Neurovascular Pathology Flashcards
What is myopia?
Short-sightedness (close objects appear clear, distant objects are hazy).
What causes myopia?
An eyeball that is too long. Cornea and lens make image form in front of retina.
What symptoms are associated with myopia?
Headaches, unable to see in distance, divergent squint in children, toddlers lose interest in sports/people, more interested in books/pictures.
How is myopia treated?
Biconcave lenses (glasses/contact lenses), laser eye surgery.
What is hyperopia?
Long-sightedness (close objects hazy, far off images clear).
What causes hyperopia?
Mostly due to eyeball being too small or cornea/lens being too fat. Image formed behind retina. Person uses accommodative power to make lens thicker to allow image to be formed on retina, so when seeing close up, they use more and more power until they cannot see properly.
What symptoms are associated with hyperopia?
Eyestrain after working/reading on computer, convergent squint in children (needs immediate correct to prevent vision loss/lazy eye).
What is astigmatism?
Image is always hazy, regardless of distance of object.
What causes astigmatism?
Surface of eye has different curvatures in different meridians, so bending of light along one axis will never be the same as that of another axis. Cornea is rugby ball shaped.
How is astigmatism treated?
Cylindrical glasses (only curved in once axis), toric lenses (weighted to be put on correctly), laser eye surgery.
How is hyperopia corrected?
Biconvex lenses (contact lenses, or glasses), laser eye surgery.
What happens in presbyopia?
With age, lens becomes less immobile/elastic. Ciliary muscle contraction is unable to change lens shape. Seeing near objects becomes increasingly difficult.
When does presbyopia tend to occur?
Usually starts in 50s.
What symptoms are associated with presbyopia?
Eyestrain, difficulty reading small print, headaches.
How is presbyopia treated?
Biconcave lenses (reading glasses).
What are the signs and symptoms of vitamin A deficiency?
(Night) blindness, Bitot’s spots (silvery triangular spot in conjunctiva), corneal ulceration and corneal melting.
What complications can result from vitamin A deficiency?
In serious cases - opacification of cornea.
What can cause vitamin A deficiency?
Any condition affecting vitamin A absorption, e.g. malnutrition, malabsorption syndromes, e.g. coeliac disease or sprue.
What do Bitot’s spots result from?
Build up of keratin.
What will damage to the right optic nerve result in?
Blindness in right eye.
What will damage to the middle of optic chiasma cause?
Bilateral temporal hemianopia.
What will damage to the right optic tract cause?
Left homonymous hemianopia.
What will damage to the right optic radiation?
Left homonymous hemianopia.
What is strabismus?
Squint - misalignment of the eyes.
What are the two types of strabismus?
Estropia (convergent squint), exotropia (divergent squint).
What are the functional consequences of strabismus?
Amblyopia, diplopia.
In what kind of patients does amblyopia happen more commonly?
If one eye if hyperopic, myopic or astigmatic.
What causes amblyopia?
Aka. - lazy eye
Brain surpasses image of one eye leading to poor vision in that eye without any pathology.
How is strabismus corrected?
Glasses.
How is amblyopia corrected?
Corrected in early years by using patches to stimulate lazy eye.
What is anioscoria?
When the pupils are different sizes - can be harmless or sign of underlying medical problems.
What can anioscoria indicate?
Horner’s syndrome.
What are reasons for the pupils reacting abnormally to light?
Abnormalities of the afferent limb/centre/efferent limb of cranial nerve III
IIIn palsy due to medical cause
Diseases of the retina (detachment, degenerations, dystrophies)
Diseases of the optic nerve, e.g. optic neuritis in MS.
What is important to remember in patients with IIIn palsy and absent pupillary reflex with diabetes?
Diabetes tends not to cause damage to the parasympathetic fibres of cranial nerve III, so if you see patient with IIIn palsy and absent pupillary reflex suspect a cerebral artery aneurysm (medical emergency).
What is the cause of Horner’s syndrome?
Occurs due to disruption of sympathetic supply to the eye, e.g. due to Pancoast tumour or stroke.
What are the signs associated with Horner’s syndrome?
Anisocoria (miosis (excessive constriction of eye), hemifacial anhydrous (loss of sweating on affected side), enophthalmos, partial ptosis.
How do you investigate Horner’s syndrome?
MRI, CT, Xray.
How do you treat Horner’s syndrome?
Treat underlying medical condition.
What causes a blowout fracture?
Blunt force hitting the eye is transmitted to the orbit (orbital rim strong but orbit weak, structures can herniate into maxillary sinus).
What are the signs of a blowout fracture?
Infraorbital nerve sensation over infraorbital foramen (where it comes out) reduced.
What symptoms are associated with a blow out fracture?
Diplopia, inability to elevate one/both eyes.
How are blow out fractures managed?
Some cases small and heal on their own, others require surgery to put a wire mesh into the floor of the orbit.
In what kind of diseases do you get orbital fat hypertrophies?
Thyroid disease.
What are the normal cornea-scleral junctions (limbus)?
Normal upper eyelid 1-2mm below cornea-scleral junction and for lower eyelid at level of corneascleral junction.
What will you see on fundoscopy if infection spreads into the eyes and sinuses? How can the infection spread to the sinuses? What can this result in?
Swollen and tortuous veins, swollen and engorged optic disc (venous drainage from orbit compromised, and unless dealt with it can spread through emissary veins to the cavernous sinus leading to cavernous sinus thrombosis and cause compression/paralysis of movement).
What symptoms will you experience if infection spreads into the eyes and sinuses?
Red, painful eyes, no eye movement, can lead to total loss of vision.
What is a coloboma? When are they present from?
Hole in one of the structures of the eye, e.g. iris coloboma, retinal coloboma, optic disc coloboma). Present from birth or develop in first few months. Can be uni/bilateral.
What causes a coloboma?
Failure of fissure fusion.
What symptoms can people with coloboma experience?
May be asymptomatic or completely blind (if large part of retina/optic disc missing).
What can blunt trauma to the eye result in?
Peripheral retinal tear, vitreous gel becomes liquified and can push through the retinal tear and detach it.
What is conjunctivitis?
Self-limiting bacteria/viral infection leading to enlargement of blood vessels in conjunctiva, sometimes causing the eyelids to stick together.
What symptoms will someone with conjunctivitis experience?
