Neurology Flashcards
Acoustic Neuroma
Vestibular schwannoma ()
account for approximately 5% of intracranial tumours and 90% of cerebellopontine angle tumours.
The classical history of vestibular schwannoma includes a combination of vertigo, hearing loss, tinnitus and an absent corneal reflex. Features can be predicted by the affected cranial nerves:
cranial nerve VIII: vertigo, unilateral sensorineural hearing loss, unilateral tinnitus
cranial nerve V: absent corneal reflex
cranial nerve VII: facial palsy
Bilateral vestibular schwannomas are seen in neurofibromatosis type 2.
Patients with a suspected vestibular schwannoma should be referred urgently to ENT. It should be noted though that the tumours are often slow growing, benign and often observed initially.
MRI of the cerebellopontine angle is the investigation of choice. Audiometry is also important as only 5% of patients will have a normal audiogram.
Management is with either surgery, radiotherapy or observation.
Loss of corneal reflex - think acoustic neuroma
Acoustic neuroma is an important differential diagnosis in patients with unilateral deafness or tinnitus
Important for meLess important
Acoustic neuroma is the correct answer and should always be considered in patients with unilateral sensorineural deafness or tinnitus. Patients may also develop facial palsy. Acoustic neuroma is a slow-growing neurofibroma and requires urgent referral to ENT for surgery.
Presbyacusis and otosclerosis are both causes of deafness but symptoms are bilateral. Additionally, otosclerosis causes a conductive, not a sensorineural deafness.
The normal ear examination and Rinne’s/Weber’s tests suggesting a sensorineural deafness exclude otitis media.
Meniere’s disease would normally present with attacks of vertigo, tinnitus, sensorineural deafness and fullness of the ear.
Bell’s palsy
Bell’s palsy may be defined as an acute, unilateral, idiopathic, facial nerve paralysis. The aetiology is unknown although the role of the herpes simplex virus has been investigated previously. The peak incidence is 20-40 years and the condition is more common in pregnant women.
Features
lower motor neuron facial nerve palsy - forehead affected*
patients may also notice post-auricular pain (may precede paralysis), altered taste, dry eyes, hyperacusis
Management
in the past a variety of treatment options have been proposed including no treatment, prednisolone only and a combination of aciclovir and prednisolone
following a National Institute for Health randomised controlled trial it is now recommended that prednisolone 1mg/kg for 10 days should be prescribed for patients within 72 hours of onset of Bell’s palsy. Adding in aciclovir gives no additional benefit
eye care is important - prescription of artificial tears and eye lubricants should be considered
Prognosis
if untreated around 15% of patients have permanent moderate to severe weakness
*upper motor neuron lesion ‘spares’ upper face
Brain lesions
Location
Parietal lobe lesions
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 lesions
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 lobes lesions
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
anosmia
inability to generate a list
Cerebellum lesions
midline lesions: gait and truncal ataxia
hemisphere lesions: intention tremor, past pointing, dysdiadokinesis, nystagmus
More specific areas
Area
Associated conditions
Medial thalamus and mammillary bodies of the hypothalamus
Wernicke and Korsakoff syndrome
Subthalamic nucleus of the basal ganglia
Hemiballism
Striatum (caudate nucleus) of the basal ganglia
Huntington chorea
Substantia nigra of the basal ganglia
Parkinson’s disease
Amygdala
Kluver-Bucy syndrome (hypersexuality, hyperorality, hyperphagia, visual agnosia
Common peroneal nerve lesion
The sciatic nerve divides into the tibial and common peroneal nerves. Injury often occurs at the neck of the fibula
The most characteristic feature of a common peroneal nerve lesion is foot drop.
Other features include:
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
The common peroneal nerve supplies the muscles of the peroneal and anterior compartment of the leg and sensation to the dorsum of the foot.
It travels through the popliteal fossa, wrapping around the head of the fibula (where it is sometimes palpable).
Habitual leg crossing, prolonged bed rest, hyperflexion of the knee, pressure in obstetric stirrups and conditioning in ballet dancers are typical ‘textbook’ examples of scenarios where peroneal neuropathy can occur as a result of nerve compression against the head of the fibular. Transient trauma at this site (as in this scenario) can cause a temporary neurapraxia, whereas prolonged or more severe trauma can result in permanent foot drop.
Brain abscess
Basics
- CNS abscesses may result from a number of causes including, extension of sepsis from middle ear or sinuses, trauma or surgery to the scalp, penetrating head injuries and embolic events from endocarditis
The presenting symptoms will depend upon the site of the abscess (those in critical areas e.g.motor cortex) will present earlier. Abscesses have a considerable mass effect in the brain and raised intra cranial pressure is common.
Although fever, headache and focal neurology are highly suggestive of a brain abscess the absence of one or more of these does not exclude the diagnosis, fever may be absent and even if present, is usually not the swinging pyrexia seen with abscesses at other sites.
Assessment of the patient includes imaging with CT scanning.
Treatment is usually surgical, a craniotomy is performed and the abscess cavity debrided. The abscess may reform because the head is closed following abscess drainage.
Cranial Nerve Lesions
Functions
I (Olfactory)
Smell
II (Optic)
Sight
III (Oculomotor)
Eye movement (MR, IO, SR, IR)
Pupil constriction
Accomodation
Eyelid opening
IV (Trochlear)
Eye movement (SO)
V (Trigeminal)
Facial sensation
Mastication
VI (Abducens)
Eye movement (LR)
VII (Facial)
Facial movement
Taste (anterior 2/3rds of tongue)
Lacrimation
Salivation
VIII (Vestibulocochlear)
Hearing, balance
IX (Glossopharyngeal)
Taste (posterior 1/3rd of tongue)
Salivation
Swallowing
Mediates input from carotid body & sinus
X (Vagus)
Phonation
Swallowing
Innervates viscera
XI (Accessory)
Head and shoulder movement
XII (Hypoglossal)
Tongue movement
Degenerative cervical myelopathy
Degenerative cervical myelopathy (DCM) has a number of risk factors, which include smoking due to its effects on the intervertebral discs, genetics and occupation - those exposing patients to high axial loading [1].
