Hypoxia

carbon monoxide (CO) poisoning shows many of\nthe same effects as other forms of\nhypoxia/ischemia but there are some notable\ndifferences in the pathological processes

- CO has a high affinity for binding with\nhemoglobin, forming carboxyhemoglobin\n\nthe effect displaced O2 binding sites in red\nblood cells, resulting in hypoxia and acidosis\n\nonce carboxyhemoglobin rises above 20-30%\nof total hemoglobin in the blood, acute effects\nare seen\n\nlevels above 50% cause coma and severe CNS\neffects\n\nnot clear whether CO is directly toxic to\nneurons, and he most sig effects are very\nsimilar to what is seen following cardiac arrest\n\n\nCO poisoning often results in delayed\nneurologic deterioration, which may occur 1-2\nweeks after exposure\n\nBasal ganglia damage is common, contributing\nto the extrapyramidal features often seen\nfollowing severe Co poisoning\n\n\nhippocampal and general brain atrophy ( as\nmeasures by ventricle to brain ratio) may be\nseen months following injury\n\nNP deficits may be seen in attn., inform\nprocessing, EF, verbal and non verbal memory

homeostatic protective mechanisms are\ntriggered when PaO2 or perfusion is disrupted,\nand these are effective w/in certain parameters

- the nervous system responds to hypoxic states\nby increasing cerebral blood flow up to 400%\n- autoregulatory response to a reduction or loss\nof perfusion pressure involves several\nmechanisms, including dilation of blood vessels\nto maintain flow

hippocampal damage historically a hallmark of\nhypoxic damage, but reviews of published cases\nw neuroimaging data shows

1. hippocampal damage is freq not noted\n\n2. when damage is visible, it usually is present in\nmultiple brain regions\n\none review showed that watershed cortex and\nthe basal ganglia were both more frequently\ndamaged than the hippocampus

the hippocampus was the sole affected structure\nin only

18% of reported cases

partial pressure of arterial oxygen (PaO2) in health adults at sea level:

95-100 mm Hg

if hypoxia is not severe enough to disrupt\nconsciousness

CNS damage is unlikely

instruments useful for evaluating individuals\nearly in recovery (acute care or early IP rehab)\nand that focus on basic functioning:

GCS\nComa Recovery Scale- Revised\nComa- Near Coma Scale\nRancho Los Amigos Level of Cog Fx

instruments useful for structured basic\nassessment of mental status

MMSE\nOrientation Log\nCognitive Log\nMOCA\nCognistat\nwith higher cog Fx early in recovery: RBANS

Assessment methods- imaging

MRI and CT initially often do not reveal sig\nchanges\n\nfollow up studies may reveal white matter\nchanges, corpus callosum atrophy, cortical\nedema, cerebellar lesions, basal ganglia\nlesions, thalamic lesions, and/or hippocampal\natrophy\n\n(OFTEN TAKE WEEKS OR MONTHS TO BE\nVISUALIZED ON SCANS)

several factors complicate attempts to\ncharacterize patterns of neuropathology and cog\nimp due to hypoxic, ischemic conditions

a broad range of conditions that cause\nhypoxic/ischemic damage\n\nmultisystem complications occur and may\nexacerbate encephalopathy\n\ncog imp from milder hypoxic/ischemic states\nmay not be recog. in the hospital setting\n\nmethodology and operational def of key terms\nvary across studies

ATP (adenosine triphosphate)

a chemical compound that provides energy for\ncells/neurons\n\nunder anoxic conditions, becomes less available\nin the neuron, leading it to catabolize itself

oxygenation of the blood is the result of

a complex process involving hemoglobin\nconcentration and O2 saturation

studies comparing patterns of recovery from\nhypoxia/anoxia to TBI have found the following\npatterns:

amount of tissue loss is more critical in\ndetermining outcome than etiology\n\nmeasures of memory correlate with\nhippocampal atrophy in both hypoxia and TBI\n\nintelligence correlates with whole brain volume\nin both conditions\n\nthose with hypoxia have similar lengths of\ninpatient stay as TBI but show slower progress\nand poor outcomes\n\nthose with hypoxic injury more likely to be\nreferred to residential care\n\nthose with hypoxia perform worse on all\nmeasures of fx outcome than TBI and have\nhave lower functional independence measure\nmotor and cognitive gains relative to those w\nTBI

