Chapter 17: Alterations in Cognitive Systems, Cerebral Hemodynamics, and Motor Function PDF

CHAPTER 17-Alterations in Cognitive Systems, Cerebral Hemodynamics, and Motor Function Know the best prognostic indicator of recovery of consciousness and functional outcome after a brain event. Outcomes depend on the cause (etiology) and extent of brain damage...

CHAPTER 17-Alterations in Cognitive Systems, Cerebral Hemodynamics, and Motor Function Know the best prognostic indicator of recovery of consciousness and functional outcome after a brain event. Outcomes depend on the cause (etiology) and extent of brain damage and duration of coma (time since onset). The Glasgow Coma Scale (GCS) is used to assess severity of brain injury. The hallmark of a severe TBI is LOC for 6 hours of more. Age and admission GCS score are important diagnostic factors in TBI. TBI classification using the GCS are: o Mild TBI with GCS score of 13 to 15 (associated with mild concussion) o Moderate TBI with GCS score of 9 to 12 (associated with structural injury such as hemorrhage or contusion) o Severe TBI with GCS score of 3 to 8 (associated with cognitive and/or physical disability or death. The Glasgow Coma Score (GCS) is scored between 3 and 15, with 3 being the worst and 15 the best. It is composed of the sum of three parameters: o Best Eye Response, Best Verbal Response, and Best Motor Response GLASSGOW COMA SCORE (GCS) SCORE BEST EYE RESPONSE (4) BEST VERBAL BEST MOTOR REPONSE RESPONSE (5) (6) 1 No eye opening No verbal response No motor response 2 Eye opening to pain Incomprehensible sounds Extension to pain 3 Eye opening to verbal command Inappropriate words Flexion to pain 4 Eyes open spontaneously Confused Withdrawing from pain 5 ---- Oriented Localizing pain 6 ---- Obeys command Know the most critical index of nervous system dysfunction/function. Level of consciousness is the most critical clinical index of nervous system function or dysfunction. Changes can indicate either improvement or deterioration of the individual’s condition and state of awareness. A person who is alert and oriented to self, others, place, and time → functioning at the highest level of consciousness (implies full use of all the person’s cognitive capacities) From this normal alert state, LOCs diminish in stages from confusion to coma Levels of Altered Consciousness:  State Definition Confusion Loss of ability to think rapidly and clearly; impaired judgment and decision making; difficulty following instructions Disorientation Beginning loss of consciousness; disorientation to time followed by disorientation to place and impaired memory; lost last is recognition of self Lethargy Limited spontaneous movement or speech; easy arousal with normal speech or touch; may not be oriented to time, place, or person Obtundation Mild to moderate reduction in arousal (awakeness) with limited response to the environment; falls asleep unless stimulated verbally or tactilely; answers questions with minimum response Stupor A condition of deep sleep or unresponsiveness from which the person may be aroused or caused to open eyes only by vigorous and repeated stimulation; response is often withdrawal or grabbing at stimulus Light coma Associated with purposeful movement on stimulation Coma No verbal response to the external environment or to any stimuli; noxious stimuli such as deep pain or suctioning yields motor movement Deep coma Associated with unresponsiveness or no response to any stimulus Know patterns of breathing with head injuries. Breathing Pattern Description Location of Injury Hemispheric Breathing Patterns Normal After a period of hyperventilation that lowers the Response of the nervous system to an arterial carbon dioxide pressure (PaCO2), the external stressor—not associated with injury individual continues to breathe regularly but with a to the central nervous system (CNS) reduced depth. Posthyperventilation Respirations stop after hyperventilation has lowered Associated with diffuse bilateral metabolic apnea (PHVA) the PaCO2 level below normal. Rhythmic breathing or structural disease of the cerebrum returns when the PaCO2 level returns to normal. (Usually, an intact cerebral cortex will trigger breathing within 10 s regardless of PaCO2.) Cheyne-Stokes Breathing pattern has a smooth increase (crescendo) Bilateral dysfunction of the deep cerebral or respirations in the rate and depth of breathing (hyperpnea), which diencephalic structures; seen with peaks and is followed by a gradual smooth decrease supratentorial injury and metabolically (decrescendo) in the rate and depth of breathing to induced coma states unrelated