UNIT 2 Study Guide NU 545 - Pathophysiology PDF

UNIT 2 STUDY GUIDE NU 545- Pathophysiology Ch. 15, 16, 17, 18 19, 20 **CHAPTER 15- Structure & Function of the Neurologic System** **Afferent (ascending) is used to describe things like nerves, blood vessels, and arteries that lead TOWARD or bring things (like blood, in the case of arteries) to a...

UNIT 2 STUDY GUIDE NU 545- Pathophysiology Ch. 15, 16, 17, 18 19, 20 **CHAPTER 15- Structure & Function of the Neurologic System** **Afferent (ascending) is used to describe things like nerves, blood vessels, and arteries that lead TOWARD or bring things (like blood, in the case of arteries) to an organ, such as the heart or brain.** **Efferent (descending) is used to describe parts that carry or lead things AWAY from organs or other parts.** A diagram of a nervous system AI-generated content may be incorrect. **Support cells of the Nervous System:** **[CNS:]** Astrocytes: - Form specialized contact between neuronal surfaces and blood vessels - Provide rapid transport for nutrient and metabolites - Thought to form an essential component of blood brain barrier - Appear to have scar-forming cells of CNS, which may be foci for seizures - Appear to work with neurons in processing information and memory storage Oligodendroglia (oligodendrocytes) - Formation of **myelin sheath** in **CNS** Microglia - Responsible for cleaning cellular debris (phagocytic properties) and the key immune cell in the CNS Ependymal Cells - Serve as a lining for ventricles and choroid plexuses involved in production of CSF **[Peripheral Nervous System:]** - **Schwann cells** - Formation of myelin sheath within **PNS** - Nonmyelinating Schwann Cells - Provide neuronal metabolic support and regeneration in PNS - Satellite glial cells - Surround sensory, sympathetic and parasympathetic nerve cell bodies and ganglia to provide protection and promote cellular communication (similar to astrocytes in CNS) **What nerves are capable of regeneration?** - Mature neurons **do not** divide and injury in the CNS causes permanent loss of damaged neurons. - Crushed nerves recover better than cut nerves. - **Myelinated fibers in the PNS can repair themselves through axonal reaction** - Local changes occur when the axon is severed: 1. 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 chromatolysis 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 - **This process is very slow, about 1mm/day, and is limited to [myelinated fibers in the PNS]**[.] - 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 - 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: - Location of the injury - The type of injury: crushing injury allows recovery more fully than does a cut injury - Crushed nerves sometimes fully recover, whereas cut nerves often form connective tissue scars that block or slow regenerating axonal branches - The presence of inflammatory responses - The process of scarring Cranial Nerve Origin & Course Function -------------------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- I. Olfactory Fibers arise from nasal olfactory epithelium & form synapses with olfactory bulbs that transmit impulses to temporal lobe Purely sensory; carries impulses for sense of smell sniff aromatic substances identify them II\. Optic Fibers arise from retina of eye to form optic nerve, which passes through sphenoid bone; two optic nerves then form optic chiasma (with partial crossover of fibers) Purely sensory; carries impulses for vision Vision and visual field tested with an eye chart and by testing point at which person first sees an object (finger) moving into visual field; inside of eye is viewed with ophthalmoscope to observe blood vessels of eye interior III\. Oculomotor Fibers emerge from **midbrain** & exit from skull & extend to eye Contains motor fiber to inferior oblique & to superior, inferior & medial rectus extraocular muscles that direct eyeball; levator muscles of eyelid; smooth muscles of iris & ciliary body; and proprioception (sensory) to brain from extraocular muscles Pupils examined for size, shape, and equality; pupillary reflex tested with a penlight (pupils should constrict when illuminated); ability to follow moving objects IV\. Trochlear Fibers emerge from posterior **midbrain** & exit from skull to run to eye Proprioceptor & motor fibers for superior oblique muscles of eye (extraocular muscles) Tested in common with cranial nerve III relative to ability to follow moving objects V. Trigeminal Fibers emerge from pons and form three divisions that exit from skull and run to face and cranial dura mater Both motor & sensory for face; conducts sensory impulses from mouth, nose, surface of eye, and dura mater; also contains motor fibers that stimulate chewing muscles Sensations of pain, touch, and temperature tested with safety pin and hot and cold objects; corneal reflex tested with a wisp of cotton; motor branch tested by asking subject to clench teeth, open mouth against resistance, and move jaw from side to side VI\. Abducens Fibers leave inferior **pons** and exit from skull, and extend to eye Contains motor fibers to lateral rectus muscle and proprioceptor fibers from same muscle to brain Tested in common with cranial nerve III relative to ability to move each eye laterally VII\. Facial Fibers leave **pons** and travel through temporal bone & extend to face Mixed: (1) supplies motor fibers to muscles of facial expression and to lacrimal and salivary glands and (2) carries sensory fibers from taste buds of anterior part of tongue Anterior two-thirds of tongue tested for ability to taste sweet (sugar), salty, sour (vinegar), and bitter (quinine) substances; symmetry of face checked; subject asked to close eyes, smile, whistle, and so on; tearing tested with ammonia fumes VIII\. Vestibulocochlear Fibers run from inner ear (hearing & equilibrium receptors in temporal bone) to enter brainstem just below **pons** Purely sensory; vestibular branch transmits impulses for sense of equilibrium; cochlear branch transmits impulses for sense of hearing Hearing checked by air and bone conduction by use of a tuning fork; vestibular tests: Bárány and caloric tests IX\. Glossopharyngeal Fibers emerge from **midbrain** and leave skull and extend to pharynx, salivary glands and tongue Mixed: (1) motor fibers serve pharynx (throat) and salivary glands, and (2) sensory fibers carry impulses from pharynx, posterior tongue (taste buds), and pressure receptors of carotid artery Gag and swallow reflexes checked; subject asked to speak and cough; posterior one-third of tongue may be tested for taste X. Vagus Fibers emerge from **medulla**, pass through skull, and descending through neck region into thorax and abdominal region Fibers carry sensory & motor impulses for pharynx; a large part of this nerve is parasympathetic motor fibers, which supply smooth muscles of abdominal organs; receives sensory impulses from viscera Same as for cranial nerve IX (IX and X are tested in common) because they both serve muscles of the throat XI\. Spinal Accessory Fibers arise from **medulla** & superior spinal cord & extend to muscles of neck & back Provides sensory & motor fibers for sternocleidomastoid and trapezius muscles of soft palate, pharynx, and larynx Sternocleidomastoid and trapezius muscles checked for strength by asking subject to rotate head and shrug shoulders against resistance XII\. Hypoglossal Fibers arise from **medulla** & exit from skull & extend to tongue Carries motor fibers to muscles of tongue & sensory impulses from tongue to brain Subject asked to stick out tongue, and any position abnormalities are noted **Review the anatomy of the brain.