expectations for NP assessment results-\n\nemotion and personality

anosognosia (impaired self awareness) is\ncommon early post injury and may persist long\nterm\n\ndepression commonly observed\n\nchanges in self regulation of emotion may\noccur due to medial frontal and frontal\nsystems injury\n\nbeh dysregulation may be seen in severe cases\nand may become a chronic feature\n\nsevere psychiatric issues are common in severe\ncases, which may incl beh dysregulation and\nmajor depression

outpatient and post acute brain injury rehab\nprograms

are appropriate and may extend treatment\ngains from IP setting\n\nfocus on compensatory strategies, skill\nacquisition, building independence, and\ncommunity reintegration\n\nfamily training and support is critical

recovery curves in pts with severe\nhypoxic/ischemic injury

are fairly flat, and return to independence is\nrarely achieved

severe OSA

assoc with greater risk for white matter\nhyperintensities and cog imp (learning and mem,\nEF, psychomotor impairments), but not\nconsistent across studies

as recovery progresses

attention deficits, distractibility, severe\nanterograde amnesia, and EF dysfunction need\nto be addressed\n\nrehab generally involves teaching compensatory\nstrategies or attempting to directly address areas\nof cog deficit

when evaluating a pt in the acute phase of recovery

be mindful of\ninterventions\nmedications\ncomorbidities\nthat can cause or contribute to encephalopathy,\nconfusing or complicating the presentation

neuropathological changes from\nhypoxia/ischemia are consistent with the\nmechanism of insult-

brain regions with high metabolic demands and\nthose at the distal end of cerebral arteries (in\nparticular, watershed regions) are more\nvulnerable

pediatric considerations

brains of infants and children req a higher\npercentage of O2 than adults (over 30% total\nbody O2 consumption from infancy to age 4)\n\nimpact of hypoxia will depend on\ndevelopmental period where it occurs\n\nneonatal hypoxia may lead to major\ndevelopmental disorders and impaired\ncognition, depending on severity and pattern\nof damage\n\ninjury to the basal ganglia and thalamus is\npredominant pattern in neonates assoc with\nlong term outcome\n\ncongenital heart defects and sleep disordered\nbreathing are also found to have a relationship\nwith cog, academic, and beh Fx\n\nsome deficits are not noted until a child starts\nschool

factors which may complicate patterns of neuropathology and cognitive dysfunction due to hypoxic/ischemic conditions:

broad range of conditions that can cause H/I damage\n \nmultisystem complications that occur and can exacerbate encephalopathy\n \ncognitive impairment from milder H/I states may not always be recognized in hospital setting\n \nmethodology and operational definitions of key terms such as hypoxia vary across studies

interpersonal relationships

can be challenging due to persistent memory\nimpairment, poor insight, exec dysfunction, and\nchanges in premorbid role Fx

NP assessment may serve the following pruposes

characterize strengths and deficits and link\nsuch patterns to daily Fx\n\nidentify target goals for continued\nrehabilitation\n\nidentify the presence and severity of\npsychological disturbance that may impact\nrecovery and rehab\n\ndetermine decision making capacity and need\nfor supervision\n\nidentify target areas for accommodations for\nreturn to school and work

in mild cases with rapid reversal of pathological\ncondition

cog imp may be transient, but some may\nexperience persistent cognitive deficits

the following are poor prognostic indicators in\nthe absence of sedation effects

coma more than 6 hours\nno spontaneous leg movements or localization\nto pain stimuli\nprolonged loss of pupillary responses\nsustained conjunctive eye deviation\nabnormal eye movements (nystagmus)\nmyoclonic seizures\nlower cranial nerve dysfunction (such as absent\ncough and gag reflexes)

rehab considerations

compensatory strategy training is critical for\npatients with memory or other cog imp\n\nemphasis should be placed on errorless learning,\nprocedural learning, attention process training\n(APT), and evidenced based cognitive\nrehabilitation Tx

Result of arterial oxygen level dropping:

complex cognitive processes such as memory and judgment become impaired

Anoxic and hypoxic damage to the brain is secondary to:

conditions that affect the cardiac and respiratory systems

the brain is highly dependent on

consistent supply of blood, O2, and glucose and\nconsumes those at levels disproportionate to its\nmass in other parts of the body

deficient oxygen supply can occur from (2):

deficient perfusion of blood to the brain\n \nreduced amount or concentration of oxygen in the blood

determinants of severity

effects vary based on the nature of the\nunderlying condition that produced the\ndisruption in O2 supply and how rapidly the\npathological process can be reversed.

