Study Guide Unit 2 Pathologic Alterations: Organs and Systems PDF

Study Guide Unit 2 Pathologic Alterations: Organs and Systems Afferent Afferent means towards Efferent means away from. vs. In this instance, it means either toward or away...

Study Guide Unit 2 Pathologic Alterations: Organs and Systems Afferent Afferent means towards Efferent means away from. vs. In this instance, it means either toward or away from the spine. Efferent Cerebral vs. Cerebellar CHAPTER 15 Key words: What nerves are capable of regenerating? (eBook key search term: “limited to myelinated fibers”) Mature neurons do not divide and injury in the CNS causes permanent loss of damaged neurons. Crushed nerves recover better than cut nerves. Peripheral nerves can repair themselves through axonal reaction  Local changes occur when the axon is severed 1. The cut ends retract and the axolemma covers the cut ends, diminishing the escape of axoplasm 2. Macrophages and Schwann cells begin to phagocytize damaged tissue 3. The cell body undergoes chromotolysis with swelling, loss of Nissl bodies, and the lateral migration of the nucleus 4. Antegrade (Wallerian) degeneration occurs in the distal axon 5. A characteristic swelling appears in the axon terminal and it degenerates and loses contact with the post synaptic membrane within 7 days 6. Macrophages and Schwann cells phagocytize the remnants of the axon terminal 7. Schwann cells proliferate, forming a column or tube of Schwann cells enclosed by the original basal lamina of the endoneurium. 8. Retrograde changes occur at the proximal end of the injured axon and are similar to antegrade changes but only back to the next node of Ranvier.  Approximately 7-14 days after the injury, new terminal sprouts project from the proximal segment guided by Schwann cells and enter the sustaining substrate of a more detailed representation of these events o This process is very slow, about 1mm/day, and is limited to myelinated fibers in the PNS. o The closer the injury is to the cell body of the nerve, the greater the chances that the nerve cell will die and not regenerate  o Peripheral nerves injured close to the spinal cord recover poorly and slowly because of the long distance between the cell body and the peripheral termination of the axon.  The regeneration of axonal constituents in the CNS is limited by an increased incidence of glial scar formation (gliosis) and the different nature of myelin formed by the oligodendrocyte  Nerve regeneration depends on many factors: 1. Location of the injury 2. The type of injury: crushing injury allows recovery more fully than does a cut injury a. Crushed nerves sometimes fully recover, whereas cut nerves often form connective tissue scars that block or slow regenerating axonal branches 3. The presence of inflammatory responses 4. The process of scarring Review the anatomy of the brain. (eBook key search term: “receives 15%”) The Brain: allows individuals to reason, function intellectually, express personality and mood, and interact with the environment.  Weighs approximately 3 lbs. but receives 15%-20% of total cardiac output THREE MAJOR DIVISIONS OF THE BRAIN Structural The Reticular Divisions of the Activating Brain System PRIMARY VESICLES SECONDARY VESICLES ASSOCIATED STRUCTURES FOREBRAIN (prosencephalon) Cerebral hemispheres Telencephalon Cerebral cortex Rhinencephalon (olfaction) Basal ganglia Epithalamus Diencephalon Thalamus Hypothalamus Subthalamus MIDBRAIN Mesencephalon Tectum (corpora quadrigemina) Connects the Pons to the diencephalon Tegmentum Red nucleus Substantia nigra Cerebral peduncles HINDBRAIN (rhombencephalon) Mentencephalon Cerebellum Pons Myelencephalon Medulla Oblongata BRAINSTEM Comprised of the midbrain, pons, and medulla oblongata Connects the left / right hemispheres, cerebellum, and spinal cord Reticular formation / reticular activating system SPINAL CORD Spinal Cord  CEREBRAL HEMISPHERES Functional areas of the cerebral cortex Left Hemisphere or cerebrum (lateral view) (midsagittal view) Functional areas of the cerebral cortex (lateral view) Cerebellum (posterior view); coordination of voluntary movement, balance, and posture  FOREBRAIN (prosencephalon) Telencephalon Frontal Lobe Prefrontal area Goal-oriented behavior, short term memory, concentration, elaboration of thought, and inhibition on limbic area (emotional region of the brain) Premotor area (Brodmann Programs motor movement (contains cell bodies that form part of the basal ganglia area 6) system - extrapyramidal system); controls eye movement (Brodmann area 8; middle frontal gyrus) Primary motor area Primary voluntary motor = somatotopic organization (Homunculus = little man); (Brodmann area 4) Cerebral cortex  central impulses control the opposite side of the body = contralateral control Broca speech area Motor aspect of speech; speech and language processing area; (Brodmann area 44, 45) dysfunction (damage from CVA) may result in inability to form words  expressive **most important in the left aphasia or dysphasia hemisphere Parietal Lobe Somatic sensory input Provides communication between motor and sensory areas; storage, analysis, and (Brodmann areas 3, 1, 2) interpretation of stimuli Temporal Lobe Primary auditory cortex (Brodmann area 41) Wernicke area Sensory speech area; responsible for reception and interpretation of speech (Brodmann area 22) (superior temporal gyrus); dysfunction / damage may result in receptive aphasia or dysphasia Secondary function of balance Memory consolidation and smell Occipital Lobe Primary visual cortex Receives input from the retinas (Brodmann area 17) Remainder of lobe Visual association (Brodmann areas 18, 19) Corpus Callosum Bundle of myelinated fibers that connects the two cerebral hemispheres (conveying contralateral projection) which is essential in coordinating activities between hemispheres Limbic System Located between the Mediates emotion and long-term memory through connections in the prefrontal cortex telencephalon and *Primitive behavioral responses and visceral reaction to emotion, feeding diencephalon and behaviors, biologic rhythms and sense of smell surrounding the corpus *Expression of affect (emotion and behavioral state)  mediated by connections callosum with limbic system and prefrontal cortex *Consolidation of memory  reverberating circuit Diencephalon (Interbrain) Surrounded by the cerebrum and sitting on top of the brainstem; has four divisions Epithalamus Forms the roof of the 3rd Controls vital functions and visceral activities ventricle; composes the Closely associated with the limbic system most superior portion Thalamus Largest component of the Major center for afferent (SENSORY) impulses to the cerebral cortex diencephalon; surrounds Cortical processing = interpretation of sensations the third ventricle Relay center for information from the basal ganglia and cerebellum to appropriate motor area Hypothalamus Forms ventral part Main functions: (a) Maintains constant internal environment; (b) implements behavioral patterns Visceral and somatic responses Affectual responses Hormone synthesis (endocrine function) Sympathetic / Parasympathetic control (autonomic nervous system function) Body temperature regulation Feeding responses Regulation of physical expression of emotions Sexual behavior Pleasure-punishment centers Level of arousal or wakefulness Subthalamus Lateral to hypothalamus Important basal ganglia center for motor activities  MIDBRAIN (mesencephalon) Connects the frontal lobe with the hindbrain; composed of 3 structures Tectum (corpora Roof of the midbrain; Superior colliculi – voluntary and involuntary visual motor movements (ability for quadrigemina) includes superior colliculi the eyes to track moving objects in the visual field and inferior colliculi Inferior colliculi – similar motor activities but involve movements affecting the auditory system (positioning the head to improve hearing); major relay center along the auditory pathway Tegmentum Floor of the midbrain; Provides communication between motor and sensory areas; storage, analysis, and includes red nucleus and interpretation of stimuli substantia nigra Red nucleus Receives ascending sensory information from the cerebellum and projects a minor motor pathway (rubrospinal tract) to the cervical spinal cord Substantia nigra Synthesizes dopamine; dysfunction of dopaminergic neurons in the substantia nigra is associated with Parkinson disease and schizophrenia Cerebral Anterior midbrain; made Contains nuclei of the 3rd and 4th (III & IV) cranial nerves peduncles up of fibers that link to Cerebral aqueduct (aqueduct of Sylvius) = carries CSF between 3 rd and 4th cortex of the brainstem ventricles  obstruction of the aqueduct is common cause of hydrocephalus HINDBRAIN Mentencephalon Cerebellum Composed of two lobes of Responsible for reflexive, involuntary fine-tuning of motor control (conscious and gray and