Neuro Flashcards
What is an essential tremor? What are the features of it?
autosomal dominant condition that affects both upper limbs
postural tremor - worse if arms outstretched
improved by alcohol and rest
moss common cause of titubation (head tremor)
Management of an essential tremor
first line - propanolol
primidone sometimes used
Causes of tremor
Parkinsonism
essential tremor
anxiety
thyrotoxicosis
hepatic encephalopathy
CO2 retention
cerebellar disease
drug withdrawal
What is motor neuron disease?
neuro condition of unknown cause
can present w/ both upper and lower signs
sensory neurones spared
rarely presents before 40yrs various patterns of disease are recognised
What are the types of motor neuron disease patterns?
amyotrophic lateral sclerosis
primary lateral sclerosis
progressive muscular atrophy
progressive bulbar palsy
Amytrophic lateral sclerosis
50% of pts
typically LMN signs in arms and UMN signs in legs
in familial cases gene responsible lies on C21 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 tongue, muscles of chewing / swallowing and facial muscles due to loss of function of brainstem motor nuclei
carries worst prognosis
What suggests a motor neurone disease diagnosis?
asymmetric limb weakness
mix of UMN and LMN signs
wasting of small hand muscles/tibialis anterior is common
fasciculations
absence of sensory signs / symptoms (vague sensory symptoms may occur early in disease but ‘never’ sensory signs
Other features of motor neurone disease
doesn’t affect external ocular muscles
no cerebellar signs
abdo reflexes usually preserved and sphincter dysfunction if present is a late feature
motor neurone disease diagnosis
clinical
nerve conduction studies = normal motor conduction, can help exclude neuropathy
Electromyography shows reduced number of action potentials w/ increased amplitude
MRI to exclude differential diagnosis of cervical cord compression and myelopathy
Motor neurone disease prognosis
poor - 50% of pts die w/in 3 yrs
Motor neurone disease management
riluzole
resp care - non-invasive ventilation (usually BIPAP) at night
nutrition - PEG
Riluzole
prevents stimulation of glutamate receptors
used mainly in amyotrophic lateral sclerosis
Signs of lower motor neurone disease
muscle wasting
reduced tone
fasciculations (muscle twitch)
reduced reflexes
Signs of upper motor neurone disease
increased tone or spasticity
brisk reflexes
upgoing plantar reflex
What is multiple sclerosis?
chronic cell-mediated autoimmune disorder characterised by demyelination in CNS
Multiple sclerosis epidemiology
3x more common in women
most commonly diagnosed in ppl 20-40
more common at higher latitudes
Multiple sclerosis genetics
monozygotic twin concordance = 30%
dizygotic twin concordance = 2%
Multiple sclerosis subtypes
Relapsing-remitting disease = most common, acute attack (1-2 months) followed by periods of remission
Secondary progressive disease = relapsing-remitting pts who have deteriorated and developed neuro signs and symptoms between relapses, gait and bladder disorders
Primary progressive disease = progressive deterioration from onset, more common in older ppl
Prevelance of multiple sclerosis types
relapsing-remitting = around 85%
around 65% of relapsing-remitting go on to develop secondary progressive w/in 15yrs
primary progressive = around 10%
Sensory and motor features of multiple sclerosis
Sensory = pins n needles, numbness, trigeminal neuralgia, Lhermitte’s syndrome
Motor = spastic weakness - most commonly in legs
Visual and cerebellar features of multiple sclerosis
Visual = optic neuritis, optic atrophy, Uhtoff’s phenomenon, internuclear ophthalmoplegia
Cerebellar = more often in an acute relapse than as presenting symptom, tremor
Uhthoff’s phenomenon
neuro features eg vision are exacerbated when body temp rises, associated w/ multiple sclerosis
Lhermitte’s syndrome
paraesthesiae in limbs on neck flexion
Lhermitte’s sign = sudden electric shock feeling that runs down neck into spine
Other features of multiple sclerosis
around 75% pts have significant lethargy
urinary incontinence
sexual dysfunction
intellectual deterioration
Multiple sclerosis investigations
diagnosis requires demonstration of lesions disseminated in time and space
MRI
CSF features
visual evoked potentials test - delayed, well preserved waveform
MRI signs in multiple sclerosis
high signal T2 lesions
periventricular plaques
Dawson fingers - often on FLAIR images - demyelinating plaques on ventricles or fluid filled spaces
CSF in multiple sclerosis
oligoclonal bands (and not in serum)
increased intrathecal synthesis of IgG
Multiple sclerosis acute relapse management
high dose steroids eg oral or IV methylprednisolone
5 days to shorten length of actual relapse
Typical indications for disease-modifying drugs to reduce risk of relapse in patients w/ MS
relapsing-remitting disease and 2 relapses in past 2 yrs and able to walk 100m unaided
secondary progressive disease and 2 relapses in past 2 yrs and able to walk 10m
Drug options for reducing risk of relapse in MS
natalizumab IV
ocrelizumab IV
fingolimod
beta-interferon
glatiramer acetate
Natalizumab
recombinant monoclonal antibody that antagonises alpha-4 beta-1 integrin found on surface of leucocytes
inhibit migration of leucocytes across endothelium across BBB
often used first line for MS
Ocrelizumab
humanised anti-CD20 monoclonal antibody
like natalizumab, considered high efficacy drug so used first line for MS
Fingolimod
sphingosine 1-phosphate (S1P) receptor modulator
prevents lymphocytes from leaving lymph nodes
Glatiramer acetate
immunomodulating drug - acts as ‘immune decoy’
along w/ beta-interferon considered ‘older drug’ w/ less effectiveness compared to monoclonal antibodies and S1P receptor modulators
Spasticity treatment
baclofen and gabapentin
other options = diazepam, dantrolene and tizanidine
physio
Bladder dysfunction treatment
US bladder
significant residual vol = intermittent self catheterisation
no significant residual vol = anticholinergics may improve urinary frequency
Oscillipsia treatment
oscillopsia = visual fields appear to oscillate
1st line = gabapentin
What is Duchenne muscular dystrophy?
x-linked recessive inherited disorder in dystrophin genes required for normal muscular function
Features of Duchenne muscular dystrophy
progressive proximal muscle weakness from 5 yrs
calf pseudohypertrophy
Gower’s sign = child uses arms to stand up from squatted position
30% have intellectual impairment
Investigations of Duchenne muscular dystrophy
raised creatinine kinase
genetic testing - replaced muscle biopsy
Management of Duchenne muscular dystrophy
largely supportive
most children can’t walk by 12
pts typically survive to around 25-30
associated w/ dilated cardiomyopathy
What is myotonic dystrophy?
dystrophia myotonica
inherited autosomal dominant myopathy w/ features developing around 20-30
affects skeletal, cardiac and smooth muscle
2 main types = DM1 and DM2
DM1 v DM2
DM1 = DMPK gene on C19. Distal weakness more prominent
DM2 = ZFN9 gene on C3. Prox. weakness more prominent, severe congenital form not seen
Features of myotonic dystrophy
myotonic facies (long, haggard appearance)
frontal balding
bilateral ptosis
cataracts
dysarthria
myotonia
weakness of arms and legs
mild mental impairment
DM
Duchenne muscular dystrophy pathology
x-linked recessive mutation in gene encoding dystrophin on Xp21
dystrophin is part of a large membrane associated protein in muscle which connects muscle membrane to actin, part of muscle cytoskeleton
frameshift mutation resulting in 1 or both binding sites lost leading to severe form
Becker muscular dystrophy
non-frameshift insertion in dystrophin gene resulting in both binding sites being preserved to milder form
develops after age of 10
intellectual impairment much less common
What is Huntington’s disease?
inherited neurodegenerative condition
progressive and incurable condition that typically results in death 20yrs after initial symptoms
Huntington’s disease genetics
autosomal dominant
trinucleotide repeat disorder of CAG
anticipation may be seen (presents earlier in successive generations)
results in degeneration of cholinergic and GABAergic neurons in striatum of basal ganglia
defect in huntingtin gene on C4
Huntington’s disease features
typically develop after 35yrs:
chorea
personality changes (irritability, apathy, depression) and intellectual impairment
dystonia
saccadic eye movements
Huntington’s disease management
no treatment options to slow or stop disease
physio
SLT
tetrabenazine - chorea
antidepressants
Causes of a brain abscess
extension of sepsis from middle ear or sinuses
trauma
surgery to scalp
penetrating head injuries
embolic events from endocarditis
Symptoms of a brain abscess
headache - dull, persistent
fever
focal neurology - due to raised intracranial pressure
nausea
papilloedema
seizures
Brain abscess investigations
CT scan
Brain abscess management
surgery - craniotomy, cavity debrided. Abscess may reform bcs head is closed following abscess drainage
IV antibiotics - cephalosporin & metronidazole
dexamethasone for intracranial pressure management
Meningitis causes 0 - 3 months
grp B streptococcus (most common in neonates)
e.coli
listeria monocytogenes
Meningitis causes 3 months - 6yrs
neisseria meningitidis
streptococcus pneumoniae
haemophilus influenzae
Meningitis causes 6yrs - 60yrs
neisseria meningitidis
streptococcus pneumoniae
Meningitis causes >60yrs
neisseria meningitidis
streptococcus pneumoniae
listeria monocytogenes
Meningitis causes in immunosuppressed ppl
listeria monoctyogenes
What is meningitis?
inflammation of the meninges (lining of brain and spinal cord), usually due to infection
CSF is contained w/in meninges (subarachnoid space)
Symptoms of meningitis
headache
fever
nausea / vomiting
photophobia
drowsiness
seizures
Signs of meningitis
neck stiffness
purpuric rash (particularly w/ invasive meningococcal disease)
Bacterial meningitis in infants
classical signs of meningitis often absent
Bacterial meningitis features
CSF appearance = cloudy
Glucose = low
Protein = high
WCs = 10 - 5000 polymorphs/mm3
Viral meningitis features
CSF appearance = clear/cloudy
Glucose = 60 - 80% of plasma glucose
Protein = normal / raised
WCs = 15 - 1000 lymphocytes/mm3
Tuberculous meningitis features
CSF appearance = slightly cloudy, fibrin web
Glucose = low
Protein = high
WCs = 10 - 1000 lymphocytes/mm3
Ziehl-Neelson sensitivity
only 20% in detection of tuberculous meningitis
PCR is sometimes used (sensitivity = 75%)
Fungal meningitis features
CSF appearance = cloudy
Glucose = low
Protein = high
WCs = 20 - 200 lymphocytes/mm3
Contraindications to lumbar puncture
any signs of raised ICP
focal neuro signs
papilloedema
significant bulging of fontanelle
disseminated intravascular coagulation
signs of cerebral herniation
meningococcal septicaemia (do blood cultures and PCR)
Meningitis management
antibiotics (<3mnths = IV amox & Iv cefotaxime. >3mnths = IV cefotaxime)
steroids
fluids
cerebral monitoring
public health notification and abx prophylaxis of contacts
Meningitis complications
Neurological sequalae - sensorineural hearing loss, seizures, focal neurological deficit
Infective - sepsis, intracerebral abscess
Pressure - brain herniation, hydrocephalus
meningococcal meningitis has risk of Waterhouse-Friderichsen syndrome (adrenal insufficiency 2nd to adrenal haemorrhage)
When is the meningitis B vaccine given?
