The Nervous System PDF Lecture 21

The Nervous System Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives Describe the normal structure and basic functions of the brain, meninges, and cerebrospinal fluid. 2. Define muscle tone and voluntary motor activity, and re...

The Nervous System Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives Describe the normal structure and basic functions of the brain, meninges, and cerebrospinal fluid. 2. Define muscle tone and voluntary motor activity, and relate these concepts to the two forms of muscle paralysis. 3. Explain the pathogenesis and clinical manifestations of closure defects of the central nervous system. Name the techniques used for prenatal diagnosis. 4. Describe the pathogenesis and manifestations of hydrocephalus, and relate them to treatment measures. 5. Describe the pathogenesis and manifestations of rabies. 6. Name the causes, manifestations, and treatment of transient ischemic attacks. 7. Differentiate the principal types of stroke in regard to pathogenesis, prognosis, and treatment. 8. Describe the pathogenesis, manifestations, and treatment of congenital cerebral aneurysms. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com 1. Learning Objectives Name the types of tumors that affect the central nervous system, and explain their origin, pathogenesis, clinical manifestations, and treatment. 10. Explain the pathogenesis, major clinical manifestations, and general principles of treatment of Parkinson disease, meningitis, multiple sclerosis, and Guillain-Barré syndrome. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com 9. Blood/Brain barrier Brain/spinal chord (CNS) is immune privilege site (Testis and eyes) ▪ Blood brain barrier cells have special tight junctions that don’t allow cell transfer seen in endothelium as easily, T cells are rare – presence in CSF indicates infection – also block pathogens/toxins ▪ Sites are easily impaired by inflammation ▪ Impaired adaptive immunity (no DC and lack of lymphatic drainage – low trafficking, antibodies can’t cross) ▪ Microglia cells, higher threshold for activation than peripheral macrophages ▪ Most drugs don’t have access – tx, need to inject directly into CSF Damaged in several neurological diseases: Alzheimer’s, ALS, Epilepsy, stroke https://www.christopherreeve.org/blog/research-news/blood-brain-barrier-the-spinal-cord Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Highly selective, semi-permeable membrane, maintained by astrocytes surrounding endothelium Nervous System Meninges: Surrounding membranes of CNS ▪ dura (firm fibrous – outer covering/ protective) ▪ Arachnoid (middle - cushioning) ▪ pia (thin – inner) covers brain, spinal cord Sub arachnoid space refers to area between pia and arachnoid layers – contains CSF, connective tissue https://en.wikipedia.org/wiki/Meninges Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Central nervous system (CNS) ▪ Brain, (cerebrum, brain stem, cerebellum) and spinal cord – protected by skull (cranium) CNS – central nervous system PNS – peripheral nervous system (nerves that branch off spinal cord) ▪ Somatic – voluntary movement ▪ Autonomic (involuntary) (Sympathetic/Parasympathetic) controls smooth muscles, glands and organ functions Sympathetic – “fight or flight” Parasympathetic – “rest and digest” Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Brain, spinal cord Nerves Neurons: Nerve cells, transmit nerve impulses Often arranged in chains – separated by synapse (neurotransmitters) Neuroglia: Supporting cells - more numerous than neurons Astrocytes • Long, star-shaped cells, numerous, highly branched process • Provide structure/support and nourishment to neurons Oligodendrocytes Small cells, scanty cytoplasm, surround nerve cell axons • Schwann (PNS), Oligodendrocytes (CNS) Microglia: Phagocytic cells – immune protection Macrophages of NS https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Life-and-Death-Neuron Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Central body: dendrites (transmit toward cell body) and axon (transmit away) emerge from it to transmit impulses Neuron signaling Myelin sheath/ nodes of ranvier (enriched in ion channels (“jumps”– improves conductions (MS)) Send message to another neuron or target cell (muscle/ gland) Depolarization – activation by electrical impulse or chemical receptors send electrical signal down axon Results in release of ions/chemical signals: another neuron, muscle or gland https://www.quizoncloud.com/blog/32/conduction-of-nerve-impulses/ Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Electric impulse carried - (250mph travel speed) activation by ion/chemical signals processed by dendrites Neurotransmitters Neurotransmitters Wide ranging effects – dysregulation