COPD

encompasses several pulmonary conditions, incl\nemphysema and bronchitis\n\nprogressive obstruction of expiration\n\ncan produce chronic hypoxia and result in cog\nimp

COPD

examples include emphysema, neuromuscular\nweakness, fibrosing lung disease\n\nresults in persistent respiratory acidosis with\nreduced arterial O2 sat and elevated carbon\ndioxide\n\ncog deficits may not occur in mild cases that do\nnot produce persistent hypoxia\n\nsevere COPD often results in cog impairment,\nlower scores on objective measures compared\nto less severely affected indiv.\n\npositive pressure ventilation with O2 may\nimprove cog Fx but not necessarily better\nquality of life

medications

for attn. and memory may be used- such as:\n\nmethylphenidate (Ritalin), other stimulants\nacetylcholinesterase inhibitors (Aricept)\nand NMDA receptor antagonists (Namenda)\n\nSSRIs or anticonvulsants may be used for\nmood stabilization\n\nevidence for support of the use of these meds\nin hypoxic injury is more anecdotal than\nevidence based

capacity

for medical and legal affairs will likely be severely\nlimited early in recovery\n\ndespite recovery, may remain impaired due to EF\nand memory imp\n\nlegal issues vary across jurisdiction

even if the causal condition is addressed and\ncirculation is restored, cerebral circulation may\nnot respond effectively

for reasons that are not well understood but that\nmay involve edema preventing reflow to small\nvessels, as well as an inability to remove toxic\nmetabolites that have accumulated

expectations for NP assessment results-\n\nlanguage

formal language d/os rarely seen\n\nthough cases involving severe watershed\ndamage trans cortical aphasia or other higher\norder language syndromes may be present

For patients recently emerging from minimally\nresponsive state, out emphasis on:

frequent reorientation\nEst consistent daily routines\nuse short treatment sessions\nattend carefully to basic physiological needs\n(nutrition, toileting, sleep)\nmaintain a quiet treatment environment\navoid overstimulation

CO is a

gas that is present naturally but also results from\na combustion of man made fuel (gasoline engine\nand furnace exhaust)

high percentage of survivors of sudden cardiac\narrest and ARDS show

generalized cog impairment\n\na higher percentage show specific/focal deficits\nin memory, attn., or processing speed

expectations for NP assessment results-\n\nattention/concentration

gross confusion apparent early\n\nattn. may be a sig prob as rehab progresses and\nmay be a long term issue\n\ndistractibility is often observed both early in\nrecovery and over the long term

personality changes

have been reported in 1/3 of survivors of severe\nhypoxia

changes in memory

have been reported in more than 50% of\nsurvivors of severe hypoxia

expectations for NP assessment results-\n\nvisuospatial

if watershed zones are affected, deficits can be\nnoticeable\n\ncortical blindness and other severe visuospatial\nimp variants have occurred\n\nlower performance on these tests may in part\nreflect slowed information processing

expectations for NP assessment results- memory

impairments in storage, capacity, and retrieval\nare common\n\nin severe cases with bilateral hippocampal\ndamage, a marked amnestic state may be\nevident\n\na subset of patients have no mem imp but\nhave motor or cog imp in other domains (eg, FX\nassoc with watershed regions)

processes differ in COPD and other advanced\npulmonary illness characterized by persistent,\ngradual reduction in arterial O2 levels.

in such individuals, arterial O2 pressure may\ngradually decrease to levels that if suffered\nacutely produce rapid onset of coma or marked\ncognitive impairment\n\n(similarly, high altitude climbers may acclimate\ngradually to lower O2 sat, though not necessarily\nwithout cog or physiological effects)

watershed regions

in the brain, refers to overlapping border zones\nbtwn distal supplies of two arteries\n\nfor example, the region supplied by the distal\nbranches of the middle and anterior cerebral\narteries is a watershed region\n\nthese regions particularly vulnerable to effects\nof hypoxia/ischemia

risk factor modification

increased supervision for safety\nexternal and internal structures\nassistance with decision making (POA,\nguardianship)\nfamily support/training

homeostatic protective mechanisms are triggered when PaO2 is disrupted within these parameters:

increasing cerebral blood flow up to as much as 400%\n \nautoregulartory response to a reduction or loss of perfusion pressure can involve dilation of blood vessels to maintain flow

