General Flashcards
Examples of 5HT3 antagonists and their mechanism?
Ondansetron and palonsetron
5HT3 receptor antagonist - centrally acting in medulla oblongata in chemoreceptor trigger zone
Side effects of 5HT3 antagonists?
Constipation
QT prolongation
Advantage of palonsetron vs ondansetron?
Second generation 5HT3 antagonist
Less QT prolongation
Who do absence seizures mostly affect?
onset of 3-10 years old and girls are affected twice as commonly as boys
Features of absence seizures?
absences last a few seconds and are associated with a quick recovery
seizures may be provoked by hyperventilation or stress
the child is usually unaware of the seizure
they may occur many times a day
EEG: bilateral, symmetrical 3Hz spike and wave pattern
EEG: bilateral, symmetrical 3Hz spike and wave pattern, suggestive of?
Absence seizure
Management of absence seizures?
sodium valproate and ethosuximide are first-line treatment
good prognosis - 90-95% become seizure free in adolescence
Cause of absent plantar reflexes + extensor planters
subacute combined degeneration of the cord
motor neuron disease
Friedreich’s ataxia
syringomyelia
taboparesis (syphilis)
conus medullaris lesion
Where is the lesion if plantar reflexes + extensor planters
lesion producing both upper motor neuron (extensor plantars) and lower motor neuron (absent ankle jerk) signs
What is acute disseminated encephalomyelitis?
autoimmune demyelinating disease of the central nervous system
post-infectious encephalomyelitis
Some causes of acute disseminated encephalomyelitis?
Common infections include measles, mumps, rubella and varicella and more
Clinical course of acute disseminated encephalomyelitis ?
Lag time, followed by acute onset multifocal neurological symptoms with rapid deterioration
Nonspecific features: Fever, nausea. vomiting, oculomotor effects
MRI imaging may show areas of supra and infra-tentorial demyelination
No biomarkers
Treatment of disseminated encephalomyelitis?
intravenous glucocorticoids and the consideration of IVIG
What is anti NMDA encephalitis?
Anti-NMDA receptor encephalitis is a paraneoplastic syndrome, presenting as prominent psychiatric features
Features of anti-NMDA encephalitis ?
agitation, hallucinations, delusions and disordered thinking; seizures, insomnia, dyskinesias and autonomic instability
Associated findings with anti-NMDA receptor encephalitis?
Ovarian teratomas are detected in up to half of all female adult patients
CSF finding in anti-NMDA receptor encephalitis ?
Pleocytosis
If not normal
Management of anti-NMDA receptor encephalitis?
based of immunosuppression with intravenous steroids, immunoglobulins, rituximab, cyclophosphamide or plasma exchange, alone or in combination. Resection of teratoma is also therapeutic.
What antibodies are associated in anti-NMDA receptor encephalitis?
Anti-GM1
Anti-MuSK
Important points about wernicke’s area
lesion of the superior temporal gyrus
Blood supply: Inferior division left MCA
Area ‘forms’ the speech before ‘sending it’ to Broca’s area.
Features of wernicke’s aphasia (receptive aphasia) ?
Lesions result in sentences that make no sense, word substitution and neologisms but speech remains fluent - ‘word salad’
Comprehension impaired
Important points about Broca’s area (expressive aphasia)?
Due to a lesion of the inferior frontal gyrus. It is typically supplied by the superior division of the left MCA
Features of Broca’s aphasia?
Speech is non-fluent, laboured, and halting. Repetition is impaired
Comprehension is normal
Features of conductive aphasia ?
Speech is fluent but repetition is poor. Aware of the errors they are making
Comprehension is normal
What causes a conductive aphasia?
Classically due to a stroke affecting the arcuate fasiculus - the connection between Wernicke’s and Broca’s area
Features of global aphasia
Large lesion affecting all 3 of the above (Brocas, wernickes and arcuate fasiculus) resulting in severe expressive and receptive aphasia
May still be able to communicate using gestures
What is an Arnold chiari malformation ?
Arnold-Chiari malformation describes the downward displacement, or herniation, of the cerebellar tonsils through the foramen magnum.
Malformations may be congenital or acquired through trauma.
Features of Arnold chair malformation?
non-communicating hydrocephalus may develop as a result of obstruction of cerebrospinal fluid (CSF) outflow
headache
syringomyelia
In ataxia telectangesia, what is the genetic mutation and its impact?
Defect in the ATM gene which encodes for DNA repair enzymes.
It is one of the inherited combined immunodeficiency disorders.
Features of ataxia telengectasia?
Autosomal recessive
cerebellar ataxia
telangiectasia (spider angiomas)
IgA deficiency resulting in recurrent chest infections
10% risk of developing malignancy, lymphoma or leukaemia, but also non-lymphoid tumours
Differences between Fredrick’s ataxia and ataxia telengectasia?
Features of autonomic neuropathy?
impotence, inability to sweat, postural hypotension
postural hypotension e.g. drop of 30/15 mmHg
loss of decrease in heart rate following deep breathing
pupils: dilates following adrenaline instillation
Causes of autonomic neuropathy?
diabetes
Guillain-Barre syndrome
multisystem atrophy (MSA), Shy-Drager syndrome
Parkinson’s
infections: HIV, Chagas’ disease, neurosyphilis
drugs: antihypertensives, tricyclics
craniopharyngioma
Mechanism of baclofen and its use?
agonist of GABA receptors
acts in the central nervous system (brain and spinal cord)
Used to treat spasticity
What is Bell’s palsy?
acute, unilateral, idiopathic, facial nerve paralysis.
Possible associated herpes simplex virus
Peak incidence 20-40 yrs
In lower motor neurological facial palsy, is forehead affected?
Yes
Features of Bell’s palsy?
lower motor neuron facial nerve palsy - forehead affected
in contrast, an upper motor neuron lesion ‘spares’ the upper face
patients may also notice post-auricular pain (may precede paralysis), altered taste, dry eyes, hyperacusis
Management in Bell’s palsy?
oral prednisolone within 72 hours of onset of Bell’s palsy
eye care is important to prevent exposure keratopathy
- prescribe tears and tape
Features of BPPV?
Vertigo with change of head position
vertigo triggered by change in head position (e.g. rolling over in bed or gazing upwards)
may be associated with nausea
each episode typically lasts 10-20 seconds
positive Dix-Hallpike manoeuvre, indicated by:
patient experiences vertigo
rotatory nystagmus
Treatment for BPPV and how successful is it?
Epley manoeuvre (successful in around 80% of cases)
teaching the patient exercises they can do themselves at home, termed vestibular rehabilitation, for example Brandt-Daroff exercises
Benign rolandic epilepsy features?
seizures characteristically occur at night
seizures are typically partial (e.g. paraesthesia affecting face) but secondary generalisation may occur (i.e. parents may only report tonic-clonic movements)
child is otherwise normal
Normally resolves by adolescence
Erbs palsy?
damage to C5,6 roots
winged scapula
may be caused by a breech presentation
Waiter’s tip
Klumpkes palsy?
damage to T1
loss of intrinsic hand muscles
due to traction
Claw hand
How do brain abscesses occur?
extension of sepsis from middle ear or sinuses, trauma or surgery to the scalp, penetrating head injuries and embolic events from endocarditis
Features of brain asbcess?
headache
- often dull, persistent
fever
- may be absent and usually not the swinging pyrexia seen with abscesses at other sites
focal neurology
e.g. oculomotor nerve palsy or abducens nerve palsy secondary to raised intracranial pressure
other features consistent with raised intracranial pressure
nausea
papilloedema
seizures
Management of brain abscess?
surgery
- a craniotomy is performed and the abscess cavity debrided
- the abscess may reform because the head is closed following abscess drainage.
IV antibiotics: IV 3rd-generation cephalosporin + metronidazole
intracranial pressure management: e.g. dexamethasone
Features of lesions in the parietal lobe?
sensory inattention
apraxias
astereognosis (tactile agnosia)
inferior homonymous quadrantanopia
Gerstmann’s syndrome (lesion of dominant parietal): alexia, acalculia, finger agnosia and right-left disorientation
Occipital lobe lesion?
homonymous hemianopia (with macula sparing)
cortical blindness
visual agnosia
Temporal lobe lesion?
Wernicke’s aphasia: this area ‘forms’ the speech before ‘sending it’ to Brocas area. Lesions result in word substituion, neologisms but speech remains fluent
superior homonymous quadrantanopia
auditory agnosia
prosopagnosia (difficulty recognising faces)
Frontal lobe lesion?
expressive (Broca’s) aphasia: located on the posterior aspect of the frontal lobe, in the inferior frontal gyrus. Speech is non-fluent, laboured, and halting
disinhibition
perseveration - repeating particular phrase
anosmia
inability to generate a list
Cerebellum lesion ?
midline lesions: gait and truncal ataxia
hemisphere lesions: intention tremor, past pointing, dysdiadokinesis, nystagmus
Area affected in Wernicke and Korsakoff syndrome
Medial thalamus and mammillary bodies of the hypothalamus
Area affected in hemiballisus
Subthalamic nucleus of the basal ganglia
Area affected by Huntington’s chorea?
Striatum (caudate nucleus) of the basal ganglia
Area affected by Kluver-Bucy syndrome (hypersexuality, hyperorality, hyperphagia, visual agnosia
Amygddala
Features of brown sequared syndrome?
Lateral hemisection of the cord
ipsilateral weakness below lesion
ipsilateral loss of proprioception and vibration sensation
contralateral loss of pain and temperature sensation
What is CADASIL?
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
rare cause of multi-infarct dementia
patients often present with migraine
What is CADASIL?
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
rare cause of multi-infarct dementia
patients often present with migraine
Uses of carbsmazepine?
Trigeminal neuralgia
Bipolar
Epilepsy
Adverse side effects of carebmazepine ?
P450 enzyme inducer
dizziness and ataxia
drowsiness
headache
visual disturbances (especially diplopia)
Steven-Johnson syndrome
leucopenia and agranulocytosis
hyponatraemia secondary to syndrome of inappropriate ADH secretion
Why may patients see new seizures after start carbamazepine ?
exhibit autoinduction,
Induces the enzyme that metabolisies it
hence when patients start carbamazepine they may see a return of seizures after 3-4 weeks of treatment.
What is cataplexy?
sudden and transient loss of muscular tone caused by strong emotion (e.g. laughter, being frightened). Around two-thirds of patients with narcolepsy have cataplexy.
Unilateral cerebellar lesions affects ipsilateral or contralateral side?
Ipsilateral
Features of cerebellar syndrome?
D - Dysdiadochokinesia, Dysmetria (past-pointing), patients may appear ‘Drunk’
A - Ataxia (limb, truncal)
N - Nystamus (horizontal = ipsilateral hemisphere)
I - Intention tremour
S - Slurred staccato speech, Scanning dysarthria
H - Hypotonia
Causes of cerebellar syndrome
Friedreich’s ataxia, ataxic telangiectasia
neoplastic: cerebellar haemangioma
stroke
alcohol
multiple sclerosis
hypothyroidism
drugs: phenytoin, lead poisoning
paraneoplastic e.g. secondary to lung cancer
Normal values for cerebrospinal fluid?
