Neuro Flashcards
How common are brain tumours?
16th most common adult cancer, and 2nd most common children cancer
20/100000
Presentation of a brain tumour?
symptoms of raise ICP: headache, reduced conscious level, nausea and vomiting
progressive neurological deficit and epilepsy
Features of a raised ICP headache?
worst on waking from sleep, increased by coughing, straining and bending forwards, can be relieved by vomiting
What is the cardinal physical sign or a brain tumour?
papilloedema
What causes papilloedema?
obstruction of venous return from the retina
caused by loss of crisp optic nerve head margins, venous engorgement, retinal oedema, haemorrhages, raise ICP, intraneuronal ischemic damagee
What types of focal neurological deficits are there?
motor, sensory, speech, visual, deafness, deteriorating memory, personality change
What type of tumours are focal siezures more common in?
motor, sensory and temporal lobe
Are primary or secondary brain tumours more common?
secondary
Treatment of secondary brain tumours?
surgery, radiotherapy, chemotherapy, best supportive care
When would surgery be considered for a brain tumour?
absent or controlled primary disease, younger than 75, good performance status
Where is the main origin for primary brain tumours to occur from?
glial cells
What is the main type of primary brain tumour?
astrocytoma (85-90%)
oligondendroglioma (5%)
What is WHOs grading for gliomas?
1 - pilocytic astrocytoma (paediatric tumour)
2 - benign premalignant tumour
3 - anaplastic astrocytoma
4 - glioblastoma multiforme (THE MOST COMMON PHENOTYPE)
If given enough time, what will all gliomas progress to?
glioblastoma multiforme (GBM) with the exception of pilocytic astrocytoma
What is the common pathway to a malignant glioma?
initial genetic error in glucose glycolysis, mutation of isocitrate dehydrogenase 1 (IDH1), resulting in excessive build up of 2-hydroxyglutarate, triggering genetic instability in glial cells and subsequent inappropriate mitosis
What is the less common pathway to a malignant glioma?
no IDH mutation, catastrophic genetic mutation, poor prognosis
Survival of GBM?
20% survive more than 18 months, even with aggressive therapy
Good prognostic factors for a glioblastoma?
under 50, aggressive surgical therapy, good performance post surgery, secondary GBM, MGMT mutatnt (as they means they should respond to chemo)
Bad prognostic factors for a glioblastoma?
over 50, poor neurological function post surgery, non radical surgery treatment, primary GBM, MGMT wild type as means they wont respond to chemo
Traditional vs updated glioblastoma therapy?
debulking surgery, radiotherapy
respective surgery, adjuvant chemo with temozolomide with RT, 6 cycles of teozolomide chemo
How does temozolomide chemo treat brain tumours?
a prodrug, activated by HCl, crosses the blood brain barrier and then methylates guanine in DNA to make replication impossible at the base site
Which tumour is resistant to Temozolomide?
MGMT, by reversing guanine methylation
When does Temozolomide treatment work best?
any age, if debulk first, if performance status if low, no wild type MGMT
What is WHOs performance status for any cancer patient?
1 - capable of light work
2 - self caring >50% of day
3 - limited self care
How does avastin treat brain tumours?
it Is an anti angiogenic agent which shuts down the tumours blood supply
Side effects of avastin?
hypertension, GI haemorrhage, expensive
How does gene therapy treat brain tumours?
inoculation of tumour with replication deficient HSV-1 retrovirus so wild type HSV-1 replicates exponentially and causes encephalitis
modified HSV-1 fails to replicate in normal brain but replicates rapidly in GBM, causing oncolysis and release of progeny virus
tumour cells killed and normal brain cells unaffected
How does dexamethasone treat brain tumours?
powerful synthetic steroid, given orally, improving brain performance, reduces tumour inflammation and oedema
In who is a benign glioma commonly seen?
in the young, rare over 45
What is the first symptoms of a benign glioma?
siezures
What causes detioration in a benign glioma?
tumour transformation into a malignant phenotype, progressive mass effect due to slow tumour growth, progressive neurological deficit from destructional tumour
Prognosis of an oligodenroglioma?
10-15yrs, can transform into anaplastic or GBM
Treatment for oligodendroglioma?
chemotherapy
What genetic deficits are in an oligodendroglioma?
chromosomes 1 and 19, IDH1 mutation positive
What causes neurological deficit in brain tumours?
mass effect of tumour and surrounding cerebral oedema, deficit depends on tumour location
What are the most common focal neurological signs seen from raised ICP in brain tumours?
3rd and 6th cranial palsy from stretching of the nerves by downward displacement of the temporal lobes
DD of brain tumour?
intercranial mass lesions e.g. cerebral abscess, tuberculoma, subdural haematoma, intercranial haematoma, stroke, benign intracranial hypertension
Investigations of a brain tumour?
imaging with CT and MRI, MR angiography, PET scan, CXR for metastases, avoid LP
Risk factors of brain tumours?
ionising radiation, genetics, male, Africa, age
What is MS?
multiple sclerosis - an autoimmune, inflammatory, demyelinating disease specific to the CNS which causes chronic neurological disability
What is the mean onset of MS?
30 years
Pathophysiology behind MS?
inflammation in white matter of the CNS, producing antibodies against EBV nuclear antigens which then attack CNS myelin due to molecular mimicry, causes demyelinations and axonal loss, causing MS plaques
Risk factors for MS?
Caucasians due to less vit D, women, predisposition to EBV in children
What is relapsing remitting MS?
random attacks over a number of years, mainly in first 3-4 years, recovery varies between patients and between attacks, disabilities accumulate with each attack
What is chronic progressive MS?
slow decline in neurological functions either from the onset (primary) or following a relapse (secondary)
What is benign MS?
few relapses and little disability
Features of active MS?
demyelination (breakdown products present), variable oligodendrocyte loss, hypercellular plaque edge due to infiltration of tissue with inflammatory cells, perivenous inflammatory infiltrate, extensive blood brain barrier disruption, older active plaques have central gliosis
Features of inactive MS?
demyelination (breakdown products absent), variable oligodendrocyte loss, hypocellular plaque, variable infllamtory infiltrate, moderate to minor blood brain barrier disruption, plaques gliosed
Common sites and symptoms of MS?
cerebral hemispheres - large variety of symptoms
spinal cord - weakness, paraplegia, spasticity, tingling, numbeness Lhermitte’s sign, bladder, sexual dysfunction
optic nerves - impaired vision and eye pain
medulla and pons - dysarthria, double vision, vertigo, nystagmus
cerebellar white matter - dysarthria, nystagmus, intention tremor, ataxia
Typical symptom of MS?
optic neuritis, spasticity, sensory symptoms and signs, Lhermittes sign, nystamus, double vision, vertigo, bladder and sexual dysfunction. gait
Atypical symptoms of MS?
aphasia, hemianopia, extrapyramidal movement disturbance, severe muscle wasting, muscle fasciculation
What are the first symptoms to present in MS?
weakness, parasthesiae and visual loss
What is the essential diagnostic criteria for MS?
two or more CNS lesions, disseminated in time and space, exclude other clinical conditions
Investigations for MS?
EP, MRI, CSF electrophoresis shows IgG oligoclonal bands, neurological examination, history, symptoms
DD for MS?
SLE, autoimmune disease, lyme disease, syphilis, AIDS, adrenomyeloneuropathy, cardiac embolic event, mitchochondrial encephalopathy
Treatment of MS?
IV methylprednisolone, SC B IFN
side effects of B IFN?
injection site reaction, flu like symptoms complex, mild intermittent lymphopenia, mild to moderate rises in liver enzymes, flu like symptoms
Treatment of spasticity in MS?
oral - baclofen, diazepam
peripheral never blocks e.g. phenol, alcohol, botox
intrathecal baclofen
functional neurosurgery
physio
remove trigger factors e.g. UTI, bed sores
Treatment of tremor in MS?
BBs, low dose barbiturates, gabapentin, isoniazid, wrist bands containing small weights, computer controlled mechanical damping devices, stereotactic thalamotomy, thalamic electro stimulation
Treatment of sexual dysfunction in MS?
sexual counselling, intracorporeal inhection of PGE, penile prosthesis, Viagra, vibrators, lubricating gels, local anaesthetics,
Psychological effects of MS?
depression, anxiety, euphoria, pathological crying/laughing, cognitive dysfunction
Characteristics of fatigue specific to MS?
fundamentally different from ordinary fatigue, exacerbating by heat, improved by cool temperatures, makes other symptoms appear worse
The cause of pain in MS?
trigeminal neuralgia, painful tonic seizures, optic neuritis, vertebral compression fractures, ulnar and peroneal palsies, haemorrhagic cystitis, dysaesthic extremity pain, painful leg spasms, chronic joint and back pain
Characteristics of paroxysmal symptoms in MS?
brief duration, occur frequently, triggered by various factors, positive symptoms, usually respond to anti convulsant therapy
What is an impairment?
any loss of abnormality or psychological or anatomical structure or function
What is a disability?
any restriction or lack of ability to perform and activity in manner or within normal range
What is a handicap?
a disadvantage for a given individual resulting from an impairment or disability that limits or prevents the fulfilment of a role that is normal for that individual
What is neurological rehabilitation?
restoration of the individual to the highest feasible functional level physically, psychologically, socially, economically with the constraints of impairemtns and disabilities and within the context of cultural mileu
Wht is involved in MS physio?
special seating, moving ad handling techniques, passive stretching, standing and weight bearing, splints, serial casting
How does GABAb baclofen treat spasticity?
reduces calcium influx, suppresses release of excitatory neurotransmitters and post synaptic increase in potassium conductance
How does Tizanidine treat spasticity?
alpha2 agonist, peaks at 2 hours
CI of Tizanidine?
hepatic impairments
SE of Tizanidine?
dry mouth, hypotension, acute hepatitis, withdrawal, weakness
How does dantrolene treat spasticity?
causes muscle relaxtion by interfering wuth calcium influx
SE of dantrolene?
diarrhoea, avoid in liver disease
How does Botox treat spasticity?
relatively localised hypertonia,
How does THC (weed) treat MS?
CB1 presynaptic receptors inhibit calcium influx, inhibits glutamate release and activates potassium channels
What causes gait in MS?
weakness, foot drop, sensory ataxia, cerebellar ataxia, spasticity, drug side effects, fatigue
Treatment of gait in MS?
treat cause, physio, fall education, walking stick, orhoptics, functional electrical stimulation, famipridine, botox
How does dalfampridine treat MS?
prevents back propagation of action potentials, inhibits postassium channels so there is better conduction along demyelinated axons
What does detrusor overactivity cause?
frequency, urgency, incontinence
What does detrusor areflexia cause?
flaccid, large bladder
What does detrusor sphincter dysnergia cause?
incomplete bladder emptying
What does sphincter over activity cause?
retention and hesitancy
What does sphincter incompetence cause?
dribbling
What is the diagnosis criteria called for MS?