white matter; unconscious muscle energy) divided by central fissure; Maintaining balance and posture (via connections with the medulla and the connected by the vermis midbrain) Control of the body = ipsilateral (same side); damage to the cerebellum is characterized by loss of equilibrium, balance, and motor coordination on the same side Pons “bridge”; below the Transmits information from the cerebellum to the brainstem (between the two midbrain and above the hemispheres) medulla Contains nuclei of the 5th-8th (V-VII) cranial nerves Aids in controlling respirations Myelencephalon Medulla Lowest portion of the Aids in controlling reflex activity (heart rate, respirations, BP, coughing, sneezing, Oblongata brainstem swallowing, and vomiting) Contains nuclei of the IX through XII cranial nerves Sleep-wake rhythms BRAINSTEM Comprised of the midbrain, pons, and medulla oblongata; connects the two hemispheres, cerebellum, and spinal cord Reticular Large network of diffuse Controls vital reflexes (cardiovascular function and respiration) Formation nuclei that connect the Vomiting, yawning, and hiccups = reflex-like motor responses brainstem to the cortex “Reticular Reticular formation + Essential for maintaining consciousness/wakefulness and attention Activating Cerebral cortex System” Which portion is responsible for keeping you awake, controlling thought, speech, emotions and behavior, maintaining balance and posture?  Reticular Formation Prefrontal area (F) Broca speech area (F) Wernicke area (F) (Brainstem) Regulates vital reflexes Goal-oriented behavior (i.e. Motor aspects of speech Reception and interpretation (cardiovascular function and ability to concentrate) (usually on left hemisphere); of speech (superior temporal respiration) gyrus) Short-term or recall memory Essential for maintaining Damage to this area (ex. CVA) Damage to this area results in wakefulness. Elaboration of thought results in inability to form difficulty understanding words words, called expressive aphasia or written language, called Inhibition on the limbic or dysphasia. receptive aphasia or dysphasia. (emotional) areas of the CNS. Limbic system (F) Hypothalamus (F) Cerebellum (H) Temporal Lobe (F) Primitive behavioral responses Maintenance of a constant Conscious and unconscious Secondary function of balance internal environment muscle synergy Visceral reaction to emotion Implementation of behavioral Maintaining balance and Feeding behaviors patterns posture Biologic rhythms Integrative centers control Damage to the cerebellum is function of the ANS characterized by ipsilateral Sense of smell (same side) loss of equilibrium, Regulation of body temperature balance, and motor coordination Expression of affect (emotional and behavioral states) Regulation of endocrine system Consolidation of memory Regulation of emotional expression. What part of the brain must be functioning for cognitive operations? (eBook key search term: “cognitive cerebral function) The neural systems essential to cognitive function are: a. Attentional systems that provide arousal and maintenance of attention over time b. Memory and language systems by which information is communicated c. Affective or emotive systems that mediate mood, emotion, and intentions. Cognitive cerebral functions require a functioning reticular activating system  regulates aspects of attention, information processing, and maintains consciousness. Awareness (content of thought) encompasses all cognitive functions (including awareness of self, environment, and affective states – moods)  Awareness is mediated by the core networks (selective attention and memory) under the guidance of executive attention networks (the networks that involve abstract reasoning, planning, decision making, judgment, error correct, and self-control)  Each attentional function is not localized in a single brain area but is a network of interconnected brain circuits. Prefrontal cortex is involved in cognitive functions such as planning and evaluating outcomes, and consequences for actions  The prefrontal area mediates several cognitive functions (executive attention functions – planning, problem solving, goal-setting) o It is responsible for goal-oriented behavior (i.e., ability to concentrate), short-term or recall memory, and elaboration of thought and inhibition on the limbic (emotional areas of the CNS) Which part of the brain controls movement of the eye? (eBook key search term: “lower portion of Brodmann area 8” and “from midbrain and exit”) Six extrinsic eye muscles (attached to the outer surface of each eye) allow gross eye movements and permit the eyes to follow a moving object.  These muscles arise from the common tendinous ring in the orbit, the eye cavity, and attach to the eyeball.  The six muscles are: lateral, medial, inferior and superior rectus muscles, and the inferior and superior oblique muscles.  The muscles, when contracting, cause movement of the eyeball, by pulling the eyeball towards the muscle. The frontal eye fields (the lower portion of Brodmann area 8), which are involved in controlling eye movements, are in the middle frontal gyrus. The superior colliculi of the midbrain are involved with voluntary and involuntary visual motor movements (e.g. the ability of the eyes to track moving objects in the visual field).  Abnormal ocular movements occur because of oculomotor, trochlear, or abducens cranial nerve dysfunction (e.g., strabismus, nystagmus, and paralysis of individual extraocular muscles)  o Oculomotor: fibers emerge from midbrain (oculomotor nucleus) o Trochlear: fibers emerge from posterior midbrain (trochlear nucleus) o Abducens: fibers leave inferior pons (abducens nucleus) The occipital lobe lies caudal to the parietooccipital sulci and superior to the cerebellum.  The primary visual cortex (Brodmann area 17) is in this region and receives input from the retinas.  Much of the remainder of this lobe is involved in visual association (Brodmann areas 18, 19). Discuss the types of mid-brain dysfunction and its physical symptoms. (eBook key search term: “nigra which synthesizes”) The midbrain is primarily a relay center for some motor and sensory tracts, as well as a center for auditory and visual reflexes, temperature control, sleep-wake cycles, arousal, and attention. Damage to the midbrain can result in a wide variety of movement disorders, difficulty with vision and hearing, and trouble with memory. 1. Corpora Quadrigemina (Tectum – roof of the midbrain): a. Disorders of selective attention related to visual orienting behavior are produced by disease that involves portions of the midbrain i. Superior colliculi: responsible for involuntary and voluntary visual motor movements (i.e. ability to track moving objects in the visual field); disease manifests as slowness in orienting attention ii. Inferior colliculi: responsible for movement affecting the auditory system (i.e. positioning head to improve hearing); relay center along the auditory pathway 2. Tegmentum (floor of the midbrain): a. Red nucleus: receives ascending sensory information from the cerebellum  minor motor pathway (rubrospinal tract)  cervical spinal cord b. Substantia nigra (inferior portion of the basal ganglia): synthesizes dopamine (neurotransmitter and precursor of norepinephrine); dysfunction of this structure is associated with Parkinson’s Disease, drug addiction, schizophrenia, Huntington’s disease, and multi-system atrophy c. Cerebral peduncles (anterior midbrain): made up of efferent fibers of the corticospinal, corticobulbar, and corticopontocerebellar tracts (tracts that link the cortex to the brainstem). d. Cerebral aqueduct (Aqueduct of Sylvius): carries CSF between 3rd / 4th ventricle  obstruction  hydrocephalus Because the midbrain houses the hypothalamus, it also plays a major role in automatic body functions. Other notable structures include:  Nuclei of the third and fourth cranial nerves (pupils)  mid-position pupils  CNS damage or disease affecting lower midbrain  Central reflex hyperpnea (brainstem breathing pattern)  Severe damage to midbrain/upper pons  decerebrate (abnormal posturing – internal rotation with hyperpronation of forearms)  Damage to tegmentum near hypothalamus and third ventricle  akinetic mutism (neither to move [akinesia] nor speak [mutism]) Syndromes associated with midbrain pathology include the Weber, Claude, Benedikt, Nothnagel, and Parinaud syndromes  Parkinsonism is a neurologic condition characterized by tremors, rigidity, hypokinesia, and postural instability because of degeneration of the corpus striatum or substantia nigra. What is the function of the CSF? (eBook key search term: “CSF is a clear”) CSF is a clear, colorless fluid like blood plasma and interstitial fluid.  