Neuro Flashcards
What do contusions involve?
The surface of the brain
2 types of contusions?
Coup (contusion at the site of impact)
Contrecoup (contusion at the opposite to the site of impact)
Common scenario for epidural haemorrhage?
Parietal/squamous temporal bone fracture with middle meningeal artery rupture
What is a ‘lucid interval’ in epidural haemorrhage?
initial consciousness level appears normal
progressive pain and LOC hours later
What causes subdural haemorrhage?
rupture of bridging veins causing haemorrhage into the potential space between the brain and the dura
Causes of subdural haemorrhage?
injury/impact (most common)
spontaneous or following trivial impact (coagulopathy)
chronic hydrocephalus
Features of chronic subdural haemorrhage?
weeks or months following injury
slowly progressive symptoms
older patients
Causes of subarachnoid haemorrhage?
Can be spontaneous (rupture of berry aneurysm)
can be caused by single punch (stretching and tearing of artery consequent to impact)
Features of intracerebral haemorrhage?
Usually associated with other trauma manifestations
take time to develop
What are deep seated haemorrhages associated with?
High-velocity blunt force trauma
What causes traumatic diffuse axonal injury (DAI)?
rotational forces leading to shearing of neuronal processes
patients have immediate prolonged coma
What is seen microscopically in DAI?
white matter haemorrhages
corpus callosum lesions
axonal retraction balls
Examples of secondary brain injury?
intracranial haemorrhage may extend brain swelling intracranial herniation syndromes global ischaemic brain damage infections
What causes ‘ring’ haemorrhages in the brain?
Fat embolism
How does a fat embolism reach the brain?
if pulmonary trapping capacity is exceeded
via a v-shunt
Consequences of head injury?
post-traumatic hydrocephalus
post-traumatic epilepsy
chronic infections or late-presenting infection
chronic traumatic encephalopathy
3 determinants of ICP?
blood brain barrier
pressure volume equilibrium
cerebrovascular autoregulation
What is average intra-cranial volume in adults?
1700ml
What is the Monroe-Kellie doctrine?
ICP can only be held stable if an increase in one component is compensated for by the other two
What are the three components of ICP?
brain tissue, blood, CSF
What is cerebral perfusion pressure?
The difference between ICP and mean arterial pressure
What does an elevated ICP that approaches MAP mean?
this results in reduced cerebral perfusion pressure- ischaemic injury to cerebral tissue
What is the major consequence of BBB failure?
Cerebral oedema
What is cerebral oedema?
a state where there is a local or diffuse increase in brain water
Causes of cerebral oedema?
Physical injury Tumours (especially mets) Inflammatory disease Pseudotumor cerebri Vascular disease Drugs and chemicals Metabolic disease
Appearance of cerebral oedema?
Increased brain weight and swelling
Possible discolorations
Where is CSF formed?
In the choroid plexus
What happens if there is increased CSF and venous pressure?
may be transmitted to the eye and cause venous distension and optic disc swelling
Herniation syndromes include?
subfalcine herniation
transtentorial herniation
cerebellar tonsillar herniation
What becomes compressed in subfalcine herniation?
the anterior cerebral arterty
What becomes compressed in transtentorial herniation?
CN III
posterior cerebral artery
What becomes compressed in cerebellar tonsillar herniation?
brainstem compression
What is a Duret haemorrhage?
Haemorrhage within the brainstem
What name is given to a haemorrhage within the brainstem?
Duret haemorrhage
Clinical manifestations of increased ICP?
Headache (worse when lying down) Nausea Vomiting Confusion LOC Localising signs due to herniation effects
What is a hydrocephalus?
accumulation of excessive CSF in the ventricular system
Causes of hydrocephalus?
overproduction due to tumour of choroid plexus (rare)
reabsorption limited by altered flow due to obstruction
Clinical features of hydrocephalus?
headache nausea and vomiting drowsiness and LOC ocular palsies and pupal dilation papilledema
Outcome of hydrocephalus?
