs used in treatment include carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, and valproate.38
Paroxysmal sympathetic hyperactivity (PSH), a complication of brain injury seen in a significant minority of patients, is characterized by hyperthermia, sweating, tachypnea, tachycardia, hypertension, and/or dystonia, typically in response to some type of external stimuli. Although studies have shown a higher prevalence of PSH seen after traumatic brain injury compared to after anoxic brain injury in the adult population, a few pediatric studies have actually shown a higher prevalence of PSH in anoxic brain injury compared to traumatic brain injury in the pediatric population.26 Although the exact pathophysiology of PSH is not clear, it is thought to result from impaired descending inhibitory pathways resulting in spinal circuit excitation. 26 Empirical pharmacologic treatment with opioids (usually morphine), benzodiazepines, clonidine, propranolol, other antihypertensives, bromocriptine, and/or baclofen can be helpful in preventing and treating paroxysms.26
Early pump placement for intrathecal baclofen dosing has been shown to be effective in treating both hypertonicity and PSH.28
Rehabilitation-specific treatment in anoxic brain injury
Physical, occupational, and speech therapies are beneficial immediately after injuries, and should be involved in all phases of recovery. Passive range of motion exercises, splinting, or bracing benefit the brain-injured child, depending largely upon the presentation of tone.
Coordination of care
Discharge planning begins on admission. An initial evaluation by team members should be communicated to patient, family, and funding source to coordinate adequate care with regard to medical care, therapies required, social needs, and required equipment (including mobility or other assistive devices, and orthoses).
A multidisciplinary team is best utilized in this situation. Team members include: physiatry, social work, physical therapy, occupational therapy, speech therapy, neuropsychology, nursing, recreational therapy, and child life specialist. Additional team members, such as wound care team or an orthotist, may be required depending on the individual patient
At time of discharge, information should be conveyed to the primary care physician and outpatient therapy team to ensure seamless care.
Patient & family education
Families should be trained regarding deficits, new care needs, and new equipment. They should be educated about use of current medications, ongoing therapy requirements, and potential course of recovery.
Families benefit from care management and social work to learn about available resources and how to navigate new health care systems. Families should be educated regarding funding and resource programs available to them.
Community integration should be individualized based on a patient’s level of function. This can include return to school, social activities, or recreational activities. It can also include, providing caregiver assistance, education regarding physical and cognitive deficits, counseling services for patient and family for coping strategies, and involvement with support groups.
Parents and families need support and understanding from the treatment team. At times, the treatment team may not agree with a family’s understanding of a condition or choices for a patient. It is important to be non-judgmental and family to make decisions that help the patient and align with the patient’s/family’s values and goals.
Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills
- Families should be given anticipatory guidance about risks for anoxic brain injury, particularly in children with medical conditions that increase risk (cardiac disease, severe respiratory disease, epilepsy)
- Aggressive management of spasticity is helpful, particularly early after emergence of increased tone.
- Paroxysmal sympathetic hyperactivity can be treated with a variety of pharmacologic options, including analgesics, benzodiazepines, antihypertensives, or early baclofen pump placement.
- Family training and education is paramount during early phases of recovery from anoxic brain injury.
Cutting Edge/ Emerging and Unique Concepts and Practice
Therapeutic hypothermia, or “cooling,” is a process by which core body temperature is purposely lowered to 32-34 degrees Celsius in order to prevent ischemic injury or death. Therapeutic hypothermia attempts to reduce anoxic brain injury by decreasing cerebral metabolism and reducing global carbon dioxide production, while also reducing oxygen consumption. For every one degree Celsius change in temperature, cerebral metabolism decreases by 6-7%. The targeted temperature is 32-34 C., and temperature modulation is achieved by surface cooling methods (cooling pad & blankets). It can also be achieved by intravascular “cooling”. On the other hand, hyperthermia, which is well studied, is known to worsen outcomes in hypoxic-ischemic brain injury.32
Therapeutic hypothermia has been shown to improve neurologic outcome. Recent research has shown that therapeutic hypothermia reduces the outcome of death or long-term neurodevelopmental disability at 18 months.29
Ongoing discussions around the field of therapeutic hypothermia include optimal temperature and duration.32
Gaps in the Evidence-Based Knowledge
Use of hyperbaric oxygen therapy, including what protocol may be useful, is controversial. Some studies show promise, but sufficient evidence for integration into clinical care is still lacking.30
- Cerebral Hypoxia Information Page – National Institute of Neurologic Disorders and Stroke. 2019 3-27-2019 [cited 2019 July 23]; Available from: https://www.ninds.nih.gov/Disorders/All-Disorders/Cerebral-Hypoxia-Information-Page#disorders-r1.