The presentation of DCM is very variable. Early symptoms are often subtle and can vary in severity day to day, making the disease difficult to detect initially. However as a progressive condition, worsening, deteriorating or new symptoms should be a warning sign.
DCM symptoms can include any combination of [1]:
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.
The most common symptoms at presentation of DCM are unknown, but in one series 50% of patients were initially incorrectly diagnosed and sometimes treated for carpal tunnel syndrome [2].
An MRI of the cervical spine is the gold standard test where cervical myelopathy is suspected. It may reveal disc degeneration and ligament hypertrophy, with accompanying cord signal change.
All patients with degenerative cervical myelopathy should be urgently referred for assessment by specialist spinal services (neurosurgery or orthopaedic spinal surgery). This is due to the importance of early treatment. The timing of surgery is important, as any existing spinal cord damage can be permanent. Early treatment (within 6 months of diagnosis) offers the best chance of a full recovery but at present, most patients are presenting too late. In one study, patients averaged over 5 appointments before diagnosis, representing >2 years.
Currently, decompressive surgery is the only effective treatment. It has been shown to prevent disease progression. Close observation is an option for mild stable disease, but anything progressive or more severe requires surgery to prevent further deterioration. Physiotherapy should only be initiated by specialist services, as manipulation can cause more spinal cord damage.
Dementia Perception Syndromes
Capgras syndrome: the delusion that a friend or partner has been replaced by an identical-looking impostor.
Othello syndrome is the irrational belief that one’s partner is having an affair with no objective evidence.
De clerambault syndrome is the delusional idea that a person whom they consider to be of higher social and/or professional standing is in love with her.
Cotard syndrome is the delusional idea that one is dead.
Fregoli syndrome is the delusional idea that the various people that the patient meets are in fact the same person.
Dermatomes
Nerve root
Landmark
C2
Posterior half of the skull (cap)
C3
High turtleneck shirt
C4
Low-collar shirt
C5
Ventral axial line of upper limb
C6
Thumb + index finger
C7
Middle finger + palm of hand
C8
Ring + little finger
T4
Nipples
T5
Inframammary fold
T6
Xiphoid process
T10
Umbilicus
L1
Inguinal ligament
L4
Knee caps
L5
Big toe, dorsum of foot (except lateral aspect)
S1
Lateral foot, small toe
S2, S3
Genitalia
DVLA neurological disorders
The guidelines below relate to car/motorcycle use unless specifically stated. For obvious reasons, the rules relating to drivers of heavy goods vehicles tend to be much stricter
Epilepsy/seizures - all patient must not drive and must inform the DVLA
first unprovoked/isolated seizure: 6 months off if there are no relevant structural abnormalities on brain imaging and no definite epileptiform activity on EEG. If these conditions are not met then this is increased to 12 months
for patients with established epilepsy or those with multiple unprovoked seizures:
→ may qualify for a driving licence if they have been free from any seizure for 12 months
→ if there have been no seizures for 5 years (with medication if necessary) a ’til 70 licence is usually restored
withdrawawl of epilepsy medication: should not drive whilst anti-epilepsy medication is being withdrawn and for 6 months after the last dose
Syncope
simple faint: no restriction
single episode, explained and treated: 4 weeks off
single episode, unexplained: 6 months off
two or more episodes: 12 months off
Other conditions
stroke or TIA: 1 month off driving, may not need to inform DVLA if no residual neurological deficit
multiple TIAs over short period of times: 3 months off driving and inform DVLA
craniotomy e.g. For meningioma: 1 year off driving*
pituitary tumour: craniotomy: 6 months; trans-sphenoidal surgery ‘can drive when there is no debarring residual impairment likely to affect safe driving’
narcolepsy/cataplexy: cease driving on diagnosis, can restart once ‘satisfactory control of symptoms’
chronic neurological disorders e.g. multiple sclerosis, motor neuron disease: DVLA should be informed, complete PK1 form (application for driving licence holders state of health)
*if the tumour is a benign meningioma and there is no seizure history, licence can be reconsidered 6 months after surgery if remains seizure free
Dystrophinopathies
Overview X-linked recessive
due to mutation in the gene encoding dystrophin, dystrophin gene on Xp21
dystrophin is part of a large membrane associated protein in muscle which connects the muscle membrane to actin, part of the muscle cytoskeleton
in Duchenne muscular dystrophy there is a frameshift mutation resulting in one or both of the binding sites are lost leading to a severe form
in Becker muscular dystrophy there is a non-frameshift insertion in the dystrophin gene resulting in both binding sites being preserved leading to a milder form
Duchenne 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
Becker muscular dystrophy
develops after the age of 10 years
intellectual impairment much less common
Overview
X-linked recessive
due to mutation in the gene encoding dystrophin, dystrophin gene on Xp21
dystrophin is part of a large membrane associated protein in muscle which connects the muscle membrane to actin, part of the muscle cytoskeleton
in Duchenne muscular dystrophy there is a frameshift mutation resulting in one or both of the binding sites are lost leading to a severe form
in Becker muscular dystrophy there is a non-frameshift insertion in the dystrophin gene resulting in both binding sites being preserved leading to a milder form
Duchenne 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
Becker muscular dystrophy
develops after the age of 10 years
intellectual impairment much less common
Epilepsy classification
The basic classification of epilepsy has changed in recent years. The new basic seizure classification is based on 3 key features:
- Where seizures begin in the brain
- Level of awareness during a seizure (important as can affect safety during seizure)
- Other features of seizures
Focal seizures
previously termed partial seizures
these start in a specific area, on one side of the brain
the level of awareness can vary in focal seizures. The terms focal aware (previously termed ‘simple partial’), focal impaired awareness (previously termed ‘complex partial’) and awareness unknown are used to further describe focal seizures
further to this, 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
Generalised
these engage or involve networks on both sides of the brain at the onset
consciousness lost immediately. The level of awareness in the above classification is therefore not needed, as all patients lose consciousness
generalised seizures can be further subdivided into motor (e.g. tonic-clonic) and non-motor (e.g. absence)
specific types include:
→ tonic-clonic (grand mal)
→ tonic
→ clonic
→ typical absence (petit mal)
→ atonic
Unknown onset
this termed is reserved for when the origin of the seizure is unknown
Focal to bilateral seizure
starts on one side of the brain in a specific area before spreading to both lobes
previously termed secondary generalized seizures
Cataplexy
Cataplexy describes the 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.