Acute- no time for compensation- collapse/death
Chronic- time for compensation- CSF pressure can return to normal limits
Where are most CNS tumours located in children?
Posterior fossa (70%)
Where are most CNS tumours located in adults?
Cerebral hemispheres (70%)
How do CNS tumours typically present?
with signs of increased ICP
Are diffuse gliomas amenable to surgical resection?
No- they typically infiltrate large volumes of brain tissue
What are the commonest primary CNS tumours in adults?
Diffuse Gliomas
Meningiomas
What are the commonest CNS tumours in children?
Gliomas Embryonal tumours (medulloblastomas)
What percent of primary brain tumours in adults are diffuse gliomas?
80%
What are ependymomas?
slow growing neoplasms that arise from an ependymal surface, usually the 4th ventricle
commonest neoplasm of the spinal cord
In who are ependymomas commonly seen?
Young children (adverse prognosis)
Where do medulloblastomas arise?
In the cerebellum in children
Features of medulloblastomas?
Present with headache and vomiting
growth rate is rapid
extensive local infiltration
spread via CSF pathways
Who do primary CNS lymphomas occur in?
middle-age
primarily in the immunosuppressed
Features of primary CNS lymphomas?
primary high grade B cell lymphomas
radiosensitive
steroid responsive
How common are meningiomas?
20% of primary brain tumours in adults
more common in women
Prognosis of meningiomas?
Usually low-grade tumours
Outcome related to completeness of surgical resection
Most common sites for mets to the brain?
breast, lung, kidney and malignant melanoma
Examples of familial brain tumours?
Turcot syndrome
Li-Fraumeni syndrome
Cowden syndrome
What is Turcot syndrome associated with?
medulloblastoma or glioblastoma
APC gene
What is Li-Fraumeni syndrome associated with?
medulloblastoma, TP53 mutations
What is Cowden syndrome associated with?
Lhermitte Duclos disease
PTEN mutations
What is the inheritance pattern of tuberous sclerosis?
Autosomal Dominance
What is tuberous sclerosis associated with?
seizures, mental retardation and autism
hamartomas and benign tumours of brain and other tissues
Translocation associated with tuberous sclerosis?
TSC1 (9q) and TSC2 (16p)
What does von Hippel Landau disease cause?
hemangioblastomas of CNS
cysts of liver, pancreas and kidneys
propensity to develop RCC and pheochromocytoma
Pattern of inheritance of vHL?
autosomal dominant
mutations of VHL 3p
Neurofibromatosis 1 features?
more common
neurofibromas of peripheral nerves, cafe au lait spots, Lisch nodules, optic nerve gliomas
Neurofibromatosis 2 features?
less common
bilateral acoustic neuromas, multiple meningiomas
Two major causes of CVAs?
Thrombosis
Haemorrhage
Why is it important to establish the cause of a CVA?
to determine treatment
thrombolysis vs anticoagulants
Why is treatment urgent in a CVA?
possibility of limiting ischaemia and secondary damage to penumbra
managing ICP
Causes of thrombotic CVA?
atherosclerosis antiphospholipid syndrome arteritis arteriopathy coagulopathy, smoking
Causes of a haemorrhagic CVA?
aneurysm arterio-venous malformation arterial HTN anticoagulants amyloid angiopathy arteritis anaplastic tumour
3 main sources of thromboembolism causing CVA?
Heart (A Fib)
Carotid bifurcation (atherosclerosis)
Aorta (spine)
What does occlusion result in?
Infarction and liquefactive necrosis
‘Pale’ infarct vs ‘Red’ infarct?
‘Pale’ infarct comes from complete infarction
‘Red’ infarct occurs when there is reperfusion
What causes hypoxic/ischaemic encephalopathy?
cardiac arrest
shock
Pathophysiology behind HIE?
glutamate release from neurons
calcium influx
free radicals and catabolic enzymes
neuronal necrosis
Which section of the brain is particularly vulnerable to HIE?