2 months
4 months
12-13 months
Causes of viral meningitis
non-polio enteroviruses eg coxsackie virus, echovirus
mumps
herpes simplex virus, cytomegalovirus, herpes zoster viruses, HIV, measles
Risk factors of viral meningitis
pts at extremes of age (<5yrs and elderly)
immunocompromised eg pts w/ renal failure, w/ DM
IV drug users
Viral meningitis management
supportive while waiting for LP
viral meningitis is self-limiting, symptoms improve after 7-14 days and complications are rare in immunocompetent pts
Aciclovir may be used if pt is suspected of having meningitis 2nd to HSV
Immediate management of bacterial meningitis
if in a pre-hospital setting, IM benzylpenicilin can be given if meningococcal disease is suspected
Bacterial meningitis warning signs
rapidly progressive rash
poor peripheral perfusion
resp rate <8 or >30 / min
pulse rate <40 or >140 / min
pH <7.3
WBC <4 *109/L
lactate >4 mmol/L
GCS <12 or drop of 2 pts
poor response to fluid resuscitation
Management of pts w/ raised intracranial pressure
critical care input
secure airway and high flow O2
IV access - blood and cultures
IV dexamethasone
IV abx
arrange neuroimaging
Bacterial meningitis investigations
GBC
renal function
glucose
lactate
clotting profile
CRP
Features of encephalitis
fever, headache, psychiatric symptoms, seizures, vomiting
focal features eg aphasia
peripheral lesions (eg cold sores) have no relation to presence of HSV encephalitis
Encephalitis pathophysiology
HSV-1 is responsible for 95% of cases in adults
typically affects temporal and inferior frontal lobes
Encephalitis investigations
Bloods
CSF- lymphocytes, elevated protein
PCR for HSV, VSV and enteroviruses
Neuroimaging - medial temporal and inferior frontal changes. Normal in 1/3 pts, MRI is better
EEG - lateralised periodic discharges at 2Hz
Encephalitis Management
IV aciclovir should be started in all cases of suspected encephalitis
Meningitis v encephalitis
both present w/ fever, headache, altered mental state
however, pts w/ meningitis have more neck stiffness and photophobia
pts w/ encephalitis present w/ focal neuro deficits eg aphasia or hemiparesis
CSF: encephalitis = lymphotic pleocytosis, meningitis = neutrophil predominance
What is Guillain-Barre syndrome?
post infectious, immune-mediated
rare, acute polyradiculoneuropathy
rapidly evolving ascending muscle weakness w/ mild sensory changes
Guillain-Barre syndrome aetiology
autoimmune
often precipitated by infection, most commonly campylobacter jejuni, epstein-barr virus or cytomegalovirus
Risk factors of Guillain-Barre syndrome
infections
vaccinations
surgery
Underlying causes of Guillain-Barre syndrome
theories:
- molecular mimicry - antibodies generated in response to infection cross-react w/ gangliosides present on periph nerves due to structural similarities, resulting in nerve damage
- bystander activation - infection leads to non-specific activation of immune system, which subsequently attacks peripheral nerves. More relevant in cases associated w/ viral infections
- correlation between anti-GM1 and clinical features. Anti-GM1 in 25% of pts
Clinical features of Guillain-Barre syndrome
- symptoms usually w/in 4 wks of triggering infection, may start as gastroenteresis
- symmetrical ascending weakness
- reduced reflexes
- peripheral loss of sensation, neuropathic pain
- can progress to CNs and cause facial weakness
- autonomic dysfunction (urinary retention, ileus or heart arrhythmias)
Guillain-Barre syndrome investigations and diagnosis
- clinical diagnosis (Brighton criteria), based on characteristic presentation of progressive, usually symmetric muscle weakness w/ or w/out sensory disturbances
- lumbar puncture - rise in protein w/ normal white cell count (in 66%)
- nerve conduction studies
Guillain-Barre syndrome management
supportive care
VTE prophylaxis (PE is leading cause of death)
1st line = IV immunoglobulins
plasmapheresis alternative to IVIG
Miller Fisher syndrome
variant of Guillain-Barre syndrome
associated w/ ophthalmoplegia, areflexia and ataxia
eye muscles typically affected first
usually presents as descending paralysis rather than ascending as seen in other forms of GBS
anti-GQ1 antibodies present (90% cases)
What is herpes zoster infection?
Shingles
acute, unilateral, painful blistering rash caused by reactivation of varicella-zoster virus (VSV)
following primary infection (chickenpox), virus lies dormant in dorsal root or cranial nerve ganglia
Herpes zoster risk factors
increasing age
HIV (15x more common)
other immunosuppressive conditions eg steroids, chemo
What are the most commonly affected dermatomes in herpes zoster?
T1-L2
Features of herpes zoster infection
Prodromal period = burning pain over affected dermatome 2-3 days, severe pain - interfere w/ sleep, around 20% get fever, headache and lethargy
Rash - initially erythematous, macular rash over affected dermatome. Quickly become vesicular, characteristically well demarcated by dermatome and doesn’t cross midline. However, ‘bleeding’ into adjacent areas may be seen
Herpes zoster diagnosis and management
diagnosis = clinical
management = remind pt they are infectious
analgesia - paracetamol, NSAIDs
anti-virals = w/in 72hrs for majority of pts - aciclovir, famciclovir or valaciclovir
How long are herpes zoster pts infectious for?
until vesicles have crusted over, usually 5-7 days following onset
Why should you prescribe antivirals for herpes zoster infection?
reduced incidence of post-herpetic neuralgia, particularly in older ppl
don’t use antivirals if pt is <50 and has ‘mild’ truncal rash associated w/ mild pain and no underlying risk factors
Herpes zoster complications
post-herpetic neuralgia
herpes zoster ophthalmicus (shingles affecting ocular division of trigeminal nerve)
herpes zoster oticus (Ramsey Hunt syndrome) - may result in ear lesions and facial paralysis
Herpes zoster ophthalmicus (HZO)
reactivation of varicella-zoster virus in area supplied by ophthalmic division of trigeminal nerve
around 10% of shingles cases
vesicular rash round eye, Hutchinson’s sign
management = oral antiviral treatment for 7-10 days, topical corticosteroids to treat secondary inflammation of eye
complications = conjunctivitis, keratitis, ptosis, post-hepatic neuralgia
What is Hutchinson’s sign?
rash on tip or side of nose
indicates nasociliary involvement and is strong risk factor for ocular involvement
Herpes simplex keratitis
usually presents w/ dendritic corneal ulcer
red, painful eye
photophobia
epiphora
treat w/ topical aciclovir and ophthalmologist referral
What 4 different species causes malaria in humans?
plasmodium falciparum - most common
plasmodium vivax
plasmodium ovale
plasmodium malariae
Protective factors of malaria
sickle cell anaemia
G6Pd deficiency
HLA-B53
absence of Duffy antigens
Falciparum malaria presentation
paroxysms of fever, chills and sweating - may occur every 48 hrs corresponding to erythrocyte cycle of parasite
GI - anorexia, nausea, vomiting, abdo pain
resp - cough
MSK - body aches and joint pains
neuro - headache, dizziness
CV - tachy, htn
Features of severe falciparum malaria
schizonts on blood film
parasitaemia >2%
hypoglycaemia
acidosis
temp >39
severe anaemia
Falciparum malaria complications
cerebral malaria - seizures, coma
acute renal failure - blackwater fever
acute resp distress syndrome
hypoglycaemia
disseminated intravascular coagulation
Uncomplicated falciparum malaria management
artemisinin-based combo therapies (ACTs)
eg artemether + lumefantrine
artesunate + amodiaquine
artesunate + mefloquine
Severe falciparum malaria management
parasite counts >2% need parenteral treatment
IV artesunate
if parasite count >10% consider transfusion
Malaria diagnosis
malaria blood film
EDTA bottle (FBC)
3 -ve samples over 3 consecutive days required to exclude malaria
Features of non-falciparum malaria
fever, headache, splenomegaly
plasmodium vivax / ovale - cyclical fever every 48hrs
plasmodium malariae - cyclical fever every 72hrs
plasmodium malariae - associated w/ nephrotic syndrome
Which malaria types have a hypnozoite stage?
ovale and vivax
may therefore relapse following treatment
Treatment of non falciparum malaria
artemisinin-based combo therapy (ACTs) or chloroquine
ovale or vivax = give primaquine following acute treatment to destroy liver hypnozoites and prevent relapse
Where is chloroquine resistant malaria strains prevelant?
certain areas of Asia and Africa
Where are the majority of brain tumours in adults?
supratentorial - above tentorium cerebelli eg cerebrum, ventricles and upper part
Where are the majority of brain tumours in children?
infratentorial
below tentorium cerebelli, separates the cerebellum from cerebrum
lower back part of brain, contains the cerebellum, brainstem, and fourth ventricle
What is the most common form of brain tumour?
metastatic brain cancer
Tumours that most commonly spread to the brain
lung
breast
bowel
skin
kidney
Glioblastoma prognosis
~1 year
What does a glioblastoma look like on imaging?
