Neurology Flashcards
What is the most prevalent type of dementia in the UK?
Alzheimer’s
What is the peak incidence of Alzheimer’s?
70
What percentage of Alzheimer’s disease is inherited autosomal dominant?
5%
An amyloid precursor gene mutation causes Alzheimer’s; what chromosome is it found on?
Chromosome 21
A presenilin one gene mutation causes Alzheimer’s; what chromosome is it found on?
Chromosome 14
A presenilin two mutation causes Alzheimer’s; what chromosome is it found on?
Chromosome 1
What genetic condition is a risk factor for Alzheimer’s?
Downs syndrome
Describe the macroscopic changes seen in Alzheimer’s
Cerebral atrophy, particularly in the cortex and hippocampus
Describe the microscopic changes seen in Alzheimer’s
- Cortical plaques
-Deposition of A-beta amyloid protein
-intraneuronal neurofibrillary tangles
What causes the neurofibrillary tangles seen in Alzheimer’s?
Abnormal aggregation of tau protein and hyperphosphorylation of tau is linked with AD
What neurotransmitter is in deficit in Alzheimer’s?
Acetylcholine
Describe the clinical features of Alzheimer’s
-Difficulties of daily living
- Onset is over months/years
-Cognitive impairment:
-Memory loss
-Difficulty learning new information
-Vague with dates
-Reasoning and communication
-Difficulty making decisions
-Dysphasia
-Behavioural/ psychological
-Depression
-agitation
-psychosis
-apathy
-disinhibition
Describe the non-pharmacological treatment of Alzheimer’s
-Social prescribing
-Group cognitive stimulation therapy (mild/ moderate cases)
-Group reminiscence therapy and cognitive inhibition
Describe the pharmacological treatment for mild-moderate Alzheimer’s
3 acetylcholinesterase inhibitors:
-donepezil
-galantamine
-rivastigmine
What is the contraindication for donepezil?
Bradycardia
What is the key side effect to remember for donepezil?
Insomnia
What drug is used in moderate Alzheimer’s intolerant of acetylcholinesterase inhibitors?
memantine
What drug is combined with acetylcholinesterase inhibitors when treating moderate/severe Alzheimer’s?
memantine
What drug is used as monotherapy in severe Alzheimer’s?
memantine
What type of drug is memantine?
NMDA
How can the non-cognitive symptoms of Alzheimer’s be treated?
-Antidepressants for depression
-Antipsychotics for those at risk of hurting themselves or others
Describe Parkinson’s disease
Progressive reduction in dopamine in the basal ganglia leads to movement disorders.
Describe the pattern of the movement disorder distribution seen in Parkinson’s disease
Asymmetrical, it affects 1 side of the body
What is the classic triad seen in Parkinson’s disease?
-Resting tremor
-Rigidity
-Bradykinesia
Describe the rigidity seen in Parkinson’s
-Resisting passive movement
-Cogwheel
Briefly describe the pathophysiology of Parkinson’s disease
-Dopamine is essential for the function of the basal ganglia
-The basal ganglia coordinate habitual movements such as walking
-The basal ganglia are involved in specific movement patterns
Describe the tremor seen in Parkinson’s
-worse on one side
- 4-6 hertz (4-6 cycles/ second)
-Pill rolling
-more noticeable at rest
-Better with voluntary movement
-worse when the patient is distracted
-Using the other hand exaggerates the tremor
Describe the features of bradykinesia seen in Parkinson’s
-Micrographia
-shuffling gait
-festinating gait
-difficulty initiating movement
-Lots of little steps when moving
-hypomimia
What are other features of Parkinson’s that are not associated with tremors or bradykinesia?
-Depression
-Sleep disturbance
-anosmia
-postural instability
-cognitive impairment
-memory problems
Describe a benign essential tremor
- symmetrical
-6-12 hertz
-improves at rest
-worse with intentional movement
-no other Parkinson’s symptoms
-improves with alcohol
Describe the Parkinson’s tremor
-Asymmetrical
- 4-6 hertz
- worse at rest
- improves with intentional movement
-other Parkinson’s features
- No change with alcohol
What condition may present mimicking Parkinson’s
-multiple system atrophy
- Multiple systems in the brain degenerate (including the basal ganglia, which can give a Parkinson’s presentation
In multiple system atrophy, how can autonomic dysfunction present?
- Postural hypotension
-constipation
-Sexual dysfunction
-abnormal sweating
In multiple systems atrophy, how can cerebellar dysfunction present?
ataxia
How is Parkinson’s disease diagnosed?
- History and examination
-UK Parkinson’s Disease Society Brain Bank clinical diagnosis criteria
What is the approach to managing Parkinson’s?
-Treating the symptoms as there isn’t a cure
What is the most effective treatment for Parkinson’s, and what is its caveat?
Levodopa (synthetic dopamine) it becomes less effective over time
What are the side effects of levodopa, and how are these managed?
- dystonia
-chorea (involuntary irregular movements)
-athetosis (continuous, slow, writhing movements)
Managed with amantadine (glutamate antagonist)
What drug are peripheral decarboxylase inhibitors combined with, and what do they do?
- Levodopa
-stop L-dopa being metabolised peripherally before it reaches the brain
Give two examples of peripheral decarboxylase inhibitors
- Carbidopa
-Benserazide
What are COMPT-inhibitors, how do they work and give an example of one?
-Catechol-o-methyl transferase inhibitors
-COMPT enzyme metabolises levodopa peripherally and centrally
-Entacapone, taken with levodopa to slow its breakdown
What are dopamine agonists, and how are they used?
-Mimic the action of dopamine in the basal ganglia
-less effective than L-dopa
- Used to delay the start of L-dopa and then used in combination with L-dopa
Name 3 dopamine agonists
-Bromocriptine
-Pergolide
-Cabergoline
What is the risk of taking dopamine agonists for a prolonged time?
Pulmonary fibrosis
What type of movements does a benign essential tremor affect?
All voluntary movement
What areas of the body are benign essential tremors most noticeable?
the hands, head, jaw and vocal cords
Describe the features of benign essential tremor
- 6-12 hertz
-symmetrical
-improves with alcohol
-more prominent with voluntary movements
-worse with fatigue, stress or caffeine
What are the key differentials of benign essential tremors?