Normal values of cerebrospinal fluid (CSF) are as follows:
pressure = 60-150 mm (patient recumbent)
protein = 0.2-0.4 g/l
glucose = > 2/3 blood glucose
cells: red cells = 0, white cells < 5/mm³
Associatied with high lymphocytes in CSF?
viral meningitis/encephalitis
TB meningitis
partially treated bacterial meningitis
Lyme disease
Behcet’s, SLE
lymphoma, leukaemia
What is the mechanism behind chorea?
Chorea is caused by damage to the basal ganglia, especially the caudate nucleus.
What is chorea?
Chorea describes involuntary, rapid, jerky movements which often move from one part of the body to another.
Causes of chorea?
Huntington’s disease, Wilson’s disease, ataxic telangiectasia
SLE, anti-phospholipid syndrome
rheumatic fever: Sydenham’s chorea
drugs: oral contraceptive pill, L-dopa, antipsychotics
neuroacanthocytosis
pregnancy: chorea gravidarum
thyrotoxicosis
polycythaemia rubra vera
carbon monoxide poisoning
cerebrovascular disease
What is athetosis?
Sinuous movement of the limbs is termed athetosis
Features of cluster headache?
pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours
clusters typically last 4-12 weeks
intense sharp, stabbing pain around one eye (recurrent attacks ‘always’ affect same side)
the patient is restless and agitated during an attack
accompanied by redness, lacrimation, lid swelling
nasal stuffiness
miosis and ptosis in a minority
Management of cluster headache?
acute: 100% oxygen (80% response rate within 15 minutes), subcutaneous triptan (75% response rate within 15 minutes)
prophylaxis: verapamil is the drug of choice. There is also some evidence to support a tapering dose of prednisolone
NICE recommend seeking specialist advice from a neurologist if a patient develops cluster headaches with respect to neuroimaging
What are the autonomic cephalgia?
cluster headache, paroxysmal hemicrania and short-lived unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT)
What does the sciatic nerve divide into?
The sciatic nerve divides into the tibial and common peroneal nerves. Injury often occurs at the neck of the fibula
Common pudenal nerve injury?
weakness of foot dorsiflexion
weakness of foot eversion
weakness of extensor hallucis longus
sensory loss over the dorsum of the foot and the lower lateral part of the leg
wasting of the anterior tibial and peroneal muscles
Types of chronic regional pain syndrome?
type I (most common): there is no demonstrable lesion to a major nerve
type II: there is a lesion to a major nerve
Features of chronic regional pain syndrome ?
progressive, disproportionate symptoms to the original injury/surgery
allodynia
temperature and skin colour changes
oedema and sweating
motor dysfunction
the Budapest Diagnostic Criteria are commonly used in the UK
Management of chronic regional pain syndrome?
early physiotherapy is important
neuropathic analgesia in-line with NICE guidelines
specialist management (e.g. Pain team) is required
Mechanism in CJD?
Progressive neurological condition caused by prion proteins. These proteins induce the formation of amyloid folds resulting in tightly packed beta-pleated sheets resistant to proteases.
Features of CJD?
Myoclonus
Dementia rapid onset
Investigation summary in CJD?
CSF is usually normal
EEG: biphasic, high amplitude sharp waves (only in sporadic CJD)
MRI: hyperintense signals in the basal ganglia and thalamus
Types of CJD?
Sporadic
New variant
Features of new variant CJD?
psychological symptoms such as anxiety, withdrawal and dysphonia are the most common presenting features
Prion protein is new variant CJD is encoded by what chromosome?
Chromosome 20
Risk factor for developing new variant CJD?
methionine homozygosity at codon 129 chromosome 20
Risk factor for developing new variant CJD?
methionine homozygosity at codon 129 chromosome 20
Other forms of prion diseases?
kuru
fatal familial insomnia
Gerstmann Straussler-Scheinker disease
Presentation of degenerative cervical myelopathy?
Pain (affecting the neck, upper or lower limbs)
Loss of motor function (loss of digital dexterity, preventing simple tasks such as holding a fork or doing up their shirt buttons, arm or leg weakness/stiffness leading to impaired gait and imbalance
Loss of sensory function causing numbness
Loss of autonomic function (urinary or faecal incontinence and/or impotence) - these can occur and do not necessarily suggest cauda equina syndrome in the absence of other hallmarks of that condition
Hoffman’s sign: is a reflex test to assess for cervical myelopathy. It is performed by gently flicking one finger on a patient’s hand. A positive test results in reflex twitching of the other fingers on the same hand in response to the flick.
What are risk factors of degenerative cervical myelopathy?
Occupation
Smoking
Genetics
Signed used to test for degenerative cervical myelopathy?
Hoffman’s sign: is a reflex test to assess for cervical myelopathy. It is performed by gently flicking one finger on a patient’s hand. A positive test results in reflex twitching of the other fingers on the same hand in response to the flick.
Best imaging for degenerative cervical cord myelopathy?
MRI
Treatment of cervical myelopathy?
Decompressive surgery
Urgent referral - should be seen / treated within 6 months of diagonosis
Prevents further damage
Drugs that cause peripheral neuropathy?
amiodarone
isoniazid
vincristine
nitrofurantoin
metronidazole
Driving advice: Once off seizure + No structural brain damage?
6 months
Driving advice: Once off seizure + structural brain damage?
12 months
Seizure free for 12 months?
Can apply for driving liscence
No seizure for 5 years - driving?
Can apply for a until 70 driving licence
Driving advice after one episode of syncope?
4 weeks once treated and explained
Driving advice for syncope when unexplained?
6 months off
Two or more episodes of syncope?
12 months off
Time off driving from stroke or TIA?
1 month
Driving advice: Multiple TIAs ?
3 months
Driving advice after craniotomy? Including transpheoidal surgery
If well - consider after 6 months
If not 1 year
Narcolepsy / cataplexy - driving?
Once symptoms satisfactorially under control
What is the function of dystrophin?
large membrane associated protein in muscle which connects the muscle membrane to actin, part of the muscle cytoskeleton
Inheritence of the muscular dystrophies?
X linked
Genetic mutation in duchene muscular dystrophy?
frameshift mutation resulting in one or both of the binding sites ( of the protein) are lost leading to a severe form
Genetic mutation in becker’s muscular dystrophy?
non-frameshift insertion in the dystrophin gene resulting in both binding sites being preserved leading to a milder form
Features of duchene muscular dystrophy?
progressive proximal muscle weakness from 5 years
calf pseudohypertrophy
Gower’s sign: child uses arms to stand up from a squatted position
30% of patients have intellectual impairment
Features of becker muscular dystrophy?
progressive proximal muscle weakness from 5 years
calf pseudohypertrophy
Gower’s sign: child uses arms to stand up from a squatted position
30% of patients have intellectual impairment
Features of infantile spasms? (West syndrome)
Brief spasms beginning in the first few months of life
key features:
- flexion of head, trunk, limbs → extension of arms (Salaam attack); last 1-2 secs, repeat up to 50 times
progressive mental handicap
- EEG: hypsarrhythmia
usually secondary to serious neurological abnormality (e.g. tuberous sclerosis, encephalitis, birth asphyxia) or may be idiopathic
Treatment of west syndrome?
possible treatments include vigabatrin and steroids
has a poor prognosis
Features of petit Mal seizure? Absence seizures?
onset 4-8 yrs
duration few-30 secs; no warning, quick recovery; often many per day
EEG: 3Hz generalized, symmetrical
good prognosis: 90-95% become seizure free in adolescence
Treatment of absence seizures?
sodium valproate, ethosuximide
Features of Lennox- gas taut syndrome?
may be an extension of infantile spasms
onset 1-5 yrs
features:
atypical absences, falls, jerks
90% moderate-severe mental handicap
EEG: slow spike
Treatment of Lennox-gas taut syndrome?
treatment: ketogenic diet may help
Features of benign rolandic epilepsy?
most common in childhood, more common in males
features: paraesthesia (e.g. unilateral face), usually on waking up
Features of juvenile myoclonic epilepsy? Jana syndrome
typical onset is in the teenage years, more common in girls
features:
infrequent generalized seizures, often in morning//following sleep deprivation
daytime
s
sudden, shock-like myoclonic seizure (these may develop before seizures)
treatment: usually good response to sodium valproate
What is a focal seizure ?
previously termed partial seizures
these start in a specific area, on one side of the brain
awareness depends on area affected
How can focal seizures be classified?
focal seizures can be classified as being motor (e.g. Jacksonian march), non-motor (e.g. déjà vu, jamais vu; ) or having other features such as aura
Must classify by awareness: focal aware vs focal impaired awareness
Features of generalised seizures?
engage or involve networks on both sides of the brain at the onset
consciousness lost immediately.
How can generalised seizure be divided?
Motor: tonic clonic
Non-motor: absence
Localising feature of temporal lobe epilepsy?
An aura occurs in most patients
typically a rising epigastric sensation
also psychic or experiential phenomena, such as déjà vu, jamais vu
less commonly hallucinations (auditory/gustatory/olfactory)
Localising feature of frontal lobe epilepsy?
Head/leg movements, posturing, post-ictal weakness, Jacksonian march
Localising features of partial lobe epilepsy?
Paraesthesia
Localising features of occipital lobe epilepsy?
Floaters/flashes
What should women with epilepsy do before becoming pregnant?
Folic acid 5mg
How much does taking anti-epileptics during pregnant increase risk of neural tube defect?
1-2% normal patients
3-4 in epilepsy
How should you aim to manage patients with epilepsy wishing to become pregnant?
Aim for mono therapy
Should not need to monitor medication levels
Congenital defect associated with sodium valporate?
Neural tube defect
Neurodevelopmental delay
Women of child bearing age should not be put on this drug if possible
Which anti-epileptic is considered to have the least teratogenic effect?
carbamazepine
Congenital defect associated with phenytoin?
cleft pallet
Is breast feeding safe?
Yes
Providing not on barbiturate
When should anti-epileptics be started?
Generally after second seizure
When should anti-epileptics be started after first seizure?
- The patient has a neurological deficit
- Brain imaging shows a structural abnormality
- The EEG shows unequivocal epileptic activity
- The patient or their family or carers consider the risk of having a further seizure unacceptable
Treatment of generalised tonic clonic seizure?
Male: sodium valproate
Female: Lamotrigene
Treatment of focal seizures?
- Lamotrigene, leveiteracetam
- carbamazepine, oxcarbazepine or zonisamide
Myoclonic seizure treatment?
males: sodium valproate
females: levetiracetam
Treatment of absence seizure?
first line: ethosuximide
second line:
male: sodium valproate
female: lamotrigine or levetiracetam
carbamazepine may exacerbate absence seizures
Treatment of tonic and atonic seizures?
males: sodium valproate
females: lamotrigine
Inheritance of essential tremor?