OSA

involves recurrent episodes of blood O2\ndesaturation due to total or partial breathing\ncessation\n\nDisrupts normal sleep architecture\n\nO2 desat may occur up to 100 times an hour\n\nneuroprotective vasodilatory response to\nhypoxia may be lacking

early neuroimaging

is variable, sometimes showing loss of\ndistinction btwn white and gray matter in the\ncortex, but also often appearing normal\n\nbasal ganglia and neocortex regions may show\ndamage on neuroimaging soon after onset\n\nhippocampal damage may not be evident on\nneuroimaging for days or weeks\n\ndiffuse atrophy may appear chronically but is\nnot expected acutely\n\nwhite matter tracts are generally preserved in\nhypoxia/ischemia but are vulnerable to carbon\nmonoxide poisoning

neuroimaging also shows time dependent\nvulnerability to damage in specific regions

lesions often evolve over weeks or months

expectations for NP assessment results-\n\nEF

may be minimally affected in milder cases, with\nthe exception of executive aspects of attn.\n\nEF deficits common and disabling in severe cases\n\nsome patients sustain orbitofrontal damage bc\nthis is a watershed region

mild hypoxia that does not lead to LOC (like high\naltitude climbing)

may induce mild cognitive and motor impairment\nnot expected to have lasting effects, though\nsome studies suggest a possible persistence of\nmild changes

rapid resuscitation efforts

may prevent escalation to permanent damage

older adults

more vulnerable to sleep disordered breathing\n\ncommunity dwelling elderly women with sleep\ndisordered breathing show increased risk of\ncognitive impairment

glutamate

most common excitatory neurotransmitter in the\nbrain\n\nunder hypoxic conditions, excessive amounts are\nreleased in the synaptic cleft, and it becomes\nexcitotoxic, contributing to deleterious processes\nin the neuron

hypoxia/ischemia triggers a cascade of neuronal\ncell processes that are multifaceted, time dependent, and neurotoxic

most energy required from neurons is derived\nfrom hydrolysis of adenosine triphosphate\n(ATP)\n\nthe brain has no inherent energy stores (in\ncontrast to other tissue) and thus is critically\ndependent on uninterrupted flow of O2 and\nglucose\n\na sudden loss of cerebral perfusion or\nanoxia/hypoxia causes a critical shortage of the\nO2 and glucose supply to neurons, and if not\nrapidly reversed, initiates processes that result\nin neuronal death

brain regions that show high vulnerability to\nhypoxia/ischemia

neocortex (layers 3,5,6)\nhippocampus (pyramidal cells in CA1)\nBasal ganglia (striatum, globus pallidus)\ncerebellar regions (Purkinje cells)\nvisual cortex\nthalamus

poor outcome

no pupillary response 3 days post injury (68%\nprevalence)\nGCS motor score of 1-2 on day 3 (73%)\nAlpha coma EEG pattern (66%)\nconvulsions or myoclonus (74%)\ntotal GCS score of 3-5 in first 24 hours (77%)\nbilateral absence of somatosensory evoked\npotential on median nerve stimulation (76%)

incidence

not clear, milder cases often unrecognized in a\nhospital setting

LOC

occurs very rapidly. when the brain is deprived of\nO2 for several minutes, damage progresses\nrapidly and if the underlying cause is not quickly\nreversed, brain death or a persistent minimally\nresponsive state may result

less than 50%

of those who require rehabilitation regain full\nindependence of daily FX, but there is much\nvariability in outcome

expectations for NP assessment results-\n\nprocessing speed

often impaired, cognitively and motorically

geriatric considerations

older brains less able to recover from an anoxic\ninjury and will likely suffer more permanent and\nsevere cog deficits due to reduced reserve\n\nfor many, there are pre-existing MCI and Fx\nimpairment or will have age related impairments

