Lecture 21 Flashcards
Blood/Brain barrier
Highly selective, semi-permeable membrane, maintained by astrocytes surrounding endothelium. Have special tight junctions that don’t allow cell transfer as easily; Easily impaired by inflammation.
What does it mean in T-cells are found in CSF?
Infection + Blocking pathogens/toxins
What diseases are caused by a damaged blood/brain barrier
Alzheimer’s, ALS, Epilepsy, stroke
Central nervous system
Brain, (cerebrum, brain stem, cerebellum) and spinal cord – protected by skull (cranium). Meninges - surround membranes of CNS
4 Layers surrounding the brain
Dura (firm fibrous – outer covering/ protective)
Arachnoid (middle - cushioning)
Sub Arachnoid (Contains CSF)
Pia (thin – inner) covers brain, spinal cord
PNS – peripheral nervous system
Nerves that branch off spinal cord, Somatic – voluntary movement, Autonomic (involuntary) (Sympathetic/Parasympathetic)
Autonomic (involuntary) NS
Controls smooth muscles, glands and organ functions
Sympathetic – “fight or flight”
Parasympathetic – “rest and digest”
Neurons
Nerve cells, transmit nerve impulses
Neurons
Nerve cells, transmit nerve impulses
Central body
Dendrites (transmit toward cell body) and axon (transmit away) emerge from it to transmit impulses
Neuroglia
Supporting cells - more numerous than neurons
Astrocytes
Long, star-shaped cells, numerous, highly branched process that 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)
Neuron signaling
Electric impulse carried - (250mph travel speed) activation by ion/chemical signals processed by dendrites and travel through Myelin sheath/nodes of Ranvier to send a message to another neuron or target cell
Depolarization
Activation by electrical impulse or chemical receptors send electrical signal down axon
Neurotransmitters
Glutamate (stimulatory) , dopamine (motivation), acetylcholine(neuromuscular), serotonin (mood) GABA (usually inhibitory), Adrenergic (norepinephrine/epinepherine)
Physical and mental health disorders associated with neurotransmitters
Schizophrenia, Mood disorders, Depression/Anxiety, PTSD, Parkinson’s, Migraines, Seizures, Addiction, Alzheimer’s, Insomnia.
What is the function of the brain and what is it composed of?
Control all bodily functions/organs (expect reflexes). It is composed of Neurons (nerve cells) and neuroglia (supporting cells) together = neuropil
Grey matter
More external (neuronal cell bodies, astrocytes and microglia)
White matter
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
How are signals of a nerve impulse transmitted?
Neurotransmitters (Acetylcholine, norepinephrine, dopamine) occur in synapses where they are released at axon terminals and received by dendrites
Cerebral Cortex
Receives sensory input and initiates voluntary motor responses
Brain Stem
Involved in control of vital functions not under voluntary control (cardiac/respiratory regulation and function) and connects cortex to cerebellum
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.
What are the 4 cavities in the brain called?
Ventricles (filled with CSF, responsible for the production (choroid plexus in each ventricle) and flow of CSF (neutral buoyancy))
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 the brain into large venous sinuses in dura which drain into jugular veins
Closed system
Increased in volume, inflammation or intruding mass (blood/tumor) will put pressure on to the brain causing injury and death
Voluntary Motor Activity
Controlled by nerve impulses originating in upper motor neurons of the cerebral cortex (cortical neurons)
Pyramidal system
Controls voluntary motor functions
Extrapyramidal system
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) that is controlled by reflex arcs
Paralysis
Muscle no longer subject to voluntary control
Flaccid paralysis (PNS damage)
Destruction of lower (peripheral) motor neurons by disease (poliomyelitis) causing low muscle tone - atrophy
Spastic paralysis (CNS damage)
Disease or Injury to cortical neurons (stroke) causing increased muscle tone
Nervous system development
In embryonic development, CNS derives from the ectoderm and first appears as a thickened band of cells (neural plate). Neural folds are formed and fuse to form the neural tube (wk4) which is filled with CSF
What do the cerebral hemispheres develop?
The forebrain
The cerebellum and medulla form what?
The hindbrain
What are the 2 most common neural tube defects?