associated with an number of physical and mental health disorders: • Schizophrenia, Mood disorders, Depression/Anxiety, PTSD, Parkinson’s, Migraines, Seizures, Addiction, Alzheimer’s, Insomnia. https://www.reddit.com/r/APPsychology/comments/bi34mx/chart_of_most_important_neurotransmitters_to/ Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com • Glutamate (stimulatory) , dopamine (motivation), acetylcholine(neuromuscular), serotonin (mood) GABA (usually inhibitory), Adrenergic (norepinephrine/epinepherine) Brain Composed of Neurons (nerve cells) and neuroglia (supporting cells) together = neuropil ▪ Grey matter is more external (neuronal cell bodies, astrocytes and microglia) ▪ White matter has more central distribution (axons and oligodendrocytes) ▪ afferent nerves (sensory): Transmits impulses to the nervous system ▪ efferent nerves (motor): Transmits impulses from brain or spinal cord to muscle ▪ Transmission signal of a nerve impulse via neurotransmitters (Acetylcholine, norepinephrine, dopamine) occurs in synapses where they are released at axon terminals and received by dendrites Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com The Brain controls all bodily functions/organs (with the exception of reflexes) Brain Cerebral Cortex – receives sensory input and initiates voluntary motor responses Cerebellum – regulates balance, muscle tone, coordination (fine motor control) Spinal cord –continuation of brain stem that conducts signals to body, also contains sensory and motor reflex neurons that are not under cortical control. Tracts conveying sensory and motor inputs cross within the brain stem (right hemisphere registers sensation and activates muscles on the from left side) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Brain Stem – involved in control of vital functions not under voluntary control (cardiac/respiratory regulation and function) and connects cortex to cerebellum Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Arterial blood supply -Large vessels enter base of skull. Vessels join to form arterial circle at base of brain (circle of Willis) Venous blood - Returned from brain into large venous sinuses in dura which drain into jugular veins ▪ Structures in the CNS are surrounded by CSF (fluid cushion) and protected by bone (cranium/vertebral column – hard protection) ▪ Closed system – increased in volume, inflammation or intruding mass (blood/tumor) will put pressure on to the brain causing injury and death Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com The brain has 4 cavities called ventricles – filled with CSF, responsible for production (choroid plexus in each ventricle) and flow of CSF (neutral buoyancy) Voluntary Motor Activity Controlled by nerve impulses originating in upper motor neurons of the cerebral cortex (cortical neurons) ▪ Extrapyramidal system (involuntary) regulates muscle groups concerned with coordinated motor functions (balance, coordination, reflexes) Muscle tone: passive firmness of muscle contraction and resistance to passive stretching (postural muscles) Controlled by reflex arcs – not under direct cortical control, but can be influenced by higher nervous system controls Lack of tone – flaccid, excess tone- spastic Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Pyramidal system controls voluntary motor functions Muscle Paralysis Paralysis – muscle no longer subject to voluntary control Spastic paralysis (CNS damage) ▪ Disease or Injury to cortical neurons (stroke) ▪ Reflex arc not disturbed ▪ Muscle retains innervation but no signals from cortex ▪ Increased muscle tone (cortex extrapyramidal signals tend to inhibit muscle tone are lost) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Flaccid paralysis (PNS damage) ▪ Destruction of lower (peripheral) motor neurons by disease (poliomyelitis) ▪ Interruption of peripheral nerve/reflex arc responsible for muscle tone ▪ Muscle deprived of innervation ▪ Low muscle tone - atrophy Nervous system development Forms neural folds that fuse to form the neural tube (wk4) which is filled with CSF Fusion begins in the tube in areas that will eventually form the hindbrain (first), midbrain and forebrain on one end of the tube – spinal cord at the other end Cerebral hemispheres develop from forebrain Cerebellum and medulla from hindbrain Neural tube defects will result if either end fails to close during development Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com In embryonic development, CNS derives from the ectoderm and first appears as a thickened band of cells (neural plate) Neural Tube Defects 2 most common congenital malformations of nervous system: (5:10 000 births – multifactorial inheritance (risk of recurrence in subsequent offspring 1:20) – folic acid