** - 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** A diagram of a brain AI-generated content may be incorrect. -- -- -- -- -- -- **THE CEREBRAL HEMISPHERE**  The Cerebral Hemispheres. +-----------------------+-----------------------+-----------------------+ | Telencephalon | | | +-----------------------+-----------------------+-----------------------+ | Frontal Lobe | **Prefrontal area** | 1. **Goal-oriented | | | | behavior** | | | | | | | | 2. Short term memory | | | | | | | | 3. Concentration | | | | | | | | 4. **Elaboration of | | | | thought** | | | | | | | | 5. Inhibition on | | | | limbic area | | | | (emotional region | | | | of the brain) | | | | | | | | 6. **Executive | | | | attention | | | | functions** | | | | (problem solving, | | | | planning) | +-----------------------+-----------------------+-----------------------+ | | Premotor area | 1. Programs motor | | | (Brodmann area 6) | movement: | | | | | | | | a. Contains cell | | | | bodies that | | | | form part of | | | | the basal | | | | ganglia | | | | system - | | | | extrapyramida | | | | l | | | | system | | | | | | | | 2. Controls eye | | | | movement | | | | | | | | b. Brodmann area | | | | 8 | | | | | | | | c. Middle | | | | frontal gyrus | +-----------------------+-----------------------+-----------------------+ | | Primary motor area | 1. Primary voluntary | | | (Brodmann area 4) | motor = | | | | somatotopic | | | | organization | | | | (Homunculus = | | | | little man) | | | | | | | | 2. Cerebral cortex | | | | central impulses | | | | control the | | | | opposite side of | | | | the body = | | | | contralateral | | | | control | +-----------------------+-----------------------+-----------------------+ | | **Broca speech area** | 1. **Motor aspect of | | | | speech** | | | (Brodmann area 44, | | | | 45) | 2. Speech and | | | | language | | | \*\*most important in | processing area | | | the left hemisphere | | | | | 3. Dysfunction | | | | (damage from CVA) | | | | may result in | | | | inability to form | | | | words | | | | **expressive | | | | aphasia or | | | | dysphasia** | +-----------------------+-----------------------+-----------------------+ | Parietal Lobe | Somatic sensory input | 1. Provides | | | (Brodmann areas 3, 1, | communication | | | 2) | between motor and | | | | sensory areas | | | | | | | | 2. Storage, | | | | analysis, and | | | | interpretation of | | | | stimuli | +-----------------------+-----------------------+-----------------------+ | Temporal Lobe | Primary auditory | | | | cortex (Brodmann area | | | | 41) | | +-----------------------+-----------------------+-----------------------+ | | **Wernicke area** | 1. **Sensory speech | | | | area** | | | (Brodmann area 22) | | | | | 2. **Reception and | | | | interpretation of | | | | speech** | | | | (superior | | | | temporal gyrus) | | | | | | | | 3. Dysfunction / | | | | damage may result | | | | in **receptive | | | | aphasia** or | | | | dysphasia | | | | | | | | 4. Secondary | | | | function of | | | | balance | +-----------------------+-----------------------+-----------------------+ | | Memory consolidation | | | | and smell | | +-----------------------+-----------------------+-----------------------+ | Occipital Lobe | Primary visual cortex | Receives input from | | | (Brodmann area 17) | the retinas | +-----------------------+-----------------------+-----------------------+ | | 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 | 1. Mediates emotion | | | telencephalon and | and **long-term | | | diencephalon and | memory** through | | | surrounding the | connections in | | | corpus callosum | the prefrontal | | | | cortex | | | | | | | | 2. Primitive | | | | behavioral | | | | responses and | | | | visceral reaction | | | | to emotion, | | | | feeding | | | | behaviors, | | | | biologic rhythms | | | | and sense of | | | | smell | | | | | | | | 3. Expression of | | | | affect (emotion | | | | and behavioral | | | | state) mediated | | | | by connections | | | | with limbic | | | | system and | | | | prefrontal cortex | | | | | | | | 4. **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 | 1. Controls vital | | | 3rd ventricle; | functions and | | | composes the most | visceral | | | superior portion | activities | | | | | | | | 2. Closely | | | | associated with | | | | the limbic system | +-----------------------+-----------------------+-----------------------+ | Thalamus | Largest component of | 1. Major center for | | | the diencephalon; | afferent | | | surrounds the third | (SENSORY) | | | ventricle | impulses to the | | | | cerebral cortex | | | | | | | | 2. Cortical | | | | processing = | | | | interpretation of | | | | sensations | | | | | | | | 3. Relay center for | | | | information from | | | | the basal ganglia | | | | and cerebellum to | | | | appropriate motor | | | | area | +-----------------------+-----------------------+-----------------------+ | Hypothalamus | Forms ventral part | 1. Main functions: | | | | | | | | a. **Maintains | | | | constant | | | | internal | | | | environment** | | | | | | | | b. **Implements | | | | behavioral | | | | patterns** | | | | | | | | 2. Visceral and | | | | somatic responses | | | | | | | | 3. Affectual | | | | responses | | | | | | | | 4. Hormone synthesis | | | | (endocrine | | | | function) | | | | | | | | 5. Sympathetic / | | | | Parasympathetic | | | | control | | | | (**autonomic | | | | nervous system | | | | function**) | | | | | | | | 6. Body | | | | **temperature** | | | | regulation | | | | | | | | 7. Feeding responses | | | | | | | | 8. Regulation of | | | | physical | | | | expression of | | | | emotions | | | | | | | | 9. Sexual behavior | | | | | | | | 10. Pleasure-punishme | | | | nt | | | | centers | | | | | | | | 11. Level of arousal | | | | or wakefulness | +-----------------------+-----------------------+-----------------------+ | Subthalamus | Lateral to | Important basal | | | hypothalamus | ganglia center for | | | | motor activities | +-----------------------+-----------------------+-----------------------+ | **MIDBRAIN** | | | | | | | | (mesencephalon) | | | +-----------------------+-----------------------+-----------------------+ | Connects the frontal | | | | lobe with the | | | | hindbrain; composed | | | | of 3 structures | | | +-----------------------+-----------------------+-----------------------+ | Tectum (corpora | Roof of the midbrain; | 1. Superior | | quadrigemina) | includes superior | colliculi -- | | | colliculi and | voluntary and | | | inferior colliculi | involuntary | | | | visual motor | | | | movements | | | | | | | | a. Ability for | | | | the eyes to | | | | track moving | | | | objects in | | | | the visual | | | | field | | | | | | | | 2. Inferior | | | | colliculi -- | | | | similar motor | | | | activities but | | | | involve movements | | | | affecting the | | | | auditory system | | | | (positioning the | | | | head to improve | | | | hearing) | | | | | | | | b. Major relay | | | | center along | | | | the auditory | | | | pathway | +-----------------------+-----------------------+-----------------------+ | Tegmentum | **Floor of the | 1. Provides | | | midbrain**; includes | communication | | | *red nucleus and | between motor and | | | substantia nigra* | sensory areas | | | | | | | | 2. Storage, | | | | analysis, and | | | | interpretation of | | | | stimuli | +-----------------------+-----------------------+-----------------------+ | | Red nucleus | 1. Receives | | | | ascending sensory | | | | information from | | | | the cerebellum | | | | and projects a | | | | minor motor | | | | pathway | | | | (rubrospinal | | | | tract) to the | | | | cervical spinal | | | | cord | +-----------------------+-----------------------+-----------------------+ | | **Substantia nigra** | 1. **Synthesizes | | | | dopamine** | | | | | | | | 2. Dysfunction of | | | | dopaminergic | | | | neurons in the | | | | substantia nigra | | | | is associated | | | | with: | | | | | | | | a. Parkinson | | | | disease and | | | | schizophrenia | +-----------------------+-----------------------+-----------------------+ | Cerebral peduncles | Anterior midbrain; | 1. Contains nuclei | | | made up of fibers | of the cranial | | | that link to cortex | nerves III & IV | | | of the brainstem | | | | | 2. Cerebral aqueduct | | | | (aqueduct of | | | | Sylvius) = | | | | carries CSF | | | | between 3rd and | | | | 4th ventricles | | | | **obstruction of | | | | the aqueduct is | | | | common cause of | | | | hydrocephalus** | +-----------------------+-----------------------+-----------------------+ | **HINDBRAIN** | | | +-----------------------+-----------------------+-----------------------+ | Mentencephalon | | | +-----------------------+-----------------------+-----------------------+ | Cerebellum | Composed of two lobes | 1. Responsible for | | | of gray and white | reflexive, | | | matter; **divided by | involuntary | | | central fissure**; | fine-tuning of | | | connected by the | motor control | | | vermis | (conscious and | | | | unconscious | | | | muscle energy) | | | | | | | | 2. Maintaining | | | | **balance and | | | | posture** (via | | | | connections with | | | | the medulla and | | | | the midbrain) | | | | | | | | 3. *Control of the | | | | body = | | | | ipsilateral (same | | | | side*) | | | | | | | | 4. Damage to the | | | | cerebellum is | | | | characterized by | | | | **loss of | | | | equilibrium, | | | | balance, and | | | | motor | | | | coordination on | | | | the same side** | +-----------------------+-----------------------+-----------------------+ | Pons | "bridge" | 1. Transmits | | | | information from | | | below the midbrain | the cerebellum to | | | and above the medulla | the brainstem | | | | (between the two | | | | hemispheres) | | | | | | | | 2. **Contains | | | | nuclei** of the | | | | **5th-8th | | | | (V-VIII)** | | | | cranial nerves | | | | | | | | 3. Aids in | | | | controlling | | | | **respirations** | +-----------------------+-----------------------+-----------------------+ | Myelencephalon | | | +-----------------------+-----------------------+-----------------------+ | Medulla Oblongata | Lowest portion of the | 1. Aids in | | | brainstem | controlling | | | | reflex activity: | | | | | | | | a. Heart rate | | | | | | | | b. BP | | | | | | | | c. Respirations | | | | | | | | d. Coughing | | | | | | | | e. Sneezing | | | | | | | | f. Swallowing | | | | | | | | g. Vomiting | | | | | | | | 2. **Contains | | | | nuclei** of the | | | | **IX through | | | | XII** cranial | | | | nerves | | | | | | | | 3. **Sleep-wake** | | | | rhythms | +-----------------------+-----------------------+-----------------------+ | **BRAINSTEM** | | | +-----------------------+-----------------------+-----------------------+ | Comprised of the | | | | midbrain, pons, and | | | | medulla oblongata | | | | | | | | Connects the two | | | | hemispheres, | | | | cerebellum, and | | | | spinal cord | | | +-----------------------+-----------------------+-----------------------+ | **Reticular | Large network of | 1. Controls vital | | Formation** | diffuse nuclei that | reflexes: | | | connect the brainstem | | | | to the cortex | a. **Cardiovascu | | | | lar** | | | | | | | | b. Respiration | | | | function | | | | | | | | 2. **Vomiting, | | | | yawning, and | | | | hiccups** = | | | | reflex-like motor | | | | responses | +-----------------------+-----------------------+-----------------------+ | "**Reticular | Reticular formation + | 1. Essential for | | Activating System**" | Cerebral cortex | maintaining | | | | consciousnessrigidity - Postural abnormalities - **Fragmented sleep**, hyposomnia - Fatigue - **Depression** - Pain - Autonomic dysfunction - Dementia with or without psychosis - Time of onset: - Primary Parkinson's disease: after 40 years of age with mean onset of 60 years of age - Men are more likely to have PD than women. - Secondary PD is neurodegenerative disease + another acquired disorder - Familial PD is 10%, with majority either sporadic or idiopathic. - Treatment: drug therapy to treat and restore dopamine levels and decrease akinesia and manage nonmotor symptoms (drug therapy may not begin until incapacitant.) **CHAPTER 18-Disorders of the Central and Peripheral Nervous Systems and the Neuromuscular Junction** **Know the characteristics of closed head injury.** 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. - Vital sign instability may occur with closed head injury: Transient cessation of respiration with brief periods of bradycardia, and a decrease in blood pressure, lasting 30 sec or less. Vital signs stabilize within a few seconds to within normal limits 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. - [Contusions:] - Blood leaking from an injured vessel found - Most commonly in the: - Frontal lobes (particularly at the poles and along the inferior orbital surfaces) - Temporal lobes - Frontotemporal junction - [Extradural hematomas:] - Bleeding between the dura mater and the skull (e.g., epidural hematomas or epidural hemorrhages) - Most common cause: MVAs - Arterial bleeding is involved 85% of the time - [Subdural hematomas:] - MVAs are most common cause - Falls (especially in older adults or in those with long-term alcohol abuse) are associated with chronic subdural hematomas) - 50% are associated with skull fractures - Acute forms develop rapidly (within 48 hours) and are usually located at the top of the skull - Occurs in 10-20% of TBIs. - S/S: headache (80% of people), drowsiness, restlessness, and agitation. - [Intracerebral hematomas:] - MVAs and falls from some distance - May be single or multiple and they are associated with contusions. - Most commonly located in the frontal and temporal lobes. - Occurs in 2-3% of TBIs - S/S: decreasing LOC; may cause contralateral hemiplegia and a positive Babinski reflex **Define concussion. Know the different grades of concussion.** **Concussion** - 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 **[MILD TBI (mild concussion)]** - [Definition:] immediate but transitory clinical manifestations without loss of consciousness OR loss of consciousness that is momentary or less than 30 minutes - Posttraumatic anterograde amnesia also may exist transiently to less than 24 hours. - [Cause:] most blunt trauma injuries cause mild TBI - [GCS:] 13 to 15 - [Diagnostics:] may be no findings with CT/MRI (lesions may be detected with advanced MRI imaging) - [S/S:] headaches, nausea and vomiting, confusion, disorientation, attention deficit, dizziness, and impaired ability to concentrate for days after the injury, **reduced level of consciousness**. - Increase symptoms with: **diffuse axonal injury**, metabolic impairment, alterations in neural activation, and cerebral blood flow perturbations - \*\*Biomarkers are under investigation to assist with diagnosis of mild TBI - [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 - Initial confusion lasts from one to several minutes with possible retrograde amnesia for events preceding the trauma - Grades of mild concussions are as follows: - Grade