Brain Abscess; Hydrocephalus; MG & LES Flashcards
Brain abscess is a focal collection of pus within the brain parenchyma. Abscesses can develop as a result of: [3]
Brain abscesses primarily originate from:
- contiguous spread of infection from sinusitis, otitis media, or dental infections;
- haematogenous spread from distant sources (e.g., endocarditis, pulmonary infections);
- or direct inoculation from trauma or neurosurgical procedures
Brain abscess pathogenesis involves four stages. What are they? [4]
The pathogenesis involves four stages:
* early/initial cerebritis (1-3 days),
* late cerebritis (4-9 days),
* early capsule formation (10-13 days), and
* capsule formation (14 days onwards).
The clinical presentation of a brain abscess can be variable, largely depending on the abscess location, size, the presence of cerebral oedema, and the host’s immune status. However, three classical symptoms are often associated with brain abscess.
Describe what they are are? [3]
Whar are other presenting features? [3]
Headache:
- This is the most common symptom, reported in 50-70% of cases. It is typically described as dull, constant and progressively worsening, often localised to the site of the abscess.
- The headache is due to increased intracranial pressure or irritation of the meninges.
Focal Neurological Deficits:
- These occur in around half of patients with brain abscesses and depend on the abscess location. Such deficits may include hemiparesis, language or speech disorders (e.g., aphasia or dysarthria), visual field defects, or other focal neurological signs.
Fever:
- Fever is present in approximately 50% of patients and may be accompanied by other signs of systemic infection such as chills or night sweats.
Also:
- Lethargy
- Seizures (due to cortical irritation)
- Papilloedema
How would you investigate for a brain abscess? [3]
MRI with gadolinium contrast is superior in detecting early cerebritis
CT is useful for detecting complications like hydrocephalus and brain herniation.
Stereotactic needle aspiration can both aid diagnosis and serve as treatment.
NB: Lumbar puncture is contraindicated due to risk of brain herniation.
What are is the mx of brain abscess? [3]
surgery
* a craniotomy is performed and the abscess cavity debrided
* the abscess may reform because the head is closed following abscess drainage.
IV antibiotics: IV 3rd-generation
* cephalosporin + metronidazole
intracranial pressure management:
* dexamethasone
What is the classic presentation of normal pressure hydrocephalus? [3]
Wet, wacky and wobbly:
gait disturbance
- unsteady, wide-based gait often described as ‘magnetic,’ where the feet appear to be stuck to the floor.
- It primarily affects the initiation of gait (start hesitation), with patients demonstrating difficulty in beginning to walk and in turning.
* gait may transition to short, shuffling steps, with decreased stride length and increased stride width. Falls become frequent, often without a clear precipitant.
cognitive impairment:
- slowness of thought
- memory difficulties
- difficulties with problem-solving tasks
urinary incontinence:
- often characterised by urgency and frequency, with progression to incontinence usually occurring later in the disease process.
What is the most common cause of hydrocephalus? [1]
What are further causes? [3]
The most common cause of hydrocephalus is aqueductal stenosis, leading to insufficiency drainage of CSF
- This blocks the normal flow of CSF out of the third ventricle, causing CSF to build up in the lateral and third ventricles.
Also caused by:
* Arachnoid cysts can block the outflow of CSF if they are large enough
* Arnold-Chiari malformation is where the cerebellum herniates downwards through the foramen magnum, blocking the outflow of CSF
* Chromosomal abnormalities and congenital malformations can cause obstruction to CSF drainage.
How do you investigate for normal pressure hydrocephalus? [1]
Imaging
* hydrocephalus with an enlarged fourth ventricle
* in addition to the ventriculomegaly there is typically an absence of substantial sulcal atrophy
Describe how you manage NPH [2+]
Shunt Surgery
- Ventriculoperitoneal shunting is the most common surgical intervention, with adjustable valve systems preferred due to their ability to regulate cerebrospinal fluid flow based on individual patient needs.
- Regular monitoring post-surgery is important to detect complications such as infection, overdrainage, underdrainage, and mechanical shunt failure.
Non-Surgical Management
* While shunting is the primary treatment modality, non-surgical options may include lifestyle modifications such as avoiding medications that can exacerbate symptoms (e.g., sedatives, anticholinergics).
* Physiotherapy may be beneficial in managing gait disturbances.