Features range from buckling knees to collapse.
Psychogenic non-epileptic seizures
Psychogenic nonepileptic seizures are sometimes referred to as pseudoseizures.
Factors favouring pseudoseizures
pelvic thrusting
family member with epilepsy
much more common in females
crying after seizure
don’t occur when alone
gradual onset
Factors favouring true epileptic seizures
tongue biting
raised serum prolactin*
Video telemetry is useful for differentiating
*why prolactin is raised following seizures is not fully understood. It is hypothesised that there is spread of electrical activity to the ventromedial hypothalamus, leading to release of a specific prolactin regulator into the hypophyseal portal system
Epilepsy: treatment
Most neurologists now start antiepileptics following a second epileptic seizure. NICE guidelines suggest starting antiepileptics after the first seizure if any of the following are present:
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
Sodium valproate is considered the first line treatment for patients with generalised seizures with carbamazepine used for focal seizures.
Generalised tonic-clonic seizures
sodium valproate
second line: lamotrigine, carbamazepine
Absence seizures* (Petit mal)
sodium valproate or ethosuximide
sodium valproate particularly effective if co-existent tonic-clonic seizures in primary generalised epilepsy
Myoclonic seizures**
sodium valproate
second line: clonazepam, lamotrigine
Focal seizures
carbamazepine or lamotrigine
second line: levetiracetam, oxcarbazepine or sodium valproate
*carbamazepine may exacerbate absence seizures
**carbamazepine may exacerbate myoclonic seizures
Seizures: acute management
Most seizures are self-limiting and stop spontaneously but prolonged seizures may be potentially life-threatening.
Basics
check the airway and apply oxygen if appropriate
place the patient in the recovery position
if the seizure is prolonged give benzodiazepines
BNF recommend dose for rectal diazepam, repeated once after 10-15 minutes if necessary
Neonate
1.25 - 2.5 mg
Child 1 month - 1 year
5 mg
Child 2 years - 11 years
5 - 10 mg
Child 12 years - 17 years
10 mg
Adult
10 - 20 mg (max. 30 mg)
Elderly
10 mg (max. 15 mg)
Midazolam oromucosal solution may also be used:
Essential tremor
Essential tremor (previously called benign essential tremor) is an autosomal dominant condition which usually affects both upper limbs
Features
postural tremor: worse if arms outstretched
improved by alcohol and rest
most common cause of titubation (head tremor)
Management
propranolol is first-line
primidone is sometimes used
Tremor
The table below lists the main characteristics of the most important causes of tremor
Conditions
Notes
Parkinsonism
Resting, ‘pill-rolling’ tremor
Bradykinesia
Rigidity
Flexed posture, short, shuffling steps
Micrographia
‘Mask-like’ face
Depression & dementia are common
May be history of anti-psychotic use
Essential tremor
Postural tremor: worse if arms outstretched
Improved by alcohol and rest
Titubation
Often strong family history
Anxiety
History of depression
Thyrotoxicosis
Usual thyroid signs e.g. Weight loss, tachycardia, feeling hot etc
Hepatic encephalopathy
History of chronic liver disease
Carbon dioxide retention
History of chronic obstructive pulmonary disease
Cerebellar disease
Intention tremor
Cerebellar signs e.g. Past-pointing, nystagmus etc
Other causes
drug withdrawal: alcohol, opiates
Tremor
The table below lists the main characteristics of the most important causes of tremor
Conditions
Notes
Parkinsonism
Resting, ‘pill-rolling’ tremor
Bradykinesia
Rigidity
Flexed posture, short, shuffling steps
Micrographia
‘Mask-like’ face
Depression & dementia are common
May be history of anti-psychotic use
Essential tremor
Postural tremor: worse if arms outstretched
Improved by alcohol and rest
Titubation
Often strong family history
Anxiety
History of depression
Thyrotoxicosis
Usual thyroid signs e.g. Weight loss, tachycardia, feeling hot etc
Hepatic encephalopathy
History of chronic liver disease
Carbon dioxide retention
History of chronic obstructive pulmonary disease
Cerebellar disease
Intention tremor
Cerebellar signs e.g. Past-pointing, nystagmus etc
Other causes
drug withdrawal: alcohol, opiates
Facial nerve palsy
The facial nerve is the main nerve supplying the structures of the second embryonic branchial arch. It is predominantly an efferent nerve to the muscles of facial expression, digastric muscle and also to many glandular structures. It contains a few afferent fibres which originate in the cells of its genicular ganglion and are concerned with taste.
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 nerve 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 this represents only 1% of total Bell’s palsy cases
Causes of unilateral facial nerve palsy - as above plus
Lower motor neuron
Bell’s palsy
Ramsay-Hunt syndrome (due to herpes zoster)
acoustic neuroma
parotid tumours
HIV
multiple sclerosis*
diabetes mellitus
Upper motor neuron
stroke
LMN vs. UMN
upper motor neuron lesion ‘spares’ upper face i.e. forehead
lower motor neuron lesion affects all facial muscles
*may also cause an UMN palsy
Path
Subarachnoid path
Origin: motor- pons, sensory- nervus intermedius
Pass through the petrous temporal bone into the internal auditory meatus with the vestibulocochlear nerve. Here they combine to become the facial nerve.
Facial canal path
The canal passes superior to the vestibule of the inner ear
At the medial aspect of the middle ear, it becomes wider and contains the geniculate ganglion.
- 3 branches:
1. greater petrosal nerve
2. nerve to stapedius
3. chorda tympani
Stylomastoid foramen
Passes through the stylomastoid foramen (tympanic cavity anterior and mastoid antrum posteriorly)
Posterior auricular nerve and branch to posterior belly of digastric and stylohyoid muscle
Glasgow Coma Scale: adults
Modality Options
Motor response
- Obeys commands
- Localises to pain
- Withdraws from pain
- Abnormal flexion to pain (decorticate posture)
- Extending to pain
- None
Verbal response
- Orientated
- Confused
- Words
- Sounds
- None
Eye opening
- Spontaneous
- To speech
- To pain
- None
Guillain-Barre Syndrome
Guillain-Barre syndrome describes an immune mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni)
Pathogenesis
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
Miller Fisher 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
Guillain-Barre syndrome is an immune-mediated demyelination of the peripheral nervous system which is often triggered by an infection. It presents with ascending motor neuropathy which is often rapidly advancing. Proximal muscles are more affected than distal muscles.