McDonalds criteria
Which nerves are never affecting in MS?
peripheral
What percent of strokes are caused by intracerebral haemorrhages
10-15%
How does an intracerebral haemorrhage present?
sudden onset headache, drowsiness, vomiting, focal deficit
What is dementia?
describing symptoms of poor memory and difficulty learning
What causes dementia?
damage to brain cells, the most common cause being Alzheimer’s
What is Alzheimer’s?
a neurodegenerative disease, mainly in the cortex, causing plaques and tangles, leading to dementia
What does the Amyloid Precursor Protein do?
helps neurons in the brain grow and repair itself after an injury
What enzyme breaks down the APP and what does this lead to?
alpha-secretase and gamma-secretase, and the broken up protein parts are soluble and go away
What happens when beta-secretase and gamma-secretase breaks down APP and what does this lead to?
the left over fragment is not soluble and forms the monomer amyloid beta which are chemically sticky and bind together outside the neurons, leading to beta amyloid plaques which can get between neurons and inhibit neuron signalling so memory is impaired and can cause an autoimmune response, damaging surrounding neurons, can also deposit around blood vessels, lead to amyloid angiopathy, increasing risk of haemorrhage, rupture and blood loss
What 3 things can amyloid beta lead to in Alzheimer’s?
beta amyloid plaques, autoimmune inflammation and amyloid angiopathy
What are tangles in Alzheimer’s?
found inside the cell
What protein holds together neurons in the brain?
tau protein
What effect do beta amyloid plaques have
inhibit neuron signally and initiates activation of kinase in the neurons, which transfer phosphate groups to the tau protein so it changes shape and then the tau protein can no longer support the microtubules, clumps together with other tau proteins and gets tangled, leading to neruofibrially tangles
What do neurofibrially tangles lead to in Alzheimer’s?
signals cannot be passed along the neurons in the brain and can lead to apoptosis leading to brain atrophy, narrow gyri, wider sulci and larger ventricles in brain
What are the two types of Alzheimer’s?
sporadic and familial
What is sporadic Alzheimer’s?
late onset, unknown cause, due to genetic and enviromental risk factors, the most common time, risk increased with age, linked to e3 allele of apolipoprotein E gene (APOE-e4), the risk increases if more of these genes were inherited
How common is sporadic Alzheimer’s?
most common Alzheimer’s
1% age 60-65
50% age 85
Function of apolipoprotein E?
breaks down beta amyloid
Why does APOE-e4 genes develop Alzheimer’s?
the gene is less effective at breaking down beta amyloid, leading to increased plaques
What is familial Alzheimer’s?
dominant gene speeds up progression, early onset, caused by
gene mutations in PSEN1 (c14) or PSEN2 (c1) gene are linked as they encode for presenilin 1 and 2 which are subunits of gamma secretase, so will change the location of APP splitting, increasing beta amyloid OR Trisomy 21 (Downs) which has an extra copy of c21 which codes for APP gene which increase amyloid plaque build up
Symptoms of Alzheimer’s?
can be undetectable in early stages then leads to short term memory, loss of motor skills, language is affected, then lose long term memory, until more disorientated and bedridden
What is the most common cause of death in Alzheimer’s?
infection e.g. pneumonia
How do you diagnose Alzheimer’s?
brain biopsy (after death) so must just exclude other causes of dementia for diagnosis
Treatment of Alzheimer’s?
no cure, few medications which help and none that hault progression
Functions of the frontal lobe?
voluntary and planned motor behaviours, motor speech area, personality, planning
What happens in fronto temporal dementia?
personality and behaviour change followed by breakdown in attention and executive function (behavioural variant FTD)
Function of the temporal lobe?
hearing, language, semantic knowledge, memory, emotional/effective behaviour
What is HM amnesic?
severe epilepsy, profound failure to create new memories
Treatment of HM amnesic?
surgery to bilateral to remove medial temporal lobes including hippocampus
What is preclinical Alzheimer’s?
amnesic prodrome which memory impairment, poor performance on episodic memory tests, cognitive function is preserved, scored on cognitive/memory screening, high risk of developing Alzheimer’s
What is used to assess cognitive function?
6CIT
What is involved in the 6CIT?
what year is it? what month is it? give an address with 5 parts? count down from 20 say months of year in reverse repeat address
definition of functional memory disorder?
acquired
>6 months
affect personal/professional life
psychosocial burden/psychological distress
verbal memory and attentional capacity >-1.5SD
absence of organic cause of cognitive memory
absence of major psychiatric disease (severe depression)
What is the criteria called for Alzheimer’s?
consensus criteria Braak
1/2 = low likelihood
3/4 = intermediate likelihood
5/6 = high likelihood
diagnosis in intermediate of high likelihood of Alzheimer’s are met and patient has clinical history of dementia
What condition is Alzheimer’s linked to?
parkinson’s disease
Investigations for Alzheimer’s?
PET and SPECT, functional MRI
Management of Alzheimer’s?
prevention, support, carers, advice, medications, socially active, cognitively active, control vascular risk factors, treat mood and anxiety
What are Caerphilly healthy behaviours for Alzheimer’s?
no smoking, BMI 18-25, 3 or more portions of fruit/veg, and less than 30% of calories from fat, walking 2 or more miles each day, or vigorous exercise as a regular habit,
What medications can be used for Alzheimer’s?
AtCh esterase inhibitors e.g. exelon, aricept, reminyl or memanrine (anti glutamate) or NMDA receptor antagonists e.g. namenda
Screening and staging instruments for mental status?
MMSE, mental state questionnaire, clinical dementia rating, global deterioration scale, ACE-R, CERAD, CAMDEX, ADAScog, MoCA
What are the 5 diffferent cognitive areas in the MMSE?
orientation, memory, attention, language, visual processing
What tests and questions are used for Alzheimer’s testing?
address, date, birth, priminister, clock drawing test, fluency test or letters and design, how many animals can you name in one minute, card sorting test, stroop test, visualspatial memory and visuocontructive abilities, constructional apraxia, closing in phenomenon, £D visuoconstructive abilities, non verbal intelligence, abstract reasoning, verbal comprehension, spontaneous speech
What preventitive drugs can be used for Alzheimer’s?
manage vascular risk, statins, antioxidants, anti inflammatory drugs, oestrogen, social interventions
What is epilepsy?
recurring, unpredictable siezures
What is a seizure?
when neurons are synchronously active in the brain, it is a paroxysmal event which changes behaviours, sensations and cognitive behaviour, caused by an abnormal burst of electrical impulses or too little inhibition
What happens in epilepsy with too much excitation?
fast of long lasting activation of NMDA which causes calcium to come in
What happens in epilepsy with too little inhibition?
There is too little GABA receptors so cannot inhibit signals
Potentially causes of epilesy?
primary, or secondary to tumours, brain injury and infection
What are common outward signs seen in epilepsy?
jerking (typically beginning in corner of mouth and thumb and spreading to the limbs), moving, losing consciousness, starts on one side and then moves to the other, can be followed by a period of complete paralysis
What are common inward symptoms seen in epilepsy?
fears, strange smells
What are the 2 types of seizures?
generalized or focal/partial - depends on how much of the brain is affected
What are the two types of partial seizure?
simple and complex
What happens in a simple parital seizure?
affects small part of brain remain conscious strange sensations and jerking movements can be a warning that another seizure is coming be aware that something is happening remember the seizure sense of deja vu
What is a Jacksonian march?
when movements start in on e group of muscles and spreads to other groups
What happens in a complex partial seizure?
impaired consciousness/impaired awareness
unresponsive
may not remember
may just be small movements e.g. smacking lips, rubbing hands, moving arms
What is Todd’s paralysis?
the paralysis post seizure
DD for blackouts?
syncope, non epileptic seizure, epilepsy
What is a generalized seizure?
When both hemispheres are affected (secondary if starts as a partial seizure)
What is a tonic seizure?
muscles become stiff and flex, can lead to a fall backwards
What is an atonic seizure?
muscles become relaxed and can lead to a forward fall
What is a colonic seizure?
violent muscle contractions (convulsions)
What are tonic-clonic seizures?
most common generalized seizure, have a tense phase when the patient stiffens up and then the muscles start to rapidly contract
What are myoclonic seizures?
short muscle twitches, can be just a single twitch or can be lots
What are absence seizures?
patient loses consciousness and then quickly regains it, the patient may just look spaced out
What is status eplilepticus?
seizure >5 mins, or multiple seizures without returning to normal
normally tonic clonic type seizure
medical emergency
Treatment of status epilepticus?
acutely with benzodiazepines, o2, cardiorespiratory monitoring, vitamins IV
How do benzodiazepines treat epilepsy?
enhance effect of the inhibitor GABA
What symptoms follow seizures?
confusion (post ictal confusion), paralysis of arms and legs (normally on one side but can last up to 15 hours - Todds paralysis)
What causes Todd’s paralysis?
temporary severe suppression of activity in the brain which was affected by the seziure
What investigations are done in epilepsy?
MRI, CT, EEG - to find anatomical abnormalities
evaluation of seizure and eye witness accoutns
Function of EEG?
detects electrical activity in the brain
Treatment of epilepsy?
anti convulsants based on the patient
epilepsy surgery if small part of the brain can be removed
nerve stimulation influences vagus nerve to influence neurotransmitter release to reduce frequency and severity of seizures
ketogenic diet so body burns fat not carbohydrates which produces ketone bodies which are used as an energy source by the brain instead of glucose
stress relievers, avoid triggers, avoid contact sports and swimming, and must be seizure free for a year to drive
deep brain stimulation implants electrode into specific areas of the brain, reducing abnormal electricity, reducing frequency of seizures
Who do absence seizures commonly affect?
children, can appear as a stop in conversation or daydream
How long do complex partial seizures last for?
around 2-3 minutes
Triggers of epilepsy?
flashing lights, CV disease, cerebral tumours, alcohol, post trauma, genetics
What anti epileptic drugs are used for focal seizures?
Lamotrigine and Carbamarzepine
pre synaptic and stop excitary signals
What anti epileptics drugs are used for generalized seizures?
lamotrigine and sodium valproate
Side effects of anti epileptic drugs?
memory problems, hepatic enzyme inhibition, weight gain, hair loss, rashes, leucopaenia
What is the dosage of anti epileptic drugs?
start low and gradually build up, until seizures stop or until you develop side effects, aim to achieve control with minimum dosage, and there is risk of intoxication which can lead to ataxia, nystagmus and dysarthria
When should to do surgery for epilepsy?
when only a single part of the brain is causing the seizures and it can be removed without causing any significant loss of brain function
Side effects of anti epileptic drugs?
it is a shock every 5 minutes for 30 seconds, hoarseness, sore throat and cough
Symptoms of non epileptic seizures?
pelvic thrusting, no tongue biting, eyes closed, crying/speaking, change in amplitude not frequency of activity
Side effects of DBS?
bleeding on the brain, depression, memory problems
What cause a non epileptic seizure?
mental process caused by psychosocial distress, and seizure instead of the emotion, it is situational and can last 1-20 minutes
What causes syncope?
fainting, changing behaviour sensation and cognitive processes, causing by insufficient blood of O2, from standing or sitting, lasting 5-30 seconds, has less warning and a history of heart disease
What is parkinsonism?
a triad of symptoms of tremor, rigidity/increased tone and bradykinseia
How common is Parkinson’s?
- 3% of population over 40
- 5 million worldwide
more common in men
most common at 65
Sign and symptoms of Parkinson’s?
tremors, rigidity, bradykinesia, postural instability
hypominia, dysphagia, hypophonia, blurred vision, eyelid opening apraxia, gait (shuffling, freezing)
reduced smell, constipation, visual hallucinations, frequency, urgency, dribbling of saliva, depression, dementia
What part of the brain is mainly affected in Parkinson’s?
basal ganglia - which is responsible for muscle tone and ease of movemt
What makes up the basal ganglia?
caudate nucleus, caudate putamen, globus pallidus (interna and externa), nucleus accumbens, subthalamic nuclei, substantia nigra (2 parts)
Function of the basal ganglia?
cerebral cortex sends signals to the basal ganglia to initiate movement. The basal ganglia will control skeletal muscle tone and coordination of learned movements and then it will send signals back to the cortex (motor) via the thalamus to then be initiated down the spinal cord, out of the ventral horn to have normal movement pattern
How is the basal ganglia affected in Parkinson’s?
problem with the output, so no normal controlled movement pattern
Function of substantia nigra?
has dopamine neurogic neurons which release dopamine into the striatum which then binds to dopamine 1 or 2 (excitory or inhibitory)
Pathophysiology of Parkinson’s?
reduced dopamine in the substantia nigra leading to apoptosis or necrosis of dopaminergic neurons
caused by protein misfolding, aggregation and toxicity, defective proteolysis, mitchondrial dysfunction, oxidative stress
demyelinataion, neuronal loss and glyosis in substantia nigra, presence of Lewy bodies
lack of dopamine mean it cannot bind to GABA neuron so the inhibitory GABA is overstimulated causing glutamate secretion, causes excessive inhibitor input to the thalamus causing suppression of thalamocorticospinal pathway, so movement is not smooth
What are Lewy bodies?
round eosinophilic intra cytoplasmic occlusions in the nuclei of neruone, made up mainly of alpha-synciclein ubiquitin and other proteins
Risk factors of Parkinson’s?
familial, GBA, CNCA, LRRK2, PARK2 and PINK1, pesticides, survivors of the encephalitis lethargica
Protective factors of Parkinson’s?
smoking, coffee, vigorous exercising, NSAIDs
Treatment of Parkinson’s?