- Allen, K.A. and D.H. Brandon, Hypoxic Ischemic Encephalopathy: Pathophysiology and Experimental Treatments. Newborn Infant Nurs Rev, 2011. 11(3): p. 125-133.
- Fatemi, A., M.A. Wilson, and M.V. Johnston, Hypoxic-ischemic encephalopathy in the term infant. Clin Perinatol, 2009. 36(4): p. 835-58, vii.
- Hopkins, R.O. and E.D. Bigler, Neuroimaging of anoxic injury: implications for neurorehabilitation. NeuroRehabilitation, 2012. 31(3): p. 319-29.
- Thaler, N.S., et al., Neuropsychological profiles of six children with anoxic brain injury. Child Neuropsychol, 2013. 19(5): p. 479-94.
- Fitzgerald, A., et al., Anoxic brain injury: Clinical patterns and functional outcomes. A study of 93 cases. Brain Inj, 2010. 24(11): p. 1311-23.
- Busl, K.M. and D.M. Greer, Hypoxic-ischemic brain injury: pathophysiology, neuropathology and mechanisms. NeuroRehabilitation, 2010. 26(1): p. 5-13.
- Bruno, M.-A., et al., From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness. J Neurol, 2011. 248(7): p. 1373-1384.
- Giacino, J.T., et al., Practice Guideline Update Recommendations Summary: Disorders of Consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Arch Phys Med Rehabil, 2018. 99(9): p. 1699-1709.
- Nguyen, K.P.L., et al., Prognostication in Anoxic Brain Injury. Am J Hosp Palliat Care, 2018. 35(11): p. 1446-1455.
- Cullen, N.K., C. Crescini, and M.T. Bayley, Rehabilitation outcomes after anoxic brain injury: a case-controlled comparison with traumatic brain injury. PM R, 2009. 1(12): p. 1069-76.
- Schmidt, J.G., J. Drew-Cates, and M.L. Dombovy, Anoxic encephalopathy: Outcome after inpatient rehabilitation. Journal of Neurologic Rehabilitation, 1997. 11(3): p. 189-195.
- Kriel, R.L., L.E. Krach, and C. Jones-Saete, Outcome of children with prolonged unconsciousness and vegetative states. Pediatr Neurol, 1993. 9(5): p. 362-8.
- Kriel, R.L., et al., Outcome of severe anoxic/ischemic brain injury in children. Pediatr Neurol, 1994. 10(3): p. 207-12.
- Adams, J.H., D.I. Graham, and B. Jennett. The neuropathology of the vegetative state after an acute brain insult. Brain, 2000. 123 (7): p. 1327-1338.
- Seshia, S.S., et al., Nontraumatic Coma in Children and Adolescents: Diagnosis and Management. Neurologic Clinics, 2011. 29(4): p. 1007-1043.
- Abrams, R.A. and S. Mubarak, Musculoskeletal consequences of near-drowning in children. J Pediatr Orthop, 1991. 11(2): p. 168-75.
- Suominen, P.K. and R. Vahatalo, Neurologic long term outcome after drowning in children. Scand J Trauma Resusc Emerg Med, 2012. 20: p. 55.
- Chang, T. and A. du Plessis, Neurodiagnostic techniques in neonatal critical care. Curr Neurol Neurosci Rep, 2012. 12(2): p. 145-52.
- Chandrasekaran, M., et al., Predictive value of amplitude-integrated EEG (aEEG) after rescue hypothermic neuroprotection for hypoxic ischemic encephalopathy: a meta-analysis. J Perinatol, 2017. 37(6): p. 684-689.
- Cheliout-Heraut, F., et al., [Cerebral anoxia in near-drowning of children. The prognostic value of EEG]. Neurophysiol Clin, 1991. 21(2): p. 121-32.