A transient ischaemic attack or stroke is usually of sudden onset and would typically cause unilateral symptoms which may include facial droop, arm weakness, slurred speech etc.
Raynaud’s disease typically affects the fingers and toes and causes numbness and pain, usually in response to cold weather or stress.
Headache: red flags
Headache is one of the most common presenting complaints seen in clinical practice. The vast majority of these will be caused by common, benign conditions. There are however certain features in a history which should prompt further action. In the 2012 guidelines NICE suggest the following:
compromised immunity, caused, for example, by HIV or immunosuppressive drugs
age under 20 years and a history of malignancy
a history of malignancy known to metastasis to the brain
vomiting without other obvious cause
worsening headache with fever
sudden-onset headache reaching maximum intensity within 5 minutes - ‘thunderclap’
new-onset neurological deficit
new-onset cognitive dysfunction
change in personality
impaired level of consciousness
recent (typically within the past 3 months) head trauma
headache triggered by cough, valsalva (trying to breathe out with nose and mouth blocked), sneeze or exercise
orthostatic headache (headache that changes with posture)
symptoms suggestive of giant cell arteritis or acute narrow-angle glaucoma
a substantial change in the characteristics of their headache
A cluster headache results in intense pain around one eye which is often accompanied by lacrimation and redness of the eye. It usually lasts 15 mins - 2 hours. Treatments for this include triptans and oxygen.
The gentleman in this question has a tension-type headache which is not treated with oxygen. He should be asked more about how he could relieve some of his stressors and also consider using alternative analgesia. Migraines, post-coital headaches and temporal arteritis are not usually treated with oxygen.
Cluster headache
Cluster headaches are known to be one of the most painful conditions that patients can have the misfortune to suffer. The name relates to the pattern of the headaches - they typically occur in clusters lasting several weeks, with the clusters themselves typically once a year.
Cluster headaches are more common in men (3:1) and smokers. Alcohol may trigger an attack and there also appears to be a relation to nocturnal sleep.
Features
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)
patient is restless and agitated during an attack
accompanied by redness, lacrimation, lid swelling
nasal stuffiness
miosis and ptosis in a minority
Management
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
Some neurologists use the term trigeminal autonomic cephalgia to group a number of conditions including cluster headache, paroxysmal hemicrania and short-lived unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). It is recommended such patients are referred for specialist assessment as specific treatment may be required, for example it is known paroxysmal hemicrania responds very well to indomethacin
Huntington’s disease
Huntington’s disease is an inherited neurodegenerative condition. It is a progressive and incurable condition that typically results in death 20 years after the initial symptoms develop.
Genetics
autosomal dominant
trinucleotide repeat disorder: repeat expansion of CAG
as Huntington’s disease is a trinucleotide repeat disorder, the phenomenon of anticipation may be seen, where the disease is presents at an earlier age in successive generations
results in degeneration of cholinergic and GABAergic neurons in the striatum of the basal ganglia
defect in huntingtin gene on chromosome 4
Features typical develop after 35 years of age
chorea
personality changes (e.g. irritability, apathy, depression) and intellectual impairment
dystonia
saccadic eye movements
Idiopathic intracranial hypertension
Idiopathic intracranial hypertension (also known as pseudotumour cerebri and formerly benign intracranial hypertension) is a condition classically seen in young, overweight females.
Risk factors
obesity
female sex
pregnancy
drugs*: oral contraceptive pill, steroids, tetracycline, vitamin A, lithium
Features
headache
blurred vision
papilloedema (usually present)
enlarged blind spot
sixth nerve palsy may be present
Management
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
*if intracranial hypertension is thought to occur secondary to a known causes (e.g. Medication) then it is of course not idiopathic
Migraine management
It should be noted that as a general rule 5-HT receptor agonists are used in the acute treatment of migraine whilst 5-HT receptor antagonists are used in prophylaxis. NICE produced guidelines in 2012 on the management of headache, including migraines.
Acute treatment
first-line: offer combination therapy with an oral triptan and an NSAID, or an oral triptan and paracetamol
for young people aged 12-17 years consider a nasal triptan in preference to an oral triptan
if the above measures are not effective or not tolerated offer a non-oral preparation of metoclopramide* or prochlorperazine and consider adding a non-oral NSAID or triptan
Prophylaxis
prophylaxis should be given if patients are experiencing 2 or more attacks per month. Modern treatment is effective in about 60% of patients.
NICE advise either topiramate or propranolol ‘according to the person’s preference, comorbidities and risk of adverse events’. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives
if these measures fail NICE recommend ‘a course of up to 10 sessions of acupuncture over 5-8 weeks’
NICE recommend: ‘Advise people with migraine that riboflavin (400 mg once a day) may be effective in reducing migraine frequency and intensity for some people’
for women with predictable menstrual migraine treatment NICE 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’
pizotifen is no longer recommend. Adverse effects such as weight gain & drowsiness are common
*caution should be exercised with young patients as acute dystonic reactions may develop
Migraine
acute: triptan + NSAID or triptan + paracetamol
prophylaxis: topiramate or propranolol
Migraine: diagnostic criteria
The International Headache Society has produced the following diagnostic criteria for migraine without aura:
Point
Criteria
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:
- unilateral location*
- pulsating quality (i.e., varying with the heartbeat)
- moderate or severe pain intensity
- aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)
D
During headache at least one of the following:
- nausea and/or vomiting*
- 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)
*In children, attacks may be shorter-lasting, headache is more commonly bilateral, and gastrointestinal disturbance is more prominent.