expectations for NP assessment results-\n\nIQ/achievement

overall scores may be reduced due to\nimpairments in processing speed and efficiency

driving

prognosis for returning to driving is not good in\nsevere cases, but may be possible with mild to\nmoderate injuries with good recovery

apoptosis

programmed cell death\n\npart of normal regulation and turnover of cells,\nbut also can result from pathological processes\nlike ischemia

recovery course

quite variable

prevalence of cog imp following cardiac arrest

range widely, from 6-100%

CPAP for OSA

reduces episodes of breathing dysfunction\n\nreduced O2 desat during sleep\n\nimproves daytime sleepiness\n\nmay lead to improvement is select areas of\ncognition presentation, disease course, and\nrecovery

necrosis

refers to death of tissue or neurons, typically due\nto inefficient blood supply

partial pressure of arterial oxygen (PaO2)

refers to pressure exerted independently by a\nspecific gas within a larger mix of gases\n\nin healthy adults at sea level is typically 95-100\nmm Hg\n\nwhen this level rapidly drops, complex\ncognitive processes such as memory and\njudgment become impaired

most severe cases

result from sudden cardiac arrest or acute\nrespiratory distress syndrome (ARDS)

anoxic/hypoxic damage

results secondary to conditions that affect the\ncardiac or respiratory system\n\ncan result from reduced concentration of O2 in\nthe blood or from deficit perfusion of blood to\nthe brain\n\ndefined as lack of or insufficient supply of O2\ncirculating to tissue in the presence of\nadequate blood flow

work

return to work is unlikely in severe cases, but\nmay be possible with mild injury and good\nrecovery\n\nfor those unable to return to competitive\nemployment, alternative vocational or volunteer\nplacement may be appropriate

functional issues

severe injuries often result in dystonia, spastic\nhemiparesis, or quadraparesis due to basal\nganglia involvement\n\nataxia may persist due to cerebellar\ninvolvement\n\nmany of these patients are unemployable and\nrequire attendant care for the rest of their lives

acute respiratory distress syndrome (ARDS)

severe, often life threatening medical condition\nwhere the lungs are compromised and damaged\nand are unlikely to supply sufficient O2 to the\narterial blood (eg hypoxemia)\n\ncan result in hypoxic damage to brain as well as\nmany other systemic px

favorable recovery

short period of impaired consciousness\n\nregain purposeful motor movements\n\npreserved memory within a few hours following\nresuscitation

a series of secondary toxic processes is also\ntriggered

sodium and calcium pumps fail, resulting in\ndepolarization of the neuronal membrane and\nrelease of excessive levels of glutamate\n\nglutamate is the most common excitatory\nneurotransmitter, but at excessive levels it\nbecomes excitotoxic to neurons\n\na further series of toxic events are triggered\nthat involve lactic acidosis from anaerobic\nmetabolism, cytotoxic edema, free cell radical\nproduction, and others\n\nnecrosis and apoptosis become factors as the\npathology evolves

ischemic-hypoxic encephelopathy

terms used together for the purposes of the\nchapter b/c in most cases where the brain\nsustains marked disruption of O2 supply, both\nprocesses become involved

expectations for NP assessment results-\n\nsensorimotor

the basal ganglia and cerebellum are high risk for\ninjury\n\nsevere anoxic injury can cause spastic\nquadiparesis, ataxia, parkinsonian syndromes,\nand other motor impairments/dysfunction

beyond a certain point, protective measures are\ninsufficient to prevent certain CNS injury

the brain depletes energy sources within several\nminutes of onset of complete ischemia, although\nconditions like hypothermia can extend that\nperiod

outcomes

the most catastrophic cases may result in brain\ndeath or persistent minimally responsive states\n\nless severe cases show variable periods of coma,\nmarked confusion in early recovery, and lasting\nsignificant cog impairment or dementia

those who emerge from prolonged coma

typically have lasting cognitive and functional\ndisability (varying degree of dementia) and may\nshow extrapyramidal syndromes like\nParkinsonianism

school/vocational training

unlikely, but may be possible with mild injury and\ngood recovery\n\nfor students in high school and younger, it is\ncritical to involve the school and educ specialists\nas early as possible to plan for academic re-entry\n(important for recovery and legally mandated)