NU 545 Unit 2 Study Guide

Know coupe and countercoup brain injuries and how they happen CH 18 pg 552. Figure 18.3 pg 553

Focal brain injury can be caused by closed blunt trauma or open penetrating trauma. Closed injury is more common and involves the head striking a hard surface, a rapidly moving object striking the head, or blast waves. The dura matter remains intact, and brain tissues are not exposed to the environment. • May be a coup injury (Injury at site of impact) (ex: head striking a wall causes direct trauma to site, shearing of subdural veins, and trauma to base of brain). • or countercoup (Injury from the brain rebounding and hitting the opposite side of the skull) or both. (ex: after the head strikes the wall, the rebound from impact causes site of impact of brain hitting opposite side of skull and shearing forces through brain. Another example of countercoup is shaken baby syndrome Objects striking FRONT of head usually produce only coup injuries (contusions and fractures), whereas objects striking the BACK of head usually result in coup and contrecoup b/c of irregularity of inner surface of the frontal bones; SIDE impact can result in either. The severity of contusion varies with the amount of energy transmitted by the skull to underlying brain tissue. The smaller the area of impact, the more sever the injury because of the concentration of force. Brain edema forms around and in damage neural tissues, contributing to increased intracranial pressure (ICP).

Define and describe the pathophysiology, clinical manifestations and etiology of Multiple Sclerosis. CH 18 pg 581

MS is a chronic inflammatory disease involving degeneration of CNS myelin, scarring or formation of plaque, and loss of axons. MS is caused by an autoimmune response to self-antigens in genetically suceptible individuals. The onset is usually between 20 and 40 years of age with a peak of age 30. MS is the most prevalent CNS demyelinating disorder and a leading cause of neurologic disability in early adulthood. The etiology is unknown. Genetic and environmental factors and interactions are implicated in disease onset. A genetic link exists in the human leukocyte antigen (HLA) complex. Vitamin D deficiency, cigarette smoking, and Epstein-Barr virus infection are environmental risk factors. The first demyelinating event, or "clinically isolated syndrome (CIS), is a single episode of neurologic dysfunction lasting greater than 24 hours that can be a prelude to MS. Characteristic episodes include optic neuritis, solitary brainstem lesions, and transverse myelitis. Pathophysiology: MS is a diffuse and progressive CNS disease that affects white and gray matter. Autoreactive T and B cells recognize myelin autoantigens and trigger inflammation in the CNS, leading to the loss of myelin sheaths and nerve conductivity and subsequently to the death of neurons. MS is described as occurring when a previous infectious insult to the nervous system has occurred in a genetically susceptible individual with a subsequent abnormal CNS immune response. Various mechanisms cause irreversible tissue damage (inflammation, oligodendrocyte injury, demyelination, scarring or plaque formation, and axonal degeneration) that characterizes MS. These degenerative processes begin early in the course of the disease and continue to progress throughout a person's life. Demyelinated axons are more fragile and susceptible to further damage and, when degeneration exceeds self-repair ability (remyelination), permanent disability results. Myelin destruction and axonal damage begin before symptom onset (early inflammatory demyelination). The innate and adaptive immune systems are activated in the pathology of MS. The immunopathology of MS involves the following events: Immunopathology: 1. Activation of CD4+ and CD8+ T cells; cells cross the blood-brain barrier and enter the CNS and attack myelin 2. Production of interlukin (IL-12) and IL-23 (pro-inflammatory cytokines) 3. Lack of IL-10 (an anti-inflammatory cytokine) 4. Production of IL-17 (pro-inflammatory cytokine) by Th17 cells 5. Expression of Integrins expressed to facilitate adherence and passage of immune cells into the CNS. 6. Promotion of Chemokine migration of immune cells and are up-regulated in MS 7. Contribution of B lymphocytes and plasma cells to the inflammatory response and direct damage myelin and axons, B cells are more active in chronic or progressive forms of MS ( B cells produce autoantibodies, secrete inflammatory cytokines, and activate T cells by presenting antigen) 8. Activation of complement (promotes inflammation) during the acute phase, may be neuroprotective during relapse 9. Presence of cells of inflammation including eosinophils, neutrophil, and macrophages Clinical Manifestations: Infection, trauma, or pregnancy could all be precipitating events before the onset or exacerbation of symptoms. Most pregnancy related exacerbations occur 3 months postpartum, suggesting a relation to the stresses of labor and the increased fatigue during the postpartum period, rather than the pregnancy itself. The major classifications of MS are relapsing-remitting, primary progressive, secondary progressive, and progressive-relapsing. There are 4 established syndromes: mixed, spinal, amaurotic, and cerebellar. • Mixed (general) type (50% of persons) ⇒ Optic signs are optic neuritis. Brain stem signs are internuclear ophthalmoplegia, diplopia, vertigo, vomiting, nystagmus, dysarthria. Cerebellar signs are usually involved with all four limbs and has a spastic/ataxic gait and ataxia of the arms. • Spinal type (30-40% of persons) ⇒ Spastic ataxia, deep sensory changes in the extremities, bladder and bowel symptoms. • Cerebellar or Pontobulbar - Cerebral Type (5% of persons) ⇒ Motor ataxia, hypotonia, asthenia. • Amaurotic forms (5% of persons) ⇒ Blindess Treatment: Main treatment goal is to prevent permanent neurological damage and treat the symptoms. Symptoms management for fatigue, weakness, vertigo, ataxia, tremor, heat intolerance, spasticity, bladder dysfunction, bowel dysfunction, sexual dysfunction, sensory sensations, pain, cognitive difficulties, depression, and psychosocial issues is essential.

Know the stages of intracranial hypertension. CH 17 pg 529

Stage 1: Cerebral blood volume is altered which causes intracranial hypertension. Vasoconstriction and external compression of the venous system occur in an attempt to further decrease the intracranial pressure. Thus in the first stage, the ICP may not change due to effective compensatory mechanisms {CSF is reduced through increased reabsorption. Blood volume is reduced by compression of intracranial veins.} and there may be few symptoms. Small increases in volume, however, cause an increase in pressure, and the pressure may take longer to return to baseline. Can be detected with ICP monitoring. Stage 2: There is continued expansion of intracranial content; the resulting increase in ICP may exceed the brain's compensatory capacity to adjust. Pressure begins to compromise neuronal oxygenation, and systemic arterial vasoconstriction occurs in an attempt to elevate the systemic blood pressure sufficiently to overcome the IICP. Clinical manifestations at this stage are usually subtle and transient, including episodes of confusion, restlessness, drowsiness, and slight pupillary and breathing changes. Stage 3: The ICP begins to approach arterial pressure, the brain tissues begin to experience hypoxia and hypercapnia, and the individuals condition rapidly deteriorates. Clinical manifestations include decreasing levels of arousal or central neurogenic hyperventilation, widened pulse pressure, bradycardia, and pupils that become small and sluggish. Stage 4: Brain tissue shifts (herniates) from the compartment of greater pressure to a compartment of lesser pressure and ICP in one compartment of the cranial vault is not evenly distributed throughout the other vault compartments. With this shift in brain tissue, the herniating brain tissue's blood supply is compromised, causing further ischemia and hypoxia in the herniating tissues. The volume of content within the lower pressure compartment increases, exerting pressure on the brain tissue that normally occupies that compartment, and impairing its blood supply. Small hemorrhages often develop in the involved brain tissue. Obstructive hydrocephalus may develop. The herniation process markedly and rapidly increases intracranial pressure. Mean systolic arterial pressure soon equals ICP and cerebral blood flow ceases at this point.

Know the function of the arachnoid villi. CH 15 pg 451

CSF is reabsorbed in venous circulation through a pressure gradient between the arachnoid villi and the cerebral venous sinuses. The arachnoid villi protrude from the arachnoid space, through the dura mater, and lie within the blood flow of the venous sinuses. The vili function as one way valves directing CSF outflow into the blood but preventing blood flow into the subarachnoid space.

Define concussion. Know the different grades of concussion. CH 18 pg 556

Concussion: a type of diffuse brain injury caused by damage to delicate axonal fibers and white matter tracts that project to cerebral cortex. Damage is caused by movements of high levels of acceleration to deceleration along with rotational and twisting movements. The severity of diffuse injury correlates with how much shearing force was applied to the brain. Mild concussion (mild traumatic brain injury): Characterized by immediate but transitory clinical manifestations without loss of consciousness, or loss of consciousness what is momentary to less than 30 minutes. Most blunt injuries cause mild TBI. The GCS is 13 to 15. • Grade I: Transient confusion and disorientation accompanied by amnesia (momentary); no loss of consciousness; symptoms resolve within 15 min. • Grade II: Transient confusion and retrograde amnesia that develops after 5-10 min (memory loss only of events occurring several minutes before injury); symptoms > 15 min. • Grade III: Any loss of consciousness (seconds or minutes); confusion and retrograde and anterograde amnesia remain from impact and persist several minutes. moderate cerebral concussion (moderate traumatic brain injury) is Any loss of copiousness lasting more than 30 minutes. A GCS of 8 and 13 is classified as moderate TBI • Grade IV: any loss of consciousness (can last up to 6 hrs) accompanied by retrograde and anterograde amnesia lasting 24 hrs or more. Severe Traumatic Brain Injury (severe concussion): Is A GCS less than 8 and is associated with brainstem signs (pupillary reaction, cardiac and respiratory symptoms, posturing) and intracranial contusions, hematoma or lacerations. Loss of consciousness lasts more than 24 hours, person experiences immediate autonomic dysfunction that resolves in weeks. Increased ICP appears 4-6 days after injury. Pulmonary complications occur frequently, with profound sensiomotor and cognitive system deficits. Severely compromised coordinated movements and verbal written communication , inability to learn and reason, and inability to modulate behavior also are evident. Sever injury causes permanent neurologic deficits and it has been shown that up to 14 percent remain in vegetative state, and 20 to 40 % end up dying as a result of brain injury or secondary complication.

Know vomiting with which CNS injuries. Ch 17 pg 509

Yawning, vomiting, and hiccups are complex reflex-like motor responses that are integrated by neural mechanisms in the lower brainstem. These responses may be produced by compression or diseases that involve tissues in the medulla oblongata. Such disorders include infection, neoplasm, or infarct, or other benign stimuli to the vagal nerve. Most CNS disorders produce N/V. V w/o N indicates direct involvement of the central neural mechanism (or pyloric obstruction). Vomiting is associated with CNS injuries that: (1) involve the vestibular nuclei (located in the lower pons and medulla oblongata) or their immediate projections, particularly when double vision (diploplia) also is present; (2) impinge directly on the floor of the fourth ventricle; or (3) produce brainstem compression secondary to increased intracranial pressure.

Define and describe the pathophysiology, clinical manifestations and etiology of Guillian Barre Syndrome. CH 18 pg 583

Guillain-Barre Syndrome - An acquired acute inflammatory demyelinating or axonal polyneuropathy with four subtypes: Acute inflammatory demyelinating polyneuropathy, acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, and fisher syndrome (only 5% of cases). Pathophysiology: Considered to be an autoimmune disease triggered by a preceding bacterial or viral infection (Etiology). Molecular mimicry (cross-activation of self-epitopes and pathogen-derived peptides by autoreactive T and B cells) is associated with the immune injury. Glycolipids, particularly gangliosides, are immune targets. The muscle innervated by the damaged peripheral nerves undergoes denervation and atrophy. If the cell body survives, regeneration of the peripheral nerve takes place and recovery of function is likely. If the cell body dies from intense root involvement in the inflammatory-degenerative process, no regeneration is possible. Collateral reinnervation from surviving axons and regenerating axons may take place. In this case, motor recovery is less complete and residual deficits persist. Clinical Manifestations:Vary depending on subtype. Typically first manifestations include numbness, pain, paresthesias, or weakness of the limbs. Motor signs manifest as an acute or subacute progressive paralysis. Proximal muscles may be involved earlier and more significantly than distal muscles. Paresis/Paralysis may be in an ascending pattern, involving the limbs, respiratory muscles, and bulbar muscles. Only bulbar muscles may be involved resulting in dysphagia and dysarthria. Weakness plateaus or improves by the fourth week in 90% of cases. Sensory symptoms include: paresthesias/dysthesias, tingling, burning, shocklike sensations (particularly in the limbs), pain, and numbness. Respiratory muscle weakness leads to vent support in 10-30% of cases. Cranial nerve weakness involves chewing, swallowing and coughing. Autonomic dysfunction shows as tachycardia, or bradycardia, hypo or hypertension, loss of or significant sweating. May undergo a respiratory or cardiac arrest. Hyponatremia caused by SIADH is also common. Diagnosis & TreatmentMajor diagnostic tests are CSF fluid examination, nerve conduction studies, and EMG. CSF shows high protein level (500mg/dl) without cellular abnormality. Nerve conduction studies help identify the subtype.Ventilatory support and management of the autonomic nervous system dysfunction are the two dominate aspects of therapeutic management. Intravenous immunoglobulin, plasmapheresis, or plasma exchanges or combination therapy with the first 2 weeks of onset of clinical manifestations may be indicated. After the disorder begins to remit, aggressive rehabilitation should be instituted.