Levodopa, dopamine agonists, monoamine oxidase B inhibitors, catechol-o-methyltransferase inhibitors, BBs, antichloinergics, physio, dietitian, language therapist, specialist nurse, counselling, surgery, DBS
How does levo-dopa treat Parkinson’s?
it is a precursor to dopamine to improve symptoms
What does levo dopa need to be prescribed with and why?
a peripheral dopadecarboyxlase inhibitor e.g. benserazide to prevent it being converted to dopamine too early in the bloodstream, and reduces it peripheral side effects (nausea and compulsive behaviours)
How do dopamine agonists treat Parkinson’s and what are the side effects?
act as a dopamine agonist and do not need to be converted in the body to become active, but risk of impulsive control disorders and excessive sleepiness
How do MAO-B inhibitors treat Parkinson’s?
e.g. selegiline and rasagiline inhibit levodopa and dopamine breakdown so the effects last longer
How do COMT inhibitors treat Parkinson’s?
prevent levodopa breakdown, so more of the dose can reach the brain
What is a myasthenia gravis?
chronic, acquired, autoimmune neuromuscular disease
Pathophysiology of myasthenia gravis?
autoantiboies to acetylcholine receptors (anti-AChR antibodies) at the post synaptic membrane, causing depletion of working post synaptic receptor sites and interfering with the neuromuscular junction
associated with HLAB8 and DR3, or induced by drugs e.g. penicillin
When does myasthenia gravis occur?
most common in young women under 40 and old men over 60
can be passed onto neonates
15/100,000 but is underdiagnosed
What diseases is myasthenia gravis associated with?
other autoimmune disease, thymic atrophy, tumour of SLE
Signs and symptoms of myasthenia gravis?
drooping eye, slurred speech, difficulty breathing, blurred/double vision, weakness in arms and legs, change in facial expression, unable to hold a steady gaze, difficulty chewing, weakness in proximal muscles, affect diaphram and resp troubles
What exacerbates and relieves myasthenia gravis?
exacerbated in exercise but relieved by rest
Causes of myasthenia gravis?
bone marrow transplant, or IFN-a medication,
Why is the thymus large at birth?
as it is responsible for immune response and the immune system is low at birth, it decreases in size as we get older
What size is the thymus in myasthenia gravis?
abnormal and large, can people can develop thymoma,
Investigations for myasthenia gravis?
examine eyes and muscles for signs of weakness
anti AChR positive or anti MuSK positive
CT and MRI look for thymoma
nerve conduction measured - fatigue will occur quicker in myasthenia gravis
single fibre EMG measure elecrtical potential form nerve to muscle, lower in myasthenia gravis
ice test, crushed ice in glove over eye for 3 minutes, which leads to imporved ptosis in myasthenia gravis
Treatment of myasthenia gravis?
increase sleep, avoid stress and excessive heat, rest, immunosuppressants e.g. prednisolone, acetylcholinesterae inhibitors inhibitors for temporary symptomatic relief by increasing ACh availiability (but beware of cholinergic crisis), osetoporosis prophylaxis, modified diet if difficultuy swallowing, thymectomy
What is myasthenia gravis cholinergic crisis?
weakness of the respiratory muscles during a relapse which is life threatening
Treatment of myasthenia gravis cholinergic crisis?
monitor FVC, ventillatory support, plasmapheresis, IV Ig, identify triggers and treat them
Prognosis of myasthenia gravis?
5% mortality with treatment
25-30% without treatment
inter current infection and hot weather aggravate it
What is Guillain Barre syndrome?
acute inflammtory demyelinating and occasional axonal polynaruopathy
Causes of Guillain Barre syndrome?
infection leading to shared epitopes with an antigen in the peripheral nerve tissue (ganglioside GM1 and GQ1b) leading to an autoantibody mediated nerve cell damage
triggers of Guillain Barre syndrome?
infection with campylobacter jejuni, EBVm CMV, post pregnancy (risk decreases during pregnancy), malignancies, vaccines
How common is Guillain Barre syndrome?
1/100,000 a year, everyone equally likely to get it, but more men than female had it and peak ages are 15-35 and 50-75
What is the first symptom in Guillain Barre syndrome?
paraesthesia and sensory loss in lower extremities
Symptoms of Guillain Barre syndrome?
ascending symmetrical weakness, neuropathic pain in legs and pain, reduced or absent reflexes early, reduced sweating, reduced heat tolerance, bladder weakness, postural hypertension, cardiac arrhythmias, urinary hesitancy
Complications of Guillain Barre syndrome?
can lead to paralysis, and can be severe if respiratory and facial muscles are involved which can cause respiratory fialure, hypo/hypertension, cardiac arrhythmia, urinary retention, ileus, pneumonia
DD for Guillain Barre syndrome?
stroke, brianstem compression, cord compression, poliomyelitis, myasthanthia gravis, hypokalaemia, vasculitis, botulism, encephalitis
Investigations for Guillain Barre syndrome?
high ADH secretion LP - increased CSF protein antibodies present nerve conduction studies ECG MRI to exclude other causes
Management of Guillain Barre syndrome?
plasma exchange, IV Ig, corticosteroids, DVT prophylaxis, ITU for ventilation and intubation, pain relied, physio, nasogastirc feeding if swallowing problems, counselling
Prognosis of Guillain Barre syndrome?
good, but 10% die from resp failure, pulmonary emboli, infection or prolonged paralysis
poorer prognosis if old, rapid progression of symptoms, prolonged ventilation, preceding diarrhea, muscle dysfuction
What is the Miller Fisher syndrome?
variant of Guillain Barre syndrome that affects cranial nerves to the eye muscles and presents with opthamoplegia and ataxia
What are the different subtypes of Guillain Barre syndrome?
AIDP (95%) AMSAN (GM1, GM1b and GD1a) AMAM ASN acute pandysautomina
What is giant cell arteritis?
aka temporal arteritis - granulomatous arteritis with inflammed medium and large arteries leading to occlusion o the lumen leading to ischemia of the optic nerve
In who does giant cell arteritis occur?
over 60s, related to polymyalgia rheumatic in 50% of cases
Symptoms of giant cell arteritis?
fever, fatigue, headache, SCALP PAIN, headache in front or on temples, JAW PAIN and claudication, diplopia, ptosis, blurred vision, amaurosis fugax, symptoms develop quickly, tenderness of temporal artery
What are the specific symptoms for giant cell arteritis?
jaw claudication and pain, scalp pain
Diagnosis of giant cell arteritis?
biopsy of temporal artery to confirm with GRANULOMATOUS CHANGES, elevated inflammatory markers, increased platelets and alkaline phosphate, decreased Hb, normonchromic, normocytic anaemia
Treatment of giant cell arteritis?
prednisolone immediately during biopsy, high dose methylprednisolone injection then prednisolone tablets, start high dose and then decrease, low dose aspirin, PPI to protect against stomach ulcers, immunosuppressants during prednisolone reduction, gastric and bone protection
Complications of giant cell arteritis?
irreversible bilateral visual loss, CV disease
What trigeminal neuralgia?
paroxysm of intense, sudden, stabbing pain in trigeminal never distribution from compression of the trigeminal nerve where it enters the brainstem, this pressure wears away at the myelin sheath causing uncontrollable pain
Symptoms of trigeminal neuralgia?
intense, sharp jabbing pain in forehead, cheek or jaw, dental pain, pain on one side of the face
Causes of trigeminal neuralgia?
MS, tumours on the nerve, compression of the nerve by a small artery or vein as it leaves the brain stem
What are the 3 branches of the trigeminal nerve and which is the least common to get trigeminal neuralgia?
mandibular, maxially and opthalamic (least common)
the pain is usually in 1 or 2 of the divisions
Triggers of trigeminal neuralgia?
washing the affected area, shaving, eating, talking, dentist, kissing, cold breeze, head movement, vibrations, hot or cold food, caffeine
DD of trigeminal neuralgia?
root canals
Investigations in trigeminal neuralgia?
rule out other conditions with MRI and history
Treatment of trigeminal neuralgia?
anticonvulsants e.g.carbamazipine to relieve nerve pain and slow down electrical impulses in the nerves and reducing the ability to transmit pain, it becomes less effective over time
gabapentin, phenytoin
thermocoagulation of the trigeminal ganglion or section of the sensory division
microvascular decompression to seoarate vessels from nerve root
stereotactic knife surgery - effective but has complications of facial numbness, hearing loss, stroke and death
injection of glycerol into the nerve
Side effects of carbamazipine?
tiredness, dizziness, confusion, nausea, double vision, leukopenia, depression
What is anesthesia dolorosa?
rare combination of numbeness and continuous pain in trigeminal neuralgia, it is virtually untreatable
What is the ganglion called where all 3 trigeminal nerve branches meet?
Gasserian ganglion
What is Huntington’s disease?
neurodegenerative disease cauign atrophy and neruonal loss of striatum and cortex, leading to depletion in GABA and ACh, also increasing lenght of CAG triplet
What is the huntington gene and what chromosome is it on?
a increased in length of a cysteine-adenosine-guanine triplet repeat in the huntington gene on c4, the longer the repeat the earlier the onset of the disease
How common is Huntington’s disease?
1/10,000, it is familial, autosomal dominant, 50:50 change of passing it on
Symptoms of Huntington’s disease?
clumpsy, restless, muscle twitches and spasms, become more difficult to perform tasks, CHOREA
poor communications and starting conversations and undersatnd
poor attention spam and memory
depression, apathy, change in sexual behavior, anxiety, aggressive,
When does Huntington’s disease usually present?
30-60years, 6% are juvinile though, people die 10-20 years after diagnosis
Pathophysiology of Huntington’s disease and the 3 types?
a normal huntington gene has 20 or less CAG repeats but in Huntington’s disease there are 3 types:
1 - 27-35 repeats
2 - 36-39 repeats
3 - over 40 repeats
all the repeats code for a mutant huntington gene with long sticky tail of glutamine which all stick together and form clumps which end up in the nucleus and is thought to disrupt signals and kills cells
the more repeats, the earlier the onset
Treatment of Huntington’s disease?
no treatment so aim to relieve symptoms, healthy lifestyle, SSRIs for depression, speech and physical therapy, occupational therapy, benzodiazepienes for chorea, levodopa and dopamine agonists for bradykinesia and rigidity
genetic testing, counselling and education
Symptoms of juvenile Huntington’s disease?
parkinsonian features, dystonia, pyramidal tract signs, dementia, epilepsy, mild or absent chorea, behavioural and learning difficulties
What is a transient ischemic attack?
a mini/warning stroke, normally last less than 5 minutes and symptoms resolved in 24 hours, caused by brief ischemia from a block blood vessel to the brain, it is not long enough to cause permanent damage
Risk factors of TIA?
age, FH, male, alcohol, hypertension, smoking, hyperlipidaemia, DM, obesity, high fat diet, stress, emoboli, south asian, african, caribbean
Pathophysiology of TIA?
emboli in carotid artery with existing stneosis and plaques, leads to impaired perfusion of the brain
Symptoms of TIA?
contralateral hemiparesis (weakness on opposite side of body), dysarthria (slurred sppech), vision problems, gait disturbance, carotid bruit from atherosclerosis, increased BP, heart murmur
Causes of TIA?
atherothromboembolism, caridoembolism, mural thrombus post MI or in AF, valve disease, prosthetic valve, hyperviscosity, polycythamia, sickle cell anemia,, leukostasis, myeloma, vasculitis
DD of TIA?
hypoglycaemia, migraine aura, focal epilepsy, hyperventilation
Tests for TIA?
carotid US, CT of head, test for hypertension , diabetes, cholesterol, ECG, eye exam, doppler and angiography
Treatment of TIA?
prevent stroke - antiplatelets, aspirin, warfarin, clopidogrel, statins for cholesterol, carotid endarterectomy to remove plaque and correct stenosis, intraoperative transcranial Doppler to monitor middle cerebral artery flow, healthy lifestyle, avoid driving for 1 month, antihypertensives, stop smoking and drinking
What is amarurosis fugax?
caused by an emboli passing into the retinal artery and causes a temporary loss of vision in one eye due to lack of blood flow to the retina
What is the risk of a stroke after TIA based on?
