Pathophysiology CONOR GILLESPIE THIRD YEAR MEDICAL STUDENT - - PowerPoint PPT Presentation
Year 2 Neurosensory Pathophysiology CONOR GILLESPIE THIRD YEAR MEDICAL STUDENT HLCGILL2@LIV.AC.UK HTTPS://WWW.LIVERPOOLGUILD.ORG/GROUPS/NEUROSOC Topics covered Stroke CNS infections Headaches Epilepsy Neuromuscular
CONOR GILLESPIE THIRD YEAR MEDICAL STUDENT HLCGILL2@LIV.AC.UK HTTPS://WWW.LIVERPOOLGUILD.ORG/GROUPS/NEUROSOC
Stroke CNS infections Headaches Epilepsy Neuromuscular junction (NMJ) disorders CSF disorders Eye disorders Disorders of motor control (Parkinson's and Huntington's) Disorders of cognition
Basic anatomy Eye disorders (see lecture) Cerebral palsy (MSK block) Pain (see lecture) Psychiatric disorders (but have included them in slides) Hearing and balance (see lecture) Rare neurological conditions (included in slides at end)
AD inherited disorder, two types (type 1 under
30, type 2 over 30)
Pathology: Inherited demyelination with
thickened ‘onion bulb’ areas of remyelination
Progressive demyelinating neuropathy with pes
cavus (concave foot) and ‘inverted champagne bottle legs’
Also get wasting of the intrinsic foot and tibial
muscles
Neurology and Neurosurgery illustrated p444
Divided into either primary or secondary, or
‘dangerous’ and ‘safe’
Primary: Migraine, Tension headache, cluster
headache, ice-pick headache, medication
Secondary: Anything i.e. tumour, haemorrhage,
space occupying lesion, infection
Dangerous: Subarachnoid haemorrhage (SAH),
meningitis, temporal arteritis (Giant cell arteritis)
Safe: Everything else
Star fish sign for subarachnoid haemorrhage
Sudden onset (seconds), ‘baseball bat’ or ‘thunderclap’ headache,
may be associated Loss of consciousness and focal neurological signs (i.e. stroke)
Pathology: Rupture of berry aneurysm (other types of aneurysm?) Causes blood in the subarachnoid space Common vessels: ACOM (40%), MCA (34%), PCOM (20%) Risk factors: Hypertension (main one) and Adult polycystic kidney
disease
Investigations: CT head (gold standard)- ‘star fish’ sign If not evident on CT use LP BUT MUST WAIT 12hrs- why? Look for Xanthochromia in CSF (bilirubin accumulation) Bilirubin comes from red blood cell breakdown which takes 12 hrs
Vasculitis affecting middle sized arteries Aetiology: W:M 2:1, Much more common over 50 (typically 70s) PC: Headache which develops insidiously, worsened by brushing
hair or touching scalp
Other key symptoms: Jaw claudication and generalised weakness Can cause inflammation of retinal vessels and blindness if untreated. Investigations: Temporal artery biopsy gold standard, ESR and CRP
VERY high on bloods
Treat with steroids
Neurology 2010 headaches chapter
Epilepsy: Two or more seizures
Seizure: A paroxysmal neurological event characterised by an abnormal discharge of neurones
Seizure specific: Tongue biting, incontinence, prolonged recovery period (vs faint/postural hypotension)
3 categories of seizure:
Focal-simple partial (consciousness retained) and complex partial (consciousness lost)- most common
Generalised (absence and tonic clonic (second most common) and variants of)
Provoked seizures- due to acute physiological abnormalities not epilepsy i.e. Trauma, metabolic abnormalities such as hypoglycaemia, hypocalcaemia, drugs or alcohol)
Also status epilepticus
Neurology 2010 p74-77
Focal: from an abnormal discharge from one part of the brain only Generalised: Absence (petit mal)- loss of awareness and a vacant
expression for <10 seconds
Tonic-clonic (grand mal)- tonic stiffening followed by phase of limb
jerking
Causes of seizures: lots (Genetic (Lennox-Gastaut syndrome), infection,
stroke, autoimmune, tumours, idiopathic (most common))
Status epilepticus-seizures occurring for 30m either continuously or
intermittently without recovery
EMERGENCY- can cause hypoxia, acidosis, hyperthermia and renal
failure
Most clinicians don’t treat a single seizure
Motor neurone disease: Progressive degenerative disease of upper
and lower motor neurons
Get progressive limb weakness with dysarthria (speech difficulty),
dysphagia (swallowing difficulty) and tongue weakness
Get muscle wasting and fasciculation with brisk reflexes are
characteristic with NO sensory involvement
Death usually occurs within 3-5 years due to respiratory failure Subtypes: Amyotrophic lateral sclerosis (ALS), Primary lateral sclerosis
(only movement affected), spinal muscular atrophy (inherited)
Autoimmune disorder of NMJ transmission, characterised by
weakness and fatigability of proximal limb and ocular muscles
Rare (4 in 100k), women 2:1 affected Pathology- Autoimmune antibodies to the postsynaptic Ach
receptor
Features: Weakness and fatigability, diplopia and ptosis often
weaker at the end of the day, reflexes present but fatigable.