Know mechanisms of heat production and heat loss. CH 16 pg 478-480

Mechanisms of Heat Production: 1) Chemical Reactions of Metabolism—these processes occur in the body core (primarily the liver) and are in part responsible for the maintenance of core temperature.The chemical reactions that occur during the ingestion and metabolism of food and those requires to maintain the body at rest (basal metabolism) require energy and produce heat. 2) Skeletal Muscle Contraction—Skeletal muscles produce heat through two mechanisms: gradual increase in muscle tone and production of rapid muscle oscillations-(shivering) - and shivering does not occur in neonates. Both increased muscle tone and shivering are controlled by the posterior hypothalamus and occur in response to cold. As perisperhal temp drops, muscle tone increases and shivering begins. 3) Chemical Thermogenesis—results from the release of epinephrine and norepinephrine that produce a rapid, transient increase in heat production by raising the body's basal metabolic rate. Chemical thermogenesis produces a quick, brief rise in BMR, whereas hormone thyroxine triggers a slow, prolonged rise. Occurs in brown and beige adipose tissue that is rich with mitochondria and blood vessels and is essential for non-shivering thermogenesis. Beige (bright) adipocytes store energy, and boon and beige adipocytes produce heat. Beige adipocytes demonstrate transdifferentiation to white adipocytes. With chronic cold exposure white to beige conversion increased thermogenesis Mechanims of Heat Loss: 1) Radiation—refers to heat loss through electromagnetic waves. These wave emanate from surfaces with temperatures higher than the surrounding air temperature. If the temperature of the skin is greater than the temp of the air, the skin and therefore the body will lose heat to the air. 2) Conduction—refers to heat loss by direct molecule-to-molecule transfer from one surface to another. Through conduction, the warmer surface loses heat to the cooler surface. Thus the skin loses heat through direct contact with the colder air, water or another surface. In the same manner the core fo the body loses heat to the cooler body surface. 3) Convection—the transfer of heat through currents of gases or liquids. It aids heat loss through conduction by exchanging warmer air at the surface of the body with cooler air in the surrounding space. Convection occurs passively as warmer air at the surface of the body rises away from the body and is replaced by cooler air; but the process may be aided by fans or wind. .4) Vasodilation— peripheral vasodilation increases heat loss by diverting core-warmed blood to the surface of the body. AS the core warmed blood passes through the periphery, heat is transferred by conduction to the skin surface and from the skin to the surrounding environment. Vasodilation occurs in response to autonomic stimulation under the control of the hypothalamus. As core temp increases, vasodilation increased until max dilation is achieved, at this point the body must use additional heat loss mechanisms. 5) Decreased muscle tone—to ↓ heat production, muscle tone may be moderately ↓ and voluntary muscle activity curtailed. Reason being feeling worn out when having high temperatures. 6) Evaporation—evaporation of body water from the surface of the skin and the linings of the mucous membranes is a major source of heat reduction. Heat is lost as surface fluid is converted top gas, so that heat loss by evaporation is increased if more fluids are available at the body surface. To speed this up, fluids are actively secreted through the sweat glands. Stimulation of sweating occurs in response to sympathetic neural activity and depends on favorable temp difference between the body and the environment. Also heat loss is affected by the relative humidity of the air. If humidity is low then sweat evaporate quickly, if humidity is high sweat does not evaporate but instead remains on the skin or drips off. 7) Increased pulmonary ventilation—exchanging air with the environment through the normal pulmonary ventilation provides some heat loss, although it is minimal. As air is inhaled the air draws heat from the upper respiratory tract. The air is further warmed in the alveoli by the blood in microcirculation. The warmed air is then exhaled into the environment. This process occurs faster at higher body temps through and increased ventilation rate, the hyperventilation is associated with hyperthermia. 8) Voluntary mechanisms—response to high body temps, people physically stretch out, thereby increasing the body surface area avaibule for heat loss. 9) Heat Adaptation: to warmer climates—the body of an individual who moves from a cooler to a warmer climate undergoes a period of adjustment that can take several days to weeks.

Know side effects of MAOIs. CH 19 pg 609

One of the three major classes of antidepressant drugs, they increase monoamine neurotransmitter levels within the synapse is the basis for the antidepressant effect. Common Side effects are: 1.sedation or agitation 2.insomnia 3.dry mouth 4.impotence 5.weight gain 6.May also induce acute and heightened levels of BP after takin tyramine rich foods (aged cheese, sour cream. pods of brand beans, pickled herring, liver, canned figs, raisins, and avocado) MAOI interactions with TCAs, SSRIs, stimulants, and OTC flu medications are dangerous and should be avoided. Because of these adverse side effect issues, MAOIS are used less often than any other antidepressants.

What part of the brain must be functioning for cognitive operations? CH 17 pg 511-514

Purposeful movement requires an intact corticospinal system. Non purposeful movement is evidence of sever dysfunction of the coricospical system. Awareness (content of thought) encompasses all cognitive functions, including awareness of self, environment, and affective stares (i.e moods). Awareness is mediated by all of the core networks under the guidance of executive attention networks, including selective attention and memory. Executive attention networks involve abstract reasoning, planning, decision making, judgement, error correction, and self control. Each attentional function is a network of interconnected brain circuits and not localized to a single brain area. Function and Disfunction: Selective attention (orienting) - ability to select specific information to be processed from available, competing environmental and internal stimuli and to focus on those stimuli. Multiple areas of the brain are involved in selective attention, including cortical areas, thalamic nuclei and the limbic system. Frontal and Parietal regions of the right hemisphere contribute to selective attention. The engage component (identifying the target of attention) is mediated by the pulvinar nucleus of the thalamus and regulate cortical synchonry. The disengagement mechanism ( shifting attention to a new target and reengaging on the new target) is mediated by the right parietal lobe. The motor consequences of attention are mediated by the superior colliculi for visual orienting and spatial attention. Memory - the recording, retention, and retrieval of information. Two types of long term memory exists: declarative and nondeclarative. Declarative = involves learning and remembrance of episodic memories (personal hx, events, experiences) and semantic memories (facts and info); mediated by domain-specific cortical areas of association areas including 1) areas of temporal, parietal, and occipital lobes, where long-term memories are thought to be stores, 2) domain-independent areas of the medial temporal lobe (i.e. hippocampus), the diencephalon (thalamic structures and hypothalamus), and the basal forebrain (located ventral to the striatum and produces acetylchoine), where it is thought distinct domain specific feature of an experience are related or bound. Non-declarative memory (nonconscious) is the memory for actions , behaviors, skills and outcomes. aka reflexive, procedural, or implicit memory, is of actions, behaviors (habits), skills, and outcomes. A motor memory, and involves the construction of the motor pattern so that the action, behavior, skills becomes increasingly automatic. The striatum of the basal ganglia supports this function (stimulus response learning) as well as probabilistic classification learning , which supports outcome prediction. All skills and habits are stored in the memory network. Cerebella memory= working memory (short term) with also motor coordination, non motor functions of cognition, emotion and learning. Emotional learning medicated by amygdala ( inner surface of temporal lobe). The prefrontal (prefrontal cortex) area mediate several cognitive functions, called executive attention functions (planning, problem solving, goal setting) The vigilance system provides the person with the ability to maintain a sustained state of alertness or concentration for searching and scanning activities and involves the right frontal areas and locus ceruleus (LC) (located in the rostral pons) Through the neurotransmitter norepinephrine from the LC, the speed of orienting (selective attention) network is increased and the detection functerm-2tion of the anterior cingulate gyrus is decreased.

Know the most critical index of nervous system dysfunction/function. CH 17 pg 505

Level of consciousness is the most critical clinical index of nervous system function or dysfunction. An alteration in consciousness indicates either improvement or deterioration of the individual's condition. Highest level of Consciousness is alert, oriented to self, others, place and time (implies full use of cognitive capacities). From this normal alert state, levels of consciousness diminish in stages from confusion and disorientation (can occur simultaneously) to coma, each of which is clinically defines. Levels of altered consciousness include: confusion, disorientation, lethargy, obtundation, stupor, coma, light coma, coma, and deep coma.

What is responsible for the tremors associated with Parkinsons Disease? find page number CH 17

(p. 567) The Parkinson tremor appears to result from instability of feedback from the basal ganglia to the cerebral cortex caused by the loss of the inhibitory influence of dopamine in the basal ganglia. 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 blocked because other motor control signals arriving in the thalamus override the abnormal basal ganglia signals.

Know most common primary CNS tumor. CH 18 pg 590

Astrocytomas are a type of glioma and the most common primary CNS tumor (75% of all brain and spinal cord tumors). Astrocytomas develop from astrocytes and grow by expansion and infiltration into the normal surrounding brain tissues. Tumor cells are believed to have lost normal growth restraint, and thus they proliferate uncontrollably. These slow-growing but infiltrative gliomas tend to form cavities (pseudocysts). Although these tumors may occur anywhere in the brain or spinal cord, they are located most commonly in the cerebrum, hypothalamus, and pons. Low grade astrocytomas tend to be located laterally or supratentorially in adults and in the posterior fossa in children. Headache and subtle neurobehavioral changes may be an early sign with other neurologic symptoms evolving slowly and IICP occuring late in the tumor's course. Onset of a focal seizure disorder between the second and sixth decade of life suggests an Astrocytoma. There are four grades: I, II, III, IV. Diagnosis of high-grade astrocytomas most commonly takes 3-6 mos. From onset on the first clinical manifestation because the person does not recognize the need to consult a healthcare provider. Grades III and IV are found predominantly in the frontal lobes and cerebral hemispheres although they may occur in the brainstem, cerebellum and spinal cord. Grade IV glioblastoma multiform (GBM) is the most lethal and common type of primary brain tumor. GBM is higher vascular and extensively irregular and infiltrative, making them difficult to remove surgically. 50 percent of glioblastomas are bilateral or at least occupy more than one lobe at the time of death. Typical clinical presentation is that of diffuse, non specific clinical signs, such as HA, irritability, and personality changes that progress to more lear cut manifestations of IICP, including HA on position change, papilledema, vomiting, seizure activity,. Symptoms may progress to include more definite focal signs such as hemiparesis, dysphasia, dyspraxia, cranial nerve palsies, and visual deficits.

Know which part of the brain controls pupillary changes. CH 17 pg 508

Brainstem areas control the pupils. Pupillary changes thus are a valuable guide to evaluating the presence and level of brainstem dysfunction.

Know pathophysiology, clinical manifestations and etiology of cerebral palsy. CH 20 pg 626

Cerebral Palsy is the term given to a diverse group of nonprogressive syndromes that affect that brain and cause motor dysfunction beginning in early infancy. It is a disorder of movement, muscle tone, or posture that is caused by injury or abnormal development in the immature brain. Although cerebral palsy is by definition nonprogressive, its clinical manifestations change with growth and maturation of the child. Pathophysiology: Several factors, alone or in combination, can produce brain damage that leads to cerebral palsy. Prenatal cerebral hypoxia, congenital malformations and placental pathology can contribute to the systemic degeneration of immature areas of the brain white matter and interfere with cell maturation. The severity of the damage depends on the gestational age at the time of the injury and the degree of injury sustained. Pyramidal/spastic CP results from damage or defects in the brains corticospinal pathways (upper motor Neuron) in either 1 or both hemispheres. Extrapyramidal/nonspastic CP caused by damage to the cells in the basal ganglia, thalamus, or cerebellum. Clinical manifestations: The syndromes associated with cerebral palsy can be classified according to the areas of the brain that are damaged, pyramidal (spastic) and extrapyramidal (dyskinetic, ataxic, or hypotonic). Pyramidal/spastic cerebral palsy results from damage or defects in the brain's corticospinal pathways (upper motor neuron) in either one of both hemispheres and accounts for approximately 70% to 80% of cerebral palsy cases. It is associated with increased muscle tone, prolonged primitive reflexes, exaggerated deep tendon reflexes, clonus, rigidity of the extremities, scoliosis and contractures. Cognitive impairment occurs in about 30% of cases. Extrapyramidal/nonspastic is caused by damage to cells in the basal ganglia, thalamus or cerebellum and includes two subtypes: dyskinetic and ataxic. Dyskinetic is associated with extreme difficulty in fine motor coordination and purposeful movements. Ataxic is associated damage to the cerebellum and manifests with gait disturbances and instability. Children with cerebral palsy often have associated neurologic disorders such as seizures, intellectual impairment ranging from mild to severe and visual impairment. Pyramidal/spastic CP: spasticity, dyskinetic, ataxic, or hypotonic movements. Extrapyramidal/nonspastic CP: Dyskinetic cerebral palsy: extreme difficulty in fine motor coordination and purposeful movements.(Jerky, uncontrolled, abrupt. (20-25% of all CP cases) Ataxic cerebral palsy: gait disturbances and instability. Hypotonia at birth leading to stiffness of trunk muscles, inability to balance body position without support. (5% of all cases). Etiology (Table 19-3)Prenatal - Maternal include metabolic diseases, nutritional deficiencies, twins or multiple births, bleeding, toxemia, blood incompatibilities, exposure to radiation, infection premature labor. Prematurity, genetic factors, congenital anomalies of the brain. Perinatal - Anesthesia during labor and delivery, mechanical trauma during delivery, immaturity at birth, metabolic disorders, electrolyte disturbances. Postnatal - head trauma, infections, cerebrovascular accidents, toxicities, environmental toxins.

