Neurology Flashcards
Describe the main functions of the brain lobes, cerebellum and brainstem
Frontal: movement and executive function
Parietal: sensory
Temporal: hearing, smell, memory, languages, facial recognition
Occipital: vision
Cerebellum: muscle coordination, balance
Brainstem: HR, BP, breathing, GI function, consciousness
Which parts of the brain are supplied by the anterior cerebral artery?
Medial frontal and parietal
Which parts of the brain are supplied by the posterior cerebral artery?
Mainly occipital, some temporal and thalamus
Which parts of the brain are supplied by the middle cerebral artery?
Lateral portions of the frontal, temporal and parietal lobes
Where are the most common sites for atherosclerosis in the brain?
Branch points, particularly of the internal carotid and middle cerebral
Describe a lacunar stroke and it’s causes
Hyaline arteriosclerosis of the deep MCA branches leads to protein-filled cyst formation in the brain
Caused by HTN and diabetes
What is a watershed infarct?
Area of the brain damaged that is at the border of two blood supplies
How does cytotoxic oedema occur as a result of an ischaemic stroke?
No glucose and oxygen so no energy
High sodium and calcium in the cells draws water in via osmosis
How do high calcium levels in the brain cells cause damage in an ischaemic stroke?
High Ca2+ causes a buildup of ROS which damage lipids in the mitochondria and lysosomes
Release of apoptosis-releasing factors and digestive enzymes
What is the major risk if inflammation damages the blood-brain barrier in an ischaemic stroke?
Vasogenic oedema which has a mass effect and pushes into the other side, can causes cingulate/ uncle herniation
If cerebellar tonsil herniation it may compress the brainstem causing breathing problems and reduced consciousness
Give two symptoms of an anterior/ middle cerebral artery ischaemia
Numbness
Muscle weakness
How would an ischaemic stroke affecting Broca’s area present?
Slurred speech
How would an ischaemic stroke affecting Wernicke’s areas present?
Difficulty understanding speech
How would you diagnose an ischaemic stroke?
Flair MRI
CT scan
Angiography
How would you treat an ischaemic stroke?
Thrombolytic enzymes: tissue plasminogen activator (TPA)
Aspirin: prevents more clots
Surgery: mechanical embolus removal in cerebral ischaemia (MERCI)
Suction removal
How could you minimise risk factors of an ischaemic stroke?
Quit smoking Healthy BP Normal cholesterol Control of diabetes Surgery Carotid endarterectomy Stent
How can HTN cause an intracerebral haemorrhage?
Micro aneurysms (Charcot-Bouchard aneurysms) Hyaline arteriolosclerosis (arteries are still and more likely to rupture)
Give 4 conditions associated with intracerebral haemorrhage
Arteriovenous malformations
Vasculitis
Vascular tumours
Cerebral amyloid angiopathy (protein deposits in the walls of arterioles making them less compliant)
How can an intracerebral haemorrhage occur as a result of ischaemic stroke?
Brain tissue death due to ischaemia, if there is reperfusion damaged cells may rupture causing a haemorrhage / haemorrhagic conversion (bleeding into dead tissue)
Where might herniation occur in an intracerebral haemorrhage?
Falx cerebri
Tentorium cerebelli
Foramen magnum
How would you treat an intracerebral haemorrhage?
Medication: anti-hypertensives and to relieve ICP
Surgery: craniotomy (relieving ICP and draining blood)
Sterotatic aspiration (CT and needle)
Where is CSF found within the meninges?
Subarachnoid space
Give 3 causes of a subarachnoid haemorrhage
Traumatic injury
Aneurysms (saccular cerebral/ berry aneurysms)
Genetic disorders: Marfan syndrome can predispose people
Can rupture with increased ICP
Arteriovenous malformation
Describe the consequences of a subarachnoid haemorrhage
Pressure on the skull, brain tissue and blood vessels
Arteries bathing in a pool of blood can start to intermittently vasoconstrict/ vasospasm
In circle of Willis there is reduced blood to the brain
Blood irritates the meninges causing inflammation and scarring of surrounding tissue, this can obstruct CSF and cause dilation of the ventricles (hydrocephalus) which increases ICP
Give 4 symptoms of a subarachnoid haemorrhage
Thunderclap headache Nuchal rigidity Seizures Vomiting Vision changes Confusion
How would you diagnose a subarachnid haemorrhage?