Ammon’s horn in the hippocampus
What is multi-infarct dementia?
impairment in multiple cognitive functions due to a vascular cause
Risk factors for multi-infarct dementia?
Elderly
DM
smoking
HTN
Where does a hypertensive haemorrhage most affect?
the basal ganglia and the brainstem
What occurs in hypertension?
Fibrinoid degeneration of the arteries
What does cerebral amyloid angiopathy occur with?
Alzheimer’s disease
Which lobes are most affected by cerebral amyloid angiopathy?
Occipital lobes
What stain is used in cerebral amyloid angiopathy?
Congo Red
What is a Congo Red stain used to identify?
Amyloid
How do neurodegenerative diseases manifest macroscopically and microscopically?
Macroscopically - atrophy
Microscopically - neuronal loss and accumulation of abnormal proteins
Other names for Motor Neuron Disease?
Amyotrophic lateral sclerosis
Lou Gehrig’s Disease
Macroscopic pathology of ALS?
atrophy of motor cortex
atrophy of motor nerves
MND prognosis?
Death within 5 years due to respiratory failure or aspiration
Histology of MND?
loss of motor neurons loss of myelinated axons gliosis Bunina bodies spherical inclusions variety of proteins (most contain TDP43)
What are akinetic-rigid disorders?
extrapyramidal
characterised by rigidity, bradykinesia and resting tremor (Parkinsonism)
Examples of akinetic-rigid disorders?
Parkinson's Multiple System Atrophy Progressive Supranuclear Palsy Corticobasal degeneration Wilson's disease, drug-induced parkinsonism, vascular parkinsonism
What causes Parkinson’s Disease?
loss of dopaminergic neurons of the nigrostriatal system
loss of melanised neurons from the substantia niagra
What protein is accumulated in Parkinson’s disease?
alpha-synuclein
Familial forms of Parkinson’s?
SNCA, PARK2, PINK1, UCHL1, DJ1, LRRK2
Hyperkinetic movement disorders are characterised by?
Chorea
Ballismus
Myoclonus
Dystonia
What is ballismus caused by?
Damage to the subthalamic nucleus
Huntington’s Disease features?
involuntary movements
psychiatric symptoms
dementia
Gross appearance of Huntington’s Disease?
cerebral atrophy
atrophy of caudate, putamen and globus pallidus
Microscopic appearance of HD?
neuronal loss and gliosis in basal ganglia
ubiquitin and huntingtin
Inheritance pattern of HD?
AD
‘CAG’ expansion- longer expansion = earlier onset
huntingtin gene on chromosome 4
Examples of degenerative ataxias?
Spinocerebellar ataxia
Friedrich ataxia
Ataxia-telangiectasia
When does Friedrich’s ataxia present?
pre-adolescence
What other diseases are associated with Friedrich’s ataxia?
Hypertrophic Cardiomyopathy (60%) Diabetes Mellitus (10%)
Friedrich’s ataxia inheritance pattern?
Autosomal recessive
chromosome 9, frataxin, GAA expansion
Features of temporoparietal, frontotemporal and subcortical dementias?
Temporoparietal - impairment of memory, later dysphasia and dyspraxia
Frontotemporal- behavioural disturbances, later memory loss
Subcortical- slowing of thought process, basal ganglia related
What is the most common form of dementia?
Alzheimer’s Disease
Where does Alzheimer’s disease occur?
Frontotemporal
Temporoparietal
What percentage of Alzheimer’s has a positive family history?
10%
Which proteins accumulate in Alzheimer’s?
Tau (tangles)
Beta-amyloid (plaques)
Macroscopic pathology of AD?
atrophy
shrinkage of gyri, widening of sulci
hydrocephalus ex vacuo
Early-onset AD forms of AD?
APP, PSEN1, PSEN2
Connection between APOE gene and Alzheimer’s?
e2 isoform is protective
e4 isoform increases risk
Classifications of human prion diseases?
Idiopathic/sporadic
Genetic
Acquired
Idiopathic prion diseases?
Creutzfeldt-Jacob disease
Fatal insomnia
protease-sensitive prionopathy
Genetic prion diseases?