Know all types of cerebral edema and what causes each type. CH 17 pg 529-530

Cerebral edema is an increase in the fluid content of brain tissue. The result is increased extracellular or intracellular tissue volume. It occurs after brain insult from trauma, infection, toxicity, hemorrhage, tumor, ischemia, infarction, or hypoxia. The harmful effects of cerebral edema are caused by distortion of blood vessels, the displacement of brain tissues, increase in ICP, and the eventual herniation of brain tissue from brain compartment to another. Three types of cerebal edema: 1) vaogenvc edema, 2) cytotoxic edema, and 3) interstitial edema 1. Vasogenic edema: clinically the most common type. It is caused by the increased permeability of the capillaries that form the blood brain barrier. Plasma proteins leaks into the extracellular spaces, drawing water to them, and increased the eater content of brain parenchyma , specifically the white matter. Vasogenic edema starts in the area of injury and spreads with fluid accumulating in the white matter of the ipsilateral side because the parallel myelinated fibers separate more easily. Edema promotes more edema because of ischemia from increasing ICP. Clinical manifestations include focal neurologic deficits, disturbances of consciousness , and severe increase in ICP. Vasogenic edema resolves from slow diffusion. 2. Cytotoxic (metabolic) edema: toxic factors directly affect the cellular elements of the brain parenchyma (neuronal, glial and endothelial cells) causing failure of the active transport systems. The blood-brain barrier is not disrupted. The cells lose their potassium and gain larger amounts of sodium because of failure of cell membrane ion pumps. Water follows by osmosis into the cells so that the cells swell (intracellular edema). Cytotoxic edema occurs principally in the gray matter and may increase vasogenic edema because of their loss of endothelial tight junctions. 3. Interstitial edema: seen most often with non-communicating hydrocephalus. The edema is caused by transependymal movement of CSF from the ventricles into the extracellular spaces of the brain tissues. The brain fluid volume this is increased predominately around the ventricles. The hydrostatic pressure within the white matter increases and the size of the white matter is reduced because of the rapid disappearance of myelin lipids.

Define and discuss the different types of stroke, which affected artery causes what data processing deficits (agnosia, dysphasia, etc).CH 18 Pg 566-567 LOOK AT TABLE 18.5 for specific arteries and their area affected.

Cerebrovascular Accident (CVA) are classified according to pathophysiology and thus are ischemic (thrombotic or embolic), cryptogenic, global hypoperfusion (shock), or hemorrhagic. Ischemic Stroke: occurs when there is an obstruction to arterial blood flow to the brain from thrombus formation, an embolus associated with atherosclerosis, or hypo-perfusion related to decreased blood volume or heart failure. The inadequate blood supply results in ischemia and can progress to infarction (death of the tissue). TIA (transient ischemic attack) brief episode of neurologic dysfunction caused by focal disturbance of brain or retinal ischemia with symptoms lasting less than 1 hour without evidence of infarction. TIA represent thrombotic particles causing intermittent blockage. Thrombotic stroke -Arise from arterial occlusions caused by thrombi formed in arteries supplying brain or in the intracranial vessels. Conditions causing increased coagulation or inadequate cerebral perfusion increase the risk of thrombosis. Clots form occluding artery and break off and travel up the vessel to distant sites where occlusion occurs producing stroke. Embolic Stroke—Involves fragments that break from a thrombus formed outside brain or heart, aorta, common carotid or thorax. Emboli infrequently arise from ascending aorta or common carotid artery. Embolus involves small vessels of the brain and obstructs at bifurcation thus causing ischemia. Embolus may plug lumen entirely and or remain in place and shatter into fragments that move up the vessel blood flow. High risk factors are atrial fibrillation, left ventricular aneurysm or thrombus, left atrial thrombus, recent MI, rheumatic valvular disease, mechanical prosthetic valve, non bacterial endocarditis, bacterial endocarditis, patent foramen ovale, and intracardiac tumors. People who experience an embolic stroke, a second stroke usually follows as the emboli continues to exist. Embolization is usually in the distribution of the middle cerebral artery ( the largest cerebral artery). Hemorrhagic Stroke: (intracranial hemmorage ICH)—Causes hypertension, ruptured aneurysms, arteriovenous malformation and fistula, amyloid angiopathy, and cavernous angioma. ICH can be secondary to TBI, bleeding into the ischemic brain infarction or tumor, or a bleeding disorder or anticoagulation. Risk factors hypertension, previous cerebral infarct, coronary artery disease and diabetes mellitus. Hypertensive hemorrhage usually occurs within the brain tissue. Mass of blood is formed and its volume increases. Hemorrhages are described as massive, small, slit, or petechial. Massive is several centimeters in diameter, small 1-2 cm . slit lies in subcortical area and petechial size of a pinhead bleed. Most common sites in the putamen of basal ganglia, the thalamus, the cortex and subcortex, the pons, caudate and cerebellar hemispheres. Lacunar Stroke: (lacunar infarct)—are usually caused by perivascular edema, thickening and inflammation of the arteriolar wall in a deep perforating artery that supplies small penetrating subcortical vessels. the ischemic lesions or lacunas are predominantly in the basal ganglia, internal capsules and pons. They are associated with hyperlipidemia, smoking, HTN, and DM. Because of locations and small area of infarction, they may have pure motor or sensory deficits. Hemodynamic Stroke: (Brain Hypoperfusion) Is associated with systemic hypo perfusion caused by cardiac failure, PE, or bleeding that results in inadequate blood supply to the brain. Symptoms are usually bilateral and diffuse. Patho: Cerebral infarction results when an area of the brain loses its blood supply because of vascular occlusion. Caused include: 1) abrupt vascular occlusion ( embolus or thrombi) 2). gradual vessel occlusion ( atheroma) 3). vessels that are stenosed but not completely occluded Cerebral thrombi and cerebral emboli most commonly produce occlusion, but atherosclerosis and hypotension are the dominant underlying process. Cerebral infarctions are ischemic of hemorrhagic . Ischemic infarctions, the affected area becomes pale and softens 6 to 12 hours after the occlusion (white infarct). Necrosis, swelling around the insult, and mushy disintegration appear by 48 to 72 hours after infarction. After occlusion of cerebral artery, anatosomes connecting the distal segments of the middle cerebral artery with distal branches of the anterior and posterior cerebral arteries can partially maintain blood flow in the ischemic penumbra and delay or precent cell death in some individuals. Vascular remodeling can occur with new arterioles sprouting from penumbra vessels that penetrate the ischemic core to reestablish collateral circulation. In hemorrhagic infarcts, bleeding occurs into the infarcted area through leaking vessels when the embolic fragments resolve and reperfusion begins to occur. Clinical Manifestations of Stroke: ischemic strokes vary depending on artery obstructed; Hemorrhagic strokes vary location and size of bleed. Focal defects in 80% altered consciousness 50%. Acute stroke treatment: "time is brain" ⇒Treatment needs to begin within 6 hours of symptom onset.

Discuss disorders of the conjunctiva of the eye. CH 16 pg 487-488

Conjunctivitis: (red eye) is an inflammation of the conjunctiva (mucous membrane covering the front part of the eyeball) may be caused by bacteria, viruses, allergies, or chemical irritations. The inflammatory response produces photophobia, visual blurring, redness, edema, pain, and lacrimation. Treatment is related to cause. Acute Bacterial Conjunctivitis: (pink eye) Highly contagious and often is caused by gram-positive organisms (Staphylococcus, Haemophilus, Streptococccus pneumoniae, Moraxella catarrhalis), although other bacteria may be involved. The onset is acute, characterized by mucopurulent drainage from one or both eyes. The disease often is self-limiting and resolves spontaneously in 10 to 14 days. Antibiotic eyedrops usually are effective. * in children under age of 6 haemophilius infection often leads to otitis media. Viral conjunctivitis: o Caused by an adenovirus. Symptoms vary from mild to severe with normally watery, redness and photophobia. Some strains of virus cause conjunctivitis and pharyngitis (pharyngoconjunctival fever), and others cause keratoconjunctivitis. Both diseases are contagious, with watering, redness, and photophobia. Treatment is symptomatic. Allergic Conjunctivitis: Associated with a variety of antigens, including pollens. Ocular itching is associated with photophobia, burning, and gritty sensations in the eye. Treatment is symptomatic and may include antihistamines, low dose corticosteroids, and vasoconstrictors. Chronic Conjunctivitis: o Is the result of any persistent conjunctivitis. The cause requires identification for effective treatment. Trachoma ( chlamydial conjunctivitis): Is caused by Chlamydia trachomatis. It often is associated with poor hygiene and is the leading cause of preventable blindness in the world. The severity of the disease varies, but it can involve inflammation with scarring of the conjunctiva and eyelids causing distorted lashes to abrade the cornea leading to corneal scarring and blindness. Chlamydial organisms are sensitive to local or systemic antibiotics.

Define depression and its types; know etiology and link to cortisol. CH 19 pg 605-608