solid tumours w/ central necrosis
rim that enhances w/ contrast
disruption of BBB and therefore associated w/ vasogenic oedema
Glioblastoma histology
pleomorphic tumour cells border necrotic areas
Glioblastoma treatment
surgical w/ post-op chemo and/or radiotherapy
dexamethasone to treat oedema
What are gliomas?
glial cell tumours in brain or spinal cord
glial cells surround and support neurones eg
astrocytes (astrocytoma - most common and aggressive glioblastoma)
oligodendrocytes (oligodendroglioma)
ependymal cells (ependymoma)
Brain tumour presentation
progressive focal neurological symptoms
raised ICP
Causes of increased intracranial pressure
brain tumours
intracranial haemorrhage
idiopathic intracranial HTN
abscesses or infection
Symptoms of raised intracranial pressure
constant headache
nocturnal
worse on waking
worse on coughing, straining or bending forward
vomiting
papilloedema
altered mental state
visual field defects
seizures
unilateral ptosis
Papilloedema on fundoscopy
blurring of optic disc margin
elevated optic disc
loss of venous pulsation
engorged retinal veins
haemorrhages around optic disc
Paton’s lines - creases or fold in retina around optic disc
What are meningiomas?
tumours growing from cells of meninges
usually benign
take up space, ‘mass effect’ can lead to raised ICP and neuro symptoms
What are vestibular schwannomas?
acoustic neuromas - benign tumours of Schwann cells that surround auditory nerve that innervates inner ear
account for approx 5% of intracranial tumours and 90% of cerebellopontine angle tumours
tumours often slow growing and benign
Vestibular schwannoma presentation
combo of vertigo, hearing loss, tinnitus and absent corneal reflex
(CN 5, 7 and 8)
usually unilateral
Vestibular schwannoma investigations and management
MRI of cerebellopontine angle, audiometry
Management = surgery, radiotherapy or observation
Pituitary tumours
tend to be benign
can press optic chiasm and cause bitemporal hemianopia (loss of outer visual fields)
What can pituitary tumours cause?
hormone deficiencies or excessive hormone release:
acromegaly
hyperprolactinaemia
Cushing’s disease
thyrotoxicosis
Pituitary tumour management
trans-sphenoidal surgery
radiotherapy
bromocriptine - block excess proalctin
somatostatin anaglogues - block excess GH
What is bulbar palsy?
impaired function of lower cranial nerves, those that arise from brainstem (9,10,11,12)
Bulbar palsy symptoms
dysphasia
absent gag reflex
slurred speech
aspirations
dysphonia
drooling
issues chewing
weak jaw / facial muscles
Bulbar palsy causes
brainstem tumours and strokes
degenerative diseases - amytrophic lateral sclerosis
autoimmune - Guillain-Barre syndrome
genetic diseases eg Kennedy disease
Treatment of bulbar palsy
no known treatment
manage symptoms :
medication for drooling
feeding tube
SLT
Cerebellar disease
DANISH
Dysdiadochokinesia, dysmetria
Ataxia
Nystagmus
Intention tremor
Slurred staccato speech, scanning dysarthria
Hypotonia
Cerebellar syndrome causes
Friedreich’s ataxia, ataxic telangiectasia
neoplastic - cerebellar haemangioma
stroke
alcohol
multiple sclerosis
hypothyroidism
drugs - phenytoin, lead poisioning
paraneoplastic eg 2nd to lung cancer
What is cerebral palsy?
movement and posture disorder
due to non-progressive lesion of motor pathways in developing brain
2/1000 live births
most common cause of major motor impairment
Causes of cerebral palsy
antenatal (80%) - cerebral malformation and congenital infection
intrapartum (10%) - birth asphyxia / trauma
postnatal (10%) - intraventricular haemorrhage, meningitis, head-trauma
Cerebral palsy manifestations
abnormal tone early infancy
delayed motor milestones
abnormal gait
feeding difficulties
Associated non-motor problems in cerebral palsy pts
learning difficulties (60%)
epilepsy (30%)
squints (30%)
hearing impairment (20%)
Cerebral palsy classification
- spastic - hemiplegia, diplegia or quadriplegia, increased tone from UMN damage
- dyskinetic - basal ganglia and substantia nigra damage, athetoid movements and oro-motor problems
- ataxic - cerebellum damage
- mixed
Cerebral palsy manamgent
MDT approach
spasticity - oral diazepam, oral and intrathecal baclofen, botulinum toxin type A, orthopaedic surgery and selective dorsal rhizotomy
anticonvulsants
analgesia as required
What is Bell’s palsy?
acute, unilateral, idiopathic, facial nerve paralysis
peak incidence = 20-40yrs
more common in pregnant women
Features of Bell’s palsy
lower motor neuron facial nerve palsy - forehead affected
post-auricular pain
altered taste
dry eyes
hyperacusis
Bell’s palsy management
oral prednisolone w/in 72 hrs of onset
eye care - prevent exposure keratopathy: artificial tears or eye lubricant
Bell’s palsy prognosis
most make full recovery w/in 3-4 months
if untreated around 15% have permanent moderate - severe weakness
How is epilepsy classified?
- where seizure begins in brain
- lvl of awareness during seizure
- other features of seizures
What are focal seizures?
start in specific area, on one side of brain
lvl of awareness varies: focal aware, focal impaired and awareness unknown
classified as motor (eg Jacksonian march), non-motor or having other features like aura
What are generalised seizures?
engage both sides of brain at onset
lose consciousness immediately
motor (tonic-clonic) and non-motor (absence)
tonic, clonic, atonic, tonic-clonic and absence
What is a focal to bilateral seizure?
starts on one side of brain in specific area before spreading to both lobes
(previously 2ndary generalised seizures)
What conditions have an association w/ epilepsy?
cerebral palsy - around 30%
tuberous sclerosis
mitochondrial diseases
Temporal lobe typical seizure type
W/ or w/out impairment of consciousness or awareness
Aura: rising epigastric sensation, psychic or experiental phenomena eg deja vu, less commonly hallucinations
typically last around 1 min, automatisms are common
Frontal lobe typical seizure type
head / leg movements
posturing
post-ictal weakness
Jacksonian march
Parietal lobe typical seizure type
sensory
paraesthesia
Occipital lobe typical seizure type
visual
floaters
flashes
Other causes of recurrent seizures
febrile convulsions
alcohol withdrawal seizures
psychogenic non-epileptic seizures
Forms of epilepsy in children
infantile spasms
Lennox-Gastaut syndrome
Benign rolandic epilepsy
Juvenile myoclonic epilepsy
Generalised seizures signs
bitten tongue
urine incontinence
Syncope episodes v seizures
syncopal episodes associated w/ short ictal period and rapid recovery
seizures usually have long post-ictal period
When are epileptic drugs considered?
after second seizure
What groups of patients should be considered during epilepsy management?
pts who drive (can’t drive 6 months following)
pts taking other medications
women wishing to get pregnant
women taking contraception
Sodium valporate
used for generalised seizures in males
increases GABA activity
should not be used in females of reproductive age
Carbamezapine
used second line for focal seizures
binds to sodium channels increasing refractory period
Lamotrigine
used for variety of generalised and focal seizures
sodium channel blocker
can be used in females
Phenytoin
no longer used 1st line due to side effects
binds to sodium channels increasing refractory period
SE: osteopenia, osteoporosis, drowsiness, headaches
Acute management of seizures
benzodiazepines eg diazepam administered if seizure doesn’t terminate after 5-10 mins
What is status epilepticus?
single seizure lasting >5mins or
>= 2 seizures w/in 5min period w/out person returning to normal between
Status epilepticus management
ABC = airway adjunct, oxygen, blood glucose
1st line = benzodiazepines, IV lorazepam if in hospital. Repeated once after 5-10 mins
If ongoing, 2nd line may be used eg levetiracetam
If no response w/in 45 mins, induce general anaesthesia or phenobarbital
Sodium valproate contraindications
maternal use associated w/ significant risk of neurodevelopmental delay in children
Generalised tonic-clonic seizure treatment
males = sodium valproate
females = lamotrigine or levetiracetam
Focal seizures treatment
1st = lamotrigine or levetiracetam
2nd = carbamezapine, oxcarbazepine or zonisamide
Absence seizures treatment
1st = ethosuximide
2nd = male: sodium valproate, female: lamotrigine or levetiracetam
Myocolonic seizures treatment
males = sodium valproate
females = levetiracetam
Tonic or atonic seizures treatment
males = sodium valproate
females = lamotrigine
What should be considered in women with epilepsy taking contraception?
- effect of contraceptive on effectiveness of anti-epileptic medication
- effect of anti-epileptic on effectiveness of contraceptive
- potential teratogenic effects of anti-epileptic if woman becomes pregnant
Clinical features of febrile convulsions
usually occur early in viral infection as temp rises
seizures usually brief, <5mins
most commonly tonic-clonic
Types of febrile convulsions
Simple = <15mins, generalised, typically no recurrence w/in 24hrs, should recover in an hr
Complex = 15-30mins, focal, may have repeat in 24hrs
Febrile status epilepticus = >30mins
Common causes of febrile convulsions
resp tract infections
otitis media
urinary tract infections
influenza
HHV-6
Ongoing management of febrile convulsions
phone ambulance if >5mins
if recurrent, benzodiazepine rescue meds considered
children who have had a first seizure or any features of a complex seizure should be admitted to paeds
Anterior cerebral artery stroke
contralateral hemiparesis and sensory loss
lower extremity > upper
Middle cerebral artery stroke
contralateral hemiparesis and sensory loss
upper extremity > lower
contralateral homonymous hemianopia
aphasia
Posterior artery stroke
contralateral homonymous hemianopia w/ macular sparing
visual agnosia
Weber’s syndrome
branches of pos. cerebral artery that supply midbrain
ipsilateral CN3 palsy
contralateral weakness of upper and lower extremity
Anterior inferior cerebellar artery stroke
Similar to Wallenberg’s but ipsilateral facial paralysis and deafness
Posterior inferior cerebellar artery stroke (Wallenberg syndrome)
ipsilateral facial pain and temp loss
contralateral limb/torso pain and temp loss
ataxia, nystagmus
Lacunar strokes
present w/ isolated hemiparesis, hemisensory loss or hemiparesis w/ limb ataxia
strong association w/ HTN
common sites = basal ganglia, thalamus and internal capsule
Other issues during stroke management
fluids
glycaemic control
BP management
feeding assessment and management
disability scales
ROSIER score
Stroke assessment
exclude hypogylcaemia first, then assess:
loss of consciousness or syncope (-1)
seizure activity (-1)
New, acute onset of: (+1)
- asymmetric facial weakness
- asymmetric arm weakness
asymmetric leg weakness
- speech disturbance
- visual field defect
stroke likely if >0
Acute ischaemic stroke CT
areas of low density in grey and white matter of territory
hyperdense artery sign corresponding w/ responsible arterial clot - tends to be visible immediately
Acute haemorrhagic stroke CT
areas of hyperdense material (blood) surrounded by low density (oedema)
Features of a TIA
unilateral weakness or sensory loss
aphasia or dysarthria
ataxia, vertigo or balance loss
visual problems (loss of vision in one eye, diplopia, homonymous hemianopia)
Examples of TIAs that require exclusion
hypoglycaemia
intracranial haemorrhage (all pts on anticoags or w/ similar risk factors should be admitted for urgent imaging to exclude haemorrhage)
How to assess territory of ischaemia in TIAs
MRI including diffusion-weighted and blood-sensitive sequences
done on same day as specialist assessment
TIA management
immediate anti-thrombotic therapy provided no contraindications or high bleeding risk
When is aspirin given as antithrombotic medication?
