Chapter 15: Neurological Disorders Flashcards
Tumors
Mass of cells whose growth is uncontrolled and that serves no useful function
Malignant Tumor
Cancerous tumor
- Infiltrating: lacks distinct border and may metastasize
Benign Tumors
No cancerous tumor
- Encapsulated: has distinct border and can’t metastasize
Metastasis
Process by which cells break off of tumor, travel through vascular system and grow elsewhere in body
Compression
Can directly destroy brain tissue or indirectly block flow of CSF and cause hydroencephalus
Benign: compression only
Malignant: compression and infiltration
Tumor Causes
- Come from cell found in the brain that are not nerve cells, or from metastases originating elsewhere in the body
- Most serious types are metastases and gliomas
Gliomas
Cancerous brain tumor composed of several types of glial cells
Tumor Initiating Cell
Cells that originate from transformations of neural stem cells, rapidly proliferate, and give rise to glioma
Glioblastoma
Tumor arise in glial cells
Astrocytoma
Tumor arise in astrocytes
Ependymoma
Tumor arise in ependymal cells from the ventricles
Oligodendrocytoma
Tumor arise in oligodendrocytes
Meningioma
Tumor arise in cells of meninges
Neurinoma
Tumor arise in Schwann cells or cells of connective tissue covering cranial nerves
Angioma
Tumor arise in cells of blood vessels
Pinealoma
Tumor arise in cells of pineal gland
Tumor Treatments
- Neurosurgeon removes as much tumor as possible
- Remaining cells are targeted by radiation
- Special type of radiation therapy called stereotactic radio surgery
- Some brain tumors respond to chemotherapy
Seizure
Period of sudden, excessive activity of neurons in the brain
- If neurons in the motor system are involved, a seizure can cause a convulsion
- Single seizure or many may occur during a lifetime
Convulsion
Violent sequence of uncontrollable muscular movements caused by a seizure
- Most don’t have convulsions
Seizure Disorders
Condition that has many causes
- preferred term for epilepsy
Partial Seizures
Have definite focus, or source of irritation
- Remain localized
- Simple partial seizure
- Complex partial sezure
Focus
Either a:
- scarred region cáusales by an old injury - developmental abnormality like malformed blood vessel
Simple Partial Seizures
Can cause changes in consciousness
Complex Partial Seizures
Lead to loss of consciousness
Generalized seizures
Widespread, involving most of the brain (grow from focus but origin not discovered)
- Grand mal seizure - Absence seizure
Grand mal seizure
Most severe form of seizure
* person experiences aura before seizures - Tonic and clonic phases
Tonic phases
First phase of grand mal seizure, in which all patient’s skeletal muscles are contracted
Clonic phases
Phase of grand mal seizures in which patient shows rhythmic jerking movements
- intense activity of ANS manifests itself in sweating and salivation
Absence Seizures
In children cause them to be unresponsive
- characterized by periods of inattention, which aren’t subsequently remembered - aka petit mal - can occur up to several hundred times a day
Aura
Sensation that precedes a seizure
- exact nature depends on location of seizure focus
Partial seizures
Include sensory changes, motor activity, or both
Status Epilepticus
Condition in which a patient undergoes a series of seizures without regaining consciousness
- Damage caused by excessive release of Glu during seizure
Seizure Disorders
Associated with withdrawal from chronic alcohol, barbiturate, and benzodiazepines
- Most common cause: scarring caused by injury, stroke, developmental abnormality, or effects of growing tumor
Seizure Treatment
Anticonvulsant drugs
- Increase the effectiveness of inhibitory synapses
Brain surgery
- Usually seizure are eliminated or greatly reduced in frequency
Vagus nerve stimulation
Hemorrhagic Strokes
Cerebrovascular accident caused by rupture of cerebral blood vessel
Ischemic strokes
Cerebrovascular accident caused by occlusion of blood vessel and interruption of blood supply to region of brain
- Thrombus
- Embolus
Thrombus
Blood clot in blood vessels
Embolus
Piece of material that breaks off and is carried through the bloodstream until it reached an artery too small to pass through
Immediate cause of neuron death
Excessive amounts of glutamate
Cerebrovascular Accidents: Treatments
- Medication to reduce blood pressure
- Brain surgery
- Dissolve or physically remove the blood clot
- Anticoagulant drugs
Clot- dissolving drug
tPA- enzyme that helps dissolve fibrin
Anticoagulant drugs
Desmoteplase, can restore blood flow if given up to nine hours after occurrence of a stroke
Cerebrovascular Accidents: Prevention
- Reduce risk factors, such as high BP, smoking, diabetes, high cholesterol
- Carotid endarterectomy to remove atherosclerotic plaque
- Placement of a stent in a narrowed carotid artery
After Stroke Treatments
- Drugs that reduce swelling and inflammation
- Physical, speech, and/or OT
- Exercise and sensory stimulation
- Constraint-induced movement therapy
Traumatic Brain Injury Types
- Open-head injuries occurs when objects fracture the skull and wound the brain
- Closed-head injuries occur from impacts but do not involve penetration of the brain