Red, watery eyes, discharge (pus), no loss of vision (if doesn’t spread to cornea).
What are the possible complications of conjunctivitis?
Blurry vision indicative of infection spread to cornea (adenovirus can do this).
How is conjunctivitis treated?
Antibiotic eye drops.
What is ptosis?
Drooping of the upper eyelid.
What can cause ptosis?
Levator palpebrae superiors paralysis (IIIn dystrophy or paralysis).
What are the signs of ptosis?
Inability to open the eyelid.
What are the two types of stye/hordeolum?
External - due to infection of sebaceous glands of the eyelids
Internal - due to infection of Meibomian glands (responsible for creating oil layer of tear film)
What is a stye/hordeolum?
Usually an abscess filled with pus caused by staphylococcus infection.
What symptoms are associated with styes?
Painful lump on inside or outside of eyelid. Vision should be affected. Eyelid or eye may be red/watery.
How can you treat styes?
Warm compress, eyelid hygiene, analgesia, may need surgical incision and curettage.
What are corneal ulcers? Which layer is important that you don’t injure? What can cause corneal ulcers?
Inflammation of the cornea (epithelium lost, storm exposed if damage passes Bowman’s layer), cornea exposed to outer environment, e.g. bacteria, viruses, fungi.
Non-infective causes include trauma, degeneration or dystrophy.
What symptoms are associated with corneal ulcers?
Red eye, pain.
What complications can result due to corneal ulcers?
Loss of vision.
How are corneal ulcers managed?
Aggressive Rx to prevent scarring, corneal transplant/keroplasty.
What are non-inflammatory corneal dystrophies?
A group of diseases affecting the cornea, which are bilateral, opacifying, non-inflammatory. These diseases will start in one layer and spread to others.
These are mostly genetically determined.
What causes the non-inflammatory corneal dystrophies?
Sometimes due to accumulation of lipids.
What are cataracts?
Clouding of the lens in the eye leading to decreased vision.
How do cataracts develop?
Develop as older embryological fibres of eye nerve shed and become compacted in the middle. There is no blood supply to the lens which depends entirely on diffusion for nutrition. Opacities can be quite immature (usually in cortex of lens (deeper part of nucleus is lens (older cells)).
What can cause cataracts?
Use of steroid eye drops, tumours, paging. Nuclear sclerosis is a type of cataract, UV rays.
What are sutural and zonular cataracts?
Types of childhood cataract due to opacification of certain zones of the lens in utero (due to mother malnutrition/German Measles contraction).
What are the risk factors for cataracts?
Diabetes, smoking.
What symptoms are associated with cataracts?
Night blindness (when pupil dilates if immature cataract), can use sympathetic agent to stimulate pupils, light sensitivity.
How are cataracts treated?
Day case surgery (small incision made, lens capsule opened, lens removed by emulsification, plastic lens is placed in capsular bag). Lens known posterior chamber intraocular lens (PCIOL).
What are the two types of glaucoma?
Open angle glaucoma or angle closure glaucoma.
What happens in a primary open angle glaucoma?
Angle between the cornea and iris is open. Drainage system slowly gets clogged over time leading to an increase in intralocular pressure. Pressure transferred to outer rim of nerve leading to peripheral vision loss. But as it increases leads to optic nerve damage, leading to loss in central vision loss as well.
Where is primary open angle glaucoma normally picked up?
Routine eye exams.
What will you see on ophthalmoscopy in primary open angle glaucoma?
Unhealthy, pale, cupped optic disc.
What are the triad of signs for the diagnosis of primary open angle glaucoma?
Raised IOP, visual field defects, optic disc changes on ophthalmoscopy.
What symptoms will someone with open angle glaucoma experience?
Can be asymptomatic for a long time, slow onset of symptoms, altered visual field and can result in total blindness.
How is primary open angle glaucoma treated?
Eye drops to decrease IOP - prostaglandin analogues, beta-blockers, carbonic anhydrase inhibitors), laser trabeculoplasty, trabeculectomy surgery (take off sclera and trabecular meshwork).
What happens in an angle closure glaucoma?
Angle between iris and cornea too small - passage for AH too narrow, leads to lens being pushed against the iris. Drainage system blocked and causes rapid pressure build up in eye. AH unable to reach trabecular meshwork, more formed and build up causes iris to ballon and close epithelium further.
What are the risk factors for angle closure glaucoma?
Tends to happen in predisposed eyes (long-sighted person, in dusk - blocks off angle).
What signs and symptoms are associated with angle closure glaucoma?
Signs - red eye, fixed dilated pupil.
Symptoms - abrupt onset of eye pain and redness, blurry vision, headaches, nausea, opacities as IOP leads to fluid leaking into cornea.
How is angle closure glaucoma managed?
Decrease IOP - IV infusion w/ or w/o therapy (CAH (acetazolamide), analgesia, anti-emetics, constrictor eye drops (pilocarpine), beta-blockers, e.g. timolol, steroid eye drops, e.g. dexamethasone, iridotomy (laser) both eyes to bypass block (make tiny hole to allow AH to come to angle and move about).
What is uveitis?
Inflammation of urea (vascular layer of eye).
What happens in anterior uveitis? What is a complication of anterior uveitis?
Inflammation of iris - inflamed anterior urea leaks plasma and white blood cells in the AH. Cells in the AC may settle inferiorly and cause a hypopyon (inflammatory cells in anterior chamber of eye (leukocytic exudate).
What is anterior uveitis seen like in the split lamp exam?
Seen in split lamp exam as a hazy anterior chamber and cells deposited in the back of cornea.
What is intermediate uveitis?
Inflammation of the ciliary body and leakage of cells and proteins leading to hazy vision and floats with little/no pain.
What is posterior uveitis?
Choroid inflammation, can spread to retina and cause blurred vision.
What can cause uveitis?
Isolated illness, non-infectious autoimmune cases, chronic TB, syphillis, toxoplasma, Herpes simplex, Lyme disease, CMV, associated with ankylosing spondylosis, Behcet’s dx, sarcoidosis, Wegner’s, systemic lupus erythematous, intraocular lymphoma, leukaemia.
What symptoms are associated with uveitis?
Blurry vision/vision loss (due to macular oedema due to leaky vessels), redness around cornea.
How do you treat uveitis?