Intracranial and spinal cord structures float in the CSF and are thereby partially protected from jolts and blows, and the buoyant properties of CSF also prevent the brain from tugging on meninges, nerve roots, and blood vessels. Know the function of the arachnoid villi. (eBook key search term: “the arachnoid villi protrude”) Protrude from the arachnoid space, through the dura mater, and lie within the blood flow of the venous sinuses.  The villi function as one-way valves, directing CSF outflow into the blood but preventing blood into the subarachnoid space. Where is the CSF produced? Where is the CSF absorbed? (eBook key search term: “choroid plexuses in the lateral”) The choroid plexus (rich network of blood vessels supplied arising from the pia mater) function to produce cerebrospinal fluids (CSF)  Lies in close contact with ventricular ependymal cells  Tight junctions of the choroid blood vessel providing a limiting barrier between the CSF and blood that functions similarly to the Blood-Brain Barrier CSF does not accumulate and is reabsorbed by means of a pressure gradient between the arachnoid villi and the cerebral venous sinuses. – it is reabsorbed into the venous circulation through the arachnoid villi, primarily located superior to the falx cerebri in the superior sagittal sinus. Thus, CSF is derived from the blood, and after circulating throughout the CNS, it returns to the blood. Review blood flow to the brain. (eBook key search term: “blood supply to the brain”) The brain receives approx. 20% of the cardiac output or 800 to 1000 mL of blood flow per minute.   CO2 serves as the primary regulator for blood flow (CO2 = powerful vasodilator that effects ensures adequate blood supply) Brain derives arterial blood supply from two systems: 1. Internal carotid arteries (anterior circulation) a. Greater amount of blood flow b. Originate from common carotid arteries  enter through cranium (base of skull)  cavernous sinus  divide into i. Anterior cerebral artery ii. Middle cerebral artery 2. Vertebral arteries (posterior circulation) a. Originate at subclavian arteries  pass through the transverse foramina of the cerebral vertebrae  entering the cranium (through the foramen magnum)  join at the junction of the pons and medulla oblongata  form the basilar artery b. Basilar artery divides at the midbrain to form three paired posterior cerebral arteries (perfuse cerebellum and brainstem): i. Posterior inferior cerebellar artery ii. Anterior inferior cerebellar artery iii. Superior cerebellar arteries c. Basilar artery also gives rise to small pontine arteries The larger arteries on the surface of the brain and their branches are called the superficial arteries (or conducting arteries), with the small branches that project into the brain called projecting arteries (or nutrient arteries) Circle of Willis (arterial circle) provides alternative route for blood flow when a contributing artery is obstructed and is comprised of:  posterior cerebral arteries  posterior communicating arteries  internal carotid arteries  anterior cerebral arteries  anterior communicating artery CHAPTER 16 Key words: What is the gate control theory of pain? (eBook key search term: “GCT integrates”) Gate control theory (GCT) integrates and builds upon features of other theories (specificity theory, pattern theory, etc.) to explain the complex multidimensional aspects of pain perception and pain modulation. Pain transmission is modulated by a balance of impulses conducted to the spinal cord where cells in the substantia gelatinosa function as a “gate” – spinal gate that regulates pain transmission to higher centers in the CNS  Nociceptive transmission (mechanical, thermal, and chemical)  opening of the gate  transmit the perception of pain o Large myelinated A-delta fibers and small, unmyelinated C fibers terminate on interneurons in the substantia gelatinosa (laminae in the dorsal horn of the spinal cord)  Non-nociceptive stimulation (from touch sensors in the skin; rubbing a painful area)  closure or partial close of the spinal gates  decreased pain perception: o Larger A-beta fibers Know the types of nerve fibers that transmit pain impulses. (eBook key search term: “lightly myelinated medium”) Nociceptors (primary order neurons) are free nerve endings in the afferent PNS that selectively respond to different chemical, mechanical and thermal stimuli. When stimulated they cause nociceptive pain. Nociceptors are categorized according to the stimulus to which they respond and by the properties of the axons associated with them. Nociception has four phases: transduction, transmission, perception, and modulation.  A-delta fibers are lightly myelinated, medium-sized fibers that are stimulated by severe mechanical deformation or by mechanical deformation and/or extremes of temperature. o Transmit sharp, well-localized “fast” pain sensations o Cause reflex withdraw of affected body part from the stimulus BEFORE a pain sensation is perceived (i.e. pulling a hand away from a hot stove)  Unmyelinated C fibers are smaller, unmyelinated polymodal fibers; stimulated by mechanical, thermal, and chemical nociceptors o Slowly transmit dull, aching, or burning sensations that are poorly localized and longer lasting  A-beta fibers are large myelinated fibers o Transmit touch and vibration sensations o Do NOT normally transmit pain but play a role in pain modulation What are the two types of fibers that transmit the nerve action potentials generated by excitation of any of the nociceptors? (eBook key search term: “coming into the gate”) Nociceptors are free nerve endings in the afferent peripheral nervous system that selectively respond to different chemical, mechanical, and thermal stimuli.  A-delta and C fibers comprise the primary, first-order sensory afferents coming into the gate at the dorsal horn of the spinal cord. o A-delta fibers: lightly myelinated, medium-sized fibers that are stimulated by severe mechanical deformation (mechanonociceptors) or by mechanical deformation and/or extremes of temperature (mechanothermal nociceptors).  Rapidly transmit sharp, well-localized “fast” pain sensations.  Responsible for causing reflex withdrawal of the affected body part from the stimulus before a pain sensation is perceived.  Unmyelinated C fibers: polymodal; stimulated by mechanical, thermal, and chemical nociceptors. o Slowly transmit dull, aching, or burning sensations that are poorly localized and longer lasting. Pain transmission is the conduction of pain impulses along the A-delta and C fibers into the dorsal horn of the spinal cord and brainstem, thalamus, and cortex. Note: A-beta fibers are large, myelinated fibers that transmit touch and vibration sensations; they do not normally transmit pain but play a role in pain modulation. Where in the CNS does pain perception occur? (eBook key search term: “conscious awareness of pain”) Define Pain perception: 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 individual responses to pain:  1. Sensory-discriminative system: mediated by the somatosensory cortex a. responsible for identifying the presence, character, location, and intensity of pain 2. Affective-motivational system: mediated through the reticular formation, limbic system, and brainstem with projections to the prefrontal cortex a. determines an individual’s conditioned avoidance behaviors and emotional responses to pain 3. Cognitive evaluative system: mediated through the cerebral cortex a. overlies the individual’s learned behavior concerning the experience of pain and can modulate perception of pain Know pain threshold / tolerance (eBook key search term: “pain threshold is the point”) Pain tolerance: the duration of time or the intensity of pain that an Pain threshold: the point at which a stimulus is perceived as pain individual will endure before initiating overt pain responses and it does not vary significantly among people or in the same  Generally decreased by person’s cultural perceptions, person over time expectations, role behaviors, physical and mental health,  Intense pain at one location may increase threshold in gender, age, fatigue, anger, boredom, apprehension, and another location – perceptual dominance – therefore, pain sleep deprivation. at one site may mask other painful areas  Tolerance may be INCREASED by alcohol consumption,  Generally DECREASED with repeated exposure to pain persistent use of pain medication, hypnosis, warmth, distracting activities, and strong beliefs or faith Know endogenous opioids (eBook key search term: “GABA and glycine”) Define: family of morphine-like neuropeptides that inhibit transmission of pain impulses in the spinal cord, brain, and periphery Their receptors play a role in various CNS, GI system, immune system, and other organ system disorders. There are 4 types of opioid neuropeptides (substances that act as neurotransmitters by binding to one or more G-protein-coupled opioid receptors): 1. Enkephalins: best known and most prevalent; 1st endogenous opioids extracted in research a. Location: found concentrated