- Chronic traumatic encephalopathy (CTE) produced neuro degeneration due to repeated head trauma
- Abnormal tau protein accumulation
- Reduced brain volume and enlarged ventricles
Traumatic Brain Injury: Primary and Secondary Treatments
- Reduce swelling and intracranial pressure
- Ensure adequate blood flow to the injured region
- Address symptoms that develop after injury
- Drug that inhibits the release of glutamate
- Similar treatments as with cerebrovascular accidents
TBI
Increased adenosine and glutamate
- promotes inflammation, which causes further damage
Teratogens
Any chemical or toxin that results in abnormal development of embryo
Fetal alcohol syndrome
Birth defect caused by ingestion of alcohol by pregnant women
- includes characteristic facial anomalies and faulty brain development
Phenylketonuria (PKU)
Hereditary disorder caused by absence of enzyme that converts Phe —> Tyr
- Accumulation of Phe causes brain damage by interfering with myelin at ion in CNS
Tay-Sachs Disease
Heritable, fatal, metabolic storage disorder
- Lack of enzymes in lysosome causes accumulation of waste products and swelling of cells in brain against folds of dura mater
Down Syndrome
Caused by presence of extra chromosome 21
Down Syndrome Interventions
Drug treatments may help learning and memory impairment
- GABA antagonists - Fluoxetine
Down Syndrome: GABA antagonists
Overactivity of GABA system may impair hippocampus synaptic plasticity and associated learning and memory
- increases risk of seizures
Transmissible Spongiform Encephalopathies
Fatal contagious Brian disease that gives the brain a spongelike appearance
- Cause by simple proteins called prions
Prions
Protein that can exist in 2 forms that differ in 3D structure
- Found in membrane of neurons
- Becomes misfolded and causes normal neurons to misfold, killing them
- Resistant to levels of heat that denature normal proteins
Accumulation of misfolded, abnormal protein may signal […]
Accumulation of misfolded, abnormal protein may signal apoptosis
- Means by which cells can commit suicide
- Can be triggered externally by chemical signal or internally by disrupted biochemical processes
- Involves production of caspase
Caspase
“Killer enzyme” that plays role in apoptosis, or programmed cell death
TSE can be […], but most cases are […]
TSE can be genetic, but most cases are sporadic
- Both forms can be transmitted to others
Sporadic
Disease that occurs rare;y and is not obviously by heredity or an infectious agent
Parkinson’s Disease Symptoms
- Degeneration of nigrostriatal system
- DA system: substantia nigra —> basal ganglia
- Muscular rigidity, slowness of movement, resting tremor, and postural instability
- Akinesia
- Lewy bodies
Akinesia
Difficulty initiating movements associated with decreased activation of supplementary motor area
Lewy bodies
Abnormal circular structures with dense core consisting of a- synuclein protein
- found in cytoplasm of nigrostriatal neurons
a-synuclein protein
Found in presynaptic membrane, where it is involved in synaptic plasticity
Parkinson’s disease: mutation on chromosome 4
- Produces abnormal a-synuclein
- Produces a toxic gain of function a protein that results in effects that are toxic to the cell
Toxic Gain fo Function
Cause by dominant mutation
Parkinson’s Disease: mutation of a gene located on chromosome 6
- Produces a gene named Parkin
- Produces a loss of function
- Defective parking fails to ubiquinate abnormal proteins, and they accumulate in the cell, eventually killing it
Parkin
Protein that plays trole in ferrying defective or misfolded proteins to proteosomes
Loss of Function
Recessive mutation
Ubiquitin
Protein that attaches itself to faulty/ misfolded proteins and targets them for destruction by proteosomes
Proteasome
Organelle responsible for destroying defective or degraded protein within cell
Parkinson’s Disease
- Most cases are sporadic
- May be caused by toxin in the environment, faulty metabolism, or unrecognized infectious disorders
- Damages only the nigrostriatal system
- Involves calcium channels
Parkinson’s Drug Treatments
L-DOPA produces more DA
- Temporary as symptoms eventually worsen
Deprenyl inhibits the activity of the enzyme MAO-B
- Slows the progression and reduces symptoms
- Does not slow degeneration of DA neurons
Parkinson’s Surgical Procedures
- Transplantation of fetal tissue
- Lesioning parts of the brain ti improve symptoms
- GPi
- Implanting electrodes that allow patient to electrically stimulate the brain
- DBS in subthalamic nucleus and GPi
Internal Division of Globus Pallidus (GPi)
Division of globus pallidus that provides inhibitory input to motor cortex via thalamus
Deep Brain Stimulus
Surgical procedure that involves implanting electrodes in particular region of brain and attaching device that permits electrical stimulation of that region through electrodes
Huntington’s Disease Symptoms
- Inherited disorder that causes degeneration of the basal ganglia
- Uncontrallable movements, cognitive, and emotional changes, and eventually death
- Begins in GABAergic medium spiny neurons in putamen
Huntington’s Disease Causes
Hereditary disorder caused by dominant gene on chromosome 4
- Produces abnormal protein called huntingtin (Htt) - Produces a toxic gain of function - Signals apoptosis