Creutzfeldt-Jacob disease
Fatal insomnia
Gerstmann-Straussler-Scheinker
Acquired prion disease?
From cows- BSE, mad cow disease
iatrogenic CJD
from humans- Kuru
Causes of secondary CNS malformations?
ischaemia/infarction congenital/intrauterine infections maternal factors (folic acid deficiency, toxins, diabetes)
Early malformations are more likely _______ than later in gestation?
Genetic
Fatal
Malformations related to early in gestation?
neural tube defects disorders of cerebral development disorders of cerebellar, hindbrain and spinal cord development vascular disorders hydrocephalus
Range of neural tube defects?
Open NTDs- craniorachischisis, anencephaly, spina bifida cystica
Closed NTDs- encephalocele, spina bifida occulta
What is raised in open NTDs?
maternal serum alpha-fetoprotein
What is folic acid important in preventing?
Neural tube defects
What is holoprosencephaly?
failure of the forebrain to develop properly
What can cause holoprosencephaly?
maternal infection, diabetes, foetal alcohol syndrome
What forms CNS and PNS myelin?
CNS - oligodendrocytes
PNS- Schwann Cells
What is demyelination?
destruction of normally formed myelin with relative preservation of axons
What is dysmyelination?
failure to form myelin normally
Primary vs. secondary demyelination?
Primary- myelin exhibits the initial and most marked damage and axons are relatively preserved
Secondary- degeneration of myelin as a result of axonal or neuronal injury
Effects of demyelination?
slowing of conduction velocity
conduction block
‘cross talk’ due to unstable demyelinated nerves
What is ‘cross talk’?
miscommunication between unstable demyelinated nerves
i.e., sensory events result in motor phenomenon (unable to move after a hot bath, positional change causes pain)
General aetiologies of demyelination?
Infective
Immune/inflammatory
Metabolic/toxic
Neoplastic
General aetiologies of dysmyelination?
Genetics
What HLA types are susceptible to MS?
A3, B7, DR2, DQ1
When does MS have its onset?
usually in twenties
Progression of MS?
exacerbations and remissions
visual or motor signs
slow progressive disability over decades
Diagnosis of MS?
history
MRI (multiple lesions in space and time)
CSF
Visual Evoked Responses
What causes death in patients with MS?
secondary complications
infection
What is the key pathology behind MS?
Demyelinating plaques (Active, Inactive, Shadow)
Where do demyelinating plaques occur?
Mostly in white matter
optic nerve, periventricular regions and spinal cord most common sites
What is found in acute and chronic demyelinating plaques?
Acute- macrophages
Chronic- astrocytic gliosis
What inflammation is seen around demyelinating plaques?
T lymphocytic perivenous inflammation
What causes neuromyelitis Optica? (Devic’s disease)
inflammation and demyelination of the optic nerve and the spinal cord
distinct from MS
2 types of NMO/Devic’s Disease?
Autoimmune (AQP4 positive)
Idiopathic (AQP4 negative)
Symptoms of NMO/Devic’s Disease?
limb weakness, paralysis, bladder dysfunction
visual blurring, blindness
Who is NMO/ Devic’s most common in?
women
African origin
What is the likelihood of recurrence in NMO?
> 90%
Outcome of NMO if left untreated?
50% are blind and wheelchair bound by 5 years
Treatment for NMO?
mycophenolate mofetil
rituximab
azathioprine
What is acute disseminated encephalomyelitis preceded by?
systemic viral illness or vaccination (few days- few weeks)
Symptoms of acute disseminated encephalomyelitis?
acute onset
headache, vomiting, weakness, stupor, seizures, pyrexia
5-20% mortality
Who does acute disseminated encephalomyelitis usually occur in?
young people
What type of reaction is involved in acute disseminated encephalomyelitis?
T-cell mediated hypersensitivity reaction
What is the name given to the more severe, hyperacute Acute disseminated encephalomyelitis?
Acute haemorrhagic leukoencephalopathy
Main infective cause of demyelination?
