Introduction to Neuropathology Flashcards
Which cells in embryology become the peripheral nervous system?
Neural crest cells
Which embryological structure creates the central nervous system?
Neural tube
Why do we have different types of neuron structure?
Because they are adapted for processing different pathways - e.g. sensory / motor
What do we have more of - neurons or glial cells?
Glial cells
86 billion neurons
100 billion glial cells
What function do astrocytes have?
Support, communication, repair & maintenance of BBB
What function do oligodendrocytes have?
Myelination of neurons in CNS
What do ependymal cells do?
Line the ventricles - make CSF
Which cells are the immune cells of the CNS?
Microglia
Which cells are responsible for myelination in the PNS?
Schwann cells
Which cells regulate the environment of the PNS?
Satellite cells
Why do some demyelinating disorders affect CNS rather than PNS and vice-versa?
Depends which type of glial cell is affected by the demyelinating disorder.
What protects the brain?
BBB & meninges
Why do some people argue that the brain is immune privileged?
Because it is separate to the immune system - no antigen-presenting cells circulate.
What information contradicts the idea that the brain may not be completely separated from the immune system?
Mice studies - mice have lymphatic system in dural venous sinuses - allows some brain cells to travel to cervical lymph nodes
Which is the main immune cell of the brain?
Microglial = brain macrophages - and also is antigen-presenting
How does the brain form a BBB?
Brain capillaries are sealed off - by astrocyte foot processes
Brain capillaries also have thick basement membrane + tight junctions
- All prevents leakage out of the brain capillaries
How does neuroinflammation work in the brain?
Vascular dilation = inc permeability + inc adhesion
Microglia activated
Macrophages recruited
Odema (vasogenic + cytotoxic)
Astrocytes repair
Demyelination
What does VITAMIN C stand for?
Vascular
Inflammation / Infection
Toxins / Drugs
Autoimmune
Metabolic
Idiopathic
Neoplastic
Congenital / Genetic
What is a tumour of the meninges called?
Meningioma
Today we can categorise tumours based on their genetic sequences and tailor our treatment in response. What is this called?
Personalised medicine (or precision cancer medicine)
Why is neuroinflammation dangerous?
Because there is limited space in the cranium - any increase to volume can cause catastrophic brain injury.
How can cancers affect the brain without inflitration?
Paraneoplastic syndromes - means that cancers can exert hormonal or autoimmune effects on the brain (e.g. antibodies can begin to attack the normal brain cells).
What is the name of a paraneoplastic syndrome that affects the peripheral nervous system?
Lambert Eaton syndrome
What is the name of a paraneoplastic syndrome that affects the central nervous system?
NMDA encephalitis
What are the symptoms of meningitis?
Headache
Nuchal rigidity (neck stiffness)
Photophobia
Inflammation of the leptomeninges is usually caused by?
Infection
Which meninges make up the leptomeninges?
Pia + Arachnoid
Which meninges make up the pachymeninges?
Arachnoid + Dura
Inflammation of the pachymeninges is usually caused by?
Cancer or TB
What is encephalitis?
Alteration in sensory/cognitive state due to inflammation (infection or AI).
What test can we use to diagnose meningitis?
LP
Where does the spinal cord end?
L2
Which part of the spine do you want to tap?
L4-5 or L5-S1
Name 4 things that can cause abnormal lumbar puncture results.
Shift (midline shift)
Trauma
Obstruction
Posterior fossa mass
What can happen as a consequence of unequal intracranial pressures?
Brain can herniate
Spinal tap results show:
High pressure
Turbid Appearance
High protein
Low glucose
Presence of neutrophils
What is the likely cause?
Bacterial infection
Protein + pus/cloudy CSF + low glucose
Spinal tap results show:
High-normal pressure
Clear appearance
Normal-high protein
Normal glucose
Presence of lymphocytes
What is the likely cause?
Viral / Aseptic
Spinal tap results show:
High-normal pressure
Fibrin web appearance
Normal-high protein
Normal-low glucose
Presence of lymphocytes
What is the likely cause?
Fungal or TB
What is the treatment for viral meningitis?
Supportive treatment as no specific treatment
Why is a patient’s age important in determining a likely diagnosis?
Because Ps at different ages are more susceptible or likely to encounter certain pathogens (e.g. Mono - uni students).
How can the following affect CSF circulation? (They all have the same effect…)
Blockage of flow
Overproduction
Reduced reabsorption
Cause pressure to become too high
What can cause the CSF circulation to have low pressure?
Trauma or spinal tap
What are the names of the foramina that the CSF exits through?
Foramina of Lushka & Magendie
How can you identify hydrocephalus on MRI?
Enlarged ventricles & shrunken white matter
What is the name for water on the brain?
Hydrocephalus
What is the name for a direct and indirect brain injury?
Direct = coup (e.g. blow to head)
Indirect = contre-coup (brain moves backwards and accelerates into the back of the skull - injury is on opposite side to where the force is implemented)
What is the name for a brain injury that has immediate and transient alteration in brain function - leading to headache, drowsiness, concentration deficits & amnesia
Concussion
What is the name for bruising of the brain tissue?
Contusion
How can contusion of the brain present?
Confusion, altered consciousness, focal neurological deficits
Name 3 secondary effects of blunt trauma
Cerebral oedema
Ischemia
Blood vessel damage
In acceleration-deceleration brain injuries - what happens to the axons?
Rotational movements = shearing forces - cause axons to stretch.
What is the name of the injury caused to axons by stretching in trauma?