ABCD2 risk
>60(1), BP>140mmHG or 90mmHg diastole(1), unilater weakness(2), speech distubrance without weakness(1), >60mins(2), 15-59mins(1), diabetes(1)
What is meningitis?
an inflammation of the lepto meninges and underlying subarachnoid CSF
What are the most common pathogens for meningitis for kids, adults, elderly and neonates?
adults - strep. pneumoniae, neisseria meningitis, listeria monocytogenes
kids - listeria monocytogenes, pneumococcus, neisseria meningitis
neonates - group b strep, e.coli
elderly - listeria monocytogenes
mainly viral > bacterial > fungal
aerobic gram negative bacilli associated with trauma/neurosurgery
Risk factors for meningitis?
immunocompromised, C5-C9 deficiency, injections, VP shunts, splenectomy, transplants, in crowds, DM, alcoholic, cirrhosis, infection, surgery, itrathecal durgs, tumours, SLE,
Symptoms of meningitis?
fever, vomiting, severe headache, stiff neck, dislike of bright lights, seizures, rash, very sleepy/difficult to stay awake, confused/delirious, altered mental sate, non blanching petechial and purpric skin rash, cold hands and feet, papiloedema, Kernigs sign (inability to extend knee when hip is flexed), Brudzinski sign (spontaneous flexion of the hip with active flexion of the neck)
DD of stiff neck?
infections in head and neck e.g. pharygitis
What are latent viral infections?
VZV, HSV, HIV, priors
Toxin mediated diseases?
botulism, tietanus
Immune mediated disease?
Guillian Barre, post infection, ADEM, HLE
Investigations for meningitis?
CBC w/diff, Chemo10, 2 blood cultures, CT head no contrast (but dont do if no focal neurological findings), LP (but obtain CT first if needed to identify ICP) and CSF studies, gram stain, HSV PCR, cryptococcal Ag, TB PCR, fungal PCR
What are bacterial CSF results like?
cloudy/yellow, increasing opening pressure, increased protein, decreased glucose, increased WBC (PMN), gram positive
What are viral CSF results like?
cloudy/clear, gram negative, increased lymphocytes
What are fungal/TB CSF results like?
cloudy/straw, increased opening pressure, increased protein, gram negative, lymphocyes
Complications of meningitis?
hydrocephalus, abscess, cerebritis and cranial nerve lesions, thrombosis, infarct, ventriculitis and ventriculopathy, extra axial collections, seizures, DIC, septic shock, SIADH, decreased hearing
DD of meningitis?
malaria, encephalitis, septicaemia, subarachnoid haemorrhage (have blood in csf), dengue, tetanus
Management of viral meningitis?
IMMEDIATE ANTIBIOTICS (55 or immunocompromised = cefotaxime and amoxicillin due to listeria risk) - they must be able to pass the blood brain barrier
aciclovir is encephalitis suspected
IV fluids and inotropes if septicaemia
TB meningitis treated for 9 months
dexamethasone if pneumococcal menigitis
vancomycin added if travelled to area of increased pneuomococcal resistance
ganciclovir for CMV infectiosn
corticosteroids if hearing loss and neurological sequelae
benzylpenicillin if penicillin sensitive organiism
Which organism has the poorest prognosis in meningitis?
pneuomococcal meningitis
What is shingles?
a skin rash caused by infection of the herpes zoster virus (also causes chicken pox)
Symptoms of shingles?
pain that precede the rash and rash in a cluster or band, headache, burning/itching in affected skin, fever
Cause of shingles?
when the herpes zoster virus becomes reactivated, it normally is dormant, but become reactivated during lowered immunity during stress,
How does the shingles rashs progress?
initial red blotches on the skin, just develops into itchy blisters which contain the virus, eventually they become yellow, flatten and dry out, leaving a scab
What is ophthalmic shingles?
when it affects one of the eyes when the reactivated virus is in the trigeminal nerve, causing rash over forehead, nose, eye, conjunctivitis, red eye and vision problems
How to prevent spread of shingles?
not sharing towels, dont swim or play contact sport, avoid work if rash is weeping and cannot be covered, avoid pregnant women who haven’t had it yet, avoid immunocompromised
Treatment of shingles?
antiviral medications e.g.acyclovir, preferably become blisters appear
prednisolone, analgesics, cool wet compresses
zinc containing ointment to dry the blisters
loose fitting clothing
anticonvulsants relieve nerve pain
side effects of antivirals?
decreased GFR, vomiting, encepahlopathy, urtcaria, nausea, abdominal pain, dizziness
Complications of shingles?
postherpetic neuralgia (severe nerve pain) and intense itching even after rash is gone, pain is in affected dermatomes, can last years and it is intolerable
opthalamic shingles, ramsay hunt syndrome, infection, scarring,
At what age are you likely to get shingles?
> 50
What is encephalitis?
inflammation of the brain normally due to an infection which can lead to brain damage, swelling, pressure and death
Risk factors of encephalitis?
exposure to viruses
In who is encephalitis most common?
young or elderly
What are the most common viruses to cause encephalitis?
herpes simplex virus, varicella zoster virus, CMV, EBV, HIV, measles, mumps, rabies, japanese B encephalitis, west nile tick, tick borne encephalitis
What are non viral causes of encephalitis?
bacterial meningitis, TB, thyphus, malaria, listeeria, Lyme disease, post vaccination, autoimmune ecephalitis, legionella, cryptococcus, vaccination, sphyllis, roundworm
Symptoms of encephalitis?
fever, headache, nausea, vomiting, joint pain, seizures, focal neurological deficits, confusion, change in personality, photophobia, hallucinations
what are the 3 types of chronic encephalitis?
subacute sclerosing panencephalitis, progressive multifocal leukodystrophy, chronic progressive HIV encephalitis
Investigations for encephalitis?
LP - increased CSF protein and lymphocytes, decreased glucose
culture and PCR of HSV within CSF
increased mononuclear cells
EEG - shows diffuse abnormalities
CT contrast - focal bilateral temporal lobe
Treatment of encephalitis?
acyclovir within 30 mins for 14days (21days if immunocompromised), supportive therapy, antibiotics, immunoglobulin therapy, plasmapheresis, corticosteroids if autoimmune, sedatives for irritability, physical/speech therapy, immunosuppressants, symptomatic treatment
Prognosis of encephalitis?
70% mortality in untreated, 20% mortality in treated
normally lasts for 1-2 weeks, but can take several months to revocer
probable reactivation
complications of encephalitis?
permanent brain damage, affecting hearing, memory, msucle control, sensation, speech and vision, personality changes, epilepsy
What is rabies and how is it transmitted?
the rhabdovirus RNA virus, transmitted by saliva of animals, which spreads to the CNS via peripheral nerves and forms Negn bodies, it replicates in the grey matter then trans-located to tissues and salivary glands
Symptoms of rabies at each stage?
prodomal stage - fever, jeadache, malaise, hyperaethesia at bite site
encephalitis - excitation, hallucinations, lucent period
brain stem dysfunction, cranial never involvement, salivation, hydrophobia
Diagnosis of rabies?
biopsy nape of neck or corneal impression smear of fluorescent antibody, salivary viral culture, PCR investigated, non specific serology
Treatment of rabies?
exposure prophylaxis, local wound cleaning, vaccine,
What is polio and how is it transmitted?
viraemia, types 1, 2 and 3, transmitted by faecal oral route, crosses the blood brain barrier causing meningocephalitis with destruction of motor nuceli of anterior horn of brain stem and spinal cord
What complications can polio lead to?
paralytic poliomeylitis, asymeme flaccid paralysis, respiratory muscle involvement
Treatment and prevention of polio?
vaccine with life attenuated types 1, 2 and 3, inactivated polio vaccine, 3 doses, boosters
What is cerebral toxiplasma, its symptoms and treatment?
reactivation of latent infection, seroprevalence rates 15-50%, CD4 usuallu
Treatment of CMV?
ganciclovir
What is tetanus?
clostridium tetani, a soil organism infecting via dirty wounds, terminal spore, gram positive anaerobe, ubigulitis, toxin secretor (tetanospasmin) and translocates via the peripheral nerve, binds to GABA receptors of inhibitory interneurone
Symptoms of tetanus?
parasthesia of wound, lock jaw, sustained muscle contractins, involvement of facial muscles, paraoxysmal generalised spasm, autoimmune dysfunction
Diagnosis of tetanus?
debride wound, benzyle penicillin, human tetanus immunoglobulin, control spasm with dantolen, baclofen, control hypertension, ITU, airway mangement, tetanus toxin vaccination, 3 doses, signle booster
What is botulism?
clostridium botulism, spore former, anaerobe, e.g. cans, a neurotoxin seen in IVDU with contaminated heroin, incubation of 18-36 hours
Symptoms of botulism?
descending paralysis with cranial neuorpathy first, diplopia, dysrathria, dysphagia peripheral weakeness
Treatment of botulism?
equine of human antitoxin
Cord compression symptoms?
acute lower back pain precedes then neurological deficits, neuropathic pain, motor and autonomic dysfunction e.g. sensory loss below lesions (one or 2 segments below), tone and reflexes reduced, leg weakness and sensory loss, arm weakness is less severe
Investigations for cord compression?
MRI - show site of compression
CXR - shows degenerative bone disease and destruction of vertebrae by infection of neoplasm
biopsy and surgical exploration
serology, ESR, FBC, syphillis serology, serum electrophoresis
What is cord compression linked to and why?
cancer patients do to the rich venous plexus which increases haematogenous spread to metastases to the spine
Red flag symptoms for cord compression needing urgent referral and why?
bladder dysfunction, sphincter disturbance, saddle anesthesia (numbess to perineal area), bilateral lower extremity weakness
can lead to complete paralysis
Treatment of spinal cord compression?
malignancy - dexamethasone IV to reduce oedema around lesion and improve outcome before radiotherpay and chemo with decompressive laminectomy
epidural abscesses surgically decompression
antibiotics
anti inflammatories
What is the cauda equina?
it is the nerve roots caudal to the spinal cord temination, provides sensory and motor innervation to the hip muscles, lower extremity muscles, urinary and anal sphincters and muscles for sexual function
What is cauda equina syndrome?
compression of the spinal cord or spinal damage from L2 down,
What is the most common cause of cauda equina syndrome?
lumbar disc prolapse from lumbar disc herniation at L4/l5 and L5/S1
Causes of cauda equina syndrome?
disc herniation, lumbar stenosis, trauma, neoplasm, infection, abscess, inflammatory disease, CIDP, pagets, ankylosing spondylitis, post operative haematoma, spondylolisthesis, sarcoidosis, congenital lumbar disease
Symptoms of cauda equina syndrome?
depend on where the lesion is compressing the nerves - weakness, anesthsia/sensory deficiency, pain, paraesthesias, loss of sphincter tone resulting in incontinence, sexual problams, fasciculations, reduced of absent DTRs, saddle numbness, back pain and radicular pain down the legs, sexual dysfunction, reduced cremasteric reflex, reduced sensation over particular dermatomes
Investigations for cauda equina syndrome?
MRI to determine level of compression CXR CSF analysis if meningismal Myelography and CT urodynamic studies to monitor recovery of bladder function post decompression studies
DD of cauda equina syndrome?
conus medullaris syndrome, mechanical lower back pain, prolapsed lumbar discm fracture of lumbar verterbraw due to trauma, spinal tumour, spinal cord compression, peripheral neuropathy, guillain barre syndrome, amyoropjhic lateral sclerosis, MS, diabetic neuropathy, spinal neoplasm
Risk factors for cauda equina syndrome?
age, cancer patient, trauma,
Treatment of cauda equina syndrome?
based on underlying cause, referred to specialist, surgical intervention for trauma, rehabilitation, anti inflammatories, physio, chemo and radiotherapy, lesion debulking for space occupying lesions
Complications of cauda equina syndrome?
paralysis, sensory abnormalities, bladder bowel and sexual dysfunction,
prognosis of cauda equina syndrome?
based on cause, but poor treatment leads to long term bladder, bowel and sexual dysfunction, and late diagnosis leads to neurological deficit, poorer diagnosis if bilateral sciatica or complete perianal anesthesia than if it was just unilateral pain.
What is motor neuron disease?
cluster of degenerative disease with selective loss of neurons in the motor cortex, cranial nerve nuclei and anterior horn cells, upper and low motor neurons are affect but no sesnory loss of sphincter disturbance
Difference between MS and MND?
MS has sensory and motor loss and causing sphincter disturbance and MDN only affects motor and no distubrance
Difference between mysasnthia gravis and MND?