Migraine with aura (seen in around 25% of migraine patients) tends to be easier to diagnose with a typical aura being progressive in nature and may occur hours prior to the headache. Typical aura include a transient hemianopic disturbance or a spreading scintillating scotoma (‘jagged crescent’). Sensory symptoms may also occur
If we compare these guidelines to the NICE criteria the following points are noted:
NICE suggests migraines may be unilateral or bilateral
NICE also give more detail about typical auras:
Auras may occur with or without headache and:
are fully reversible
develop over at least 5 minutes
last 5-60 minutes
The following aura symptoms are atypical and may prompt further investigation/referral;
motor weakness
double vision
visual symptoms affecting only one eye
poor balance
decreased level of consciousness.
Motor neuron disease
Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognised including amyotrophic lateral sclerosis, progressive muscular atrophy and bulbar palsy.
There are a number of clues which point towards a diagnosis of motor neuron 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
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
The diagnosis of motor neuron disease is clinical, but nerve conduction studies will show normal motor conduction and can help exclude a neuropathy. Electromyography shows a reduced number of action potentials with increased amplitude. MRI is usually performed to exclude the differential diagnosis of cervical cord compression and myelopathy
*vague sensory symptoms may occur early in the disease (e.g. limb pain) but ‘never’ sensory signs
Multiple sclerosis
Patient’s with multiple sclerosis (MS) may present with non-specific features, for example around 75% of patients have significant lethargy.
Diagnosis can be made on the basis of two or more relapses and either objective clinical evidence of two or more lesions or objective clinical evidence of one lesion together with reasonable historical evidence of a previous relapse.
Visual
optic neuritis: common presenting feature
optic atrophy
Uhthoff’s phenomenon: worsening of vision following rise in body temperature
internuclear ophthalmoplegia
Sensory
pins/needles
numbness
trigeminal neuralgia
Lhermitte’s syndrome: paraesthesiae in limbs on neck flexion
Motor
spastic weakness: most commonly seen in the legs
Cerebellar
ataxia: more often seen during an acute relapse than as a presenting symptom
tremor
Others
urinary incontinence
sexual dysfunction
intellectual deterioration
Multiple sclerosis: management
Treatment in multiple sclerosis is focused at reducing the frequency and duration of relapses. There is no cure.
Acute relapse
High dose steroids (e.g. oral or IV methylprednisolone) may be given for 5 days to shorten the length of an acute relapse. It should be noted that steroids shorten the duration of a relapse and do not alter the degree of recovery (i.e. whether a patient returns to baseline function)
Disease modifying drugs
Beta-interferon has been shown to reduce the relapse rate by up to 30%. Certain criteria have to be met before it is used:
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)
reduces number of relapses and MRI changes, however doesn’t reduce overall disability
Other drugs used in the management of multiple sclerosis include:
glatiramer acetate: immunomodulating drug - acts as an ‘immune decoy’
natalizumab: a recombinant monoclonal antibody that antagonises Alpha-4 Beta-1-integrin found on the surface of leucocytes, thus inhibiting migration of leucocytes across the endothelium across the blood-brain barrier
fingolimod: sphingosine 1-phosphate receptor modulator, prevents lymphocytes from leaving lymph nodes. An oral formulation is available
Some specific problems
Fatigue
once other problems (e.g. anaemia, thyroid or depression) have been excluded NICE recommend a trial of amantadine
other options include mindfulness training and CBT
Spasticity
baclofen and gabapentin are first-line. Other options include diazepam, dantrolene and tizanidine
physiotherapy is important
cannabis and botox are undergoing evalulation
Bladder dysfunction
may take the form of urgency, incontinence, overflow etc
guidelines stress the importance of getting an ultrasound first to assess bladder emptying - anticholinergics may worsen symptoms in some patients
if significant residual volume → intermittent self-catheterisation
if no significant residual volume → anticholinergics may improve urinary frequency
Oscillopsia (visual fields apper to oscillate)
gabapentin is first-line
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a rare but dangerous condition seen in patients taking antipsychotic medication. It carries a mortality of up to 10% and can also occur with atypical antipsychotics. It may also occur with dopaminergic drugs (such as levodopa) for Parkinson’s disease, usually when the drug is suddenly stopped or the dose reduced.
The pathophysiology is unknown but one theory is that the dopamine blockade induced by antipsychotics triggers massive glutamate release and subsequent neurotoxicity and muscle damage.
It occurs within hours to days of starting an antipsychotic (antipsychotics are also known as neuroleptics, hence the name) and the typical features are:
pyrexia
muscle rigidity
autonomic lability: typical features include hypertension, tachycardia and tachypnoea
agitated delirium with confusion
A raised creatine kinase is present in most cases. Acute kidney injury (secondary to rhabdomyolysis) may develop in severe cases. A leukocytosis may also be seen
Management
stop antipsychotic
patients should be transferred to a medical ward if they are on a psychiatric ward and often they are nursed in intensive care units
IV fluids to prevent renal failure
dantrolene may be useful in selected cases
thought to work by 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
Neuropathic pain
Neuropathic pain may be defined as pain which arises following damage or disruption of the nervous system. It is often difficult to treat and responds poorly to standard analgesia.
Examples include:
diabetic neuropathy
post-herpetic neuralgia
trigeminal neuralgia
prolapsed intervertebral disc
NICE updated their guidance on the management of neuropathic pain in 2013:
first-line treatment*: amitriptyline, duloxetine, gabapentin or pregabalin
if the first-line drug treatment does not work try one of the other 3 drugs
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)
pain management clinics may be useful in patients with resistant problems
*please note that for some specific conditions the guidance may vary. For example carbamazepine is used first-line for trigeminal neuralgia
Neuropathic pain
Neuropathic pain may be defined as pain which arises following damage or disruption of the nervous system. It is often difficult to treat and responds poorly to standard analgesia.
Examples include:
diabetic neuropathy
post-herpetic neuralgia
trigeminal neuralgia
prolapsed intervertebral disc
NICE updated their guidance on the management of neuropathic pain in 2013:
first-line treatment*: amitriptyline, duloxetine, gabapentin or pregabalin
if the first-line drug treatment does not work try one of the other 3 drugs
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)
pain management clinics may be useful in patients with resistant problems
*please note that for some specific conditions the guidance may vary. For example carbamazepine is used first-line for trigeminal neuralgia
Parkinson’s disease: management
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
*Domperidone does not cross the blood-brain barrier and therefore does not cause extra-pyramidal side-effects.