- Liauw, L. Hypoxic-Ischemic BI in Young Infants. Ann Acad Med Singapore, 2009. 38: p. 788-794.
- Pierro, M.M., et al., Anoxic brain injury following near-drowning in children. Rehabilitation outcome: three case reports. Brain Inj, 2005. 19(13): p. 1147-55.
- Levy, D.E., et al., Predicting Outcome from Hypoxic-Ischemic Coma. Jama-Journal of the American Medical Association, 1985. 253(10): p. 1420-1426.
- McMahon, M.A., et al. Effects of Amantadine in Children with Impaired Consciousness Caused by Acquired Brain Injury: A Pilot Study. Am J Phys Med Rehabil, 2009. 88(7): p. 525-532.
- Meyfroidt, G., Baguley, I. J., & Menon, D. K. (2017). Paroxysmal sympathetic hyperactivity: the storm after acute brain injury. The Lancet Neurology, 16(9), 721-729.
- Turner, M.S. Early use of intrathecal baclofen in brain injury in pediatric patients. In: Katayama Y. (eds) Neurosurgical Re-Engineering of the Damaged Brain and Spinal Cord. Acta Neurochirurgica Supplements, vol 87; 2003. Springer, Vienna.
- Davidson, J.O., et al. Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy – Where to from Here?. Front Neurol, 2015. 6: 198.
- Ostrowski, R.P., et al. Hyperbaric oxygen modalities are differentially effective in distinct brain ischemia models. Med Gas Res, 6(1): p. 39-47.
- Eapen, Blessen C, David X. Cifu. Brain Injury Medicine: Board Review. 2021: 342
- Zasler, Nathan D., Katz, Douglas I., Zafonte, Ross D. Brain Injury Medicine: Principles and Practice. Demos Medical. 2022: 654-660
- Zollman, Felise S. Manual of Traumatic Brain Injury: Assessment and Management. Demos Medical. 2022:206
- Sekhon, MS. Ainslie PN, Griesdale DE. Clinical pathophysiology of hypoxic ischemic brain injury and cardiac arrest: a “two-hit” model. Crit Care. 2017 Dec
- Zasler, Nathan D., Douglas I. Katz, and Ross D. Zafonte, eds. Brain injury medicine: principles and practice.Demos Medical. 2013: 556
- 1. Hallett M.: Physiology of human posthypoxic myoclonus. Mov Disord 2000; 15 Suppl 1: pp. 8-13.
- Ong, M. T., Sarrigiannis, P. G., & Baxter, P. S. (2017). Post-anoxic reticular reflex myoclonus in a child and proposed classification of post-anoxic myoclonus. Pediatric Neurology, 68, 68-72.
- Englander, J., Cifu, D. X., Diaz-Arrastia, R., & Center, M. S. K. T. (2014). Seizures after traumatic brain injury. Archives of physical medicine and rehabilitation, 95(6), 122
- Sawyer KN, Calloway, CW, Wagner AK. Life after death: surviving cardiac arrest—an overview of epidemiology, best acute care practices, and considerations for rehabilitation care. Curr Phys Med Rehabil Rep. 2017; 5 (1): 30-39
- Schultz BA, Bellamkonda E. Management of medical complications during the rehabilitation of moderate to severe traumatic brain injury. Phys Med Rehabil Clin North Am. 2017: 28 (2): 259-270
- Harvey, D.W., Morrall, M., Neilly, E. and Murdoch-Eaton, D., 2012. Question 3 Should stimulants be administered to manage difficulties with attention, hyperactivity and impulsivity following paediatric acquired brain injury?. Archives of disease in childhood, 97(8), pp.755-758.
Original Version of the Topic
Rajashree Srinivasan, MD, Cristina Sanders, DO. Pediatric Anoxic Brain Injury. 9/20/2013
Previous Revision(s) of the Topic
Andrew Collins, MD, Priya Bolikal, MD, SheanHuey Ng, MD. Pediatric Anoxic Brain Injury. 10/20/2019
Cristina Marie Sanders, DO
Nothing to Disclose
Rajashree Srinivasan, MD
Nothing to Disclose
Priya Chitta Nangrani, MD
Nothing to Disclose