CT
MRI
Lumbar puncture (red blood: fresh/ yellowish blood (bilirubin): old)
How would you treat a subarachnoid haemorrhage?
Emergency surgery: clip artery and apply pressure
Use catheter to insert coil to promote clot formation
Medication: CCB to prevent vasospasms
Give the diagnostic criteria for a TIA
<24 hours of symptoms, no evidence of infarct on imaging
Describe an extra/ epidural haemorrhage
Bleeding that occurs between the skull and dura mater
Give 4 causes of an epidural haemorrhage
Trauma
Motor vehicle accident
Falls
Assault
What percentage of epidural haemorrhages include a skull fracture?
70-95%
Describe the clinical manifestation of an epidural haemorrhage
Altered consciousness Headache Vomiting Confusion/ seizures Aphasia Pupil asymmetry
How would you diagnose an epidural haemorrhage?
CT/ MRI:lens shaped lesion, well circumscribes
X-ray: may show fractures of the skull
Which investigation is contraindicated in an epidural haemorrhage?
Lumbar puncture
How would you treat an epidural haemorrhage?
Urgent decompression
ABCD, high flow oxygen
Sit up in bed
Neurosurgery: blood is evacuated
Describe epilepsy
Recurring and unpredictable seizures, neutrons are synchronously active
Give the main excitatory neurotransmitter in the brain and the primary receptor
Glutamate
NMDA (Ca2+ enters)
Give the main inhibitory neurotransmitter in the brain and the primary receptor
GABA GABA receptor (Cl- enters)
Give 3 ways in which the excitatory and inhibitory receptors in the brain can be affected
Tumours
Brain injury
Infection
Describe a focal seizure without impaired awareness
One hemisphere/ lobe affected
Strange sensations, jerking movements
Jacksonian march: starts in one group, spreads
Awake/ alert, often remembers
Describe a focal seizure with impaired awareness
Focal seizure with loss of awareness or responsiveness
May not remember
Describe the following generalised seizures: Tonic Atonic Clonic Tonic-clonic Myoclonic Absence
Stiff/ flexed, fall back Relaxed, fall forward Convulsions 2 phases Short muscle twitches "Spaced-out"
Describe status epilepticus
If seizure lasts longer than 5 minutes, is ongoing/ without returning to normal (usually tonic-clonic)
Often treated with benzodiazepines which enhance GABA
Give 2 main post-seizure symptoms
Postictal confusion
Paralysis (Todd’s paralysis: arms and legs)
Lasts around 15 hours, temporary and severe suppression of seizure-affected brain area
How would you diagnose epilepsy?
Imaging to look for abnormalities (MRI, CT)
EEG
How would you treat epilepsy?
Daily medication: Anticonvulsants Epilepsy surgery- remove cause Vagus nerve stimulation Ketogenic diet
Describe Parkinson’s disease
Degeneration of dopamine-producing neutrons of the substantia nigra causing a progressive movement disorder
Give the two genes in which a mutation may cause Parkinson’s
PINK1, PARKIN
Give 2 risk factors for Parkinson’s
Pesticide exposure
Genetic variants
Describe the substantia nigra and it’s function
Part of basal ganglia that connects to the motor cortex and controls movement
What is the feature found in neutrons before they die in Parkinson’s disease?
Lewy bodies (eosinophilic, alpha-synuclein)
Which part of the substantia nigra is affected in Parkinson’s disease?
Pars compacta
What does the nigrostriatal pathway connect and what is it’s purpose?
Substantia nigra to striatum (caudate and putamen)
Helps stimulate cerebral cortex to initiate movement
Describe the motor clinical features of Parkinson’s
Resting tremor
Rigidity, stooped posture, almost expressionless
Postural instability
Bradykinesia, hypokinesia, akinesia (difficulty initiating movement) : legs freeze up, shuffling gait
How does Parkinson’s differ from motor cortex/ corticospinal pathway diseases?