Describe the complications of NPH [2]
Ventriculo-peritoneal shunt complications:
- These include infection, obstruction, over-drainage leading to subdural haemorrhages and shunt malfunction
- Regular follow-up and monitoring are necessary to mitigate these risks.
Surgical complications:
- Any surgical intervention carries inherent risks such as anaesthetic reactions, bleeding, infection or damage to surrounding structures during surgery.
VP shunt complications:
- [] haemorrhage during shunt related surgery
Intraventricular haemorrhage during shunt related surgery
What is meant by Lambert-Eaton syndrome? [1]
Lambert Eaton syndrome (LES) is a rare autoimmune disorder in which antibodies are formed against pre-synaptic voltage-gated calcium channels in the neuromuscular junction.
A significant proportion of those affected have an underlying malignancy, most commonly small cell lung cancer.
It is therefore regarded as a paraneoplastic syndrome.
How do you investigate for LES? [1]
EMG
- incremental response to repetitive electrical stimulation
How does a patient with Lambert-Eaton syndrome present? [5]
Weakness in muscles of the proximal arms and legs
Weakness effects legs more than arms (causes difficulty climbing stairs / rising from seat)
Weakness is noramlly relieved temporarily after start of exercise
Autonomic dysfunction, causing dry mouth, blurred vision, impotence and dizziness
Reduced or absent tendon reflexes
NB:
- ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)
Lambert-Eaton syndrome arises due to which type of lung cancer?
small-cell lung cancer
large cell lung cancer
adenocarcinoma
squamous cell cancer
Lambert-Eaton syndrome arises due to which type of lung cancer?
small-cell lung cancer
large cell lung cancer
adenocarcinoma
squamous cell cancer
Explain how you treat Lambert-Eaton syndrome [4]
treatment of underlying cancer
immunosuppression, for example with prednisolone and/or azathioprine
Amifampridine works by blocking voltage-gated potassium channels in the presynaptic membrane, which in turn prolongs the depolarisation of the cell membrane and assists calcium channels in carrying out their action.
intravenous immunoglobulin therapy and plasma exchange may be beneficial
A 40-year-old man is investigated for increasing shortness of breath. He has smoked for the past 25 years. Pulmonary function tests are performed and are reported as follows:
FEV1 1.4 L (predicted 3.8 L)
FVC 1.7 L (predicted 4.5 L)
FEV1/FVC 82% (normal > 75%)
Which one of the following disorders is most consistent with these results?
Asthma
Bronchiectasis
Neuromuscular disorder
Chronic obstructive pulmonary disease
Laryngeal malignancy
Neuromuscular disorder: Lambert Eaton syndrome
Shows a restrictive pattern on spirometry
Describe what is meant by mysanthenia gravis [3]
Myasthenia gravis (MG) is a chronic autoimmune condition of the post-synaptic membrane at the neuromuscular junction in skeletal muscle
Circulating antibodies against the nicotinic acetylcholine receptor (AChR) or associated proteins impair neuromuscular transmission
These antibodies also activate the complement system within the neuromuscular junction, leading to cell damage at the postsynaptic membrane, further worsening symptoms.
Describe the classic clinical presentation of mysanthenia gravis [+]
The critical feature is weakness that worsens with muscle use and improves with rest. Symptoms are typically best in the morning and worst at the end of the day.
The symptoms most affect the proximal muscles of the limbs and small muscles of the head and neck, with:
- Difficulty climbing stairs, standing from a seat or raising their hands above their head
- Extraocular muscle weakness, causing double vision (diplopia)
- Eyelid weakness, causing drooping of the eyelids (ptosis)
- Weakness in facial movements
- Difficulty with swallowing
- Fatigue in the jaw when chewing
- Slurred speech
- generalized weakness, including respiratory muscle involvement, which can be life-threatening (myasthenic crisis).
Which three antibodies are found in MG? [3]
Acetylcholine receptor (AChR) antibodies
Muscle-specific kinase (MuSK) antibodies
Low-density lipoprotein receptor-related protein 4 (LRP4) antibodies
MuSK and LRP4 are important proteins for the creation and organisation of the acetylcholine receptor. Destruction of these proteins leads to inadequate acetylcholine receptors.
MG has a strong link with which other pathology? [1]
There is a strong link with thymomas (thymus gland tumours). 10-20% of patients with myasthenia gravis have a thymoma. 30% of patients with a thymoma develop myasthenia gravis.