Diffuse axonal injury
What can a diffuse axonal injury cause?
Loss of consciousness
Coma
What imaging can determine a diffuse axonal injury?
Not CT
MRI (T2-Flair) - may show hyperintensity at grey-white junction - white matter may also look less white due to removed myelin.
What are the possible symptoms of increased cerebral pressure?
Headaches
Meningism
Vision changes
Papilloedema (optic nerve swelling)
CN6 palsy - abduction of eye impaired
Loss of consciousness
High BP –> reflexive bradycardia & irregular respirations
What is Cushing’s reflex
High intercranial pressure - widening pulse pressure, reflexive bradycardia & irregular respirations
What do repetitive brain injuries put Ps at risk of developing?
Chronic Traumatic Encephalopathy
How does CTE present pathologically?
Tauopathy (lots of Tau protein accumulations) present in superficial cortical layers. (+ inc tau-immunoreactive astrocytes)
Deposition of β-amyloid is far less common in these Ps
Which is the primary protein seen in all three of these diseases:
- Chronic Traumatic Encephalopathy
- Progressive Supranuclear Palsy
- Corticobasla Degeneration
Tau (Tauopathies)
Which is the primary protein seen in all of these diseases:
- Alzheimer’s Disease
- Cerebral Amyloid Angiopathy
- Posterior Cortical Atrophy
- Agrammatic Primary Progressive Aphasia
Β-amyloid (Amyloidopathies)
Which protein is seen in high levels of these diseases:
- Parkinson’s Disease
- Dementia with Lewy Bodies
- Multiple System Atrophy
Α-synuclein (Synucleinopathies)
Which protein is seen in v-CJD (new variant Creutzfeld-Jakob) & Kuru?
Prions
Which protein is found in MND & Amyotrophic Lateral Sclerosis?
TAR DNA-Binding Protein 43 (AKA TDP-43)
Can you know for certainty which dementia a P actually has?
Cannot make definitive classification until autopsy - clinically we look at “possible and probable”.
What is a secondary headache?
One caused by something else in the body - e.g. infection, malignancy, stroke, medications, toxins & homeostasis imbalance
What is a primary headache?
Not caused by something else in the body - literally pain from the brain.
Name 3 types of primary headache
Tension-type
Migraine
Trigeminal autonomic cephalagias (inc cluster headaches)
When do you need to investigate a headache for cause (to determine if secondary or primary)?
- Increases with Valsalva (pinch nose & blow)
- Wakens OUT of sleep (not waking up with it)
- Change in character of the headache
- Age of onset
- Sudden onset (thunderclap)
- Focal neurological deficits
- Constitutional symtoms (fever, meningism, rash & weight loss)
What is the mnemonic for red flags for headaches?
SNNOOP 10
Systemic symptoms
Neoplasm history
Neurological deficit
Onset sudden
Older age
Pattern change
Positional
Precipitated by sneezing, coughing or exercise
Papilloedema (optic disc swelling - vision disturbances)
Progressive headache + atypical presentation
Pregnancy / Pueperium (6 weeks post birth)
Painful eye with ANS features
Post-traumatic onset
Pathology of immune system (e.g. HIV)
Painkiller overdose
Which is the most common type of primary headache?
Tension-type headache
How does a tension-type headache present?
Featureless, band-like pressure - squeezing / vice pressure
Bilateral
No usual associated features (but photophobia or phonophobia can occur)
How can you determine whether a headache is frequent or infrequent?
Frequent = 10 episodes occurring on 1-14 days per month for > 3 months
What is the definition of a chronic headache?
> 15 days/month for >3 months
What are the symptoms of migraine?
Photophobia
Incapacity
Nausea
(PIN)
What is a migraine termed that happens on 15 or more days per month >3 months (and for 8 of those days has migraine features?)
Chronic migraine
What is the difference between a common and classical migraine?
Common migraine = without aura
Classical migraine = with aura
What is the name for a migraine that lasts longer than 72 hours?
Status migrainosus
How common are cluster headaches?
Very rare - 1 in 1000
How do cluster headaches present?
Sharp, excruciating pain - can cause agitation
Lasting 15-180 mins
Up to x8 per day - for weeks
Unilateral side pain
Stabbing eye pain
Has associated autonomic features (ptosis, mitosis, nasal congestion & lacrimation)
How do migraines present
Can last 4-72 hours
Unilateral (mostly)
Throbbing pain
Nausea + vomiting + photo/phonophobia
Aura possible
What is the latest theory on the cause of headaches?
Neuromuscular theory - that sensory neurons in trigeminocervicocomplex = source of pain
How is it thought that headaches are triggered in the sensory pathway?
Trigeminal ganglion is stimulated (1st order)
Stimulates the pars caudalis (pain & temp) in 2nd order
Stimulates the ventromedial nucleus of thalamus (3rd order)
Stimulates the sensory cortex of the Insula Cingulate (4th order)
Which is the main complex that is associated with headaches?
Trigeminocervical complex (TCC)
Which pathway is thought to be dysregulated in TAC (cluster) headaches?
Trigeminal Autonomic Reflex Pathway
How can you prevent medication overuse headaches?
Triptans <10 days
Non-opiod analgesics <15 days
Opioids <10 days
What is it called when the brain cells are deprived of oxygen?
Anoxic brain injury
What can anoxic brain injuries cause clinically?
Seizures
Myoclonus (twitching of muscles)
Coma / Minimally conscious states / Unresponsive wakefulness syndrome)
Brain death