No weakness in Parkinson’s
Give 4 non-motor symptoms of Parkinson’s
Depression
Dementia
Sleep disturbances
Difficulty smelling
Why can Parkinson’s not be treated with dopamine?
Dopamine cannot cross the blood-brain barrier
What would the first line of Parkinson’s treatment be and why might side effects be seen?
Levodopa (dopamine precursor) can cross the BBB and is then converted to dopamine by dopa decarboxylase
Peripheral dopa decarboxylase may convert Levodopa before it crosses the BBB and then produce epinephrine which can cause arrhythmias
Which drug would you give with L-dopa to prevent side effects?
Carbidopa: dopa decarboxylase inhibitor that cannot cross the BBB
How would you treat Parkinson’s other than L-dopa?
Amantadine (antiviral that increases dopamine production)
Dopamine agonists: bromocriptine, pramipexole
Inhibitors of COMT (COMT degrades dopamine): entacapone, tolcapone
Since a loss of dopamine increases relative acetylcholine: anticholinergics- improve tremors: benzotropine
Give examples of other diseases in which Parkinsonism may be seen
Lewy body dementia
Wilson disease
Pick disease
Give examples of medications which may cause Parkinsonism as a side effect
Antipsychotics (haloperidol: blocks dopamine receptors)
Metoclopramide (dopamine antagonist, anti-emetic)
Describe multiple sclerosis
Demyelinating disease of the central nervous system
Which cells produce myelin in the CNS?
Oligodendrocytes
Describe the chain reaction as T cells are activated by myelin in multiple sclerosis
Stimulates the BBB to express more T-cell receptors and allow more immune cells to cross
T-cells release cytokines which dilate blood vessels so more immune cells can cross the BBB
Cytokines attract B cells and macrophages which produce antibodies against myelin sheath proteins, oligodendrocytes are engulfed and destroyed leaving behind areas of scar tissue
Give 2 genetic and 2 environmental risk factors for multiple sclerosis
Female, genes encoding for (HLA-DR2)
Infections, vit D deficiency
Describe the following patterns of MS
Relapsing-remitting
Secondary progressive
Primary progressive
Progressive-relapsing
Describe the 3 components of Charcot’s neurological triad
Nystagmus: plaques in nerves of eyes, involuntary rapid eye movements, loss/ blurred vision, pain/ double vision
Intention tremor: plaques along motor pathways, muscle weakness and ataxia
Dysarthria: plaques in brainstem, difficult/ unclear speech
Interfere with conscious movements, unconscious (swallowing)
Describe the symptoms that would result from plaques in sensory pathways in MS
Numbness
Pins and needles
Paresthesias
What is Lhermitte’s sign (in MS)?
Electric shock that runs down back and radiates to limbs when bending the neck forward
Describe the symptoms that would result from plaques in the autonomic nervous system in MS
Bowel/ bladder symptoms
Sexual dysfunction
How would you diagnose MS?
MRI: white matter plaques
CSF: high levels of antibodies
Visual evoked potential: measures response to visual stimuli
How would you treat MS?
RRMS:
Medications: corticosteroids, cyclophosphamide, IV Ig
Plasmapheresis: remove autoantibodies
Immunosuppressants: recombinant B-INF, decreased release of inflammatory cytokines in the brain and increased T-reg cells
Progressive MS:
Manage symptoms
Physical therapy
CBT
Describe the components making up CSF
70% lymphocytes
30% monocytes
Proteins and glucose
(Pressure 15mmHg/ 100-180mmH20)
What is the normal total CSF volume and how much is produced each day?
150ml total
500ml produced/ day
Describe meningitis
Inflammation of the leptomeninges (arachnoid, pia mater)
Give 3 inflammation triggers for meningitis
Autoimmune disease
Adverse reaction to medication: Intrathecal therapy (injected directly into CSF
Infection: Neisseria meningitidis, Herpes simplex
How can meningitis arise from direct spread of infection?
Through overlying skin
Through nose
Anatomical defect: spina bifida/ skull fracture
How can meningitis arise from haematogenous spread of infection?
Binding to surface receptors
Areas of damage
Vulnerable spots e.g Choroid plexus
What is the normal volume of WBCs in the meninges?