Autosomal dominant
Features of essential tremor?
postural tremor: worse if arms outstretched
improved by alcohol and rest
most common cause of titubation (head tremor)
Treatment of essential tremor?
propranolol is first-line
primidone is sometimes used
Mechanism of ethosuximide?
blocks T-type calcium channels in thalamic neurons
What is the afferent and efferent function of the facial nerve?
It is a mostly efferent nerve
Afferent: Taste (genicular ganglion)
Efferent: muscles of facial expression, digastric muscle and glands
Supply - ‘face, ear, taste, tear’
face: muscles of facial expression
ear: nerve to stapedius
taste: supplies anterior two-thirds of tongue
tear: parasympathetic fibres to lacrimal glands, also salivary glands
Causes of bilateral facial palsy?
sarcoidosis
Guillain-Barre syndrome
Lyme disease
bilateral acoustic neuromas (as in neurofibromatosis type 2)
as Bell’s palsy is relatively common it accounts for up to 25% of cases f bilateral palsy, but bilateral is only 1% of total Bell’s palsy cases
Causes of lower motor neurone facial nerve palsy?
Lower motor neuron
Bell’s palsy
Ramsay-Hunt syndrome (due to herpes zoster)
acoustic neuroma
parotid tumours
HIV
multiple sclerosis*
diabetes mellitus
Cause of upper motor neurone facial nerve?
Stroke
How do you determine a LMN vs a UMN facial palsy?
upper motor neuron lesion ‘spares’ upper face i.e. forehead
lower motor neuron lesion affects all facial muscles
Where are the sensory and motor nuclei of the facial nerve?
Motor: Pons
Sensory: Nervus intermedius
petrous temporal bone into the internal auditory meatus with the vestibulocochlear nerve. Here they combine to become the facial nerve.
What is facioscapulohumeral dystrophy?
Autosomal dominant dystrophy
facial muscles are involved first - difficulty closing eyes, smiling, blowing etc
weakness of the shoulder and upper arm muscles
abnormal prominence of the borders of the shoulder blades - ‘winging’
lower limb: hip girdle weakness, foot drop
Causes of foot drop?
Occurs due to weakness in foot dorsiflexors
common peroneal nerve lesion - the most common cause
L5 radiculopathy
sciatic nerve lesion
superficial or deep peroneal nerve lesion
other possible includes central nerve lesions (e.g. stroke) but other features are usually present
Features of an isolated peroneal nerve neuropathy?
if the patient has an isolated peroneal neuropathy there will be weakness of foot dorsiflexion and eversion. Reflexes will be normal
weakness of hip abduction is suggestive of a L5 radiculopathy
CN IV palsy?
supplies superior oblique (depresses eye, moves inward)
vertical diplopia
classically noticed when reading a book or going downstairs
subjective tilting of objects (torsional diplopia)
the patient may develop a head tilt, which they may or may not be aware of
when looking straight ahead, the affected eye appears to deviate upwards and is rotated outwards
Genetic mechanism behind Fredrick’s ataxia?
Autosomal recessive, trinucleotide repeat disorder characterised by a GAA repeat in the X25 gene on chromosome 9 (frataxin).
Does not demonstrate anticipation
Fredrick’s ataxia phenotype?
Gait ataxia and kyphoscoliosis are the most common presenting features.
Neurological features
absent ankle jerks/extensor plantars
cerebellar ataxia
optic atrophy
spinocerebellar tract degeneration
Other features:
hypertrophic obstructive cardiomyopathy (90%, most common cause of death)
diabetes mellitus (10-20%)
high-arched palate
Causes of gingival hyperplasia?
Drug causes of gingival hyperplasia
phenytoin
ciclosporin
calcium channel blockers (especially nifedipine)
Other causes of gingival hyperplasia include
acute myeloid leukaemia (myelomonocytic and monocytic types)
What triggers Guillain barre syndrome?
Triggered by an infection (classically Campylobacter jejuni)
Pathogenesis of Guillain barre syndrome?
cross-reaction of antibodies with gangliosides in the peripheral nervous system
correlation between anti-ganglioside antibody (e.g. anti-GM1) and clinical features has been demonstrated
anti-GM1 antibodies in 25% of patients
What is Miller Fischer Syndrome?
variant of Guillain-Barre syndrome
associated with ophthalmoplegia, areflexia and ataxia. The eye muscles are typically affected first
usually presents as a descending paralysis rather than ascending as seen in other forms of Guillain-Barre syndrome
anti-GQ1b antibodies are present in 90% of cases
Features of Guillain barre syndrome?
Initial symptom: Backpain
Guillain-Barre syndrome is progressive, symmetrical weakness of all the limbs.
Weakness is typically ascending
Reduced / absent reflexes
Other features
- There may be a history of gastroenteritis
- Respiratory muscle weakness
- Cranial nerve involvement
1.diplopia
2.bilateral facial nerve palsy
3.oropharyngeal weakness is common
- Autonomic involvement
urinary retention
diarrhoea
Investigations in Guillain barre syndrome?
lumbar puncture
rise in protein with a normal white blood cell count (albuminocytologic dissociation) - found in 66%
Nerve condution studies may be performed
decreased motor nerve conduction velocity (due to demyelination)
prolonged distal motor latency
increased F wave latency
Management of Guillain barre?
- Intravenous immunoglobulin
- REGULAR MONITORING OF RESPIRATORY FUNCTION
- Plasma exchange
Poor prognostic factors for Guillain barre?
age > 40 years
poor upper extremity muscle strength
previous history of a diarrhoeal illness (specifically Campylobacter jejuni)
high anti-GM1 antibody titre
need for ventilatory support
Factors indicating a head CT within 1 hour?
GCS < 13 on initial assessment
GCS < 15 at 2 hours post-injury
suspected open or depressed skull fracture
any sign of basal skull fracture (haemotympanum, ‘panda’ eyes, cerebrospinal fluid leakage from the ear or nose, Battle’s sign).
post-traumatic seizure.
focal neurological deficit.
more than 1 episode of vomiting
Factors indicating a head CT within 8 hours?
age 65 years or older
any history of bleeding or clotting disorders including anticogulants
dangerous mechanism of injury (a pedestrian or cyclist struck by a motor vehicle, an occupant ejected from a motor vehicle or a fall from a height of greater than 1 metre or 5 stairs)
more than 30 minutes’ retrograde amnesia of events immediately before the head injury
warfarin who have sustained a head injury with no other indications for a CT head scan, perform a CT head scan within 8 hours of the injury.
What is a primary brain injury?
focal (contusion/haematoma) or diffuse (diffuse axonal injury)
diffuse axonal injury occurs as a result of mechanical shearing following deceleration, causing disruption and tearing of axons
Headinjury: Haematoma vs contusion?
haematomas can be extradural, subdural or intracerebral, while contusions may occur adjacent to (coup) or contralateral (contre-coup) to the side of impact
What is a secondary brain injury?
occurs when cerebral oedema, ischaemia, infection, tonsillar or tentorial herniation exacerbates the original injury. The normal cerebral auto regulatory processes are disrupted following trauma rendering the brain more susceptible to blood flow changes and hypoxia
What is Cushing’s reflex?
hypertension and bradycardia) often occurs late and is usually a pre terminal event
Where is the bleed in a extradural bleed?
Bleeding into the space between the dura mater and the skull
Bleed from middle meningeal artery
Exhibit a lucid interval –> crash
Features: Raised intracranial pressure
Where is the bleed in a subdural haematoma?
Bleeding into the outermost meningeal layer. Most commonly occur around the frontal and parietal lobes.
Risk factors include old age, alcoholism and anticoagulation.
Slower onset of symptoms than a epidural haematoma. There may be fluctuating confusion/consciousness
Features of migraine?
Severe headache which is usually unilateral and throbbing in nature
May be be associated with aura, nausea and photosensitivity
Aggravated by, or causes avoidance of, routine activities of daily living. Patients often describe ‘going to bed’.
In women may be associated with menstruation
Features of tension headache?
Recurrent, non-disabling, bilateral headache, often described as a ‘tight-band’
Not aggravated by routine activities of daily living
Cluster headache features?
Pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours with clusters typically lasting 4-12 weeks
Intense pain around one eye (recurrent attacks ‘always’ affect same side)
Patient is restless during an attack
Accompanied by redness, lacrimation, lid swelling
More common in men and smokers
Temporal arteritis?
Typically patient > 60 years old
Usually rapid onset (e.g. < 1 month) of unilateral headache
Jaw claudication (65%) - tiredness of muscles of mastication
Tender, palpable temporal artery
Raised ESR
Medical overuse headache?
Present for 15 days or more per month
Developed or worsened whilst taking regular symptomatic medication
Patients using opioids and triptans are at most risk
May be psychiatric co-morbidity
Causes of acute headache?
meningitis
encephalitis
subarachnoid haemorrhage
head injury
sinusitis
glaucoma (acute closed-angle)
tropical illness e.g. Malaria
Causes of chronic headache?
chronically raised ICP
Paget’s disease
psychological
Damage to what causes hemiballism?
Subthalamic nucleus
What is hemiballism?
involuntary, sudden, jerking movements which occur contralateral to the side of the lesion.
ballisic movements primarily affect the proximal limb musculature whilst the distal muscles may display more choreiform-like movements
Treatment of hemiballism?
Anti-dopamine
Halloperidol
What lobes of the brain does herpes simplex encephalitis typically affect?
Temporal lobes most
Can affect inferior frontal
Features of herpes simplex encephalitis?
fever, headache, psychiatric symptoms, seizures, vomiting
focal features e.g. aphasia
peripheral lesions (e.g. cold sores) have no relation to the presence of HSV encephalitis
What virus is implicated in hopers simplex encephalitis?
HSV1
Investigation finding in herpes simplex encephalitis?
CSF: lymphocytosis, elevated protein
PCR for HSV
CT: medial temporal and inferior frontal changes (e.g. petechial haemorrhages) - normal in one-third of patients
MRI is better
EEG pattern: lateralised periodic discharges at 2 Hz
Investigation in herpex simplex encephalitis?
CSF: lymphocytosis, elevated protein
PCR for HSV
CT: medial temporal and inferior frontal changes (e.g. petechial haemorrhages) - normal in one-third of patients
MRI is better
EEG pattern: lateralised periodic discharges at 2 Hz
Treatment of herpes simplex encephalitis?
Intravenous acyclovir
What is charco-marie tooth called now?
Hereditary sensorimotor neuropathy
What are the two types of HSMN?
HSMN type I: primarily due to demyelinating pathology
HSMN type II: primarily due to axonal pathology
Features of HSMN type 1 ?
autosomal dominant
due to defect in PMP-22 gene (which codes for myelin)
features often start at puberty
motor symptoms predominate
distal muscle wasting, pes cavus, clawed toes
foot drop, leg weakness often first features
Features of Huntington disease?