Topical anti-inflammatories, systemic steroids, systemic immunosuppressants.
What does corneal abrasion result from? What symptoms does it cause?
Trauma to cornea.
Redness and pain.
Tends to heal very quickly.
What symptoms are experienced in pre-septal cellulitis?
Redness, lid-swelling, systemically well.
What can cause pre-septal cellulitis?
Lid cyst or insect bite.
What symptoms are experienced in orbital cellulitis?
Pain, redness, systemically unwell, diplopia, limitation in EOEM, conjunctivitis/chemosis, exophthalmos, blurred vision, fever.
What can cause orbital cellulitis?
Sinusitis/dental infections via haematological spread.
What complications can arise as a result of orbital cellulitis?
Brain abscesses and loss of vision, if not treated promptly.
How do you treat orbital cellulitis?
Drain fluid from eye.
What is multiple sclerosis?
Multiple episodes of demyelination in space and time with variable site and severity.
Involves patchy loss of myelin sheath in CNS, affecting nerve conduction, leading to progressive disability.
What is the pathophysiology of MS?
Autoimmune process whereby T cells cross blood brain barrier, become activated by myelin, and release cytokines (dilated BVs) and other immune cells enter past BBB and damage the oligodendrocytes.
Cytokines attract B cells (and macrophages) which produce antibodies that mark oligodendrocytes for macrophages to destroy them.
No myelin to cover nerves and scarring of nerves leads to plaques/sclera.
What kind of hypersensitivity is MS?
Type IV.
How does the body calm down the hypersensitivity reaction in MS? Why is this not effective in the long run?
Regulatory T cells come in and calm down the immune response. In early MS, re-myelination can occur.
But overtime, olgiodendrocytes die off, leading to irreversible loss of axons. Post-inflammatory gliosis may have functional deficit.
Which country has the highest incidence of MS in the world?
Scotland.
What do investigations show in MS?
Whitish plaques of demyelination and black holes, lateral cerebral atrophy may be visible.
Olgioclonal bands present in CSF (lumbar puncture) but not serum.
How many lesions related to one relapse?
10 lesions for every 1 relapse.
NB - scan and patients symptoms don’t necessarily correlate.
What investigations can you use to investigate MS?
MRI, CTs, LP, visual/somatosensory evoked response, bloods, CXR.
What will you see on examination of someone with MS?
Afferent pupillary defect, nystagmus, abnormal eye movements, cerebellar signs, sensory signs, weakness, spasticity, hyperreflexia, plantar’s extensor.
What are the two diagnostic criteria for MS?
Clinical - Posers criteria
MRI - MacDonald criteria
Diagnosis based on evidence of demyelination based over time and space.
What is Charcot’s triad?
Some of the clinical signs of MS: dysarthria (plaques in brainstem), nystagmus, intention tremor.
What are thought to be causes of MS?
?viral (EBV), associated with autoimmune disease, genetic factors (females, HLS-DR2), fit D deficiency?, commoner in temperate climates, age of exposure.
What is L’hermitte’s sign?
Electric shock running down back and radiating to limbs when bending the neck forward.
Can be a sign of MS, transverse myelitis, B12 deficiency etc.
What are common relapse symptoms in MS?
Optic neuritis, sensory symptoms (paraesthesias, numbness = plaques in sensory pathways), limb weakness, spinal cord problems (bilateral symptoms/signs +/- bladder), cranial nerve involvement, diplopia, ponsinternuclear ophthalmoplegia (e.g. vertigo, nystagmus, ataxia, upper motor neurone changes in the limb).
What diseases can cause similar symptoms to MS?
Neuromyelitis optica, sarcoidosis, ischaemic optic neuropathy, Wegner’s granulomatosis, local compression, Leber’s hereditary optic neuropathy, acute disseminated encephalomyelitis, other autoimmune diseases, e.g. SLE, vasculitis, infections, e.g. Lyme disease, HTVL-1, adrenoleucodystrophy etc.
What are the different types of MS? Explain how they differ.
Relapsing remitting - most common, bouts of attacks happen months/years apart, different symptoms appear and can get better or worse. Typically no increase in disability between bouts. Tend to go on to develop SPMS.
Secondary progressive (SPMS) - initially similar to RRMS but over time immune attack becomes constant - leading to steady progression in disability.
Primary progressive - constant attack on myelin (no relapses), steady increase in disability. Often presents in 50-60s with spinal and bladder problems. Poor prognosis.
Progressive relapsing - constant attack but bouts superimposed.
Sensory
Malignant
What do the progressive phases of MS involve?
Accumulation of signs and symptoms, e.g. fatigue, temperature sensitivity, sensory problems, stiffness/spasms, balance problems, slurred speech, swallowing, bladder and bowel problems, diplopia, oscillopia, visual loss, cognitive dementia/emotional irritability.
What are the first line treatments of MS?
Diet/general health
1st line Rx: beta-interferons/glatiramer acetate (reduces relapses, weekly im/sc), teriflunomide (oral), dimethyl fumigate (oral).
What are the side effects of first line treatment of MS?
Flu-like symptoms, injection site reactions, abnormalities of blood count and liver function.
What are the second line treatments for MS?
Natalizumab (reduce relapse rate, monthly infusion), fingolimoid tablets, alemtuzumab.
What are the ADRs for fingolimoid?
Cardiac ADRs.
What are the ADRs for alemtuzumab?
Autoimmune thyroid disease, good pastures/immune thrombocytopenic purpura.
What can be used for symptomatic treatment?
Spasticity - muscle relaxants/anti-spasmoidcs/physiotherapy
Dyseasthesia - amitriptyline gabapentin
Urinary - anti-cholingeric Rx, bladder stimulator/catheterisation
Constipation - laxatives
Sexual dysfunction, fatigue - graded exercise, mediation
Depression - CBT, meds
Cognitive - memory aids etc
Speech and swallowing - SALT
Motor impairment - MDT
How are acute relapses managed?
Look for underlying infection, exclude worsening of usual symptoms with intercurrent illness.
Oral prednisolone (IV), rehab, symptomatic Rx.
Why is it important to vaccinate MS patients?
Relapses can be associated with viral infections.
How does pregnancy affect relapse rate in MS?
Reduces relapses during pregnancy, increased risk 3 months post-partum.
What is the prognosis like in MS?