in the hypothalamus, the periaqueductal gray (PAG) matter, the nucleus raphe magnus of the medulla, and the dorsa; horns of the spinal cord b. Binds to the δ receptors i. Two types: 1. Methionine-enkephalin (ratio to leucine-enkephalin is 4:1) 2. Leucine-enkephalins 2. Endorphins (endogenous morphine): 1st discovered in the human PAG a. Location: produced in the hypothalamus and pituitary gland b. Binds to μ receptors in the hypothalamus and pituitary gland c. Function: produces the greatest sense of exhilaration or “high” than all other endorphin types; strong mu-receptor agonist and believed to provide substantial natural pain relief 3. Dynorphins: most potent endogenous neurohormone a. Location: found in the hypothalamus, brainstem, PAG-rostral ventromedial medulla (RVM) system, and spinal cord b. Binds strongly with the κ receptors c. Function: serves to impede pain signals in the brain but can, in certain circumstances, incite pain through mechanisms of up-regulation (paradoxically stimulating chronic pain); plays a role in mood disorders and drug addiction 4. Endomorphins: potent analgesic, GI, and anti-inflammatory effects a. Location: Endomorphins 1 and 2 are peptides isolated from the brain and spinal cord and show highest affinity and selectivity for the (μ) mu-opiate receptor b. Binds to almost all tissue in body; receptors throughout the brain, brainstem and GI tract c. Function: can modulate stress and anxiety, feeding behavior, cough suppression, immune and inflammatory responses, and alcohol intake Know different clinical descriptions of pain (acute, chronic, neuropathic) (eBook key search term: “it begins suddenly”) ACUTE PAIN (nociceptive pain) CHRONIC PAIN (persistent pain) NEUROPATHIC PAIN Define: normal protective mechanism that Define: pain lasting well beyond the Define: chronic pain initiated or caused by alerts the individual to a condition or expected normal healing time. primary lesion or dysfunction in the nervous experience that is immediately harmful to Function: serves no purpose; often system and leads to long-term changes in the body and mobilizes the individual to take accompanied by anxiety and depression and pain pathway structures and abnormal prompt action to relieve it causes suffering. It often appears to be out processing of sensory information. Duration: lasts seconds to days, and of proportion to apparent tissue injury. Function: amplification of pain without sometimes up to 3 months Duration: lasts for more than 3 to 6 months; stimulation by injury or inflammation Patho: relieved after chemical mediators may be ongoing (low back pain) or S/S: burning, shooting, shock-like, tingling; that stimulate pain receptors are removed intermittent (migraine headaches) characterized by hyperalgesia (increased S/S: stimulation of ANS  increased HR, sensitivity to a normally painful stimulus – HTN, diaphoresis, and dilated pupils *Changes in PNS and CNS that cause touch, pressure, pinprick, cold, and heat) and Etiology: arises from cutaneous and deep dysregulation of nociception and pain allodynia (induction of pain by normally somatic tissue or visceral organs and can be modulation processes (peripheral and central nonpainful stimuli) classified as: sensitization) are thought to lead to chronic  Somatic: arises from muscle, bone, pain Types of Neuropathic pain: joints, and skin; either sharp and well-  Chronic neuropathic pain: leads to localized (especially fast pain carried **Persistent pain allows for physiologic long-term plastic changes along by a-fibers) or dull, aching, throbbing, adaptation  normal heart rate and BP  somatosensory pathways from the and poorly localized (polymodal C leads to mistakenly conclude that people periphery to the cortex and abnormal fiber transmissions) with chronic pain are malingering because processing of sensory information by  Visceral Pain: transmitted by C fibers they don’t appear to be in pain the PNS and CNS. and refers to pain in internal organs  Peripheral neuropathic pain: caused and the lining of body cavities with an by peripheral nerve trauma, diabetic or aching, gnawing, throbbing, or alcohol abuse-induced neuropathy, intermittent cramping quality; poorly carcinoma, nutritional deficiencies, and localized; associated with nausea, HIV. vomiting, hypotension, restlessness,  Central neuropathic pain: caused by a shock (rare); radiates (spreads away lesion or dysfunction in the CNS, from) the actual site or is referred including brain or spinal cord trauma,  Referred Pain: pain felt in an area tumors, vascular lesions, MS, removed or distant from its point of Parkinson disease, postherpetic origin. The area of referred pain is neuralgia (PHN), phantom limb pain, supplied by spinal segment as the and reflex sympathetic dystrophy. actual site of pain.  Deafferentation pain syndromes: o Can be acute or chronic neuropathies that result from lesions in the PNS or CNS that interrupt the spinothalamic pathways at any level of the nervous system and are associated with hyperexcitability of the somatosensory thalamus and cortex.  Hemiagnosia pain: form of central pain associated with stroke that produces paralysis and hypersensitivity/allodynia on one half of the body.  Phantom limb pain: pain in an amputated limb after the stump has completely healed.  Sympathetically mediated pain (SMP) or complex regional pain syndromes (CRPSs): can occur after peripheral nerve or extremity injuries (usually develop 1-2 weeks after), and include two types: o Type I: associated with injury but no apparent nerve injury. o Type II: evidence of nerve injury. What is the relationship between epinephrine and body temperature? (eBook key search term: “epinephrine causes vasoconstriction”)  Heat production: hypothalamus + endocrine system  hypothalamic hormone called thyroid stimulating hormone release hormone TSH-RH  stimulates anterior pituitary to release TSH  acts on thyroid gland to stimulate release of thyroxine (T4)  acts on adrenal medulla, causing release of epinephrine into the bloodstream   Epinephrine causes vasoconstriction (improves thermal regulation), stimulates glycolysis, and increases metabolic rate, thus increasing body heat. Heat is distributed by the circulatory system. Know mechanisms of heat production and heat loss. (eBook key search term: “produce heat through two”) In human, body temperature is maintained around 37C (98.6F) and rarely exceeds 41C. The normal range is 36.2C to 37.7C.  Temperature regulation (thermoregulation) is mediated by the hypothalamus; peripheral thermoreceptors in the skin and abdominal organs (unmyelinated C fibers and thinly myelinated A-delta fibers) and central thermoreceptors in the spinal cord and trigeminal ganglia provide the hypothalamus with information about skin and core temperatures. HEAT PRODUCTION HEAT LOSS a. Chemical reactions of metabolism: the chemical a. Radiation: heat loss through electromagnetic waves; these reactions that occur during ingestion and metabolism of waves emanate from surfaces with temperatures higher than food and those required to maintain the body at rest (basal the surrounding air temperature. (temperature of the skin is metabolism) require energy and produce heat. These higher than that of air, the skin and the body lose heat to the processes occur in the body core (primarily the liver) and air) are in part responsible for the maintenance of core b. Conduction: heat loss by direct molecule-to-molecule temperature. transfer from one surface to another, with warmer surfaces losing heat to cooler surfaces. (skin loses heat through direct b. Skeletal muscle contraction: produces heat through two contact with cooler air, water, or another surface) mechanisms (both which are controlled by the posterior c. Convection: the transfer of heat through currents of gases or hypothalamus and occur in response to cold): liquids and occurs passively as warmer air at the surface of i. Gradual increase in muscle tone. the body rises away from the body and is replaced by colder ii. Production of muscle oscillations – shivering; air which does not occur in neonates) i. Process may be aided by fans or wind  combined effect of conduction and convection by wind is c. Chemical thermogenesis: also called nonshivering or conventionally measured as the wind-chill factor. adrenergic thermogenesis; results from release of d. Vasodilation: peripheral vasodilation increases heat loss by epinephrine and norepinephrine  a rapid, transient diverting core-warmed blood to the surface of the body. As increase in heat production by raising the body’s basal the core-warmed blood passes through the periphery, heat is metabolic rate. transferred by conduction to the skin surface and from the i. Occurs in brown adipose tissue (rich with skin to the surrounding environment. mitochondria and blood vessels) and is essential i. Occurs in response to autonomic stimulation under for nonshivering thermogenesis. the control of the hypothalamus. e. Decreased muscle tone: to decrease heat production, muscle tone may be moderately reduced and voluntary muscle activity curtailed; this may explain in part the “washed-out” feeling associated with high temperatures and warm weather. f. 