Progressive Multifocal Leukoencephalopathy (PML)
What is involved in progressive multifocal leukoencephalopathy?
subacute viral infection of oligodendrocytes
latent in host- reactivated in T-cell deficiency
Treatment and outcome of Progressive Multifocal Leukoencephalopathy?
resistant to therapy
treatment aims to reduce immune suppression
usually fatal within 6 months
Histology of Progressive Multifocal Leukoencephalopathy?
multiple demyelinated foci
inclusions in oligodendrocytes nuclei
enlarged ‘giant’ astrocytes
What causes central pontine myelinolysis?
rapid correction of hyponatremia due to metabolic disorders
alcoholism, malnutrition, hyperemesis
Symptoms of central pontine myelinolysis?
rapid onset confusion limb weakness conjugate gaze palsies hypotension most cases fatal within weeks
What are leukodystrophies?
genetic disorders of myelin formation
How does X linked leukodystrophy present?
seizures
abnormal behaviour
muscle spasms
What is involved is adrenoleukodystrophy?
adrenal insufficiency and dysmyelination
Name 3 myelin proteins and state whether involved in CNS or PNS?
Proteolipid Protein (PLP)- >50% in CNS, minimal in PNS
Peripheral myelin protein 22 (PMP22)- 5% of PNS, not in CNS
Myelin Basic Protein (MBP)- in both CNS and PNS
What is Guillain-Barre syndrome?
acute inflammatory demyelinating polyneuropathy (AIDP)
Symptoms of Guillain-Barre syndrome?
acute onset
ascending flaccid paralysis
usually 2 weeks after viral or infective illness
What antibodies are circulating in Guillain-Barre syndrome?
anti-myelin
antiganglioside
What classifies chronic inflammatory demyelinating polyneuropathy?
> 2 months
recurring episodes of demyelination with remyelination and inflammation
What percentage of patients with vasculitis also have peripheral neuropathy?
33%
What is neurogenic muscle disease and what causes it?
denervation of muscle leads to muscle atrophy
caused by any process that affects the anterior horn cell or its axon (MND, spinal muscular atrophy)
Causes of myopathies?
Acquired (inflammatory, toxins/drugs, paraneoplastic)
Genetic (dystrophies, congenital myopathies, protein inclusion myopathies)
Types of inflammatory myopathies (myositis)?
inclusion body myositis
polymyositis
dermatomyositis
Features of inflammatory myopathies?
myalgia muscle weakness muscle tenderness elevated inflammatory markers muscle biopsy useful
Two types of skeletal muscle dystrophinopathy?
Duchenne muscular dystrophy
Becker muscular dystrophy
What cardiac disease is related to dystrophinopathy?
X-linked dilated cardiomyopathy
What will be raised in muscle dystrophy?
muscle creatinine kinase (CK) due to muscle necrosis
Structural abnormalities associated with congenital myopathies?
central nuclei
defects of the sarcomere network
nemaline rods
When do symptoms of congenital myopathies usually present?
At birth or in early childhood
Metabolic myopathies include defects in?
Glycogen storage/ glucose metabolism
Lipid metabolism
mitochondrial myopathies/cytopathies
Glycogen storage disorders symptoms are induced by?
Exercise
Most common enzymes involved in glycogen storage disorders are?
myophosphorylase (mcArdles)
phosphofructokinase
What do 90% of Myasthenia Gravis patients have and what do the remaining 10% have?
anti-ACh receptor antibodies
remaining 10% have anti-tyrosine kinase receptor antibodies
Symptoms of myasthenia gravis?
fatigable muscles
ptosis
painless muscle weakness
thymic hyperplasia
Which HLAs are associated with myasthenia gravis?
A1, B7, DRW3
What is acted on in Lambert-Eaton myasthenic syndrome?
Voltage-gated Calcium channels
What is the major cause of Lambert-Eaton myasthenic syndrome?
Underlying malignancy
particularly Small Cell Lung Cancer
Which is the most common form of meningitis?