MND never affects eye movements unlike MG
What are the 4 clinical types of MND?
1 - progressive muscular atrophy - LMN lesion, causing weakness, wasting and fasciculation (spontaneous, irregular and brief contractions of part of a muscle) in hands and arms, affects distal first
2 - amyotrophic lateral sclerosis - combination of lateral corticospinal tracts and anterior horn cells producing progressive spastic tetraparesis or paraperesis UMN signs with added LMN signs
3 - progressive bulbar and pseudobulbar palsy - from destruction of UMN and LMN in lower cranial nerves with dysarthria, dysphagia, wasting and fasciculation of the tongue, cranial nerves 9-12
4 - primary lateral sclerosis - rare with progressive tetraparesis, loss of Betz cells in motor cortex so mainly UMN signs with spastic leg weakness and pseudobulbar palsy, no cognitive decline
Cause of MND?
5-10% familial, trauma, electric shocks, infection
events at the ALD-FTD locus explain 87% of familial ALS and is autosomal dominant
How common is MND?
5/100,000 and rare below 30, increasingly common over 50, often fatal within 2-4years
What symptoms are linked to a worse prognosis in ALS MND?
bulbar onset, increased in age, decreased FVC, split hand sign with thumb adrift due to wasting around it
What are UMN signs in MND?
spasticity, brisk reflexes, increased plantars
What are LMN signs in MND?
signs, wasting, fasciculation on tongue, abdomen, back, thigh
Investigations of MND?
diagnosis is clinical, fasciculation is characteritic
EMG shows muscle denervation
MRI excludes structural causes
LP excludes inflammatory causes
DD of MND?
cervical spine lesion, idiopathic multifocal motor neuropathy
Treatment of MND?
Riluzole - a sodium channel blocker that inhibts glutamate release, slow progression slightly
propantheline and amitriptyline for drooling
ventilatory support helps prolong survival and for resp failure
feeding via PEG helps dysphagia
spasticity drugs
neurlogists, dietitian, physio, speech therapist, palliative care
SE of Riluzole?
vomiting, increased pulse, somnolence, headache, vertigo and increased LFTs
What is a spinal muscular atrophy?
rare disorder which detroys anterior horn cells of the spinal cord, slowly progressive with symmetrical wasting weakness of the limbs
What are the 3 types of peripheral neuropathy?
sensory (affects touch, temperatire, pain and other sensations), motor (affects movement) and autonomic (affects involuntary bodily processes
can have a combination of them at one time e.g. sensorimotor polyneuropathy
What is peripheral neuropathy?
group of conditions in which the periopheral nervous system is damaged
Symptoms of sensory neuropathy?
tingling in the affected body part, numbeness, reduced feeling of pain and changes in temperature (feet), burning/sharp pain in feet and legs, allodynia (pain from light touch), loss of balance or coordination
Symptoms of motor neuropathy?
twitching, muscle cramps, muscle weakness and paralysis, muscle wasting, foot drop
Symptoms of autonomic neuropathy?
depends on location, constipation, diarrhea, nausea, bloating, hypotension, tachycardia, excessive or lack of sweating, sexual dysfunction, bowel incontinence, dysphagia
What is a mononeuropathy?
affects a single nerve caused by acute compression, particularly where the nerves are exposed anatomically or entrapment where the nerve passes through a relatively tight anatomical passage (carpal tunnel) or caused by direct damage
what is the most common form of mononeuropathy?
carpal tunnel syndrome, leading to tingling, pain or numbness in the fingers due to irritation of the median nerve
What is mononeuritis multiplex?
a systemic disorder, when 2 or more peripheral nerves are affected and it is a systemic cause
Symptoms of carpal tunnel syndrome?
tingling, numbness and pin i the thumb, index finger, middle finger and half of ring finger
discomfort in hand and arm, paraesthesia in hand, dry skin, swelling, hypoaesthesiia, atrophy of muscles, worse pain on repetitive use or in same position, impaired dexterity, drop things a lot, Tinnel’s sign
Risk factors for carpal tunnel syndrome?
25% FH, pregnancy, menopause, injuries to wrist, manual labour, playing an intrument, diabetes, arthritis, hypothyroidism, obesity in the young, breast cancer medications, abnormal wrist structure
Investigations of carpal tunnel syndrome?
assess ability of hand and arm, look for weakness and wasting around thumb, Tinnel’s sign, flexing wrist or holding above head will cause pain, nerve conduction study, EMG, x-ray, US of median nerve
Treatment of carpal tunnel syndrome?
avoid triggers, treat underlying cause, wrist splint to prevent bending of wrist which can aggrevate symptoms, no direct pressure on it, corticosteroids for inflammation (tablets of injection into wrist), carpal tunnel decompression surgery
Complications of carpal tunnel syndrome and surgery?
infection, recurring pain, scarring, nerve injury, post op bleeding, failure to separate root of carpel tunnel resulting in persistent symptoms
What is a polyneuropathy?
symmetrical disease process, can be sensory, motor or autonomic, and leads to symptoms of numbness, tingling, pins and needles, pain in extremities, unsteadiness of feet, weakness, postural hypotension, urinary retention, erectile dysfunction, diarrhea, dimished sweating, impaired pupillary reponses, cardiac arrhythmias
Causes of polyneuropathy?
DM, guillain barre sundrome, toxins, vitamin deficiency, leprosy, renal failure
Investigations in polyneuropathy?
FBC, ESR, serum vit b12, glucose, urea, electrolytes, LFTs, nerve conduction tests
Cause of vitamin B1 deficiency neuropathy (thiamin)?
chronic alcohol dependent patients when little food is consumed, starvation, beriberi
Symptoms of vitamin B1 deficiency neuropathy?
Wernicke Korsakoff syndrome, polyneuropathy and cardiac failure
Treatment of vitamin B1 deficiency neuropathy?
thiamin for 3 days, anaphylaxis in parenteral thiamin, given before IV glucose in high risk patients
Causes and treatment of vitamin E6 deficiency neuropathy (pyridoxine)?
isoniazid therapy for TB, give prophylactic pyridoxine with isoniazid, it mainly cuases a sensory neuropathy
Symptoms of vitamin B12 deficiency neuropathy?
polyneuropathy with subacute combined degeneration of the cord, distal sensory loss, absent ankle jerks, evidence of cord disease
Treatment of vitamin B12 deficiency neuropathy?
IM vit B12 to reverse peripheral nerve damage but has little affect on the CNS
What is hereditary sensorimotor neuropathy?
large and complex group with variable mutations, most common being Charcit-Marie-Tooth disease (peroneal muscular atrophy)
Symptoms of hereditary sensorimotor neuropathy?
distal limb wasting and weakness that progresses over many years, mostly in legs with variable loss of sensation and reflexes, legs can resemble inverted champagne bottles due to the wasting
What are the 2 types of diabetic neuropathy?
progressive and reversible
What are the 2 types of progressive diabetic neuropathy?
symmetrical sensory polyneuropathy and autonomic neuropathy
What are the 3 types of reversible diabetic neuropathy?
acute painful neruopathy, mononeuropathy and mononeuritis multiplex with cranial nerve or isolated peripheral never lesions, diabetic amyotrophy
What causes isolated mononeuropathies?
occlusion of the vase nervorum (small arteries that supply the peripheral nerves)
Where do diffuse neuropathies occur from?
accumulation of fructose and sorbitol (metabolized from glucose in the peripheral nerve) which disrupts the structure and function of the nerve
What is the most common form of neuropathy?
symmetrical mainly sensory neuropathy
Symptoms of symmetrical mainly sensory neuropathy?
affects the feet first, loss of vibration sense, pain sensation and temperature sensation in the feet, then ‘walking on cotton wool’ and lose balance due to impaired proprioception, hand involvement is uncommon.
Complications of symmetrical mainly sensory neuropathy?
trauma, blistering from ill fitting shoes causing ulceration, abnormal mechanical stress, repeated minor trauma, neuropathic arthropathy (Charcot’s joints) in ankle and knee, distorted foot with high arch, clawing of toes, insensitive foot ulceration
What is acute painful neuropathy’s symptoms and treatment?
burning or crawling pains in lower limbs, worse at night and with bed clothes pressure, treat with good diabetic control, tricyclic antidepressants, gabapentin and carbamazepine
Which are the most common cranial mononeuropathies and their presentation?
3rd and 6th, which supply the extraoccular muscles, presenting with unilateral pain, ptosis and diplopia with sparing of pupillary function
Symptoms of diabetic amyotrophy?
painful wasting, usually asymmetrical, or quadriceps, wasting may be marked and knee reflexes may be diminished or absent
Symptoms of autonomic neuropathy?
affects CV system (tachycardia, loss of sinus arrhythmia, postural hypotension, peripheral vasodilation), GI (diarrhea, gastroparesis and intractable vomiting), bladder (incomplete emptying) and male ED - treatment is symptomatic
Treatment of peripheral neuropathy?
treat symptoms, physio, splints, viagra, male prosthesis, catheter, botulinum toxin, stand up slowly, amitiptyline, duloxteine, pregabalin, tramadol, lidocaine plasters
What is a stroke?
a rapid onset of neurological deficit caused by blood flow to the brain being stopped by a blockage or rupture
What are the types of stroke and what causes them?
ischemia - caused by blockage from emboli of thrombus
haemorrhagic - caused by breakage in blood vessel in the brain of the membrane surrounding the brain
intracranial venous thrombus - caused by space occupying lesion in the brain e.g. tumoru, abscess, MS
carotid or vertebral artery dissection - allowing blood to track the wall of the artery and occlude the lumen - 20% of young strokes
What is the difference between a completed stroke and evolutary stroke?
a completed stroke has reached it’s maximum in 6 hours, turns into evolution when the signs and symptoms are getting worse, usually within 24 hours of onset
What is classed as a mini stroke?
patient recovers without a significant neurological deficit and recovers in about 1 week
Symptoms of a stroke?
difficulty walking, loss of balance and coordination, dysarthria and difficulty understanding, unilateral face paralysis and weakness, blurred or darkened vision, sudden headache with nausea, vomiting and dizziness
Common symptoms for a cerebral stroke?
sensory loss, hemiplegia, dysphagia, homonymous hemianopia, visual spatial deficit
Common symptoms in a brainstem stroke?
quadriplegia, disturbances of gaze and vision, locked in syndrome
Common symptoms in Lacunar stroke?
ataxic hemiparesis, pure motor, pur sensory, sensorimotor and dysarthria
Risk factors for stroke?
hypertension, DM, smoking, hyperlipidaemia, obesity, oestrogen containing oral contraceptive, excessive alcohol consumption, polycythaemia, atrial fibrillation, migraine, vasculitis, cocaine, antiphospholipid syndrome, thrombophilia
Investigations in a stroke?
check reflexes, vision, speaking and senses, check for carotid bruit which indicated abnormal blood flow, blood tests, angiogram to find location of black, carotid US, CT, MRI, ECHO, carotid artery stenosis, doppler uS (>70% stenosis is significant), vasculitis shows increased ESR and ANA positive, hyperviscosity with polycythaemia and sickle cell disease
Complications of a stroke?
difficulty speaking, moving, thinking which can improve but others need care, aspiration pneumonia, contractures, depression, constipation, stress in spouse
Immediate treatment of stroke?
protect airway, urgent CT/MRI, thrombolysis, nil by mouth, hydrate, antiplatelets
Primary prevention of stroke?
control risk factors, antihypertensives, treat DM and hyperlipidaemia, exercise, folate supplements, smoking cessation, lifelong anticoagulation if rhuematic or prosthetic heart valves, chronic non rheumatic atrial fibrillation
Secondary prevention of stroke?
antiplatelet drugs e.g. clopidogrel monotherapy, anticoagulation, lower BP, repair ruptured blood vessel, remove blockage with clot dissolving drugs or blood thinners
What is the mortality after 1st stroke?
12% die by day 56
What are primary causes of headache?
migraine, cluster or tension type
hemicrania continua, new daily persistant headache, chronic paraoxysmal hemicrania
Secondary causes of a headache?
meningitis, subarachnoid haemorrhage, GCA, idiopathic intracranial hypertension, medication overuse, low CSF pressure, post traumatic
Red flags in headache history?