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. Insensible water loss accounts for about 600ml of water loss per day. Sweating may result in 2.2L of fluid lost per hour. Electrolytes are also lost. Large volume loss through sweating may result in decreased plasma volume, decreased BP, weakness, & fainting. Heat loss by sweating/evaporation is affected by: i. Sympathetic neural activity. ii. Favorable temperature difference between the body and the environment. iii. Humidity: when high, sweat does not evaporate and instead remains on the skin or drips, when low, evaporates quickly. g. Increased pulmonary ventilation: exchanging air with the environment through the normal pulmonary ventilation provides some heat loss, although it is minimal in humans. This normal process occurs faster at higher body temperatures through and increase in ventilator rates; thus, hyperventilation is associated with hyperthermia. h. Voluntary mechanisms: in response to high body temperatures, people physically “stretch out,” thereby increasing the body surface area available for heat loss. They also “take it easy,” thereby decreasing skeletal muscle work, and they “dress for warm weather” in garments that reflect heat and promote convection, conduction, and evaporation  (light-colored, loose-fitting clothes). i. Heat adaptation: the body of an individual who goes from a cooler to a much warmer climate undergoes a period of adjustment, a process that takes several days to several weeks. Know heat exhaustion and heat stroke. (eBook key search term: “heat exhaustion or collapse”) HEAT EXHAUSTION / COLLAPSE HEAT STROKE Most common heat related injury; result of prolonged high core or Rectal temp > 41C or 106F; a potentially lethal result of breakdown environmental temperatures. in control of an overstressed thermoregulatory center.  High temperatures cause the appropriate hypothalamic response of profound vasodilation and profuse sweating  Causes/Patho: overexposure to environmental heat or impaired (prolonged period) produce dehydration, decreased plasma physiologic mechanisms for heat loss  sweat cools the person volumes  hypotension, decreased cardio output, and starting with the face and forehead, and fanning the face enhances tachycardia this mechanism  brain cannot tolerate temperatures greater than 40.5C (104.9F)  cardiovascular and thermoregulatory system stops S/S: Individual feels weak, dizzy, nauseated, and faint. functioning  body’s heat loss mechanisms fail  sweating ceases  Ceasing activity = decreases muscle work  decreased heat (skin becomes dry and flushed; irritability, confusion, stuporous, production and lying down redistributes vascular volume. comatose with possible visual disturbances)  Should be encouraged to drink warm fluids to replace fluid lost through sweating. Continued progression  high core temperatures and vascular collapse  cerebral edema, degeneration of the CNS, swollen dendrities, renal tubular necrosis, hepatic failure with delirium, multi-system organ failure Coma or death results unless immediate, effective treatment is initiated Treatment: remove from warm environment, use cooling blankets or cool water bath, or ice packs on head, neck, axillae, and groin area. *Care must be taken to prevent too rapid cooling of the surface, which causes peripheral vasoconstriction and prevents core cooling. Children more susceptible to heat stroke than adults because:  They produce more metabolic heat when exercising.  They have greater surface area to body mass ratio.  Their sweating capacity is less. Define the different stages of sleep. (eBook key search term: “sleep is an active”) Sleep is an active, multiphase, complex brain process that provides restorative functions and promotes memory consolidation. Normal sleep has two phases that can be documented by EEG: a. Rapid eye movement (REM) sleep b. Non-REM (NREM) or slow-wave sleep Sleep cycle (NREM and REM sleep alternate – each cycle lasting for approximately 9-100 minutes) 1. Awake: wakefulness with eyes closed and predominated by alpha waves. 2. NREM sleep (75-80% of sleep time) a. N1: light sleep with alpha waves interspersed with low-frequency theta waves; slow eye movements cycle lasts 10-12min (3-8% of sleep time) b. N2: further slowing of EEG with the presence of sleep spindles and slow eye movements; cycle lasts 30-60 min; 45-55% of sleep time; temperature drops c. N3: low-frequency high-amplitude delta waves with occasional sleep spindles (known as slow-wave sleep); no slow eye movements; 13-23% of sleep time 3. REM sleep: time of most dreaming; 20-25% of sleep time; characterized by low-voltage, fast activity that occurs for 5-60min about every 90 minutes. REM SLEEP NREM SLEEP Etiology: controlled by the pontine and reticular formation; Etiology: initiated by the withdrawal of neurotransmitters from the vivid dreaming; also known as paradoxic sleep because the EEG reticular formation and by the inhibition of arousal mechanisms in pattern is like the normal awake pattern. the cerebral cortex.  Patho: Patho:  bursts of conjugate rapid eye movement in all directions  respiration is DEPENDENT and controlled by metabolic  atonia of antigravity muscles processes.  suppressed temperature regulation  Basal metabolic rate is decrease by 10-15%.  alteration in heart rate/blood pressure/respiration  Temperature decreased 0.5C to 1C.  penile erection in men/clitoral engorgement in women  HR decreases by 10-30 beats per minute.  high rate of memorable dreams  Respiration, BP, and muscle tone all decrease, pupils  Steroids released in short bursts constrict, and knee jerk reflexes are absent.  Respiratory control thought to be largely INDEPENDENT of metabolic requirements and oxygen variation. During N1 and N2  cerebral blood flow to brainstem and  Cerebral blood flow to both hemispheres is increased. cerebellum is decreased. *Respiratory obstruction common because of loss of tongue muscle During N3  cerebral blood flow to cortex is decreased and control growth hormone is released, with depressed levels of **Loss of REM sleep impairs memory and learning. corticosteroids and catecholamines. Discuss disorders of the conjunctiva of the eye. (eBook key search term: “front part of the eyeball”) Conjunctivitis is an inflammation of the conjunctiva (mucous membrane covering the front part of eyeball). The inflammatory response produces photophobia, visual blurring, redness, edema, pain, and lacrimation (treatment related to cause) 1. Acute bacterial conjunctivitis (“pinkeye”): highly contagious; often caused by gram-positive bacteria (Staphylococcus, Haemophilus, Proteus); children ages 6 and under  Haemophilus may lead to otitis media a. onset is acute; disease is often self-limiting, resolving spontaneously in 10-14 day b. S/S: mucopurulent drainage from one or both eyes c. Tx: preventing spread of organism with handwashing and use of separate towels; 2. Viral conjunctivitis: contagious; caused by an adenovirus (some strains of virus cause conjunctivitis and pharyngitis, and others cause keratoconjunctivitis) a. S/S: watering, redness, and photophobia b. Tx: symptomatic 3. Allergic conjunctivitis: associated with a variety of antigens (pollens) a. S/S: Ocular itching, photophobia, burning/gritty feel in eye b. Tx: antihistamines, low-dose corticosteroids, mast cell stabilizers, and vasoconstrictors. 4. Chronic conjunctivitis: result of any persistent conjunctivitis, and cause requires identification for effective treatment. 