deficiency plays a role Anencephaly ▪ Upper part (cephalic end) of neural tube fails to close ▪ Exposed brain tissue degenerates to mass of vascular connective tissue mixed with degenerated nervous tissue ▪ Failure of normal development of brain and cranial cavity ▪ Incompatible with life Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Spina bifida and Anencephaly Spina bifida Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Failure of closure of spinal cord (caudal end) of neural tube results in failure of closure of vertebral arches ▪ Occult –fusion failure in lower lumbar region (no clinical symptoms) Clinical manifestations are present when meninges and nerve tissue protrudes through defect in vertebral arches: ▪ Meningocele – only meninges ▪ Meningomyelocele – meninges and spinal cord and or nerve roots Severe neurological deficits in regions below sac protrusion. https://achievementcenteroftexas.org/special-needs/spina-bifida-center/ Diagnosis/screening: ▪ Alpha-fetoprotein (AFP) leaks from fetal blood into amniotic fluid through open neural tube defect; higher levels found in amniotic fluid compared to regular pregnancy ▪ Confirmed by ultrasound screening at 16 weeks Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Treatment: ▪ Occult – none required ▪ Meningocele: Uncomplicated surgical repair ▪ Meningomyeolocele – complicated, poor prognosis for return of motor function/sensation, bowel and bladder function impairment CSF (protective cushion for CNS) ▪ provides cushion, homeostasis (exchange of substances - neurotransmitters), metabolism (nutrients/wastes) ▪ Immunologic protection ▪ CSF circulates from ventricles to subarachnoid space and around brain and spinal cord. ▪ Resorbed in large venous sinuses in dura by arachnoid granulations- return to jugular vein Blockage of circulation through the ventricles results in buildup of CSF, dilation of ventricles and compression/atrophy of brain tissue ▪ 150ml CSF capacity – 500 ml production/day Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Constantly produced by choroid plexuses of lateral ventricles – derived from and closely resembles plasma Obstructive hydrochepalus Acquired hydrocephalus ▪ Obstruction of CSF by tumor or fibrous adhesions (formed after case of bacterial meningitis) blocking opening in fourth ventricle ▪ Can also be caused by trauma/brain hemorrhage, overproduction of CSF ▪ Ventricles dilate but head does not enlarge because cranial structures are fused Increased ICP can cause nausea, vomiting, headaches seizures and decreases LOC (coma) Treatment – shunting of CSF by placing tube into dilated ventricle and draining into peritoneal cavity of right atrium Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Congenital hydrocephalus ▪ From congenital obstruction/abnormality in ventricle system. ▪ Aqueduct blockage or openings in 4th ventricle (to dura/spinal cord) are most common ▪ Head enlarges as ventricles dilate because cranial structures have not fused ▪ If blockage is pre delivery – enlarged head may complicate delivery, usually develops slowly after birth Cerebral Injury Chronic Traumatic Encephalopathy (CTE): repeated injury can cause long lasting damage and chronic effects – associated with depression and neurodegenerative brain disorders later in life Contusions (bruise) more severe blow to head that can fracture skull and injure brain, causing decreased LOC and neurologic disturbances depending on severity and location. Swelling of brain due to injury can interrupt surface intracerebral blood vessels and cause increased ICP (life threatening Injuries to brain from force can cause damage to adjacent and also opposite sides from blow. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Concussion – mildest form, caused from blow to the head (typically acquired in contact sports) – often accompanied by headaches, loss of memory, confusion, light sensitivity Head injury can damage large blood vessels over surface of brain that may be torn by force of injury ▪ Subdural hemorrhage (between dura and arachnoid) – tends to develop slower due to venous source (even months after injury) ▪ Subarachnoid hemorrhage (between arachnoid and pia) – can result from trauma or rupture of cerebral aneurysms Characterized by rapid onset of severe headache, decreased LOC and seizure – major medical emergency Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Epidural hemorrhage (between outer dura and cranium) – associated with skull fractures. If torn, arteries in the space fill the area rapidly and the developing hematoma can compress the brain leading to brain damage and death if not corrected. Stroke: Cerebrovascular Accident (CVA) Any injury to brain tissue from disturbance of blood supply to