Kumar +Clark p889-890
Rare autoimmune syndrome with antibodies against calcium channels of the
presynaptic motor neuron channel
‘Disordered communication between muscles and nerves’ Paraneoplastic in 40-70% (mainly small cell lung cancer) Weakness is improved on repeated movement as are reflexes (opposite of MG)
Flesh and Bones P264- 267
Definition: Rapid onset of neurological deficit characterised by cerebral, spinal
retinal or focal infarction.
Transient ischaemic attack (TIA): Brief episode of neurological
dysfunction due to ischaemia not infarction.
Difference: TIA is completely reversible, stroke is not 85%: ischaemic (thrombotic, cardio-embolic (AF) 10%: haemorrhagic (Intracranial haemorrhage, SAH) 5%: rare causes
Kumar and Clark p828- 838
Pathology: Ischaemia followed by infarction and neuronal cell
death
Fall in ATP with release of glutamate, which opens calcium channels
with release of free radicals, leading to inflammatory damage, necrosis and apoptosis.
Risk factors: Age, Smoking, AF, Diabetes, hyperlipidaemia, obesity,
inactivity, genetics, previous TIA (30% have a stroke 5 years after a TIA)
Depends on the artery occluded, all usually sudden onset 69% involve the Middle cerebral artery (MCA), 11% Anterior cerebral
artery (ACA) and 9% PCA
General: Contralateral hemiparesis or hemiplegia, facial weakness,
hemi sensory neglect and loss, aphasia and homonymous hemianopia
Anterior circulation: all of general plus Amaurosis fugax (temporary
loss of vision in one eye)
Posterior circulation: Ataxia, vomiting, vertigo, diplopia MCA: Lots of these, generally face and arm weakness>leg ACA: Leg weakness>arm and face with more frontal lobe defects
(apathy or aphasia)
The stroke book 2nd edition
Risk factors: Age and hypertension are the main ones Most caused by rupture of small aneurysms Affects the brain tissue itself (parenchyma) so also called
intraparenchymal haemorrhage.
Features are similar to ischaemic due to sudden onset, occurs in 3
places generally:
Basal ganglia (80%), pons (10-15%), cerebellum (5-10%)
CT head in acute setting, MRI if CT contraindicated or outside
thrombolysis window, Lumbar Puncture If considering a SAH
Treat: thrombolysis for ischaemic (not haemorrhage) Occasionally surgery to evacuate blood Thrombolysis: dissolves clots, but must be given within 4.5 hrs of
symptom onset and has a high risk of causing bleeds
Afterwards: Anti-platelet medication (Aspirin, clopidogrel)
Extradural: Rupture of middle meningeal artery from trauma to
pterion (weak area formed by bony connections)
Lucid interval (temporary recovery before deteriorating) Subdural Often following minor head trauma Old and alcoholics: main risk factors (cortical atrophy stretches
blood vessels=more liable to rupture)
Rupture of cortical bridging veins not arteries
Dilation of the ventricles when an imbalance exists between CSF
production and resorption
3 types: Obstructive (non-communicating)- obstruction of CSF
flow within the ventricular system itself
Communicating- Obstruction to CSF flow outside the
ventricular system i.e. a blockage in the subarachnoid space
Normal pressure- Dilation of ventricles but normal CSF
pressure on LP
Normal pressure classic triad: Dementia, gait ataxia,
urinary incontinence
Neurology and neurosurgery illustrated p374-377
Symptoms related to increased ICP (Monroe-
Kellie doctrine)
Pathology: CSF obstruction, which permeates
through the ependymal lining into the periventricular white matter, causing damage
Symptoms of raised ICP: Headache often worse
in the morning, nausea, vomiting, LOC, false localising signs
Treat with Ventriculoperitoneal shunt
Development of a CSF filled cavity (syrinx) within the central canal
Common in patients with Chiari formation Clinical features: Upper limb pain, weakness and wasting of muscles
vibration and proprioception in a CAPE distribution
Due to spinothalamic tract decussating close to the syrinx Unique pattern- only similar is Anterior spinal artery occlusion (due to