-Parkinson’s
-MS
-Huntingtons chorea
-hyperthyroidism
-fever
-dopamine antagonists (antipsychotics)
How is benign essential tremor managed?
-doesn’t usually require intervention
-medications may improve symptoms:
Propanalol (non selective beta blocker)
Primidone (barbituarate anti-epileptic)
What is the 2nd most common type of dementia?
-Vascular dementia
Describe vascular dementia
A group of syndromes of cognitive impairment caused by mechanisms inducing ischaemia or haemorrhage secondary to cerebrovascular disease
List the RF for vascular dementia
-History of TIA
-AF
-Hypertension
-DM
-Hyperlipidaemia
-smoking
-obesity
-CHD
-FH of stroke of CVD
How can vascular dementia be inherited?
-CADASIL
-Cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy
How can vascular dementia be classified?
- Stroke-related (multi-infarct or single-infarct dementia)
-Subcortical (small vessel disease)
-Mixed (VD and Alzheimer’s)
What is the timescale of deterioration in vascular dementia?
-months/ years
List the symptoms of vascular dementia
-Focal neurological abnormalities (visual disturbance, sensory or motor symptoms)
-Difficulty with attention and focus
-seizure
-memory disturbance
-Gait disturbance
-speech disturbance
-emotional disturbance
How is vascular dementia diagnosed?
-History and examination
-formal screen for cognitive impairment
-medical review to exclude prolonged medication use as a cause
-MRI
What are the MRI changes seen in vascular dementia?
-Infarcts
-White matter changes
How is vascular dementia treated?
- Treat the symptoms
-managed CVD RF
-Cognitive stimulation programmes, multisensory stimulation, music and art therapy, animal-assisted therapy
-No pharmacological treatment for VD alone
Describe motor neurone disease
-Variety of specific diseases affecting motor nerves
-Progressive, eventually fatal, where motor neurons stop working
-No sensory signs
What is the most common type of MND, and what % of diagnoses does it account for?
-Amyotrophic lateral sclerosis
-50%
What is the distribution of disease seen in amyotrophic lateral sclerosis?
-LMN signs in the upper limbs
-UMN signs in the lower limbs
What chromosome is affected in amyotrophic lateral sclerosis with an inherited element, and what protein does it make?
-chromosome 21
-superoxide dismutase
What is the 2nd most common type of MND?
-Progressive bulbar palsy
Which type of MND has the worst prognosis?
-Progressive bulbar palsy
Describe progressive bulbar palsy
- Affects muscles of talking and wallowing
-due to loss of motor nuclei in the brainstem
Which type of MND has the best prognosis?
-Progressive muscular atrophy
Describe progressive muscular atrophy
-distal muscle affected before proximal muscles
-LMN signs only
Describe the pathophysiology of MND
-exact mechanism unknown
What % of MND is inherited?
5-10%
What factors is MND linked to?
-Smoking
-exposure to heavy metals
-exposure to pesticides
Describe the presentation of MND
- 40-60 yr old
- more commonly male
-has an affected relative
-Insidious, progressive asymmetrical muscle weakness affecting the limbs, trunk, face and speech
-Weakness 1st noticed in the upper limbs - wasting of the small muscles of the hands and tibialis anterior
-Increased fatigue when exercising
-clumsiness, dropping things, tripping over
slurred speech (dysarthria)
What is a late sign of MND?
sphincter dysfunction
Are there ever sensory signs in MND?
-No, there can be sensory symptoms (limb pain) early in the disease onset, however
How can the features of MND be used to rule out other diseases?
- No external ocular muscle weakness like myasthenia gravis
- No cerebellar signs
-Abdominal reflexes maintained
Describe the UMN signs
- Increased tone and spasticity
- Brisk reflexes
- upgoing plantar reflexes
Describe the LMN signs
- Muscle wasting
- decreased tone
- Fasciculations (muscle twitching)
-Decreased reflexes
How are alternative diagnoses excluded before diagnosing MND?
- Nerve conduction studies will appear normal and will exclude neuropathy as the cause of symptoms
-MRI excludes cervical cord compression and myelopathy
What test would indicate MND?
Electromyography will show reduced action potential and an increased amplitude
How well can MND currently be managed?
Not particularly well, no treatment halts or reverses the disease process
How does riluzole work, and for what type of MND is it prescribed?
-Prevents stimulation of glutamate receptors
- used mainly in ALS
-Extends life by 3 months
What support is given when respiratory muscles weaken?
-non-invasive ventilatory support (BIPAP)
How is symptom control managed in MND disease?
- Baclofen is used in muscle spasticity
- Antimuscarinics are used for excessive saliva production
-Benzodiazepines to help with breathlessness exacerbated by anxiety
Describe multiple sclerosis
-Chronic
-autoimmune
demyelination of the CNS
How much more common is MS in women?
3x
What is the age that MS is most commonly diagnosed?
20-40
Describe the geographical distribution of MS
More common at higher latitudes (further from the equator)
What cells make myelin in the CNS?
oligodendrocytes
Which cells make myelin in the PNS?
Schwann cells
Describe the pathophysiology of MS
-Inflammation and immune infiltration damages the myeline, affecting the electrical signals
-Early in disease there is remyelination, causing symptom resolution
-Remyelination is incomplete later in the disease, so symptoms become permanent
Are all CNS lesions likely to cause symptoms?
NO, if someone has an MS attack, there are likely more lesions not causing symptoms throughout the CNS
What are the causes of MS?
-Multiple genes
-EBV
-Low vitamin D
-Smoking
-Obesity
Describe the duration of an initial MS attack
- over more than 24 hours
-lasts weeks or days
-Resolves if it’s the 1st presentation
What is the most common presentation of MS?
-Optic neuritis
What causes optic neuritis?
demyelination of the optic nerve
Describe the symptoms of optic neuritis
- Unilaterally reduced vision developing over hours-days
-pain with eye movement
-impaired colour vision
Describe the signs of optic neuritis
-Central scotoma (enlarged blind spot)
- Relative afferent pupillary defect
Describe the different ways there can be an afferent pupillary defect in MS
-Pupil in the affected eye constricts more when shining light in the contralateral eye than when shining directly
-Reduced response in the affected eye in direct pupillary response
-Normal response in the affected eye when testing consensual pupillary reflex
Other than MS, name 7 causes of optic neuritis
- Sarcoidosis
-SLE
-measles
-mumps
-neuromyelitis optica
-Lyme disease
What should be done if someone presents with optic neuritis
-Urgent ophthalmology review
-High-dose steroids
-MRI
When someone presents with optic neuritis, what can the MRI results indicate?