Depression- When emotional states, such as sadness, become chronic and uncontrollable, individuals may be diagnosed with depression; there are two major classifications of mood disorder: major/clinical depression & bipolar disorder. Major depression- Most common mood disorder and the leading cause of disability in the US and throughout the world; intense and sustained unpleasant state of sadness and hopelessness Bipolar disorder: Bipolar I disorder features manic episodes and at least one major depressive episode. Bipolar II disorder is characterized by recurrent major depressive episodes with one or more hypomania. Symptoms of Depression- five or more symptoms present in a two week period with at least one symptom as either depressed mood or loss of interest or pleasure: 1. Depressed or irritable mood 2. Loss of interests and pleasure 3. Significant(>5%) weight gain or loss in a month 4. Insomnia or hypersomnia 5. Psychomotor agitation or retardation 6. Fatigue or loss of energy 7. Feelings of worthlessness or excessive guilt 8. Poor concentration or indecisiveness 9. Recent thoughts of death or suicide Symptoms of Manic Episode—three or more (four if mood only irritable) during distinct period of abnormally and persistently elevated, expansive, or irritable mood occurring for at least one week: 1. Elevated Mood 2. Irritable mood 3. Inflated self esteem 4. Decreased need for sleep 5. Excessive talking 6. Racing/crowded thoughts 7. Distractibility 8. Increase in goal-directed activity 9. Excessive risky activities ETIOLOGY: Genetic and environmental influences! (Environmental triggers such as psychosocial stress can facilitate onset of depression to those with a genetic vulnerability.) Depression: 1. Reduction in brain monoamine neurotransmission (monoamine hypothesis of depression, page 653, 6th Ed.) 2. Deficit of norepinephrine, dopamine and/or serotonin, 3. increased cortisol (increased plasma cortisol stays elevated throughout evening and early morning) 4. abnormal thyroid hormones 5. life stressors and potential dysfunction of serotonin (5-HT) elevates risk 6. persons with copies of two s alleles more than likely will develop major depression and have suicidal thoughts in response to stress 7. alterations in blood flow to prefrontal and limbic brain regions (amygdala = emotional behavior) Bipolar (Mania): 1. Elevated brain monoamine neurotransmission2. Loci on chromosomes 18 and 22, also linked with schizophrenia and deficits in reelin expression linked to genetic loci located on chromosome 22 with susceptibility to schizophrenia. Found in both Depression and Bipolar Disorder: 1. Structural brain alterations: reduced frontal lobe and limbic system volumes NEUROCHEMICAL DYSREGULATIONMonoamine Hypothesis of Depression ⇒ A deficit in the concentration of brain norepinephrine, dopamine, and or serotonin is the underlying cause of depression. Three major classes of antidepressants are MAOI's, TCAs, and SSRIs. Dietary consumption of trytophan and AMPT produces a rapid return to depression in those successfully treated. This is all neurochemical dysregulation. NEUROENDOCRINE DYSREGULATION Stress and HPA dysregulation ⇒ The HPA plays an important role in the response to stress. Chronic activation of the HPA system and elevated glucocorticoid secretion are found in the later percentage of people with major depression. Antidepressant drugs effective in normalizing HPA are associated with a food clinical response, whereas persist and dysregulation of the HPA system is related to continued depression or relapse. Hypothalmic-Pituitary-Thyroid Stress Dysregulation ⇒ Approximately 20-30% of persons with MDD have an altered HPT system. Individuals exhibit increased CSF levels of thyrotropin releasing hormone, blunted thyroid stimulating hormone response to TRH challenge, and decreased nocturnal rise in TSH level that normally occurs between midnight and early morning. Abnormalities in thyroid function are also observed in bipolar disorder, especially among individuals with rapid cycling. NEUROANATOMIC AND FUNCTIONAL ABNORMALITIES There's a widespread decrease in serotonin 5-HT1A receptor subtype binding in the frontal, temporal, and limbic cortex, and hippocampus. Structural abnormalities associated with mood disorders, especially in frontal and limbic regions such as the amygdala. There are also reports of reduced frontal lobe volume in depressed individuals and decreased or asymmetric temporal lobe volume with bipolar illness and depression. Cortisol and Depression: The Glutamate System Because of the delayed actions of current antidepressants and poor remission rates, there is a new search for drugs. New evidence suggests that elevated cortical levels of glutamate, the major excitatory neurotrasnmitter in the CNS may be involved in the pathophysiology of major depression. A potential target being glutamate N-methyl-D-aparate (NMDA) receptor.

What is the relationship between epinephrine and body temperature? CH 16 pg 478/

Epinephrine's relationship to body temp (P.478) Epinephrine causes vasoconstriction, stimulates glycolysis, and increases metabolic rates, thus increasing heat production. Epinephrine and norepinephrine produce a rapid, transient increase in heat production by raising the body's basal metabolic rate in Chemical thermogenesis. Pathogenesis of Fever (p.480) -Endogenous pyrogens are produced by phagocytic cells as they destroy microorganisms within the host. The endogenous pyrogens act on the preoptic nucleus of the hypothalamus. Centers in the hypothalamus and brainstem signal an increase in heat production and heat conservation to raise body temperature to the new set point. Peripheral vasoconstriction occurs with shunting of blood from the skin to the body core. Epinephrine release increases metabolic rate, and muscle tone increase. Decreased release of vasopressin reduces the volume of body fluid to be heated. Shivering may occur. Body temperature is maintained at the new level until the fever breaks.

Know heat exhaustion and heat stroke? CH 16 Pg 482

Heat Exhaustion—results from prolonged high core or environmental temperatures which causes profound vasodilation and profuse sweating, leading to dehydration, decreased plasma volumes, hypotension, decreased cardiac output, and tachycardia. Symptoms include: dizziness, weakness, and nausea, confusion and fainting Heat exhaustion symptoms cause the individual to stop work, lie down and rest. Ceasing activity decreases muscle work causing decreased heat production. Lying down redistributes vascular volume. The individual should be encouraged to drink cool fluids to replace fluid lost through sweating. Heat Stroke—Potentially lethal consequence of an overstressed thermoregulatory center. Heat stroke can be caused by exertion, by overexposure to environmental heat, or from impaired physiological mechanisms for heat loss. With core temps over >40C /104F; the regulatory center may cease to function appropriately and the body's heat loss mechanisms fail. Symptoms include high core temps, absence of sweating, rapid pulse rate, confusion, agitation, and coma. Complications include cerebral edema, degeneration of the CNS, swollen dendrites, renal tubular necrosis, and hepatic failure with delirium, coma and eventual death if treatment is not undertaken.

Define and describe the pathophysiology, clinical manifestations and etiology of Huntington disease. CH 17 pg 535- 536

Huntington Disease also known as chorea, is a relatively rare, hereditary, degenerative hyperkinetic movement disorder diffusely involving the basal ganglia and cerebral cortex. Pathophysiology: The major pathologic feature of HD is severe degeneration of the basal ganglia and the frontal cerebral cortex. Degeneration of the basal ganglia and the substantia nigra exhibit a depletion of neurons that secrete GABA (an inhibitory neurotransmitter). GABA depletion leads to an excess of dopaminergic activity that causes hypotonia and hyperkinesia (involuntary, fragmentary movements). Clinical Manifestations: Abnormal movement and progressive dysfunction of intellectual processes (dementia) and emotional lability. Chorea (involuntary, quick movements of the feet or hands comparable to dancing) is the most common type of abnormal movement affecting individuals with HD. It begins in the face and arms, eventually affecting the entire body. Symptoms of frontal lobe dysfunction include attention deficits, short term memory loss, reduced capacity to plan, organize, and sequence, as well as bradyphrenia (slow thinking); and apathy. Etiology: HD (Chorea) is a rare, hereditary (autosomal dominant)-degenerative disorder diffusely involving the basal ganglia and cerebral cortex, commonly manifests between 25-45 years of age, and occurs in all races. The abnormality is manifested on the short arm of chromosome 4. Treatment: No known treatment is effective in halting the degenerative process in HD. The chorea can be treated with dopamine receptor-blocking or depleting agents, and medical and non- medical care for depression and aggressive behavior may be required.

Know normal intracranial pressure. How does body compensate for increased ICP? CH 17 pg 528

ICP is normally between 5 to 15 mmHG of 60- 180mm H20. Increased ICP may occur with an increase in inter cranial content (tumor growth), edema, excess CSF or hemorrhage. It needs an equal reduction in volume of the other cranial contents. The most available to displace is CSF. If ICP remains high after CSF displacement out of the cranial vault cerebral blood volume and flow are altered. Dramatic sustained rises in ICP are not seen until all compensatory mechanisms have been exhausted. Dramatic rises in ICP occur over a very short period. Autoregulation, the compensatory alteration in the diameter of the intracranial blood vessel designed to maintain a const blood flow during changes in cerebral perfusion pressure, is lost with progressively increased ICP. Accumulating CO2 may still cause vasodilation locally, but without auto regulation this vasodilation causes the hydrostatic BP in the vessels to drop and blood volume to increase. The increases pressure may obstruct venous outflow. The brain volume is thus further enhanced, and ICP continues to rise., and the pressure takes much longer to return to baseline As the ICP approaches systematic blood pressure, cerebral perfusion pressure falls and cerebral perfusion slows dramatically. The brain tissues experiences severe hypoxia, hypercapnia, and acidosis all of which cause cerebrovascular dilation.

Define and describe the pathophysiology, clinical manifestations and etiology of Mysthenia Gravis CH 18 pg 585-587

Is a chronic autoimmune disease mediated by acetylcholine receptor (AChR) antibodies that act at the neuromuscular junction. Pathophysiology: Myasthenia gravis results from a defect in nerve impulse transmission at the neuromuscular junction. The main defect is the formation of autoantibodies (an IgG antibody) against receptors at the ACh binding site on the postsynaptic membrane. The autoantibodies block the AChR or cause complement- mediated loss of AChRs from the neuromuscular junction. The cause of this auto sensitization is not known. The destruction of receptor sites causes diminished transmission of the nerve impulses across the neuromuscular junction. Muscle depolarization is incomplete or not achieved. Clinical Manifestations: Myasthenia gravis typically has an insidious onset. clinical manifestations may first appear during pregnancy, during postpartum period, or in conjunction with the administration of certain anesthetic agents. The foremost complaint is muscular fatigue and progressive weakness. The individual often complains of fatigue after exercise and has a recent history of reoccurring upper respiratory tract infections. The muscles of the eyes, face, mouth, throat, and neck usually are affected first. The extra occular eye muscles and the levator muscles are most affected. Manifestations include diplopia, ptosis, and ocular palsies. The muscles of facial expression mastication, swallowing, and speech are the next most involved. The results are facial droop and an expressionless face; difficulty chewing and swallowing. The muscles of the neck, shoulder girdle, and hip flexors are affected less frequently. When involved the person experiences fatigue requiring periods of rest, weakness of the arms and legs that improves with rest, and difficulty in maintaining head position. The respiratory muscles of the diaphragm and the chest wall become weak, and ventilation is impaired. Impairment n deep breathing and coughing predisposes the individual to atelectasis and congestion. In the advance stage of the disease, all the muscles are weak. Etiology: The etiology of myasthenia gravis is unknown. Some persons have genetic susceptibility related to variants in AChR genes, as well as the major histocompatibility genes.diagnosis: The diagnosis of MG is made on the basis of a response to endeophonium chloride (Tensilon), results of repetitive single-fiber EMG, and detection of AchR and MuSK antibodies. Treatment: Treatment is individualized. Anticholinesterase drugs, corticosteroids, immunosuppressant drugs, azithroprine, and cyclosporine are used to treat MG. Plasmapheresis (plasma is separated from cells and is replaced) may be life-saving during a crisis.

What nerves are capable of regeneration? CH 15 pg 435-437

Myelinated axons ONLY in the PNS. When an axon is severed wallerian degeneration occurs in the portion of the axon distal to the cut: 1) a characteristic swelling appears 2) the neurofilaments hypertrophy 3) the myelin sheath shrinks and disintegrates 4) this axon portion degenerates and disappears. The myelin sheaths reform into Schwann cells that line up in a column between the cut and the effector organ. At the proximal end of the injured axon, similar changes occur but only as far back as the next node of Ranvier. The cell body responds to trauma by swelling and then dispersing the Nissl substance (chrmatolysis). During the repair process the cell increases in metabolic activity, protein synthesis, and mitochondrial activity. This process is limited to myelinated fibers and generally doesn't occur outside of the PNS. The regeneration of axonal constituents in the CNS is limited by increased scar formation and the different nature of myelin formation by the oligodendrocyte. Nerve regeneration depends on many factors, such as location of injury, type of injury, the inflammatory responses, and the process of scarring. The closer the cell body of the nerve, the greater the chances that the nerve cell will die and not regenerate. A crushing injury allows recovery more fully than a cut. Crushed nerves sometimes recover whereas, cut nerves often form connective tissue scars that block or slow regenerating axonal branches.

What are the two types of fibers that transmit the nerve action potentials generated by excitation of any of the nociceptors. CH 16 ph 470

Nociceptors are categorized according to the stimulus to which they respond and by the properties of the axons associated with them. Nociception involves 4 phases: transduction (stimulation of noncioceptors in the peripherally), transmission (axonal conduction), perception (cortical processing of stimuli), and modulation (descending pathways and neurotransmitters that inhibit or amplify pain). A-delta fibers: lightly myelinated, medium-sized fibers that are stimulated by severe mechanical deformation (mechanonociceptors) and/or by extremes of temperature (mechanothermal nociceptors). These fibers rapidly transmit sharp, well-localized "fast" pain sensations and are responsible for casing reflex withdrawal of the affected body part from the stimulus before a pain sensation is perceived. C-fibers: polymodal; smaller; unmyelinated stimulated by mechanical, thermal, and chemical nociceptors. They slowly transmit dull, aching, or burning sensations that are poorly localized and longer lasting. A-beta fibers: large myelinated fibers that transmit touch and vibration sensations. They do not normally transmit pain but do play a role in pain modulation.

Where in the CNS does pain perception occur? CH 16 pg 470-471

Pain perception is the conscious awareness of pain that occurs primarily in the reticular and limbic systems and the cerebral cortex. Three systems interact to produce the perception of pain and it changes with age: I. The sensory-discriminative system: mediated by the somatosensory cortex and is responsible for identifying the presence, character, location and intensity of pain. II. The affective-motivational system:determines an individual's conditioned avoidance behaviors and emotional responses to pain. It is mediated through the reticular formation, limbic system, and brainstem with projections to the prefrontal cortex. III: The cognitive-evaluative system: overlies the individual's learned behavior concerning the experience of pain and can modulate perception of pain. Mediated through the cerebral cortex. *Pain threshold, and tolerance are subjective phenomenon that influence an individual's perception of pain. They can be influenced by genetics, gender, cultural perceptions, expectations, role socializations, physical and mental health and age.