brain Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Types of stroke ▪ Cerebral thrombosis: Most common; thrombosis of cerebral artery narrowed by arteriosclerosis ▪ Cerebral embolus: Occurs less frequently; blockage of cerebral artery by fragment of arteriosclerotic plaque in carotid artery or blood clot from heart (mural- from previous MI, diseased mitral/aortic valve or atrial fibrillation) ▪ Cerebral hemorrhage: Most serious type of stroke; usually from rupture of a cerebral artery in person with hypertension Stroke: Cerebrovascular Accident (CVA) Tissues break down – cleaned up by macrophages leaving a cystic cavity resulting in encephalomacia (softening/loss of brain tissue) ▪ Ischemic infarct: No blood leaks into brain (more common with thrombotic infarct) ▪ Hemorrhagic infarct: Blood leaks into damaged brain tissue (embolic, aneurysm infarct) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Cerebral infarct : necrosis and degeneration of brain tissue from lack of oxygen supply to brain tissues Arteriosclerosis of extracranial arteries ▪ Sclerosis of carotid artery that supplies the brain ▪ thrombi can develop on roughened surface of plaque, eventually breaking loose ▪ In rare cases, arteries can become completely blocked by thrombus developing on plaque – large cerebral infarction Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ arteriosclerotic plaques narrow lumen and reduce cerebral blood flow Cerebral Hemorrhage Blood escapes under high pressure and causes rapid- extensive damage (fatal) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Most serious type of stroke- usually from rupture of a cerebral artery in person with hypertension Stroke: Cerebrovascular Accident Treatment: ▪ Carotid endarterectomy (surgical plaque removal) ▪ Occlusion of bleeding artery (metal clip) ▪ Less-invasive methods: Similar to balloon angioplasty and stent insertion procedures used to treat coronary artery plaques ▪ Clot busting drugs - TPA Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Diagnosis ▪ Cerebral angiogram (xray with dye to detect artery blocked) ▪ CT scan: Can distinguish a cerebral infarct from cerebral hemorrhage ▪ MRI: Provides similar information and is equally effective ▪ Important to determine if stroke is hemorrhagic in nature if clot busting drugs are considered Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com https://www.joeniekrofoundation.com/understanding/brain-basics/ Manifestations of stroke https://ib.bioninja.com.au/options/option-a-neurobiology-and/a2-the-human-brain/brain-sections.html Many patients require rehabilitation to regain ability to relearn self care activities, walk talk etc. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Wide ranging - Depends on location and amount of brain tissue effected. Stroke on left side will typically impact right side of body (weakness, paralysis, sensation disturbances) Other Types of Neurologic Dysfunction Multi-infarct vascular dementia -Cumulative brain damage from small strokes, second most common cause of dementia, treated by addressing underlying cause, such as hypertension Cerebral aneurysm – can emerge in larger arteries of brain (Circle of Willis, usually congenital) eventually forms over years into young adulthood that can rupture (severe/fatal subarachnoid hemorrhage) High BP, atheroscerosis - Increased risk of rupture Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Transient ischemic attack (TIA) – brief episodes lasting minutes to hours “mini stroke” caused by small clots that are dissolved/repaired. 1/3 will progress to stroke within 5y Infections of the Nervous System Meningitis: Infection affecting meninges (stiff neck/headache/fever vomiting) Encephalitis: Infection of brain tissue (altered LOC and neurologic symptoms depending on brain area) Meningoencephalitis: Affects both meninges and brain tissue CNS infection diagnosed by testing CSF for elevated WBC and protein in presence of infection: lymphocytes (viral), neutrophils (bacterial) bacterial and fungal pathogens can also be detected in CSF Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Many types of organisms can infect the nervous system ▪ Bacterial ▪ Fungal ▪ Viral Meningitis from Bacteria and Fungi Also caused by Haemophilus influenzae (less frequent now due to prevalence of vaccination) Menigococcal vaccines are also available and are of decreasing incidence Menigitis is often preceded by mild URI where small numbers of bacteria get access to blood stream, travel to brain and cause infection of meninges TB or fungal meningitis is rare and are spread from lungs in chronic infections, typically in immunocompromised individuals Suppurative meningitis: Pus-producing; caused by bacteria (no pus in viral meningitis) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Most