Levodopa should be offered for patients with newly diagnosed Parkinson’s who have motor symptoms affecting their quality of life
Essential tremor is an AD condition that is made worse when arms are outstretched, made better by alcohol and propranolol
Parkinsons disease should only be diagnosed, and management initiated, by a specialist with expertise in movement disorders. However, it is important for all doctors to be aware of the medications used in Parkinson’s given the prevalence of this condition. NICE published guidelines in 2017 regarding the management of Parkinson’s disease.
For first-line treatment:
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
Specific points regarding Parkinson’s medication
NICE reminds us of the risk of acute akinesia or neuroleptic malignant syndrome if medication is not taken/absorbed (for example due to gastroenteritis) and advise against giving patients a ‘drug holiday’ for the same reason.
Impulse control disorders have become a significant issue in recent years. These can occur with any dopaminergic therapy but are more common with:
dopamine agonist therapy
a history of previous impulsive behaviours
a history of alcohol consumption and/or smoking
If excessive daytime sleepiness develops then patients should not drive. Medication should be adjusted to control symptoms. Modafinil can be considered if alternative strategies fail.
If orthostatic hypotension develops then a medication review looking at potential causes should be done. If symptoms persist then midodrine (acts on peripheral alpha-adrenergic receptors to increase arterial resistance) can be considered.
Consider glycopyrronium bromide to manage drooling of saliva in people with Parkinson’s disease.
Further information regarding specific anti-Parkinson’s medication
Levodopa
usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) to prevent peripheral metabolism of levodopa to dopamine
reduced effectiveness with time (usually by 2 years)
unwanted effects: dyskinesia (involuntary writhing movements), ‘on-off’ effect, dry mouth, anorexia, palpitations, postural hypotension, psychosis, drowsiness
no use in neuroleptic induced parkinsonism
it is important not to acutely stop levodopa, for example if a patient is admitted to hospital. If a patient with Parkinson’s disease cannot take levodopa orally, they can be given a dopamine agonist patch as rescue medication to prevent acute dystonia
Dopamine receptor agonists
e.g. bromocriptine, ropinirole, cabergoline, apomorphine
ergot-derived dopamine receptor agonists (bromocriptine, cabergoline) have been associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on Safety of Medicines advice that an echocardiogram, ESR, creatinine and chest x-ray should be obtained prior to treatment and patients should be closely monitored
patients should be warned about the potential for dopamine receptor agonists to cause impulse control disorders and excessive daytime somnolence
more likely than levodopa to cause hallucinations in older patients. Nasal congestion and postural hypotension are also seen in some patients
MAO-B (Monoamine Oxidase-B) inhibitors
e.g. selegiline
inhibits the breakdown of dopamine secreted by the dopaminergic neurons
Amantadine
mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses
side-effects include ataxia, slurred speech, confusion, dizziness and livedo reticularis
COMT (Catechol-O-Methyl Transferase) inhibitors
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
Antimuscarinics
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)
Peripheral neuropathy
Peripheral neuropathy may be divided into conditions which predominately cause a motor or sensory loss
Predominately motor loss
Guillain-Barre syndrome
porphyria
lead poisoning
hereditary sensorimotor neuropathies (HSMN) - Charcot-Marie-Tooth
chronic inflammatory demyelinating polyneuropathy (CIDP)
diphtheria
Predominately sensory loss
diabetes
uraemia
leprosy
alcoholism
vitamin B12 deficiency
amyloidosis
Alcoholic neuropathy
secondary to both direct toxic effects and reduced absorption of B vitamins
sensory symptoms typically present prior to motor symptoms
Vitamin B12 deficiency
subacute combined degeneration of spinal cord
dorsal column usually affected first (joint position, vibration) prior to distal paraesthesia
Epileptic Drugs
Sodium valproate
Sodium valproate is used in the management of epilepsy and is first-line therapy for generalised seizures. It works by increasing GABA activity.
Adverse effects
P450 inhibitor
gastrointestinal: nausea
increased appetite and weight gain
alopecia: regrowth may be curly
ataxia
tremor
hepatotoxicity
pancreatitis
thrombocytopaenia
teratogenic
hyponatraemia
hyperammonemic encephalopathy: L-carnitine may be used as treatment if this develops
Sodium valproate may cause weight gain
Phenytoin
Phenytoin is used in the management of seizures.
Mechanism of action
binds to sodium channels increasing their refractory period
Adverse effects
Phenytoin is associated with a large number of adverse effects. These may be divided into acute, chronic, idiosyncratic and teratogenic. Phenytoin is also an inducer of the P450 system.
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
Monitoring
Phenytoin levels do not need to be monitored routinely but trough levels, immediately before dose should be checked if:
adjustment of phenytoin dose
suspected toxicity
detection of non-adherence to the prescribed medication
*although not listed in the BNF
Radial nerve
Continuation of posterior cord of the brachial plexus (root values C5 to T1)
Path
In the axilla: lies posterior to the axillary artery on subscapularis, latissimus dorsi and teres major.
Enters the arm between the brachial artery and the long head of triceps (medial to humerus).
Spirals around the posterior surface of the humerus in the groove for the radial nerve.
At the distal third of the lateral border of the humerus it then pierces the intermuscular septum and descends in front of the lateral epicondyle.
At the lateral epicondyle it lies deeply between brachialis and brachioradialis where it then divides into a superficial and deep terminal branch.
Deep branch crosses the supinator to become the posterior interosseous nerve.