5 WBC/mm3
Which type of meningitis has a particularly high percentage of PMNs?
Bacterial
Which type of meningitis has a particularly high percentage of lymphocytes?
TB meningitis
Which type of meningitis can you see the highest volume of WBCs?
Viral
How do pressure, glucose conc and protein levels change in meningitis?
Pressure increases, glucose conc decreases, protein levels increase
Give the common bacterial causes of meningitis in newborns, children and adults
Newborns: Group B strep, E.coli, Listeria
Children: Neisseria meningitidis, strep pneumoniae
Adults: strep pneumoniae, listeria monocytogenes
Give a cause of tick-bourne meningitis
Borrelia Burgdoferi (cause of lyme disease)
Give 5 viral causes of meningitis
Enterovirus Herpes simplex HIV Mumps Varicella zoster
Give 2 fungal causes of meningitis
Cryptococcus genuses
Coccidioids genuses
Give a cause of parasitic meningitis
P. falciparum
Give 5 symptoms of meningitis
Headache Fever Nuchal rigidity Photophobia Phonophobia
What is Kerning’s sign?
Lay on back, knee at 90 degrees, pain in back
What is Brudzinski’s sign?
Lay on back, head lifted, knees bend
How would you diagnose meningitis?
Lumbar puncture: needle between L3 and L4, takes CSF, measure pressure, analyse WBCs, protein and glucose
PCR: look for HIV, enterovirus, HSV, TB
How would you treat meningitis?
Cause-dependent
Bacterial:
Steroids (to prevent injury to leptomeninges: dexamethasone)
Drugs: anti-vitals, bacterials, fungals, parasitics
Vaccine: Neisseria meningitidis, disseminated TB
Prophylactic Abx
Give 4 causes of secondary headaches
Sub-arachnoid
Medication induced
Infection: meningitis
Giant cell arteritis
Give 5 red flags accompanying headaches that may indicate a brain tumour
Cluster headaches
Seizures
New onset headache (associated with a Hx of cancer)
Significantly altered consciousness, memory, confusion, coordination
Papilloedema
Describe the symptoms and pattern of a migraine
4-72 hours Unilateral, pulsing, worse with activity Moderate to severe Nausea and vomiting Photophobia and phonophobia
Which factors may worsen a migraine?
Cheese Hangover Orgasm Chocolate Oral contraceptive Lie in Alcohol Tumult Exercise
Describe the symptoms and pattern of a tension headache
30mins-7 days Mild-Moderne Bilateral Pressing/ tightening Not aggravated by physical activity Photo/ photophobia NO nausea/ vomiting
Describe the symptoms and pattern of a cluster headache
Most severe pain Unilateral orbital/ suborbital 15-180 minutes Sense of restlessness/ agitation Frequent
How would you treat a migraine?
Triptan and NSAID/ paracetamol
Anti-emetic
How can a medication overuse headache occur?
Underlying headache disorder
Frequent use of analgesics
Rebound headaches occur usually daily
Become chronic daily headaches
Give 4 medications which commonly cause overuse headaches
Triptans
Ergotamines
Analgesics
Opioids
Give the 2 other possible names for motor neurone disease
Amyotrophic lateral sclerosis
Lou Gehrig’s disease
Describe how ALS is classified by onset
Limb onset: upper and lower motor neurone death, limbs affected first
Bulbar onset: motor neurons in the medulla oblongata die first with lower motor neurons
Muscles in the face, mouth and throat are affected first
Faster progression and poorer prognosis
How would limb onset ALS present compared to bulbar onset ALS?
Limb: “dropped foot”, awkwardness running
Bulbar: slurred speech, dysphagia, dysphasia
Describe the general symptoms of motor neurone disease
Muscle cramps, dysphagia, dysarthria, hyperreflexia, spasticity, Babinski’s sign, muscle weakness
Late stages: difficulty chewing/ swallowing: increased risk of aspiration
Decreased strength of intercostals: loss of lung function
Give 2 possible causes/ risk factors of ALS
Genetics
Head injury
(90% no FHx)
How would you manage motor neurone disease?