resolved TIA symptoms, awaiting specialist review w/in 24hrs
When is aspirin and clopidogrel given as antithrombotic therapy?
reviewed by specialist, initial 21 days when at high risk of further events
When is clopidogrel given as antithrombotic medication?
long-term secondary prevention after 21 days
Further investigations in a TIA
carotid imaging - carotid duplex ultrasound
carotid endarterectomy recommended if pt has suffered stroke or TIA in carotid territory and is not severely disabled
(considered if stenosis >50% according to NASCET criteria)
What is a subarachnoid haemorrhage?
intracranial haemorrhage
presence of blood w/in subarachnoid space - deep to subarachnoid layer of meninges
Most common cause of subarachnoid haemorrhage
traumatic - head injury
Causes of spontaneous subarachnoid haemorrhage
intracranial aneurysm (saccular ‘berry’ aneurysm) (~85%)
arteriovenous malformation
pituitary apoplexy
mycotic (infective) aneuryms
Presenting features of subarachnoid haemorrhage
headache - thunderclap, sudden onset. Severe, occipital
nausea and vomiting
meningism
coma
seizures
ECG change - ST elevation
Subarachnoid haemorrhage investigations
non-contrast CT head - blood in basal cisterns, sulci and sometimes ventricular system
IF CT head done w/in 6hrs of symptoms onset and is normal = no LP
IF CT head done >6hrs of symptom onset and is normal = LP
(LP should be performed at least 12hrs following symptom onset)
If CT shows SAH, refer to neurosurgery
Lumbar puncture findings in subarachnoid haemorrhage
xanthochromia (RBC breakdown)
normal or raised opening pressure
Further investigations of subarachnoid haemorrhages
after spontaneous SAH confirmed, try to find causative pathology that needs treatment
CT intracranial angiogram - vasc lesion
+/- digital subtraction angiogram
Management of confirmed aneurysmal subarachnoid haemorrhage
- supportive - bed rest, analgesia, venous thromboembolism prophylaxis, discontinuation of antithrombotics
- vasospasm prevention - nimodipine
-intracranial aneurysms need prompt intervention, preferably w/in 24hrs
Intracranial aneurysm treatment
coil by interventional neuroradiologists, minority require craniotomy and clipping by neurosurgeon
Complications of aneurysmal SAH
rebleeding
hydrocephalus
vasospasm
hyponatraemia due to SIADH
seizures
Important predictive factors in SAH
conscious level on admission
age
amount of blood visible on CT head
What is a subdural haemorrhage?
bleeding in space between dura mater and arachnoid layers of meninges
typically result of significant head trauma leading to rupture of bridging veins, can also present spontaneously or after minor injuries
Subdural haemorrhage risk factors
age
alcoholism
anticoagulant therapy
trauma
vasc malformations
coagulopathies
How are subdural haematomas classified?
acute - fresh blood, usually trauma
subacute
chronic - blood collection present for wks to months (presentation usually several wk to month progressive history of either confusion, reduced consciousness or neuro deficit)
Investigations of acute subdural haematoma
CT imaging
crescentic collection, not limited by suture lines
hypERdense in comparison to brain
large subdural haematomas will push on brain and cause midline shift or herniation
Investigations of chronic subdural haematoma
CT
crescentic shape, not restricted by suture lines and compress brain
hypOdense compared to substance of brain
Acute subdural haematoma management
observed conservatively
surgical = monitor ICP, decrompressive craniectomy
Chronic subdural haematoma management
if incidental finding or small w/ no neuro deficit = conservative
if neuro deficit or severe imaging findings = surgical decompression w/ burr holes
Subdural haemorrhage complications
raised ICP
cerebral oedema
herniation syndromes
infection
hydrocephalus
venous infarction
epilepsy
What is an extradural haematoma?
collection of blood between skull and dura
almost always caused by trauma, most typically by ‘low-impact’ trauma
Where do extradural haematomas usually occur?
temporal region - thin skull at pterion overlies middle meningeal artery - vulnerable
Presentation of an extradural haematoma
pt who initially loses, briefly regains and then loses consciousness again after low-impact head injury
‘lucid interval’ - lost eventually due to expanding haematoma and brain herniation
As haematoma expands, uncus of temporal lobe herniates around tentorium cerebelli and pt develops fixed and dilated pupil due to compression of parasympathetic fibres of 3rd CN
Extradural haematoma investigations
imaging - appears biconcave, hyperdense collection around surface of brain
limited by suture lines of skull
Extradural haematoma management
no neuro deficit = cautious clinical and radiological observation
otherwise, craniotomy and evacuation of haematoma
What is temporal arteritis?
giant cell arteritis
vasculitis predominantly affecting medium and large arteries, particularly branches of carotid artery
Temporal arteritis contributing factors
genetic predisposition - HLA alleles
environmental factors - seasonal and geographical clustering
age - 70-80
sex - female
ethnicity - N. Europe
Temporal arteritis pathology
antigenic trigger
T-cell activation - CD4+ T-cells, initiate inflammatory cascade
macrophage and giant cell formation
vasc inflammation and damage - results in intimal thickening, narrowing and ischaemia
Temporal arteritis presentation
rapid onset headache
jaw claudication
scalp tenderness
visual disturbances
temporal artery abnormality - tenderness, thickening or reduced pulsation
Temporal arteritis investigations
raised inflam markers: ESR>50mm/hr, raised CRP
temporal artery biopsy - skip lesions may be present
creatine kinase and EMG normal
Temporal arteritis investigations guidelines
low clinical probability (<20%) = temporal and axillary US
medium probability (20-50%) = US may be prior to biopsy
high probability (>50%) = +ve US makes diagnosis
Temporal arteritis classification
American College of Rheumatology
3 or more = highly suspected:
age >50
new onset headache
temporal artery abnormality
ESR > 50mm/hr
abnormal artery biopsy
Temporal arteritis differentials
migraine
central retinal artery occlusion
acute glaucoma
trigeminal neuralgia
multiple sclerosis
Temporal arteritis management
high dose corticosteroids- prednisolone - vision loss
adjunctive therapy w/ low-dose aspirin - ischaemic complications
temporal artery biopdy w/in 14 days of starting steroids to confirm diagnosis
immunosuppressants can be used if can’t tolerate steroids eg methotrexate
Temporal arteritis complications
vision loss
ocular complications
stroke
aortic aneurysm and dissection
large vessel involvement
polymyalgia rheumatica
Glasgow coma scale eye opening
4 - spontaneous
3 - to sound
2 - to pressure
1 - none
Glasgow coma scale verbal response
5 - orientated
4 - confused
3 - words
2 - sounds
1 - none
Glasgow coma scale - motor response
6 - obeys commands
5 - localising
4 - normal flexion
3 - abnormal flexion
2 - extension
1 - none
Glasgow coma scale scores
13-15 = mild
9-12 = moderate
3-8 = severe
Causes of migraines
genetics
environment - stress, hormonal changes, sleep disturbances, dietary factors, sensory stimuli, medications
Migraine pathology - cortical spreading depression
characterised by wave of transient neuronal depolarisation followed by prolonged period of suppressed neuronal activity
implicated in initiation of migraine aura and subsequent headache phase
Migraine pathology - neurovascular changes
changes in cerebral blood flow and vascular function
during early phase of attack, there’s decrease in cerebral blood flow, followed by vasodilation and increased blood flow
process may contribute to activation of nociceptive trigeminal nerve fibres, leading to release of vasoactive neuropeptides and inflammation
Migraine pathology - neuropeptides and neurotransmitters
- CGRP - vasodilater, activates trigeminal nerve fibres, promotes inflammation and pain transmission
- Serotonin (5-HT) - vasoactive, modulates pain pathways
- Glutamate - excitatory neurotransmitter, initiates and maintains CSD and sensitisation of trigeminal nociceptive neurons
How can migraines be classified?
with or without aura
chronic
probable migraine
episodic syndromes associated w/ migraine
Migraine w/out aura
most common
moderate to severe pulsating headache lasting between 4 and 72 hrs, usually unilateral
other symptoms include photophobia, phonophobia, nausea and vomiting, aggravation by routine physical activity
Migraine w/ aura
1/4 of migraines
- typical aura - visual, sensory, speech or language, motor, brainstem or retinal symptoms preceding headache phase
- hemiplegic migraine - reversible motor weakness as aura
- retinal migraine - transient monocular visual loss or blindness
What is a chronic migraine?
headache on 15 or more days per month for at least 3 months
migraines on at least 8 days per month
What are complicated migraines?
migraines appear to directly cause neuro damage or other complications
- migrainous infarction - ischaemic stroke that occurs during typical attack of migraine w/ aura
- migraine aura-triggered seizure
- persistent aura w/out infarction - aura symptoms for 1wk or more, w/out evidence of stroke
Episodic syndromes that may be associated w/ migraine
cyclic vomiting syndrome
abdominal migraine
benign paroxysmal vertigo of childhood
Clinical features of migraines
severe, unilateral, throbbing headache
associated w/ nausea, photophobia and phonophobia
last up to 72hrs
precipitated by aura
What is aura?
