Neurological Disorders Flashcards
Label the following:
Optic nerve, Lens, Anterior chamber, Posterior chamber, Sclera, Vitreous body, Cornea, Ora serrata, Iris, Retina, Uvea
Label the following:
Bruch’s membrane, Sclera, Inner limiting membrane, Inner nuclear layer, Ganglion layer, Outer nuclear layer, Region of rods and cones, Choroid, Axon layer, Inner plexiform layer, Outer plexiform layer, Retinal pigmented epithelium, Outer limiting membrane
Explain the pathogenesis of glaucoma
- Increased intraocular pressure
- Blocks flow through intraocular vessels in the uvea
- Reduced blood flow deprives retina of nutrients
- Retinal atrophy
What causes increased intraocular pressure? (2)
- Increased production of vitreous humor
- Decreased drainage of vitreous humor
How does glaucoma present clinically?
- Retinal damage → blurred vision and impaired dark adaptation
- Corneal damage → halos around light
- Optic nerve atrophy
Label the following:
Facial nerve (CN VII), Tympanic membrane, Stapes, Malleus, Incus, Vestibulocochlear nerve (CNVIII), Round window, Vestibular branch of CN VIII, External acoustic meatus, Tympanic cavity, Cochlear branch of CN VIII, Oval window, Vestibule, Cochlea, Internal acoustic meatus
What is otosclerosis?
- Bony growth around the oval window
- Failure of resorption
- Immobilization of the stapes
What is transient tinnitus?
- Rining in the ears not associated with diseases
- Excessive stimulation of hair cells
What is persistent tinnitus?
- Ringing in the ears associated with hearing loss
- Associated with cochlear dysfunction or cranial nerve VIII dysfunction
Terminals of motor axons synapse with _____. Neurotransmitter is _____.
- Sarcolemma
- Acetylcholine
What is myasthenia gravis?
- Auto-antibodies against acetylcholine receptors
- Induce aggregation and degradation of receptors
- Antibodies can also interact with thymus
Explain the clinical presentation of myasthenia gravis
- Fluctuating weakness
- Diplopia (double vision) and ptosis (eyelid drooping)
- Decreased muscle responsiveness upon repeated stimulation
How can myasthenia gravis be treated? (3)
- Acetylcholinesterase inhibitors
- Immunosuppressive therapy or plasmapheresis
- Thymectomy for patients with thymoma
_____ is an autoimmune disease that targets components of the myelin sheath
Multiple sclerosis (MS)
True or false. In MS, lesions are usually softer than the surrounding tissue.
False. Firmer (hence sclerosis)
What are the common signs and symptoms of MS?
- Unilateral visual impairment
- Brainstem involvement
- Spinal cord lesions
What symptoms in MS are associated with damage to the brain stem? (4)
- Cranial nerve signs
- Ataxia
- Nystagmus
- Internuclear ophthalmoplegia
By what mechanisms can ethanol damage the CNS? (3)
- Hepatic encephalopathy
- Thiamine deficiency
- Ethanol toxicity
What is hepatic encephalopathy?
- Damaged liver (by EtOH) cannot remove toxins from blood
- elevated ammonia and pr-inflammatory cytokines
- Glial cells in CNS respond to toxins (cerebral cortex & basal ganglia)
- Astrocytes get enlarged nuclei and minimal reactive cytoplasm (Alzheimer Type II cells)
What is Wernicke encephalopathy?
- Acute thiamine deficiency associated with EtOH abuse
What are the symptoms of Wernicke’s encephalopathy? How is it treated?
- Psychotic symptoms
- Ophthalmoplegia
- Reversible with thiamine supplementation
What is Korsakoff syndrome? How is it treated?
- Chronic thiamine deficiency due to ethanol abuse
- Irreversible
What are the symptoms of Korsakoff syndrome? They are typically associated with a lesion to what area of the brain?
- Short term memory problems
- Confabulation
- Associated with lesion to thalamus
_____ dysfunction is seen in 1% of chronic alcoholics
Cerebellar
How does cerebellar damage present clinically in patients with chronic ethanol toxicity?
- Truncal ataxia
- Unsteady gate
- Nystagmus
Cerebral edema is caused by_____
- Accumulation of excess fluid within brain parenchyma
- Caused by excess fluid leakage from blood vessels or CNS cellular damage
Explain the vasogenic pathway of cerebral edema
- BBB disruption and and increased vascular permeability
- Allows fluid to move from within vasculature to within parenchymal space
Explain the cytotoxic pathway of cerebral edema
- Secondary to cell membrane injury (neuron, glia, endothelium)
- Generalized hypoxia/ischemia
- Ionic homeostasis disruption
Limited to no blood flow to a specific area of the brain is known as ______. If sustained, it will result in _____.
- Focal cerebral ischemia
- Cerebral infarct
Explain the normal cellular response to cerebral edema
- Neuronal stress (red neurons)
- Macrophages and reactive gliosis clean up damage + neovascularization
- Repair - removal of tissue, loss of architecture, gliosis
What are prions?
Abnormal forms of proteins (PrP)
What is Creutzfeldt-Jakob disease?