Changes on the MRI can help predict which patients will go on to develop MS
Lesions to which cranial nerves cause diplopia and nystagmus?
CN3, CN4 and CN6
What is oscillopsia?
The visual sensation that the environment is moving and is unable to create a stable image
What are the signs of internuclear ophthalmoplegia?
-Impaired adduction in the ipsilateral eye
-nystagmus in the quadrilateral eye
In internuclear ophthalmoplegia, where is the lesion?
The medial longitudinal fasciculus
-Connects the cranial nerve nuclei that control eye movements, meaning that they are unable to coordinate movements
A lesion to which cranial nerve causes conjugate lateral gaze disorder?
-CN4
Describe how conjugate lateral gaze disorder presents
When the person is attempting to look laterally to the side affected, the unaffected eye will look medially and the affected eye will look straight on
Describe 4 different focal neurological symptoms that MS may present with
-Incontinence
-Horner’s syndrome
-facial nerve palsy
-limb paralysis
Describe 4 focal sensory symptoms that MS may present with
-trigeminal neuralgia
-numbness
-paraesthesia
-Lhermitte’s sign
What is Lhermitte’s sign?
-Sensation of electric shock which travels down the spine and into the limbs when flexing the neck
Describe the pathology behind Lhermittes spine
Disease in the cervical spine in the dorsal column, the demyelinated dorsal column is stretched
What is the word to describe sensory ataxia?
pseudoathetosis
What causes sensory ataxia?
loss of proprioception, possibly by a lesion in the dorsal columns
What causes cerebellar ataxia?
a cerebellar lesion
What test would indicate sensory ataxia?
a positive Romberg’s test
What is the most common disease pattern for MS?
mild relapsing-remitting
Describe the relaxing-remitting MS pattern
-symptoms are inn different areas with each episode
-Active: new symptoms, new lesion
-Inactive: no new symptoms, no new lesions
-Worsening: Overall worsening of disability over time
- Not worsening: no overall worsening over time
Describe clinically isolated syndrome MS
-1st episode of demyelination, neurological signs and symptoms
- may never have another episode or may develop MS
In clinically isolated syndrome, what makes someone more likely to develop MS?
A lesion being found on MRI
Describe the primary progressive disease pattern of MS
the disease and neurological symptoms worsen from the initial episode
describe the secondary progressive disease pattern of MS
the disease is initially relapsing-remitting, but then symptoms worsen and progress with incomplete remission, becoming more permanent
How is MS diagnosed?
-MRI scan for lesions
-LP
What findings on an MRI indicate MS?
-Periventricular plaques
- Dawson fingers
What are Dawson fingers?
Hyperintense lesions perpendicular to the corpus collosum
What lumber puncture findings would indicate MS?
-Oligoclonal bands in the CSF, however not in the serum
-Increased intrathecal IgG
Describe the basic management of MS
- DMARDS to induce long-term remission
-relapses are treated with 500mg oral steroids (methylprednisolone) 5 days or 1g daily 3-5 days
What is an indicator for IV steroids over oral steroids in MS relapses?
-Previous failure with oral or a very severe relapse
What is the use of steroids in treating MS relapses?
- shortens the length of an acute relapse, doesn’t alter the disease progression
Describe symptomatic management of MS
-Exercise to maintain activity and strength
-fatigue: amantadine, modafinil or SSRI’s
-Neuropathic pain: amitriptyline or gabapentin
-Depression: SSRI’s
-urge incontinence: antimuscarinics (solifenacin)
-spasticity: Baclofen or gabapentin
-Oscillopsia: gabapentin or memantine
What are the indications for DMARD’s in someone with a relapsing-remitting MS pattern
2 relapses in 2 years, walks 100m unaided
What are the DMARD’s indications in secondary-progressive MS?
2 relapses in 2 yeras, able to walk 10m unaided
What DMARD is used 1st line in MS?
Natalizumab
Describe the action of natalizumab in ms?
-inhibits migration of leucocytes across the endothelium in the blood brain barrier
- strongest evidence for preventing relapses
- IV
Describe how ocrelizumab is used in MS management
- Humanised anti- CD20 monoclonal antibody
- High efficacy, can be used 1st line
- IV
Describe how fingolimod can be used in MS treatment
- sphingosine 1-phosphate receptor modulator
- prevents lymphocytes leaving lymph nodes
- oral option
Name 2 older drugs used in MS management
- beta interferon
-glatiramer acetate
What is the most common type of muscular dystrophy and what is it’s inheritance pattern?
-Duchennes muscular dystrophy
-X-linked
Describe the mutation in Duchenne’s muscular dystrophy
-defective dystrophin gene due to a frameshift mutation which leads to a blockage of one or both binding sites
-the dystrophin gene helps to hold muscles together at a cellular level
How are females affected by Duchenne’s muscular dystrophy?
- X-linked disease, females have 2 copies of the dystrophin gene so are rarely symptomatic but are carriers, there’s a 50% chance of a daughter being a carrier and a 50% chance of a son having the disease
When does Duchenne’s muscular dystrophy present?
3-5 years
How does Duchenne’s muscular dystrophy present?
- pelvic girdle weakness
-progressive, eventually all muscles are affected - Gower’s sign
What is Gower’s sign?
- demonstrates proximal muscle weakness
-child can’t stand up without assistance from arm muscles
-crouching dog position, shifts weights onto legs
when do boys with Duchenne’s muscular dystrophy usually become reliant on wheelchair use?
by teenage years
what is the life expectancy of someone with Duchenne’s muscular dystrophy?
25-35 years, with goof management of cardiac and respiratory complications
What treatments can improve Duschenne’s muscular dystrophy?
-Steroids: can slow the progression by 2 years
-Creatinine: can give slight improvement of muscle strength
What sign of Duchenne’s muscular dystrophy may be observed in the calves?
pseudohypertrophy
What percentage of boys with Duchenne’s muscular dystrophy have an intellectual impairment ?
30%
Describe the mutation in Becker’s muscular dystrophy
non- frameshift mutation, both binding sites are preserved
when does Becker’s dystrophy present?
8-12 years old
When may patients with Becker’s muscular dystrophy require wheelchair assistance?