1/4 of MS patients will have their activities of daily living affected, 15% severely disabled. 1/4 will require a wheelchair at some point.
What are the good prognostic indicators in MS?
Females, presenting with optic neuritis, long intervals between 1st and 2nd relapse, few relapses in first 5 years.
What are the bad prognostic indicators in MS?
Male, older age, multifocal symptoms and signs, motor symptoms and signs.
What is myelitis?
Infection/inflammation of the white or grey matter of the spinal cord.
What are the two types of myelitis and how do they differ?
Transverse (complete) - affecting the whole width of the spinal cord.
Partial - affecting part of width of the spinal cord.
What is myelopathy?
Injury to the spinal cord due to severe compression. Can be cervical or thoracic normally.
What symptoms/signs does myelopathy cause?
Sensory and motor issues at level affected, UMN symptoms/signs below lesion.
What are the long tract signs in myelopathy?
Clonus, upgoing planters, increased tone, Hoffman sign, brisk reflexes, proprioception impairment, Romberg’s test (tandem walking).
What is progressive multifocal leukencephalopathy?
Rare but serious demyelinating disease of the brain. It is caused by a lytic infection of oligodendrocytes by JC polyomavirus (JCV).
How are patients with progressive multifocal leukencephalopathy screened?
MRI annually, JC antibody blood and urine 6-monthly.
What are the risk factors for developing progressive multifocal leukencephalopathy?
Immunosuppressed patients (AIDS, natalizumab, dimethyl fumarate, fingolimoid).
What is neuromyelitis optic spectrum disorder?
Aka. Delvic disease. Very rare autoimmune disease in which there are episodes of optic neuritis and transverse myelitis.
What will you find in most patients with neuromyelitis optic spectrum disorder?
aquaporin-4 antibodies.
What symptoms do patients with neuromyelitis optic spectrum experience?
Varied - eye pain, loss of vision, reduced colour vision, limb weakness, pain in limbs, bladder, bowel and sexual problems.
Why do you need to be on alert for neuromyelitis optic spectrum disorder?
MS treatment can make these patients a lot worse! Despite the fact it is very rare.
NB - can be one off or relapsing.
How is neuromyelitis optic spectrum disorder treated?
Immunosupression.
What is motor neurone disease?
Aka. amyotrophic lateral sclerosis.
Occurs when motor neurones stop working properly (neurodegeneration with NO inflammation).
In which sex and age group is motor neurone disease most prevalent?
Men, over 60s.
What is the diagnosis of motor neurone disease based on?
A unique combination of UMN, LMN signs and EMG (showing lots of muscles affected and widespread denervation).
What are the risk factors for motor neurone disease?
Hereditary, age (40-60s), male, genetics.
What are the signs of motor neurone disease?
Lesion of UMN above decussation = contralateral spastic paralysis and hyperreflexia.
Lesion of UMN below decussation = ipsilateral paralysis and hyperreflexia.
Lesion of LMN = ipsilateral flaccid paralysis, areflexia, muscle atrophy.
Other signs - weakened grip, weakness in shoulder leading to difficulty raising arm, foot drop, dragging of leg, dysarthria.
What symptoms are associated with motor neurone disease?
Usually limb onset, lateral bulbar and respiratory involvement.
Difficulty walking, tripping/falling, weakness in legs/ankles/feet, hand weakness and clumsiness, slurred speech, trouble swallowing, muscle cramps and twitching in arms, shoulder and tongue.
What is an epileptic seizure?
Intermittent stereotyped disturbance of consciousness, behaviour, emotion, motor function or sensation. These can march over the body.
What is epilepsy?
A condition in which seizures recur, normally spontaneously.
Why is there a J-shaped curve in the age related incidence of epilepsy?
Commonest in babies and elderly (due to microdx) but incidence low in young adults.
After how many unprovoked attacks is epilepsy normally diagnosed?
2
How do you investigate people presenting with epileptic seizures?
MRI (esp. in <50s with possible focal onset seizures and to exclude serious cases over this age), CT (for tumours etc.), EEG (incl. with hyperventilation, photic stimulation, sleep deprivation), can do video telemetry if uncertain about diagnosis.
How would you investigate a first fit?
Blood sugar, ECG, consider alcohol/drugs, CT head (criteria), enquire about employment, dangerous activities.
What must you be sure to do in epilepsy patients?
Explain driving regulations.
What is thought to be the cause of epilepsy?
Abnormal neuronal discharges.
How is epilepsy classified?
ILAE using clinical data and EEG have separated it into two epilepsy syndromes:
Generalised seizures
Focal partial seizures
What are generalised seizures?
Both hemispheres of the brain affected. May begin as focal and quickly develop into generalised (known as focal onset bilateral tonic-clonic seizure). Tends to have no warning.
What are focal seizures?
Unpredictable brain activity localised to one hemisphere/lobe of brain. May get aura.
What are the different types of generalised seizure and how do they differ?
Tonic-clonic - most common, tonic phase (muscles seize up), clonic phase (muscle convulsions).
Myoclonic - short muscle twitches.
Clonic - violent muscle convulsions.
Tonic - muscles stiff/flexed. Can cause patient to fall BACK.
Atonic - muscles go floppy. Can cause patient to fall FORWARD.
Absence - impaired awareness or responsiveness.
What are the different types of focal/partial seizure and how do they differ?
Without impaired awareness - affects small area of brain, causes strong sensations or jerking (depending on nerves affected). Patient often remembers what happened/will know something is happening.
With impaired awareness - loss of awareness/responsiveness, usually can’t remember seizure.
What is important to remember what classifying seizures?
Some patients (esp. those with learning difficulties) have unclassifiable seizures unique to them).
What are some signs of epilepsy?
Myoclonic jerks, esp. first thing in the morning, absences, strange feeling with flickering light (primary generalised epilepsy), déjà vu, rising sensation from abdomen, episodes where look blank with lip smacking, fiddling with clothes (focal onset epilepsy).
What symptoms can result from epilepsy?
Post-ictal confusion, paralysis of arms/legs (usually unilateral).
What complications can arise from epileptic seizures?
Status epilepticus.
What is status epilepticus?
Prolonged/recurrent tonic-clonic seizures persisting for more than 30 mins with no recovery between seizures.. Usually happens with no previous epilepsy history.