> 50, HIV, cancer, trauma, change in personality, vomiting, jaw claudication, severe eye pain, change in frequency, postural, sudden onset, exercise, focal neuorlogical symptoms, fever, altered consciousness, neck stiffness etc
What does a thunderclap headache suggest?
subarachnoid haemorrhage
Symptoms of idiopathic intracranial hypertension?
not benign, headache with raised ICP, visual disturbance with acuity/fields, papilloedema, normal constituents of CSF
Risk factors of idiopathic intracranial hypertension?
obesity, drugs e.g. tetracycline
idiopathic intracranial hypertension management?
modify risk factors, monitor visual fields with Goldman fields, acetazolamide/topiramate/diuretics
repeated LPs, CSF shunt, optic nerve fenestration
GCA criteria?
> 50, new headache with localised pain, tenderness, decreased pulsation, raised ESR, abnormal biopsy
What is a chronic daily headache?
headache on 15 or more day per month
How common are migraines?
1/4 women and 1/12 men develop it at some point, commonly starts in childhood or as a young adult, many stop in adult life, can be several attacks a week or once every few years
What are the 2 types of migraine?
with aura (classic) and without aura (common)
Symptoms of a migraine (without aura)?
headache on one side of head, typically at front or side, sometimes both, then spreads all over, throbbing pain
nausea, vomiting, photophobia, being off food, blurred vision, poor concetration, stuffy nose, hunger, abdo pain, pale, sweating
When is migraine pain worse?
most often in morning, but can be at any time, then gradually gets worse and peaks 2-12 hours after and then eases off, can last from 4-72 hours
What is a migraine with an aura?
a warning sign before a migraine, which can be visual, numbness, speech, smells etc lasts a few minutes but can last up to an hour, then the migraine develops soon after
Examples of migraine auras and which are most common?
visual aura - temporary loss of vision, flashed of light, objects rotate, shake or boil
numbness, pins and needles, travel up the arm and involve face, lips and tongue
problems with speech
old smells, food craving, feeling odd
What are the phases of a migraine?
irritability, aura, headache, irritable
What are less common types of migraine?
menstrual - only during periods
abdominal - in children, with nausea, and turns to normal migraine in later years
ocular - temporary loss
hemiplegic - severe, on one side of the body, can cause severe dizziness, double vision, hearing problems
basilar type - in the back of the head
What causes an aura?
narrowed blood vessels in the brain, which then soon dilate, causing the headache
Causes/triggers of migraine?
increased signals in the brain, confusing the brain, familial, dieting too fast, irregular meals, smokey rooms, glaring light, flickering TV, loud noises, depression, tiredness, stress, HRT, contraceptibe pill, periods, shift work, bad sleep patterns, menopause
Treatment of migraine?
paracetamol, aspirin, NSAISs, anti emetics, oral triptam medicine e.g. almotriptan which interfere with 5HT (don’t take too early on in attack though),
CI in pregnant women, even though migraine can rarely be worse in pregnancy but migraine improves in most cases with pregnacy and breatfeeding
Preventative treatment for a migraine?
topiramate or propanolol, acupuncture, amityriptaline, riboflavin, botulinum toxin type A
How common is a tension type headache?
the most common type of headache, 50% of adults have it at least every month and 1/30 adults have chronic tension type headaches
What is the difference between episodic and chronic type headache?
episodic = occur on less than half of the days in the month
chronic = occur more than half of the days in the month
Symptoms of tension type headache?
band across the forehead, uncomfortable, tiring, worse on activity, sensitive to light and noise, sore neck
How long do tension type headaches last for?
from few hours to several days, usually a few hours, they don’t disturb sleep and most people can work through them, you are normally well in between headache
Cause of tension type headache?
tightness of neck muscles or ones over the scalp, poor posture, stress, anything that can make the back of the neck muscles tense, may be more genetically prone to develop them due to being stressed and anxious, painkillers too often due to increasing the number of pain receptors in the head and they become excessively sensitive
When should a tension headache suggest something more serious?
significant head injury in past few months, pain getting worse, accompnaying fever, problems with speech, balance or memory, headache start when coughing/sneezing, worse when sitting or standing, red or painful eyes, worse headache than ever, low immunity, previous cancer
Lifestyle treatment of tension headache?
exercise, change routine, shoulder massage, hot flannel on neck, warm batch, less caffeine, balanced diet, more water, less pillows, avoid excessive noise and reading in low light, diary of frequent headaches, avoid stress triggers
Treatment of tension headache?
paracetamol but not for more than a couple of days at a time, codeine, amitriptyline
What is a cluster headache?
severe unilateral pain, localised in or around the eye with ipsilateral autonomic features, rare
What is an episodic cluster headache?
occurs in periods lasting from several days to one year, usually 2-9 weeks, separated by pain free periods of a month or longer
What is a chronic cluster headache?
CHs occuring for one year without remission or short lived remissions of less than a month (can start as this or develop from episodic)
How common is cluster headache?
rare, 1/1000, more men than female, with a bigger difference between them in chronic then episodic but episodic being more common overall, usually occurs 20-40 years
What signs suggest an episodic cluster headache is turning into chronic?
later onset, sporadic attacks occur, higher frequency of cluster periods, shorter periods of remission
Causes of cluster headache?
1/20 have a 1c family member, associated with HCRTR2 gene
Pathophysiology or cluster headaches?
ipsilateral hypothalamic grey matter has dysfunction causing dilation of cranial vessels mediated by trigeminoparasympathtic reflexes, changes in melatonin in relation to the light and dark cycle affect CH
Clinical features of cluster headaches?
rapid onset of pain over 10 minutes which maintains intensity, excruciating, sharp and penetrating, centered behind the eye/temple/forehead (occasional neck), unilateral pain, lacks 45-90 minutes, 1-2x/day
ipsilateral lacrimation, rhinorrhoea, nasal congestion, eyelid swelling, facial sweating, flushing, conjunctival injection
restless (unlike migraine), band head against wall, nausea
Triggers of cluster headaches?
alcohol, heat, exercise, solvents, disruption of sleep habits
What is the diagnostic criteria of a cluster headache?
for at least 5 attacks:
severe unilateral orbital, supaorbital and/or temporal pain lasting 15-180 minutes if untreated
and at least one:
Ipsilateral conjunctival injection and/or lacrimation.
Ipsilateral nasal congestion and/or rhinorrhoea.
Ipsilateral eyelid oedema.Ipsilateral forehead and facial sweating.
Ipsilateral miosis and/or ptosis
Restlessness or agitation.
One every other day to eight times daily.
DD of CH?
paroxysmal hemicrania
short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)
Red flags of a headache?
change in pattern of headache, new headache aged 50, seizures, headache with systemic illness, personality change, raised ICP symptoms, worst headache ever
Management aim of CH?
suppress attack and reduce frequency and severity of attack
Management of CH?
stop smoking, abstain from alcohol, regular sleep pattern and good hygiene
acute attack - SC sumatriptam and 100% o2, antiinflammatories, lidocaine
Prophylaxis of CH?
verapamil, ECG monitoring, prednisolone, lithium is verapamil not effective, melatonin, sodium valproate in chronic, ergotamine before predicted attack, deep brain stimulation, trigeminal nerve blockage, acupuncture
Side effects of verapamil?
constipation, flushing
What is a subarachnoid hemorrhage?
a spontaneous arterial bleed into the subarachnoid space
How common and in who does subarachnoid hemorrhage occur?
6/100,00 pa, usually around 50years and more common in women
Causes of subarachnoid hemorrhage?
rupture of berry aneurysm (80%) or congenital arteriovenous malformations
Symptoms of unruptured aneurysm?
sight problems, pain on one side of face or around the eye, persistent and severe headaches, painful third nerve palsy, nausea, vomiting, loss of consciousness, meningeal irritation, focal neurological signs, sub hyaloid haemorrhages between the retina and vitreous membrane with or without papilledema, coma, drowsiness
Risk factors for subarachnoid hemorrhage?
smoking, high blood pressure, excessive alcohol consumption, family history, bleeding disorders, mycotic aneurysm, post menopause from decrease in oestrogem, ADPKD, Ehlers Danlos Syndrome, coartation of aorta
Investigations in subarachnoid hemorrhage?
CT shows subarachnoid blood, lumbar punctureshows biliruibin or oxyHb, must be at least 12 hours after symptoms so that Hb can degrade into the bilirubin and turn the CSF xanthochromic (yellow) which can then be detected by spectrophotometry of the supernatant after centrifugation, should therefore be protected from light, MRA find the source of the bleeding
Treatment of subarachnoid hemorrhage?
hydrate to maintain cerebral perfusion, treat hypertension, CCB (nimodipine), analegics, anticonvulsants, antiemtics, intracranial stents, neurosurgical clipping, endovascular coiling, occupational therapist, antidepressants, CBT
What is the difference between neurosurgical clipping and endovascular coiling?
clipping to shut off the aneurysm to prevent it growing or rupturing again
coiling inserts a catheter into an artery in the leg into head and passes coils through the aneurysm so blood can’t enter it again so cant rupture, it has increased survival over clipping but increased risk of bleeding
Complications of subarachnoid hemorrhage?
rebleeding (commonest cause of death), delay cerebral ischemia from vasospasm causing vessel to narrow, hydrocephalus, hyponatraemia, epilepsy, cognitive dysfunction, depression, PTSD
Prognosis of subarachnoid hemorrhage?
50% die suddenly or soon after haemorrhage, 10-20% from rebleeding, variable outcome, glasgow coma score on admission has the most prognostic significance which checks level of consciousness and brain injury severity (12 or more has good prognosis)
What 3 things does the Glasgow coma scale base on?
eye opening response, best verbal response, best motor response
What is a subdural haematoma?
where the blood collects in the subdural space following a rupture of a vein running from the hemisphere to the saggital sinus, increasing pressure on the brain (intracranial hypertension) causing brain damage (head injury)
When do symptoms occur in subdural haematoma?
develop soon or can be days or weeks after
Symptoms of subdural haematoma?
progressively bad hangover, feeling and being sick, confusion, personality changes, drowsiness, speech problems, problems with vision, paralysis on one side of the body, problems with walking, frequent falls, seizures, loss of consciousness, localising neurlogical symptoms (unequal pupils)
In who is subdural haematoma most commonly seen?
older, blood thinning medication, drink excessively, accident prone, atrophic brains which makes the connecting veins more susceptible to rupture due to the increased tension
Diagnosis of subdural haematoma?
CT and MRI to rule out other illnesses
shows clot and midline shift and a CRESCENT shape collection of blood over 1 hemisphere
Treatment of subdural haematoma?
surgery to remove haematoma, or if small, monitor to see if they can heal spontaneously
Complications of subdural haematoma surgery?
further bleeding on the brain, infection, deep vein thrombosis, seizures, stroke
What is an extradural hemorrhage?
an injury that fractures the temporal bone and ruptures the underlying middle meningeal artery causing a collection of blood in the potential space between dura and bone
In who is extradural hemorrhage seen?
males, rare in small children due to the plasticity of the skull, less common over 60 due to dura being tightly adherent
What happens shortly after an extradural hemorrhage?
there is a brief period of unconsciousness followed by a lucid interval of recovery which can be a few hours to a few days before a bleed with decrease GCS from rising ICP with rapid deterioration with focal neurological signs and deterioration in consciousness level if surgical drainage is not immediately carried out
What causes a spontaneous extradural hemorrhage?
a coagulation or platelet defect
Symptoms of extradural hemorrhage?
increasingly severe headache, nausea, vomiting, seizures, confusion, bradycardia indicating raised ICP, skull fractures, haematomas, lacerations, CSF otorrhoea or rhinorrhoea, alteration in consciousness and deterioation of the glasgow coma scle, unequal pupils, facial never injury, weakness of limbs, hemiparesis, visual field defects, numbness, coma, death from respiratory arrest
Investigations of extradural hemorrhage?
x ray - skull fracture, fracture lines crossing the middle meningeal vesicles
ct san - haematoma LENS SHAPE (not sickle like subdural) as the tough dural attatchments to the skull keep it more localised
MRI -
AVOID LUMBAR PUNCTURE
fbc, u and e
Management of extradural hemorrhage?