to neurologic the point of apnea when the cycle repeats itself. The dysfunction; may see also in congestive hyperpneic phase lasts longer than the apneic phase heart failure (CHF) (represents an amplitude change). Brainstem Breathing Patterns Central reflex Deep rapid, regular pattern (hyperpnea) occurs, May result from CNS damage or disease that hyperpnea (central with a decreased PaCO2 and a corresponding involves the lower midbrain and upper neurogenic increase in pH and increased PO2. pons; seen after increased intracranial hyperventilation) pressure and blunt head trauma Apneusis A prolonged inspiratory cramp (a pause at full Indicates damage to the respiratory control inspiration) occurs. A common variant of this is a mechanism located at the pontine level; brief end-inspiratory pause of 2 or 3 s, often most commonly associated with pontine alternating with an end-expiratory pause. infarction but documented with hypoglycemia, anoxia, and meningitis Cluster (Biot) A cluster of breaths has a disordered sequence with Dysfunction in the lower pontine and high breathing irregular pauses between breaths. medullary areas Ataxic breathing Completely irregular breathing occurs, with random Originates from a primary dysfunction of the shallow and deep breaths and irregular pauses. Often medulla the rate is slow. Gasping breathing A pattern of deep “all-or-none” breaths is Indicative of a failing medullary respiratory pattern (agonal gasps) accompanied by a slow respiratory rate. center Know vomiting with which CNS injuries.  Vomiting, yawning, and hiccups are complex reflex motor responses that are integrated by neural mechanisms in the lower brainstem. Most CNS disorders produce nausea and vomiting. These responses may be produced by: o Compression or diseases involving tissues of the medulla oblongata (e.g., infection, neoplasm, infarct, or other more benign stimuli to the vagal nerve). o Direct involvement of the central neural mechanism (e.g., pyloric obstruction) – usually vomiting occurs without nausea. o Injuries that involve the vestibular nuclei or its immediate projections, particularly when double vision is present (diplopia). o Injuries that impinge directly on the floor of the fourth ventricle. o Injuries that produce brainstem compression secondary to increased ICP. Know diagnostic criteria for vegetative state and brain death. Brain death (or total brain death): occurs when irreversible brain damage is so extensive that the brain has no potential for recovery and no longer can maintain the body’s internal homeostasis. State laws define brain death as irreversible cessation of function of the entire brain, including the brainstem and cerebellum. This is to be distinguished from cerebral brain death, which is the death of the cerebral hemispheres exclusive of the brainstem and cerebellum. Clinical criteria for brain death: o Completion of all appropriate and therapeutic procedures with no possibility of brain function recovery. o Unresponsive coma (absence of motor and reflex movements). o No spontaneous respiration (apnea) – a PaCO2 that rises above 60mmhg without breathing efforts, providing evidence of a nonfunctioning respiratory center (apnea challenge). o No brainstem function (ocular responses to head turning or caloric stimulation; dilated fixed pupils; no gag or corneal reflex). o Isoelectric (flat) EEG (electrocerebral silence) for 6-12 hours for patients who are not hypothermic and have not ingested depressant drugs o Persistence of these signs for an appropriate observation period Persistent vegetative state (PVS): complete unawareness of the self or surrounding environment and complete loss of cognitive function (unresponsive wakefulness syndrome) Diagnostic criteria for PVS: o Periods of eye opening (spontaneous or following stimulation). o Potential for subcortical responses to external stimuli, including generalized physiologic responses to pain, such as posturing, tachycardia, diaphoresis, and subcortical motor responses, such as grasp reflex. o Return of vegetative autonomic functions, including sleep-wake cycles and normalization of respiratory and digestive system functions. o Occasional roving eye movements without concomitant visual tracking ability. o There may possibly be random hand, extremity, or head movements. The individual can maintain BP and breathing without support. Brainstem reflexes are intact, but cerebral functions are lost. o No discrete localizing motor responses are present, and the individual does not speak any comprehensive words or follow commands.  