How is status epilepticus treated?
1st line - midazolam (buccal/intranasal, repeat after 10 mins if req), lorazepam (bolus, repeat after 20m if req), diazepam (IV/rectal, repeat after 15 min if req).
2nd line - valproate/phenotyoin infusion.
3rd line - propofol/thiopentone (anaesthetics).
How is epilepsy treated?
Anti-convulsants.
What is the first line treatment for epilepsy?
Sodium valproate, lamotrigine, levetriacetam for generalised epilepsy.
Lamotrigine or carbamazepine for partial or secondary generalised seizures.
Ethosuzamide for absence seizures.
What is the second line treatment for epilepsy?
Topiramate, zonisamide, carbamazepine for generalised epilepsy.
Sodium valproate, topiramate, leviteracetam, gabapentin, preganilin, lacosamide, premapanel, benzodiazepines for partial seizures.
Levetiracetam IV considered for status/near status.
What are the ADRs for sodium valproate?
Tremor, weight gain, ataxia, nausea, drowsiness, transient hair loss, pancreatitis, hepatitis.
What are the ADRs for carbamazepine?
Ataxia, drowisness, nystagmus, blurred vision, low serum sodium, skin rashes.
What are the ADRs for lamotrigine?
Difficulty sleeping, skin rash.
What are the ADRs for levetiracetam?
Irritability/depression.
What are the ADRs for Topiramate?
Weight loss, word-finding difficulties, tingling hands/feet.
What are the ADRs for zonisamide?
Bowel upset, cognitive problems.
What are the ADRs for lacosamide?
Dizziness.
What are the ADRs for pregablin?
Weight gain.
What are the ADRs for vigabatrin?
Behavioural problems, visual field defects.
What are the driving regulations for epilepsy?
After first seizure - can drive car after 6m if Ix normal, no further events. Drive HGV/PSV after 5y if Ix normal and no further events and not on anti-epileptics.
Patients can hold a group 1 license once they have been seizure free for a year/only had seizures arising from sleep for a year.
If they ever had a daytime seizure, nocturnal pattern must be established for 3 years before they can start driving (10 years and not on anti-epileptics for HGV/PSV).
What can cause status epilepticus?
Stroke, tumour, alcohol.
What is a blackout?
Transient dull or loss of vision, consciousness or memory.
What must you gather fro the history?
What they were doing at the time. Warning feelings? Doing the night before? Alcohol? Anything like this before? How did they feel after? Injury? Tongue biting? Continence?
From witness:
Level of responsiveness, motor phenomena, PMH of head injury, birth trauma, febrile convulsions, FH.
What can cause a blackout?
Syncope, first seizure, concussive seizure, cardiac arrhythmias, non-epileptic attack (narcolepsy, movement disorder, migraine).
What are the differences between syncope and seizure?
Syncope - upright posture, seizure - any posture
Syncope - pallor common, seizure - pallor uncommon
Syncope - gradual onset, seizure - sudden onset
Syncope - injury rare, seizure - injury more common
Syncope - incontinence rare, seizure - incontinence common
Syncope - rapid recovery, seizure - slow recovery
Syncope - precipitants common, seizure - precipitants rare
What does vasovagal syncope result from?
Occurs in response to trigger than slows HR, blood vessels in legs widen and blood pools in the legs, which lowers BP. This reduces blood flow to the brain and causes a brief loss of consciousness.
What are the triggers for vasovagal syncope?
Prolonged standing, standing up quickly, trauma, venipuncture, micturition (fainting shortly after urination), long coughing fit.
What symptoms can some experience before a vasovagal syncope?
Predome (light headed, nausea, hot, sweating, tinnitus, tunnel vision).
If you stand up too quickly after a vasovagal syncope what can happen?
Risk of fainting again.
How can you prevent a vasovagal syncope if you feel it coming on?
Lie down and raise legs in the air.
What causes a hypoxic seizure?
Occurs when patients are kept upright during a faint, e.g. in aircrafts, at the dentists, people meaning well. Seizure-like activity may occur.
What causes a concussive seizure?
A blow to the head.
What heart problems can seizures cause?
Cardiac arrhythmias.
When would you want to be considering if there is FH of sudden death or cardiac history?
If a young person is collapsing during exercise.
What are non-epileptic attacks?
May resemble tonic-clonic seizure, involve swooning or bizarre movements. Can be frequent and prolonged. May have history of medically unexplained symptoms/history of drug abuse.
What are primary headaches? What sort of headaches fall into this category?
No underlying medical cause. Includes tension type headache, migraine and cluster headaches.
What are secondary headaches?
These have identifiable structural or biochemical cause (e.g. tumour, meningitis, vascular disorders, systemic infection, head injury, drug-induced). Not all are sinister.
What are tension type headaches? What can cause these?
Milk-bilateral headache which is often tight/pressing. No significant associated features and not worsened by routine physical activity. Life-time prevalence almost 50%. Stress, squinting, poor posture, tiredness, dehydration, missing meals, lack of exercise, bright sun light, noise…
What are the types of tension type headaches?
Infrequent ETTH <1 day/month, frequent ETTH 1-14 days/month, chronic TTH 15+ days/month.
How do you treat a tension type headache?
Aspirin/paracetamol, NSAIDs (limit to 10 days/month to avoid MOH). Preventative Rx: tricyclic antidepressants (amitryptline, dopthiepine, nortriptyline; rarely req).
What is a migraine?
Complex chronic disorder with episodic attacks involves integrated brain mechanisms and CNS structures (cortex, brainstem, trigeminal system, meninges).
The brain of the migraineur is hypersensitive to stimuli. could be to do with a number of things (insufficient cortical inhibition, reduced pre-activation of sensory cortices as a result of thalamocortical drive).
Give examples of migraine triggers.
Normal life events (diet, environmental stimuli, low oestrogen in women, stress, hunger, dehydration, sleep distruabcnce.
What symptoms are associated with migraine?
Throbbing unilateral headache, photophobia, photophobia, nausea.
Symptoms between attacks incl. enduring predisposition to future attacks, anticipatory anxiety.
What is an aura with migraine?
33% of migraineurs get this.
Transient neurological symptoms resulting from brainstem/cortical dysfunction. May involve visual, sensory, motor or speech systems. Slow evolution of symptoms. Duration: 15-60 minutes. Can be confused with TIA.