Riluzole: protects motor neurone by reducing activity (prolongs survival) Medications to control symptoms: Baclofen and diazepam Glycopyrrolate (trouble swallowing saliva) Analgesics Breathing support Therapy Nutritional advice
Describe the differences between UMN lesions and LMN lesions
UMN: Damage anywhere along corticospinal tracts weakness affects groups spasticity Increased tone Hyperreflexia \+ve Babinski sign
LMN: Damage anywhere from the anterior horn cells distally
Affected muscles show wasting and fasciculation
Hypotonia/ flaccidity
Reflexes are reduced/ absent
Give 3 symptoms of autoimmune encephalitis
Catatonia
Psychosis
Abnormal movements
Give 4 causes of viral encephalitis
Herpes simplex
Rabies
Poliovirus
Measles
Give 3 causes of bacterial encephalitis
Syphilis
Meningitis
Malaria (immunocompromised)
Give 4 symptoms of limbic encephalitis
Disorientation
Disinhibition
Memory loss
Seizures
Give 4 general symptoms of encephalitis
Fever
Headache
Confusion
Seizures
How would you diagnose encephalitis?
MRI EEG Lumbar puncture Blood test Urinalysis
How would you treat encephalitis?
Antiviral medication Abx Steroids to reduce swelling Sedatives for restlessness Acetaminophen for fever
How might herpes zoster virus present?
Chicken pox: fever, malaise headache, abode pain
Rash: pruritic, erythematous, crust (infectious 1-2 days pre and 5 days post-rash development)
Shingles: painful, hyper-aesthetic area, then macular becomes a vesicular rash
May become a disseminated infection if immunosuppressed
How would you treat herpes zoster virus infection?
Oral aciclovir/ valaciclovir (within 48 hours of rash)
IV aciclovir if pregnant/ immunosuppressed
What percentage of childhood tumours are brain tumours?
20%
In general, where are brain tumours found in adults and where in children?
Adults: supratentorial compartment
Children: infratentorial compartment
How might a brain tumour present?
Cluster headaches Papillary oedema Focal deficits Seizures: olfactory aura and deja vu Loss of function Drowsiness Nausea/ vomiting
How might brain tumours be classified according to cells affected?
60% neuroepithelial: astrocytic/ oligodendritic 7% cranial/ spinal nerve tumours 28% meningeal 4% lymphomas 1% germ cell tumours
What is the WHO grading system for brain tumours?
Grade 1: Pilocytic astrocytoma (benign)
Grade 2: Diffuse astrocytoma (pre-malignant: 5-7 year prognosis)
Grade 3: Anaplastic astrocytoma (2-5 year prognosis)
Grade 4: Glioblastoma, most common type (<1 year prognosis)
Which mutations are associated with an astrocytoma and an oligodendroglioma?
Astrocytoma: IDH1 mutant
Oligodendroglioma: IDH1 and 1P 19Q mutant
Describe a medulloblastoma
WHO grade 4 most commonly
“Small blue tumour” of the cerebellum
Common in childhood
Rapidly fatal if untreated
Where are the common sites of brain metastases?
Lung Breast GI Kidney Melanoma
How would you treat a brain tumour?
Aggressive surgery if possible
Radiotherapy with adjuvant chemo (Temozolomide)
Give 4 causes of spinal cord compression
Tumour
Vertebral fracture
Abscess
Ruptured intervertebral disc
How might tumours grow within the spinal cord?
Causing vertebral displacement (mass effect on cord)
Tumours can grow para-spinally into the foramen
Epidural: between the disc then superiorly and inferiorly
Describe the 4 symptom groups of spinal cord compression
Back pain: first symptom, progressively worse, localised pain
Motor weakness: paralysis if severe
Sensory changes: less common, clinically useful
Bladder and bowel dysfunction: urinary retention and outflow incontinence
Give 4 common sources of mets in the spinal cord
Breast
Myeloma
Nasopharynx
Prostate
How would you diagnose spinal cord compression?
MRI
CT with contrast (can’t see spinal oedema/ lesions well)
How would you manage spinal cord compression?