1/3 of migraine pts
visual, progressive
last 5-60 mins
transient hemianopic disturbance or spreading scintillating scotoma
Migraine investigations
usually diagnosed by history and physical exam
neuroimaging to rule out other
blood tests - rule out systemic conditions
MRI
lumbar puncture
invasice angiography
International headache society’s migraine w/out aura diagnostic criteria
A - at least 5 attacks fulfilling criteria B-D
B - headache lasts 4-72hrs
C - characteristics: 1.unilateral, 2. pulsating quality, 3. moderate or severe pain intensity, 4. aggravation by routine physical activity
D - at least one of: 1, nausea or vomiting, 2. photophobia and phonophobia
E - not attributed to another disorder
Migraine differentials
tension-type headache
cluster headache
temporal artertitis
Tension type headache vs migraine
TTH presents as bilateral, pressing or tightening sensation of mild to moderate intensity (band around head)
Migraine is unilateral, pulsating quality of pain
TTH no accompanies by nausea or vomiting
Migraine usually exacerbated by routine physical activity
Cluster headache vs migraine
Cluster headache - unilateral pain usually centred around eye or temple, piercing or burning, more intense than typical migraine attacks
Cluster headache has shorter duration (15mins - 3hrs) but occur more frequently
Cluster headache associated w/ ipsilateral autonomic symptoms eg lacrimation, nasal congestion or rhinorrhoea
Temporal arteritis vs migraine
TA typically affects individuals over 50
TA is new-onset, persistent and localised to temples or occiput, no pulsating
TA may have systemic symptoms
ESR and CRP typically elevated in TA
Migraine management
1st: combo therapy of oral triptan and NSAID or oral triptan and paracetamol
12-17yrs = nasal triptan
If above not effective, consider metoclopramide or prochlorperazine and add non-oral NSAID or triptan
Migraine prophylaxis
propanolol
topiramate - avoid in women of child bearing age
acupuncture course
riboflavin
menstrual migraines = frovatriptan or zolmitriptan
Migraine management general rule
5-HT receptor agonists used in acute treatment
5-HT receptor antagonists used in prophylaxis
Migraine acute complications
- status migrainosus - debilitating migrain for >72hrs, lead to dehydration and stroke
- migrainous infarction - ischaemic stroke during migraine w/aura
- persistent aura w/out infarction - visual or sensory symptoms of aura last longer than 1wk after headache resolved
Chronic complications of migraine
- chronic migraine - >15days per month for at least 3months
- medication overuse headache
- transformed migraine - chronic daily headache, progression from episodic to pattern of daily or near daily headaches
- psychiatric comorbidities
- cardiovascular complications
Features of a tension-type headache
most prevalent primary headache disorder
bilateral
non-pulsatile
mild to moderate pain w/ pressing or tightening quality
tight-band around head
not associated w/ aura, nausea/vomiting or aggravated by routine physical activity
Tension-type headache classification
ICHD-3 criteria:
Infrequent episodic = <1 day of headache per month
Frequent episodic = 10+ episode of headache occurring on <15 days per month average, for >3months
Chronic = >15 days of headache per month, for more than 3 months in absence of medication overuse
Acute treatment for tension-type headahe
aspirin, paracetamol or NSAID
Prophylaxis for tension-type headache
up to 10 session of acupuncture over 5-8wks
low-dose amitriptyline
non-pharmacological = relaxation training, biofeedback and CBT
avoid triggers
Cluster headache risk factors
male gender (3:1)
smoking
alcohol may trigger attack
Features of cluster headache
pain - intense, stabbing pain around one eye
typical occurs once or twice a day, episode lasting 15mins - 2hrs
clusters typically last 4-12wks
restlessness and agitation
redness, nasal stuffiness, lacrimation, lid swelling
minority may have miosis and ptosis
Cluster headache investigations
neuroimaging, MRI w/ gadolinium contrast - brain lesion may be found
Cluster headache classification
ICHD-3:
A = at least 5 attacks fulfilling B-D
B = severe or v. severe unilateral orbital, supraorbital and/or temporal pain 15-180mins
C = either one or both 1. ipsilateral: conjunctival injection and/or lacrimation, nasal congestion and/or rhinorrhoea, eyelid oedema, forehead and facial sweating, miosis and/or ptosis. 2. sense of restlessness or agitation
D = occurring w/ frequency between one every other day and 8 per day
E = not better accounted by for another ICHD-3 diagnosis
Cluster headache management
Acute = 100% oxygen, subcutaneous triptan
Prophylaxis = verapamil
seek specialist if pt develops headaches w/ respect to neuroimaging
What is trigeminal autonomic cephalgia?
grp of conditions including cluster headache, paroxysmal hemicrania and short-lived unilateral neuralgiform headache w/ conjunctival injection and tearing (SUNCT)
refer pts for specialist assessment
Features of trigeminal neuralgia
unilateral disorder characterised by brief electric shock-like pains, abrupt in onset and termination, limited to 1 or more divisions of trigeminal nerve
pain commonly evoked by light touch, occurs spontaneously
small areas in nasolabial fold or chin may be particularly susceptible to precipitation of pain
pains usually remit for variable periods
Red flag symptoms suggesting serious underlying cause of trigeminal neuralgia
sensory changes
deafness or other ear problems
history of skin or oral lesions that could spread perineurally
pain only in ophthalmic division of trigeminal nerve (eye socket, forehead and nose), or bilaterally
optic neuritis
FH of multiple sclerosis
onset before <40
Trigeminal neuralgia management
1st = carbamazepine
failure to respond to treatment or atypical features eg <50 = refer to neuro
What is Horner’s syndrome?
rare sympathetic nervous system condition
underlying cause varies eg tumours, injuries or neuro disorders
treat depending on underlying cause
Clinical features of Horner’s syndrome
Ptosis - weakness of Muller’s muscle
Miosis on affected side
Anihydrosis ipsilateral over forehead, face and neck regions
May see heterochromia iridium
rarely - enophthalmos
Horner’s syndrome diagnosis
thorough physical exam - pupil size assessment and response to light
imaging tests - identify underlying cause
Traumatic causes of peripheral nerve injuries / palsies
fractures and dislocations
penetrating injuries
stretch injuries
Compressive causes of peripheral nerve injuries / palsies
carpal tunnel syndrome
cubital tunnel syndrome
Inflammatory causes of peripheral nerve injuries / palsies
vasculitis
sarcoidosis
Metabolic causes of peripheral nerve injuries / palsies
diabetes mellitus
Infectious causes of peripheral nerve injuries / palsies
Lyme disease
HIV
Neoplastic causes of peripheral nerve injuries / palsies
direct invasion
paraneoplastic syndromes
Iatrogenic causes of peripheral nerve injuries / palsies
surgical procedures
Risk factors of peripheral nerve injuries
advanced age
presence of comorbid conditions eg diabetes or rheumatoid arthritis
occupations involving repetitive movements
high-risk sports
substance use
Peripheral nerve injury / palsy pathophysiology
- Initial mechanical insult that disrupts normal architecture of nerve
- Wallerian degeneration distal to lesion site - breakdown of axon and myelin sheath, macrophage recruitment for debris clearance and Schwann cell proliferation forming Bangs of Bungner
- Axonal regeneration and remyelination
- Reinnervation - regenerated axons make functional connections w/ target tissues, but due to slow rate of regeneration, muscles may undergo atrophy or target organs may be lost before innervation occurs, leading to incomplete recovery of function
What are Bands of Büngner?
formed when uninnervated Schwann cells proliferate and the remaining connective tissue basement membrane forms endoneurial tubes
- act as guides for regenerating axons
How does axonal regeneration and remyelination occur?
Regeneration initiated by changes in gene expression w/in injured neurons
growth cones form at tips of regenerating axons, guided by chemical cues towards their target tissues
Remyelination occurs due to Schwann cells enveloping new axon sprouts in layers to form a new myelin sheath
Pathological changes in peripheral nerve injuries / palsies
nerve regeneration may lead to non-functional outcomes eg- Neuromas - disorganised growths of nerve tissue that can cause pain or sensory dysfunction
Synkinesis - misdirection of regenerating axons towards incorrect end organs, resulting in simultaneous and uncoordinated movements
What are the Seddon’s 3 categories of peripheral nerve injury / palsy classification?
neuropraxia
axonotmesis
neurotmesis
Peripheral nerve injuries / palsies: neuropraxia
mildest form of nerve injury - temporary blockage of nerve conduction w/out any anatomical disruption to nerve or its surrounding structure
- transient motor and sensory loss
- no Wallerian degeneration observed
- rapid recovery w/in days to wks
Peripheral nerve injuries / palsies: axonotmesis
damage to axon w/ preservation of endometrium, perineurium and perineurium
typically caused by crush or stretch injuries
- motor and sensory loss below inury lvl
- Wallerian degeneration distal to injury site
- potential for regeneration at rate of 1mm/day w/ variable recovery outcomes depending on severity and location of injury
Peripheral nerve injuries / palsies: neurotmesis
most severe form, complete transection or disruption of nerve fibre including all its encapsulating structures
- total motor and sensory loss below injury lvl
- complete Wallerian degeneration
- no spontaneous recovery, surgical intervention required for potential functional return
What is Sunderland’s classification of peripheral nerve injuries / palsies?