-late 20’s or 30’s
-may be able to walk with assistance into adulthood
How is Becker’s muscular dystrophy managed?
similarly to Duchenne’s muscular dystrophy
How common is intellectual impairment in Becker’s muscular dystrophy?
Not very common
When does myotonic muscular dystrophy present?
in adulthood
How is myotonic muscular dystrophy characterised?
- progressive muscle weakness
prolonged muscle contractions (unable to let go after a handshake/ after holding a door handle)
-cataracts
-cardiac arrhythmias
When does facioscapulohumeral muscular dystrophy present?
-childhood
How does facioscapulohumeral muscular dystrophy present?
- weakness around the face, progressing to the shoulders and arms
what are 3 signs of facioscapulohumeral dystrophy?
- sleeping with eyes slightly open
-weakness pursing lips
-unable to blow out cheeks without letting air out of the mouth
How does oculopharyngeal muscular dystrophy present?
-bilateral ptosis
-restricted eye movement
-swallowing problems
-muscles around the limb girdles are affected differently
when does oculopharyngeal muscular dystrophy present?
- in late childhood
When does limb girdle weakness present?
teenage years
When and how does Emery-Dreifuss muscular dystrophy present?
-Childhood
- Contractures
-progressive weakness and wasting of muscles
What is the inheritance pattern of Huntington’s disease?
Autosomal dominant
What are the chances of the child of someone with Huntington’s disease developing the condition?
50%
Describe the pathology of Huntington’s disease
-Trinucleotide repeat disorder
-Mutation on the HTT gene on chromosome 4 which codes for the huntingtin protein
-Degeneration of cholinergic GABAergic neurons in the striatum of the basal ganglia
When do symptoms usually start for people with Huntington’s disease?
30-50 years
Name 4 other trinucleotide disorders other than Huntington’s disease
- Myotonic dystrophy
-Fragile X-syndrome
-Spinocerebellar ataxia
-friedreich ataxia
Describe the concept of genetic anticipation
- progressive generations have more trinucleotide repeats
-early onset of symptoms and more severe disease
Describe the presentation of Huntington’s disease
-Insidious onset of psychiatric, cognitive and mood problems followed by movement disorders
What movement disorders may come with Huntington’s disease?
- Chorea: involuntary, random, irregular and abnormal movements
- Dystonia and irregular posture due t dystonia
-rigidity: resistance to passive movement
-dysarthria
-dysphagia
How is Huntington’s disease diagnosed?
Genetic testing
What is the treatment for Huntington’s disease?
There currently is no treatment to change alter the disease progression
How may Huntington’s disease be managed?
MDT approach
-genetic counselling
-physiotherapy
-SALT
-Advanced directive’s
-End of life care
What drugs may be used in Huntington’s disease management?
-SSRI’s for depression
-Tetrabenazine, for chorea symptoms
What is the prognosis for Huntington’s disease?
10-20 years after diagnosis
Describe the pathogenesis of a brain abscess
-Focal intracranial infection that begins as a localised area of cerebritis and evolves into a collection of puss surrounded by a well vascularised capsule
Which types of organisms may cause abscesses?
-Streptococcus
-staphylococcus
-anaerobes
-fungi
-parasites
What may cause brain abscesses?
-Secondary to infections elsewhere in the body
-direct inoculation from trauma or surgery
-complication of meningitis
I what demographic are brain abscesses most common?
males aged 20-30
Why can diagnosing a brain abscess be difficult?
-Vague symptoms
-mimics other neurological conditions
What are the risk factors for a brain abscess?
-immunosuppression
-recent neurosurgery
-chronic ear or sinus infections
-systemic infection and new onset neurological symptoms
How will the presentation of a brain abscess differ in someone who is immunosuppressed?
-Symptoms will be more subtle
What type of headache would a brain abscess present with?
-dull
-constant
-progressively worse
-localised (to the area where the abscess is)
What percentage of patients with a brain abscess have focal neurological symptoms and what may these be?
-50%
-hemiparesis
-language/speech disorders
-visual field defects (oculomotor or abducens nerve palsy)
What percentage of patients with brain abscesses present with fever?
50%
What non-specific features may indicate a brain abscess?
-lethargy
-altered mental status
-seizures
When are seizures more likely from a brain abscess?
- When the abscess is in the cerebral cortex due to cortical irritation
Name 4 features of someone presenting with a brain abscess
-headache
-non-specific features
-focal neurological symptoms
-fever
What contrast agent is used in MRI when scanning for an abscess and what may it show?
-gadolinium
-early cerebritis
What complications may be indicated by a CT when scanning a brain abscess?
-hydrocephalus
-herniation
What situations should you order a CT before a LP?
if raised intracranial pressure is suspected
Why is a LP contraindicated in a suspected brain abscess?
Herniation risk
What technique may provide diagnostic information and treatment for a brain abscess?
stereotactic needle aspiration
Describe the management for a brain abscess
-Surgery: craniotomy for cavity debridement, the abscess may come back after the head is closed
-IV antibiotics: 3rd generation cephalosporin and metronidazole
- Dexamethasone for raised ICP
List 6 bacteria that cause meningitis
-Neisseria meningitidis
-streptococcus pneumoniae
-Haemophilus influenzae
-Group B streptococcus (streptococcus agalactiae)
-Listeria monocytogenes
-Escheria coli
What type of bacteria are neisseria meningitidis?
Gram negative diplococci
Name 3 bacteria that neonates in particular are susceptible to causing meningitis
-Group B streptococcus (streptococcus agalactiae, it colonises the vagina)
-Listeria monocytogenes
-E. coli
Which pathogen causes the typical non-blanching rash associated with meningitis?
-Neisseria meningitidis, when it causes meningococcal septicaemia
Compared with bacterial, how quick is the onset of viral meningitis?
more gradual
Compared with bacterial, describe the prognosis of viral meningitis
-good
-often patients are fully recovered in 7-10 days and need little treatment
Name 5 viruses which may cause meningitis
-Enteroviruses (coxsackie virus)
-Herpes simplex virus
-Varicella zoster virus
-Arboviruses
-mumps
-HIV
Which viruses causing meningitis should be treated with acyclovir?
-Herpes simplex virus
-varicella zoster virus
Name 3 non-infective causes of meningitis?