Features typical develop after 35 years of age
chorea
personality changes (e.g. irritability, apathy, depression) and intellectual impairment
dystonia
saccadic eye movements
Genetics behind Huntington’s disease?
autosomal dominant
trinucleotide repeat disorder: repeat expansion of CAG
- anticipation occurs
results in degeneration of cholinergic and GABAergic neurons in the striatum of the basal ganglia
due to defect in huntingtin gene on chromosome 4
Risk factors of idiopathic intracranial hypertension?
obesity
female sex
pregnancy
drugs*
combined oral contraceptive pill
steroids
tetracyclines
vitamin A
lithium
Features of idiopathic intracranial hypertension
headache
blurred vision
papilloedema (usually present)
enlarged blind spot
sixth nerve palsy may be present
Management of idiopathic intracranial hypertension
weight loss
diuretics e.g. acetazolamide
topiramate is also used, and has the added benefit of causing weight loss in most patients
repeated lumbar puncture
surgery: optic nerve sheath decompression and fenestration may be needed to prevent damage to the optic nerve. A lumboperitoneal or ventriculoperitoneal shunt may also be performed to reduce intracranial pressure
Where is the lesion in internuclear ophthalmoplegia ?
Lesion in the medial longitudinal fasciculus (MLF)
controls horizontal eye movements by interconnecting the IIIrd, IVth and VIth cranial nuclei
located in the paramedian area of the midbrain and pons
Features of internuclear ophthalmoplegia?
impaired adduction of the eye on the same side as the lesion
horizontal nystagmus of the abducting eye on the contralateral side
Causes of internuclear ophthalmoplegia?
MS
Vascular disease
Features of intracranial venous thrombosis?
headache (may be sudden onset)
nausea & vomiting
reduced consciousness
Investigations for intracranial venous thrombosis?
MRI venography is the gold standard
CT venography is an alternative
non-contrast CT head is normal in around 70% of patients
D-dimer levels may be elevated
Specific syndrome associated with intracranial venous thrombosis ?
Sagittal sinus thrombosis
may present with seizures and hemiplegia
parasagittal biparietal or bifrontal haemorrhagic infarctions are sometimes seen
‘empty delta sign’ seen on venography
Cavernous sinus thrombosis
other causes of cavernous sinus syndrome: local infection (e.g. sinusitis), neoplasia, trauma
periorbital oedema
ophthalmoplegia: 6th nerve damage typically occurs before 3rd & 4th
trigeminal nerve involvement may lead to hyperaesthesia of upper face and eye pain
central retinal vein thrombosis
Management of intracranial venous thrombosis?
anticoagulation
typically with low molecular weight heparin acutely
warfarin is still generally used for longer term anticoagulation
Features of saggital sinus syndrome?
may present with seizures and hemiplegia
parasagittal biparietal or bifrontal haemorrhagic infarctions are sometimes seen
‘empty delta sign’ seen on venography
Features of cavernous sinus thrombosis?
other causes of cavernous sinus syndrome: local infection (e.g. sinusitis), neoplasia, trauma
periorbital oedema
ophthalmoplegia: 6th nerve damage typically occurs before 3rd & 4th
trigeminal nerve involvement may lead to hyperaesthesia of upper face and eye pain
central retinal vein thrombosis
Features of lateral sinus thrombosis?
6th and 7th cranial nerve palsies
Pathophysiology behind Lambert eaton syndrome?
antibody directed against presynaptic voltage-gated calcium channel in the peripheral nervous system.
Features of Lambert eaton syndrome?
repeated muscle contractions lead to increased muscle strength (in contrast to myasthenia gravis)
limb-girdle weakness (affects lower limbs first)
hyporeflexia
autonomic symptoms: dry mouth, impotence, difficulty micturating
ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)
Findings on EMG in Lambert eaton syndrome?
incremental response to repetitive electrical stimulation
Management of Lambert eaton syndrome?
treatment of underlying cancer
immunosuppression, for example with prednisolone and/or azathioprine
3,4-diaminopyridine is currently being trialled
IVIG
Plasma exchange
Adverse effect of lamotrigine?
Steven Johnson syndrome
Mechanism of lamotrigine?
Sodium channel blocker
What is lateral medullary syndrome also known as?
Wallenburg syndrome
Pathophysiology behind lateral medullary syndrome?
Occlusion of posterior inferior cerebellar artery
Features of lateral medullary syndrome?
Cerebellar features + brainstorm features
Cerebellar features:
1. Ataxia
2. Nystagmus
Brainstem features:
1. ipsilateral: dysphagia, facial numbness, cranial nerve 2. palsy e.g. Horner’s
3. contralateral: limb sensory loss
Adverse effect of levodopa?
dyskinesia
‘on-off’ effect
postural hypotension
cardiac arrhythmias
nausea & vomiting
psychosis
reddish discolouration of urine upon standing
Why is levodopa used with a decarboxylase inhibitor?
Prevents peripheral metabolism of levodopa to dopamine
Cause of macroglossia?
hypothyroidism
acromegaly
amyloidosis
Duchenne muscular dystrophy
mucopolysaccharidosis (e.g. Hurler syndrome)
Down syndrome has apparent marcoglossia due to face hypoplasia
Features of Ménière’s disease?
Unknown cause - path ins endolymph system dilation
recurrent episodes of vertigo, tinnitus and hearing loss (sensorineural). Vertigo is usually the prominent symptom
a sensation of aural fullness or pressure is now recognised as being common
other features include nystagmus and a positive Romberg test
episodes last minutes to hours
typically symptoms are unilateral but bilateral symptoms may develop after a number of years
What is Romberg’s test?
determines if your balance issues are related to the function of your dorsal column by removing the visual and vestibular components that contribute to maintaining balance
Feet together - close eyes
Management of Meniere’s?
ENT assessment
Must tell DVLA
Acute attacks: buccal or intramuscular prochlorperazine. Admission is sometimes required
prevention: betahistine and vestibular rehabilitation exercises may be of benefit
Meningitis complications?
Neurological sequalae:
- sensorineural hearing loss (most common)
- seizures
- focal neurological deficit
Pressure
- brain herniation
- hydrocephalus
What is the risk with mengineal meningitis?
Waterhouse-Friderichsen syndrome (adrenal insufficiency secondary to adrenal haemorrhage).
Diagnostic criteria for migraine?
A At least 5 attacks fulfilling criteria B-D
B Headache attacks lasting 4-72 hours* (untreated or unsuccessfully treated)
C Headache has at least two of the following characteristics:
1. unilateral location*
2. pulsating quality (i.e., varying with the heartbeat)
3. moderate or severe pain intensity
4. aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)
D During headache at least one of the following:
1. nausea and/or vomiting*
2. photophobia and phonophobia
E Not attributed to another disorder (history and examination do not suggest a secondary headache disorder or, if they do, it is ruled out by appropriate investigations or headache attacks do not occur for the first time in close temporal relation to the other disorder)
Migraine mangement
Acute:
1. Triptan and Paracetamol or NSAID
2. Young people consider nasal triptan
3. Then consider non-oral antiemetics, triptan, NSAID
Prophylaxis:
Give if experience > 2 episodes per month
1. Topiramte or Propanolol
- Give propanolol in women - topiramate is teratogenic
2. Riboflavin may reduced frequency of attacks
Treatment of menstrual migraine prophylaxis?
recommend either frovatriptan (2.5 mg twice a day) or zolmitriptan (2.5 mg twice or three times a day) as a type of ‘mini-prophylaxis’
Other prophylaxis options for migraine, not on NICE guidance?
Candesartan
monoclonal antibodies directed against the calcitonin gene-related peptide (CGRP) receptor: examples include erenumab
How to treat acute migraine in a pregnant woman?
paracetamol 1g is first-line
NSAIDs can be used second-line in the first and second trimester
avoid aspirin and opioids such as codeine during pregnancy
Acute treatment of migraine with pregnancy?
mefanamic acid or a combination of aspirin, paracetamol and caffeine. Triptans are also recommended in the acute situation
Causes of miosis?
Causes of miosis (small pupil)
Horner’s syndrome
Argyll-Robertson pupil
senile miosis
pontine haemorrhage
congenital
Drugs causes
opiates
parasympathomimetics: pilocarpine
organophosphate toxicity
Features of motor neurone disease?
fasciculations
the absence of sensory signs/symptoms*
the mixture of lower motor neuron and upper motor neuron signs
wasting of the small hand muscles/tibialis anterior is common
Things MND does not do?
Other features
doesn’t affect external ocular muscles
no cerebellar signs
abdominal reflexes are usually preserved and sphincter dysfunction if present is a late feature
Treatment of motor neurone disease?
Riluzole
- prevents stimulation of glutamate receptors
- used mainly in amyotrophic lateral sclerosis
- prolongs life by about 3 months
Respiratory:
-non-invasive ventilation (usually BIPAP) is used at night
studies have shown a survival benefit of around 7 months
MND types?
Amyotrophic lateral sclerosis (50% of patients)
typically LMN signs in arms and UMN signs in legs
in familial cases the gene responsible lies on chromosome 21 and codes for superoxide dismutase
Primary lateral sclerosis
UMN signs only
Progressive muscular atrophy
LMN signs only
affects distal muscles before proximal
carries best prognosis
Progressive bulbar palsy
palsy of the tongue, muscles of chewing/swallowing and facial muscles due to loss of function of brainstem motor nuclei
carries worst prognosis
Pathophysiology of MS?
Type 4 hypersensitivity
Central demyelination
Risk factors for MS?
High latitude
Women
Genetics ( monozygotic twins 30%)
Trajectories / subtypes of MS?
Relapsing-remitting disease
most common form, accounts for around 85% of patients
acute attacks (e.g. last 1-2 months) followed by periods of remission
Secondary progressive disease
describes relapsing-remitting patients who have deteriorated and have developed neurological signs and symptoms between relapses
around 65% of patients with relapsing-remitting disease go on to develop secondary progressive disease within 15 years of diagnosis
gait and bladder disorders are generally seen
Primary progressive disease
accounts for 10% of patients
progressive deterioration from onset
more common in older people
Visual symptoms in MS?
optic neuritis: common presenting feature
optic atrophy
Uhthoff’s phenomenon: worsening of vision following rise in body temperature
internuclear ophthalmoplegia
Sensory features in MS?
pins/needles
numbness
trigeminal neuralgia
Lhermitte’s syndrome: paraesthesiae in limbs on neck flexion
urinary incontinence
sexual dysfunction
intellectual deterioration
Motor features in MS?
ataxia: more often seen during an acute relapse than as a presenting symptom
tremor
Investigations in MS?
MRI:
high signal T2 lesions
periventricular plaques
Dawson fingers: often seen on FLAIR images - hyperintense lesions penpendicular to the corpus callosum
CSF analysis in MS?
oligoclonal bands (and not in serum)
increased intrathecal synthesis of IgG
Acute management of MS?
High-dose steroids (e.g. oral or IV methylprednisolone) may be given for 5 days to shorten the length of an acute relapse
Indication for initiating long term treatment in MS?