ABC, O2, full trauma assessment, IV fluids to preserve cerebral perfusion, osmotic diuretics if ICP raised, intubation and ventilation and mannitol if ICP decreased, Burr holes to evacuate haematoma, DVT prophylaxis
Complications of extradural hemorrhage?
neurological deficits (temporary or permanent), death, PTS seizures 1-3 months post injury
What are delayed effects of extradural hemorrhage?
post concussion syndrome which has headaches, dizziness, vertigo, restlessness, emotional liability, inability to concentrate and fatigue
Symptoms of spinal extradural hemorrhage?
spasticity, neuropathic pain, urinary complications
Prognosis of extradural hemorrhage?
excellent in children, low GCS is bad prognosis, prognosis worse if older, intradural lesions, volume of haematoma, temporal location, rapid clincal porogrssion, pupillary abnormalities, increased ICP
What are Charcot Bouchard aneurysm?
0.3-0.9mm, a hypertensive hemorrhage arising from deep perforator arteries that can lead to lacunar infarct, microbleeds and hemorrhage
What are lobar haemorrhages?
large and superficial, common in elderly people
Treatment of an anticoagulant related ICH?
warfarin check urgent INR, consider reversal with Beriplex and vitamin K, if low platelets have platelet transfusion
Treatment of infratentorial bleed with brainstem compression?
surgical decompression
Treatment of hydrocephalus?
external ventricular drain
When should a neurosurgeon be called in a hemorrhage?
deteriorating GCS, hydrocephalus, coning, large cerebellar hemorrhage >3cm, distortion of the 4th ventricle with gcs >8
How are head injuries classified?
on type of injury, distribution of the lesions, time course of damage following the traumatic event
What are the types of distribution of head injuries?
focal: scalp - contusions, lacerations skull - facture meninges - haemorrhage, infection brain - contusion, lacerations, hemorrhage, infection
diffuse: diffuse axonal injury diffuse vascular injury hypoxia-ischemia swelling
What does a focal head injury suggest?
considerable force, increased risk of haematoma and infection and aerocele
angled or pointed objects cause localised fractures that are open or depressed
flat surfaces cause linear fractures that can extend into skull base and be called contrecoup factures
What is the difference in focal brain damage mechanisms?
contact damage - at or just deep to point of impact
acceleration/deceleration damage - causes differential movement of skull, brain and brain tissue causing traction and damage blood vessels
contusions - superficial bruises of the brain, coup at site of impact/contre coup away from site of impact, first become haemorrhagic then become brown and soft then indented and cavitated after months
lacerations - when the contusion is sufficientlu severe to tear the pia mater
What are the different types of diffuse lesions?
diffuse axonal injury - a clinicopathological syndrome of widespread axonal damage
diffuse traumatic axonal injury
traumatic axonal inury - involving acceleration and decelaration
axonal injury
swelling - increasing ICP, caused by vasodilation, increased cerebral blood volume, extravasation of oedema fluid from damaged vessels, increased water content of neurons and glia
hypoxia-ichemia -
diffuse vasuclar injury - results in near immediate death, multiple petechial hemorrhages throughout the brain
What causes herniation?
bleeding and brain swelling
What is a missile head injury?
can be a depressed injury that does not penetrate the skull, penetrating injuries, or perforating injuries
What is chronic traumatic ecephalopathy?
a neurodegenerative condition seen 8-10 years after repetitive mild traumatic brain injury, 1/3 are progressive
initally irritability, impulsivity, aggression, depression, memory loss
e.g. dementia, gait, speech problems, parkinsonism
How does chronic traumatic encephalopathy appear?
an atrophic neocortex, hippocampus, diencephalon and mamillary bodies
enlarged ventricles with fenustrated cavuum septum
tau positive neurofibrillary and astrocytic tangles
frontal and temporal cortex and limbic regions especially around depths of sulci and limbic regions
What is dystonia?
a state of abnormal muscle tone resulting in muscular spasm and abnormal posture usually caused by a neurological disease, side effect of drug therapy and trauma
Why does vibration induce illusion of movement?
either subnormal muscle spindles responsiveness to stretch improves with fatigue of the muscle or subnormal responsiveness of the CNS to the afferent input improves after fatigue of muscle
What is dopa dysregulation syndrome?
result of presynaptic neuron loss and post synpatic receptor supersensitivity
Symptoms of anterior carotid artery stroke?
leg weakness, sensory disturbance in legs, gait apraxia, truncal ataxia, incontinence, drowsiness, akinetic mutism, decrease in spontaneous speech, stuporus state
Symptoms of middle carotid artery stroke?
contralateral arm and leg weakness, contralateral sensory loss, hemianopia, aphasia, dysphasia, facial droop
Symptoms posterior carotid artery stroke?
contralateral homonymous hemianopia, cortical blindness with bilater involvement of the occipital lobe branches, visual agnosia, prosopagnosia, dyslexia, anomic, aphasia, colour naming, discrimination problems, unilateral heaches
Symptoms of posterior circulation strokes?
motor deficits, dysarthria, speech impairment, vertigo, nausea, vomiting, visual disturbances, altered consciousness
What makes up a muscle?
muscle fibres, which are long multinucleated structures bound by sarcolemma
What are myofibrils?
the contractile element within the myofibre, with thin (I actin) or thick (A myosin) filaments, they are multinucleated and bound by sarcolemma
How do myofibrils work?
excitation force along the whole length simultaneously, and release calcium from SR, it is a T tubule system with invaginations of sarcolemma
What mechanisms can cuase muscular dystrophies?
loss of structural proteins, defective enzymes, disruption of sarcolemma repair, loss of signalling molecules, non coding region mutations, defective post translational modifications
What is a muscular dystrophy?
a group of familial disorders causing replacement of muscle tissue with fibrous connective tissue causing progressive muscle weakness and muscle wasting
What is Duchenne muscular dystrophy?
X linked inheritance (Xp21), muscle degeneration, large deletions and duplications and point mutations disrupting the reading frame causing absence of dystrophin (which connects cytoskeleton to ECM to protect the muscle during force of contraction)
What is the most common muscular dystrophy in children and the prognosis?
DMD 1/3500 males, manifesting at 5 years of age, leading to wheelchair dependence by 13, survival is rare over 30
Symptoms of DMD?
muscle degeneration, thin weak thighs, tip toeing, weak stomach muscles causing stomach to protrude out, shoulders and arms back awkwardly, swayed back, weak butt muscle pushing body out further, thick calves from fat, tight leg muscles, poor balance, awkward walking, cardiac involvement
What is Beckers muscular dystrophy?
DMD but less severe, slower progression, later onset in 20s, and death around 40, worse cardiac involvement
What is myotonic dystrophy?
autosomal dominant, with a CTG trinucelotide repeat expansion in DMPK on c19, most common muscular dystrophy in adults
mutation causes RNA toxicity, downstream, effect causing missplicing of proteins, the CLCN1 is misspliced
Symptoms of myotonic dystrophy?
sustained involuntary contraction (difficult releasing grip after hand shake) as the muscles are still contracting, prominent forehead, narrow face, boldness, cataracts, poorly developed chin, dysphagia and difficulty breathing, diabetes, frontal balding
Treatment of DMD?
supportive, scoliosis corrective surgery in children, manage heart problems, NIV for resp failure, steroids (prednisolone with slows down disease progression given when motor functions plateau), gene therapy (anti sense oligonucleotides weekly sc injections to promote ribosomal read)
Treatment of MD?
supportive, treat cardiac complications, experimental AON knows down expansions, fleicanide of mexilitine for symptom relief of myotonia
What is facialscapulohumeral muscular dystrophy?
autosomal dominant, presenting at 20 years, 20% need a wheel chair, normal life expectancy, contraction in macrosatallite repeat D4Z4 on 4q35, only occurs if polyadenylated, usually 11-100 repeats but only
Symptoms of FSHD?
scapular fixators and ankle dorsiflexor weakness, retinal telangectasia and sensorineural hearing loss
What is acute pain?
sudden onset, in response to injury and infection which resolves as the condition resolves, recurrent acute pain is not chronic pain
What is chronic neuropathic pain?
a neurological condition resulting from damage to or dysfunction of the sensory nervous system, persists in the absence of tissue damage
Clinical features of chronic neuropathic pain?
burning hot and cold sensations, electric shocks, shooting pains, deep severe ache, poorly localised, numbness, paraesthesiae, recognisable dermatomal pattern, skin area may be hypersensitive, exacerbated by contact with hot or cold air, worse at night, distracted by activity associated with depression
What increases risk of chronic pain?
cultural beliefs, ongoing litigation, claims, benefits, work pressures, social circumstances, family support
What causes chronic neuropathic pain?
poorly understood level of damage to sensory pathway, pain fibres small unmyelinated C fibres, increased afferent activity or increased synaptic transmission at level of spinal cord in pain pathway
Neuropathic pain terms?
neuralgia, neuropathy, hyperalgesia, causalgia, hyperpathia, allodynia, lumbagp
Chronic pain management?
try and find cause, neurological examination to identify nerve root compression, X rays, MRI spine, serology, MDT approach, pain management programme, reassurance, encourage activities, exercise
drugs - opioids (pre synaptic inhibition), antidepressants, anti convulsants, N-Methyl D-aspartate receptor antagonists (pre synaptic excitation)
nerve blocks to support physiotherapy and increased activities, TEN stimulators, spinal cord nerve stimulator implantation, dorsal column fiber ablation
capsaicin topical cream and lignocaine gel, acupuncture
Prevention of chronic pain?
regional blocks as an adjuvant to surgery to reduce post amputation phantom limb pain, peri operative gabapentin or pregabelin, holistic approach to surgery
Tolerance to opioid analgesic drugs?
tolerance, increased metabolism, down regulation of opioid receptors, neuroplasticity of CNS target areas
What is involved in the aortic arch?
the brachiocephalic trunk dividing into the right common carotid and subclavian arteries and the aortic arch splits into the left common carotid, subclavian and vertebral
At what level do the common carotid arteries bifuricate?
C3-C4
What are the different point of the internal carotid and their characteristics?
cervical - no narrowings, dilations or branches, lies posterior and lateral to ECA at origin, ascending behind then medial to the ECA
petrous - penetrates temporal bone, running horizontally in the carotid canal, small branch to middle/inner ear, vidian artery to ECA
cavernous - turns superiorly at foramen lacerum entering cavernous sinus, piercing dura, small branches supply dura, cranial nerves 3-6 and posterir pituitary, and connects to ECA via ILT
supraclinoid - opthalmic artery (to optic canal), superior hypophyseal (to pituitary gland, stalk, hypothalamus, optic chiasm), posterior communicating artery and anterior chorodial artery (choroid plexus, optic tract, cerebral peduncle, internal capsule, medial temporal artery)
What does the middle cerebral artery supply?
the lateral lenticulostriate arteries (lentiform nucleus, caudate nucleus, internal capsule), insular cistern, onto brain surface to supply vessel on brain surface
What does the anterior middle cerebral artery supply?
medial lenticulostriate arteries to supply head of caudate nucleus and internal capsule, recurrent artery of Heubner, cortical branches from calllosomarginal and pericallosal arteries
What do the extra cranial VA branches supply?
neck muscles, spinal meninges, spinal cord, anastomoses with other neck vessels
Where do verterbral arteries arise from?
the subclavian arteries (left can arise directly from arch)
What are the intracranial VA branches?
anterior spinal artery, small meduallry perforators and posterior inferior cerebellar artery to supply the medulla and the inferior cerebellum
What does the posterior cerebel artery supply?
cortical territories including the inferior temporal lobe, posterior third of the interhemispheric surface and visual cortex and occipital lobe
How many vertebrae and nerves are in each of the spinal cord?
cervial - 7 - 8 thoracic - 12 - 12 lumbar - 5 - 5 sacral - sacrum - 5 coccygeal - coccyx - 1
What structures are in the grey and white mater?
grey - dorsal horn, intermeddiate zone, ventral horn, lateral horn
white - dorsal funiculus, dorsolateral funiculus, ventrolateral funiculus, ventrolmedial funiculus
How do the internal structure differ in the spinal cord?
white mater decreases down the spine, grey mater increased in the cervical and lumbosacral enlargements, lateral horn is present in the thoracic and upper lumbar segments
What is a stretch reflex?
monosynaptic reflex, important postural reflex, basis of tendon jerk
What is a flexor reflex?
polysynaptic reflex, withdrawal of a limb in response to pain
What is the ventral horn?