- Prion disease that results in neurodegeneration
- Scrapie in sheep and goats
True or false. Oftentimes in CJD the disease progresses so rapidly that no noticeable atrophy is seen on gross examination of the brain.
True
What is the average survival for someone with CJD?
7 months
What are the symptoms of CJD? (3)
- Changes in memory/behavior
- Dementia
- Startle myoclonus
What is bovine spongiform encephalopathy?
- Variant of CJD
- Mad cow disease
- Triggered by ingestion of prions from contaminated beef or blood transfusions
Extracellular aggregates of PrPSC are known as ____. They are typically found in the _____.
- Kuru plaque
- Cerebellum
What stain can be used to detect Kuru plaques?
- Periodic acid-Schiff
- Congo Red
_______ is the loss of lower motor neurons in the brain, brainstem, and spinal cord
Amyotrophic lateral scerlosis (ALS)
“Amyotrophic” refers to what in ALS?
- Muscular paralysis with absence of atrophy
- Hypertonia (rigidity) and exaggerated deep muscle tendon flexes
What does “lateral sclerosis” refer to in ALS?
- Degeneration of corticospinal tracts
- Produces upper and lower motor neuron paralysis in extremities
In ALS, which surface of the spinal cord is damaged?
Anterior surface; has motor neuron roots
In 25% of cases of familial ALS, what gene is mutated and what type of mutation is it?
- Copper-zinc superoxide dismutase (SOD1)
- Gain-of-function mutation
Aside from SOD1, mutations in what other genes can lead to familial ALS? (3)
- Dynactin (retrograde transport)
- VAMP-associated protein B (regulation of vesicle transport)
- Alsin (regulates endosomal trafficking)
What is the consequence of a mutation in SOD1?
Unfolded protein response (UPR) by misfolded SOD1
ALS pathogenesis is possible by what mechanisms? (5)
- SOD1 mutation
- ALtered axonal transport
- Neurofilament abnormalities
- Glutamate toxicity (increases intracellular calcium)
- Protein aggregates (Bunia bodies) in the cytoplasm
Explain the clinical presentation of ALS
- Loss of motor neurons → hand weakness; arm and leg spasticity/cramping
- Eventually → muscle strength and bulk decrease; Fasciculations
Death in ALS usually results from involvement of ______
Respiratory muscles
Parkinson’s disease is described as degeneration of _____
Substantia nigra (SN) in the basal ganglia
What are the symptoms of Parkinson’s disease? (3)
- Tremor
- Rigidity
- Bradykinesia
True or false. Patients with Parkinson’s disease are not responsive to L-DOPA.
False. They are responsive
Describe the pathology of parkinson’s disease
- SN pallor (B); loss of pigmented neurons
- Degeneration of dopaminergic neurons
- Lewy bodies (eosinophilic cytoplasmic inclusions; α-synuclein fibers
What is the normal function of α-synuclein?
- Lipid binding protein associated with synapses
- Activates melanin production in neurons
Familial PD is associated with gain of function mutations in ____ (4) or loss of function mutation in ______.
GoF:
- Leucine-rich repeat kinase 2 (LRRK2)
- α-synuclein
- DJ-1
- PINK1
LoF:
- Parkin (associated with juvenile form)
Of the genes associated with familial PD, which ones respond to stress responses (UPR, ROS)?
- α-synuclein
- DJ-1
Of the genes associated with familial PD, which one if mutated leads to defective proteasome function?
Parkin
Of the genes associated with familial PD, which ones if mutated result in altered mitochondrial function?
- DJ-1
- PINK1
What is MPTP? What disorder can it cause?
- Byproduct of synthetic opiod production (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
- Common contaminant in street drugs
- Causes Parkinsonian disorder
Explain the mechanism by which MPTP induces Parkinsonian disorder
- Converted to MPP+ in astrocytes
- Inhibits complex I of electron transport chain
- Reduced ATP production and oxygen metabolism
- Increased ROS generation
- Selectively targets dopaminergic neurons (mechanism unknown)
What is dementia?
Impairment of memory and other cortical functions, while alertness is preserved
What is Alzheimer Disease?
- Most common cause of dementia (>50%)
- Presence of specific amyloid plaques and neurofibrillary tangles (NFTs)
- Synaptic loss and presence of reactive astrocytosis and microglial proliferation
How long is the disease course of Alzheimer Disease after diagnosis?
5-10 years
What is the first sign of Alzheimer diseases?
Impaired learning and recall of recent memories
What are amyloid plaques?
- Extracellular amyloid accumulation
- Cerebral cortex and blood vessel walls (meningeal and cerebral)
What is reactive astrocytosis?
- Increased size and number of astrocytes in response to traumatic injury
- Synthesis and release of cytokines
- Induce migration of immune cells to CNS
- Decreased glutamate
What are neurofibrillary tangles (NFTs)?
- Paired helical filaments containing hyperphosphorylated tau protein
- Not specific for AD
What proteins are associated with Alzheimer Disease (3)?
- Presenilins (amyloid processing)
- Apolipoprotein E4 (LDL binding receptor)
- Amyloid β