-Malignancies: leukemia or metastatic cancers
-Drugs: NSAIDs, some antibiotics (trimethoprim-sulfamethoxazole), intrathecal therapies
-Autoimmune conditions: SLE, Behet’s disease, sarcoidosis
Which ages are most susceptible to meningitis?
Under 5’s and over 60’s
Name 5 risk factors for meningitis
-Age
-Immunocompromised
-Crowded living conditions
-splenectomy or spleen dysfunction
What is the classic triad for meningitis?
-Fever
-Neck stiffness
-altered mental state
How may meningitis present?
-Fever
-neck stiffness
-altered mental state
-vomiting
-headache
-photophobia
-seizures
what non-specific symptoms in neonates may indicate meningitis?
-Hypotonia
-poor feeding
-lethargy
-hypothermia
-bulging fontanelle
-high pitched cry
When would you LP a child?
-under 1 month, fever
-1-3 months, unwell with a high/low WCC
Which tests would you perform which may indicate if someone has meningitis?
-Kernig’s test
-Brudzinski’s test
Describe Kernig’s test
patient supine, hip and knee flexed to 90 degree’s, slowly straighten the knee whilst keeping the hip flexed, this creates stretch in the meninges
+ve if there’s spinal pain or resistance to moving
Describe Brudzinki’s test
patient supine, lift head and neck of the bed and flex the chin the the chest
+ve if involuntary flexion of hips and knees
Where does the spinal cord end?
L1-L2
Where is the needle inserted in an LP?
L3-L4 or L4-L5
What tests are performed on CSF obtained via LP?
-Bacterial culture
-Viral PCR
-Cell count
-Protein
-Glucose
Why should a blood glucose be performed when doing an LP?
to compare the blood glucose to the CSF glucose, CSF glucose will be about 40% CSF glucose in bacterial meningitis
Describe CSF findings in bacterial meningitis
-Cloudy
-high protein
-low glucose
-high neutrophils
-+ve culture
Describe CSF findings in viral meningitis
-Clear
-protein mildly high or normal
-glucose normal
-high lymphocytes
-Ve culture
If a child presented to primary care with suspected meningitis, what would the correct course of action be ?
-IM/IV benzylpenicillin
- if true penicillin allergy, don’t delay hospital transfer to find alternative
-Don’t delay transfer for ABx
What are the dosages of benzylpenicillin in primary care for suspected meningitis?
-Under 1= 300mg
-1-9 = 600mg
-over 10 =1200mg
In hospital which antibiotics are used to treat meningitis?
-Under 3 months ceftriaxone and amoxicillin to cover listeria
-above 3 months cefotaxime
-acyclovir if viral meningitis is suspected
What investigations should be done in someone with suspected meningitis?
- Blood cultures and LP before antibiotics if possible without delaying AbX administration
-Meningococcal PCR, it’s quicker than cultures
What treatment is given to close contacts of people with meningococcal meningitis?
a single dose of ciprofloxacin ASAP
List 5 complications of meningitis
-Hearing loss
-seizures and epilepsy
-cognitive impairment and learning disability
-memory loss
-focal neurological deficits (limb weakness or spasticity)
In the context of the pathology of meningitis, what are the 3 stages in the Invasion stage?
-colonisation
-invasion
-crossing the blood brain barrier
in the context of pathology in meningitis, describe colonisation
- Nasopharynx
- usually by the causative bacteria ( Neisseria meningitidis, streptococcus pneumoniae, haemophilus influenzae)
in the context of pathology in meningitis, describe invasion
-Pathogens invade the blood stream
- This bacteriaemia transient or sustained
in the context of pathology in meningitis, describe the 3 methods of crossing the BBB
1) transcellular penetration (directly through endothelial cells)
2) paracellular (between endothelial cells)
3) Trojan horse mechanism (via infected phagocytes)
in the context of pathology in meningitis, what are the 3 stages involved in survival and replication in the host?
- Evasion of host immune response
- Bacterial proliferation and inflammation
-Tissue damage
in the context of pathology in meningitis, describe evasion of host immune response
-antigenic variation
-inhibition of complement system
-intracellular survival inside phagocytes
-biofilms
-immunomodulatory molecules
Where do bacteria multiply in the CNS in meningitis, why do they do it here and what is the overall effect?
- Subarachnoid space
-there’s a lack of effective immune response in this space - raised ICP
Describe the inflammatory response of the host during meningitis
-cell wall components trigger an inflammatory response
-cytokines and chemokines are released, inflammatory cells are recruited to the site
How is tissue damage sustained during meningitis?
-Inflammation
-damages neuronal tissue and the BBB
What are the clinical manifestations of the BB being damaged during meningitis?
-headache
-fever
-neck stiffness
-neurological deficits
Which group of patients are at risk of fungal meningitis?
- Immunocompromised
What pathogens may cause fungal meningitis?
-Cryptococcus neoformans
-cryptococcus immitis
List 3 parasites which may cause meningitis?
- Toxoplasma gondii
-taenia solium
-amoebae
What does primary meningitis mean?
CNS infection, no concurrent or prior infection
what does secondary meningitis mean?
Infection latter to neurosurgery or penetrating head trauma
What does acute meningitis mean?
symptoms develop over hours to 2 days
What does subacute meningitis mean?
symptoms develop over 1-2 weeks
What does chronic meningitis mean?
symptoms persist for more than 4 weeks
What are the 3 most likely differential diagnoses of meningitis?
-Encephalitis
-subarachnoid haemorrhage
-Brain abscess
What features differentiate encephalitis to meningitis?
- encephalitis is inflammation of the brain parenchyma, which causes fever, headache and altered mental state
-focal neurological signs (hemiparesis or aphasia) are more common in encephalitis
-neck stiffness is less common
-seizures at onset of illness are more indicative of meningitis
How may a subarachnoid haemorrhage present similarly to meningitis
-sudden, severe headache
-nausea
-vomiting
-photophobia
How may a subarachnoid haemorrhage present differently to meningitis?
- SAH, loss of consciousness at onset is less common
-SAH, no fever
-SAH LP findings: xanthochromia due to the breakdown of RBC’s if performed 12hr+ after onset
How may a brain abscess present similarly to meningitis?
- fever
-headache
-change in mental status
What is Guillain-Barre syndrome?
-Acute polyneuropathy affecting the peripheral nervous system
- causes acute, symmetrical ascending weakness and sensory symptoms
- usually triggered by an infection
What infections are associated with Guillain-Barre syndrome?