dorsal columns being spared as supplied by the posterior spinal artery)
Consist of: Meningitis Encephalitis Cerebral abscess CJD and toxoplasmosis Syphilis
Inflammation of the meninges and CSF within the subarachnoid space 4 key symptoms: Fever, headache, neck stiffness, altered consciousness level Causes: Bacterial, viral, fungal, parasites, prions, autoimmune (ADEM) Pathology: purulent exudate travels through the subarachnoid space Although not directly invaded underlying brain becomes congested,
Cranial nerves and blood vessels damaged due to inflammation 10% Mortality rate so recognition is essential
Headache Fever Neck stiffness Altered consciousness level Photophobia Seizures (focal or generalised) Focal neurological signs in 10% (i.e. hemiparesis) Purpuric rash if meningococcal (not always) Positive kernigs sign and brudzinskys sign
Bacterial tends to be acute (over hours/days) Viral tends to be chronic (days/weeks) TB tends to have other TB features
sweats, weight loss) Fungal tends to be immunocompromised patients (e.g. HIV, Chemotherapy)
Neonatal- Group B streptococcus or E.coli Children- H.influenzae (first decade), Neisseria meningitidis (second
decade and students)
Older adults: Strep. Pneumoniae, meningococcus, Listeria
monocytogenes
Viral: Enteroviruses (80%), Herpes simplex Fungal: Cryptococcus neoformans, candida Spirochetes: Treponema pallidum (Syphilis meningitis) TB Investigations: LP essential, Blood cultures if rash, CT head if mass
lesion suspected (coning)
Robbins and Cotran pathological basis of disease p1271- 1280
Normal CSF: Normal pressure, clear appearance, no neutrophils, low
protein, glucose >60% plasma glucose concentration
Bacterial: High pressure, cloudy, Presence of polymorphonuclear
leukocytes (Neutrophils), elevated white cell count, low glucose (<40%), high protein (>50mg/dl)
Viral: Normal pressure, clear, elevated white cell count
(lymphocytes), normal glucose, high protein
Fungal: High pressure, cloudy, lymphocytes, low glucose, high
protein
TB: same as bacterial except VERY low glucose
Dyskinesia: Involuntary, uncoordinated movements Chorea: Irregular, sudden fidgeting movements Athetosis: Slow writhing movements Dystonia: simultaneous contraction of agonist and antagonist
muscles giving a twisting appearance
Myoclonus: brief, electric shock like jerks
Illustrated textbook of paediatrics p486
Loss of dopamine producing neurons at the substantia nigra leads
to reduced movement
Symptoms: TRAP (Tremor, rigidity, akinesia (bradykinesia), postural
instability
Additional features: Micrographia (small handwriting, cogwheel
rigidity
Can also have Parkinson plus syndromes Huntington's: AD, Attrition of cells that project to the EGP which
leads to underactive subthalamic nucleus activity=less motor inhibition and more activity
In a very young patient with Parkinson like symptoms (age 10-30)
consider Wilson’s disease
Lippincott physiology ch11
Immune mediated, T helper cells cross the BBB and initiate an
inflammatory cascade leading to the appearance of plaques of demyelination.
Typical Patient is a young woman (20-40yrs) Symptoms: Previous optic neuritis (blurring of vision with slow
recovery), unilateral leg weakness, disordered bladder control, ataxia, sensory disturbances (numbness and paraesthesia),
All of these should make you think MS Clinical pattern is of relapses and remissions followed by a
secondarily progressive disease
Immune mediated rapidly progressing ascending polyneuropathy Usually postinfection with a Campylobacter jejuni diarrhoeal
infection most common, followed by Epstein Barr and Herpes Simplex virus
Rare and occurs in 1/1000 Campylobacter infections Cell mediated immune response directed against myelin in
response to the infection, causing nerve damage
Clinical features: 2-4 weeks post infection (usually diarrhoea),
weakness in proximal limbs, may cause cardiac arrhythmias, respiratory failure and rarely locked in syndrome.
