Neurocognitive Health Flashcards
What are the two most important questions to ask when diagnosing neurological disease?
- where is the lesion? (location)
- what is the lesion? (diagnosis)
What are the different types of tests to investigate neurologic diseases? (6)
- medical imaging
- electrophysiological studies
- cerebrospinal fluid (CSF) studies
- Microscopy, light & electron microscopy
- molecular genetics and cytogenetics
- biochemical analysis
What are the three layers of the brain?
- dura
- arachnoid
- pia
What is the space between the brain and the skull?
Epidural space
What is the Frontal lobe responsible for?
Thinking, feelings, & motion, speech (motor component)
What is the Temporal Lobe Responsible for?
Hearing and memory (medial)
What is the Parietal Lobe responsible for?
Sensation, speech (sensory component)
What is the Occipital lobe responsible for?
Vision
What is the Brainstem responsible for?
Eye & facial movement, breathing & heartbeat
What is the Cerebellum responsible for?
Balance and coordination
What is the most common section (slice) used in neuropathology?
cornoal slice
What are the tissues that are unique to the CNS? (7)
- neurons
- astrocytes
- oligodendroglia
- ependyma
- microglia
- choroid plexus
- leptomeninges
What tissues are specifically Glia? (4)
- astrocytes
- oligodendroglia
- ependyma
- microglia
What tissues can be found in the rest of the body?
- connective tissue
- blood vessels
- phagocytes
What are Neurons?
- cells that initiate & transmit impulses
- points of connection = synapses
What are Astrocytes?
- scaffolding, insult nerve fibres
- responsible for growth and nutrition of neurons & maintaining environment of CNS including blood brain barrier
- repair of injuries
What are Oligodendrocytes?
Cells that maintain myelin and conduction velocity of nerve fibres
What are Microglia?
Cells that are responsible for defensive (immunologic) responses
What are the different CNS reactions to injuries and diseases? (8)
- Neuronal degeneration
- axonal degeneration
- glial reaction
- demyelination
- microglia
- vascular changes
- cerebral edema
- migration of systemic inflammatory cells to CNS
What is Neuronal degeneration?
Atrophy, damage or necrosis of the neurons
What is Axonal degeneration?
axonal swellings or loss
What is Glial reaction?
astrocytic hyperplasia, proliferation = astrocytosis/gliosis
What is Demyelination?
damage to myeline or oligodendrocytes
What occurs when there is an injury to the Microglia?
Proliferation
What is Vascular changes?
Vasculitis and vasospasm (ischemia), vasogenic edema (breakdown of blood brain barrier)
What is Cerebral Edema?
vasogenic or cytotoxic
What is Vasogenic Edema?
breakdown of BBB with accumulation in extracellular fluid
What is Cytotoxic Edema?
Intracellar swellings of neurons and glia
What is Migration of systemic inflammatory cells to CNS?
Neutrophils, lymphocytes, macrophages
What are the different Nervous System Disorders? (6)
- neoplastic
- infectious
- vascular
- Traumatic
- neurodegenerative
- demyelinating
What are the different CNS Tumours?
- Primary
- Secondary
What are Primary CNS Tumours?
Tumours that arise from neuroepithelial cells in the brain
What are Secondary CNS Tumours?
Tumours that originate outside the brain, the metastasize into the brain
What are the different Primary CNS Tumours?
- Intrinsic = Gliomas
- Extrinsic = Meningiomas, Schwannomas
What is needed to diagnose a Glioma?
3 tiered diagnosis
- histology
- molecular alterations
- WHO grade
What is the Incidence of Primary CNS tumours?
Adults: 11.3/100,000 person-year
Children: 2.3/100,000 person-year
What is the Incidence of Secondary CNS Tumours?
- difficult to assess prevalence
- Common
- perhaps 1 for every 2 primary tumours resected in london, ontario
What are the Primary tumours typically found in adults?
- Astrocytomas (including glioblastoma) and Oligodendrogliomas
> 90% supratentorial (upper part of the brain)
What are the Primary tumours typically found in children?