I -- transient confusion and disorientation accompanied by amnesia, no loss of consciousness, and symptoms resolve within 15 minutes. - Grade II -- transient confusion and retrograde amnesia that develops after 5-10 minutes, and symptoms last no more than 15 minutes. - Grade III -- any loss of consciousness, confusion, and amnesia remain present from impact and persist for several minutes. - Grade IV (NOT MILD, called classical cerebral concussion): any loss of consciousness (can last up to 6 hours) accompanied by retrograde and anterograde amnesia. **[MODERATE TBI (moderate cerebral concussion)]** - [Definition:] - any loss of consciousness lasting more than 30 minutes - accompanied by posttraumatic anterograde amnesia lasting 24 hours or more - [GCS:] 8 to 13 - [Possible complication:] basal skull fracture with NO brainstem injury - There is transitory decerebration or decortication with unconsciousness lasting days or weeks. - [S/S:] confused and experiences a long period of posttraumatic amnesia; permanent deficits in selective attention, vigilance, detection, working memory, data processing, vision or perception, and language, as well as mood and affect changes ranging from mild to severe. **[SEVERE TBI (severe concussion)]** - [Definition:] Loss of consciousness lasts more than 24 hours. The person experiences immediate autonomic dysfunction that resolves in a few weeks. Increased ICP appears 4 to 6 days after injury. - [GCS]: less than 8 associated with brainstem signs (pupillary reaction, cardiac and respiratory symptoms, posturing) and intracranial contusions, hematomas, or lacerations. - Pulmonary complications occur frequently, with profound sensorimotor and cognitive system deficits. - [S/S:] severely compromised coordinated movements and verbal and written communication, inability to learn and reason, and inability to modulate behavior - [Prognosis:] severe injury causes permanent neurologic deficits (20% of adults) and it has been shown that up to 14% remain in a vegetative state, and 20% to 40% of patients end up dying as a result of brain injury or secondary complications. - Goal of treatment: maintain cerebral perfusion and oxygenation, promote neuroprotection, and mitigate long-term neurologic deficits. - **Corticosteroid Randomisation After Significant Head Injury (CRASH)** trial showed corticosteroids increase mortality with acute TBI; consequently, these drugs are no longer used. - Some of the effects of a concussion may persist for weeks or months, depending on the severity of the injury. - Approximately 15% to 30% of persons have a **post-concussive syndrome** that includes headache, nervousness or anxiety, irritability, insomnia, depression, inability to concentrate, forgetfulness, and fatigability. - Treatment entails reassurance, symptomatic relief, and close observation for 24 hours with follow-up care for persistent symptoms. **Coupe and countercoup brain injuries and how they happen.** Coup and countercoup injuries are types of focal brain injuries, which result from compression of the skull at the point of impact and rebound effects. **[Coup injury:]** focal injury is directly below the point of impact. Objects striking the front of the head usually produce only coup injuries (e.g., contusions and fractures). **[Countercoup Injury]**: focal injury is on the pole opposite the site of impact (e.g., objects striking the back of head or side of head). - The force of impact (translational acceleration) typically produces localized brain contusions. - Injuries to the vault, other vessels, and supporting structures can produce epidural hemorrhage and subdural and intracerebral hematomas. **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?** - Immediately after a spinal cord injury, normal activity of spinal cord cells at and below the level of injury stops because of loss of the continuous tonic discharge from the brain or brainstem and inhibition of suprasegmental impulses, thus causing spinal shock. - **Spinal shock**: - Complete **loss of spinal reflex function**, flaccid paralysis, sensory deficit, and loss of bladder/rectal control in all segments below level of injury. - Disruption of central communication with **sympathetic spinal nerves** causes: - A transient drop in BP - Poor venous circulation - **Disturbed thermal regulation**. - **Hypothalamus** cannot regulate **body heat through vasoconstriction and increased metabolism therefore individual's body temperature assumes the temperature of the air**. - This damage causes **faulty control of diaphoresis (sweating)** and heat radiation through capillary dilation. - Indications that spinal shock is terminating include the reappearance of reflex activity, hyperreflexia, spasticity, and reflex **emptying of the bladder.** - Initial **clinical manifestations** with acute spinal cord injury: - Rapid loss of voluntary movements in body parts below the level of injury. - Bladder incontinence - Sensations in the lower extremities and possibly lower trunk (depending on the level of injury). - Loss of deep tendon reflexes - Spinal and autonomic reflexes below the level of injury. - Flaccid paralysis - Spinal cord injuries are **life threatening** because they could possibly lead to - **AUTONOMIC DYSREFLEXIA** (or autonomic hyperreflexia) - A syndrome of sudden and massive sympathetic discharge associated with spinal cord injury at level T5-T6 or above -- causing life *threatening hypertension*. - Supraspinal control of the SNS is disrupted, causing an imbalance between the SNS and parasympathetic nervous systems. - S/S: paroxysmal HTN (up to 300mmHg systolic), bradycardia (30-44bpm), pounding headache, blurred vision, sweating above the level of the lesion with skin flushing, nasal congestion, nausea, and piloerection - Symptoms may develop singly or in combination and are often associated with somatic (distended bladder or rectum) or sensory stimulation. - REQUIRES IMMEDIATE TREATMENT CVA IS POSSIBLE - Spinal cord injuries most often occur at vertebrae C1 to C2 (cervical), C4 to C7, and T10 to L2 (thoracic lumbar) because these are the most mobile portions of the spine. **Define and discuss the different types of stroke** **[ISCHEMIC STROKE]** - Thrombotic strokes (cerebral thrombosis): - Arise from arterial occlusions caused by thrombi formed in the arteries supplying the brain or in the intracranial vessels - Thrombotic CVAs develop most often from atherosclerosis and inflammatory disease processes that damage vessel walls. - Atherosclerosis form at branching and curves in cerebral circulation platelets and fibrin adhere to the damaged wall, with clot formation and artery occlusion clots detach and travel to distant sites where occlusion occurs, producing stroke symptoms - Transient ischemic attacks (TIAs): - Transient episodes of neurologic dysfunction (weakness, numbness, sudden confusion, loss of balance, loss of vision, and sudden severe headache) - Resulting from focal cerebral ischemia - Embolic stroke: - Involves fragments that break from the thrombus formed outside the brain or in the heart, aorta, or common carotid artery. - Other sources of embolism include fat, air, tumor, bacterial clumps, and foreign bodies. - The embolus usually involves small vessels and obstructs at a bifurcation or other point of stenosis, thus causing ischemia. - Embolization is usually in the distribution of the middle cerebral artery (the largest cerebral artery). - Note: Cerebral infarction results when an area of the brain loses blood supply and becomes ischemic because of vascular occlusion (embolic or thrombotic). - High-risk sources for the onset of embolic stroke are **atrial fibrillation** (15% to 25% of strokes), left ventricular aneurysm or thrombus, left atrial thrombus, recent myocardial infarction, rheumatic valvular disease, mechanical prosthetic valve, nonbacterial thrombotic endocarditis, bacterial endocarditis, patent foramen ovale, and primary intracardiac tumors. - Lacunar stroke: - A **microinfarct smaller** than 1 cm in diameter and involves occlusion of the small perforating arteries, predominantly in the basal ganglia, internal capsules, and pons. - Usually caused by perivascular edema hyperlipidemia, smoking, HTN, and DM. - May have pure motor and sensory deficits due to subcortical location and small area of infarction. **[HEMORRHAGIC STROKE]** Spontaneous bleeding into the brain. - Most common cause of primary hemorrhage strokes are **HTN**. - Most common sites: putamen in basal ganglia, thalamus, cortex and subcortex, pons, and cerebellar hemispheres. - Focal neurologic deficits are found in 80% of people experiencing hemorrhagic strokes. **Which affected artery causes what data processing deficits (agnosia, dysphasia, etc).** +-----------------------------------+-----------------------------------+ | AFFECTED ARTERY | DATA PROCESSING DEFICIT | +===================================+===================================+ | **Middle cerebral artery** (MCA), | Boca area and deep fibers in the | | either stem or branches | dominant hemisphere | | | | | | - Speech: expressive (motor) | | | disorder with anomia (left | | | hemisphere most commonly | | | affected) with nonfluent | | | **aphasia** and some | | | comprehension defects | | | | | | Boca area and deep fibers in the | | | nondominant hemisphere | | | | | | - Speech: dysarthria | +-----------------------------------+-----------------------------------+ | **Anterior Cerebral Artery | Main stem (complete occlusion is | | (MCA)** | uncommon, thus areas affected | | | differ and collateral circulation | | | may alleviate signs or symptoms); | | | medical aspect of fontal lobes | | | caudate nucleus, and corpus | | | callosum are supplied by the ACA | | | | | | - Motor**: Contralateral | | | paralysis or paresis (greater | | | in foot and thigh);** mild | | | upper extremity weakness | | | | | | - Sensory: Mild contralateral | | | lower extremity deficiency | | | with loss of vibratory and/or | | | position sense, loss of two | | | point discrimination | | | | | | - Frontal lobe releasing signs | | | (grasp, snout, root, and suck | | | reflexes) | | | | | | - Apraxia | +-----------------------------------+-----------------------------------+ | Basilar Artery | Midline structure of pons | | | (paramedian branches); three | | | general areas of infarction are | | | common: | | | | | | 1. Medial pontine syndrome | | | | | | 2. Medial midpontine syndrome | | | | | | 3. Medial superior pontine | | | syndrome | | | | | | - Motor: contralateral | | | hemiparesis or hemiplegia, | | | ipsilateral lower motor | | | neuron facial palsy, "locked | | | in syndrome" | | | | | | - Sensory: contralateral loss | | | of vibratory sense, sense of | | | position with dymetria, loss | | | of two point discrimination, | | | impaired rapid alternating | | | movements | | | | | | - Visual: inferior pontine: | | | diplopia; impaired abduction | | | of ipsilateral eye: | | | internuclear opthalmoplegia; | | | medial superior; diplopia, | | | internal nuclear | | | opthalmoplegia, skewed | | | deviation | +-----------------------------------+-----------------------------------+ | Posterior Cerebral Artery | Inability to real, color anomia | | | | | | Sensory: contralateral sensory | | | loss of all modalities without | | | agraphia | | | | | | Function: prosopagnosia | | | (inability to recognize familiar | | | faces), topographic | | | disorientation, memory deficits, | | | alexia | +-----------------------------------+-----------------------------------+ **Know characteristics of AV malformation (arteriovenous malformation)** - AVM is a mass of dilated vessels between the arterial and venous systems (arteriovenous fistula) that lack a muscularis layer and have the absence of an intervening capillary bed - arteries feed directly into veins through a vascular tangle of malformed vessels - Exhibit a delayed age of onset, and symptoms most commonly occur before 30 years of age. - Usually rupture in the second and third decades of life. - They are developmental abnormalities that represent persistence of embryonic patterns of blood vessels, do not have normal blood vessel structure, and are abnormally thin - Clinical manifestations: - 20% have chronic, nondescript headache (although some experience migraine) - 50% - seizure disorders - 50% - intracerebral, subarachnoid, or subdural hemorrhages with progressive neurologic deficits - Bleeding from an AVM into the subarachnoid space causes clinical manifestations identical to those associated with a ruptured aneurysm. If bleeding is into the brain tissue, focal signs progress over a short period of time. - 10% - hemiparesis or other focal signs (caused by compression or rupture) - Non-communicating hydrocephalus (large AVM that extends into ventricle lining) - 1% - sudden death - Evaluation: a **systolic bruit** over the carotid in the neck, the mastoid process, or (in young person) the eyeball = AVM - Diagnostics: confirm with CT and MRI/MRA - Treatment: direct surgical excision, endovascular embolization, or radiotherapy - Complications: hemorrhagic stroke, epilepsy, chronic headache, or focal neurologic deficits **Know clinical manifestations & presenting signs of meningitis** **Definition:** inflammation of the brain or spinal cord; may be acute, subacute, or chronic **[BACTERIAL MENINGITIS]** - Etiology: primarily affects the pia mater and arachnoid villi, subarachnoid space, ventricular system, and the CSF - Cause: Neisseria meningitis and Streptococcus pneumoniae are most common pathogens - The clinical manifestations: - Systemic infection: include fever, tachycardia, and chills. - Meningeal irritation: severe throbbing headache, severe photophobia, nuchal rigidity, and positive Kernig and Brudzinski signs. - Neurologic signs: a decrease in consciousness, focal neurologic deficits (such as hemiparesis/hemiplegia and ataxia), and seizures. The irritation and damage to the cranial nerves produced by the inflamed sheaths manifest as follows: - Cranial nerve II: papilledema, blindness - Cranial nerves III, IV, and VI: ptosis, visual field deficits, diplopia - Cranial nerve V: photophobia - Cranial nerve VII: facial paresis - Cranial nerve VIII: deafness, tinnitus, vertigo - Neck stiffness and pain, and possibly head retraction = irritability of spinal accessory and cervical spinal nerves - Often the vomiting center is irritated, causing projectile vomiting. - Confusion and decreasing responsiveness = cortical involvement - In meningococcal meningitis, petechial or purpuric rash involving the skin and mucous membranes occurs. - As ICP increases, papilledema may develop with declining levels of consciousness **[VIRAL MENINGITIS ]** - Etiology: limited to the meninges and identifiable bacterium or specific pathogen cannot be found in the CSF - Most common viruses are enteroviral viruses - Immune response lead to release of inflammatory cytokines with increased permeability of the blood brain barrier and entry of circulating immunoglobulins that combat the virus - The clinical manifestations (mild compared to bacterial meningitis): - Mild generalized throbbing headache - Mild photophobia - Mild neck pain - Stiffness - Fever - Malaise - Treatment: primarily supportive and the disease usually resolves within 7 to 10 days. **Clinical manifestations and presenting signs of brain abscess.