1st degree = neuropraxia
2nd degree = axonotmesis w/ preservation of endoneurium
3rd degree = axon and endometrium damage, intact perineurium and epineurium
4th degree = only epineurium intact, surgical intervention often required due to neuromas
5th degree = neurotmesis - complete transection requiring surgical repair or grafting
Clinical features of peripheral nerve injuries / palsies
- Sensory deficits: loss of sensation or abnormalities - tingling, burning in distribution of affected nerve
- Motor weakness: muscle weakness, fine motor skills compromised, deep tendon reflexes diminished / absent
- Autonomic dysfunction: changes in skin temp, sweating abnormalities and trophic changes
Peripheral nerve injury / palsy sensory deficit on examination
reduced or absent:
tactile discrimination
temp perception
proprioception
vibratory sensation
pattern can help determine mononeuropathy or polyneuropathy
Additional features of peripheral nerve injuries/ palsies
- may experience neuropathic pain described as burning, shooting or stabbing - spontaneous firing of damaged nerve fibres
- Tinnel’s - tingling sensation elicited by tapping injured nerve
- Phalen’s - wrist flexion causing parasthesia in median nerve distribution
- long-standing peripheral nerve injury pts may develop compensatory changes eg modified gait or posture
Peripheral nerve injury / palsies investigations
- Electrodiagnostic studies - nerve conduction studies (assess speed and degree of myelination) and electromyography (evaluates muscle activity to determine whether there’s denervation)
- MRI - identify lesions and tumours
- High-resolution ultrasound
- Bloods - DM, B12 deficiency, thyorid issues, connective tissues disorders
Peripheral nerve injuries / palsies management
Non-surgical = pain - NSAIDs, opioids, gabapentin or pregabalin
physiotherapy
Surgical - for severe injuries eg grade 4 and 5 lesion, failed conservative treatment or presence of sharp penetrating trauma. Primary repair, nerve grafting or nerve transfers
Follow-up and rehabilitation
Causes of peripheral neuropathy
diabetes
alcohol misuse
vitamin deficiencies eg B12 and E
hereditary disorders - Charcot-Marie-Tooth
autoimmune eg Guillain-Barre syndrome
infections eg Varicella zoster, HIV
toxins
malignancies
idiopathic
Risk factors of diabetic neuropathy
duration of diabetes
glycaemic control
age
HTN
dyslipidaemia
smoking and alcohol use
Causes of diabetic neuropathy
- hyperglycaemia-induced metabolic changes - chronic hyperglycaemia triggers series of metabolic changes
- microvascular insufficiency - nerve hypoxia and ischaemia, damaging vasa nervorum
- autoimmune response - lead to demyelination and axonal regeneration
- inflammation
- oxidative stress - directly damages, promotes inflammation, AGE formation and PKC activation
Chronic hyperglycaemia leads to…
increased intracellular glucose w/in peripheral nerves, activating polyol pathway
results in accumulation of sorbital and fructose, causing osmotic stress and reduced nerve conduction velocity
Also causes advanced glycation end-products (AGEs) to form
What do AGEs (advanced glycation end-products) do?
bind to their specific receptors (RAGE) on neuronal cells and evoke oxidative stress, inflammatory responses and apoptosis
formed due to persistent hyperglycamia
How does oxidative stress exacerbate nerve damage?
promotes…
Mitochondrial dysfunction = mitochondrial electron transport chain becomes impaired leading to energy deficit in neurons
DNA damage = reactive oxygen species (ROS) generated from oxidative stress cause direct DNA damage, including cell death pathways
Lipid peroxidation = ROS also attack polyunsaturated fatty acids in cellular membranes, results in lipid perioxidation which alters membrane fluidity and function therefore contributing to neuronal injury
What does chronic hyperglycaemia induce?
activation of protein kinase C, particularly PKCβ isoforms
implicated in vasc abnormalities and neuronal dysfunction in diabetic neuropathy
What happens to nerve growth factor in diabetic neuropathy?
production and utilisation of NGF is compromised
deficiency leads to impaired nerve regeneration and contributes to degeneration of peripheral nerves
Typical presentation of diabetic neuropathy
‘stocking and glove’ distribution of symptoms, characterised by bilateral numbness, tingling or burning sensations in hands and feet
progression generally from distal to proximal
Presenting features of diabetic neuropathy
Sensory - paraesthesia, dysesthesia, hypoesthesia or anaesthesia
Motor - muscle weakness and atrophy
Autonomic - gastroparesis, erectile dysfunction, neurogenic bladder, orthostatic hypotension, sudomotor dysfunction
Initial investigations of diabetic neuropathy
Blood tests - FBC, renal function, liver function, TFT, B12, serum protein electorphoresis, HbA1c
Urinalysis - microalbuminaemia
Focused neurological investigations of diabetic neuropathy
Nerve conduction studies - speed of conduction of impulse through nerve
Quantitative sensory testing - tests large and small fibre function
Skin biopsy
Diabetic neuropathy management
Glycaemic control
Pain managment - tricyclic antidepressant or gabapentinoid
Treat complications - check for ulcers, complete foot exams regularly
Lifestyle modifications - diet, physical activity, stop smoking
Referral to specialist
Diabetic neuropathy complications
peripheral vascular disease
gastroparesis
cardiovascular autonomic neuropathy
hypoglycaemia unawareness
erectile dysfunction and urinary incontinence
severity of complications usually correlates w/ degree of glucose control
Mechanical causes of radiculopathies
disc herniation
spinal stenosis
spondylolisthesis
trauma or injury
Systemic conditions contributing to radiculopathies
diabetes mellitus - chronic hyperglycaemia
infections - herpes zoster (shingles)
malignancies
Risk factors of radiculopathies
obesity
tobacco use
aging
What are radiculopathies?
disorders affecting spinal nerves or nerve roots, leading to pain, numbness, weakness or difficulty controlling specific muscles
Most common causes of radiculopathies in different parts of the spine
Cervical = degenerative changes that narrow space where nerve roots exit spine
Lumbar = herniated disc
Thoracic = variety of conditions eg herpes zoster
Describe the initial pathogenesis of radiculpathies
Mechanical compression leads to decreased blood flow and ischaemia. Impairs axonal transport, leading to build-up of neurotoxic waste products and causing neuronal injury. Subsequent reperfusion leads to oxidative stress exacerbating injury
Inflammatory mediators released from degenerated disc material or 2ndary to systemic conditions can incite infammatory response in nerve root. Mediators eg cytokines (IL-1) and TNF-alpha, causes vasodialtion, increased vasc permeability and recruitment of inflammatory cells
Combo leads to oedema and further increases pressure on root
Pathophysiology of radiculopathies
- Damage to nerve roots elicits electrochemical response: altered ion channel, ectopic discharges from demyelinated regions of neurons
- Demyelination allows for abnormal cross-talk between sensory fibres, Ephaptic transmission
- Neuronal injury and subsequent inflammation leads to nociceptor activation, Peripheral sensitisation
- Central sensitisation results in heightened pain sensitivity (hyperalgesia) or pain response from non-painful stimuli (allodynia)
- Chronic radiculopathies may result in structural changes in NS, may contribute to persistent pain even after resolution of initial causative pathology
What is Ephaptic transmission?
cross-talk between sensory fibres that normally carry non-painful stimuli (large myelinated A-beta fibres) and those that carry painful stimuli (small unmyelinated C fibres and thinly myelinated A-delta fibres)
contributes to sensation of pain in radiculopathies
What are nociceptors?
sensory receptors that respond to potentially damaging stimuli by sending ‘possible threat’ signals to spinal cord and brain
What is central sensitisation?
continued nociceptive input to CNS induces changes in dorsal horn neurons
leads to increased response to peripheral stimuli
results in hyperalgesia or allodynia
What structural changes may occur in the nervous system due to chronic radiculopathies?
neuronal loss
alterations in synaptic connectivity
neurochemical changes
Sensory symptoms of radiculopathies
pain - sharp, shooting, electric-like, follows dermatomal distribution
paresthesia - tingling or prickling
numbness
hypersensitivity
Motor symptoms of radiculopathies
muscle weakness
muscle atrophy
fasciculations / twitching
Radiculopathies secondary symptoms
decreased reflexes
gait abnormalities
Radiculopathies investigation
Imaging: MRI, CT, x-ray
Nerve conduction studies and electromyography
Serological testing
CSF analysis
Radiculopathies differentials
- Peripheral neuropathies - usually symmetrical, no accompanying localised spinal pain, use NCS and EMG to differentiate
- Myelopathies - signs more diffuse, UMN signs, MRI to distinguish
- MSK conditions - pain usually exacerbated by specific movements or positions, present w/ localised pain and dysfunction
Radiculopathies management
Pharmacological - NSAIDs for pain relief, corticosteroids
Physiotherapy and pt education
Lifestyle modifications
Surgical interventions eg disectomy, laminectomy and spinal fusion
Spinal cord injury risk factors
age
gender
alcohol and substance abuse
osteoporosis
Underlying causes of spinal cord injury
- trauma
- diseases - cancer, arthritis, osteoporosis and inflammation
- surgical complications
- non-traumatic spinal cord ischaemia - aortic anyeursms/dissections, severe htn or aorta complications
Primary mechanism of spinal cord injury
compression, contusion, laceration or transection
severity - force and direction of impact
physical disruption leads to immediate neural cell death in grey matter and axonal damage in white matter tracts
vascular damage leading to haemorrhage and disruption of BBB
can lead to 2ndary injury from biochemical cascades
Secondary mechanism of spinal cord injury explained
- Inflammation - activation of resident microglia and astrocytes along infiltration by neutrophils and macrophages. Release cytokines and TNF-a, and reactive oxygen species causing further tissue damage
- Excitotoxicity results from excessive release and impaired re-uptake of glutamate, causes persistent activation of NMDA receptors. Leads to intracellular calcium overload resulting in mitochondrial dysfunction and free radical generation
- Apoptosis triggered by activation of caspases, increased by cytochrome C release from damaged mitochondria
- Free radicals and perioxidation cause oxidative stress leading to damage to lipids, protein and nucleic acids in neural cells. This exacerbates inflammation and apoptosis causing further injury
Secondary mechanism of spinal cord injury stages
Inflammation
Excitotoxicity
Apoptosis
Free radical formation
Lipid perioxidation
Spinal cord injury classification based on level of injury
- Cervical: C1-C7, upper = C1-4, lower = C5-7, quadriplegia
- Thoracic: T1-T12, paraplegia
- Lumbar: L1-L5, loss of function in hips and legs
- Sacral: S1-S5, loss of bowel and bladder function, sexual dysfunction
Spinal cord injury classification based on severity
Complete = total loss of sensory and motor function below injury lvl
Incomplete = some sensory or motor function remains below injury lvl. Degree of function depends on extent and location of damage
Spinal cord injury classification based on clinical syndromes
Central cord syndrome
Anterior cord syndrome
Brown-Sequard syndrome
Conus medullaris syndrome
Cauda equina syndrome
What is central cord syndrome?