- Astrocytomas
- ependymomas
- medulloblastomas
- > 90% infratentorial (lower part of the brain)
If a tumour cell resembles Oligodendroglial cells, what is the classification?
Oligodendroglioma
If a tumour cell resembles Ependymal cells, what is the classification?
Ependymoma
If a tumour cell resembles Astrocytes cells, what is the classification?
Astrocytoma
What are the Histological Features that suggest a higher grade tumour and poor prognosis? (5)
- increasing cellularity
- mitoses
- nuclear pleomorphism
- endothelial proliferation
- necrosis
What is the IDH mutation?
- IDH1 R132H mutation most common
- early “initiating” mutation in LG gliomas
- indicates better prognosis
What is Chromosomal Alteration?
- indication of glioma
- 1p/19q Co-Del
What are Meningiomas? (4)
- derived from meninges
- dome shaped, based on dura
- middle to old age
- various histological patterns (psammoma body, ‘whorl’ characteristic)
How are Meningiomas cured?
Resection
What are Metastatic Tumours of the CNS?
- difficult to assess prevalence
- the most common CNS neoplasm in adults
- primary sites: lung, breast, melanoma, renal cell carcinoma and colorectal
Where are Metastatic Tumors of the CNS commonly located?
In the cerebral hemispheres at the gray- white mater junction; also seen cerebellum (15%) and brain stem (<5%)
What is Meningitis?
an inflammation (swelling) of the protective membranes covering the brain and spinal cord. A bacterial or viral infection of the fluid surrounding the brain and spinal cord usually causes the swelling
What are the signs and symptoms of Meningitis? (7)
- fever
- neck stiffness
- headache
- confusion
- CSF cloudy
- inflammatory cells
- positive culture
What are the common bacteria that cause Meningitis in Neonates?
- E. coli
- Group B Streptococcus
What are the common bacteria that cause Meningitis in Children?
- H. Influenza
- N. Meningitides
What are the common bacteria that cause Meningitis in Adults?
- S. pneumoniae
- N. Meningitides
What are the common viruses that cause Meningitis?
- Enterovirus
- HSV
- HIV
- Arbovirus
What are the common Fungi that cause Meningitis?
- Candida
- Cyrptococcus
What is Encephalitis?
an uncommon but serious condition in which the brain becomes inflamed (swollen), caused most by viruses
What are the symptoms of Encephalitis?
- headache
- fever
- seizure
- loss of consciousness
What pathogen is the most common for causing Encephalitis?
Viruses
What is a Cerebral Abscess?
a pus-filled pocket of infected material in your brain
What are the ways Cerebral Abscesses spread?
- Direct spread (50% of cases)
- Hematogenous spread (25% of cases)
- Trauma and Iatrogenic
What are the causes of Direct Spread Cerebral Abscesses?
- Middle ear, paranasal sinus and dental infections
- Mixed flora especially anaerobe, Streptococcus Milleri
What are the causes of Hematogenous Spread Cerebral Abscesses?
- Bronchiectasis
- Congenital heart disease
- Bacterial Endocarditis
- Streptococcus Viridans
- Mixed Flora
What is a Stroke?
When there is rapidly developing clinical signs of focal (or global) disturbance of cerebral function, with symptoms lasting 24 hours or longer or leading to death, with no apparent cause other than of vascular origin
What are the two types of Stroke?
- Ischemic Stoke (infarction)
- Hemorrhagic Stroke (non-traumatic)
What are the two types of Hemorrhagic Stroke?
- Intracerebral
- Subarachnoid
What are the two types of Ischemic Stroke?
- Atherosclerotic Stroke
- Embolic Stroke
What is a Cerebral Infarct?
Localized area of tissue necrosis supplied by a recognized vascular pattern involves neurons, glia, and blood vessels etc.