** - Definition: abscesses are localized collections of pus within the parenchyma of the brain or spinal cord and are rare. - Immunosuppressed persons are particularly at risk. - Brain abscesses are classified as extradural, subdural, or intracerebral. - Extradural brain abscesses (empyemas) are associated with osteomyelitis in a cranial bone. - Subdural brain abscesses (empyemas) arise from a sinus infection or a vascular source. - Intracerebral brain abscesses arise from a vascular source. - **Progression:** localized inflammation to a necrotic core with the formation of a connective tissue capsule, usually within 14 days or longer. - Brain abscesses evolve through four stages regardless of infecting microorganism, except in the immunosuppressed host where the process may be incomplete. - The stages are as follows: - Early cerebritis (days 1 to 3): - A localized inflammatory process develops in which perivascular infiltration and inflammatory cells, composed of neutrophils, plasma cells, and mononuclear cells, surround a central core of coagulative necrosis - marked cerebral edema surrounds the area - Late cerebritis (days 4 to 9): - The necrotic center is surrounded by an inflammatory infiltrate of macrophages and fibroblasts; rapid new blood vessels form around the abscess; a thin capsule of fibroblasts and reticular fibers gradually develops; the area is still surrounded by cerebral edema. - Early capsule formation (days 10 to 13): - The necrotic center decreases in size; the inflammatory infiltrate changes in character and contains an increasing number of fibroblasts and macrophages; mature collagen evolves, forming a capsule. - Late capsule formation (days 14 and longer): - A well-formed necrotic center surrounded by a dense collagenous capsule develops. - The development of symptoms may be very insidious, often making an abscess difficult to diagnose: - Early manifestations: low-grade fever, headache (most common symptom), nausea and vomiting, neck pain and stiffness, confusion, drowsiness, sensory deficits, and communication deficits. - Later manifestations (associated with an expanding mass): decreased attention span, memory deficits, decreased visual acuity and narrowed visual fields, papilledema, ocular palsy, ataxia, cognitive deficits, and seizures. - Extradural brain abscesses are associated with localized pain, purulent drainage from the nasal passages or auditory canal, fever, localized tenderness, and neck stiffness; occasionally the individual experiences a focal seizure. - Evaluation: suggested on the basis of clinical features and confirmed with MRI or contrast-enhanced CT - Treatment: stereotactic surgical aspiration identification of the pathogen and for decompression of the abscess. - Antibiotics are initiated clinical suspicion of an abscess. - Multiple or surgically inaccessible abscesses are treated with antibiotics (+ corticosteroid therapy to treat the cerebral edema) - In addition, ICP or hydrocephalus, or both, require management. **Define and describe the pathophysiology, clinical manifestations and etiology of Multiple Sclerosis.** - Definition: chronic inflammatory disease involving degeneration of CNS myelin, scarring or formation of plaque, and loss of axons. - Etiology: - Onset: usually between 20 and 40 years of age; more common in women; men may have a more severe progressive course - Risk factors: smoking, vitamin D deficiency, Epstein-Barr virus infection - Pathophysiology: - Diffuse and progressive CNS inflammatory 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 the death of neurons. - Etiology: an autoimmune response to self-antigens in genetically susceptible individuals; unknown cause - Genetic and environmental factors and interactions are implicated in disease onset. - 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. - Clinical manifestations (REPLAPSING AND REMITTING) -- Individuals with CIS may or may not progress to Multiple Sclerosis: - Clinically isolated syndrome (CIS) -- acute neurologic episode -- - 1st manifestation of the disease; the first demyelinating event or a single episode of neurologic dysfunction lasting greater than 24 hours in the absence of fever, infection, or encephalopathy and caused by inflammation and demyelination in the CNS - S/S MULTIfocal: paresthesia of the face, trunk, limbs; weakness; impaired gait; visual disturbances; urinary incontinence (diffuse CNS involvement) - S/S MONOfocal (caused by single lesion): optic neuritis (one eye with progressive blurring of vision and pain with eye movement), spinal cord syndrome (both sensory and motor tracks starting on one side and progressing to the other), solitary brainstem lesions, transverse myelitis - Brainstem syndromes can involve facial sensory loss or weakness, vertigo, or double vision. - Cerebellar syndromes demonstrate lack of coordination, tremor, gait instability, and ataxia. - Lesions in the cerebrum present as hemifacial weakness, pain, and motor impairments. - Cognitive deficits, including memory and attention problems, are common later in the disease as well as psychiatric disorders, depression, and dementia. - Multiple Sclerosis is diagnosed by MRI-detected brain or spinal cord lesions - Initial syndrome depends on the portion of the CNS that is most involved - After years of disease, 50% of individuals appear to have established syndromes of multifocal involvement. - The four symptom subtypes of Multiple Sclerosis are: - [Relapsing/remitting]: - Most common type of MS - Characterized by relapses or exacerbations (flares) of previous symptoms or worsening of neurologic symptoms - After a relapse, a period of full or partial recovery lasts for days, weeks, or months - More common in women - [Primary progressive MS:] - Least common - Characterized by a gradual progression of the disease without periods of remission. - Men and women seem to be equally affected (most common age of onset between late 30s and early 40s) - Disease activity is more prevalent in the spinal cord and is less likely than other forms to affect cognitive function. - Gradual loss of power in the lower limbs that can be asymmetric, and bowel and bladder symptoms. - Symptom acuity has the potential to level off. - [Secondary progressive Multiple Sclerosis:] - Follows an initial period of relapsing/remitting Multiple Sclerosis followed by a gradual worsening of the symptoms between relapses - Although there may be short intervals of symptom remission, these periods decrease over time and are often accompanied by more severe symptoms - [Progressive relapsing multiple sclerosis (PRMS):] - Characterized by steadily worsening symptoms from the onset with clear acute relapses but often with more severe symptoms - Evaluation: no single test available to diagnose or rule out MS; McDonald Criteria -- clinical exam in combo with MRI to demonstrate MS lesions in time and space (most sensitive and available method for detecting demyelinated plaques and monitoring disease and quantifying macrophage infiltration and abnormal iron deposition - Treatment: - Prevent exacerbations - Decrease MRI lesion burden, and control symptoms - Disease-modifying drugs are initiated with diagnosis (include corticosteroids, immunosuppressants, and immune system modulators) - Acute remissions -- treated with steroids to speed recovery; vitamin d supplements may reduce the risk of MS; stem cell therapy is under investigation **Define and describe the pathophysiology, clinical manifestations and etiology of Guillian Barre Syndrome.