greater motor impairment in upper limbs than lower limbs
bladder dysfunction
varying degree of sensory loss below injury lvl
What is anterior cord syndrome?
damage to anterior part of spinal cord, results in loss of motor function and pain and temp sensation, but preservation of proprioception and touch
What is Brown-Sequard syndrome?
damage to one half of spinal cord
results in loss of motor function, proprioception and vibration sense ipsilaterally and loss of pain and temp sensation contralaterally
What is conus medullaris syndrome?
injury at terminal part of spinal cord, leading to areflexic bowel, bladder and lower limbs
What is cauda equina syndrome?
injury to lumbar and sacral nerve roots resulting in areflexic bowel, bladder, variable motor/sensory loss in lower limbs
Typical presentation of spinal cord injury
sudden onset of neurological deficits, primarily motor and sensory dysfunction, which are often associated w/ pain or discomfort in back, neck or head
Clinical features of spinal cord inury
Motor dysfunction - weakness or paralysis below lesion lvl, spasticity, hyperreflexia, Babinski sign
Sensory dysfunction - sensation, pain, temp and proprioception below lesion lvl
Pain
Autonomic dysregulation - cardiovasc instability, resp compromise, bladder dysfunction, sexual dysfunction
Bulbar symptoms - dysphagia and dysarthria
What is spinal shock?
in acute phase after injury, characterised by flaccid paralysis, reflexes loss, sensation loss below injury lvl
temporary, lasts from several hrs - several wks
Spinal cord injury investigations
radiographs - anterior-posterior and lateral cervical spine
CT
MRI
SSEP - somatosensory evoked potentials - integrity of sensory pathways
MEP - motor evoked potentials - motor pathway function
Electromyography (EMG) and nerve conduction studies
Spinal cord injury management
Acute resuscitation
Steroid therapy - high-dose methylprednisolone w/in 8hrs of injury
Surgical management - decompression and stabilisation
Rehabilitation
Long term care of chronic complications
Spinal cord injury complications
Neuro: spinal. shock, autonomic dysreflexia, syringomyelia
Pulmonary: ventilatory impairment, pneumonia
GI: gastric dilatation and ileus, bowel dysfunction
MSK and skin: osteoporosis, fractures, pressure ulcers
GU: neurogenic bladder
Pain and psychological: chronic pain, depression, anxiety, PTSD
What is spinal stenosis?
narrowing of part of spinal canal, resulting in compression of spinal cord or nerve roots
usually affects cervical or lumbar spine
common in pts over 60
Where is spinal stenosis most commonly found?
Lumbar
What are the types of spinal stenosis?
Central - narrowing central spinal canal
Lateral - narrowing nerve root canals
Foramina - narrowing intervertebral foramina
Causes of spinal stenosis
- congenital
- degenerative changes - facet joint changes, disc disease and bone spurs
- herniated discs
- thickening of ligamenta flava or pos. longitudinal ligament
- spinal fractures
- spondylolisthesis
- tumours
Symptoms of central spinal stenosis
gradual onset
intermittent neurogenic claudication
- lower back pain
- buttock and leg pain
- leg weakness
occur w/ standing and walking
bending forward improves, standing straight worsens
Symptoms of lateral and foramina stenosis
sciatica
Spinal stenosis investigations
MRI
investigations to exclude peripheral arterial disease - ankle-brachial pressure index, CT angiogram
Spinal stenosis management
exercise and weight loss
analgesia
physiotherapy
decompression surgery where conservative treatment fails
laminectomy
What is a laminectomy?
removal of part or all of lamina from affected vertebra
laminae = bony parts that form posterior part of vertebral foramen, attaches to spinous process
What is cauda equina syndrome?
rare neurosurgical/orthopaedic emergency
compression of cauda equina leads to bladder, bowel and/or sexual dysfunction w/ peri-anal sensory loss
Common causes of cauda equina syndrome
lumbar disc herniation
degenerative lumbar canal stenosis
neoplastic space occupying lesion
spinal trauma
Uncommon causes of cauda equina syndrome
infection
haematoma
spina bifida
late-stage ankylosing spondylitis
neurosarcoidosis
inferior vena cava thrombosis
spinal haemorrhage
Cauda equina syndrome pathology
distal to conus medullaris, lower lumbar nerve roots, sacral nerve roots and coccygeal nerve root continue to travel through vertebral canal to respective exit foramina as part of nerve bundle - cauda equina
cauda equina stops growing at age 4, vertebral column continues to lengthen
What are the neurones w/in the causa equina responsible for?
sensory and motor innervation to lower limbs
sensory innervation to saddle area
motor innervation to anal sphincters
parasympathetic innervation to bladder
Why are the nerve roots in the cauda equina highly susceptible to injury?
compared to peripheral nerves, they have a poorly developed epineurium surrounding their sheaths and don’t have a segmental blood supply
Damage to the cauda equina nerve roots may result in…
reduces sensation or sensory loss
lower motor neurone signs and symptoms - hyporeflexia or areflexia, hypotonia or atonia, flaccid weakness or paralysis, local muscle atrophy, fasciculations
What are the patterns of onset in cauda equina syndrome?
Acute = sudden onset, rapidly progressing symptoms which worsen over several hrs or days
Chronic = insidious onset w/ slow progression of symptoms
What are the two groups of cauda equina syndrome symptoms?
Core diagnostic: urinary, bowel, sexual dysfunction, saddle anaesthesia
Accompanying symptoms: lower back pain w/ or w/out sciatica, lower limb sensory loss, lower limb lower motor neurone signs (can be unilateral or bilateral)
Cauda equina syndrome classification
Cauda equina syndrome w/ retention
Incomplete cauda equina syndrome
Cauda equina syndrome investigations
Diagnosis suspected after identification of saddle anaesthesia, bladder, bowel and sexual dysfunction
urgent MRI
once confirmed diagnosis, further investigations of blood tests and lumbar puncture
Cauda equina syndrome differentials
- conus medullaris syndrome
- herniated lumbar disc
- degenerative lower back pain +/- sciatica
- spinal cord compression
- neoplastic spinal lesions
- lumbar radiculopathy
Cauda equina syndrome management
if cause is suspected to be traumatic, pts spine should be immobilised
surgical decompression
if primary or metastatic malignancy = IV dexamethasone prior to surgical intervention to reduce oedema
Who is suitable for spinal decompressive surgery?
- cauda equina syndrome
- spinal trauma and fractures
- haematomas
- space occupying lesions w/ radiological imaging indicating likely surgical removal
- spinal stenosis
Who is not suitable for surgical decompression surgery?
inflammory disease eg late stage ankylosing spondylitis
infection
spinal neoplastic disease
Cauda equina syndrome prognosis
late diagnosis and delayed treatment increases risk of permanent neuro deficit in pts
may be left w/ paralysis of lower limbs or permanent bladder, bowel and sexual dysfunction
What is Meniere’s disease?
disorder of inner ear of unknown cause
characterised by excessive pressure and progressive dilation of endolymphatic system
more common in middle-aged adults but may be any age
Risk factors of Meniere’s disease
age: 20-50
gender: some studies suggest higher prevalence in women
family history: genetic predisposition
Clinical features of Meniere’s disease
recurrent episodes of vertigo, tinnitus and hearing loss
sensation of aural fullness or pressure
nystagmus
+ve Romberg test
episodes lasting mins - hrs
Meniere’s disease management
ENT assessment to confirm
inform DVLA
acute attacks = buccal or IM prochlorperazine
prevention = betahistine and vestibular rehab exercises
Meniere’s disease prognosis
symptoms resolve in majority of pts after 5-10yrs
majority of pts left w/ degree of hearing loss
psychological distress is common
What is chronic fatigue syndrome?
persistent fatigue that’s not relieved by rest, often accompanied by other symptoms eg muscle pain, headaches and cognitive impairment
Chronic fatigue syndrome diagnosis criteria
- Substantial reduction or impairment in ability to engage in pre-illness lvls of occupational, educational, social or personal activities that persists for >6 months and is accompanied by fatigue
- Post-exertional malaise
- Unrefreshing sleep despite adequate hrs spent asleep
- Cognitive impairment affecting attention, memory, information processing speed or executive function
- orthostatic intolerance manifested by lightheadedness, dizziness or fainting upon standing up
Clinical features of chronic fatigue syndrome
Immune = recurrent sore throat, tender lymph nodes, muscle pain, joint pain w/out swelling, flu-like symptoms
Neuro = headaches, photophobia, phonophobia, blurred vision, balance and coordination issues
Autonomic = neurally mediated htn, POTS, palpitations and GI disturbances
Cognitive = issues w/ concentration, memory, information processing speed, attention
Sleep disturbances
Pain syndromes = fibromyalgia, temporomandibular joint disorder, interstitial cystitis, chronic pelvic pain
NICE recommend we suspect CFS if:
- person has all of persistent symptoms for min. 6wks in adults and 4wks in children
- person’s ability to engage in occupational, educational, social or personal activities is significantly reduced from pre-illness levels
- symptoms not explained by another condition
Chronic fatigue syndrome management
- refer to CFS specialist
- energy management: self-management strategy
- physical activity and exercise based on a specific programme
- cognitive behavioural therapy - supportive
What is Wernicke’s encephalopathy?
condition of acute thiamine (B1) deficiency
most commonly associated w/ chronic alcoholics, can occur secondary to other causes of malnutrition
Causes of Wernicke’s encephalopathy
Alcohol abuse: high carb load leads to high thiamine requirement
Reduced thiamine absorption eg fasting, severe diarrhoea, bariatric surgery, hyperemesis
increased metabolic requirements
Wernicke’s encephalopathy paathophyisiology
thiamine is essential in metabolisis of carbohydrates and lipids - Krebs cycle coenzyme
Insufficent glucose metabolism causes oxidative stress and mitochonrial dysfunction
- localised area of low pH due to lactic acidosis 2nd to metabolic dysfunction further damage neural tissue
- thiamine deficiency also associated w/ deranged glutamate transport and resultant neural excitotoxicity
Neurotoxic effects are maximal in areas of brain that require highest glucose turnover, have highest thiamine demands
Where does Wernicke’s encephalopathy lead to neural damage?
mamillary body
areas of brainstem associated w/ CN3, 4, 6, 8 and 10 nuclei
How does the damage in Wernicke’s encephalopathy lead to the triad of symptoms?