o Recovery unlikely if persist longer than 12 months Clinical manifestations and presenting signs of Creutzfeldt-Jacob Creutzfeldt-Jakob disease is a progressive, fatal, dementing neurologic illness caused by an infectious protein known as a prion. Prior = composed of misfolded proteins unable to self-replicate → spongiform encephalopathy within grey matter Rare; 1 in 1.5 million annually; 10% of cases are genetic (most cases are sporadic) o Molecular mechanism: PrPsc proteins type 1 and 2 o Causal Genes (Chromosome): Prior (20); up to 15% of cases carry these dominant mutations o Susceptibility Genes: PRNP codon 129 homozygosity for methionine or valine Diagnosis: clinical evaluation, MRI, electroencephalography; CSF fluid shows (14-3-3 protein or human prior protein PrPsc and it is also detected in olfactory epithelium, blood, and/or urine samples) Clinical manifestations: Progressive dementia and at least 2 of the following 4 features: o myoclonus, visual or cerebellar disturbance, pyramidal or extrapyramidal signs, and akinetic mutism Prognosis: fatal – average lifespan of 8 months Treatment: no treatment exists Clinical manifestations and presenting signs of brain abscess Abscesses are localized collections of pus within the parenchyma of the brain or spinal cord and are rare. Immunosuppressed persons are particularly at risk. Brain abscesses are classified as extradural, subdural, or intracerebral. o Extradural brain abscesses (empyemas) are associated with osteomyelitis in a cranial bone. o Subdural brain abscesses (empyemas) arise from a sinus infection or a vascular source. o Intracerebral brain abscesses arise from a vascular source. Progression: localized inflammation to a necrotic core with the formation of a connective tissue capsule, usually within 14 days or longer. Brain abscesses evolve through four stages regardless of infecting microorganism, except in the immunosuppressed host where the process may be incomplete. Stages: 1. Early cerebritis (days 1 to 3): localized inflammatory process develops in which perivascular infiltration and inflammatory cells, composed of neutrophils, plasma cells, and mononuclear cells, surround a central core of coagulative necrosis marked cerebral edema surrounds the area 2. Late cerebritis (days 4 to 9): The necrotic center is surrounded by an inflammatory infiltrate of macrophages and fibroblasts Rapid new blood vessels form around the abscess; a thin capsule of fibroblasts and reticular fibers gradually develops; the area is still surrounded by cerebral edema. 3. Early capsule formation (days 10 to 13): The necrotic center decreases in size  the inflammatory infiltrate changes in character and contains an increasing number of fibroblasts and macrophages mature collagen evolves, forming a capsule 4. Late capsule formation (days 14 and longer): A well-formed necrotic center surrounded by a dense collagenous capsule develops. The development of symptoms may be very insidious, often making an abscess difficult to diagnose: o Early manifestations: ▪ low-grade fever ▪ headache (most common symptom) ▪ nausea and vomiting ▪ neck pain and stiffness ▪ confusion ▪ drowsiness ▪ sensory deficits ▪ communication deficits o Later manifestations (associated with an expanding mass): ▪ decreased attention span ▪ memory deficits ▪ decreased visual acuity and narrowed visual fields ▪ papilledema ▪ ocular palsy ▪ ataxia ▪ cognitive deficits ▪ seizures Extradural brain abscesses are associated with localized pain, purulent drainage from the nasal passages or auditory canal, fever, localized tenderness, and neck stiffness; occasionally the individual experiences a focal seizure. Evaluation: suggested based on clinical features and confirmed with MRI or contrast-enhanced CT Treatment: o Stereotactic surgical aspiration → identification of the pathogen and for decompression of the abscess. o Antibiotics are initiated → clinical suspicion of an abscess. o Multiple or surgically inaccessible abscesses are treated with antibiotics (+ corticosteroid therapy to treat the cerebral edema) o In addition, ICP or hydrocephalus, or both, require management. Characteristics of Alzheimer’s disease. Leading cause of severe cognitive dysfunction in older adults (most common in women) GREATEST RISK FACTORS are age and family history  PROTECTIVE FACTORS are lifelong activity, the presence of apoE2 and antioxidant substances, omega-3 fatty acids, estrogen replacement at the time of surgical menopause, low-calorie diet, and use of nonsteroidal anti-inflammatory agents Characterized by 3 forms: Nonhereditary sporadic or late onset Alzheimer’s Disease (70-90%): a. Most prevalent, does not have a specific genetic association but