Typical indications for disease-modifying drugs include:
relapsing-remitting disease + 2 relapses in past 2 years + able to walk 100m unaided
secondary progressive disease + 2 relapses in past 2 years + able to walk 10m (aided or unaided)
Mechanism of natalizumab?
a recombinant monoclonal antibody that antagonises alpha-4 beta-1-integrin found on the surface of leucocytes
inhibit migration of leucocytes across the endothelium across the blood-brain barrier
generally considered to have the strongest evidence base for preventing relapse of the disease-modifying and hence is often used first-line
given intravenously
Mechanism of ocrelizumab?
humanized anti-CD20 monoclonal antibody
like natalizumab, it is considered a high-efficacy drug that is often used first-line
given intravenously
Mechanism of fingolimod?
sphingosine 1-phosphate (S1P) receptor modulator
prevents lymphocytes from leaving lymph nodes
oral formulations are available
Mechanism of glatiramer?
immunomodulating drug - acts as an ‘immune decoy’
given subcutaneously
along with beta-interferon considered an ‘older drug’ with less effectiveness compared to monoclonal antibodies and S1P) receptor modulators
DMARD drugs in MS?
Natalizumab
Ocrelizumab
Fingolimod
Beta interferon
glatiramer acetate
Treatment of spasticity in MS?
baclofen and gabapentin are first-line. Other options include diazepam, dantrolene and tizanidine
Treatment of bladder dysfunction in MS?
if significant residual volume → intermittent self-catheterisation
if no significant residual volume → anticholinergics may improve urinary frequency
What is Oscillopsia? How should it be managed in MS?
Oscillopsia (visual fields appear to oscillate)
gabapentin is first-line
Prognostic features of MS?
Good prognosis features
female sex
age: young age of onset (i.e. 20s or 30s)
relapsing-remitting disease
sensory symptoms only
long interval between first two relapses
complete recovery between relapses
What are the types of multisystem atrophy?
1) MSA-P - Predominant Parkinsonian features
2) MSA-C - Predominant Cerebellar features
What are the features of mutlisystem atrophy?
parkinsonism
autonomic disturbance
erectile dysfunction: often an early feature
postural hypotension
atonic bladder
cerebellar signs
What is the mechanism behind myasthenia gravis?
Antibodies to acetylcholine receptors
Features of myasthenia gravis?
muscles become progressively weaker
extraocular muscle weakness: diplopia
proximal muscle weakness: face, neck, limb girdle
ptosis
dysphagia
Associations with myasthenia gravis?
thymomas in 15%
autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders, rheumatoid, SLE
thymic hyperplasia in 50-70%
Investigations in myasthenia ?
Single fibre electromyography: high sensitivity (92-100%)
CT thorax to exclude thymoma
CK normal
antibodies to acetylcholine receptors
Management of myasthenia?;
long-acting acetylcholinesterase inhibitors - pyridostigmine is first-line
Immunosuppression note started at diagnosis - eventually needed:
- prednisolone initially
- azathioprine, cyclosporine, mycophenolate mofetil may also be used
Management of myasthenic crisis
plasmapheresis
intravenous immunoglobulins
Myasthenia gravis exacerbating factors?
penicillamine
quinidine, procainamide
beta-blockers
lithium
phenytoin
antibiotics: gentamicin, macrolides, quinolones, tetracyclines
Genetics behind myotonic dystrophy?
autosomal dominant
a trinucleotide repeat disorder
DM1 is caused by a CTG repeat at the end of the DMPK (Dystrophia Myotonica-Protein Kinase) gene on chromosome 19
DM2 is caused by a repeat expansion of the ZNF9 gene on chromosome 3
Features of DM1 mutation myotonic dystrophy ?
- DMPK gene on chromosome 19
- Distal weakness more prominent
Features of DM2 mutation myotonic dystrophy ?
- ZNF9 gene on chromosome 3
- Proximal weakness more prominent
- Severe congenital form not seen
What are the features of myotonic dystrophy?
General:
myotonic facies (long, ‘haggard’ appearance)
frontal balding
bilateral ptosis
cataracts
dysarthria
Other features:
myotonia (tonic spasm of muscle)
weakness of arms and legs (distal initially)
mild mental impairment
diabetes mellitus
testicular atrophy
cardiac involvement: heart block, cardiomyopathy
dysphagia
Features of narcolepsy?
early onset of REM sleep
typical onset in teenage years
hypersomnolence
cataplexy (sudden loss of muscle tone often triggered by emotion)
sleep paralysis
vivid hallucinations on going to sleep or waking up
What is the HLA association of narcolepsy?
associated with HLA-DR2
Investigation of narcolepsy?
multiple sleep latency EEG
associated with low levels of orexin (hypocretin),
Management of narcolepsy?
daytime stimulants (e.g. modafinil) and nighttime sodium oxybate
Features of lymphoma?
Rubbery, painless lymphadenopathy
The phenomenon of pain whilst drinking alcohol is very uncommon
There may be associated night sweats and splenomegaly
Features of thyroglossal cyst?
More common in patients < 20 years old
Usually midline, between the isthmus of the thyroid and the hyoid bone
Moves upwards with protrusion of the tongue
May be painful if infected
Features of thyroid swelling?
May be hypo-, eu- or hyperthyroid symptomatically
Moves upwards on swallowing
Features of pharyngeal pouch?
More common in older men
Represents a posteromedial herniation between thyropharyngeus and cricopharyngeus muscles
Usually not seen but if large then a midline lump in the neck that gurgles on palpation
Typical symptoms are dysphagia, regurgitation, aspiration and chronic cough
Features of cystic hygroma?
A congenital lymphatic lesion (lymphangioma) typically found in the neck, classically on the left side
Most are evident at birth, around 90% present before 2 years of age
Features of branchial cyst?
An oval, mobile cystic mass that develops between the sternocleidomastoid muscle and the pharynx
Develop due to failure of obliteration of the second branchial cleft in embryonic development
Usually present in early adulthood
Features of cervical rib?
More common in adult females
Around 10% develop thoracic outlet syndrome
Features of carotid aneurysm?
Pulsatile lateral neck mass which doesn’t move on swallowing
How does a nerve conduction study demonstrate axonal pathology?
Axonal
normal conduction velocity
reduced amplitude
How does a nerve conduction study demonstrate demyelinating pathology?
Demyelinating
reduced conduction velocity
normal amplitude
Features of neurofibromatosis 1?
Café-au-lait spots (>= 6, 15 mm in diameter)
Axillary/groin freckles
Peripheral neurofibromas
Iris hamatomas (Lisch nodules) in > 90%
Scoliosis
Pheochromocytomas
Features of neurofibromatosis 2?
Bilateral vestibular schwannomas
Multiple intracranial schwannomas, mengiomas and ependymomas
Difference between neurofibromatosis and tuberous sclerosis
Features of neuroleptic malignant syndrome?
Taken antipsychotic
pyrexia
muscle rigidity
autonomic lability: typical features include hypertension, tachycardia and tachypnoea
agitated delirium with confusion
Rhabdomyolysis
Mechanism of neuroleptic malignant syndrome?
dopamine blockade induced by antipsychotics triggers massive glutamate release and subsequent neurotoxicity and muscle damage.
Treatment of neuroleptic malignant syndrome?
stop antipsychotic
IVF
Dantrolene
- decreasing excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor, and decreasing the release of calcium from the sarcoplasmic reticulum
bromocriptine, dopamine agonist, may also be used
Mechanism of dantrolene?
- decreasing excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor, and decreasing the release of calcium from the sarcoplasmic reticulum
Features of Neuromyelitis optica?
Diagnosis requires bilateral optic neuritis, myelitis and 2 of the following 3 criteria:
1. Spinal cord lesion involving 3 or more spinal levels
2. Initially normal MRI brain
3. Aquaporin 4 positive serum antibody (NMO IgG)
What is neurmyelitis optica?
Neuromyelitis optica (NMO) is a monophasic or relapsing-remitting demyelinating CNS disorder
involves the optic nerves and cervical spine, with imaging of the brain frequently normal. Vomiting is also a common presenting complaint.
Treatment of neuromyelitis optica?
immunosuppressant e.g. with anti-CD20 agent rituximab)
Causes of neuropathic pain?
diabetic neuropathy
post-herpetic neuralgia
trigeminal neuralgia
prolapsed intervertebral disc
Treatment of neuropathic pain?
amitriptyline, duloxetine, gabapentin or pregabalin
tramadol may be used as ‘rescue therapy’ for exacerbations of neuropathic pain
topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)
Features of normal pressure hydrocephalus?
urinary incontinence
dementia and bradyphrenia
gait abnormality (may be similar to Parkinson’s disease)
Mechanism behind normal pressure hydrocephalus?
reversible cause of dementia
secondary to reduced CSF absorption at the arachnoid villi. These changes may be secondary to head injury, subarachnoid haemorrhage or meningitis.
Imaging in normal pressure hydrocephalus?
hydrocephalus with ventriculomegaly in the absence of, or out of proportion to, sulcal enlargement
Management of normal pressure hydrocephalus?
ventriculoperitoneal shunting
around 10% of patients who have shunts experience significant complications such as seizures, infection and intracerebral haemorrhages
Lesions that cause an upbeat nystagmus location?
Upbeat nystagmus
cerebellar vermis lesions
Lesions that cause an downbeat nystagmus location?
Arnold-Chiari malformation
What is osteosclerosis?
Autosomal dominant condition
replacement of normal bone by vascular spongy bone
progressive conductive deafness due to fixation of the stapes at the oval window
Features of osteosclerosois
Onset is usually at 20-40 years - features include:
conductive deafness
tinnitus
normal tympanic membrane*
positive family history
What is Lambert eaton syndrome associated with?
Small cell lung cancer
antibody directed against pre-synaptic voltage gated calcium channel in the peripheral nervous system
can also occur independently as autoimmune disorder
What is anti-Hu antibody associated with?
associated with small cell lung carcinoma and neuroblastomas
sensory neuropathy - may be painful
cerebellar syndrome
encephalomyelitis
What is anti-Yo associated with?
associated with ovarian and breast cancer
cerebellar syndrome
What is anti- GAD antibody associated with?
associated with breast, colorectal and small cell lung carcinoma
stiff person’s syndrome or diffuse hypertonia
What is anti-Ri associated with?
associated with breast and small cell lung carcinoma
ocular opsoclonus-myoclonus
What is Purkinje cell antibody associated with?
- peripheral neuropathy in breast cancer
What is the classic triad of Parkinson’s disease?
Classic triad of features: bradykinesia, tremor and rigidity.