5. Trachoma (chlamydial conjunctivitis): caused by Chlamydia trachomatis, often associated with poor hygiene and is the leading cause of preventable blindness in the world a. S/S: inflammation with scarring of the conjunctiva and eyelids  distorted lashes to abrade the cornea  corneal scarring and blindness b. Tx: surgery for in-turned lashes, systemic or local antibiotics, facial cleanliness, and environmental improvement (WHO “SAFE” strategy for treatment) 6. Keratitis: inflammation of the cornea that can be noninfectious or caused by bacteria, viruses, or fungi: a. Bacterial infections  corneal ulceration; require intensive antibiotic treatment (Staphylococcus aureus is the most common bacterial infection) b. Virus (Type 1 herpes simplex) can involve the cornea and conjunctiva c. Causes: contact use, trauma, and penetrating keratoplasty (corneal grafting) d. S/S: photophobia, pain, and lacrimation; severe ulcerations with residual scarring require corneal transplantation. CHAPTER 17 Key words:  Know the best prognostic indicator of recovery of consciousness & functional outcome after a brain event. (eBook key search term: “cause and extent of brain damage”) Outcomes depend on the cause (etiology) and extent of brain damage and duration of coma (time since onset). a. The Glasgow Coma Scale (GCS) is used to assess severity of brain injury. The hallmark of a severe TBI is LOC for 6 hours of more. Age and admission GCS score are important diagnostic factors in TBI. b. TBI classification using the GCS are: i. Mild TBI with GCS score of 13 to 15 (associated with mild concussion) ii. Moderate TBI with GCS score of 9 to 12 (associated with structural injury such as hemorrhage or contusion) iii. Severe TBI with GCS score of 3 to 8 (associated with cognitive and/or physical disability or death. GLASSGOW COMA SCORE (GCS) SCORE BEST EYE RESPONSE (4) BEST VERBAL RESPONSE BEST MOTOR REPONSE (6) (5) 1 No eye opening No verbal response No motor response 2 Eye opening to pain Incomprehensible sounds Extension to pain 3 Eye opening to verbal command Inappropriate words Flexion to pain 4 Eyes open spontaneously Confused Withdrawing from pain 5 -- Oriented Localizing pain 6 -- -- Obeys commands The Glasgow Coma Score (GCS) is scored between 3 and 15, with 3 being the worst and 15 the best. It is composed of the sum of three parameters: Best Eye Response, Best Verbal Response, and Best Motor Response (Mild Brain ate Brain Injury, 9 to 12; Severe Brain Injury, 8 or less) Know the most critical index of nervous system dysfunction/function. (eBook key search term: “most critical clinical index”) Level of consciousness is the most critical clinical index of nervous system function or dysfunction. Changes can indicate either improvement or deterioration of the individual’s condition and state of awareness.  A person who is alert and oriented to self, others, place, and time  functioning at the highest level of consciousness (implies full use of all the person’s cognitive capacities)  From this normal alert state, LOCs diminish in stages from confusion to coma Know patterns of breathing with head injuries.  Know vomiting with which CNS injuries. (eBook key search term: “vomiting, yawning, and hiccups”) Vomiting, yawning, and hiccups are complex reflex motor responses that are integrated by neural mechanisms in the lower brainstem. Most CNS disorders produce nausea and vomiting. These responses may be produced by:  Compression or diseases involving tissues of the medulla oblongata (e.g., infection, neoplasm, infarct, or other more benign stimuli to the vagal nerve).  Direct involvement of the central neural mechanism (e.g., pyloric obstruction) – usually vomiting occurs without nausea.  Injuries that involve the vestibular nuclei or its immediate projections, particularly when double vision is present (diplopia).  Injuries that impinge directly on the floor of the fourth ventricle.  Injuries that produce brainstem compression secondary to increased ICP. Know diagnostic criteria for vegetative state and brain death. (eBook key search term: “brain death (total brain death)” and “complete unawareness”) a. Brain death (or total brain death): occurs when irreversible brain damage is so extensive that the brain has no potential for recovery and no longer can maintain the body’s internal homeostasis. State laws define brain death as irreversible cessation of function of the entire brain, including the brainstem and cerebellum. This is to be distinguished from cerebral brain death, which is the death of the cerebral hemispheres exclusive of the brainstem and cerebellum. i. Clinical criteria for brain death: 1. Completion of all appropriate and therapeutic procedures with 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 60mmhg 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) for 6-12 hours for patients who are not hypothermic and have not ingested depressant drugs 6. Persistence of these signs for an appropriate observation period b. Persistent vegetative state (PVS): complete unawareness of the self or surrounding environment and complete loss of cognitive function (unresponsive wakefulness syndrome) i. Diagnostic criteria for PVS: 1. Periods of eye opening (spontaneous or following stimulation). 2. Potential for subcortical responses to external stimuli, including generalized physiologic responses to pain, such as posturing, tachycardia, diaphoresis, and subcortical motor responses, such as grasp reflex. 3. Return of vegetative autonomic functions, including sleep-wake cycles and normalization of respiratory and digestive system functions. 4. Occasional roving eye movements without concomitant visual tracking ability. 5. There may possibly be random hand, extremity, or head movements. The individual can maintain BP and breathing without support. Brainstem reflexes are intact, but cerebral functions are lost. No discrete localizing motor responses are present, and the individual does not speak any comprehensive words or follow commands. 6. Recovery unlikely if persist longer than 12 months Know clinical manifestations and presenting signs of Creutzfeldt-Jacob. (eBook key search term: “creutzfeldt-jakob disease is a”) Creutzfeldt-Jakob disease is a progressive, fatal, dementing neurologic illness caused by an infectious protein known as a prion.  Prior = composed of misfolded proteins unable to self-replicate  spongiform encephalopathy within grey matter  Rare; 1 in 1.5 million annually; 10% of cases are genetic (most cases are sporadic) o Molecular mechanism: PrPsc proteins type 1 and 2 o Causal Genes (Chromosome): Prior (20); up to 15% of cases carry these dominant mutations o Susceptibility Genes: PRNP codon 129 homozygosity for methionine or valine Diagnosis: clinical evaluation, MRI, electroencephalography; CSF fluid shows (14-3-3 protein or human prior protein PrPsc and it is also detected in olfactory epithelium, blood, and/or urine samples) Clinical manifestations: Progressive dementia and at least 2 of the following 4 features:  myoclonus, visual or cerebellar disturbance, pyramidal or extrapyramidal signs, and akinetic mutism Prognosis: fatal – average lifespan of 8 months Treatment: no treatment exists Characteristics of Alzheimer’s disease. (eBook key search term: “three forms of AD”) Leading cause of severe cognitive dysfunction in older adults (most common in women)  GREATEST RISK FACTORS are age and family history  PROTECTIVE FACTORS are lifelong activity, the presence of apoE2 and antioxidant substances, omega-3 fatty acids, estrogen replacement at the time of surgical menopause, low-calorie diet, and use of nonsteroidal anti-inflammatory agents Characterized by 3 forms: 1. Nonhereditary sporadic or late onset AD (70-90%): most prevalent, does not have a specific genetic association but cellular pathology is the same as gene associated early and late onset AD. a. Pathologic alterations in the brain-1) accumulation of extracellular neuritic plaques with a core of abnormally folded amyloid beta and tau proteins. 2) intraneuronal neurofibrillary tangles. **Neurotic plaques and neurofibrillary tangles are more concentrated in the cerebral cortex and hippocampus** 3) degeneration of basal forebrain cholinergic neurons with loss of acetylcholine, synapses, and other neurotransmitters contributes to decline in memory, attention and loss of other cognitive functions. b. Failure to process and clear amyloid precursor protein results in the accumulation of amyloid beta protein toxic fragments that leads to 1) formation of diffuse neuritic plaques, 2) disruption of nerve impulse transmission, and 3) death of neurons-result is brain atrophy with decreases in weight and volume. c. Aging and injury can cause changes that contribute to the development and progression of AD. 2. Early-onset familial AD (FAD): autosomal dominant; linked to 3 genes with mutations on chromosome 21. Gene-associated late onset- major genetic risk is related to apolipoprotein E gene-allele 4 (apoE4) on chromosome 19 (apoE4 interferes with amyloid beta clearance from the brain and is processed into neurotoxic fragments found in the plaques and tangles in the brain of people with AD) 3. Early-onset AD: very rare; genetic susceptibility tests for PSEN1, PSEN2, and APP are used for screening. Clinical Manifestations: AD has a long preclinical and prodromal course. Progresses from mild short-term memory deficits to total loss of cognition and executive functions (see table above) Evaluation: diagnosis is made by ruling out other causes. Definitive diagnosis can only be made by autopsy.  Clinical history (including mental status exams, clock drawing, and geriatric depression scale), CSF analysis, brain imaging of structure, blood flow and metabolism; and the course of the illness is used to assess progression of AD.  