Steroids to reduce inflammation e.g prednisolone
+/- surgery/ radiotherapy
Describe and explain the symptoms of cauda equina syndrome
Compression of the cauda equina nerves, usually disc herniation from above
This can cause bladder/ bowel dysfunction
+ saddle/ perianal numbness
+ severe paralysis down the legs/ tingling and numbness
How would you manage cauda equina syndrome?
Laminectomy
How can you differentiate cauda equina syndrome from sciatica?
Sciatica doesn’t cause bladder and bowel dysfunction
Give the 4 types of sensory fibres affected in peripheral neuropathies and the associated symptoms
A-alpha: loss of proprioception, sensory ataxia
A-beta: loss of light touch, pressure and vibration sensations
A-delta: myelinated- pain and cold temp (loss of)
C fibres: unmyelinated- pain and warm temp (loss of)
Give 5 motor symptoms of peripheral neuropathy
Muscle cramps Weakness Fasciculations Atrophy High arches
Describe the 3 clinical phenotypes of peripheral neuropathy
Symmetrical sensory motor: longest fibres, hands and feet, initially sensory
Asymmetrical sensory: uncommon, patchy distribution of symptoms, dorsal route ganglia affected (sensory ganglionopathy)
Asymmetrical sensory motor: mononeuritis multiplex
How would you diagnose peripheral neuropathy?
Clinical exam: reduced tendon reflexes, sensory deficits, muscle atrophy/ weakness
Neurophysiological exams: nerve stimulation- how well it transmits to determine whether it’s demyelinating or axonal damage
(Demyelination: reduced conduction, axonal: reduced amplitude)
Give 6 systemic diseases associated with axonal damage
Diabetes Vit D deficiency Coeliac Excess alcohol CKD Hypothyroidism Connective tissue diseases Amyloidosis
Give 5 Inflammatory/ immune conditions associated with axonal damage
HIV
Hepatitis
Lyme disease
Vasculitis
Give two immune mediated conditions associated with demyelination
Chronic inflammatory demyelinating PN
Multifactorial motor neuropathy
Give a genetic cause of demyelination
Charcot-Marie-Tooth disease
Describe Gullian-Barre syndrome
Acute neuropathy
Demyelinating/ axonal motor/ sensory motor
Rapidly ascending paralysis and sensory defects
Caused by infection elsewhere/ autoimmune
How would you manage peripheral neuropathy?
Treat underlying cause/ symptoms
Balance: physio
Cramps: quinine
Pain: amitryptaline, gaba-pentin, gaba-bal
How would you manage Gullian Barre syndrome?
IVIg, plasma exchange (plasmapheresis)
Which nerve is affected in Bell’s palsy and what are the associated symptoms?
Facial nerve (VII) Symptoms: Flattening of the forehead Sagging of the eyebrow Difficulty closing the eye and mouth (ipsilaterally) Problems with feeding/ speech
Give 6 causes of oculomotor nerve palsy (III)
Autoimmune: myasthenia gravis Complication of surgery Vascular disorders Tumours/ lesions Inflammation/ infection Trauma Demyelinating disease (MS)
How might the eye be affected in oculomotor nerve palsy?
Affected eye pupil rolls down and out (inferio-laterally)
Ptosis (drooping of eyelid)
Mydriasis (pupil dilation)
Limitations of eye movement, unable to maintain normal alignment can cause diplopia
Describe typical trigeminal neuralgia
Episodes of severe, sudden, shock-like pain in one side of the fat that lasts for seconds-a few minutes
Episodes may be triggered by any touch to the face
Give 5 causes of trigeminal neuralgia
Loss of myelin around trigeminal nerve due to: Compression from a blood vessel MS Stroke Trauma Tumour Arteriovenous malformation
How would you treat trigeminal neuralgia?