Huntingtin (Htt)
Protein that may serve to facilitate production transport of brain-derived neurotrophic factor
- accumulates in nucleus
Huntington’s Disease Treatments
Happ1, an antibody that acts intracellularly
- Targets a portion of the Huntington protein
Injection of small interfering RNAs
-Blocks the transcription of the Htt genes
Dementia
Loss of cognitive abilities such as memory, perception, verbal ability, and judgement
Alzheimer’s Disease
Progressive loss of memory and other cognitive function
- Memory deficit most critically involved recent events - Abnormal structures develop: amyloid plaques and neurofibrillary tangles
Amyloid plaques
Extracellular deposite containing dense core of B-amyloid protein surrounded by degenerating axons and dendrites and activated microclima and reactive astrocytes
Neurofibrillary tangles
Dying neuron containing intracellular accumulations of abnormally phosphorylated tau-proteins filaments that formerly served as cell’s internal skeleton
Alzheimer’s Disease Abnormal Structure
Abnormal accumulation of long-form AB but little tau protein
- Induces the release of chemicals that destroy cells
Tau Protein
Protein that normally serves as components of microtubules, which provide the cell’s transport mechanism and cytoskeleton
B-Amyloid Protein
Protein found in excessive amounts in brains of patients with Alzheimer’s disease
Amyloid precursor (APP)
Protein produced and secreted by cells that serves as precursor for B-amyloid that serves a precursor for B-amyloid protein
Secretase
Class of enzyme that cut B-amyloid precursor into smaller fragments, including B-amyloid
Causes of Alzheimer’s Disease
- Some forms appear to be hereditary
- Mutation of gene that produces APP located on chromosome 21
- Mutation of two presenilin genes located on chromosomes 1 and 14
- Mutation for the gene for apolipoprotein E (ApoE)
Presenilin
Produced by faulty gene that causes B-amyloid precursor protein to be converted to abnormal short form
Apolipoprotein E (ApoE)
Glycoprotein that transports cholesterol in blood and plays role in cellular repair
- presence of E4 allele of ApoE gene increases risk of late-onset Alzheimer’s disease
Alzheimer’s Risk Factors
- TBI
- Obesity, hypertension, high cholesterol levels, and diabetes
- Lower levels of formal education
- Cognitive activity delays the appearance of Alzheimer’s
Treatments of Alzheimer’s Diseases
- AChE inhibitors and NMDA receptor antagonists
- No effect on process of neural degeneration and don’t prolong survival
- Noncompetitive NMDA receptor blocker produces slight improvement in symptoms
- Vaccine that destroys AB by sensitizing the immune system to the protein
- Cause inflammation
Korsakoff’s Syndrome
- Characterized by symptoms of anterograde amnesia
- Caused by environmental factors, usually related to chronic consumption of alcohol
- Sometimes occurs in people who have been severely malnourished and then received intravenous infusions of glucose
- Deficiency of thiamine produces brain damage
Encephalitis Symptoms
- Infection that invades the entire brain
- caused by bacteria, virus, or toxic chemicals
- Symptoms include fever, irritability, and nausea
- often followed by convulsions, delirium, and signs of brain damage
Encephalitis Causes
- Herpes simplex virus
- Acute anterior poliomyelitis
- Rabies
- HIV
Herpes simplex virus
Attacks the frontal and temporal lobes
- normally lives in trigeminal nerve ganglia
Acute anterior poliomyelitis
(Polio)
- causes specific damage to motor neurons of the brain and spinal cord
Rabies
Passed from saliva by a bite wound
- Damage CNS and peripheral organs
HIV
Causes damage to synapses and death of neurons
Meningitis
- Inflammation of meningitis
- Caused by viruses or bacteria
- Symptom: include headache, stiff neck, and sometimes convulsion, confusion or loss of consciousness, and death
- Bacterial meningitis causes brain damage
Amyotrophic Lateral Sclerosis
- Spasticity, exaggerated stretch reflexes, progressive weakness and muscular atrophy, and paralysis
- Degenerative disorder that attacks spinal cord and cranial nerve motor neurons
- 10% heredity: mutation in SOD1 gene as chromosome 21
- Toxic gain of function
- 90% sporadic: abnormality in RNA editing
Amyotrophic Lateral Sclerosis Treatment
- Riluzole: drug that reduces Glu-induced excitotoxicity
Multiple Sclerosis Symptoms
Autoimmune demyelinating disease
- increase in intensity and then decrease, followed by another increase after varying periods of time (remitting-relapsing MS)
- Progressive MS is characterized by slow, continuous increase in symptoms
Multiple Sclerosis Causes
- Risk factors include growing up in places far from the equator and being born in late winter or early spring
- May come from a virus
- Causes the immune system to attack own myelin
- Weaken the BBB
- Attaches itself to myelin
Multiple Sclerosis Treatment
- Interferon B, a protein that modulates the responsiveness of the immune system
- Glatiramer acetate suppresses the activity of immune cells that would otherwise attack the myelin
- Both are only partially effective treatments for remitting-relapsing form of MS
- Transplantation of autologous hemapoietic stem cells