Pathophysiology in Parkinson’s?
degeneration of dopaminergic neurons in the substantia nigra
Features of bradykinesia?
poverty of movement also seen, sometimes referred to as hypokinesia
short, shuffling steps with reduced arm swinging
difficulty in initiating movement
Tremor associated in Parkinson’s disease?
most marked at rest, 3-5 Hz
worse when stressed or tired, improves with voluntary movement
typically ‘pill-rolling’, i.e. in the thumb and index finger
Features or rigidity in Parkinson’s ?
lead pipe
cogwheel: due to superimposed tremor
Other than classic features, what else is seen in Parkinson’s?
mask-like facies
flexed posture
micrographia
drooling of saliva
psychiatric features: depression is the most common feature (affects about 40%); dementia, psychosis and sleep disturbances may also occur
impaired olfaction
REM sleep behaviour disorder
fatigue
autonomic dysfunction:
postural hypotension
Features that are different in drug induced Parkinson’s?
motor symptoms are generally rapid onset and bilateral
rigidity and rest tremor are uncommon
Treatment in Parkinson’s disease?
if the motor symptoms are affecting the patient’s quality of life: levodopa
if the motor symptoms are not affecting the patient’s quality of life: dopamine agonist (non-ergot derived), levodopa or monoamine oxidase B (MAO‑B) inhibitor
In the case that levodopa does not work, what else can be added in Parkinson treatment?
dopamine agonist, MAO‑B inhibitor or catechol‑O‑methyl transferase (COMT) inhibitor as an adjunct
What are Parkinson patients at risk of if they don’t take their medication?
Acute akinesia
Neuroleptic malignant syndrome
Management of hyper salivation in Parkinson’s?
Glycoperoneum
Side effects of levodopa?
dry mouth
anorexia
palpitations
postural hypotension
psychosis
When do patients with Parkinson’s get dyskinesia?
At peak dose
dystonia, chorea and athetosis
Examples of dopamine receptor agonists?
bromocriptine, ropinirole, cabergoline, apomorphine
Adverse effects of dopamine receptor agonists?
pulmonary, retroperitoneal and cardiac fibrosis
impulse control disorders and excessive daytime somnolence
What MAO-B is used in parsons and what is it mechanism?
e.g. selegiline
inhibits the breakdown of dopamine secreted by the dopaminergic neurons
Mechanism of amantadine?
mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses
Side effects of amantadine?
side-effects include ataxia, slurred speech, confusion, dizziness and livedo reticularis
Mechanism of COMT inhibitors in Parkinson’s?
e.g. entacapone, tolcapone
COMT is an enzyme involved in the breakdown of dopamine, and hence may be used as an adjunct to levodopa therapy
used in conjunction with levodopa in patients with established PD
Treatment in drug induced Parkinson’s?
block cholinergic receptors
now used more to treat drug-induced parkinsonism rather than idiopathic Parkinson’s disease
help tremor and rigidity
e.g. procyclidine, benzotropine, trihexyphenidyl (benzhexol)
Causes of Parkinsonism?
Parkinson’s disease
drug-induced e.g. antipsychotics, metoclopramide*
progressive supranuclear palsy
multiple system atrophy
Wilson’s disease
post-encephalitis
dementia pugilistica (secondary to chronic head trauma e.g. boxing)
toxins: carbon monoxide, MPTP
Causes of motor peripheral neuropathy ?
Guillain-Barre syndrome
porphyria
lead poisoning
hereditary sensorimotor neuropathies (HSMN) - Charcot-Marie-Tooth
chronic inflammatory demyelinating polyneuropathy (CIDP)
diphtheria
Causes of sensory peripheral neuropathy?
diabetes
uraemia
leprosy
alcoholism
vitamin B12 deficiency
amyloidosis
Demyelinating peripheral neuropathy causes?
Guillain-Barre syndrome
chronic inflammatory demyelinating polyneuropathy (CIDP)
amiodarone
hereditary sensorimotor neuropathies (HSMN) type I
paraprotein neuropathy
Axonal peripheral neuropathy causes?
alcohol
diabetes mellitus*
vasculitis
vitamin B12 deficiency*
hereditary sensorimotor neuropathies (HSMN) type II
Mechanism of phenytoin?
Mechanism of action
binds to sodium channels increasing their refractory period
Adverse effects of phenytoin?>
Acute
initially: dizziness, diplopia, nystagmus, slurred speech, ataxia
later: confusion, seizures
Chronic
common: gingival hyperplasia (secondary to increased expression of platelet derived growth factor, PDGF), hirsutism, coarsening of facial features, drowsiness
megaloblastic anaemia (secondary to altered folate metabolism)
peripheral neuropathy
enhanced vitamin D metabolism causing osteomalacia
lymphadenopathy
dyskinesia
Idiosyncratic
fever
rashes, including severe reactions such as toxic epidermal necrolysis
hepatitis
Dupuytren’s contracture*
aplastic anaemia
drug-induced lupus
Teratogenic
associated with cleft palate and congenital heart disease
How should phenytoin be monitored?
Trough immediately before next dose
What is pituitary apoplexy?
Sudden enlargement of a pituitary tumour (usually non-functioning macroadenoma) secondary to haemorrhage or infarction.
Precipitating causes of pituitary apoplexy?
Precipitating factors
hypertension
pregnancy
trauma
anticoagulation
Features of pituitary apoplexy?
sudden onset headache similar to that seen in subarachnoid haemorrhage
vomiting
neck stiffness
visual field defects: classically bitemporal superior quadrantic defect
extraocular nerve palsies
features of pituitary insufficiency
e.g. hypotension/hyponatraemia secondary to hypoadrenalism
Management of pituitary apoplexy?
urgent steroid replacement due to loss of ACTH
careful fluid balance
surgery
How long does post LP headache last?
Up to a couple of days
Typical features
usually develops within 24-48 hours following LP but may occur up to one week later
may last several days
worsens with upright position
improves with recumbent position
Management of post LP headache?
supportive initially (analgesia, rest)
if pain continues for more than 72 hours then specific treatment is indicated, to prevent subdural haematoma
treatment options include: blood patch, epidural saline and intravenous caffeine
Features of progressive supra nuclear palsy?
postural instability and falls
patients tend to have a stiff, broad-based gait
impairment of vertical gaze (down gaze worse than up gaze - patients may complain of difficultly reading or descending stairs)
parkinsonism
bradykinesia is prominent
cognitive impairment
primarily frontal lobe dysfunction
What is Ramsay hunt syndrome ?
Ramsay Hunt syndrome (herpes zoster oticus) is caused by the reactivation of the varicella zoster virus in the geniculate ganglion of the seventh cranial nerve.
Features of Ramsay hunt syndrome?
auricular pain is often the first feature
facial nerve palsy
vesicular rash around the ear
other features include vertigo and tinnitus
Management of Ramsay hunt syndrome?
oral aciclovir and corticosteroids are usually given
Clincial features of restless legs syndrome?
uncontrollable urge to move legs (akathisia). Symptoms initially occur at night but as condition progresses may occur during the day. Symptoms are worse at rest
paraesthesias e.g. ‘crawling’ or ‘throbbing’ sensations
movements during sleep may be noted by the partner - periodic limb movements of sleeps (PLMS)
Associations of restless legs syndrome?
there is a positive family history in 50% of patients with idiopathic RLS
iron deficiency anaemia
uraemia
diabetes mellitus
pregnancy
What investigation should be done for restless legs syndrome?
Ferritin
Management of restless legs syndrome
simple measures: walking, stretching, massaging affected limbs
treat any iron deficiency
dopamine agonists are first-line treatment (e.g. Pramipexole, ropinirole)
benzodiazepines
gabapentin
What is Reyes syndrome?
Reye’s syndrome is a severe, progressive encephalopathy affecting children that is accompanied by fatty infiltration of the liver, kidneys and pancreas
Management of Reyes syndrome?
The peak incidence is 2 years of age, features include:
there may be a history of preceding viral illness
encephalopathy: confusion, seizures, cerebral oedema, coma
fatty infiltration of the liver, kidneys and pancreas
hypoglycaemia
Mechanism of sodium valproate?
Increases GABA activity
Adverse effects of sodium valproate
P450 inhibitor
gastrointestinal: nausea
increased appetite and weight gain
alopecia: regrowth may be curly
ataxia
tremor
hepatotoxicity
pancreatitis
thrombocytopaenia
hyponatraemia
hyperammonemic encephalopathy: L-carnitine may be used as treatment if this develops
Causes of spastic paresis?
describes a upper motor neuron pattern of weakness in the lower limbs
demyelination e.g. multiple sclerosis
cord compression: trauma, tumour
parasagittal meningioma
tropical spastic paraparesis
transverse myelitis e.g. HIV
syringomyelia
hereditary spastic paraplegia
osteoarthritis of the cervical spine
Describe the spinal cord tract?
Definition of status epileptics ?
Status epilepticus is defined as:
a single seizure lasting >5 minutes, or
>= 2 seizures within a 5-minute period without the person returning to normal between them
Treatment of status epileptics?
First-line drugs are IV benzodiazepines such as diazepam or lorazepam
in the prehospital setting PR diazepam or buccal midazolam may be given
in hospital IV lorazepam is generally used. This may be repeated once after 10-20 minutes
Features of stroke in the anterior cerebral artery?
Contralateral hemiparesis and sensory loss, lower extremity > upper
Features of stroke in the middle cerebral artery?
Contralateral hemiparesis and sensory loss, upper extremity > lower
Contralateral homonymous hemianopia
Aphasia
Features of stroke in the posterior cerebral artery?
Contralateral homonymous hemianopia with macular sparing
Visual agnosia
stroke to toe basilar artery?
locked in syndrome
Features of weber syndrome?
Ipsilateral CN III palsy
Contralateral weakness of upper and lower extremity
branches of the posterior cerebral artery that supply the midbrain)
Features of Lacunar stroke?
present with either isolated hemiparesis, hemisensory loss or hemiparesis with limb ataxia
strong association with hypertension
common sites include the basal ganglia, thalamus and internal capsule
When should anti-hypertensive be used in stroke?
post ischaemic stroke if there is a hypertensive emergency with one or more of the following serious concomitant medical issues (according to the NICE guidelines):
Hypertensive encephalopathy
Hypertensive nephropathy
Hypertensive cardiac failure/myocardial infarction
Aortic dissection
Pre-eclampsia/eclampsia
Or if thrombolysis has been carried out
Management of blood pressure in stroke?
UptoDate suggest using intravenous labetalol, nicardipine and clevidipine as first-line agents, due to the possibility for rapid and safe titration to control blood pressure
Post thrombolysis what is the blood pressure target post stroke?
However, in patients who are candidates for thrombolytic therapy for acute stroke, blood pressure should be reduced to 185/110mmHg or lower
Elevated BP can affect thrombolytic eligibility and delay treatment
Timely management of elevated BP is crucial when patients are otherwise eligible for intravenous thrombolysis
After thrombolytic therapy, UptoDate recommend ensuring that the blood pressure is stabilised and maintained at or below 180/105mmHg for at least 24 hours after treatment
First line imaging for suspected stroke?
Non contrast CT
Features of a stroke?
The following criteria should be assessed:
1. unilateral hemiparesis and/or hemisensory loss of the face, arm & leg
2. homonymous hemianopia
3. higher cognitive dysfunction e.g. dysphasia
Diagnostic criteria for total anterior circulation stroke?
involves middle and anterior cerebral arteries
All 3 criteria must be present:
The following criteria should be assessed:
1. unilateral hemiparesis and/or hemisensory loss of the face, arm & leg
2. homonymous hemianopia
3. higher cognitive dysfunction e.g. dysphasia
Diagnostic criteria for a partial anterior circulation stroke?
involves smaller arteries of anterior circulation e.g. upper or lower division of middle cerebral artery
2 criteria of below must be satisfied:
The following criteria should be assessed:
1. unilateral hemiparesis and/or hemisensory loss of the face, arm & leg
2. homonymous hemianopia
3. higher cognitive dysfunction e.g. dysphasia
Diagnostic criteria for lacunar infarcts?
involves perforating arteries around the internal capsule, thalamus and basal ganglia
presents with 1 of the following:
1. unilateral weakness (and/or sensory deficit) of face and arm, arm and leg or all three.