What are the causes of a Intracerebral Hemorrhage? (8)
- Hypertension (most common)
- leukemia and blood disorders
- tumours
- vascular malformation, aneurysms
- amyloid angiopathy
- vasculitis, immune mediated
- Sepsis
- Medication
What are the causes of a Subarachnoid Hemorrhage? (5)
- developmental, berry aneurysm (most common
- vasculitis, immune mediated
- inflammatory aneurysm, septic vasculitis
- amyloid angiopathy
- arteriovenous malformation
Where are the common sites of Hypertension Hemorrhage?
- basal ganglia
- thalamus regions (most)
- pons
- cerebellum
What are the results of Hypertension Hemorrhage?
Fatal hemorrhage rupture into ventricles, or resulting in massive brain swelling
What is a Cerebral Amyloid Angiopathy?
deposition of amyloid (beta-amyloid) weakening the wall of subarachnoid and cortical vessels leading to rupture giving rise to lobar (intracerebral) and subarachnoid hemmorhages
What populations does Cerebral Amyloid Angiopathy occur in?
Usually elderly, strong association with Alzheimers
What is Berry (Saccular) Aneurysm?
- Developmental defect in media, results in weakening of arterial wall
- 5-6% of general population
What are the common sites of Berry (Saccular) Aneurysm?
- anterior communication artery (40%)
- Bifurcation of middle cerebral artery (34%)
- Bifurcation of internal carotid artery (20%)
What are the manifestations of Berry Aneurysm?
- local pressure; isolated 3rd cranial nerve palsy
- rupture = hemorrhage
What can Berry Aneurysm lead to? (5)
- subarachnoid hemorrhage
- Brain swelling with uncal or tonsillar herniation
- Duret’s hemorrhage
- Infarction
- Hydrocephalus
What is Duret’s Hemorrhage?
Secondary brain stem hemorrhage
What is Hydrocephalus?
Blood clots in ventricles and subarachnoid space
What is the leading cause of death in people under 45 years old?
Head injury
What are the mechanisms of Traumatic brain injury?
impact/blunt force injury
What is the pattern of TBI?
Focal
What are the characteristics of a Skull Fracture?
- radiate out from or pass through impact site
- not always associated with brain damage
What are the different patterns of Skull Fractures?
- Linear (single line)
- Comminuted (multiple lines)
- Compound (communicates with cranial cavity)
- Depressed (Fracture margins pushed into cranial cavity)
- Hinge (Fracture extends across the base of the skull)
What is Traumatic Intracranial Hemorrhage?
Bleeding inside the cranium that is caused by trauma
Where can Traumatic Intracranial Hemorrhage occur? (5)
- Epidural (outside the dura)
- Subdural (under the dura)
- Subarachnoid (under the arachnoid)
- Intracerebral (in the brian)
- Intraventricular (in the cerebral ventricles)
What is an Epidural Hematoma?
bleeding between the inside of the skull and the outer covering of the brain (dura)
What does Epidural Hematoma result from?
- fracture of the squamous temporal bone causing contact damage to the underlying middle meningeal artery or vein
- 30% associated with “lucid interval”
What are the characteristics of Acute Subdural Hemorrhage?
- may clinically mimic an acute epidural hemorrhage
- Usually associated with other brain trauma
- caused by fall or blow to head
What are the causes of Acute Subdural Hemorrhage? (3)
- Venous tears
- Tear of Subarachnoid or superficial cortical artery
- Tear of middle meningeal artery
What are the Characteristics of Chronic Subdural Hemorrhages?
- lingering (missed” acute subdural hemorrhage
- Gradual expansion of, then bleeding into, subdural ‘hygroma’
What is a Brain Contusion?
- hallmark of brain damage in head injury
- a bruise on the surface of the brain
- the overlying pia mater is intact
What is a Laceration of the brain?
Pia mater is torn
How do Contusions and Laceration look?
Involve the crest of gyri contact with protuberances within the skull:
- frontal lobe
- temporal lob
- cortex above/below Sylvian fissure
What are the Characteristics of Coup Brain Contusions?
- occur under the sites of an impact
- are usually the result of a blow
What are the Characteristics of Contre-coup Contusions?