Regions innervated
Motor (main nerve)
Triceps
Anconeus
Brachioradialis
Extensor carpi radialis
Motor (posterior interosseous branch)
Supinator
Extensor carpi ulnaris
Extensor digitorum
Extensor indicis
Extensor digiti minimi
Extensor pollicis longus and brevis
Abductor pollicis longus
Sensory
The area of skin supplying the proximal phalanges on the dorsal aspect of the hand is supplied by the radial nerve (this does not apply to the little finger and part of the ring finger)
Muscular innervation and effect of denervation
Anatomical location
Muscle affected
Effect of paralysis
Shoulder
Long head of triceps
Minor effects on shoulder stability in abduction
Arm
Triceps
Loss of elbow extension
Forearm
Supinator
Brachioradialis
Extensor carpi radialis longus and brevis
Weakening of supination of prone hand and elbow flexion in mid prone position
Patterns of damage
wrist drop
sensory loss to small area between the dorsal aspect of the 1st and 2nd metacarpals
Axillary damage
as above
paralysis of triceps
Sciatic nerve lesion
Basics
sciatic nerve is supplied by L4-5, S1-3
divides into tibial and common peroneal nerves
Supplies
hamstring muscles
adductor muscles
Features of sciatic nerve lesion
motor: paralysis of knee flexion and all movements below knee
sensory: loss below knee
reflexes: ankle + plantar lost, knee jerk intact
Causes
fracture neck of femur
posterior hip dislocation
trauma
The common reflexes are listed below:
Reflex
Root
Ankle
S1-S2
Knee
L3-L4
Biceps
C5-C6
Triceps
C7-C8
Stroke: a very basic introduction
Strokes represent an important cause of morbidity and mortality. In the UK alone there are over 150,000 strokes per year, with over 1.2 million stroke survivors. Stroke is the fourth largest cause of death in the UK and kills twice as many women than breast cancer each year.
The prevention and treatment of strokes has undergone significant changes over the past decade. What was previously considered a devastating but untreatable condition is now viewed more as a ‘brain attack’, a condition which requires emergency assessment to see if patients may benefit from new treatments such as thrombolysis.
Pathological specimen showing the results of an ischaemic stroke to the occipito-parietal region of the cerebrum. Note there has been some secondary haemorrhage in the affected area.
What is a stroke?
A stroke (also known as cerebrovascular accident,CVA) represents a sudden interruption in the vascular supply of the brain. Remember that neural tissue is completely dependent on aerobic metabolism so any problem with oxygen supply can quickly lead to irreversible damage.
There are two main types of strokes:
ischaemic: these can be further subdivided between into episodes which last greater than 24 hours (termed an ischaemic stroke) and episodes where symptoms and signs last less than 24 hours (transient ischaemic attacks, TIAs, sometimes termed ‘mini-strokes’ by patients)
haemorrhagic
Symptoms and signs
Stroke is defined by the World Health Organization as a clinical syndrome consisting of ‘rapidly developing clinical signs of focal (at times global) disturbance of cerebral function, lasting more than 24 hours or leading to death with no apparent cause other than that of vascular origin’. In contrast, with a TIA the symptoms and signs resolve within 24 hours.
Features include:
motor weakness
speech problems (dysphasia)
swallowing problems
visual field defects (homonymous hemianopia)
balance problems
Cerebral hemisphere infarcts may have the following symptoms:
contralateral hemiplegia: initially flaccid then spastic
contralateral sensory loss
homonymous hemianopia
dysphasia
Brainstem infarction
may result in more severe symptoms including quadriplegia and lock-in-syndrome
Lacunar infarcts
small infarcts around the basal ganglia, internal capsule, thalamus and pons
this may result in pure motor, pure sensory, mixed motor and sensory signs or ataxia
An example of a lacunar infarct affecting the internal capsule.
One formal classification system that is sometimes used is the Oxford Stroke Classification (also known as the Bamford Classification), whichclassifies strokes based on the initial symptoms. A summary is as follows:
The following criteria should be assessed:
- unilateral hemiparesis and/or hemisensory loss of the face, arm & leg
- homonymous hemianopia
- higher cognitive dysfunction e.g. dysphasia
Ischaemic strokes
Urgent neuroimaging classifies the stroke as either ischaemic or haemorrhagic. If the stroke is ischaemic, and certain criteria are met, the patient should be offered thrombolysis. Example criteria include:
patients present with 4.5 hours of onset of stroke symptoms
the patient has not had a previous intracranial haemorrhage, uncontrolled hypertension, pregnant etc
Once haemorrhagic stroke has been excluded patients should be given aspirin 300mg as soon as possible and antiplatelet therapy should be continued.
Transient ischaemic attacks
Remember with TIAs the, by definition, symptoms last less than 24 hours although in the vast majority of cases the duration is much shorter, typically 1 hour or so. For this reason most patients symptoms will have resolved before they see a doctor.
The ABCD2 prognostic score has previously been used to risk stratify patients who present with a suspected TIA. However, data from studies have suggested it performs poorly and it is therefore no longer recommended by NICE Clinical Knowledge Summaries. Instead, NICE recommend:
Immediate antithrombotic therapy:
give aspirin 300 mg immediately, unless contraindicated e.g. the patient has a bleeding disorder or is taking an anticoagulant (needs immediate admission for imaging to exclude a haemorrhage)
If the patient has had more than 1 TIA (‘crescendo TIA’) or has a suspected cardioembolic source or severe carotid stenosis:
discuss the need for admission or observation urgently with a stroke specialist
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
Haemorrhagic strokes
If imaging confirms a haemorrhagic stroke neurosurgical consultation should be considered for advice on further management. The vast majority of patients however are not suitable for surgical intervention. Management is therefore supportive as per haemorrhagic stroke. Anticoagulants (e.g. warfarin) and antithrombotic medications (e.g. clopidogrel) should be stopped to minimise further bleeding. If a patient is anticoagulated this should be reversed as quickly as possible. Trials have shown improved outcomes in patients who have their blood pressure lowered acutely and this is now part of many protocols for haemorrhagic strokes.
A 69-year-old gentleman presents to the emergency department with sudden onset right-sided numbness, with no other symptoms. He has a background of poorly controlled hypertension and diabetes mellitus. A CT head was arranged which reported no haemorrhage or mass. He is diagnosed as having had a lacunar stroke.
Transient ischaemic attack
The original definition of a transient ischaemic attack (TIA) was time-based: a sudden onset of a focal neurologic symptom and/or sign lasting less than 24 hours, brought on by a transient decrease in blood flow. However, this has now changed as it is recognised that even short periods of ischaemia can result in pathological changes to the brain. Therefore, a new ‘tissue-based’ definition is now used: a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischaemia, without acute infarction.
Patients often use the term ‘mini-stroke’ for TIAs.