Genetic susceptibility tests for PSEN1, PSEN2, and APP are used to screen for early-onset AD Treatment: there are no disease modifying therapies, and treatment is directed at using devices to compensate for the impaired cognitive function (memory aids, maintaining unimpaired cognitive functions; and maintaining or improving the general state of hygiene, nutrition, and health  Cholinesterase inhibitors (used in mild-moderate cases of AD)  NMDA receptor antagonist blocks glutamate activity and may slow the progression of disease in moderate-severe AD  Anti-myeloid drugs are in clinical trials Define seizure and status epilepticus. What is the medical significance of status epilepticus? Know benign febrile seizures. (eBook key search term: “seizures are classified” and “seizures associated with fever”) SEIZURE STATUS EPILEPTICUS Seizure: a sudden, transient alteration of brain function caused by an Status epilepticus: abrupt explosive, disorderly discharge of cerebral neurons.  In adults, it is a state of continuous seizures lasting more than 5 minutes OR Types of Seizures (see Table 17.17)  Rapidly recurring seizures before the person has fully regained consciousness from the preceding seizure OR S/S: LOC, apnea, hypoxia, acidosis, and lactate accumulation with  A single seizure lasting more than 30 minutes. resulting brain tissue injury and destruction (overall medical Cause: often results from abrupt discontinuation of antiseizure concerns for seizures) medications but also may occur in untreated or inadequately treated persons with seizure disorders. **This situation is a medical emergency because of the resulting cerebral hypoxia, as well as the risk of aspiration, intellectual disability, dementia, and even death. Long-term Complications: neuronal death, neuronal injury, and alteration of neuronal networks. Patho: a group of neurons may exhibit a paroxysmal depolarization shift and function as an epileptogenic focus  These neurons are hyperexcitable (more easily activated by hyperthermia, hypoxia, hypoglycemia, hyponatremia, repeated sensory stimulation, and certain sleep phases)  Epileptogenic neurons fire more frequently and with greater amplitude When the intensity reaches a threshold point, cortical excitation spreads  excitation of the subcortical, thalamic, and brainstem areas:  Tonic phase (muscle contraction with increased muscle tone) = loss of consciousness When inhibitory neurons in the cortex, anterior thalamus, and basal ganglia react to the cortical excitation  seizure discharge is interrupted:  Clonic phase (alternating contraction and relaxation of muscles) = intermittent; gradually decrease and finally cease  epileptogenic neurons are exhausted During seizure activity – cerebral blood flow , oxygen consumption (60% greater than normal)  rapidly depleting O2 and glucose  lactate accumulates in brain tissue  (severe seizure continues) progressive brain injury and irreversible damage **If seizure focus in the brain is active for a prolonged period  a mirror focus may develop in contralateral normal tissue  seizure activity (particularly with focal epilepsy - i.e., temporal or frontal lobe) Etiology: a seizure disorder is a manifestation of disease, NOT a specific disease. Onset of seizures may point to the present of:  an ongoing primary neurological disease (including cerebral lesions, biochemical disorders, cerebral trauma, and epilepsy) OR  conditions such as metabolic defects, congenital malformations, genetic predisposition, perinatal injury, postnatal trauma, myoclonic syndromes, infection, brain tumor, and vascular disease OR  hypoglycemia, fatigue, emotional or physical stress, fever, hyponatremia, constipation, blinking lights, use of stimulant drugs, loud noises, certain odors, and withdrawal from drugs/alcohol. Phases of seizures: Two types of symptoms signal the preictal phase of a generalized tonic-clonic seizure: 1. Prodroma: early manifestations occurring hours to days before a seizure (may include anxiety, depression, or inability to think clearly 2. Focal seizure or aura that immediately precedes the onset of a generalized tonic-clonic seizure. a. Both may become familiar to the person and may enable the person to prevent injuries during the seizure.  The ictus is the episode of the epileptic seizure with tonic-clonic activity. Airway maintenance needs to be ensured. The postictal state follows an epileptic seizure and can include signs of headache, confusion, aphasia, memory loss, paralysis and deep sleep that may last hours or a day or two. Diagnosis: Treatment:  Heath history (most critical aspect of diagnosis, establishing  Correct or control cause (#1) – if not possible… the cause and onset) o Anti-seizure medications (goal: complete suppression o Supplemented with physical exam, lab tests of blood of seizure activity without intolerable side effects or and urine (glucose, serum Ca+, BUN, urine Na+, drug resistance) creatinine clearance) – identify any systemic diseases  Dietary treatments  Ketogenic diet or modified Atkins diet o CT/MRI scans and CSF serology – identify any (60 cause the juvenile form of the disease. Fathers, but not mothers, with high normal alleles do not develop HD but are at risk for transmitting potentially penetrant HB alleles (> or = 36) to their offspring, who can develop HD. c. The genetic defect of HD is on the short arm of chromosome 4. There is an abnormally long polyglutamine tract in the huntingtin (htt) protein that is toxic to neurons and is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion (40 to 70 repeats instead of 9 to 34)  produces tangles of protein that collect in brain cells and chains of glutamine on the abnormal molecules that adhere to each other (exact mechanism of neuronal death is unknown)  Clinical Manifestations (SLOW PROGRESSION): a. Excess of dopaminergic activity = hypotonia and hyperkinesia. b. Loss of excitatory glutamate = impaired modulation of movement later during the disease. c. Build-up of lactic acid = difficulty producing energy for the brain. d. S/S: involuntary fragmentary movements (occur without conscious effort), emotional lability, and progressive dysfunction of cognitive processes (dementia) that may precede motor symptoms.  Chorea is the most common type of abnormal movement  Begins in the face and arms, eventually affecting the entire body  Chorea can be combined with athetosis (twisting and writhing) and ballism (flailing of limbs)  Cognitive deficits  loss of working memory and reduced capacity to plan, organize, and sequence. Thinking is slow, and apathy is present. Restlessness, disinhibition, and irritability are common. Euphoria or depression may be present.  Prognosis: FATAL Define dyskinesia. Types? Characteristics? (eBook key search term: “dyskinesias”) a. Dyskinesias: unnatural movements or abnormal involuntary movements (and are included in the general category of hyperkinesia, which are excessive movements.) Huntington’s disease is the hallmark of excess movement. (i.e. tick-like jerky movements, smacking lips, or flicking the tongue, unsteady gait, rocking back and forth.) i. Paroxysmal dyskinesia: abnormal, involuntary movements that occur as spasms. ii. Tardive (slow onset) dyskinesia: involuntary movement of face, trunk, and extremities due to Parkinson disease or prolonged antipsychotic usage. Most common symptom of tardive dyskinesia is rapid, repetitive, stereotypic movements (e.g., continual chewing with intermittent protrusions of the tongue, lip smacking, etc.)  b. Hypokinesia: decreased amplitude of movement. c. Bradykinesia: decreased speed of movement. d. Akinesia: absence of voluntary movements. i. Parkinson’s disease is the hallmark of lack of movement What is responsible for the tremors associated with Parkinson’s Diseases? (eBook key search term: “instability of feedback”) Cause: appear to result from instability of feedback from the basal ganglia to the cerebral cortex, caused by loss of the inhibitory influence of dopamine in the basal ganglia a. Increased oscillation in the normal feedback cycles of the motor outflow feedback circuit when the muscles are at rest produces the tremor. b. When the individual performs voluntary movements, the tremor becomes temporarily block, presumably because other motor control signals arriving the thalamus override the abnormal basal ganglia signals. Primary Patho: degeneration of the basal ganglia with formation of Lewy bodies in the substantia nigra and dorsal striatum  depletion of dopamine (inhibitory neurotransmitter) and relative excess of cholinergic (excitatory) activity in the feedback circuit are manifested by hypertonia (tremor and rigidity) and akinesia  syndrome of abnormal movement called parkinsonism Hallmark pathologic features: 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 (normally facilitates movement) and overactivity of the indirect motor loop (normally inhibits movement). Symptoms appear after 70-80% loss of pigmented nigral neurons and 60-70% loss of striated dopamine. Overall, a loss or decrease in DOPAMINE is responsible Define and describe pathophysiology/clinical manifestations/etiology of Parkinson’s disease. (eBook key search term: “complex motor disorder”) Define: complex motor disorder accompanied by systemic nonmotor and neurologic symptoms. a. Pathophysiology: i. The main disease feature is degeneration of the basal ganglia (corpus striatum, globus pallidus, subthalamic nucleus, and substantia nigra) involving the dopaminergic nigrostriatal pathway. ii. The pathogensis of primary PD is unknown, though several PD genes have been identified. iii. The hallmark pathologic features of PD are loss of dopaminergic pigmented neurons in the substantia nigra (SN) pars compacta with dopaminergic deficiency in the putamen portion of the striatum. 