Treat: IV immunoglobulin, 5% mortality
Dementia: acquired loss of higher mental function affecting tow or
more cognitive domains including episodic memory, apraxia and visuospacial function
‘Keeps leaving the hobs on’ Causes: Alzheimer's (60% total)-deposition of B-amyloid and tau protein Dementia with Lewy bodies (10%)- Characterised by visual
hallucinations, Parkinson like symptoms and sleep disturbances
Vascular (multi-infarct) dementia (20%)- common form and the result of
multiple strokes over time
Frontotemporal dementia (Pick’s disease) (5%)- asymmetrical frontal
and temporal lobe atrophy, features reflect this (personality change, apathy)
In a young adult (30s-40s) consider Huntington's
Neurology and neurosurgery illustrated p125-134
Dementia mimics- give signs of dementia but from a
different/reversible pathology
Depression, thyroid disease, encephalitis, Wernicke Korsakoff
(thiamine deficiency)
Wernicke (acute)- Triad of abnormal eye movements, ataxia and
confusion
Korsakoff’s: long term manifestation of this deficiency, leading to
disturbed short term memory function
Pathology: Destruction of mammillary bodies Often caused by long term alcohol abuse
Astrocytoma: most common, GBM is a grade 4 astrocytoma Gliblastoma multiforme (GBM): Bad (most dead in 15 months) Ependymoma: causes hydrocephalus due to blockage of CSF Medulloblastoma: causes ataxia, usually affects children Neurofibromas: Benign peripheral nerve sheath tumours, associated
with NF1 and NF2 (inherited disorders)
Meningiomas: Masses that compress the brain not invade it (can
compress optic nerve and cause visual loss)
Choroid plexus papilloma: produce CSF
Robbins basic pathology ch22
Broca’s aphasia- Anterior, expressive aphasia, comprehension often
not impaired
Wernicke's aphasia- Posterior receptive dysphasia, comprehension
impaired, language is present but words are incomprehensible or made up with the patient unaware
Causes are similar: Tumour, stroke, trauma, infections etc Horner's syndrome 4 classic signs: Ptosis, miosis (constricted pupil), enopthalmos (sinking of eyeball into
socket), facial anhidrosis (lack of sweating on affected side)
Loss of pain and temperature on one side and loss of fine touch,
proporioception and weakness on the other side
‘One leg weak and the other leg numb’: Brown-Sequard syndrome (hemi-cord lesion of spine) Loss of pain and temperature but preserved vibration and
proprioception: Syringomyelia or Anterior spinal artery occlusion (rare)
‘Glove and stocking sensory loss’: Peripheral neuropathy Lots of causes: DM, Alcohol, medications, CMT, Vitamin B12
deficiency
Only dorsal column loss: Neurosyphilis (unlikely to come up in exams)
1. A 55 year old man presents to A&E with an abrupt onset of right
sided weakness, with power grades of 4/5 on legs and 1/5 on arms. He also has expressive aphasia. He is right handed. A stroke is diagnosed.
What artery is most likely to be occluded? Answer: Middle cerebral artery (not ACA as there would be no
aphasia and power would be weaker in legs)
2. A 60 year old woman presents 30 minutes after a sudden onset of
severe headache. She describes the headache as like being ‘hit
shows Xanthochromia.
Answer: Subarachnoid haemorrhage
Neurology 2010 (covers everything quickly) Flesh and Bones (introductory text) Kumar and Clark-gold standard Robbins basic pathology (ideal pathology but not for neuro
specifically)
Neurology and Neurosurgery illustrated (best content and amazing
diagrams)
For slides see Neurosoc facebook page
hlcgill2@liv.ac.uk https://www.liverpoolguild.org/groups/neurosoc Slides: https://gilesdoesmedicine.wordpress.com
IIH: Almost always occurs in females aged 15-45 Cause unclear but associated with Obesity Clinical features: Generalised headache, made worse by positions that
increase ICP- Coughing, lying flat, RELIEVED BY UPRIGHT POSTURE
Can also have transient visual disturbances and papilloedema Confirmed by elevated CSF pressure on LP Treat: Weight loss (best), therapeutic LP, Shunt Venous sinus thrombosis: similar PC, contraceptive pill and malignancy
are risk factors.