-campylobacter jejuni
-cytomegalovirus
-EBV
There are 2 potential mechanisms for Guillain-Barre syndrome, name them
-Molecular mimicry
-Bystander activation
Describe the mechanism of molecular mimicry
B cells make antibodies that correspond with the antigens of the triggering pathogen. These antibodies also correspond with the antigens of the peripheral nervous system, either the myelin sheath or the nerve axon itself.
Describe the mechanism of bystander activation
Non-specific immune system activation which attacks peripheral nerves. Thought to be more likely in GBS triggered by viral infection.
How does GBS present?
- symptoms begin within 4 weeks of a triggering infection and peak within 2-4 weeks
-history of gastroenteritis
-Symmetrical ascending weakness (lower limbs affected first, however proximal muscles more likely to be affected before distal) - reduced reflexes
-peripheral loss of sensation
-neuropathic pain
Why may facial weakness be a symptom of GBS?
if the peripheral neuropathy affects the cranial nerves
How may autonomic dysfunction in GBS manifest?
-Urinary retention
-Ileus
-arrhythmias
What criteria is used to diagnose GBS?
The Brighton criteria
Outline the 5 points in the Brighton criteria for diagnosing GBS
-Flaccid limb weakness
-Areflexia
-A monophasic course of less than 28 days
-albuminocytological dissociation in the CSF
-Suggestive findings in nerve conduction studies
-Absence of alternative diagnosis
What LP results would indicate GBS?
- High proteins (albuminocytological dissociation)
-Normal cell count
-glucose
Outline the management of GBS
- Supportive care
-VTE prophylaxis
-Iv immunoglobulins
-plasmapheresis if IVIG inappropriate
-Severe cases may develop respiratory failure and require intubation and ventilation and ICU admission
Describe the prognosis of GBS
-Recovery months- years
-function may return up to 5 years later
-Full recovery or minor persistent symptoms for most
- 20% left with a significant disability
5% mortality due to respiratory/ cardiovascular complications
Why does GBS cause respiratory complications?
Diaphragmatic weakness
Name 3 risk factors for GBS
-Infections
-Vaccinations (very small risk)
-surgery
Give 3 differentials for GBS
- Acute transverse myelitis
-Chronic inflammatory demyelinating polyneuropathy
-Botulism
How may acute transverse myelitis present similarly to GBS?
- rapid spinal cord dysfunction, which may mimic the ascending weakness seen in GBS
How does acute transverse myelitis differ from GBS?
-ATM has a clear spinal level
-bladder/ bowel dysfunction is more common in ATM
-MRI findings in ATM show a T2 weighted image with hyperintense lesions on the spinal cord
How is chronic inflammatory demyelinating polyneuropathy similar to GBS?
- they’re both peripheral polyneuropathies
How does chronic inflammatory demyelinating polyneuropathy differ from GBS?
-CIDP develops over at least 2 months, BGS more acute
-CIDP responds well to immuno-supression and may require long term treatment, GBS is usually self limiting
How does botulism differ from GBS?
- eyelid ptosis and fixed pupils are early signs of clostridium botulinum poisoning but not GBS
-History of ingesting food which has been canned at home, preserved or fermented
-Descending pattern f paralysis
What are the 2 different causes of encephalitis?
-infective
- autoimmune
What is the most common cause of encephalitis in children in the UK?
-HSV-1
- from cold sores
What is the most common cause of encephalitis in neonates in the UK?
HSV-2
-genital herpes, contracted during birth
Other than HSV, what other viruses can cause encephalitis?
-Varicella zoster virus
-Cytomegalovirus
-Epstein-barr virus
-enterovirus
-adenovirus
-influenza virus
-Polio, measles, mumps, rubella if unvaccinated
Which antibodies are associated with autoimmune encephalitis?
-anti-NMDA receptor antibodies
How can autoimmune encephalitis be treated?
-corticosteroids
-immune therapies
How may encephalitis present?
-altered consciousness
-altered cognition
-unusual behaviour
-acute onset of neurological symptoms
-acute onset of focal seizures
-fever above 38
-severe, persistent, diffuse headache
-meningeal irritation
What Investigations should be performed in suspected encephalitis?
-LP
-CT if LP contraindicated
-MRI after LP
-EEG if mild/ ambiguous symptoms
-Nasal and throat swabs
-HIV testing
What are the contraindications of LP?
-GCS below 9
-Haemodynamically unstable
-active seizures
-post ictal
- Signs of raised ICP
What would the CSF show in encephalitis?
- High lymphocytes
-viral DNA
Describe the management of encephalitis
-Acyclovir for HSV or VZV
-Ganciclovir for CMV
-Repeat LP’s for test of cure before stopping antivirals
List the complications of encephalitis
-Lasting fatigue and prolonged recovery
-change in personality or mood
-changes to memory or cognition
-Learning disability
-headaches
-chronic pain
-movement disorders
-sensory disturbance
-seizures
-hormonal imbalance
Roughly, there are 3 phases in the pathophysiology of encephalitis, what are these phases?
-entry of pathogen
-neuronal tissue invasion
-inflammatory response
What are the 2 possible mechanisms of pathogen entry in encephalitis?
-Haematogenous
-Neuronal retrograde transmission
Describe neuronal retrograde transmission and give an example of a virus which does this.
- Varicella zoster virus
-neurotropic virus enters the peripheral nerves and travel to the CNS
Describe neuronal tissue invasion in encephalitis pathophysiology.
-Viral replication inside neurons and glial cells induces cellular damage, causes necrosis and apoptosis of cells, causing neurological dysfunction
- Cytotoxic T-cells recognise and destroy infected cells, contributing to tissue damage
Describe the inflammatory response in encephalitis
-cytokines and chemokines released from affected cells trigger the acute immune response, macrophages and lymphocytes are recruited into the CNS
-The cerebral oedema causes raised ICP
Name 2 neurological complications which may arise from raised ICP
-coma
-seizures
How is meningitis similar to encephalitis?
-Fevere, headache, altered mental state, signs of meningeal irritation
What are the 3 differential diagnoses for encephalitis?
-Brain abscess
-stroke
-Brain abscess
What is more specific to meningitis than encephalitis?
-Neck stiffness
-photophobia
What is more specific to encephalitis than meningitis?
focal neurological deficit’s like aphasia or hemiparesis
What is more specific to a stroke than encephalitis?