Carbamazepine (anti-convulsant)
Gabapentin (treat neuropathic pain)
Amitriptyline
Baclofen (to treat spasticity)
Describe Brown-Sequard syndrome
Hemiparaplegia
Hemianaesthesia (on contralateral side)
Describe anterior cord syndrome
Below injury level, motor paralysis and loss of pain/ temp
Proprioception, touch and vibration preserved
Describe posterior cord syndrome
Motor function preserved
Loss of pressure, stretch and proprioception
Describe central cord syndrome
Results from cervical spine injury
Greater motor loss in upper body compared to lower
Variable sensory loss
Describe carpal tunnel syndrome
Compression of the median nerve causing pain, numbness and tingling, usually due to inflammation of nearby tendons and tissues
Describe the components of the carpal tunnel
Bony carpal arch: posterior, floor of carpal tunnel
Flexor retinaculum: Palmar side, roof of carpal tunnel
Running through: flexor tendons for fingers and thumbs, median nerve
Describe the symptoms of carpal tunnel syndrome
Initially dull ache/ discomfort
Eventually pins and needles, sharp pain/ parasthesia can extend up forearm
Muscle weakness
Thenar muscle wastage
Why is there no loss of central palmar sensation in carpal tunnel syndrome?
Palmar branch is unaffected
Give 3 risk factors for carpal tunnel syndrome
Obesity
Pregnancy
Underlying conditions (rheumatoid arthritis)
How would you diagnose carpal tunnel syndrome?
Electrophysiological testing
Description of symptoms
Physical tests
What is Tinel’s sign for carpal tunnel syndrome?
Tapping median nerve, symptoms of tingling/ pins and needles
What is Phalen’s manoeuvre for carpal tunnel syndrome?
Flex wrists for 1 min, numbness in innervated areas
What is Durkan’s test for carpal tunnel syndrome?
Manually compress transverse carpal ligament for 30s
Symptoms arise
How would you treat carpal tunnel syndrome?
Behaviour modification Physical therapy Splinting Corticosteroids Surgical division of the transverse carpal ligament
Describe myasthenia gravis
Autoimmune disease affecting skeletal muscle, patients often wake up feeling fine but weak by the end of the day
Which groups are preferentially affected by myasthenia gravis?
Young women 20-30s
Older men 60s-70s
Describe the pathology of myasthenia gravis
B-cells produce antibodies which bind to nicotinic acetylcholine receptor on muscle cell membrane, preventing acetylcholine binding
Antibodies also activate the classical compliment pathway causing inflammation and muscle cell destruction
B-cells also produce muscle specific receptor tyrosine kinase antibodies which target proteins in muscle cells
How can myasthenia gravis present as paraneoplastic syndrome?
Underlying cancer
Bronchogenic carcinoma/ thyme neoplasm
Causes a B-cell autoimmune response
What is a myasthenic crisis?
Decrease in function of muscles controlling breathing
How would you treat myasthenia gravis?
Acetylcholinesterase inhibitors (neostigmine/ pyridostigmine): stops Ach breakdown Immunosuppressive drugs: prednisone (reduce production of autoantibodies Surgical removal of the thymus: reduces muscle weakness
Describe the mutation that causes Huntington’s disease
Autosomal dominant
Huntingtin (HTT): chromosome 4 contains a triplet repeat
How many repeat and of which sequence would usually cause Huntington’s?
> 36 CAG repeats (which codes for amino acid glutamine)
How does the mutated Huntingtin protein cause symptoms of Huntington’s?
Mutated protein builds up in the putamen and caudate of the basal ganglia, causing cell death (excitotoxicity) this causes excessive signalling and an increase in intracellular Ca2+
Describe what is meant by anticipation in the context of Huntington’s
Due to divisions, child can inherit more CAG repeats than the parents had
More repeats often means earlier onset
How does the parent affected change the likelihood of anticipation in Huntington’s?
Repeated expansion happens more with sperm production than egg
Anticipation and new disease alleles are more likely to happen if the father is affected
Describe the symptoms of Huntington’s disease
Movement problems: Chorea: dance-like/ jerking movements Athetosis: slow movements Abnormal eye movements Poor co-ordination
Psychological problems:
Dementia
Personality changes
Depression
What is the result of dorsal striatum neuronal death in Huntington’s?
Loss of brain tissue and expansion of lateral ventricles
What is the typical age of onset of Huntington’s?
40 y/o
What is the effect on neurotransmitter levels in Huntington’s?
Loss of GABA
Loss of acetylcholine
Increased levels of dopamine
How might you treat chorea as a symptom of Huntington’s?
Neuroleptics: dopamine receptor antagonists
Tetrabenazine: depletes dopamine