** - Definition: - Landry-Guillain-Barré syndrome, idiopathic polyneuritis, acute inflammatory demyelinating polyradiculopathy, **acute autoimmune neuropathy** - A rare **demyelinating disorder caused by a humoral (antibody) and cell-mediated immunologic reaction** directed at the peripheral nerves - Pathophysiology - Molecular mimicry (cross-activation of self-epitopes and pathogen-derived peptides by autoreactive T and B cells) is associated with immune injury. - Glycolipids, particularly gangliosides, are immune targets in the subtypes of GBS. - Etiology: - GBS is considered to be an autoimmune disease triggered by **a preceding bacterial or viral infection**. Frequently preceded by mild respiratory or intestinal infections. - Clinical manifestations: may vary depending on the subtype - Typical first manifestations are numbness, pain, paresthesias, or weakness in the limbs. - Motor signs manifest as an acute or subacute progressive paralysis, with proximal muscles involved earlier and more significantly than distal muscles. - Paresis/paralysis may be present in an ascending bilateral pattern involving limbs, respiratory muscles, and bulbar muscles. - Persons may undergo a respiratory arrest or cardiovascular collapse, a cause of death. - Progresses over hours to days; minimal muscle atrophy; symmetrical paralysis. **Define and describe the pathophysiology, clinical manifestations and etiology of Myasthenia Gravis** - Definition: a chronic autoimmune disease mediated by acetylcholine receptor (AchR) antibodies that act at the neuromuscular junction (NMJ). - Subtypes include generalized AchR, ocular, and neonatal - Pathophysiology - Results from a defect in nerve impulse transmission at the NMJ. - Autoantibodies block the AchR or cause complement-mediated loss of AchRs from the NMJ. - The main defect is T-cell dependent formation of autoantibodies (an IgG antibody) against receptors at the Ach-binding site on the postsynaptic membrane. - Result is destruction of receptor sites, causing diminished transmission of nerve impulses across the NMJ. - Etiology: unknown; some persons have genetic susceptibility related to variants in acetylcholine genes, as well as the major histocompatibility genes, and they can present with varying clinical phenotypes. - Clinical manifestations: - *Hallmark symptom:* exertional fatigue & weakness that worsens with activity and improves with rest. - Muscle weakness - Individual may have recent hx of recurring URIs. - Muscles of the eye, face, mouth, throat, and neck are affected first, with the eyes being the most affected. - Other symptom include: diplopia, ptosis and ocular palsies, facial droop and expressionless face, difficulty chewing and swallowing, drooling, and weakness of the arms and legs and eventually weakness of the diaphragm, impairing ventilation. - Concerns include myasthenic crisis and cholinergic crisis. **Know types of tumors and its site of development/origination.** - Brain tumors - Primary intracerebral tumors: originate from brain substance - Neuroglia - Neurons - Primary extracerebral tumors: originate outside of the brain - Meningioma - Acoustic nerve tumors - Tumors of pituitary and pineal glands - Metastatic (secondary) carcinoma - Spread from another area in the body to the brain - Gliomas - Include astrocytomas, oligodendrogliomas, mixed oligoastrocytomas, and glioblastoma multiforme - Clinical manifestations - Seizures, visual disturbances, loss of equilibrium, cranial nerve dysfunction - Treatment - Surgical or radiosurgical excision - Surgical decompression if total excision is not possible - Chemotherapy, radiation therapy, or a combination of both - Blood--brain barrier is an obstacle to the delivery of chemotherapeutic agents. - Astrocytoma: - Develop from astrocytes and grow into the normal surrounding brain tissues - **Most common** primary CNS tumors (50% of all brain and spinal cord tumors) - Clinical manifestations - Headache and subtle neurobehavioral changes are early symptoms. - Generalized seizures or focal seizures may occur. - Treatment - Grade I: Surgery - Grade II: Surgery and conventional external radiation, local radiation, or stereotactic radiosurgery - Oligodendroglioma: - Low-growing, well-differentiated tumors, often with cysts and calcification - Clinical manifestations - Seizures - Increased ICP at the time of diagnosis and surgery - Treatment - Surgery and radiotherapy - Ependymoma - Rare gliomas that arise from ependymal cells that form the walls of the ventricles or the spinal canal - Not encapsulated - Clinical manifestations - Seizures, visual changes, contralateral weakness of a body part on one side of the body - Treatment - Surgery and radiotherapy of the tumor region and operative site - Meningiomas - Slow-growing, often encapsulated tumors arising from arachnoid (meningeal) cap cells in the dural coverings of the brain - Clinical manifestations - Seizures - Treatment - Surgical resection - Stereotactic radiotherapy for incomplete resection or recurrence - Conventional radiotherapy - Hydroxyurea and somatostatin - Nerve sheath tumors - Neurofibromas or schwannomas - Associated with altered chromosomes - Clinical manifestations - Headache, tinnitus, hearing loss, impaired balance, unsteady gait, facial pain, loss of facial sensations - Treatment - Surgical excision and radiotherapy - Metastatic brain tumors - Lung and breast are the most common tumors to have brain metastases. - Clinical manifestations - Include headache, seizures, and alterations in cognition, mental status, and behavior - Treatment - Surgery, Radiotherapy, Whole-brain radiation - Spinal Cord Tumors: - Intramedullary tumors: originating in neural tissue - Produce dysfunction by invasion and compression - Extramedullary tumors: originating from outside the cord - Produce dysfunction by compression of adjacent tissue, not by direct invasion - Intradural tumors: tumors originating in the meninges or nerve roots - Extradural tumors: tumors originating in the epidural tissue or vertebral structures - Metastatic tumors - From the breast, lung, prostate, lymphomas, myelomas - **Clinical manifestations** - Gradual and progressive - Compressive syndrome (sensorimotor) - Irritative syndrome (radicular) - Syringomyelic syndrome (inflammation of the spinal cord) - **Treatment** - Surgery - Radiation - Chemotherapy - Hormonal therapy - Pain management **Know most common primary CNS tumor.** - Brain tumors are the most common solid tumor and cause of cancer death in children. - Adults: - Gliomas comprise 50% to 60% of all adult primary brain tumors including: - Astrocytomas - Oligodendrogliomas - Mixed oligoastrocytomas - Glioblastoma multiforme - Approximately 70% to 75% of all intracranial tumors diagnosed in adults are located supratentorially (above the tentorium cerebella). - Astrocytomas are a type of glioma and the most common primary CNS tumor (50% of all brain and spinal cord tumors). - Astrocytomas develop from astrocytes and grow by expansion and infiltration into the normal surrounding brain tissues. - These tumor cells are believed to have lost normal growth restraint, and thus they proliferate uncontrollably. - Generally located in the cerebrum, hypothalamus, or pons. - Grade IV astrocytoma -- Glioblastoma Multiform is the most lethal. - Children: nearly 75%-80% of all pediatric brain tumors are either: - Medulloblastoma - Ependymoma - Gliomas (astrocytoma, brain stem glioma, and optic nerve glioma) - Craniopharyngioma - Approximately 70% of all intracranial tumors in children are located infratentorially (below the tentorium cerebelli) **CHAPTER 19- Neurobiology of Schizophrenia, Mood Disorders & Anxiety Disorders** **What is schizophrenia? What part of the brain is associated with the S/S of this disorder?