-deficits related to specific vascular territories
-no systemic symptoms
How may a stroke present similarly to encephalitis?
focal neurological deficits
How may a brain abscess present similarly to encephalitis?
-Headache
-fever
-focal neurological deficits
What is the peak age of contracting chickenpox?
6-15
Is the herpes zoster virus different to the herpes simplex virus?
Yes
What 5 illnesses does the herpes zoster virus cause?
-Chicken pox
-shingles
-herpes zoster ophthalmicus
- Ramsay-Hunt syndrome
-Eczema herpeticum
Describe the rash seen in chickenpox
-Widespread
-erythematous
-vesicular
-blistering
-spreads outwards from trunk and face
-spreads over 2-5 days
At what stage will the rash in chickenpox indicate that the child is no longer infectious?
when it scabs over
How is chickenpox spread?
-Direct contact with lesions
- droplet
What illness other than chickenpox may someone come into contact with and then develop chickenpox?
Shingles
How long after coming into contact with herpes zoster will someone become symptomatic of chickenpox?
10 days- 3 weeks
When is chickenpox most infectious?
1-2 days before the rash appears
Name 4 signs and symptoms of chickenpox
-rash
-fever
-itch
-general malaise and fatigue
Name 5 possible complications of chickenpox
- Bacterial superinfection
-dehydration
-conjunctival lesions
-pneumonia
-encephalitis - Reactivation of virus as shingles or Ramsay Hunt syndrome
What makes developing a bacterial superinfection more likely in chickenpox?
using NSAIDs
How would encephalitis as a complication of chickenpox present?
Ataxia
If a pregnant lady has had chickenpox previously, is she at risk of developing antenatal chickenpox if exposed to herpes zoster?
No she would be immune
What can be used to protect pregnant women who aren’t immune to chickenpox but have come into contact with it?
Varicella zoster immunoglobulins
Until what week of gestation is someone at risk of developing congenital varicella syndrome?
28 weeks
What can be a consequence of a mother having chickenpox during delivery?
-life threatening neonatal infection
-Treat with acyclovir and varicella zoster immunoglobulins
Describe the management of chickenpox
-Usually self limiting and requires no support in generally healthy children
-acyclovir given in immunocompromised, adult (over 14 presenting within 24 hours of rash onset) and neonatal patients at risk of complications
-calamine lotion for itching
-keep cool and trim nails
What is the peak age of incidence for shingles?
70+ yrs
Is it possible for someone to have shingles without having had chickenpox previously?
Yes but it’s incredibly unlikely
-This is thought to be because the triggers of reactivation are so numerous it may be caused by a different process
Briefly describe the pathophysiology of shingles
- Initial infection
- varicella zoster remains dormant in the dorsal root or cranial nerve ganglia
-Trigger
-Virus multiplies along the affected sensory nerve until it reaches the skin
-The inflammation and destruction of the nerve leads to rash and neuropathic pain
List the possible triggers of the reactivation of the herpes zoster virus in shingles
- emotional stress
-immunosuppression via chemo or high dose steroids
-recent illness or surgery
-skin injury via sunburn or taruma
What are the 3 stages of the clinical features of shingles?
-Prodrome
-Infectious rash
-Resolution
Describe the clinical features seen in the prodrome stage of shingles
- Acute neuralgia
-non-specific symptoms
-enlarged lymph nodes
How long does the infectious rash last in shingles?
7-10 days
Describe the infectious rash seen in shingles
-single dermatome with a band like distribution
-Unilateral
-erythematous to macular to erythematous papules to vesicles and bullae by day 7
- vesicles become haemorrhagic or pustular near the end before crusting over
-pain in affected region
How long may crusted lesions in shingles take to crusts over?
up to 1 month
Name 5 differentials of shingles
-herpes simplex virus
-impetigo
-dermatitis herpetiformis
-drug eruptions
-contact dermatitis
How may herpes simplex present similarly to shingles?
may be recurrent, individual lesions may appear similar
How may you differentiate herpes simplex virus form shingles?
shingles: single band like distribution
herpes: clusters
How may impetigo present similarly to shingles?
initially erythematous sores which blister and burst
How may impetigo be differentiated from shingles?
Impetigo: painless, itchy, school children, mouth and nose
How may dermatitis herpetiformis present similarly to shingles?
Both are small, clustered papules and vesicles
How can you differentiate shingles from dermatitis herpetiformis?
dermatitis herpetiformis: symmetrical and bilateral (elbows, knees, buttocks, back and scalp< usually symmetrical and bilateral
How can rashes caused by drug eruptions be differentiated from shingles?
for drug related eruptions there will be a causative agent such as NSAID ABx, anti-epileptics
- This rash may be symmetrical and bilateral
How can a rash caused by contact dermatitis be distinguished from a rash caused by shingles?
Contact dermatitis: not painful but severely itchy
Describe the management for shingles
-Analgesia (for mild pain paracetamol, paracetamol+/- codeine, paracetamol +/- NSAID) (moderate-severe pain: amitriptyline, duloxetine gabapentin, pregabalin)
-Calamine lotion
-topical capsaicin
-cool compress
- Possibly antivirals
Describe antiviral therapy in shingles
- Give within 72hrs of rash onset if immunocompromised, non-truncal, moderate-severe pain
- Consider if 50+ to reduce risk of post herpetic neuralgia
-oral acyclovir, famciclovir, valaciclovir
give corticosteroids if giving antivirals in immunocompromised adults with severe, localised symptoms
Describe prevention for shingles
-Vaccination
-70+ yrs or earlier if predisposing condition
-single subcut dose
-contraindicated in immunocompromised, pregnancy and children as it’s a live vaccine
Describe what causes herpes zoster ophthalmicus
-Reactivation of the Varicella zoster virus in the opthalmic branch of the trigeminal nerve
Why is herpes zoster ophthalmicus concerning?
-Vision threatening infection
How does herpes zoster ophthalmicus present?
- Preherpetic neuralgia
-vesicular rash in the 1st division of the trigeminal nerve
What are the complications of herpes zoster ophthalmicus?
-Keratitis
-Uveitis
-glaucoma
-retinal necrosis
How is herpes zoster ophthalmicus diagnosed?
-fluorescent antibody testing
-Viral PCR
What is the management of herpes zoster ophthalmicus?