Spina bifida and Anencephaly
Anencephaly
Upper part (cephalic end) of neural tube fails to close and exposed brain tissue degenerates to mass of vascular connective tissue mixed with degenerated nervous tissue; Incompatible with life
Spina bifida (3 types)
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) - hard to detect
Meningocele – only meninges (surgery)
Meningomyelocele – meninges and spinal cord and or nerve roots (complicated, poor prognosis for return of motor function/sensation, bowel and bladder function impairment)
Diagnosis/screening for Spina bifida
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
CSF
Constantly produced by choroid plexuses of lateral ventricles – derived from and closely resembles plasma that provides cushion, immunologic protection, homeostasis (exchange of substances - neurotransmitters), and metabolism (nutrients/wastes); 150ml CSF capacity – 500 ml production/day
Congenital hydrocephalus
Congenital issues in the ventricle system cause head to enlarge as ventricles dilate because cranial structures have not fused. Can causes complications in delivery or develop slowly after birth
Acquired hydrocephalus (+treatment)
Obstruction of CSF by tumor or fibrous adhesions (formed after case of bacterial meningitis) blocking opening in fourth ventricle
and by trauma/brain hemorrhage, overproduction of CSF. Causes 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
Concussion
Mildest form, caused from blow to the head (typically acquired in contact sports) – often accompanied by headaches, loss of memory, confusion, light sensitivity
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)
A more severe blow to head that can fracture skull and injure brain, causing decreased LOC and neurologic disturbances depending on severity and location. Also, causes swelling of the brain
Epidural hemorrhage (between outer dura and cranium)
Due to 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.
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
Stroke: Cerebrovascular Accident (CVA) + types
Any injury to brain tissue from disturbance of blood supply to the brain (3 types: cerebral thrombosis, embolus, hemorrhage)
Cerebral thrombosis
Most common stroke; thrombosis of cerebral artery narrowed by arteriosclerosis
Cerebral embolus
A stroke that 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 a person with hypertension (Blood escapes under high pressure and causes rapid- extensive damage (fatal))
Cerebral infarct
Necrosis and degeneration of brain tissue from lack of oxygen supply to brain tissues
Ischemic infarct
No blood leaks into brain (more common with thrombotic infarct)
Hemorrhagic infarct
Blood leaks into damaged brain tissue (embolic, aneurysm infarct)
Arteriosclerosis of extracranial arteries
Sclerosis of the carotid artery that supplies the brain, plaques reduce cerebral blood flow and thrombi can develop on the surface of plaque
Diagnosis and treatment for a stroke
Diagnosis: Cerebral angiogram (X-ray with dye to detect artery blocked), CT scan, and MRI (distinguish a cerebral infarct from cerebral hemorrhage)
Treatment: Carotid endarterectomy (surgical plaque removal), Occlusion of the bleeding artery (metal clip), Clot-busting drugs (TPA)
Frontal lobe
Motor control, problem solving, and speech production
Temporal lobe
Auditory processing, language comprehension, memory/information retrieval
Brainstem
Involuntary responses
Parietal Lobe
Touch perception, body orientation, and sensory discrimination
Occipital lobe
Sight, Visual reception and interpretation
Cerebellum
Balance and coordination
Transient ischemic attack (TIA)
Brief episodes lasting minutes to hours “mini strokes” caused by small clots that are dissolved/repaired. 1/3 will progress to stroke within 5y
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 the brain (Circle of Willis, usually congenital) and eventually forms over years into young adulthood that can rupture (severe/fatal subarachnoid hemorrhage)
Meningitis
Infection affecting meninges (stiff neck/headache/fever vomiting); Most commonly caused by Meningococcus (Neisseria meningiditis), Pneumococcus (Streptococcus pneumoniae), and Haemophilus influenzae)
Vaccination is used for treatment
Encephalitis
Infection of brain tissue (altered LOC and neurologic symptoms depending on brain area)
Meningoencephalitis
Affects both meninges and brain tissue
How does CSF testing help in CNS infection diagnosis?
Testing for elevated WBC and protein in presence of infection: lymphocytes (viral), neutrophils (bacterial), bacterial and fungal pathogens
Suppurative meningitis
Pus-producing; caused by bacteria (no pus in viral meningitis)
Viral Infections That Affect the CNS
Measles, mumps, herpes simplex virus, intestinal and respiratory viruses, cytomegalovirus, poliomyelitis virus, rabies, arboviruses
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); often left with permanent neurologic deficits, antivirals for symptomatic treatment
Rabies
Invariably fatal without treatment but deaths are rare in North America. Destroys the brain stem and causes severe encephalitis
Treatment: Postexposure vaccination and/or anti-rabies gamma globulin (from immune donors)
Arboviruses
Responsible for many cases of meningitis and encephalitis; “arthropod-borne -ArBo” – named for the location of discovery (ex. Zika virus)
Zika syndrome
Microcephaly and severely impaired neurological development at birth
West Nile virus
Originated in Africa, transmitted by mosquitos (first case in 1999 in NYC, 80% asymptomatic)
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 the nervous system and patients develop muscle weakness and flaccid paralysis; most fully recover - eradicated by vaccination in developed world