commonly caused by Meningococcus (Neisseria meningiditis) or Pneumococcus (Streptococcus pneumoniae) Viral Infections That Affect the CNS Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Many viruses: measles, mumps, herpes simplex virus, intestinal and respiratory viruses, cytomegalovirus, poliomyelitis virus, rabies, arboviruses Manifestations ▪ Viral meningitis: Systemic symptoms (fever, fatigue etc.) aka Aseptic meningitis: caused by a virus, typically mild symptoms (stiff neck/headache) with complete recovery ▪ Viral Encephalitis: Brain tissue involvement – much more serious (confusion/disorientation/coma) and can be fatal (rabies – close to 100% fatality) Patients often left with permanent neurologic deficits No specific treatment – symptomatic treatment with antivirals in some cases and with limited impact Rabies Invariably fatal without treatment Deaths are rare in north America. (routine immunization of pets– still responsible for 50 000 deaths/year) worldwide Virus is carried in saliva, travels to peripheral nerves and spreads up the spinal cord to the brain (10 days – several months) Destroys brain stem and causes severe encephalitis Treated by postexposure vaccination and/or anti-rabies gamma globulin (from immune donors) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Caused by bite from rabid animal (typically bats (70%) dogs (most others)– also racoons, wolves, foxes, skunks) Viral Infections That Affect the CNS Arboviruses: Responsible for many cases of meningitis and encephalitis Types of viral infections that lead to encephalitis ▪ Western or Eastern equine encephalitis – most dangerous of Arboviruses ▪ St. Louis encephalitis ▪ California encephalitis ▪ West Nile virus: originated in Africa; first case identified in 1999 in New York City area – has spread to Canada/Mexico, transmitted by mosquitos (80% asymptomatic, 20% mild-moderate aseptic meningitis with severe fatal encephalitis in fewer than 1%) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Name comes from vector – “arthropod borne -ArBo” – named for location of discovery ▪ RNA Viruses infect birds, animals, humans; transmitted by mosquitoes - includes Zika virus (initially from Asia, spread through north/central/south America) Transmitted by mosquitos or sexual contact – most are asymptomatic, but can have effect on fetus: 14% of infections develop Zika syndrome: microcephaly and severely impaired neurological development at birth Poliomylitis ▪ Devastating childhood disease that infects GI tract. Most cases are asymptomatic or mild flu-like symptoms, but in rare cases (0.5%) the infection travels into nervous system and patients develop muscle weakness and flaccid paralysis (most often affecting legs) most fully recover (fatality of 2-5% of children, 15% of adults) ▪ Postpolio syndrome: Slow muscular atrophy of affected muscles in 25-40% of recovered acute cases of flaccid paralysis No specific treatment – physio, mild exercise and lung exercises if respiratory muscles affected Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Existed for thousands of years, virus was first identified in 1909 – since eradicated by vaccination (1952 –Jonas Salk) in developed world HIV: Neurologic Manifestations 2. AIDS related tumors of the Nervous system (due to immunosuppression) 3. Nervous system infections caused by opportunistic pathogens Manifestations depend on location and extent of damage ▪ Herpesvirus ▪ Cytomegalovirus ▪ Cryptococcus neoformans ▪ Toxoplasma gondii Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com 1. Nervous system infections directly caused by AIDS virus –HIV infected monocytes travel to brain and release virus ▪ Polyneuritis ▪ Acute viral meningitis ▪ AIDS encephalopathy: Chronic and progressive (similarities to Alzheimer's) Creutzfeldt-Jakob Disease Caused by small protein particle produced as a result of gene mutation (proteinaceous infectious particle –prion) CJD – mostly sporadic, some cases linked to inherited mutations. Characterized by rapid onset dementia with neurologic disturbances – typically older adults (mean 65yo) – usually fatal within 6 mo after symptom onset Prion disease: ▪ Normal form of protein: Good prion designated as PrPc ▪ Abnormal form of protein: Bad prion designated as PrPsc – identical in sequence, but folded abnormally Infectious – will convert other normal proteins to abnormal folding pattern (accumulation disrupts function) Causes vacuole formation, neuron degeneration and astrocytes proliferate to fill voids (spongiform encephalopathy), no inflammation occurs Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Kuru: first prion disease discovered – found in Cannibalistic tribes of New Guinea Mad cow disease ▪ Cows become