What is the gate control theory of pain? CH 16 pg 469

Pain transmission is modulated by a balance of impulses conducted to the spinal cord where cells in the substantial gelatinous function as a "gate". The spinal gate regulates pain transmission to higher centers in the CNS. Large myenlated A-delta fibers and small unmyenlated C fibers respond to a brave range of painful stimuli (mechanical, thermal, and chemical). These fibers terminate on interneurons in the substantia gelatinosa (lamine in the dorsal horn of the spinal cord) and "open" the spinal gate to transmit the perception of pain. Closure or partial closure of the spinal gates can occur from nonnociceptive stimulation (i.e from touch sensors on the skin) carried on large A-beta fibers decreasing pain perception. This is why rubbing a pain area may alleviate some of the discomfort. The CNS, through efferent pathways may also close, partially close, or open the "gate".

What happens to a patient after an acute spinal cord injury? Why is it life threatening? Describe the clinical manifestations. Why would their temperature fluctuate? CH 18 pg 557-559

Primary spinal cord injury occurs with the initial mechanical trauma and immediate tissue destructions from shearing, compression, or penetration. Can also occur if an injured spine is not aequately immobilized immediately following injury. Can occur in the absence of vertebral fracture or dislocation from longitudinal stretching of the cord with or without flexion or extension of the vertebral column, or both. The stretching causes altered axon transport, edema, myelin degeneration , or retrograde or wallerian degeneration. Secondary spinal cord injury is a pathophysiological cascade of vascular, cellular and chemical events that begins within a few minutes after injury and continues for weeks. 1.) Microscopic hemorrhages appear in the central gray matter and pia arachnoid and increases in size until the entire grey matter is hemorrhagic and necrotic. 2.) Edema in the white matter occurs, impairing the microcirculation of the cord. 3.) Localized hemorrhaging and edema therefore are followed by loss of auto regulation, vasospasm, impaired venous drainage, and reduced vascular perfusion with development of ischemic areas which is maximal at the level of injury and two cord segments below and above it. 4). Cellular and sub cellular alterations with myelin disruption, axonal degeneration, and tissue necrosis occurs. Impaired perfusion is aggravated by systemic responses, including neurogenic or hemorrhagic shock, and dysrhythmias . 5). Cord swelling increases the individuals level of dysfunctions, making it difficult to distinguish functions permanently from those temporally impaired. 6.) Circulation in the white matter tracts of the spinal cord returns to normal in about 24 hours, but gray matter circulation remains altered. 7)Phagocytes appear 36 to 48 hours after injury and microglia proliferate with altered astrocytes promoting inflammation. RBS begin to disenergrate and reprobation of hemorrhage and edema begins. 8.) Degenerating axons are engulfed by macrophages in the first 10 days after injury. The traumatized cord is replaced acellular collagenous tissue usually in to 2 -3 weeks, and the meninges thicken as part of the scarring process. Why is it life threatening? In the cervical region, cord swelling, may be life threatening because of the possibility of resulting impairment of the diaphragm function (phrenic nerves exit C3-C5) and vegetative functions mediated by the medulla oblongata. Cardiovascular and respiratory functions mediated by the medulla oblongata can be lost. Clinical manifestations of acute spinal cord injury: Following spinal cord injury, loss of normal cellular activity below the site of injury ensues following the disruption of the tonic (continuous) discharge from the brain. Inhibition of suprasegmental impulses immediately following the injury causes spinal shock. Spinal shock is characterized by the complete loss of reflex function in all areas below the injury (lesion), and involves all skeletal muscles, bladder, bowel, sexual function, and autonomic control. Spinal shock may last for 7 to 20 days or as little as a few days or as long as 3 months. Signs that spinal shock is resolving include the reappearance of reflex activity, hyperreflexia, spasticity, and reflex emptying of the bladder. Severe injury to the spinal cord will result in obvious changes below the lesion including: paralysis and flaccidity in muscles, absence of sensation, loss of bladder and rectal control, transient drop in blood pressure and poor venous circulation. Flexion reflexes return first involving the toes, feet, then legs. The initial clinical manifestations of associated with acute spinal injury include 1) rapid loss of voluntary movements in the body parts below the level of injury 2) loss of sensation in the lower extremities and possibly lower truck (depending of level of injury) 3) loss of spinal and autonomic reflexes below the level of injury Depending on the degree of damage either of the following can occur 1). motor, sensory, reflex and autonomic functions return to normal; or 2) autonomic neural activity in the isolated segment develops. Injury to the cervical and upper thoracic cord may result in a condition called neurogenic shock in addition to spinal shock. Neurogenic shock (also called vasogneic shock) occurs with cervical or upper thoracic cord injury above T6 and may be seen in addition to spinal shock. It is caused by the absence of sympthateic activity thought loss of suprspinal control and unopposed parasympathetic tone mediated by the intact vagus nerve and last up to 5 weeks after injury. Symptoms include vasodilation, hypotension, bradycardia and hypothermia (FX of body temp regulation). Autonomic hyperreflexia (dysreflexia) is a syndrome of sudden, life threatening massive reflex sympathtic discharge associated with spinal cord injury at level T6 or above where descending inhibition is blocked. Characteritics include: paroxysmal hypertension (systolic up to 300mmHG), pounding headache, blurred vision, sweating above the lesion with flushed skin, nasal congestion, nausea, piloerection caused by pilomotor spasm and bradycardia (30 -40 bpm). Dysreflexia is elicited by stimulation of sensory receptors below the site if injury (i.e. distended rectum or bladder).Emptying of the bladder of the bowelusuaolly relieves the syndrome and HOB should be elevated. Temperature fluctuation: Following spinal cord injury relates to damage of the sympathic nervous system that causes faulty control of sweating and radiation through capillary dilation. The hypothalamus cannot regulate body heat through vasoconstriction and increased metabolism; therefore, the individual assumes the temperature of the air.

What is schizophrenia? What part of the brain is associated with the S/S of this disorder? CH 19 pg 601-603

Schizophrenia - definition, part of brain associated, and prenatal and perinatal contributing factors(p. 642-647) Schizophrenia is a serious psychiatric illness that strikes 1% of the population; equally prevalent in males and females, emerging in young adults during late teens and early twenties. The term was coined by Eugen Bleuler in 1911 to describe a collection of illnesses characterized by thought disorders, reflecting a break in reality or splitting of the cognitive from emotional side of personality. (+) symptoms include auditory hallucinations, paranoid delusions, formal thought disorder, and bizarre behavior. (-) symptoms are flat affect, alogia (lack of speech), anhedonia (absence of pleasure), attention deficits and apathy. Prenatal & Perinatal Contributors & Parts of brain associated Early development may involve issues from environmental factors (viral infection during pregnancy, prenatal nutritional deficiencies, prenatal birth complications, and perinatal complications such as birth defects and neonatal hypoxia) which may interfere with genetic programming of neural development leading to alterations in brain structure and function. There is a strong genetic component. Structural brain abnormalities present on imaging. Enlargement of cerebroventricles and widening of fissures and sulci in frontal cortex. Reduction in the volume of the thalamus, disrupting communication among cortical brain regions, and the TEMPORAL LOBE, which may be RESPONSIBLE FOR MANIFESTATIONS OF POSITIVE SYMPTOMS. Frontal lobe has a progressive loss of volume and worsening of negative symptoms even with use of antidepressants. Functional alterations in the dorsolateral prefrontal cortex, (reduced blood flow and metabolism) compromise abilities to engage in goal-directed and cognitive problem - solving behavior. Abnormalities of Schizoid brains is in the neurochemicals dopamine and excitatory amino acid neurotransmission.Structural brain abnormalities present on imaging include enlargement of lateral and third ventricles and widening of the frontocortical fissures and sulci. With cerebral ventricular changes, the patient is likely to have cognitive impairments and negative symptoms. They also respond poorly to treatment. With temporal lobe alterations, patient has positive symptoms. With dorsal prefrontal cortex changes, negative symptoms are present. Especially with dorsolateral prefrontal cortex (DLPFC), initiation and maintenance of goal oriented activities and solving cognitive problems in relation to working memory is impaired

Know when the neural tube forms during embryonic development. CH 20 pg 619

The central nervous system develops from a dorsal thickening of the ectoderm known as the neural plate. This plate appears around the middle of the third gestational week and unfolds to form a neural groove and neural folds. During the FOURTH gestational week then neural groove deepens, its folds develop laterally, and it closes dorsally to form the neural tube, epithelial tissue that ultimately becomes the CNS. The neural tube closes first in the cervical region and then "zippers" in two directions - cranially and caudally.

Discuss the types of mid-brain dysfunction and its physical symptoms. find page number

The midbrain is part of the brainstem. The midbrain is composed of three structures: 1.)corpora quadrigemina (composed of the superior and inferior colliculi), 2.) tegmentum (containing the red nucleus and substantia nigra) 3.) basis pedunculi. The superior colliculi are involved with voluntary and involuntary visual motor movement. Inferior colliculi involve movement affecting the auditory system (moving the head to improve sound). The red nucleus is a major motor output center that is influenced by the cerebellum. Substantia nigra: Most inferior part of the basal ganglia (corgus striatum, globus palidus, subthalamic nucleus, and sustantia nigra); synthesizes dopamine which is a neurotransmitter and precursor of norepinephrine. Its dysfunction is associated with Parkinson Disease and drug addiction. Parkinson disease is a complex motor disorder accompanied by systemic nonmotor and neurologic symptoms. The main disease feature is degeneration of the basal ganglia which include the substantia nigra. Hallmark feature of PD is loss of dopaminergic pigmented neurons in the substantia nigra pars compacta with dopaminergic deficiency in the putamen portion of the striatum. Degeneration of the dopaminergic nigrostriatal pathway to the basal ganglia results in underactivity of the direct motor pathway and over activity of the indirect motor loop. This results in inhibition of the motor cortex manifested with bradykinesia and rigidity. Classic symptoms are bradykinesia (poverty of associated and voluntary movements), tremor at rest, rigidity (muscle stiffness), hypoakinesia (poverty of movement), and postural abnormalities. (p. 459, 564 7th ed) Other notable structures of this region are the nuclei and tracts of the third and fourth cranial nerves. The cerebral aqueduct (aqueduct of Sylvius), which carries CSF, also traverses this structure. The obstruction of this aqueduct is often the cause of hydrocephalus.Hydrocephalus occurs because of interference with CSF flow caused by increased fluid production, obstruction within the ventricular system, or defective reabsorption of the fluid. Symptoms include the person deteriorating rapidly into a deep coma or it might develop slowly overtime. An unsteady, broad gate with a history of falling is common. Apathy, inattentiveness, urinary incontinence, and indifference to self, family, and the environment

What is the medical significance of a seizure? Ch 17 pg 526

The onset of seizures may point to the presence of an ongoing primary neurological disease, etiologic factors, and seizures include: 1. Cerebral lesions 2. Biochemical disorders 3. Cerebral trauma 4. Epilepsy Conditions that may produce a seizure or metabolic defects congenital malformations genetic predisposition, prenatal injury, postnatal trauma, myoclonic Syndromes infection brain tumor and vascular disease. It may also be precipitated by hypoglycemia, fatigue, lack of sleep, emotional or physical stress, fever, large amounts of water ingestion hyponatremia, constipation, use of stimulant drugs, withdrawal from depressant drugs or alcohol hyperventilation or respiratory alkalosis. Some environmental stimuli such as blinking lights poorly adjusted television screens, loud noises, certain odors are merely being startled

Know different clinical descriptions of pain (acute, chronic, neuropathic); pain threshold/tolerance CH 16 pg 473-474