2. pure sensory stroke.
3. ataxic hemiparesis
Diagnostic criteria of posterior circulation infarction?
Posterior circulation infarcts (POCI, c. 25%)
involves vertebrobasilar arteries
presents with 1 of the following:
1. cerebellar or brainstem syndromes
2. loss of consciousness
3. isolated homonymous hemianopia
What causes subacute degeneration of the spinal cord?
due to vitamin B12 deficiency
dorsal columns + lateral corticospinal tracts are affected
Features of subacute degeneration of the spinal cord?
dorsal columns + lateral corticospinal tracts are affected
joint position and vibration sense lost first then distal paraesthesia
upper motor neuron signs typically develop in the legs, classically extensor plantars, brisk knee reflexes, absent ankle jerks
if untreated stiffness and weakness persist
Most common type of subarachnoid haemorrhage?
Traumatic subarachnoid haemorrhage
Causes of spontaneous subarachnoid haemorrhage?
Causes of spontaneous SAH include:
Intracranial aneurysm* (saccular ‘berry’ aneurysms): this accounts for around 85% of cases. Conditions associated with berry aneurysms include adult polycystic kidney disease, Ehlers-Danlos syndrome and coarctation of the aorta
Arteriovenous malformation
Pituitary apoplexy
Arterial dissection
Mycotic (infective) aneurysms
Perimesencephalic (an idiopathic venous bleed)
Features of subarachnoid haemorrhage?
Classical presenting features include:
Headache: typically sudden-onset (‘thunderclap’ or ‘baseball bat’), severe (‘worst of my life’) and occipital
Nausea and vomiting
Meningism (photophobia, neck stiffness)
Coma
Seizures
Sudden death
ECG changes including ST elevation may be seen
How should subarachnoid haemorrhage be confirmed?
- Computed tomography (CT) head
- Acute blood (hyperdense/bright on CT) is typically distributed in the basal cisterns, sulci and in severe cases the ventricular system.
- CT is negative for SAH (no blood seen) in 7% of cases. - Lumbar puncture (LP)
- Used to confirm SAH if CT is negative.
- LP is performed at least 12 hours following the onset of symptoms to allow the development of xanthochromia (the result of red blood cell breakdown).
- Xanthochromia helps to distinguish true SAH from a ‘traumatic tap’ (blood introduced by the LP procedure).
- As well as xanthochromia, CSF findings consistent with subarachnoid haemorrhage include a normal or raised opening pressure
Once SAH confirmed, what test needs to be completed?
CT intracranial angiogram (to identify a vascular lesion e.g. aneurysm or AVM)
+/- digital subtraction angiogram (catheter angiogram)
Complications post aneurysmal SAH?
Re-bleeding
Vasospasm (also termed delayed cerebral ischaemia), typically 7-14 days after onset
Hyponatraemia (most typically due to syndrome inappropriate anti-diuretic hormone (SIADH))
Seizures
Hydrocephalus
Death
How is vasospasm prevented in SAH?
nimodipine (a calcium channel inhibitor targeting the brain vasculature)
Predictive factors in SAH?
conscious level on admission
age
amount of blood visible on CT head
How can subdural haemorrhages be classified?
Subdural haematomas can be classified in terms of their age:
Acute
Subacute
Chronic
How does an acute subdural haemorrhage look?
subdural space and is most commonly caused by high-impact trauma
associated with high-impact injuries, there is often other brain underlying brain injuries.
hey will appear hyperdense (bright) in comparison to the brain. Large acute subdural haematomas will push on the brain (‘mass effect’) and cause midline shift or herniation.
Where is the bleed in a chronic subdural haemorrhage?
Rupture of the small bridging veins within the subdural space rupture and cause slow bleeding.
How do chronic subdural appear differential to acute subdural?
In contrast to acute subdurals, chronic subdurals are hypodense (dark) compared to the substance of the brain.
What is Syriangomyelia? Or a syrinx?
Syringomyelia (‘syrinx’ for short) describes a collection of cerebrospinal fluid within the spinal cord.
Causes of a syrinx?
Causes include:
a Chiari malformation: strong association
trauma
tumours
idiopathic
Features of a syrinx?
A ‘cape-like’ (neck, shoulders and arms)
Loss of sensation to temperature but the preservation of light touch, proprioception and vibration
classic examples are of patients who accidentally burn their hands without realising
- this is due to the crossing spinothalamic tracts in the anterior commissure of the spinal cord being the first tracts to be affected
spastic weakness (predominantly of the lower limbs)
neuropathic pain
upgoing plantars
autonomic features:
Horner’s syndrome due to compression of the sympathetic chain, but this is rare
bowel and bladder dysfunction
scoliosis will occur over a matter of years if the syrinx is not treated
What is the best imaging modality for a syrinx?
MRI
Features of a third nerve palsy?
eye is deviated ‘down and out’
ptosis
pupil may be dilated (sometimes called a ‘surgical’ third nerve palsy)
Causes of a third nerve palsy?
diabetes mellitus
vasculitis e.g. temporal arteritis, SLE
false localizing sign* due to uncal herniation through tentorium if raised ICP
posterior communicating artery aneurysm
- pupil dilated
- often associated pain
cavernous sinus thrombosis
Weber’s syndrome: ipsilateral third nerve palsy with contralateral hemiplegia -caused by midbrain strokes
other possible causes: amyloid, multiple sclerosis
Features of a thyroglossal cyst?
Features
usually midline, between the isthmus of the thyroid and the hyoid bone
moves upwards with protrusion of the tongue
may be painful if infected
If a patient has sudden onset senorsineural hearing loss, waht should be considered?
Acoustic neuroma
Drugs that cause tinnitus?
Aspirin/NSAIDs
Aminoglycosides
Loop diuretics
Quinine
If a patient has pulsatile tinnitus, what should be completed?
Imaging for a possible aneurysm
MRI best choice
What is the mechanism of topiramate ?
blocks voltage-gated Na+ channels
increases GABA action
carbonic anhydrase inhibition: this results in a decrease in urinary citrate excretion and formation of alkaline urine that favours the creation of calcium phosphate stone
What are adverse effects of topiramate?
reduced appetite and weight loss
dizziness
paraesthesia
lethargy and poor concentration
rare but important: acute myopia and secondary angle-closure glaucoma
Enzyme inducer - may affect taking contraception
Features of transient global amnesia?
acute onset of anterograde amnesia (the inability to form new memories)
Features
patients may appear anxious and repeatedly ask the same question
episodes are self-limited and resolve within 24 hours
Definition of a TIA?
a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischaemia, without acute infarction.
Features of a TIA?
Features typically resolve within 1 hour:
unilateral weakness or sensory loss.
aphasia or dysarthria
ataxia, vertigo, or loss of balance
visual problems
- sudden transient loss of vision in one eye (amaurosis fugax)
- diplopia
- homonymous hemianopia
Management of TIA?
Immediate antithrombotic therapy:
give aspirin 300 mg immediately,
UNLESS
- the patient has a bleeding disorder or is taking an anticoagulant (needs immediate admission for imaging to exclude a haemorrhage)
- the patient is already taking low-dose aspirin regularly: continue the current dose of aspirin until reviewed by a specialist
- Aspirin is contraindicated: discuss management urgently with the specialist team
What score can be used to determine if a patient has had a stroke?
Rosier score
Rosier Scale
Has there been LOC or syncope?
Has there been seizure activity?
NEW ACUTE onset (or on awakening from sleep)?
Asymmetric facial weakness Asymmetric arm weakness Asymmetric leg weakness Speech disturbance Visual field defect
TOTAL SCORE
Stroke is likely if total scores are >= 1.
Scores <1 have a low possibility of stroke but are not completely excluded
What is a crescendo TIA?
patient has had more than 1 TIA (‘crescendo TIA’)
When is a specialist review required for TIA?
- if the patient has had more than 1 TIA (‘crescendo TIA’) or has a suspected cardioembolic source or severe carotid stenosis:
- If the patient has had a suspected TIA in the last 7 days: arrange urgent assessment (within 24 hours) by a specialist stroke physician
- if the patient has had a suspected TIA which occurred more than a week previously: refer for specialist assessment as soon as possible within 7 days
Advise not to drive until seen by specialist*
What imaging is require for TIA?
CT not required unless other diagnosis suspected
MRI best to determine area of ischaemia
Carotid imaging - assessment for atheoscleorsis and embolic events
Management of TIA?
clopidogrel is recommended first-line (as for patients who’ve had a stroke)
Causes of transverse myelitis?
Causes of transverse myelitis
viral infections: varicella-zoster, herpes simplex, cytomegalovirus, Epstein-Barr, influenza, echovirus, human immunodeficiency virus
bacterial infections: syphilis, Lyme disease
post-infectious (immune mediated)
first symptom of multiple sclerosis (MS) or neuromyelitis optica (NMO)
What are the features of transverse myelitis?
s include weakness and numbness of the limbs, deficits in sensation and motor skills, dysfunctional urethral and anal sphincter activities, and dysfunction of the autonomic nervous system
often a “sensory level” at the spinal ganglion of the segmental spinal nerve, below which sensation to pain or light touch is impaired. Motor weakness occurs due to involvement of the pyramidal tracts and mainly affects the muscles that flex the legs and extend the arms.[1]
Features of trigeminal neuralgia?
a unilateral disorder characterised by brief electric shock-like pains, abrupt in onset and termination, limited to one or more divisions of the trigeminal nerve
the pain is commonly evoked by light touch, including washing, shaving, smoking, talking, and brushing the teeth (trigger factors), and frequently occurs spontaneously
small areas in the nasolabial fold or chin may be particularly susceptible to the precipitation of pain (trigger areas)
the pains usually remit for variable periods
Red flags with trigeminal neuralgia?
Sensory changes
Deafness or other ear problems
History of skin or oral lesions that could spread perineurally
Pain only in the ophthalmic division of the trigeminal nerve (eye socket, forehead, and nose), or bilaterally
Optic neuritis
A family history of multiple sclerosis
Age of onset before 40 years
Management of trigeminal neuralgia?
carbamazepine is first-line
failure to respond to treatment or atypical features (e.g. < 50 years old) should prompt referral to neurology
Mechanism of triptans?
Triptans are specific 5-HT1B and 5-HT1D agonists used in the acute treatment of migraine.
Genetic inheritance of tuberous sclerosis?
Autosomal dominant
Features of tuberous sclerosis ?
