Introduction to Neuropathology Flashcards by Hannah Wilkinson

Which cells in embryology become the peripheral nervous system?

Neural crest cells

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Which embryological structure creates the central nervous system?

Neural tube

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Why do we have different types of neuron structure?

Because they are adapted for processing different pathways - e.g. sensory / motor

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What do we have more of - neurons or glial cells?

Glial cells
86 billion neurons
100 billion glial cells

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What function do astrocytes have?

Support, communication, repair & maintenance of BBB

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What function do oligodendrocytes have?

Myelination of neurons in CNS

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What do ependymal cells do?

Line the ventricles - make CSF

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Which cells are the immune cells of the CNS?

Microglia

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Which cells are responsible for myelination in the PNS?

Schwann cells

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Which cells regulate the environment of the PNS?

Satellite cells

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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.

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What protects the brain?

BBB & meninges

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Why do some people argue that the brain is immune privileged?

Because it is separate to the immune system - no antigen-presenting cells circulate.

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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

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Which is the main immune cell of the brain?

Microglial = brain macrophages - and also is antigen-presenting

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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

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How does neuroinflammation work in the brain?

Vascular dilation = inc permeability + inc adhesion
Microglia activated
Macrophages recruited
Odema (vasogenic + cytotoxic)
Astrocytes repair
Demyelination

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What does VITAMIN C stand for?

Vascular
Inflammation / Infection
Toxins / Drugs
Autoimmune
Metabolic
Idiopathic
Neoplastic
Congenital / Genetic

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What is a tumour of the meninges called?

Meningioma

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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)

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Why is neuroinflammation dangerous?

Because there is limited space in the cranium - any increase to volume can cause catastrophic brain injury.

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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).

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What is the name of a paraneoplastic syndrome that affects the peripheral nervous system?

Lambert Eaton syndrome

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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?

Where does the spinal cord end?

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