- occur ‘at a distance’ from (often opposite) the site of an impact
- are usually the result of a fall
- is most obvious with an occipital impact (fall back vs fall forward)
In what Neurologically Degenerative Disease does Neurofibrillary Tangles and Neuritic Plaques occur?
Alzheimer’s
What are the most common form of neurological disease?
Degenerative Disease
What are Degenerative Diseases?
- progressive death of neurons
- specific proteins accumulation in neurons, glia, or extracellular space
What are the different types of Degenerative Diseases?
- cortical degeneration
- movement disorders
- motor neuron disease
What are examples of Cortical degenerration?
- Alzheimer’s
- Lewy body disease
- Frontotemporal lobar degeneration
what are examples of Movement Disorders?
- Parkinson’s
- Huntington
What are examples of Motor Neuron Disease?
- Amyotrophic Lateral Sclerosis (ALS)
What are the Molecular classifications of Degenerative Diseases?
- Tauopathy
- a-Synucleinopathy
- TDP-43
- Polyglutamine
What is Alzheimer’s Disease?
- slow progressive dementia
- impaired cognition; motor and sensory systems intact
- 50-70% of cases of dementia
What is the Gross pathology of Alzheimers?
Atrophy especially in the frontal and temporal lobes
What is the Micro pathology of Alzheimers? (3)
- neuronal loss in cerebral cortex
- Gliosis (astrocyte proliferation and hypertrophy)
- Amyloid deposits, neurofibrillary tangles, neuritic plaques
What are the different stages of Alzheimers?
- Thal stages (A)
- Braak and Braak stages (B)
- CERAD stages (C)
What is Parkinson’s Disease?
Chronic neurological condition, slowly progressive, affecting movement
What are the symptoms of Parkinson’s Disease? (4)
- resting tremor
- generalized slowness of movement
- stiffness of limbs
- gait or balance problems
What is Dopamine (DA)?
- neurotransmitter produced by the pigmented neurons in substantia nigra (SN)
- important to control of movement
What occurs to Dopamine in Parkinson’s?
- selective damage to Dopamine in the Substantia nigra
- damage to it gives imbalance of neurotransmitters in the basal ganglia
What are the Gross pathology findings of Parkinson’s?
loss of pigments in the substantia nigra of the midbrain
What are the Microscopic pathology of Parkinson’s?
- loss of pigments neurons in the substantia nigra with eosinophilic inclusions (lewy bodies) in cytoplasm of some remaining neurons
- increased astrocytes (gliosis) reacting to neuronal loss
What are Lewy Bodies?
Eosinophilic inclusions that express neurofilament protein & alpha-synuclein
What does the mutation of Alpha-Synuclein cause?
Familial Parkinson’s with early onset
What are lewy bodies in cerebral cortex associated with it?
Dementia
What is Primary Demyelination?
Involved the damage and breakdown of myelin with relative sparing of axons ex. ms
What is Secondary Demyelination?
Involves myeline breakdown along the course of injured or dying axons ex. neurodegenerative diseases
What is the Incidence of Primary Demyelination? (3)
- common in temperate latitudes
- onset 20-40 years
- more common in females
What is the Etiology of Primary Demyelination? (3)
- Uncertain cause
- genetic predisposition (family, racial, twin, HLA studies)
- environmental
What is the Pathogenesis of Primary Demyelination?
autoimmune reaction against oligodendroglia or CNS myelin associated with T- lymphocyte sensitization
What is the Clinical Manifestations of Primary Demyelination?
- Unilateral weakness
- paresthesia
- optic neuritis or Charcot’s triad
What is the Charcot’s Triad?
- nystagmus (involuntarily eye movements)
- tremor
- dysarthria (difficulty speaking)
What are the Macroscopic Findings of MS?
Multiple scattered, grey, sharply defined plaques (demyelinated areas) throughout the white matter
What are the Microscopic Findings of MS?
- Oligodendroglia lost or decrease
- demyelinated areas coalesce to form macroscopically visible MS plaques with inflammation at the border
- Chronic lesions show gliosis
Where do MS lesions frequently occur?
- periventricular white matter
- brain stem
- spinal cord
- optic nerves