Acute Pain: A normal protective mechanism that alerts the individual to a condition or experience that is immediately harmful to the body and mobilizes the individual to take prompt action to relieve it; transient, usually lasting seconds to days and sometimes up to 3 months. It begins suddenly and relieved after the chemical mediators that stimulate pain receptors are removed. Acute pain arises from cutaneous and deep somatic tissue, or from visceral organs and can be classified as acute somatic, acute visceral, and referred. 1: Somatic Pain: arising from muscle, bone, joints and skin; either sharp and well-localized (esp fast pain carried by A-delta fibers), or dull, aching, throbbing, and poorly localized as seen in polymodal C fiber transmissions. 2: Viceral Pain: is transmitted by C fibers and refers to pain in the internal organs and lining of body cavities w/ aching, gnawing, throbbing, or intermittent cramping quality. Transmitted by sympathetic afferents and is poorly localized b/c of the lesser # of nociceptors in visceral structures. Assoc. w/ N/V, hypotension, restlessness, and in some cases, shock. It often radiates (spreads away from the actual site of the pain) or is referred. 3. Referred Pain: Pain felt in an area removed or distant from its point of origin. The area of referred pain is supplied by the same spinal segment as the actual site of pain. Impulses from many cutaneous and visceral neurons converge on the same ascending neuron, and the brain cannot distinguish between the two. Because the skin has more receptors the painful sensation is experienced at the referred site instead of the site of origin. Referred pain can be acute or chronic. Chronic Pain: Usually defined as lasting more than 3-6 months and pain lasting well beyond the expected healing time following the initial onset of tissue damage or injury. Chronic or persistent pain serves no purpose, is poorly understood, to often accompanied by anxiety, depression, and causes suffering. It often appears to be out of proportion to any observable tissue injury; it may be ongoing, or intermittent. Changes in the peripheral and central nervous systems that cause dysregulation of nociception and pain modulation processes are thought to lead to chronic pain. Neuroimaging studies have demonstrated brain changes in those with chronic pain that may lead to cognitive deficits and decreased ability to cope with pain. 1. Neuropathic pain is chronic pain initiated by primary lesion of dysfunction in the nervous system and leads to long term changes in pain pathway structures and abnormal processing of sensory information. neuropathic pain is often described as boring, shooting, shock-like, or tingling. it is characterized by hyperalgesia, increased sensitivity to a normally painful stimulus( touch, pressure, pinprick, cold and heat) or allodynia, the induction of pain by normally non painful stimuli. Neuropathic pain is classified as with periperhral or central and is associated with central and peripheral sensitization. 1A. peripheral neuropathic pain: is caused by peripheral nerve lesions and an increased in sensitivity and excitability of primary sensory neurons and cells in the the dorsal root ganglion (peripheral sensitization). ex nerve entrapment, diabetic neuropathy, or chronic pancreatitis. 2A. central neuropathic pain is caused by lemon or neuroplastic changes in the brain or spinal cord. Progressive repeated stimulation of group c neurons (wind up) in the dorsal horn leads to increased sensitivity of central pain signaling neurons (central sensitization) This results in pathologic changes in the CNS that cause chronic pain. ex: brain or spinal cord trauma, tumors, vascular lesions, MS, Parkinson disease, phantom limb pain and postherpetic neuralgia. Pain Threshold: Pain threshold is the point at which a stimulus is perceived as pain and it does not vary significantly among people or in the same person over time. Intense pain at one location may cause an increase in threshold in another location. For example, a person w/ severe pain in one knee is less likely to experience chronic back pain that is less intense; this is called perceptual dominance. Because of this pain at one site may mask other painful areas. Pain Tolerance: Pain tolerance is the duration of time or intensity of pain that an individual will endure before initiating overt pain responses and is generally decreased w/ repeated exposure to pain. Pain tolerance is influenced by the person's cultural perceptions, expectations, role behaviors, physical and mental health, gender, age fatigue, anger, boredom, apprehension and sleep deprivation. Tolerance may be increased by alcohol consumption, persistent use of pain medication, hypnosis, warmth, distracting activities, and strong beliefs or faith.

Know the characteristics of closed head injury. CH 18 pg 552

Are specific, grossly observable skull and brain lesions that occur in a precise location. Injury to the cranial vault , vessels and supporting structures can produce more severe damage, including contusions and epidural, subdural, subarachnoid and intracerbral hematomas. . The Dura mater remains intact, and brain tissues are not exposed to the environment. Compression of the skull at the point of impact produces contusions or brain bruising from blood leaking from an injured vessel. injury may be coup (injury at site of impact) or countercoup ( injury from brain rebounding) or both. •The smaller the area of impact, the more sever the injury because of the concentration of force. •brain edema from around and in damaged neural tissues, con tributing to increased ICP. •multiple hemorrhages, edema, infarction and necrosis can occur within the contused areas. •contusions are found most commonly in the frontal lobes • they cause changes in attentions, memory, executive function, affect, emotions and behavior. A closed brain injury may be evidenced by immediate (generally accepted to last no longer than 5 minutes) loss of consciousness, loss of reflexes (individual falls to the ground), transient cessation of respiration, brief period of bradycardia and decrease in blood pressure (lasting 30 sec to few minutes) Increased CSF pressure and ECG and EEG changes occur. on impact. Vital signs may stabilize to normal in a few seconds reflexes then return and the person regains consciousness over minutes to days. Residual deficits may persist, some may never regain a full level of consciousness.

Know characteristics of AV malformation. CH 18 pg 571-572

Arteriovenous malformation (AVM) is a mass of dilated vessels between the arterial and venous systems (arteriovenous fistula) that lack a muscular layer and have the absence of an intervening capillary bed. They can cause hemorrhagic stroke, epilepsy, chronic HA, or focal neurologic deficits. Patho: AVMs are developmental abnormalities that represent persistence of embryonic patters of blood vessels, do not have a normal blood vessel structure, and are abnormally thin. Their size is variable. The direct shunting of arterial blood into the venous vasculature without the dissipation of the arterial blood pressure increased risk for rupture. Over or several arteries may feed the AVM, and over time , they become tortuous and dilated. With moderate to large AVMs, sufficient blood is shunted into the malformation to deprive surrounding tissue of adequate blood perfusion. Clinical Manifestation: 20% of people with AVM have a characteristic chronic nondescript headache, although some experience migraine;50% experience seizure disorders caused by compression. The other 50% suffer an intracerebral, a subarachnoid, or a subdural hemorrhage with progressive neurological deficits. Bleeding from an AVM into the subarachnoid space causes clinical manifestation identical to those associated with a ruptured aneurysm. If bleeding is into the brain tissue, focal signs that develop over a short period of time. 10% of person experience hemiparesis or other focal signs. Hemiparesis usually is caused by compression or rupture. At times non-communicating hydrocephalus develops with a large AVM that extends into the ventricle lining. AVM accounts for up to 1% of all sudden deaths. Evaluation and Tx: systolic bruit over the carotid in the neck, the mastoid process, or (in a young person) the eyeball is almost always diagnostic of an AVM. Confirming diagnosis is made from CT, and MRI followed by MRA (magnetic resonance angiography) Treatment options are direct surgical incision end-vascular embolization or radiotherapy.

Define dyskinesia. Types? Characteristics? CH 17 pg 534-536

Dyskinesia -Uncontrolled, involuntary muscle movement. Unnatural movements that occur w/ variety of CNS dysfunctions which alter muscular innervation; neurotransmitter dopamine plays a role in motor function. Some movement disorders result from too little dopaminergic activity where as other result from too much dopaminergic activity; all related to dopamine function. Movement disorders are not associated with necessarily mass, strength or tone, but are neurologic dysfunctions with either an excess of movement or lack of voluntary movement. Hyperkinesia: excessive, purposeless movement (chorea, athetosis, ballism, hyperactivity, wandering, akathisia, Parkinsonian Tremor, asterixis, cerebellar, rubral, myoclonus) (Huntington's disease is hallmark for this) Paroxysmal dyskinesia: abnormal, involuntary movements that occur as spasms Tardive dyskinesia: involuntary movement of the face, trunk, and extremities. Usually occurs as a side effect of prolonged use of first or second generation antipsychotic drugs that cause denervation hypersensitivity, thereby mimicking the effect of excessive dopamine. The most common symptom of TD is rapid, repetitive, stereotypic movements, such as continual chewing with intermittent protrusions of the tongue, lip smacking, and facial grimacing. Other movement disorders with this are (1) complex repetitive movements, including automatism (unconscious behavior) , stereotypy (ritulistic behavior such as rocking) complex tics such as Tourette syndrome, compulsions, preservations, and (3) paroxysmal excessive activity, including cataplexy and excessive startle reaction. Hypokinesia: (decreased movement) is decreased amplitude of movement more specifically. Overall is a loss of voluntary movement despite preserved consciousness and normal peripheral nerve and muscle function. Bradyinesia: is decreased speed of movement; slowness of voluntary movements. All voluntary movements become slow, labored and deliberate with difficulty in (1) initiating movements,(2) continuing movements slowly, and (3) performing synchronus (at the same time) and consecutive tasks. Akinesia: is absence of voluntary movement. A decrease in voultary and associated movements. It is related to dysfunction in the extrapyridiamal system and caused by either a deficiency in dopamine or a defect of the postsynaptic dopamine receptors which occurs in Parkinson's. -both akinesia and bradykinesia involve a delay in the time it takes to start to perform a movement. -all terms that represent a deficit of voluntary movement. Parkinson disease symptoms are hallmark of lack of voluntary movement.

How Does ECT (electroconvulsive therapy) treat depression? CH 19 pg 609

ECT is used when individuals fail to respond to antidepressants or when they are severely depressed, pregnant, suicidal, or psychotic. ECT effectively alleviates depressive symptoms in 50-80% of people who then may begin to respond to antidepressant medications. ECT increases the volume of the hippocampus and amygdala, brain structure linked to emotion, mood and cognitive functions. Depressed people with relatively small hippcampal volumes were most likely to show hippocampal volume increases and improved clinical response after ECT. Neutriptopic processes activated bt ECT, including neurogenesis, may underlie these structural changes and clinical benefits. Electrodes are implanted into the subcallosal cingulate gyrus (SCG) and attached to an implanted pulse generator through SQ extension wires. The SCG is targeted because abnormal SCG brain activity, a suggested pathophysiologic cause of major depression, is reversed by effective antidepressant treatment.

Define encephalocele, meningocele, spina bifida, myelomeningocele. Where is the defect located in each? CH 20 pg 621

Encephalocele - definition and location of defect(p. 664) a herniation or protrusion of the brain and meninges through a defect in the skull, resulting in a sac like structure. Encephalocele occurs during the first weeks of pregnancy. When the defect contains only meninges, it is referred to as a cranial meningocele. Most encephaloceles occur in the occipital area, with the remainder found in the frontal, parietal, or nasopharyngeal regions Meningocele - definition and location of defect(p. 664) Type of spina bifida; saclike cyst of meninges filled with spinal fluid. It develops during the first four weeks of pregnancy when the neural tube fails to close completely. Meningocele is a structural anomaly of the posterior arch of the vertebra. The cystic dilation of meninges protrudes through the vertebral defect and around the malformed tube. The dura mater may be missing and the arachnoid layer of the meninges bulges beneath the skin. This defect does not involve the spinal cold. Meningoceles occur with equal frequency in the cervical, thoracic and lumbar spines. At birth the infant has a protruding sac on the back at level of the defect. Spina bifida - definition and location of defect(p. 664-666) When defects of the neural tube closure occur, such as meningocele or myelomenigocele, an accompanying vertebral defect allows the protrusion of the neural tube contents. This defect is called spina bifida (split spine). The cause of spina bifida is unknown. Periconceputal maternal folate deficiency and genetic alternations are commonly associated with the defect. It is also possible for the defect to occur without any visible exposure of meninges or neural tissue. This is referred to as spina bifida occulta. In spina bifida occulta the posterior vertebral laminae have failed to fuse. 80% of these vertebral defects are located in the lumbosacral regions, most commonly in the 5th lumbar vertebra and the first sacral vertebra Myelomeningocele - definition and location of defect(p. 665) Type pf spina bifida more common than meningocele and one of the most common developmental anomalies of the nervous system; cystic dilation of meninges and protuberance of various amounts of the spinal cord through the vertebral defect and assoc. w/ more severe complications than a meningocele. D/t changes in CSF flow, they are likely to be assoc. w/ a Chiari II malformation (downward placement of the cerebellum, brainstem, and fourth ventricle). The Chiari II compresses and stretches the posterior region of the cerebellum and brainstem downward through the foramen magnum ⇒ hydrocephalus, ↑ ICP from obstructed CSF flow, syringomyelia (causes cysts at multiple levels of spinal cord), and cognitive and motor deficits. *Location is evident at birth as a defect on the infant's back, 80% are located on in the lumbar and lumbosacral region, the last region to close up.