cellular pathology is the same as gene associated early and late onset Alzheimer’s Disease. b. Pathologic alterations in the brain: i. Accumulation of extracellular neuritic plaques with a core of abnormally folded amyloid beta and tau proteins ii. Intraneuronal neurofibrillary tangles **neurotic plaques and neurofibrillary tangles are more concentrated in the cerebral cortex and hippocampus** iii. Degeneration of basal forebrain cholinergic neurons with loss of acetylcholine, synapses, and other neurotransmitters contributes to decline in memory, attention and loss of other cognitive functions. c. Failure to process and clear amyloid precursor protein results in the accumulation of amyloid beta protein toxic fragments that leads to formation of diffuse neuritic plaques disruption of nerve impulse transmission death of neurons-result is brain atrophy with decreases in weight and volume d. Aging and injury can cause changes that contribute to the development and progression of Alzheimer’s Disease. Early-onset Familial Alzheimer’s Disease (FAD): a. Autosomal dominant; linked to 3 genes with mutations on chromosome 21 b. Gene-associated late onset- major genetic risk is related to apolipoprotein E gene-allele 4 (apoE4) on chromosome 19 (apoE4 interferes with amyloid beta clearance from the brain and is processed into neurotoxic fragments found in the plaques and tangles in the brain of people with AD) Early-onset Alzheimer’s Disease: a. very rare; genetic susceptibility tests for PSEN1, PSEN2, and APP are used for screening Clinical Manifestations: o Alzheimer’s Disease has a long preclinical and prodromal course. o Progresses from mild short-term memory deficits to total loss of cognition and executive functions Evaluation: diagnosis is made by ruling out other causes. Definitive diagnosis can only be made by autopsy. o Clinical history (including mental status exams, clock drawing, and geriatric depression scale), CSF analysis, brain imaging of structure, blood flow and metabolism; and the course of the illness is used to assess progression of Alzheimer’s Disease o Genetic susceptibility tests for PSEN1, PSEN2, and APP are used to screen for early-onset Alzheimer’s Disease Treatment: o No disease modifying therapies o Treatment is directed at using devices to compensate for the impaired cognitive function ▪ memory aids, maintaining unimpaired cognitive functions; and maintaining or improving the general state of hygiene, nutrition, and health o Cholinesterase inhibitors (used in mild-moderate cases of Alzheimer’s Disease) o NMDA receptor antagonist blocks glutamate activity and may slow the progression of disease in moderate-severe Alzheimer’s Disease o Anti-myeloid drugs are in clinical trials Define seizure and status epilepticus. What is the medical significance? Know benign febrile seizures. SEIZURE STATUS EPILEPTICUS  Defined as a sudden, transient alteration of brain In adults, it is a state of continuous seizures lasting function caused by an abrupt explosive disorderly more than 5 minutes OR discharge of cerebral neurons Rapidly recurring seizures before the person has fully Sudden, explosive, disorderly discharge of brain cells regained consciousness from the preceding seizure Types of Seizures see attachment OR S/S: LOC, apnea, hypoxia, acidosis, and lactate A single seizure lasting more than 30 minutes. accumulation with resulting brain tissue injury and Cause: often results from abrupt discontinuation of destruction (overall medical concerns for seizures) antiseizure medications but also may occur in untreated or inadequately treated persons with seizure disorders. **medical emergency d/t resulting cerebral hypoxia, **important to provide oxygen ** aspiration, intellectual disability, dementia, & death Long-term Complications: neuronal death, neuronal injury, and alteration of neuronal networks. Patho: a group of neurons may exhibit a paroxysmal depolarization shift and function as an epileptogenic focus These neurons are hyperexcitable (more easily activated by hyperthermia, hypoxia, hypoglycemia, hyponatremia, repeated sensory stimulation, and certain sleep phases) Epileptogenic neurons fire more frequently and with greater amplitude When the intensity reaches a threshold point, cortical excitation spreads → excitation of the subcortical, thalamic, and brainstem areas: Tonic phase (muscle contraction with increased muscle tone) = loss of consciousness When inhibitory neurons in the cortex, anterior thalamus, and basal ganglia react to the cortical excitation → seizure discharge is interrupted: Clonic phase (alternating contraction and relaxation of