What is a visual aura in migraine?
Most common. Involves loss of vision (e.g. scotoma), a blind spot that spreads across the visual field, or loss of vision in one field (hemianopia less common).
What is a sensory aura in migraine?
Paraesthesia (tingling) typically starts in one hand, spreading to arm, elbow, face, lips and tongue.
What is a motor aura in migraine?
Typically experienced on one side, affecting the hand and arm.
What other rare type of aura can you get in migraine? (aside from motor, sensory and visual).
One affecting the brainstem, results in quadriplegia, loss of consciousness or cranial nerve deficits.
How are migraines treated?
Aspirin/NSAID, triptans (use less than 10x/month to avoid MOH).
Prophylaxis - propanolol, candesartan, anti-epileptics (topiramate, valproate, gabapentin), tricyclic antidepressants (amtitryptiline, dothiepin, nortryptiline), venaflaxine.
What are the 5 migraine phases?
Premonitory phase (70%) - mood alterations, muscle pain, cravings, cognitive changes, fluid retention, yawning.
Aura phase
Early headache phase - mild pain without associated migraine symptoms.
Advanced headache phase - moderate to severe pain with associated symptoms (nausea, photophobia, phonophobia, disability).
Postdrome - migraine associated symptoms beyond the resolution of the headache (can last 1-2 days).
What is believed to cause the aura phase of migraines?
Believed to arise from electrical disturbance called cortical spreading depression.
What do you call migraines that involve auras not followed by a headache?
Acephalgic migraines.
What is a classed as a chronic migraine?
Headache on 15+ days of the month, more days have to be migraine than headache, for more than 3 months.
What is a transformed migraine?
History of episodic migraine, increasing frequency of headaches over weeks/months/years, migrainous symptoms become less frequent/severe.
Many patients have episodes of severe migraine on background of less severe featureless frequent/daily headache.
Transformation can occur w or w.o escalation in medication use.
How does taking patients with medication overuse headaches off their medication help affect their headaches?
Usually dramatically improves headache frequency.
What is a medication overuse headache?
Headache present on 15+ days/month which has developed or worsened whilst taking regular symptomatic medication. Can occur in any primary headache, migraineurs particularly prone (even if taking meds for another reason).
What drugs can cause medication overuse headache?
Triptans, ergots, opoids and combination analgesics more than 10 days/month.
Simple analgesics >15 days/month.
Caffiene overuse can also cause MOH.
Does migraine without aura get better or worse during pregnancy?
Better usually.
Does migraine with aura get better or worse during pregnancy?
Usually doesn’t change.
Can the first migraine occur during pregnancy?
Yes (usually with aura).
What is contraindicated if patients have migraine with aura?
Combined OCP contraindicated in migraine with aura (okay if no attacks for more than 5 years, stop in aura recurs).
What sort of drugs must you avoid in the pregnant or women of childbearing age?
Anti-epileptics.
Or must counsel about teratogenicity and ensure contraception.
What medications are okay to use for headaches in the pregnant?
Paracetamol or preventative propanolol or amitriptyline.
What are trigeminal autonomic cephalgias?
Primary headaches with a common clinical phenotype consisting of trigeminal pain with autonomic signs.
What types of trigeminal autonomic cephalgias are there?
Cluster Hedaache
Paroxysmal hemicranias
SUNCT (short lasting unilateral neuralgiform headache with conjunctival injection and tearing)
SUNA (short lasting unilateral neuralgiform headache with autonomic symptoms
What sort of symptoms do you get in trigeminal autonomic neuralgias?
Unilateral severe head pain (mostly V1), cranial autonomic symptoms, incl. conjunctival injection/lacrimal, nasal congestion/rhinorrhea, eyelid oedema, forehead/facial sweating, miosis/ptosis (Horner’s).
Attack frequency and duration differ.
What often do attacks occur in cluster headache?
1-8 per day.
What often do attacks occur in paroxysmal hemicrania?
1-40 per day.
What often do attacks occur in SUNCT?
3-200 per day.
How long do attacks tend to last in cluster headache?
15-180 mins.
How long do attacks tend to last in paroxysmal hemicrania?
2-30 mins.
How long do attacks tend to last in SUNCT?
5-240 secs.
What sort of pain is experienced in cluster headache?
Sharp and throbbing.
What sort of pain is experienced in paroxysmal hemicrania?
Sharp and throbbing.
What sort of pain is experienced in SUNCT?
Stabbing pain.
How intense is the pain in the trigeminal autonomic cephalgias?
Very severe.
What is the circadian periodicity like in cluster headache, paroxysmal hemicrania, and SUNCT?
Cluster headache- 70% - attacks tend to occur at same time each day.
Paroxysmal hemicrania - 45%
SUNCT - absent
Why is cluster headache so called?
Episodic in 80-90%. Attacks tend to cluster into bouts typically lasting 1-3 months with periods of remission lasting at least 1 month.
What is a chronic cluster headache?
10-20% have this. Bouts last <1y without remission or remission lasts less than 1 month.
What can trigger attacks in cluster headaches?
Alcohol during a bout but not in remission.
What symptoms are experienced in cluster headache?
Pain mainly orbital and temporal. Rapid onset (max within 9 mins in most) with rapid cessation of pain. Very severe. Patients restless and agitated during an attack. Prominent ipsilateral autonomic symptoms, migranous symptoms, premonitory symptoms, nausea, vomiting, photophobia, phonophobia, typically aura.
How are cluster headaches treated?
s/c sumatriptan 6mg or nasal solmatriptan 5mg
100% oxygen 7-12L/min via tight fitting non-rebreathing max is effective.
Headache bout - occipital depomedrone injection (same side as headache) or tapering course of oral prednisolone.
Preventative - verapamil (high dose), lithium, methysergide (risk of retroperitoneal fibrosis), topiramate.
What are the two different types of paroxysmal hemicrania?
80% have chronic, 20% have episodic.
What are 1/10th of attacks be precipitated by?
Bending/rotating of the head.
What are the signs/symptoms of paroxysmal hemicrania?
Sudden onset of excruciating orbital/temporal unilateral pain. Half of people are restless and agitated during an attack. Prominent ipsilateral autonomic symptoms, migrainous symptoms may be present. Background continuous pain can be severe.