Cutaneous features
depigmented ‘ash-leaf’ spots which fluoresce under UV light
roughened patches of skin over lumbar spine (Shagreen patches)
adenoma sebaceum (angiofibromas): butterfly distribution over nose
fibromata beneath nails (subungual fibromata)
café-au-lait spots* may be seen
Neurological features
developmental delay
epilepsy (infantile spasms or partial)
intellectual impairment
Also
retinal hamartomas: dense white areas on retina (phakomata)
rhabdomyomas of the heart
gliomatous changes can occur in the brain lesions
polycystic kidneys, renal angiomyolipomata
lymphangioleiomyomatosis: multiple lung cysts
Features of viral labrynthitis?
Recent viral infection
Sudden onset
Nausea and vomiting
Hearing may be affected
Features of vestibular neuronitis?
recurrent vertigo attacks lasting hours or days
nausea and vomiting may be present
horizontal nystagmus is usually present
no hearing loss or tinnituss
Features of BPV?
Gradual onset
Triggered by change in head position
Each episode lasts 10-20 seconds
Features of Vertebrobasilar ischaemia?
Elderly patient
Dizziness on extension of neck
Features of acoustic neuroma?
Hearing loss, vertigo, tinnitus
Absent corneal reflex is important sign (blinking)
Associated with neurofibromatosis type 2
Management of vestibular neuritis?
- buccal or intramuscular prochlorperazine
- Short course of oral prochlorperazine
- Vestibular rehab
What is vigabatrin?
Antiepileptic. Inhibitors GABA transaminase - potentiates GABA
Adverse effects of vigabatrin?
40% of patients develop visual field defects, which may be irreversible
visual fields should be checked every 6 months
What is von hipel Linda syndrome?
autosomal dominant condition predisposing to neoplasia. It is due to an abnormality in the VHL gene located on short arm of chromosome 3
Features of von hippel lindau syndrome?
cerebellar haemangiomas: these can cause subarachnoid haemorrhages
retinal haemangiomas: vitreous haemorrhage
renal cysts (premalignant)
phaeochromocytoma
extra-renal cysts: epididymal, pancreatic, hepatic
endolymphatic sac tumours
clear-cell renal cell carcinoma
What is the cause of werincke’s encephalopathy?
Thiamine deficiency
A classic triad of ophthalmoplegia/nystagmus, ataxia and encephalopathy may occur.
Fetures of wernicke’s encephalopathy?
Features
oculomotor dysfunction
nystagmus (the most common ocular sign)
ophthalmoplegia: lateral rectus palsy, conjugate gaze palsy
gait ataxia
encephalopathy: confusion, disorientation, indifference, and inattentiveness
peripheral sensory neuropathy
REMEMBER CAN OPEN
Confusion
Ataxia
Nystagmus
Ophthamoplegia
PEripheral
Neuropathy
Investigations of wernicke’s encephalopathy?
MRI
Red cell transketolase deficiency
If wernicke’s is untreated, what can it become?
Korsakoff syndrome
Amnesia
Confabulation
Bitemporal hemianopia: upper quadrant defect > lower quadrant defect = ?
inferior chiasmal compression, commonly a pituitary tumour
Bitemporal hemianopia: lower quadrant defect > upper quadrant defect = ?
superior chiasmal compression, commonly a craniopharyngioma
In neuropathic pain, how should medications be added?
Medications should be removed, then new one started. Do not add drugs
When should mechanical thrombectomy be considered?
6-24 hours
if there is the potential to salvage brain tissue, as shown by imaging such as CT perfusion or diffusion-weighted MRI sequences showing limited infarct core volume
Palatal myoclonus - where is the lesion?
Olivary nucleus
Fluctuating consciousness ?
Consider subdural haematoma
Sited of action of 5HT3 inhibitors?
Medulal oblongata
Headache + CN III palsy
Increased ICP
Uncle herniation
Migainres: Why get pro kinetics + paracetamol?
There is delayed gastric emptying
painful cn iii palsy?
posterior communicating artery aneurysm
lobe affected for change in behaviour?
Temporal
What is Parinaud syndrome ?
a lesion at the dorsal midbrain
Upward gaze palsy, often manifesting as diplopia
Pupillary light-near dissociation (Pseudo-Argyll Robertson pupils)
Convergence-retraction nystagmus
What controls vertical gaze?
Rostral interstitial nucleus of medial longitudinal fasciculus lies at the dorsal midbrain and control vertical gaze. They project to the vestibular nuclei.
Causes of parinaud syndrome?
Brain tumours in the midbrain or pineal gland (pinealoma)
Multiple sclerosis
Midbrain stroke
Treatment of absence seizures?
- Sodium v alporate / ethosuxiadmie
- Lamotigrene
What medications makes absence seizures worse?
Carbamazepine
What type of drugs is ropinirole for restless legs?
Dopamine antagonist
Trinucledotide repeat GAA?
Friedrick ataxia
Trinucleotide repeat CGG?
fragile X syndrome
Trinucleotide repeat CTG
myotonic dystrophy
Temporal lobe epilepsy localising features?
Lip smacking + post-ictal dysphasia
Acalcula - which lobe?
Parietal
Acalcula - which lobe?
Parietal
what is the time interval for thrombolysis?
4.5 hours
In Guillain barre how is respiratory function monitored?
FVC - forced vital capacity
Essential tremor prophylaxis when asthmatic?
Primidone
What can topiramate do to eyes?
Acute angle closure glaucoma
Ergot-derived dopamine agonist?
bromoCRIPTINE / dihydroergoCRTPTINE
lisuRIDE
pergoLIDE
cabergoline
Non-ergot dopamine agonist not associated with fibrosis?
Ropinirole
Drugs used in relapsing remitting MS?
glatiramer acetate
beta-interferon
fingolimod
ocrelizumab
natalizumab
What is Shy Drager syndrome?
Form of multi system atrophy
parkinsonism
autonomic disturbance
erectile dysfunction: often an early feature
postural hypotension
atonic bladder
cerebellar signs
Demyelinating pathology?
Guillain-Barre syndrome
chronic inflammatory demyelinating polyneuropathy (CIDP)
amiodarone
hereditary sensorimotor neuropathies (HSMN) type I
paraprotein neuropathy
Axonal pathology?
alcohol
diabetes mellitus*
vasculitis
vitamin B12 deficiency*
hereditary sensorimotor neuropathies (HSMN) type II
What is a Jacksonian march?
characteristically starts by affecting a peripheral body part such as a toe, finger or section of the lip and then spreads quickly ‘marches’ over the respective foot, hand or face.
What is a Jacksonian march?
characteristically starts by affecting a peripheral body part such as a toe, finger or section of the lip and then spreads quickly ‘marches’ over the respective foot, hand or face.
Parts of the cord involved in subacute degernation?
Dorsal + Lateral
What are triptans contraindicated in?
Ischaemic heart disease
What anti-emetic is likely to give extrapyramidal signs
Metoclopramide
Foster Kennedy syndrome?
frontal lobe tumour - usually a meningioma in this age group - leading to ipsilateral optic atrophy and papilloedema
Features of von hippie Lindau?
Von - Vitreous haemorrhages
Hippel - Haemangiomas (cerebellar + retinal)
Lindau - Lots of cysts (renal + extrarenal)
Syndrome- sadly, cancers (renal clear cell + endolymphatic sac)
Homonymous hemianopia?
homonymous quadrantanopias: PITS (Parietal-Inferior, Temporal-Superior)
congruous defects?
congruous defects= optic radiation lesion or occipital cortex
Difference in kidney lesions in tuberous sclerosis vs von hippie Linda?
Angiomyolipoma = Tuberous sclerosis
Angiomatosis = Von Hippel Lindau syndrome
What stroke syndrome can be caused by PICA strokes?
Lateral medullary syndrome
Neurofibromatosis chromosome ?
Chromosome 17 - Type 1
Chromsone 22 - Type 2
VHL chromosome?
Chromosome 3p
Most common ECG changes in myotonic dystrophy?
PR lengthening
What is Alexia, and where is the lesion ?
inability to read out writing
Corpus collosum
Hockey stick sign ?
CJD
If cannot tolerate clopidogrel for secondary prevention?
Aspirin + dipyridamole lifelong
Anterior spinal cord syndrome?
Bilateral spastic paresis and loss of pain and temperature sensation - anterior spinal artery occlusion
areflexia, ataxia, ophthalmoplegia
Miller Fischer syndrome (bad guillaine barre)
Side effects of natalizumab?
Natalizumab can cause reactivation of the JC virus causing progressive multifocal leukoencephalopathy (PML)
facial weakness (e.g. difficulty closing eyes, smiling, blowing), winged scapula and weakness of the shoulderm upper arm and hip girdle muscles
facioscapulohumeral dystrophy
How does phenytoin cause bleeding?
Phenytoin induces vitamin K metabolism, which can cause a relative vitamin K deficiency, creating the potential for heamorrhagic disease of the newborn
tachycardia + hyporeflexia + flacid paralysis?
guillaiin barre
How does subacute cord degeneration present?
Loss of proprioception, vibration sense and hyperreflexia
Damage craniopharyngoma removal causes weight gain? why?
ventromedial area of the hypothalamus is often invaded by craniopharyngiomas. This area of the thalamus controls the satiety center and it is removed during surgery, the patient can have uninhibited hunger leading to significant weight gain.
What part of the hypothalamus is responsible for ADH?
supraoptic nucleus of the hypothalamus is responsible for the synthesis of antidiuretic hormone and oxytocin, which are transported to the posterior hypothalamus for storage and release.
Unicentric castleman disease?
lymphoproliferative disorder associated in a subset of cases with HIV and HHV-8.
follicles with atrophic and hyalinized germinal centres surrounded by prominent mantle zones containing small lymphocytes
Treatment for spasticity in MS?
Baclofen
Gabapentin
What type of drug is procyclidine?
Anti-muscarinic
Loss of corneal reflex?
Think acoustic neuroma
What type of drug is pyridostigmine?
long acting acetylcholinesterase inhibitor
Features of progressive supra nuclear palsy?
postural instability and falls
patients tend to have a stiff, broad-based gait
impairment of vertical gaze (down gaze worse than up gaze - patients may complain of difficultly reading or descending stairs)
parkinsonism
bradykinesia is prominent
cognitive impairment
primarily frontal lobe dysfunction
Poor response to leva dopa
Trigger for cluster headaches?
Alcohol
Features of transient global amnesia?
Transient global amnesia is characterized by the acute onset of anterograde amnesia (the inability to form new memories). The aetiology is unknown, thought to be due to transient ischaemia to the thalamus (in particular the amygdala and hippocampus).
Features
patients may appear anxious and repeatedly ask the same question
episodes are self-limited and resolve within 24 hours
Type of peripheral neuropathy in uraemia?
Sensory peripheral neuropathy?
. It is found on T2-weighted MRI imaging which reveals poorly-defined hyperintensities in the subcortical white matter.
acute disseminated encephalomyelitis
IV phenytoin causes?
hypotension
Chronic subdural haematoma?
chronic subdural haematoma will appear as a hypodense (dark), crescentic collection around the convexity of the brain