Intracranial hypotension: opposite (headache relived by lying down)
Flesh and bones p274- 277
Disease of the posterior fossa, with misshapen parts of the
cerebellum which protrude through the foramen magnum with resultant headaches, tinnitus and hydrocephalus
Two types: Type 1- less severe, misshapen cerebellar tonsils that protrude
through the foramen magnum, often asymptomatic but hydrocephalus in 10%
Type 2 (Arnold-chiari)- misshapen cerebellar vermis through the
foramen magnum and almost always hydrocephalus
Do not need to know this depth
Inflammation of the brain parenchyma (not meninges) Causes neuronal and glial damage with associated inflammation
and oedema
Frontal and temporal lobes most affected Presents with altered behaviour, seizures, confusion, or coma Can also mimic a stroke (confusion, dysphasia, hemiparesis) Causes: Viral- Herpes simplex (most common), varicella zoster,
Epstein Barr virus and adenovirus
Investigations: PCR of CSF gold standard, treat with Acyclovir
(antiretroviral)
Syphilis: Spirochaetal infection (now rare) by the organism
Treponema pallidum
Usually sexually acquired, majority are asymptomatic Causes 3 symptom types often years after exposure 1. Meningeal syphilis: chronic meningitis 6-12 months after infection 2. Meningovascular syphilis: years after infection, a young stroke 3. Tabes dorsalis: chronic damage to the cauda equina from
meningitis causes loss of proprioception and vibration (dorsal column affected)
AKA Neuroborreliosis Caused by spirochete Borrelia Burgdorferi Characterised by relapsing and remitting arthralgia associated with
a characteristic skin rash (Erythema chronicum migrans)
Carried by ticks, treat with penicillin
Mononeuropathy: disorder of a single named nerve usually due to
trauma or compression e.g carpal tunnel (what signs?)
Mononeuritis multiplex- disorder of multiple named nerves, usually
from a chronic disease such as DM or vasculitis
Peripheral Neuropathy: Spreads symmetrically in a ‘glove and
stocking’ pattern, legs affected before arms
Causes: DM (most common), Chronic alcohol abuse, GBS, CMT,
renal failure (uraemic), drugs (amiodarone, isoniazid), vitamin b12 deficiency (subacute combined degeneration of cord)
Flesh and Bones P264-267
Peripheral neuropathy due to vitamin B12 deficiency Causes: Pernicious anaemia, Crohn’s, Veganism Easily treatable Autonomic neuropathy- damage to the nerves of the ANS usually
from DM leads to symptoms such as Constipation, erectlye dysfunction, dry mouth, blurred vision, postural hypotension (ANS dependent)
Neuroses: Illnesses where symptoms vary only in severity from normal experiences i.e. depressive illnesses
Psychoses: symptoms are different to normal experiences e.g hallucinations
Depression: pervasive lowering of mood, triad of low mood, anhedonia (loss of enjoyment in formerly pleasurable activities), decreased energy (anergia)
Anxiety: an unpleasant emotional state involving subjective fear, bodily discomfort and physical symptoms
Divided into:
Generalised anxiety disorder (GAD)
Panic disorder
Phobias
OCD
PTSD
Bipolar disorder- characterised by periods of mania (elevated mood
with euphoria and over activity) and hypomania
Hypochondriasis- preoccupation with an assumed serious disease
and it’s consequences
Dissociative/conversion disorders- An unresolved conflict is
converted into physical symptoms i.e. a weak limb with no clinical signs of a stroke
Delirium- illusions and hallucinations that may accompany a
confused state
4 features: Acute onset and fluctuating course, inattention,
disorganised thinking, altered level of consciousness
Subacute sclerosing paraencephalits- Rare syndrome of cognitive
decline, seizures, myoclonus leading to tetraparesis and dementia in children and young adults
Cause is from previous measles infection (get your vaccine) JC virus- Causes progressive multifocal leukoencephalopathy in
immunocompromised patients if JC virus reactivated in later life
Creutzfeld-Jacob disease (CJD): The rarest (1 in 1m), accumulation
infecting other proteins
Presents with dementia in a young patient, ataxia, myoclonus AKA Mad cow disease but in humans- incurable and death usually
in 12 months
Toxoplasmosis: parasite that affects immunocompromised patients
(HIV primarily)
Presents with focal neurological deficit, headache or seizures CT= Ring enhancing lesions with surrounding oedema