** - Schizophrenia is the term coined by Eugen Bleuler in 1911 to describe a collection of illnesses characterized by thought disorders, which reflect a break in reality or splitting of the cognitive from the emotional side of one's personality. - It is a heritable disorder, though not a simple genetic disorder in which inherited disease alleles will always lead to illness -- it likely involves several genes located on different chromosomes and thus differs from mendelian disorders. - Affects 1% of the world's population. - Related to genetic predisposition and prenatal/perinatal vulnerability factors. - Brain abnormalities in schizophrenia are believed to originate in the **prenatal period** of cell proliferation and migration - Maternal illnesses such as having **viral infections** results from neurodevelopmental defects that occur in fetal life - Neurochemical and neuroanatomic alterations of patients with schizophrenia: - Under activation of glutamate receptors also contributes to schizophrenia - Level of **glutamic acid decarboxylase** a major enzyme in **GABA biosynthesis**, is *reduced*, which likely impairs normal cognitive/emotional functions. - Negative symptoms and cognitive alterations in schizophrenia are proposed to result from reduced **dopaminergic neurotransmission** in the **mesocortical dopamine pathway**. - Another neurotransmitter system that may underlie the pathogenesis is the **excitatory neurotransmitter glutamate** and its actions on the **NMDA (N-methyl-D-aspartate**). - Enlargement of the lateral and third ventricles and widening of the frontocortical fissures and sulci. Individuals with cerebral ventricle enlargement often exhibit cognitive impairments and negative symptom and respond poorly to treatment. - Reduction in the **thalamus and temporal lobe areas** (amygdala, hippocampus, and parahippocampal gyrus). - Reduction in thalamus size may disrupt neurotransmission between the cortex and primary sensory and motor areas. - **Temporal lobe** alterations may contribute to **positive symptom**. - Brain studies in adolescents with early onset reveal progressive loss of cortical gray matter in temporal lobes, somatosensory and motor cortices, and the dorsolateral cortex. - The progressive loss in **frontal lobe** volume is accompanied by increased severity of negative symptom and further reduction in cognitive functioning. - Functional alterations in the **dorsolateral prefrontal cortex** (reduced blood flow and metabolism) compromise abilities to engage in goal-directed and cognitive problem-solving behavior. - Reelin, an extracellular matrix protein involved in neuronal migration during development and in synaptic function during adulthood, is reduced Structural Brain Abnormalities PRESENTATION ----------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------ Cerebral ventricular changes Cognitive impairments and negative symptoms; also respond poorly to treatment. Temporal lobe alteration Positive symptoms present Dorsal prefrontal cortex changes (especially DLPFC) Negative symptoms are present; impaired initiation and maintenance of goal-oriented activities and cognitive problem-solving in relation to working memory - Disorganized thought in schizophrenia is characterized by positive and negative symptoms, including auditory hallucinations, paranoid delusions, and cognitive deficits. - **Positive** symptoms: linked to **[excess] dopamine** - Delusions - Hallucinations - Disturbances in thought - Bizarre behavior - **Negative** symptoms: linked to **prefrontal pathologies** - Loss of affect (flattened affect) - Lack of speech (alogia) - Absence of pleasure (anhedonia) - Attention deficits - Apathy - Catatonia - Immobility **Define depression and its types** - Mood disorders: when emotional states, such as sadness (or mania), become chronic and uncontrollable. - Alterations in **hypothalamic-pituitary-adrenal (HPA) system**, **serotonin (decrease)**, norepinephrine, and dopamine are related to **depression symptoms**. - Two major classifications of mood disorders: - Unipolar, or major or clinical depression. - Bipolar disorder. - Genetic, environmental, neurochemical dysregulation, and neuroendocrine dysregulation have been found to play a role in the pathogenesis and/or etiology of depression. - Major depression: unremitting feelings of sadness and despair, dysphoric mood accompanied by frequent insomnia, loss of appetite and loss of body weight, and reduced interest in pleasurable activities and interpersonal relationships. - Most common mood disorder and the leading cause of disability in the U.S. and throughout the world. - Diagnosed by the presence of five or more of the following symptoms in a two weeks period, with at least one symptom being either depressed mood or loss of interest of pleasure: - Depressed or irritable mood - Loss of interests or pleasure - Significant (\>5%) weight gain or loss in a month - Insomnia or hypersomnia - Psychomotor agitation or retardation - Fatigue or loss of energy - Feelings of worthlessness or excessive guilt - Poor concentration or indecisiveness - Recent thoughts of death or suicide - Theories of Etiology: - [Genetic predisposition and environmental influences]: current view of mood disorders is that the illness stems from a complex interplay between susceptible genes and environmental influences, such as the interplay between life stressors and a potentially dysfunctional serotonin system, which appears to elevate the risk of depression. - [Neurochemical dysregulation]: monoamine hypothesis of depression found that a deficit in the concentration of brain norepinephrine, dopamine, and/or serotonin = underlying cause of depression; also found a reduction of monoamine metabolites in the CSF in depressed clients. - [Neuroanatomic and functional abnormalities] - Norepinephrine receptor alterations have been found in the frontal cortex of some suicide victims. - In depressed individuals, there is a widespread decrease in serotonin 5-HT1A receptor subtype binding in the frontal, temporal, and limbic cortex, as well as serotonin transporter binding in the cerebral cortex and hippocampus. - There are also reports of reduced frontal lobe volume in depressed individuals and decreased or asymmetric temporal lobe volume with bipolar illness and depression. - [Neurochemical dysregulation:] - **Chronic activation of the HPA system** and elevated glucocorticoid secretion are found in **major depression**. - Antidepressant drugs effective in normalizing the mechanisms responsible for increased HPA hormone secretion are associated with a good clinical response. - Psychosocial stress-induced activation of the immune system increases secretion of proinflammatory cytokines, such as interleukin-1α (IL-1α) and IL-β, tumor necrosis factor--alpha (TNF-α), and IL-6, which modulates signaling pathways throughout the periphery and brain and augments further secretion of HPA hormones and monoamine metabolism. This may lead to chronic elevations in cortisol levels. - A reduction in the development of new hippocampal neurons (neurogenesis), and a deficit in hippocampal brain-derived-neurotrophic factor (BDNF) levels have been identified