receives >20,000 synaptic contacts, has primary efferent tracts from the dorsal root, with interneurons and descending tracts, primary sensory afferent neurones
What are the fasciculus cuneatus and gracilis do?
ascending fibres, ipsilateral
discriminative touch, sensation and proprioception
cuneatus (lateral) - arms
gracilis (medial) - legs
Name nerves?
olfactory -s optic - s occulomotor - m trochlear - m trigeminal nerve - opthalamic, mandibular, maxially - b abducens - m facial - b vestibulacochlear - s glossopharengeal - b vagus - b accessory - m hypoglossal - m
Function, damage, cause and symptoms of olfactory nerve?
olfaction (smell)
damage causes anosmia (loss of smell) and hyposmia (reduced smell) and calcosmia (smell a bad smell always)
causes by trauma, meningitis, nasal congestion, tumours on floor of anterior fossa
Function, damage, cause and symptoms of optic nerve?
for visual acuity, colour vision
damage can cause optic atrophy, visual field defects, blurred vision, scotomata (decreased vision in visual field)
What controls papillary responses?
optic and oculomotor nerve
damage caused by ichemia, edema, hemorrhage and trauma
What are the 3 main main types of visual field defect and the causes?
monocular - damage to eye or nerve
bitemporal - lesion at chiasm
homonymous hemianopia - lesions in tract, radiation or lesion in visual cortex
What does a retinal lesion cause?
paracentral scotoma
What does optic nerve lesion cause?
mononuclear field loss (if complete destruction, leads to blindness and loss of pupillary light reflex)
What does a chiasmal lesion cause?
bitemporal hemianopia
What does an optic tract lesion cause?
homoymous hemianopia (macular involvement)
What does a temporal lesion cause?
homoymous quandrantopia (macular involvement)
What does a parietal lesion cause?
homonymous quadrantopia (macular involvement)
What does a occipital cortex or optic radiation cause?
homoymous hemianopia (macular sparing)
What does an occipital pole lesion cause?
homoymous hemianopia (macular sparing)
Causes of an optic nerve lesion?
demyelination, nerve compression, occlusion of retinal artery, trauma, papilloedeme, severe anemia, drugs, toxins
What causes a defect in the optic chiasm?
pituitary adenoma compressing the decussating fibres from the nasal half of each eye, craniopharyngioma, secondary neoplasm
What causes a defect of the optic tract and radiation?
tumour, vascular accident
Why is the macular region spared in occipital cortex defects?
in ischemic lesions due to the dual blood supply of this area from the middle and posterior cerebral arteries
Symptoms of papiloedema?
disc oedema develops, enlargement of a blind sport and blurring of vision, leading to optic neuritis and visual loss
Causes of papilloedema?
raised ICP from tumour, abscess of meningitis, retinal vein obstruction form thrombosis or compression, optic neuritis from demyelination causing inflammation or accelerated hypertension
What causes the pupil to constrict?
bright light, stimulates the Edinger-Westphal nucleus in the midbrain (via the optic tract and the convergence centre in the midbrain) and oculommotor nerve causing contriction
What causes pupil dilation?
sympathetic fibres in the hypothalamus running through the brainstem into the cervical cord and emerge in the spinal cord at T1 to ascend to the neck
Causes of persistent pupillary dilation?
third cranial nerve palsy, antimuscarinic eyedrops, myotonic pupil (Holmes-Adie pupil) which is a delayed/absent reaction to light and convergence seen in young women
Causes of persistent pupillary constriction?
parasympathetic eyedrops for glaucoma, Horner’s syndrome, Argyll Robertson pupil, opiate addiction
What is Horner’s syndrome?
interruption of the sympathetic fibres to one eye, causing unilateral pupillary constriction, slight ptosis, enophthalmos, loss of sweating on ipsilateral side of the face
What is Argyll Robertson pupil?
small irregular pupil fixed to light and contricts on convergence, caused by neruosyphilis and DM
Function, damage, cause and symptoms of occulomotor nerve?
control ciliary muscles in the eye, change the shape of the eyes for accommodation for viewing objects
damage can cause dipilopia (double vision), unilater complete ptosis and ocular nerve palsy
causes deviation down and out of the eyes
caused by trauma or berry aneurysm in the posterior communicating artery which runs alongside the nerve
Function, damage, cause and symptoms of the trochlear nerve?
Controls extrinsic eye muscles (suoerior oblique muscle)
damage can cause eye problems and vertical diplopia (WHEN LOOKING DOWN OR AWAY FROM AFFECTED SIDE) and nerve palsy (weakness or inability of the nerve)
caused by grave’s disease
Function, damage, cause and symptoms of the trigeminal nerve?
for mastication muscles and skin sensation of face and scalp, supplies mucus membranes of sinuses, nose, mouth, tongue and teeth
damage can cause face pain (forehead) and difficulty clenching the jaw, pain when eating, jaw deviates to side of lesion
caused by neurlagia, herpes virus, carcinoma
Function, damage, cause and symptoms of the abducens never?
extrinsic eye movement via the lateral rectus muscle
damage causes one eye to face inwards permanently this produces a squint and diplopia when looking at the side of the lesion
caused by nerve palsy, cerebral vascular accidents, combined damage from cranial nerve 4
Function, damage, cause and symptoms of facial nerve?
for taste, saliva and tear secretion and facial expression
damage causes lack of facial expression on the affected side of the face (bells palsy), impaired taste
severe damage can cause face paralysis
caused by versticular voster virus and trauma
What does 7th nerve palsy, cerebellar signs and 5th, 6th and 8th nerve involvement suggest?
lesion of the cerebellopontine angle, from a meningioma or acoustic neuroma
What do cavernous sinus lesions involve?
oculomotor nerves, opthlamic, maxialy division
What conditions can affect the cranial nerves?
DM, sarcoidosis, vasculitis, syphilis, brain stem tumours, MS, infarction
What is Bell’s palsy and when does it occur?
acute isolater unilateral facial nerve palsy caused by a viral infection (herpes simplex) cause swelling of the 7th nerve within the petrous temporal bone, peak incidence between 65-74 and more common in pregnancy
Function, damage, cause and symptoms of vestibulocochlear nerve?
for hearing and vestibular function (balance)
damage can cause sensorineural deafness and tinnitus (noise ringing in ear), veritgo (illusion of movement which can cause vomiting), loss of air conduction in ear, nystagmus and loss of balance
caused by perilymph fistula, cochlear concussion and auditory oscicle disruption and damage to nerve directly
What is nystagmus?
rhythmic oscillation of the eyes can be pendular (pendular movement of the eyes, no rapid phase, occurs with poor visual fixation or congental lesion) or jerk (fast and slow component)
What is the difference between horizontal and veritical nystagmus?
horzontal can be peripheral (transient minutes or hours) or central lesions (weeks, months)
Function, damage, cause and symptoms of the glossopharengeal nerve?
taste, tongue sensation, saliva secretion, o2 and co2 monitoring in blood
damage causes pain in tongue, throat, tonsils and ear from compression of nerve
damage caused by combination to 10 and 11
Function, damage, cause and symptoms of vagus nerve?
taste, pharyngeal activity, epiglottis sensation, innervation of GI tract, control trachea and cardiac muscles
damage causes dysphgaia, difficulty speaking, vocal cord weakness, damage to nuclear amygus, cause aphonia (harsh voice), pain
Function, damage, cause and symptoms of the accessory nerve?
pharynx, larynx and soft palate muscles, sternocleoidmastoid and trapezius muscles
damage causes paralysis of the sternocleoidmastoid muscle leadness to flatness of neck and inability to rotate the neck, paralysis of trapezius muscle causing drooping of muscle and inability to raise shoulders
damage usually involves nerves 9 and 10, cuased by wound to neck
Function, damage, cause and symptoms of the hypoglossal nerve?
for tongue muscles
damage cause lingual paralysis, dysarthria, and dysphagia, muscle tongue atrophy, so half of tongue cannot be controlled and deviates to side of lesion.
caused by tumour, stroke, infection
Function of spinal nerves?
carry information between CNS and periphery
What are the two pathways that the peripheral ascend to the thalamus and the cerebral cortex?
posterior columns - carrying sensory modalities for vibration, joint position sense, two point discrimination and light touch, they ascend uncrossed to the gracile and cuneate nuclei in the medulla, then the second oder neurons cross the midline to form the medial lemniscus and pass to the thalamus
spinothalamic tracts - carry sensations of pain and temperature, fibres synapse in the dorsal horn of the cord, crossing the midline and ascend as the spinothalamic tracts to the thalamus
What are the main symptoms of posterior column and spinothalamic tract lesions?
paraesthesiae, numbness and pain
Symptoms of peripheral nerve lesions?
felt in the distribution of the affected peripheral never e.g. median nervem has bilateral symmetrical, distal sensory loss and burning
Symptoms of spinal root lesions?
symptoms in the dermatome supplied by that root, tinglign discomfort (if it was a lesion of the sensory tract there would be general symptoms no specific dermatomes
Symptoms of spinal cord lesions?
evident below level of lesion
spinothalamic leads to contralateral pain and temperature sensation loss below lesions
proprioception lesion results in loss of this ipsilaterally below lesion
Symptoms of a pontine lesion?
loss of all forms of sensation on opposite side of lesion
Symptoms of thalamaic lesions?
complete contralateral sensory loss and spontaenous pain (caused by thalamic infarct)
Symptoms of cortical lesions?
sensory loss, neglect of one side of the body, subtle disorders of sensation , no pain
Upper motor neuron lesion symptoms?
oppssite side to lesion
fasciculation absent, no muscle wasting, spasticity, clonus, weakness in arm extensors and leg flexors, exaggerated tendon reflexes, extensor plantar response, drift of the outstretched hand downwards
Lower motor neuron lesion symptoms?
signs are on the same side
fasiculation present, wasting, hypotonia, loss of tendon reflexes
What is fasciculation?
visible contraction of single motor units, appearing as a twitch
Symptoms of acute injury to upper motor neurons?
transient flaccid weakness and hyporeflexia
What are the 2 main patterns of clinical features that occur in UMN disorders?
hemiparesis - weakness of the limbs on one side, usually caused by lesion within brain or brainstem e.g. stroke
paraparesis - weakness of legs, bilateral damage to corticospinal tracts caused by lesions below T1, tetraparesis in quadriplegic, weakness of arms and legs indicating high cervical cord damage from trauma - cord lesions result in UMN signs below lesion, LMN signs at lesion and unaffected muscle above lesion
What mainly causes LMN lesions?
anterior horn cell lesions (MND and poliomyelitis)
spinal root lesions (cervical and lumbar disc lesions)
peripheral nerve lesions (trauma, compression, polyneuropathy)
Based on rapidity of onset, what does vision loss suggest the cause?
sudden - vascular (GCA)
acute - inflmmatory/infectious (optic neuritis, TB)
subacute - inflammatory/infectious/neoplastic
chronic - neoplastic/degenerative
episodic - migraine
Based on symptoms, what is the suggesting cause of vision loss?
headache - migraine, tumour, raised ICP
malaise, fever, myalgia, headache, jaw claudication - giant cell arteritis
painful monocular visual loss - optic neuritis
systemic weakness, dysarthria, dysphagia - MG
dysarthria and ataxia - posterior fossa lesion
What social factors could lead to vision loss?
smoking, alcohol - carcnoma and tobacco alcohol amblyopia
diet - nutritional optic neuropathy
occupation
What genetic disorders can cause vision loss?
Leber’s herditary optic neruopathy and AD/R optic neuropathy, MS
What is the papillomacular bundle?
contains >90% of all retinal nerve fibres in the optic nerve, projecting images from the macula, with a high metabolic activity
lesions causes a central or centro caecal scotoma (lebers hereditary optic neuropathy, toxic and nutritional optic neurpathy and optic neuritis)
What causes a superior homonymous quadtrantanopias?
lesion of Meyers loop
inferior striate cortex below the calcarine fissure lesion
What causes an inferior homonymous quadrantanopias?
parietal lobe lesions and superior striate cortex lesions
What is an incongruous visual field defect?
the defects do not match up between the two eyes
When does macular sparing occur?
with occipital lesions that spare the posterolateral striate cortex due to the contralateral blood supply
What are the different causes of ptosis?
partial - horners syndrome
complete - third nerve palsy
varying/fatiguing - MG