Assessment and referral
The ABCD2 prognostic score has previously been used to risk stratify patients who present with a suspected TIA. However, data from studies have suggested it performs poorly and it is therefore no longer recommended by NICE Clinical Knowledge Summaries. Instead, NICE recommend:
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
If the patient has had more than 1 TIA (‘crescendo TIA’) or has a suspected cardioembolic source or severe carotid stenosis:
discuss the need for admission or observation urgently with a stroke specialist
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 the person not to drive until they have been seen by a specialist.
Further management
Antithrombotic therapy
clopidogrel is recommended first-line (as for patients who’ve had a stroke)
aspirin + dipyridamole should be given to patients who cannot tolerate clopidogrel
these recommendations follow the 2012 Royal College of Physicians National clinical guideline for stroke. Please see the link for more details (section 5.5)
these guidelines may change following the CHANCE study (NEJM 2013;369:11). This study looked at giving high-risk TIA patients aspirin + clopidogrel for the first 90 days compared to aspirin alone. 11.7% of aspirin only patients had a stroke over 90 days compared to 8.2% of dual antiplatelet patients
With regards to carotid artery endarterectomy:
recommend if patient has suffered stroke or TIA in the carotid territory and are not severely disabled
should only be considered if carotid stenosis > 70% according ECST* criteria or > 50% according to NASCET** criteria
*European Carotid Surgery Trialists’ Collaborative Group
**North American Symptomatic Carotid Endarterectomy Trial
Antiplatelets
TIA: clopidogrel
ischaemic stroke: clopidogrel
Importance: 80
Carotid artery endarterectomy is recommend if the patient has suffered a stroke or TIA in the carotid territory and is not severely disabled. It should only be considered if the carotid stenosis is greater than 70% or 50%, depending on the reporting criteria used - please see below.
NICE Clinical Knowledge Summaries state the following:
Antiplatelet therapy is initiated by secondary care on diagnosis of ischaemic stroke or TIA without paroxysmal or permanent atrial fibrillation for long-term vascular prevention:
The standard treatment is clopidogrel 75mg daily (licenced for use in ischaemic stroke, off-label use in TIA).
Modified-release dipyridamole 200 mg twice daily may be used if both clopidogrel and aspirin are contraindicated or cannot be tolerated.
Aspirin 75mg daily may be used if both clopidogrel and modified-release dipyridamole are contraindicated or cannot be tolerated.
Aspirin 75 mg daily with modified-release dipyridamole 200 mg twice daily may be used if clopidogrel cannot be tolerated.
The 2012 Royal College of Physicians National clinical guidelines for stroke now recommend using clopidogrel following a TIA. This brings it in line with current stroke guidance.
Trigeminal neuralgia
Trigeminal neuralgia is a pain syndrome characterised by severe unilateral pain. The vast majority of cases are idiopathic but compression of the trigeminal roots by tumours or vascular problems may occur.
The International Headache Society defines trigeminal neuralgia as:
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
NICE Clinical Knowledge Summaries list the following as red flag symptoms and signs suggesting a serious underlying cause:
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
carbamazepine is first-line
failure to respond to treatment or atypical features (e.g. < 50 years old) should prompt referral to neurology
This woman has symptoms typical of trigeminal neuralgia. The first line treatment for this is carbamazepine, which should be started at 100 mg twice daily and slowly titrated up until pain is relieved.
Tuberous sclerosis
Tuberous sclerosis (TS) is a genetic condition of autosomal dominant inheritance. Like neurofibromatosis, the majority of features seen in TS are neurocutaneous.
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
Ulnar nerve
Overview
arises from medial cord of brachial plexus (C8, T1)
Motor to
medial two lumbricals
aDductor pollicis
interossei
hypothenar muscles: abductor digiti minimi, flexor digiti minimi
flexor carpi ulnaris
Sensory to
medial 1 1/2 fingers (palmar and dorsal aspects)
Path
the ulnar nerve travels through the posteromedial aspect of the upper arm to the flexor compartment of the forearm
it then enters the palm of the hand via the Guyon’s canal, superficial to the flexor retinaculum and lateral to the pisiform bone
Visual field defects
The main points for the exam are:
left homonymous hemianopia means visual field defect to the left, i.e. Lesion of right optic tract
homonymous quadrantanopias: PITS (Parietal-Inferior, Temporal-Superior)
incongruous defects = optic tract lesion; congruous defects = optic radiation lesion or occipital cortex
A congruous defect simply means complete or symmetrical visual field loss and conversely an incongruous defect is incomplete or asymmetric. Please see the link for an excellent diagram.
Homonymous hemianopia
incongruous defects: lesion of optic tract
congruous defects: lesion of optic radiation or occipital cortex
macula sparing: lesion of occipital cortex
Homonymous quadrantanopias*
superior: lesion of temporal lobe
inferior: lesion of parietal lobe
mnemonic = PITS (Parietal-Inferior, Temporal-Superior)
Bitemporal hemianopia
lesion of optic chiasm
upper quadrant defect > lower quadrant defect = inferior chiasmal compression, commonly a pituitary tumour
lower quadrant defect > upper quadrant defect = superior chiasmal compression, commonly a craniopharyngioma
*this is very much the ‘exam answer’. Actual studies suggest that the majority of quadrantanopias are caused by occipital lobe lesions. Please see the link for more details.
Wernicke’s encephalopathy
Wernicke’s encephalopathy is a neuropsychiatric disorder caused by thiamine deficiency which is most commonly seen in alcoholics. Rarer causes include: persistent vomiting, stomach cancer, dietary deficiency. A classic triad of ophthalmoplegia/nystagmus, ataxia and confusion may occur. In Wernicke’s encephalopathy petechial haemorrhages occur in a variety of structures in the brain including the mamillary bodies and ventricle walls
Features
nystagmus (the most common ocular sign)
ophthalmoplegia
ataxia
confusion, altered GCS
peripheral sensory neuropathy
Investigations
decreased red cell transketolase
MRI
Treatment is with urgent replacement of thiamine
Relationship with Korsakoff syndrome
If not treated Korsakoff’s syndrome may develop as well. This is termed Wernicke-Korsakoff syndrome and is characterised by the addition of antero- and retrograde amnesia and confabulation in addition to the above symptoms.