Know endogenous opioids. CH 16 pg 472-473

Endogenous opioids (p.490) a family of morphine-like neuropeptides that inhibit transmission of pain impulses in the spinal cord, brain, and periphery. They also have a role in various CNS, GI, immune system, and other organ system disorders. In addition to analgesic effects, endogenous opioids are involved in a variety of other functions throughout the body, including modulation of stress and anxiety, feeding behavior, cough suppression, immune and inflammatory responses, and alcohol intake. Endogenous opioids of one type or another are found to bind to almost all tissues in the. body and thus affect numerous biological functions. There are four types of neuropeptides: (1) enkephalins, (2) endorphins, (3) dynophines, (4) endmorphins - These neurohormones act as neurotransmitters by binding to one or more G-protein coupled opioid receptors. There are there specific types of neuro opioid receptors (Kappa, delta, mu) A fourth receptor subtype is nociception-opiod peptide (NOP) and its ligand is nociceptin/orphanin FQ - each receptor type binds differntly with the various types of opioids. They inhibit ion channels in the dorsal horn, preventing the release of excitatory neurotransmitters , such as substance P and glutamate, or other of the brain such as the PAG or rostral ventromedial nuclei in the brainstem. Enkephalins—2 types: Met-enkephalin and Leu-enkephalin and their ratio is 4:1, respectively. They are the most prevalent of the natural opioids and bind to delta opioid receptors. They are found concentrated in the hypothalamus, the PAG matter, the nucleus raphe magnus of the medulla, and the dorsal horns of the spinal cord. Endorphins— (endogenous morphine). These are produced in the brain. B-endorphin binds to mu receptors in the hypothalamus and pituitary gland. The synthesis and activity of B-endorphin are concentrated in the hypothalamus and the pituitary gland. It is purported to produce a greater sense of exhilaration than all of the other endorphin types and most natural pain relief. Endomorphins 1 and 2 bind with mu receptors throughout the brain , brainstem and GI tract and have analgesic and anti-inflammatory effects. Dynorphins—Are the most potent of the endogenous neurohormones and binds strongly with kappa receptors to impede pain signals in the brain. They play a role in mood disorders and drug addiction and paradoxically in stimulating chronic pain. Nociceptin/orphanin FQ produces antiopioid hyperalgesic effects in the supraspinal pain pathways, while excepting analgesic properties in spinal pain pathways. It does not interact with opioid receptors. The nociceptin receptor is widely distributed throughout the peripheral and central nervous system; is associated with inflammation, immune regulation, feeding behavior, and mood elevation, and blunts addictive behavior.

Know the best prognostic indicator of recovery of consciousness and functional outcome after a brain event. find page number

Evaluation is based on history, LOC using the Glasgow Coma Scale, imaging (CT, MRI, PET), and assessment of vital parameters (ICP and EEG). Glasgow Coma Scale (used to assess severity of injury); *hallmark of severe TBI is loss of consciousness for 6 hours or more. (1) Mild TBI w/ mild concussion = score of 13-15; (2) moderate TBI w/ structural injury such as hemorrhage or contusion = score of 9-12; (3) severe TBI w/ cognitive and/or physical disability or death = score of 3-8. An isoelectric, or flat, EEG (electrocerebral silence) for 6-12 hours in a person who is not hypothermic and has not ingested depressant drugs indicates that no mental recovery is possible; the brain is dead Alterations in arousal - determine extent of brain dysfunction and identify ↑ or ↓ CNS function: Level of consciousness - most critical clinical index of nervous system function/dysfunction. Pattern of breathing - evaluates level of brain dysfunction; rate, rhythm, and pattern should be assessed. Pupillary changes - valuable guide to evaluate presence/level of brainstem dysfunctionOculomotor responses - resting, spontaneous, and reflexive eye movements and oculovestibular (caloric) reflexes change at various levels of brain dysfunction. (*All of these are on p. 505-511) Motor responses - evaluates the level of brain dysfunction and determining side of brain that is maximally damaged; responses may be purposeful, inappropriate, or not present.

Define generalized anxiety disorder. What is the underlying defect? Know characteristics. CH 19 pg 611-612

Excessive and persistent worries are the hallmarks in GAD. Worries about life events, marital relationships, job performance, health, money, or social status. The prevalence rate is 4.1-6.6% and higher rate in women. GAD emerges in early twenties but also can occur in childhood. There are 6 major symptoms: restlessness, muscle tension, irritability, easily fatigued, difficulty concentrating, and difficulty sleeping. They suffer from depression and panic attacks. GAD tends to be chronic, but may lessen with age. Substance abuse is a frequent complication (drug and alcohol to self-medicate). This is caused by abnormalities in norepinephrine and serotonin systems that include: reduction in a2-adrenergic receptor binding, decreased serotonin levels in CSF, a reduction in platelet binding paroxetine, an SSRI. Also a reduction of BZ binding in left temporal hemisphere. GAD is diagnosed when a person spends at least 6 months worry excessively and engages in at least 3 of the 6 major symptoms. 5-HT/norepinephrine reuptake inhibitors, such as venlafaxine or the SSRIs paroxetine and escitalopram, have become first-line therapeutics for management of GAD.

What is the function of the CSF? Where is it produced? Where is it absorbed? CH 15 pg 450

Is a clear colorless fluid. the intracranial and spinal cord structures float in CSF and are thus protected by this fluid from jolts and blows. The buoyant properties of CSF also prevent the brain from tugging on the meninges , nerve roots, and blood vessels. Aprox 600 ml of CSF is produced daily. The choroid plexus in the lateral, third and fourth ventricles produce the major portion of CSF. The CSF exerts pressure within the brain and spinal cord. CSF flor results from the pressure gradient between the arterial system and the CSF filled cavities. Beginning in the lateral ventricles the CSF flows through the intraventricular foramen into the third ventricle and then pass through the cerebral aqueduct into the fourth ventricle. From the ventricle , the CSF may pass through either the paired lateral apertures or the median aperture before communicating with the subarachnoid spaces of the brain and spinal cord. CSF is produced continually but does not accumulate. Instead it is reabsorbed in the venous circulation through a pressure gradient between the arachnoid villi and the cerebral venous sinuses. Thus the CSF is formed from the blood and, after circulating throughout the CNS it returns to the blood.

Know pathophysiology, clinical manifestations and etiology of PKU. CH 20 pg 629

Is an inborn error in the metabolism of amino acids, is characterized by phenylalanine hydroxyls deficiency and results in the inability of the body to convert the essential amino acid phenylalanine to tyrosine. PKU is an autosomal recessive characterized by mutations of the phenylalanine hydroxylase (PAH) gene. Pathophysiology - Characterized by mutations of the phenylalanine hydroxylase (PAH) gene. Most natural food proteins contain about 15% phenylalanine. Loss of PAH results in phenylalanine hydroxylase deficiency and the inability of the body to convert the amino acid phenylalanine to tyrosine. It is the accumulation of phenylalanine that causes damage to the CNS. Clinical Manifestations - When a baby born with PKU and begins a regular diet high in phenylalanine, buildup occurs, brain growth slows, and the child exhibits developmental delays or intellectual disability, concomitant with jerking movements, seizures, skin rashes and attention problems. Children with PKU have a phenotype that includes blonde hair, blue eyes and fair skin- due to the biosynthesis of melanin. Individuals with PKU need to be screened for response to BH4, which decreases blood phenylalanine levels when given an oral supplement. Treatment - restriction of phenylalanine in the diet and supplementation with other essential amino acids. Treatment must be continued for life and strict adherence for pregnant women.

Define the different stages of sleep. CH 16 pg 483-484

Normal sleep has two phases that can be documented by EEG: REM (rapid eye movement) and non-REM, or slow wave sleep. The first cycle of the night begins with N1, then to N2 and N3 and REM sleep. A new cycle beginning with N2 follows each REM sleep,; with each successive cycle, the amount of time spent in N3 decreases and the amount of time spent in REM sleep increases. The person who is awakened begins the next cycle at N1. NREM sleep is divided into 3 stages, based on changes in EEG patterns: (N1, N2, N3) The phases of sleep are based on changes in the EEG pattern. o awake: wakefulness with eyes closed and predominated by alpha waves (8-25 Hz) NREM Sleep: o N1 - light sleep with alpha waves (6-8 Hz) interspersed with low frequency theta waves; slow eye movements , cycle lasts about 1- to 12 minutes (3-8% of sleep time) o N2 - further slowing of the EEG (4-7 Hz) with the presence of sleep spindles and slow eye movements; cycles last 30 to 60 min(45-55% of sleep time) o N3 - low frequency (1-3 Hz) high amplitude delta waves with occasional sleep spindles; no slow eye movements (13-23% of sleep time) REM sleep: Time of most dreaming (20-25% of sleep time); occurs about every 90 minutes beginning after 1-2 hours of NREM sleep begins; characterized by conjugate rapid eye movement in all directions. Inititiated by REM-on and REM-off neurons in the pons and mesencephalon. REM-on uses the transmitter gamma-aminobutyric acid (GABA), glycine, acetylcholine, and glutamate. REM-off cells use the transmitters norepinephrine, epinephrine, serotonin, histamine, and GABA Non-REM (NREM) slow wave sleep is initiated when inhibitory signals are released from the hypothalamus. Sympathetic tone is decreased and parasympathetic activity is increased during NREM sleep, creating a state of reduced activity.

Define panic disorder. What are the complications? CH 19 pg 611-612

Panic disorder consists of multiple disabling panic attacks and is characterized by intense autonomic arousal involving wide variety of symptoms: light headedness, rapid heart rate, difficulty breathing, chest discomfort, generalized sweating, general weakness, trembling, abdominal distress, chills or hot flashes. Between panic attacks, individuals worries about future panic attacks and fear of losing control or dying. Symptoms occur spontaneous and vary in length from several minutes to hours. A notable complication from panic disorder is the development of agoraphobia or phobic avoidance of places or situations where escape or help is not readily available. They avoid being away from home, standing in lines, crowds, traveling in a train, plane, or automobile. Severe agoraphobia individuals become housebound.

Where is the primary defect in Parkinson's disease and Huntington's?

Parkinson Disease, where is the primary defect? (p.564) The main disease feature is degeneration of the basal ganglia (corpus striatum, globus pallidus, subthalmic nucleus, and substantia nigra) involving the dopaminergic nigrostriatal pathway. Huntington Disease - where is the primary defect? (p.562) The principal pathologic feature of HD is severe degeneration of the basal ganglia, particularly the caudate and putamen nuclei and the frontal cerebral cortex. The degeneration of the basal ganglia leaves enlarged lateral ventricles.

Define and describe the pathophysiology, clinical manifestations and etiology of Parkinsons disease. CH 17 pg 536-538

Parkinsons Disease (PD) is a complex motor disorder accompanied by systemic nonvoter and neurologic symptoms. Etiologic classification of Parkinsonism includes primary and secondary Parkinsonism. Pathophysiology: The hallmark pathologic features of Parkinson disease are loss of dopaminergic pigmented neurons in the substantia nigra (SN) pars compacta with dopaminergic deficiency in the putamen portion of the striatum (the striatum includes the putamen and caudate nucleus). Dopamine loss in other brain areas including the brainstem, thalamus, and cortex also occurs. Degeneration of the dopaminergic nigrostriatal pathway to the basil ganglia results in underactivity of the direct motor pathway (normally facilitates movement) and over activity also influences the limbic system accounting for emotional signs and symptoms. Neuronal loss within the cerebral cortex is found in one half of individuals with PD. Manifestations: Onset of symptoms is insidious and symptoms appear after 70% to 80% loss of pigmented nifral neurons and loss of 60% to 90% of striatal dopamine. The classic motor manifestations of PD are bradykinesia, tremor at rest (resting tremor), rigidity (muscle stiffness), hypoakinesia (poverty of movement), and postural abnormalities. These manifestations may develop alone or in combinations, but as the disease progresses, all four are usually present to at least some degree, there is no true paralysis. Etiology: Etiologic classifications of parkinsonism includes primary parkinsonism and secondary parkinsonism (BOX 17-5 on p. 565 gives all of the causes of each). The onset of PD occurs after 40 years of age, with mean onset of 60 years of age. Equal incidence occurs in both sexes. PD is one of the most prevalent of the primary CNS disorders and a leading cause of neurologic disability in individuals older than 60 years. Evaluation & Treatment: The diagnosis of PD is made on the basis of the four cardinal symptoms: resting tremor, cogwheel rigidity, akinesia, and postural instability.The aim of treatment is to restore striatal dopamine levels using oral drugs such as levodopa, a precursor of dopamine.