muscles) = intermittent; gradually decrease and finally cease → epileptogenic neurons are exhausted During seizure activity – cerebral blood flow increases, oxygen consumption (60% greater than normal) → rapidly depleting O2 and glucose → lactate accumulates in brain tissue → (severe seizure continues) progressive brain injury and irreversible damage **If seizure focus in the brain is active for a prolonged period → a mirror focus may develop in contralateral normal tissue → seizure activity (particularly with focal epilepsy - i.e., temporal or frontal lobe) Etiology: a seizure disorder is a manifestation of disease, NOT a specific disease. Onset of seizures may point to the present of: An ongoing primary neurological disease (including cerebral lesions, biochemical disorders, cerebral trauma, and epilepsy) OR Conditions such as metabolic defects, congenital malformations, genetic predisposition, perinatal injury, postnatal trauma, myoclonic syndromes, infection, brain tumor, and vascular disease OR  Hypoglycemia, fatigue, emotional or physical stress, fever, hyponatremia, constipation, blinking lights, use of stimulant drugs, loud noises, certain odors, and withdrawal from drugs/alcohol. Phases of seizures: Two types of symptoms signal the preictal phase of a generalized tonic-clonic seizure: Prodroma: early manifestations occurring hours to days before a seizure (may include anxiety, depression, or inability to think clearly Focal seizure or aura that immediately precedes the onset of a generalized tonic-clonic seizure. Both may become familiar to the person and may enable the person to prevent injuries during the seizure. The ictus is the episode of the epileptic seizure with tonic-clonic activity. Airway maintenance needs to be ensured. The postictal state follows an epileptic seizure and can include signs of headache, confusion, aphasia, memory loss, paralysis and deep sleep that may last hours or a day or two. Diagnosis of seizures: Health history (most critical aspect of diagnosis, establishing the cause and onset) Supplemented with physical exam, lab tests of blood and urine (glucose, serum Ca+, BUN, urine Na+, creatinine clearance) – identify any systemic diseases CT/MRI scans and CSF serology – identify any neurologic diseases EEG – identify the type of seizure and determine its focus MRI + EEF – identify neural networks involved in epileptic activity Treatment of seizures: Correct or control cause (#1) – if not possible… Anti-seizure medications (goal: complete suppression of seizure activity without intolerable side effects or drug resistance) Dietary treatments → Ketogenic diet or modified Atkins diet (60 cause the juvenile form of the disease. o Fathers, but not mothers, with high normal alleles do not develop Huntington disease but are at risk for transmitting potentially penetrant HB alleles (> or = 36) to their offspring, who can develop Huntington disease. o The genetic defect of Huntington disease is on the short arm of chromosome 4. o There is an abnormally long polyglutamine tract in the huntingtin (htt) protein that is toxic to neurons and is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion (40 to 70 repeats instead of 9 to 34) → produces tangles of protein that collect in brain cells and chains of glutamine on the abnormal molecules that adhere to each other (exact mechanism of neuronal death is unknown) Clinical Manifestations (SLOW PROGRESSION): o Excess of dopaminergic activity = hypotonia and hyperkinesia. o Loss of excitatory glutamate = impaired modulation of movement later during the disease. o Build-up of lactic acid = difficulty producing energy for the brain. o S/S: involuntary fragmentary movements (occur without conscious effort), emotional lability, and progressive dysfunction of cognitive processes (dementia) that may precede motor symptoms. ▪ Chorea is the most common type of abnormal movement ▪ Begins in the face and arms, eventually affecting the entire body ▪ Chorea can be combined with athetosis (twisting and writhing) and ballism (flailing of limbs) ▪ Cognitive deficits → loss of working memory and reduced capacity to plan, organize, and sequence. Thinking is slow, and apathy is present. Restlessness, disinhibition, and irritability are common. Euphoria or depression may be present.  