Postpolio syndrome
Slow muscular atrophy of affected muscles in 25-40% of recovered acute cases of flaccid paralysis (physio, mild exercise and lung exercises if respiratory muscles affected)
What viruses do HIV infected monocytes release when in the brain
Polyneuritis, Acute viral meningitis, AIDS encephalopathy (chronic and progressive)
Opportunistic pathogens in nervous system infections
Herpesvirus, Cytomegalovirus, Cryptococcus neoformans, and Toxoplasma gondii
Creutzfeldt-Jakob Disease
Caused by small protein particle produced as a result of gene mutation (proteinaceous infectious particle –prion). Mostly sporadic and characterized by rapid onset dementia with neurologic disturbances – typically older adults. Usually fatal within 6 months
Normal form of protein
Good prion designated as PrPc
Abnormal form of protein
Bad prion designated as PrPsc – identical in sequence but folded abnormally
Mad cow disease
Prion disease affects cows through ingested animal feed mixed with protein-rich tissue from sheep infected with scrapie. Eating infected beef causes variant Creutzfeldt-Jakob disease in humans – earlier age onset (25) and slower development course of disease
Alzheimer Disease
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) due to loss of neurons and histologic changes; 6-8 years of mental decline until diagnosis
Neurotic beta amyloid plaques
Clusters of thick, broken neurofilaments
Multiple Sclerosis
Chronic/progressive autoimmune disease where activated T lymphocytes, and monocytes target myelin proteins, destroy myelin sheath (autoantibodies to myelin proteins in CSF) and turn into MS plaques (impairs nerve conduction). Onset in young adulthood (15-45) and characterized with periods of recovery and remission (unpredictable)
Diagnosis and treatment for MS
Diagnosis: Symptom history, MRI – detection of lesions, CSF – evidence of inflammation in the absence of an infectious agent
Treatment: No treatment to stop the progression, corticosteroids can reduce symptoms during attacks, shorten recovery periods, and Physical therapy
Parkinson Disease
Chronic disease (1% of individuals over 60) Most cases are of unknown etiology (some evidence of drug/ chemical toxicity, genetic predisposition) due to a progressive loss of neurons in the substantia nigra of the midbrain.
Symptoms: Rigidity of voluntary muscles, increased muscle tone, tremors of fingers and extremities, difficulty walking
Substantia nigra
The midbrain region - a critical role in the modulation of motor movements
Treatment and Histology of Parkinson’s Disease
Histology: presence of Lewy bodies
Treatment: does not halt progression, symptoms can be relieved by L-dopa, dopamine agonists, deep brain stimulation in early stages (5years) + Embryonic stem cells
Huntington Disease (manifestations + treatment)
Uncommon, hereditary autosomal dominant disease, an abnormal gene contains too many CAG triplet repeats, the greater number of repeats, the earlier the onset (occurs during spermatogenesis) causing progressive mental deterioration, abnormal jerky and writhing movements; usually occurs between ages 30-50 years and progresses for 15 to 20 years.
Treatment: Drugs can help control some symptoms but not stop disease progression
Spinocerebellar Degenerative Disease
Group of over 25 diseases of genetic origins resulting in symptoms of cerebellar disturbance (ataxia, loss of control of motor function, coordination and speech) due to degeneration of upper and lower neurons
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.
Amyotrophic Lateral Sclerosis (ALS)/Lou Gehrig disease
Mostly has no know cause, Onset typically 50 yo - affects upper and lower motor neurons, Loss of both upper and lower motor neuron degeneration (leads to progressive twitching, weakness and eventual Flaccid paralysis of muscles, then total loss of muscle control and dementia) - No cure, die from respiratory failure within 2-4 years
Peripheral nerve tumors
Can be solitary or multiple; typically from Schwann cells (Schwannomas) – rarely malignant. Multiple nerve tumors occur in multiple neurofibromatosis (NF-1) - Transmitted as autosomal dominant trait and can be removed surgically (Neuroma hard to remove surgically)
Glioma (Primary tumor of the brain/spinal cord)
Mostly poor prognosis with deep location in brain; surgery, radiation, chemotherapy; includes ependymoma and medulloblastoma (5 types)
5 types of Glioma (Brain/ Spinal Cord Tumors)
- 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
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)
Example of injury: Lacerations, fractures, crush injury
Nerve entrapment neuropathy (single nerve) –carpal tunnel syndrome/sciatica
Causes pain, tingling, numbness (paresthesia), weakness due to external compression by fibrous band/muscle
Median (carpal tunnel) or sciatic (sciatica) nerve commonly involved May require surgical release if unresponsive to conservative treatment (corticosteroids/ physical therapy)
Polyneuritis (peripheral neuritis) – multiple nerves + treatment
Characterized by progressive muscle weakness, numbness/tingling, pain distal to injury from systemic disease (diabetes, autoimmune), drugs/toxins, alcoholism (B vitamins deficiency)
Treatment: underlying cause
Guillain-Barré syndrome (idiopathic polyneuritis) + treatment
Widespread, patchy demyelination of nerves and nerve roots with mild inflammation and sometimes axon degeneration from an autoimmune reaction to myelin triggered by preceding viral infection (2-3 weeks after); progressive weakness and then complete recovery (not all recover and acute phases can be fatal)
Treatment with intravenous immunoglobulin (IVIG) or plasmapheresis, supportive care