How is paroxysmal hemicrania treated?
No abortive Rx.
Prophylaxis with indomethacin (alternatives: COX-II inhibitors, topiramate).
What triggers trigger a SUNCT attack?
Wind, cold, touching, chewing.
What symptoms are experienced in a SUNCT attack?
Unilateral, suprobital or temporal stabbing or pulsating pain, conjunctival injection and lacrimation.
How is SUNCT/SUNA treated?
No abortive Rx.
Prophylaxis - lamotrifine, topiramate, gabapentin, carbamezapine/oxccarbazepine.
What is trigeminal neuralgia?
Paroxysmal attacks of laminating pain. More common in middle age/elderly.
What causes trigeminal neuralgia?
Vascular loop causing compression of fifth cranial nerve in posterior fossa (BV rubs on nerve and irritates it).
What can trigger an attack of trigeminal neuralgia?
Wind, cold, touch, chewing.
What symptoms are experienced in trigeminal neuralgia?
Unilateral maxillary or mandibular pain > ophthalmic division. Stabbing pain lasting 5-10s. Attack frequency similar to SUNCT but has refractory period (unlike SUNCT), autonomic features also common.
How is trigeminal neuralgia treated?
No abortive Rx.
Prophylaxis: carbamazepine, oxcarbamezepine.
Surgical intervention: glycerol ganglion injection, stereotactic radiosurgery, decompressive surgery.
What kinds of presentation would be indicative of sinister causes of secondary headache?
Associated with head trauma, first or worse headache, sudden (thunderclap headache) onset, new daily persistent headache, change in headache pattern or returning patient headache.
What are the red flags for patients presenting with headache?
New onset New or change in headache and over 50 Immunosupressed/cancer patient Change in headache frequency Characteristics/associated symptoms Focal neurological symptoms Non-focal neurological symptoms Abnormal neurological examination Neck stiffness High pressure Headache worse lying down Wakening the patient up Precipitated by physical exertion/Valsalva Risk factors for cerebral venous sinus thrombosis Low pressure (headache precipitated by sitting/standing up) GCA (jaw claudication or visual disturbance) Prominent or beaded temporal arteries
What can cause a thunderclap headache?
PRIMARY: migraine, primary thunderclap headache, primary exceptional headache, primary headache associated with sexual activity
SECONDARY: SAH, intracerebral haemorrhage, TIA, stroke, carotid/vertebral dissection, cerebral venous sinus thrombosis, meningitis, encephalitis, pituitary apoplexy, spontaneous intracranial hypotension.
What symptoms are experienced during a thunderclap headache?
High intensity headache reaching maximum intensity i less than a minute. Majority peak instaneously.
From where do aneurysms tend to arise in the brain?
Circle of Willis.
What is the common presentation of SAH?
1 in 10 patients with thunderclap have a SAH.
What mostly causes SAHs?
85% aneurysmal.
How do you investigate a patient that has presented with a thunderclap headache?
All patients presenting with sudden, severe headache that peaks within a few mins and lasts less than an hour, even if exam normal, must consider SAH. Same day hospital appointment - history, exam, CT brain, LP (must be done in >12 hours after headache onset). CT +/- LP unreliable after 2wks, angiography must be done after this time.
Exclusion is by absence of blood products in CSF.
What are the risk factors for SAH?
Smoking (3x), high blood pressure.
What are the possible complications of SAH?
Hydrocephalus, vasospastic infarcts, disability.
How do you manage a SAH?
If ruptured aneurysm: endovascular coil embolisation, surgical clipping, treatment of complications.
Note - 50% mortality, 20% survivors remain dependent.
Why is raised intracranial pressure a problem?
Cranium is hard, rigid and closed. For pressure to be stable, there must be the correct amount of brain tissue/blood/CSF. The brain cannot go through the falx (but can go around it –> herniation), it cannot go through the skull (but can go round foramen magnum –> coning).
How do you monitor patients with raised ICP?
Brain tissue oxygenation monitoring (probe to monitor oxygenation of tissue, detect and treat low oxygenation to increase CPP), micro-dialysis (Ix brain metabolism, implantation of specially designed catheters to collect small molecular weight substances to help measure neurotransmitters, peptides and other substances).
How is motor neurone disease managed?
Supportive - PEG, NIV, physiology, OT, care.
Riluzole (prolongs survival by 2 months).
How does riluzole work in treating motor neurone disease?
It is an anti-glutamate that blocks the effects of glutamate. Glutamate is one of the things that causes nerve damage as excess glutamate over-stimulates nerves.
What is the life expectancy in motor neurone disease?
3-5 years from symptom onset.
Most die as a result of respiratory failure.
Its an incurable disease.
What is brown-sequard syndrome a result of?
Damage to one half of the spinal cord.
E.g. - herniated disc, tumour, trauma, ischaemia or infection disrupting pyramidal, spinothalamic, posterior column tracts on affected side.
What symptoms are experienced in Brown-Sequard syndrome?
Paralysis, loss of proprioception on same side as lesion, loss of pain, temperature sensation on contralateral side of lesion.
NORMAL sensation above level of lesion.
What is kinetosis?
Aka. motion sickness.
Powerful, maintained stimulation of the vestibular system can give rise to this. More likely to happen if the visual and vestibular inputs to cerebellum are in conflict. Cerebellum generates sickness signal to hypothalamus to bring about ANS changes.
What are the symptoms of kinetosis?
Nausea/vomiting, reduced BP, dizziness, sweating, pallor (ANS symptoms).
What is thought to cause menieres disease?
Over production of endolymph leading to increased pressure.
What are the symptoms of menieres disease?
Vertigo, nausea, nystagmus, tinnitus.
What drugs can damage the inner ear?
Streptomycin, gentamicin.
What sort of lesions cause nystagmus at rest?
Brainstem lesions.
What can cause raised ICP?
Cerebral oedema (can be post-traumatic) Space occupying lesions - tumours (e.g. glioblastoma multiforme), cerebral abscess, venous infarct with focal area of haemorrhage, meningioma, hydrocephalus, papilloedema, abscesses.
What are the signs associated with raised ICP?
Pupillary dilatation (stretch on Cr. N III - uncal herniation tends to put pressure on it), brainstem death due to coning, 6th nerve palsy, cognitive impairment, focal symptoms/signs, non-focal symptoms/signs, e.g. personality changes, drowsiness/altered consciousness, CSF obstruction can present with hydrocephalus).
