CNS-II Flashcards
Def. of early onset dementia
o Cases of dementia in adults ranging from 18 to 65 years of age
Learning and memory
Can’t be independent anymore
what is the most common cause of dementia in adults
alzheimers disease
what are the neuropathologic changes that occur in the brain in Alzheimers disease
• Essential neuropathologic changes”
o Neuritic plaques
o Extracellular deposits of amyloid beta peptides
o Neurofibrillary tangles (tau proteins)
Pathogenesis of AD
- Amyloid precursor protein (APP) cleaved by beta-secretase and gamma-secretase
- Mutations in presenilin 1 (PSEN1) or presenilin 2 (PSEN2) production of amyloid beta plaques
what do the tau proteins cause in the brain
• Tau:
o hyperphosphorylated and aggregates → Causes an inflammatory response
Genetic risk factors for early-onset AD
o Early-onset Alzheimer’s
Younger than age 65 (40s and 50s)
Mutations in APP, PSEN1, and PSEN2
ANY OF THESE THREE MUTATE AND THERE WILL BE A 100% CHANCE OF AD
Genetic risk factors for late-onset AD
People age 65 and older
Carries of APOE e4
Pre-symptomatic period occurs due to ?
genetic mutations in APP1, PSEN1 or PSEN2
Cardinal Clinical symptoms of AD
o Memory impairment
o Executive function and judgement/problem solving behavioral and psychological symptoms
Pathogenesis of Parkinson’s
– Interplay of genes and the environment
o Basal ganglia circuits
Dopamine depletion in the substania nigra ultimately results in:
Increased inhibition (GABA) of the thalamus
Reduced excitatory input (glutamate) into the motor cortex
hallmark pathology of Parkinsons disease
lewy body
The brain compensates for the dopamine depletion by?
o Increasing the synthesis of dopamine in surviving neurons
o Proliferation of dopamine receptors
o Gap junctions allowing rapid communications between neurons increase dramatically
Clinical Features of PD
o Tremor
“rest tremor” and intermittent
o Bradykinesia
Generalized slowness of movement
o Rigidity
Increased resistance to passive movement about a joint
Pts feel like it’s taking them forever to do something
o Postural Instability
An impairment of postural reflexes that cause a feeling of imbalance and a tendency to fall
Amyotrophic Lateral Sclerosis (ALS) is defined by?
• Definition: persistently progressive neurodegenerative disorder that causes:
o Muscle weakness (motor neuron degeneration)
o Disability
o Eventually death
Amyotrophic Lateral Sclerosis (ALS) established risk factors and environmental factors ?
• Sporadic: 90 to 95%→ Sporadic and familial ALS. Approximately 90% cases of ALS are called “sporadic,” meaning the cause or causes of the disease are unknown. • Established risk factors o Age o Family history • Environmental factors o Smoking o Environmental toxin exposure o Military Service
Etiology of ALS
• Etiology (unknown, but they’re hypothesis) o Abnormalities in RNA metabolism o Excitotoxicity o Viral Infections o Inflammatory Responses
Pathology of ALS
o Intracellular inclusions in degenerating neurons and glia
→ Characterized by motor neuron degeneration and death with gliosis
→ Spinal cord becomes atrophic
→ The affected muscles show denervation atrophy
Clinical Features of ALS
o Upper motor neuron:
findings of weakness with slowness, hyperreflexia, and spasticity
Due to degeneration of Frontal Motor Neurons
o Lower motor neurons:
Findings of weakness, atrophy, and fasciculations (muscle twitch)
Due to degermation of lower motor neurons in the brainstem and spinal cord
pathogenesis of multiple sclerosis and alternate theories
o Immunopathology:
Begins as an inflammatory immune-mediated disorder
Microglia forms a complex with the activated T-cells leads to destruction of myelin and oligodendrocytes
Areas of CNS affected are referred to as “lesions” or “plaques”
o Alternate Theories:
A possible immune (but not autoimmune) etiology
Genetically determined
Main Disease Patterns of multiple sclerosis?
o Clinically isolated syndrome
First attack of a disease with inflammatory demyelination, but has yet to fulfill MS diagnostic criteria
With no previous evidence of MS: newly diagnosed
o Relapsing-Remitting (RR)
Clearly defined relapses with fully recovery
o Secondary Progressive (SP)
Initial RR disease course followed by gradual worsening (transitional)
o Primary progressive (PP)
Progressive accumulation of disability (w/ or w/o remission)
Symptoms of multiple sclerosis
• Symptoms: (polysymptomatic onset)
o Sensory in limbs
o Visual loss
o Motor (subacute)
What are gliomas
o Gliomas are primary brain tumors that show histologic features of glial cells
Glial cells are the cells that support the nerve cells (astrocytes, oligodendrocytes, ependymal cells)
what type of brain tumors are diffuse gliomas?
o Astrocytomas Diffuse Gliomas o Oligodendrogliomas Diffuse Gliomas o Ependymomas o Mixed Gliomas
Gliomas can be classified into three categories they are?
• Classifications of diffuse gliomas
o Mutation of the IDH -OR- IDH Wildtype (stays normal) astrocytomas
Enzyme in kreb’s cycle
o Mutation of IDH -AND- Co-Chromosomal deletion of chromosome 1 and 19( causes loss of tumor suppressor gene)oligodendrogliomas
o IDH-mutant -OR- IDH- wild type glioblastoma
• Systemic symptoms
Systemic symptoms of diffuse gliomas
• Systemic symptoms
o Headache ICP
o Seizures ICP
o N/V ICP
o Depressed level of consciousness perfusion to brain
o Neurocognitive dysfunction perfusion to brain
Focal symptoms of diffuse gliomas
• Focal Symptoms
o Weakness
o Sensory loss
Astrocytoma
• Formation of astrocytoma: grade II astrocytoma is associated with:
o Mutations in IDH1
o Inactivation of the TP53
o Mutations in the chromatin regulator gene
• IDH and its link to gliomas:
o Acquiring a somatic mutation in either IDH-1 or IDH-1 accumulation of the oncometabolite 2-hydroxyglutarate (2-HG)
o Elevated levels in 2-HG can cause
Changes in DNA and histone methylation (epigenetic)
Abnormalities in cellular differentiation
Tumorigenesis (oncogenic)
The transition from low-grade to high grade (malignant) glioma is associated with?
o Cell cycle checkpoint inactivation
o Tumor suppressor gene inactivation
o Angiogenesis
what brain tumors are considered High-grade gliomas?
o Anaplastic gliomas
o Glioblastoma
what is a meningioma
• Definition:
o Predominantly benign tumors of adults arising from the meninges
What are risk factors for a Meningioma
o Prior radiation therapy (ionizing radiation) to the head and neck, typically decades earlier
Therapeutic -cancer
Atomic bomb survivors
What is the etiology of a meningioma and what are the clinical features?
• Etiology:
o Abnormal chromosome 22
• Clinical Features
o Usually slow-growing tumors
o Headache and weakness in an arm or leg are the most common symptoms
o Often express progesterone receptors
Tumor will grow faster in pregnant women ( due to high progesterone levels)
The most common brain tumor in adults is?
What are the common most primary sites of this tumor
o Lung ** o Skin (melanoma) o Kidney o Breast o GI tract
How do metastatic tumors come to be?
o Circulating tumor cells use the bloodstream or lymph system initially migrate and enter the lungs, then move on to the brain
What are the clinical features of metastatic brain tumors
o Headache
o Focal neurologic dysfunction: Hemiparesis
o Cognitive dysfunction