- damage to cranial nerve nuclei controlling ocular muscles = ophthalmoplegia
- damage to cerebellar vermis and motor cortical tracts = ataxia
diffuse nature of damage = variable changes in mental state
Symptoms of Wernicke’s encephalopathy
Ophthalmoplegia
Nystagmus
Ataxia
Cognitive: confusion, memory deficits, apathy or agitation
hypothermia
altered consciousness
GI symptoms
tachycardia
Wernicke’s encephalopathy investigations
diagnosed clincally on presence of 1 or more of triad (due to risk of harm through delayed treatment)
Serum thiamine available, but normal result doesn’t rule out WE
Wernicke’s encephalopathy differential diagnosis
delirium tremens
hepatic encephalopathy
stroke
normal pressure hydrocephalus
Wernicke’s encephalopathy management
urgent administration of parenteral (not oral) thiamine for minimum 5 days
thiamine must be administered before or concurrently w/ any glucose administration
What is myasthenia gravis?
chronic autoimmune neuromuscular disease characterised by fluctuating muscle weakness and fatigue, increases during period of activity and improves after rest
Myasthenia gravis causes
Genetic
Environmental - infections (EPV, H.pylori), hormones, drugs
Thymomas
Autoimmunity
Autoimmune disorders
Myasthenia gravis genetics
HLA-B8, DR3 haplotype = early onset
HLA-B7, DR15/16 = late-onset
non-HLA = PTPN22 and CTLA4
What drugs may exacerbate myasthenia gravis?
penicillamine
quinidine, procainamide
beta-blockers
lithium
phenytoin
antibiotics - gentamicin, macrolides, quinolones, tetracyclines
Myasthenia gravis autoantibodies
autoantibodies target nicotinic AChR at post-synaptic neuromuscular junction
autoantibodies produced by B cells under T-helper cells’ influence, leading to complement-mediated destruction of AChR and neuromuscular transmission impairment
MuSK antibodies may be identified, which is involved in clustering ACRs at NMJs.
LRP4 also sometimes found in MG pts
Myasthenia gravis pathophysiology
Production of autoantibodies against components of NMJ, particularly nicotinic acetylcholine receptor
Binding to nAChRs initiate:
- complement activation leading to membrane attack complex formation
- cross-linking and subsequent endocytosis of nAChRs
- functional blockage of acetylcholine binding
Results in reduction in no and function of nAChRs at post-synaptic membrane
Diminished nAChR density leads to decreased safety factor for NM transmission, which manifests as muscle weakness
What are the autoantibodies usually produced against NMJ in myasthenia gravis?
IgG1 and IgG3 subclasses
produced by B cells under direction of T-helper cells
Clinical features of myasthenia gravis
fluctuating muscle weakness that worsens w/ repetitive activity
ocular, bulbar and limb muscles
- ptosis
- diplopia
- dysarthria
- dysphagia
- proximal limb weakness
can vary from generalised weakness to resp muscle involvement
Myasthenia gravis investigations
- Electrophysiological studies: repetitive nerve stimulation (RNS), single-fiber electromyography (SFEMG)
- Serological testing: AChR, MuSK, LRP4
- imaging: CT or MRI (look for thymoma)
- edrophonium test
Myasthenia gravis differentials
Lambert-Eaton syndrome
Guillain-Barre syndrome
Botulism
Myasthenia gravis pharmacological management
Pyridostigmine - ACh inihibitor
Immunosuppresive agents - corticosteroids (pred, azathioprine)
IVIg - severe cases or during crisis
consider monoclonal antibodies eg rituximab in refractory cases
Other management of myasthenia gravis
Surgical - thymectomy
In pregnancy, close monitoring needed due to potential exacerbations
Pts should receive vaccinations as per guidelines, live vaccines used w/ caution
Myasthenic crisis management
immediate hospitalisation
intensive resp support - intubation and mechanical ventilation
rapid short term control by plasma exchange or IVIg
What is myasthenic crisis?
acute exacerbation of muscle weakness, leads to resp failure. Requires immediate intervention w/ vent support and plasmapheresis or IVIg
Myasthenia gravis complications
myasthenic crisis
resp infections
aspiration pneumonia
thymoma
cortcosteroid complications
cholinergic crisis
mood disorders
What is cholinergic crisis?
overmedication w/ anticholinesterase drugs can cause muscle fasciculations, increased salivation, diarrhoea and bradycardia
What are the cranial nerve palsies?
3rd = at rest eye points ‘down and out’
4th = upwards and inwards, worse looking up and down
6th = medially deviated, worse looking side to side
Cranial nerve palsies investigations
CT / MRI to look for compressive leisons
Bloods
LP
Nerve conduction studies
Cranial nerve palsy treatment
treat underlying cause
blood sugar control in diabetic neuropathy
immunosuppression in MS
Spinal cord compression
back pain
weakness below lvl
urinary / faecal incontinence constipation
hypertonia
hyperreflexia
clonus
sensory loss
UMN symptoms
Spinal cord compression investigation and management
MRI whole spine
Tx = major trauma centre referral, immobilise pt
If metastatic, give high dose steroids, PPI and surgical decompression
What is neurofibromatosis?
grp of genetic disorders characterised by growth of neurofibromas - benign tumours that affect nerve tissue
Typical presentation of neurofibromatosis
cafe-au-lait macules (pigmented patches appearing at birth or early childhood) and neurofibromas (benign tumours that develop from nerve sheath, may not be apparent until later in life)
Clinical features of neurofibromatosis
Cutaneous: cafe-au-lait macules, neurofibromas, freckling
Ocular: Lisch nodules, optic pathway gliomas
Skeletal: scoliosis, pseudarthrosis
Neuro: learning disability, epilepsy, malignant nerve sheath tumours
Diagnostic criteria for neurofibromatosis type 1
2 or more of:
- 6+ cafe-au-lait macules >5mm in diameter in prepubertals and >15mm in postpubertals
- 2+ neurofibromas
- optic glioma
- 2+ lisch nodules
- distinctive osseous lesion
- 1st degree relative w/ NF1
Diagnostic criteria for neurofibromatosis type 2
less common than NF1, either:
- bilateral vestibular schwannomas, diagnosed using MRI
- 1st degree relative w/ NF2 and either unilateral vestibular schwannoma before 30, or any 2 of: meningioma, glioma, schwannoma, cataract / juvenile posterior subscapular lenticular opacity
Neurofibromatosis medical management
analgesia - NSAIDs or opioids
antihypertensives - ACE inhibitors or CCBs for HTN 2nd to renal artery stenosis
malignant peripheral nerve sheath tumours - require surgery, radiation and chemo. MEK inhibitor selumetinib also effective
Neurofibromatosis surgical management
plexiform neurofibromas - surgical debulking, attempt complete resection (may not be possible due to infiltrative nature)
optic pathway gliomas - surgery, but can have risk due to proximity to critical structures
scoliosis - orthopaedic intervention, spinal fusion
Other management of neurofibromatosis
ophthalmological = lisch nodules - regular assessments
psychological and educational support - increased risk of learning disabilities, ADHD and autism
Genetic counselling - autosomal dominant inheritance pattern
Neurofibromatosis complications
cutaneous and subcutaneous neurofibromas
plexiform neurofibromas
optic pathway gliomas
skeletal abnormalities
cognitive impairments
CV issues
aqueductal stenosis and hydrocephalus
meningiomas and astrocytomas
GISTs
What is the triad of normal pressure hydrocephalus?
gait disturbance
cognitive impairment
urinary incontinence
Causes of normal pressure hydrocephalus
idiopathic
2ndary:
- subarachnoid haemorrhage
- meningitis
- traumatic brain injury
- intracranial tumours
- ventricular shunting or lumbar puncture
Normal pressure hydrocephalus pathophysiology
- imbalance between production and absorption of CSF, leads to progressive ventricular dilation
- ventricular enlargement exerts mechanical stress on surrounding periventricular white matter tracts. Leads to stretching and compression of fibres, particularly frontal white matter tracts
- mechanical stress also disrupts BBB integrity w/in periventricular regions, induces localised inflammation
- inflammatory response further exacerbates white matter damage, leading to gliosis and demyelination. Chronic inflammation may impair glymphatic clearance of interstitial solutes
- ventricular dilation and subsequent brain parencyma compression can lead to alterations in cerebral perfusion. Reduced cerebral blood flow and impaired autoregulation
Normal pressure hydrocephalus pathophysiology summarised
ventricular dilation
periventricular stress
disruption of blood-brain barrier
inflammatory response
cerebral perfusion changes
How do the pathophysiological changes in normal pressure hydrocephalus correlate w/ clinical manifestations
gait disturbance - damage to motor pathways, especially corticospinal tract
cognitive impairment - disruption of fronto-striatal circuits
urinary incontinence - dysfunction of frontal lobes and periventricular white matter tracts involved in incontinence
Clinical features of normal pressure hydrocephalus
gait disturbance - unsteady, wide based gait, ‘magnetic’
cognitive impairment - deficits in attention, concentration and executive functions
urinary incontinence - urgency and frequency
also headaches, changes in personality or behaviour
Normal pressure hydrocephalus investigations
imaging - hydrocephalus w/ and enlarged 4th ventricle, in addition to ventriculomegaly there’s absence of substantial sulcal atrophy
Normal pressure hydrocephalus differential diagnosis
alzheimer’s
parkinson’s
vascular dementia
Normal pressure hydrocephalus management
- ID suitable candidates for intervention via cranial imaging and invasive testing eg LP
- shunt surgery - ventriculoperitoneal shunt w/ adjustable valve systems
- post-op follow up and regular monitoring
- non-surgical management = lifestyle modifications eg avoid medications that exacerbate, physiotherapy
What medications can exacerbate normal pressure hydrocephalus?
sedatives
anticholinergics