What symptoms are associated with raised ICP?
Progressive headache (worse in morning/waking patient from sleep), visual obscurations, diplopia, blurred vision, pulsatile tinnitus, nausea, vomiting, somnolence.
What complications can result from raised ICP?
Herniation between the intracranial spaces, leading to ischaemia.
What are the different types of herniations that can result from raised ICP?
Right to left
Left to right
Uncal/tentorial - cerebellum moves inferiorly over edge of tentorium crushing cerebral aqueduct
Subfalcine - midline shift (cingulate gyrus pushed over to side and herniates under falx, crushing ventricle and displacing it downwards)
Coning - cerebellum moves into foramen magnum
Cerebellar tonsillar herniation - causes brainstem
How is raised ICP treated?
Head end elevation to facilitate venous return, osmotic agents (e.g. mannitol/hypertonic saline), hyperventilation (decrease CSF), barbiturate coma (decrease cerebral metabolism/coronary blood flow, maintain good PO2), surgical decompression.
What is a haematoma?
A localised area of haemorrhage.
Where do intracranial tumours tend to be in adults?
Above the tentorium.
Where do intracranial tumours tend to be in children?
Below the tentorium.
How do you investigate a suspected intracranial tumour?
History, examination, CXE, abdomen/pelvis/chest CT, mammography, biopsy skin lesions/lymph nodes (thinking of secondary sources), CT, mRI, biopsy, angiography if haemangioblastoma suspected.
What are the signs of a intracranial tumour?
Tumour close to/in CSF pathway (esp. posterior fossa) tend to block cerebral aqueduct or median/lateral apertures (esp. in children) causing hydrocephalus.
What symptoms are associated with intracranial tumours?
Focal neurological deficit (e.g. hemiparesis, dysphagia, hemianopia, cognitive impairment, cranial nerve palsy, endocrine disorder).
If on precentral gyrus weakness can indicate where lesion is.
If close to 4th ventricle can press on vomiting centre - N&V.
Presence of tumours above tentorium can focal/generalised epilepsy (1st fit - 20% tumour)
What is Gerstmann Syndrome?
Results from damage to the inferior parietal lobule of the dominant (left) side - it gives a typical set of symptoms (dysgraphia/agraphia, dyscalculia/acalculia, finger agnosia/anomia, left-right disorientation.
How are intracranial tumours treated?
Accurate tissue diagnosis, corticosteroids (dexamethasone), treat epilepsy (anti-convulsants), analgesics, anti-emetics, consuelling, radiotherapy, surgery, chemotherapy, endocrine replacement.
What are the various types of benign malignant primary intracranial tumours?
Those resembling glial cells - glioblastoma, astrocytoma, oligodendrolioma, ependymoma.
Childhood malignant tumour - medulloblastoma (resembles embryonic neural cells).
What are the types of benign intracranial tumours?
Meningioma (from arachnoidal cells)
Schwannoma, neurofibroma (from nerve sheath cells)
Adenomas (of the pituitary gland)
Lymphoma (from lymphoid cells)
Haemangioblastomas (from capillary vessels)
What sort of appearance to gliomas take on?
Diffuse edges, not encapsulated, malignant but do not metastasise outside the CNS.
What different types of astrocytes can you get?
Low grade astrocytoma (bland cells, similar to normal astrocytes, slow growing small cells with single nuclei).
Glioblastoma multiforme (most malignant astrocytoma, high grade, large tumour with necrosis, cellular, atypical, fast growing. Cells of tumour are large with multiple/irregular nuclei, this cancer spreads through the white mater and CSF pathway.
How do you treat a glioblastoma multiforme?
Complete surgical excision impossible, biopsy or debunk only, steroids, anticonvulsants, radiotherapy, chemotherapy (temazolamide).
What is the life expectancy with glioblastoma multiforme?
1 year.
What are meningiomas? How do they present?
From arachnocytes (cells that make the covering of brain). Benign, do not metastasise, but can be locally aggressive). Slow growing, extra-axial, often resectable.
Presentation - headache.
Where do meningiomas most commonly occur?
Along the falx, convexity, or sphenoid bone.
What is the appearance of meningiomas microscopically?
Bland cells forming groups sometimes with calcification.
Small groups of cells whorl around each other resembling an arachnoid granulation.
NB - calcification sometimes known as a psammoma.
How is meningioma treated?
Usually cured by surgery.
What is 8th vestibulochcochlear nerve schwannoma sometimes called? Where does this tend to occur and how does it present?
Acoustic neuroma. At angle between pons and cerebellum. Unilateral deafness. NB - it is benign.
What do adenomas of the pituitary gland often secrete?
Pituitary hormones.
How can pituitary adenomas present?
Visual disturbance (if impinges on optic chiasma), hormone imbalance.
What are lymphomas? What issues are there with treatment of lymphoma of the brain?
High grade neoplasms, usually diffuse large B cell lymphoma. Often deep and central site in brain (difficult to treat and biopsy). Generally doesn’t spread out CNS.
Difficulties in Rx - deep and central site, drug doesn’t cross BBB.
What are haemangioblastomas?
Tumours of the BVs, space occupying and may bleed (often into the cerebellum)
Why should you perform a lumbar puncture on a patient with a suspected IC mass?
DO NOT perform a LP on a patient with a suspected intracranial mass, as you could cause a herniation syndrome which could be fatal.
From where do cerebral metastases most commonly arise?
Breast, lung, kidney, colon, melanoma (mostly carcinomas).
NB - histological status identical to primary.
Where do brain tumours mostly commonly metastasise to?
Liver, lungs.
How common are cerebral mets?
15-30% of cancer patients get them. But rare in children.
How are cerebral mets treated?
Steroids, anti-convulsants, radiotherapy (whole brain, stereotactic), surgery.
If more than one lesion, radiotherapy is best.
How must you investigate if there is intracranial hypotension?
MRI brain and spine.
What can cause intracranial hypotension?
Spontaneous, iatrogenic (post LP), dural CSF leak.
What symptoms are associated with intracranial hypotension?
Headache (w. postural component, develops/worsens soon after assuming upright position, resolves/lessens after lying down).
Once headache becomes chronic, it loses its postural component.