Prognosis: FATAL Define dyskinesia. Types? Characteristics? Dyskinesias: unnatural movements or abnormal involuntary movements (and are included in the general category of hyperkinesia, which are excessive movements.) o Paroxysmal dyskinesia: abnormal, involuntary movements that occur as spasms. o Tardive (slow onset) dyskinesia: involuntary movement of face, trunk, and extremities due to ▪ Parkinson disease ▪ Prolonged antipsychotic drug usage d/t increase of dopamine ▪ S/S: rapid, repetitive, stereotypic movements (e.g., continual chewing with intermittent protrusions of the tongue, lip smacking, etc.) o Hypokinesia: decreased amplitude of movement. o Bradykinesia: decreased speed of movement o Akinesia: absence of voluntary movements. Parkinson’s disease is the hallmark of lack of movement Huntington’s disease is the hallmark of excess movement. (i.e. tick-like jerky movements, smacking lips, or flicking the tongue, unsteady gait, rocking back and forth.) What is responsible for the tremors associated with Parkinsons Disease? Cause: result from instability of feedback from the basal ganglia to the cerebral cortex, caused by loss of the inhibitory influence of dopamine in the basal ganglia Tremors are the result of atrophy of the neurons in the Substantia nigra which produces dopamine Increased oscillation in the normal feedback cycles of the motor outflow feedback circuit when the muscles are at rest produces the tremor. When the individual performs voluntary movements, the tremor becomes temporarily block, presumably because other motor control signals arriving the thalamus override the abnormal basal ganglia signals. Primary Patho: o Degeneration of the basal ganglia with formation of Lewy bodies in the substantia nigra and dorsal striatum o → depletion of dopamine (inhibitory neurotransmitter) and relative excess of cholinergic (excitatory) activity in the feedback circuit are manifested by hypertonia (tremor and rigidity) and akinesia o → syndrome of abnormal movement called parkinsonism Hallmark pathologic features: o Loss of dopaminergic pigmented neurons in the substantia nigra pars compacta with dopaminergic deficiency in the putamen portion of the striatum. o Degeneration of the dopaminergic nigrostriatal pathway to the basal ganglia results in underactivity of the direct motor pathway (normally facilitates movement) and overactivity of the indirect motor loop (normally inhibits movement). Symptoms appear after 70-80% loss of pigmented nigral neurons and 60-70% loss of striated dopamine. Overall, a loss or decrease in DOPAMINE is responsible Define and describe the pathophysiology, clinical manifestations and etiology of Parkinson’s disease. Definition: complex motor disorder accompanied by systemic nonmotor and neurologic symptoms. Pathophysiology:  o Degeneration of the basal ganglia (corpus striatum, globus pallidus, subthalamic nucleus, and substantia nigra) involving the dopaminergic nigrostriatal pathway ▪ Common autonomic symptoms in Parkinson disease include: inappropriate diaphoresis, gastric retention, constipation, and urinary retention. o Pathogenesis of primary Parkinson’s disease is unknown, though several Parkinson’s disease genes have been identified. Hallmark features of Parkinson’s disease are: o loss of dopaminergic pigmented neurons in the substantia nigra (SN) pars compacta with dopamine deficiency in the putamen portion of the striatum o Dopamine loss occurs in the brainstem, thalamus, and cortex o Depletion of dopaminergic nigrostriatal pathway to basal ganglia → underactivity or direct motor pathway (normally facilitates movement) and overactivity of indirect motor loop normally inhibits movement → inhibition of motor cortex, with s/s of bradykinesia and rigidity. o Subthalamic nucleus overactivity influences limbic system, which leads to emotional symptoms. Etiology classification of parkinsonism: o Primary parkinsonism and secondary parkinsonism o There are molecular events associated with neurodegeneration of parkinson’s disease. Clinical manifestations: o Parkinsonian tremor is usually the first symptom to appear. More common in the upper extremities versus the lower extremities and increases with anxiety or stress. o Resting tremor o Bradykinesia o Akinesia (poverty of movement) o Muscular stiffness/rigidity o Postural abnormalities o Fragmented sleep, hyposomnia o Fatigue o Depression o Pain o Autonomic dysfunction o Dementia with or without psychosis Time of onset: o Primary Parkinson’s disease: after 40 years of age with mean onset of 60 years of age o Men are more likely to have PD than women. o Secondary PD is neurodegenerative disease + another acquired disorder o Familial PD is 10%, with majority either sporadic or idiopathic. Treatment: drug therapy to treat and restore dopamine levels and decrease akinesia and manage nonmotor symptoms (drug therapy may not begin until incapacitant.) o ave a characteristic phenotype that includes blond hair, blue eyes, and fair skin.