1. Dopamine loss occurs in the brainstem, thalamus, and cortex. 2. Depletion of dopaminergic nigrostriatal pathway to basal ganglia  underactivity or direct motor pathway (normally facilitates movement) and overactivity of indirect motor loop (normally inhibits movement  inhibition of motor cortex, with s/s of bradykinesia and rigidity. 3. Subthalamic nucleus overactivity influences limbic system, which leads to emotional symptoms. b. Etiology classification of parkinsonism: primary parkinsonism and secondary parkinsonism (Box 17.7) i. There are molecular events associated with neurodegeneration of PD. c. Clinical manifestations: i. Resting tremor, bradykinesia/akinesia (poverty of movement), muscular rigidity, and postural abnormalities. Manifestations may develop alone or in combination; however, as the disease progresses, all four are usually present to some degree. There is no true paralysis. a. Parkinsonian tremor is usually the first symptom to appear. More common in the upper extremities versus the lower extremities and increases with anxiety or stress. ii. Nonmotor s/s include: hyposomnia, fatigue, pain, autonomic dysfunction, sleep fragmentation, depression, and dementia with or without psychosis. d. Time of onset: primary PD (after 40 years of age with mean onset of 60 years of age) i. Men are 150% more likely to have PD than women. ii. Secondary PD is neurodegenerative disease + another acquired disorder iii. Familial PD is 10%, with majority either sporadic or idiopathic. e. Treatment: drug therapy to treat and restore dopamine levels and decrease akinesia and manage nonmotor symptoms (drug therapy may not begin until incapacitant.)  CHAPTER 18 Key words: Know the characteristics of closed head injury. (eBook key search term: terms “head striking a hard”) Involves either the head striking a hard surface or a rapidly moving object striking the head.  Dura matter remains intact, and brain tissues are not exposed to the environment.  Most closed trauma is mild (75% to 90%) and causes mild concussion and classic cerebral concussion. Note: focal brain injuries can occur with either blunt (closed) or open brain trauma and can be associated with skull fractures. Focal brain injuries are specific, grossly observable brain lesions that occur in a precise location (e.g., cortical contusions, epidural hemorrhage, subdural hemorrhage, intracerebral hematoma). They may be a coup injury or a contrecoup injury. 1. Contusions: blood leaking from an injured vessel; found most commonly in the frontal lobes (particularly at the poles and along the inferior orbital surfaces), in the temporal lobes, and the frontotemporal junction. 2. Extradural hematomas: bleeding between the dura mater and the skull (e.g., epidural hematomas or epidural hemorrhages); caused most commonly by MVAs a. Arterial bleeding is involved 85% of the time 3. Subdural hematomas: MVAs are most common cause; 50% are associated with skull fractures. Falls (especially in older adults or in those with long-term alcohol abuse) are associated with chronic subdural hematomas a. Acute forms develop rapidly (within 48 hours) and are usually located at the top of the skull. b. Occurs in 10-20% of TBIs. c. S/S: headache (80% of people), drowsiness, restlessness, and agitation. 4. Intracerebral hematomas: usually associated with MVAs and falls from some distance. a. May be single or multiple and they are associated with contusions. b. Most commonly located in the frontal and temporal lobes. c. Occurs in 2-3% of TBIs d. S/S: decreasing LOC; may cause contralateral hemiplegia and a positive Babinski reflex Define concussion / Different Grades of Concussion (eBook key search term: terms “biomarkers and concussion”) Concussion has been described as a set of symptoms with or without neuropathologic damage that may or may not involve loss of consciousness following TBI. Cause: damage to the delicate axonal fibers and white matter tracts that project to the cerebral cortex. Biomarkers: 2 biomarkers [Glial fibrillary acidic protein (GFAP) and have been studied to Ubiquitin C-terminal hydrolase L-1 (UCH-L1)] have been studied and show promise for diagnosis of TBI and mild to moderate concussion. These markers have shown to distinguish mild to moderate concussion with and without neurosurgical intervention and provided data consistent with CT with 97% accuracy. Both biomarkers cross BBB after TBI and are detectable in the blood.  GCS: 9-15 with LOC, amnesia, or disorientation = biomarkers detectable within 1 hour of injury  GFAP peaks in 20 hours and declines over 72 hours  UCH-L1 rises rapidly and peaks in 8 hours MILD TBI MODERATE TBI SEVERE TBI (mild concussion) (moderate cerebral concussion) (severe concussion) Define: immediate but transitory clinical Define: any loss of consciousness lasting Define: Loss of consciousness lasts more manifestations without loss of more than 30 minutes, accompanied by than 24 hours. The person experiences consciousness OR loss of consciousness posttraumatic anterograde amnesia lasting immediate autonomic dysfunction that that is momentary or less than 30 minutes 24 hours or more resolves in a few weeks. Increased ICP  Posttraumatic anterograde amnesia appears 4 to 6 days after injury. also may exist transiently to less GCS: 8 to 13 than 24 hours. GCS: less than 8 associated with brainstem Possible complication: basal skull fracture signs (pupillary reaction, cardiac and with NO brainstem injury respiratory symptoms, posturing) and  Cause: most blunt trauma injuries cause  There is transitory decerebration or intracranial contusions, hematomas, or mild TBI decortication with lacerations. unconsciousness lasting days or GCS: 13 to 15 weeks. Pulmonary complications occur frequently, with profound sensorimotor and Diagnostics: may be no findings with S/S: confused and experiences a long cognitive system deficits. CT/MRI (lesions may be detected with period of posttraumatic amnesia; permanent advanced MRI imaging) deficits in selective attention, vigilance, S/S: severely compromised coordinated detection, working memory, data movements and verbal and written S/S: headaches, nausea and vomiting, processing, vision or perception, and communication, inability to learn and confusion, disorientation, attention deficit, language, as well as mood and affect reason, and inability to modulate behavior dizziness, and impaired ability to changes ranging from mild to severe. concentrate for days after the injury. Prognosis: severe injury causes permanent neurologic deficits (20% of adults) and it Increase symptoms with: diffuse axonal has been shown that up to 14% remain in a injury, metabolic impairment, alterations in vegetative state, and 20% to 40% of neural activation, and cerebral blood flow patients end up dying as a result of brain perturbations injury or secondary complications. **Biomarkers are under investigation to assist with diagnosis of mild TBI Goal of treatment: maintain cerebral perfusion and oxygenation, promote neuroprotection, and mitigate long-term neurologic deficits.  The Corticosteroid Randomisation After Significant Head Injury (CRASH) trial showed corticosteroids increase mortality with acute TBI; consequently, these drugs are no longer used. Mild concussion (mild traumatic brain injury): CSF pressure rises, ECG and EEG changes occur without loss of consciousness, Glasgow Coma Scale (GCS) is 13-15, and initial confusion lasts from one to several minutes with possible retrograde amnesia for events preceding the trauma. Grades of mild concussion: Grades of mild concussions are as follows: 1. Grade I – transient confusion and disorientation accompanied by amnesia, no loss of consciousness, and symptoms resolve within 15 minutes. 2. Grade II – transient confusion and retrograde amnesia that develops after 5-10 minutes, and symptoms last no more than 15 minutes. 3. Grade III – any loss of consciousness, confusion, and amnesia remain present from impact and persist for several minutes. 4. Grade IV (NOT MILD, called classical cerebral concussion): any loss of consciousness (can last up to 6 hours) accompanied by retrograde and anterograde amnesia. Some of the effects of a concussion may persis