Viral > bacteria
but viral is less severe also
Most common bacterial cause of meningitis?
Neisseria meningitides
Three ages of meningitis?
Infant (most common)
Toddler (second most common)
Over 4s- adult
Causes of meningitis in an infant?
Group B strep
E coli
Listeria
Causes of meningitis in a toddler and adult?
N. meningitidis
S. pneumoniae
3 ‘NHS bacteria’ for meningitis?
Neisseria meningitidis
Haemophilus influenza B
Streptococcus pneumoniae
What is the bacterial meningitis paradox?
mucosal pathogens commonly colonise the oropharynx but rarely go on to cause bacterial meningitis
How much of the population’s nasopharynx is colonised by N. meningitidis?
5-30%
What is the most major risk for bacterial meningitis?
Close contact (household contact) inc. 400x
Clinical features of meningococcal sepsis?
headache, fever, vomiting, drowsiness
haemorrhagic rash, neck stiffness
infants- poor feeding, bulging fontanelle
neonates- respiratory distress
Meningococcal septicaemia vs meningitis?
Sepsis- rash, bleeding, hypotension, 20% fatal, +/- meningism
Meningitis- no/mild rash, no bleeding, normotensive, 5% fatal, meningism and raised ICP
How do people present with meningococcal syndromes?
55% present with septicaemia and meningitis
20% present with meningitis alone
25% present with septicaemia alone
Contraindications of lumbar puncture in suspected meningitis?
Raised ICP
Shock
Respiratory distress
Treatment of bacterial meningitis?
Early antibiotics
fluid resuscitation
10mg dexamethasone
Is there evidence of increased risk in close contacts in NHS meningitis?
N- yes, 400x
S- no, no need for prophylaxis
Types of CNS infection?
bacterial (brain abscess) viral (herpes, polio, measles) fungal parasitic prion (CJD)
Bacteria behind brain abscesses?
60% aerobic- staph, strep, gram neg bacilli
32% anaerobic- Bacteroides, fusarium
Routes of infection for brain abscesses?
Direct (N.B., head injury, skull fracture)
Blood spread
Iatrogenic
site of abscess reflects route of entry
Mortality from brain abscesses?
10%
Who are at risk for a CNS Tuberculous infection?
children and immunosuppressed
Features of CNS Tuberculous infection?
caseous necrosis with granulomas subacute onset meningitic signs drowsiness cranial nerve palsies increased ICP
Where are tuberculomas endemic?
Indian subcontinent
What bacteria causes syphilis?
Treponema pallidum
What causes Lyme disease?
Borrelia burgdorferi spirochete
transmitted by ticks
3 stages of Lyme disease?
1st - skin, erythema marginatum
2nd- weeks or months later- neurological or cardiac signs
3rd- years later, CNS and arthritis
What can Lyme disease be confirmed by?
Western blot
What accounts for over 80% of aseptic meningitis?
Enteroviruses
What can cause viral encephalitis?
Herpes simplex Herpes zoster Enteroviruses Rabies Measles Cytomegaloviruses Polyoma viruses HIV
What are poliomyelitis and polio-encephalitis?
Poliomyelitis- inflammation of the grey matter of the spinal cord
Polio-encephalitis- inflammation of the grey matter of the brain
2 types of cytomegalovirus?
Congenital (maternal infection usually asymptomatic)
Acquired (usually complicates immunosuppression)
Main complications of congenital cytomegalovirus?
deafness, convulsions, mental retardation, seizures, chorioretinitis
What percentage of AIDs patients have CNS involvement?
80%
3 causes of brain disease in AIDs patients?
direct HIV infection
opportunistic infections
tumours (cerebral non-Hodgkin lymphoma)
Toxoplasmosis is carried by?
Cats
When does transplacental spread of toxoplasmosis occur?
when the infection occurs during pregnancy, greatest risk between 10-24 weeks
Commonest site involved in toxoplasmosis?
Basal ganglia
What causes cerebral malaria?
Plasmodium falciparum