Know diagnostic criteria for vegetative state and brain death. CH 17 pg 510-511

Persistent Vegetative State (VS) or unresponsive wakefulness syndrome is complete unawareness of the self surrounding environment and complete loss of cognitive function. Diagnostic Criteria: 1) does not speak any comprehensible words or follows commands 2) sleep wake cycles are present, eyes open spontaneously and blood pressure and breathing are maintained without support 3) Brain stem reflexes (pupillary, oculocephalic, chewing, swallowing) are intact but cerebral function is lost 4). there may be random hand, extremity or head movements 5). recovery is unlikely if state persists for 12 months Brain death (total brain death) occurs when brain damage is so extensive that ic can never recover (irreversible) and cannot maintain the body's internal homeostasis. An isoelectric, or flat, electroencephalogram (EEG) (electrocerebral silence) for a period of 6-12 hours in a person who is not hypothermic and has not ingested depressant drugs indicates that no mental recovery is possible and usually means that the brain is already dead. Brain death in children has same criteria as adults but a longer observation period. Summary of criteria: 1. Completion of all appropriate and therapeutic procedures w/ no possibility of brain function recovery 2. Unresponsive coma (absence of motor and reflex movements) 3. no spontaneous respiration (apnea)—a PaCO2 that rises above 60 mmHg without breathing efforts, providing evidence of a nonfunctioning respiratory center (apnea challenge) 4. No brainstem function (ocular responses to head turning or caloric stimulation; dilated, fixed pupils; no gag or corneal reflex) 5. Isoelectric (flat) EEG (electrocerebral silence)6. Persistence of these signs for 30 mins- 1hour and for 6 hours after onset of coma and apnea 6. Persistence of these signs for an appropriate observation period

Know patterns of breathing with head injuries. CH 17 pg 506

Respiratory patterns help evaluate the level of brain dysfunction and coma. Breathing patterns can be categorized as hemispheric or brainstem. With normal breathing, a neural center in the forebrain (cerebrum) produces a rhythmic breathing pattern. When consciousness decreases, lower brainstem center regulate the breathing pattern by responding only to changes in PaCO2 levels, called post hyperventilation apnea (PHIVA) Cheyne-Stokes respiration is an abnormal rhythm of ventilation (periodic breathing) with altering periods of hyperventilation and apnea (crescendo-decresendo pattern). In the damaged brain, higher levels of PaCO2 are required to stimulate ventilation, and increased in PaCO2 lead to tachypnea. The PaCO2 level then decreases to below normal, and breathing stops (apnea) until the CO2 accumulates again stimulates tachypnea. Central Neurogenic hyperventilation is a respiratory pattern of sustained hyperventilation caused by a lesion in the central pons. Apneustic respirations have prolonged inspiratory and expiatory phases caused by injury to the pons or upper medulla. Cluster respirations are characterized by periods or clusters of rapid respirations of near equal death resulting from trauma or compression to the medulla from chronic opioid abuse. Ataxic respirations are irregular respirations with prolonged periods of apnea associated with damage to the medulla.

Define seizure and status epilepticus. What is the medical significance? Know benign febrile seizures. CH 17 pg 524 CH pg 634

Seizure disorders are sudden, transient disruption in brain electrical function caused by abnormal excessive discharges of cortical neurons. Are autonomous discharge of electrical activity within the brain. When. a sufficient number of neurons become overexcited, they discharge abnormally which can result in seizures and cause alterations in motor function, sensation, autonomic function behavior and consciousness. Benign febrile seizure(p.526/635) They are defined as seizures associated with fever in the absence of CNS infection. Most common childhood syndrome. Common in children younger than 5 to 6 years of age; brief (less than a few minutes) generalized convulsions associated with high fever; important to exclude meningitis as cause of seizures; usually do not develop epilepsy. Pathogenesis is unknown; a familial incidence indicates a genetic predisposition. Contributing factors are age, degree and rate of temperature elevation, and nature of the particular fever-inducing illness. 1. simple febrile seizures sally occur between 3 months and 5 years of age. 2. the convulsion occurs with a rise in temp to greater than 39 C or 102.2 F. 3. Acute respiratory tract infection or ear infection is present, not a CNS infections 4. most seizures occurs in the first 24 hrs of illness. 5. the collusion is short 15 min or less, generalized and more predominantly tonic. 6. interical (period between seizures) on EEG is normal 7. The seizure normally does not reoccur during the same infection 8. no acute systematic metabolic disorder is present. Status epilepticus (p.526) Continuing or recurring seizure activity in which recovery from seizure activity is incomplete; unrelenting seizure activity can last 30 min or more, other forms can evolve into SE, it is a medical emergency that requires immediate intervention. In adults is a state of continuous seizure lasting more than 5 minutes, or rapidly reoccurring seizures before the person has fully regained consciousness from the preceding seizure, or seizure lasting more than 30 minutes. Status epilepticus can arise abnormal persistence of the excessive excitation or ineffective recruitment of inhibition

Review blood flow to the brain. pg 452 Ch 15

The brain derives its arterial supply from two systems: the internal carotid arteries (anterior circulation) and the vertebral arteries (posterior circulation) The internal carotid arteries supply a proportionaly greater amount of blood flow. They originate at the common carotid arteries, enter the cranium through the base of the skull and pass through the cavernous sinus. After entering the skull, these arteries divide into the anterior and middle cereal arteries. The vertebral arteries originate at the subclavian arteries and pass through the transverse foramina of the cervical vertebrae, entering the cranium through the foramen magnum. They join at the junction of the ins and medulla omblongata to form the basilar artery, the basil artery divides at the level of the midbrain to form paired posterior cerebral arteries. Three major paired arteries perfuse the cerebellum and brainstem: the posterior inferior cerebella artery, the anterior inferior cerbeller artery, and the superior cerebella arteries. They originate from the basilar artery. The basilar artery also gives rise to small pontine arteries. The large arteries on the surface of the brain and their branches are called superficial arteries. Small branches that project into the brain are term projecting arteries. The circle of willis provides an alternate route for blood flow when one the contributing arteries is obstructed. The circle of willis is formed by the posterior cerebral arteries , posterior communicating arteries, internal carotid arteries, anterior cerebral arteries, and anterior communicating artery. The anterior cerebral , middle cerebral, and posterior cerebral arteries leave the arterial circle and extend to various brain structures. Brain blood flow (p.467-469) The brain receives about 20% of the cardiac output. Carbon dioxide serves as a primary regulator for blood flow within the CNS as it is a potent vasodilator. The brain derives its arterial supply from two systems: the internal carotid arteries and the vertebral arteries.• Internal Carotid Arteries: o The ICAs supply blood to the anterior portion of the brain. They originate from the common carotid arteries, enter the cranium through the base of the skull, and pass through the cavernous sinus; after giving off some small branches, they divide into the anterior and middle cerebral arteries. • Vertebral Arteries:o The VAs supplies the posterior portion of the brain. They originate as branches off the subclavian arteries, pass through the transverse foramina of the cervical vertebrae, and enter the cranium through the foramen magnum. They join at the junction of the pons and medulla oblongata to form the basilar artery. • Basilar Artery: o Divides at the level of the midbrain to form paired posterior cerebral arteries. Three major paired arteries perfuse the cerebellum and brainstem and originate from the posterior arterial supply: the posterior inferior cerebellar artery, off the vertebral artery; and the anterior inferior cerebellar and superior cerebellar arteries, off the basilar artery. The basilar artery also gives arise to small pontine arteries. The large arteries on the surface of the brain and their branches are called superficial arteries. The small branches that project into the brain are termed projecting arteries. • Circle of Willis: o A structure credited with the ability to compensate for reduced blood flow from any one of the major contributors. Formed by the posterior cerebral arteries, posterior communicating arteries, internal carotid arteries, anterior cerebral arteries, and anterior communicating artery. *Cerebral venous drainage does NOT parallel its arterial blood supply; whereas the venous drainage of the brainstem and the cerebellum DOES parallel the arterial supply of the structures. The veins drain into the venous plexuses and dural sinus and eventually join the internal jugular veins at the base of the skull.

Which part of the brain controls movement of the eye? CH 17 pg 488

The optic nerve is composed of retinal cell axons. Nerve impulses pass through the optic never after leaving the retinas. The optic chasm the fibers from the inner halves of the retinas cross the opposite side, where they join fibers from the outer (temporal) halves of the retinas to form the optic tracts. The fibers of the optic tracts synapse in the dorsal lateral geniculate nucleus, and form the geniculocalcarine fibers pass by way of the optic radiation to the primary visual cortex in the occipital lobe of the brain. to understand vision. The brainstem: Pons. A deep part of the brain, located in the brainstem, the pons contains many of the control areas for eye and face movements.

Know the type of nerve fibers that transmit pain impulses. CH 16 pg 469-470)

The processing of potentially harmful (noxious) stimuli through a normally functioning nervous system is called nociception. Nociceptors are free nerve endings in the afferent peripheral nervous system that selectively respond to different chemical, mechanical and thermal stimuli. When stimulated they cause nociceptive pain. Nociceptors are unevenly distributed throughout the body, so the relative sensitivity to pain differs according to their location. For example fingertips have more nociceptors than the skin fo the back, and all skin has many more nociceptors than internal organs. Primary nociceptive afferents have the ability to detect a wide range of stimuli. To do this, nociceptors are equipped with an array of transduction channels that can sense different forms of noxious stimulation and at different intensities. Nociceptors are categorized according to the stimulus to which they respond and by the properties of the axons associated with them: A-delta fibers: lightly myelinated, medium-sized fibers that are stimulated by severe mechanical deformation and/or by extremes of temperature. These fibers rapidly transmit sharp, well-localized "fast" pain sensations and are responsible for casing reflex withdrawal of the affected body part from the stimulus. C-fibers: polymodal; stimulated by mechanical, thermal, and chemical nociceptors. They slowly transmit dull, aching, or burning sensations that are poorly localized and longer lasting. A-beta fibers: large myelinated fibers that transmit touch and vibration sensations. They do not normally transmit pain but do play a role in pain modulation.

Review the anatomy of the brain. Which portion is responsible for keeping you awake, controlling thought, speech, emotions and behavior, maintaining balance and posture? CH 15 pg 440

The three major structural divisions of the brain are 1) the forebrain (prosencephalon) which includes the telencephalon and diencephalon. 2) the midbrain (the mesencephalon, which connects the pons to the diencephalic;pn and the includes the corpora quadrigemina, tegmenjtum and cerebral peduncles; and 3). the hind brain (rhombencephalon), which connects the hemispheres of the brain, cerebellum and spinal cord. Reticular formation: is collection of nuclei within the brainstem collectively, and is a large network of diffuse nuclei that connect the brainstem to the cortex and control vital reflexes, such as CV function and respiration. It is essential for maintains wakefulness and attention and thus us referred to as the reticular activating system. Cerebral hemisphere: Part frontal lobe: prefrontal area is responsible for goal oriented behavior/ the ability to concentrate, short term memory recall, and the elaboration of thought and inhibition on the limbic (emotional) areas of the CNS. The premotor area is involved in programming motor movements. The Broca area in the inferior frontal lobe is an important center for speech and language processing. Injury to this area results in difficulty to form words (expressive aphasia/ or dysphasia) The hind brain: the cerebellum is responsible for reflexive, involuntary fine tuning of motor control and for maintaining balance and posture through extensive neural connections with the medulla and with the midbrain

Characteristics of Alzheimer's disease. CH 17 Pg 520-522

There are three forms of AD: nonhereditary sporadic (late onset AD), early onset familial AD (FAD) and early onset AD which is very rare . Occurs mostly in women Greatest risk factors are age and family history Other risk factors include diabetes, midlife hypertension, hyperlipidemia, midlife obesity, smoking, depression, cognitive inactivity, low educational attainment, female, estrogen deficit at time of menopause, physical inactivity, head trauma, neuroinflammation, high sodium homocysteine and cholesterol. Clinical Manifestations: Has a long preclinical and prodromal course and pathophysical changes can occur decades before the clinical symptoms of dementia syndrome occur. Progresses from mild short term memory deficits to total loss of cognition and executive functions. Initial clinical symptoms are attributed to forgetfulness, emotional causes, and other illness. A person becomes more forgetful over time more so in relation to current events. Memory loss increases as the disorder advances and the person becomes disoriented, confuses, and loses the ability to concentrate. Abstraction, problem solving and judgment gradually deteriorate with failure in mathematical calculation ability, language and visuospatial orientation. Dyspraxia occurs, mental status changes causes behavioral changes such as irritability, agitation and restlessness. Mood changes may also occur with depression, hostility, anxiety, emotionally labile, and mood swings. Motor changes may occur if posterior frontal lobes are involved causing rigidity flexion posturing. Weight loss can be significant Great variability in age of onset, intensity and sequence of symptoms and location and extent of brain abnormalities is common. See Table 17. 15 for progression of disease.