infected from animal feed mixed with protein-rich tissue from sheep infected with scrapie (Prion disease of sheep/goats) ▪ Change in feeding practices has decreased incidence – mostly in UK where first outbreak in ’85 was discovered. ▪ Eating infected beef causes variant Creutzfeldt-Jakob disease in humans – earlier age onset (25) and slower development course of disease Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Prion disease affecting cows Other Diseases of the Nervous System ▪Multiple Sclerosis ▪Parkinson disease ▪Huntington disease Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪Alzheimer disease Alzheimer Disease Anatomic and biochemical features ▪ Loss of neurons, atrophy of cerebral cortex associated with: ▪ Histologic changes -Neurofibrillary tangles of cytoskeletal elements from degenerative changes (mostly composed of hyperphosphorlyated tau proteins) -Neurotic beta amyloid plaques: Clusters of thick, broken neurofilaments ▪ Biochemical abnormalities and brain enzyme deficiencies: Acetylcholine and acetylcholine-synthesizing enzyme 6 years of mental decline until diagnosis – fatal in 6-8years after Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Characteristics – most common cause of dementia - elderly ▪ Progressive mental deterioration in older adults (over 65) ▪ Memory loss, difficulty reasoning/thinking/judgement and emotional disturbances (irritability anxiety, depression) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Diagnosis of exclusion: PET/MRI imaging can be informative No specific treatment can halt disease progress: some drugs may temporarily improve cerebral function in some cases Multiple Sclerosis ▪ Chronic/progressive autoimmune disease ▪ demyelination of nerve fibers (brain, spinal cord) followed by glial scarring (by astrocytes) of demyelinated regions called MS plaques – impairs nerve conduction ▪ Neurologic symptoms depend on location of plaques (visual disturbances, muscle weakness, paresthesia etc.) ▪ onset in young adult hood (15-45 yo) ▪ Periodic onset of acute neural disturbances (1-2x/year) – depending on location of plaques ▪ Characterized with periods of recovery and remission (unpredictable – some triggers in some cases like stress) ▪ Eventually disturbances are permanent Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Activated T lymphocytes, monocytes target myelin proteins, destroy myelin sheath (autoantibodies to myelin proteins in CSF) Multiple Sclerosis Treatment: • No treatment to stop progression • corticosteroids can reduce symptoms during attacks, shorten recovery periods • Physical therapy Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Diagnosis: • Symptom history • MRI – detection of lesions • CSF – evidence of inflammation in the absence of infectious agent Parkinson Disease Treatment: does not halt progression, symptoms can be relieved by L-dopa, dopamine agonists, deep brain stimulation in early stages (5years) ▪ Embryonic stem cells may be key to successful treatment; possible to induce stem cells to differentiate into dopamine-producing neurons to treat disease Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Chronic disease (1% of individuals over 60) Most cases are of unknown etiology (some evidence of drug/ chemical toxicity, genetic predisposition) ▪ Progressive loss of neurons (dopamine producing) in substantia nigra of midbrain causing drop in dopamine level in substantia nigra ▪ Substantia nigra: midbrain region - critical role in modulation of motor movements ▪ Rigidity of voluntary muscles, increased muscle tone ▪ Tremors of fingers and extremities, difficulty walking ▪ Disease progresses to involve higher cortical areas causing dementia in late-stage disease Histology: presence of Lewy bodies (intracellular inclusion bodies in damaged neurons) Huntington Disease Uncommon, hereditary autosomal dominant disease Manifestations ▪ Progressive mental deterioration; abnormal jerky and writhing movements ▪ Caused by progressive atrophy of basal ganglia neurons – regulate coordinated muscle movements ▪ First manifestations occur between ages 30 and 50 years, progressive and usually fatal within 15 to 20 years ▪ Late stage also associated with cortical deterioration - dementia ▪ No way to arrest progression of disease ▪ Drugs may help control some symptoms Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Abnormal gene contains too many CAG triplet repeats, the greater number of repeats, the earlier the onset (occurs during spermatogenesis) Spinocerebellar Degenerative Disease ▪ causes degeneration of upper and lower neurons ▪ Causes weakness, paralysis, respiratory problems ▪ No specific treatment Spinocerebellar ataxias (SCA) – gradual loss of body movement over a period of years Freidreich ataxia (FA) - progressive loss of ability to move (15y) evident in early teens – fatal by 45. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Group of over 25 diseases of genetic origins resulting in symptoms of cerebellar disturbance (ataxia, loss of control of motor function, coordination and speech) Amyotrophic Lateral Sclerosis (ALS) Lou Gehrig disease (Stephen Hawking)– most (80%) have no known cause, 10% familial genetic, 10% sporadic mutation Lower motor neuron degeneration: leads to progressive twitching, weakness and eventual Flaccid paralysis of muscles Followed by upper motor neuron degeneration: total loss of muscle control/atrophy, cognitive/ behavioral dysfunction (about half) and dementia (10%) No Cure – symptomatic treatment (mechanical ventilation, feeding tubes) Death usually from Respiratory failure within 2-4y Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Onset typically 50 yo - affects upper and lower motor neurons Tumors of the nervous system Peripheral nerve tumors Neuromas of cranial nerves: Usually involves acoustic nerve; difficult to remove surgically Multiple nerve tumors occur in multiple neurofibromatosis (NF-1) ▪ Transmitted as autosomal dominant trait ▪ Disfiguring skin nodules, thickened patches of skin, focal hyperpigmentation of skin ▪ Tumors can be removed surgically if the encroach on vital organs or cosmetic reasons Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Can be solitary or multiple; typically from Schwann cells (Schwannomas) – rarely malignant Brain/ Spinal Cord Tumors Metastatic tumors from other regions are more common than primary tumors Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Primary tumors (do not occur in neurons) ▪ Glioma: Mostly poor prognosis with deep location in brain; surgery, radiation, chemotherapy; includes ependymoma and medulloblastoma Types of Glioma: ▪ Astrocytoma (most common) – highly malignant – can’t be removed surgically (chemo/radiation) Glioblastoma multiforme – rapidly growing and highly variable astrocytoma, poor prognosis ▪ Oligodendroglioma – also highly invasive, better prognosis ▪ Lymphoma – common in immunosuppressed patients (post transplant/AIDS) ▪ Meningioma – tumor of meninges, arises from cells in arachnoid layer Causes ICP, surgical removal Symptoms: depend on region/ size of tumor – headache common Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Peripheral Nerve Disorders Traumatic injury: Lacerations, fractures, crush injury Nerve entrapment neuropathy (single nerve) –carpal tunnel syndrome/sciatica ▪ External compression by fibrous band/muscle ▪ Causes pain, tingling, numbness (paresthesia), weakness ▪ Median (carpal tunnel) or sciatic (sciatica) nerve commonly involved May require surgical release if unresponsive to conservative treatment (corticosteroids/ physical therapy) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Peripheral nerve injury Can result in demyelinating neuropathy (remyelination possible) of injury to cell body/axon (cause degeneration, poor chance of repair depending on extent of injury) Peripheral Nerve Disorders ▪ Characterized by progressive muscle weakness, numbness/tingling, pain distal to injury ▪ Sensory and motor dysfunction in glove and stocking distribution (proximal sensation and motor function preserved) ▪ From systemic disease (diabetes, autoimmune), drugs/toxins, alcoholism (B vitamins deficiency) ▪ Treatment: underling cause Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Polyneuritis (peripheral neuritis) – multiple nerves Peripheral Nerve Disorders Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Guillain-Barré syndrome (idiopathic polyneuritis) ▪ Widespread, patchy demyelination of nerves and nerve roots with mild inflammation and sometimes axon degeneration ▪ Autoimmune reaction to myelin triggered by preceding viral infection (2-3 weeks after) ▪ Progressive weakness (1-2 weeks) in legs that spreads to trunk and upper extremities followed by complete recovery for most over weeks to years (remyelination) ▪ Some cases (1/3) do not recover fully and have some long-term disability ▪ Acute phase can progress to respiratory/cardiac failure and death (about 15%) Treatment with intravenous immunoglobulin (IVIG) or plasmapheresis, supportive care Mental/Physical health Tied together!! Positive – placebo effect Negative – loneliness/depression/anxiety ▪ Physical – weight, circulation, immune suppression, insomnia, pain sensitivity/resilience ▪ Mental – preoccupation/memory/motivation to complete treatment, dietary choices/physical health Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Brain/ cognition can have wide ranging effects on health and disease outcomes The Nervous System Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com.