-Systemic antiviral therapy
-topical treatments
-possibly steroids
What is Ramsay Hunt syndrome also known as?
Zoster oticus
Describe what causes Ramsay Hunt syndrome
Reactivation of the varicella zoster virus in CN 7
What age is Ramsay Hunt syndrome likely to happen in?
70+yrs
How may Ramsay HUnt syndrome present?
-Severe otalgia
-Sudden ipsilateral facial paralysis (partial or complete)
-altered taste perception in ant. 2/3s tongue
-reduced lacrimation
-hyperacusis
-vestibular disturbances (vertigo or tinnitus)
Describe the otalgia seen in Ramsay Hunt syndrome
-Vesicular rash in the external auditory canal, auricle or mucous membrane of the oropharynx
What are the 3 differentials of Ramsay Hunt syndrome?
-Bell’s palsy
-Herpes simplex herpeticus
-Acute peripheral facial palsy
How is Bell’s palsy similar to Ramsay Hunt Syndrome?
Sudden onset unilateral facial paralysis
How is Bell’s palsy different to Ramsay Hunt syndrome?
-No otalgia
-No vesicular eruptions
-Quicker onset of symptoms
How is herpes simplex oticus similar to Ramsay Hunt syndrome?
-otalgia
-facial paralysis
How is herpes simplex oticus different to Ramsay Hunt syndrome?
-No vesicular eruptions in the auditory canal or auricle
-Systemic signs
How is Ramsay Hunt syndrome similar to acute peripheral facial palsy?
-sudden unilateral facial weakness/paralysis
How is Ramsay Hunt syndrome different to acute peripheral facial palsy?
Peripheral facial palsy:
-No rash
-ipsilateral ear pain
How is Ramsay Hunt syndrome managed?
-oral acyclovir
-corticosteroids
what was eczema herpeticum previously known as?
kaposi varicelliform eruption
What most commonly causes eczema herpeticum?
HSV-1
What is eczema herpeticum commonly associated with?
cold sores and patients with pre-existing skin conditions
Describe the presentation of eczema herpeticum
-Widespread painful, vesicular rash
-systemic symptoms
lymphadenopathy
Describe the rash seen in eczema herpeticum
- painful
-vesicular
-whole body
-itchy
-pustular
-contain fluid
-when it bursts it leaves small punched out ulcers with a red base
how is eczema herpeticum managed?
viral swabs
-acyclovir
What type of organism causes malaria?
Protozoa
What are the 4 different types of malaria?
-P. falciparum
-P. ovale
-P. vivax
-P. malariae
What is the most common and most severe type of malaria?
P.falciparum
Describe the general lifecycle of malaria sporozoites to schizonts
-Spread by female anopheles mosquitoes
-Mosquito feeds on an infected person and the parasites reproduce in the GIT of the bug, making sporozoites
-The mosquito bites someone else and injects them with sporozoites which travel to the liver
-The sporozoites reproduce asexually for 10 days in the liver, maturing into schizont
Describe the life cycle of malaria schizonts to merozoites
-Schizont become merozoites when they emerge from the liver
Describe the life cycle of malaria as merozoites
-merozoites spread from the liver to the blood, infecting the RBC’s
-Merozoites reproduce in RBC’s causing RBC rupture and releasing more merozoites
Which types of malaria can stay dormant for 4 years and through what mechanism do they do this?
-P. ovale and P. vivax
-They become hypnozoites in the liver and are not affected by normal antimalarial drugs
Which part of the parasites life cycle in malaria causes haemolytic anaemia?
The merozoites rupturing RBC’S
Each type of malaria has a different rupture and release cycle, how long is the rupture and release cycle of P. ovale and P. vivax, and what type of fever does this cause?
-48 hours
-tertian malaria
Each type of malaria has a different rupture and release cycle, how long is the rupture and release cycle of P. falciparum, and what type of fever does this cause?
- more frequent but irregular
-subtertian fever
Each type of malaria has a different rupture and release cycle, how long is the rupture and release cycle of P. malariae, and what type of fever does this cause?
-72 hours
-quartan
Who should you suspect of having malaria?
-Anyone who has travelled to an endemic area, incubation is usually 1-4 weeks however p.ovale and p. vivax can be dormant for up to 4 years
What may prolong the presentation of someone with malaria?
-partial immunity
-antimalarial prophylaxis
-symptoms may be gradual or abrupt
What are the symptoms of someone with malaria?
-Fever up to 41 degrees
-sweats
-rigors
-fatigue
-myalgia
-headache
-nausea
-vomiting
-headache
What are the signs of someone with malaria
-pallor
-hepatosplenomegaly
-jaundice
How is malaria diagnosed, and what do the results of this investigation tell us?
-Blood film
-Type of parasite and concentration
What stain is used in a blood film for malaria?
- Giesma
Which blood collection bottle is used to send a sample for a blood film?
-EDTA
-same as for FBC
What type of blood film is used when diagnosing malaria?
- thick (sensitive to malaria)
-Thin ( determines species)
How many blood films must be done to exclude malaria?
-3 on 3 consecutive days due to the cyclical nature of merozoite eruption
What is the most likely treatment for malaria?
- admission
-if complicated admission to ICU or HDU
-Artesunate 1st line
-Iv quinine dihydrochloride
What is a common side effect of artesunate?
haemolysis
List the complications of malaria
-Cerebral malaria
-seizures
-reduced consciousness
-AKI
-pulmonary oedema
-DIC
-Severe haemolytic anaemia
-multi-organ failure
-metabolic acidosis
What precautions should someone take when traveling to a malaria endemic area?
- mosquito spray
-mosquito nets and barriers
-seek medical advice if symptomatic
-antimalarial medication
Name 4 antimalarial medications
-Progranulin with atovaquone
-doxycycline
-mefloquine
-chloroquine with proguanil
How is progranulin with atovaquone taken as prophylaxis and what are its pros and cons?
- 2days before travelling 7 days after
- most expensive
-least side effects
How is doxycycline taken as prophylaxis for malaria and what are it’s cons
- 2 day -4 weeks after travel
-increased sunlight sensitivity
-diarrhoea and thrush
How is mefloquine used as prophylaxis and what are its cons
- once a week for 2 weeks before - 4 weeks after travelling
- depression, anxiety, abnormal dreams, seizures of psychosis