What investigations do you conduct for MG [4]
Ztf:
.1. Antibody testing:
- AChR antibodies (around 85%)
- MuSK antibodies (less than 10%)
- LRP4 antibodies (less than 5%)
.2. A CT or MRI of the thymus gland is used to look for a thymoma.
.3. Edrophonium test:
- Patients are given intravenous edrophonium chloride
- Normally, cholinesterase enzymes in the neuromuscular junction break down acetylcholine. Edrophonium blocks these enzymes, reducing the breakdown of acetylcholine
- As a result, the level of acetylcholine at the neuromuscular junction rises, temporarily relieving the weakness.
- A positive result suggests a diagnosis of myasthenia gravis.
PM:
Repetitive nerve stimulation (RNS):
- repetitive electrical stimulation of a peripheral nerve while recording the compound muscle action potentials (CMAPs) from a target muscle.
- A decline in the amplitude of CMAPs after repetitive nerve stimulation, known as decrement, supports the diagnosis of MG.
Single-fiber electromyography (SFEMG):
- This is the most sensitive test for MG, which measures the variability in the time it takes for individual muscle fibres to respond to nerve stimulation (jitter) and the failure of some fibres to respond at all (blocking).
- Abnormal jitter and blocking are indicative of impaired neuromuscular transmission in MG.
NB:
- due to the potential side effects and limited specificity, edrophonium test has been largely replaced by more specific and sensitive diagnostic tests.
Describe 4 treatment options for MG [4]
Pyridostigmine is a cholinesterase inhibitor that prolongs the action of acetylcholine and improves symptoms. First-line
Immunosuppression (e.g., prednisolone or azathioprine) suppresses the production of antibodies
Thymectomy can improve symptoms, even in patients without a thymoma
Rituximab (a monoclonal antibody against B cells) is considered where other treatments fail
Intravenous immunoglobulin (IVIg) or plasma exchange may be considered in severe cases or during myasthenic crisis.
MG presents with what results on spirometry? [1]
Restrictive pattern
How do you differentiate LES vs MG? [3]
Clinically, LES typically presents with proximal muscle weakness that improves with repeated use (unlike MG where symptoms worsen with use).
Autonomic symptoms such as dry mouth or impotence are common in LES but rare in MG.
Ophthalmoplegia and bulbar symptoms are less common in LES compared to MG.
Management of Myasthenic Crisis? [2]
In a myasthenic crisis, immediate hospitalisation is required.
Intensive respiratory support may be necessary, including intubation and mechanical ventilation if there is impending respiratory failure.
Rapid short-term symptom control can be achieved by plasma exchange or IVIg.
Describe possible risks of overmedication w treating MG? [1]
Cholinergic Crisis:
- Overmedication with anticholinesterase drugs can cause muscle fasciculations, increased salivation, diarrhoea, and bradycardia. Differentiation from myasthenic crisis is critical for appropriate management.
Pyridostigmine
Pyridostigmine - acetylcholinesterase inhibitor
edrophonium
- Tensilon test: IV edrophonium reduces muscle weakness temporarily - not commonly used any more due to the risk of cardiac arrhythmia
Acetylcholinesterase inhibitor
proximal muscle weakness (repeated contractions lead to increased strength), hyporeflexia, autonomic symptoms
A 65-year-old man with lung cancer develops muscle weakness in his legs. He finds that repeated muscle contractions lead to increased muscle strength. Hyporeflexia and weakness are found on examination - Lambert-Eaton syndrome
Lecture:
Describe the EMG seen in MG c.f. non-MG person [2]
A normal NMJ has enough reserve to generate normal CMAP (compound muscle action potential)
A myasthenic NMJ doesn’t have enough reserve to generate normal CMAPs (decrement >10%) due to blocking antibodies at post-synaptic Acetylcholine receptors.
Lecture
Describe how someone in MG crisis would present in an assessment ?
Assessment:
- Tiring in conversation,
- Increased RR
- accessory muscles
- unable to lie flat (FVC reduces 20% on lying down)
- ** weak neck flexion** (same spinal levels as phrenic nerve C2-4).
In MG Resp. crisis - what investigation would you do and how would this inform your mx plan? [2]
Assessment: BEDSIDE SPIROMETRY - FVC (not peak flow/FEV1):
- >20ml/kg (1.5-2.0L) – on repeated measures – ABG and Rapid response/anaesthetic review – consideration of HDU/ITU
- >15ml/kg (1L) – urgent Rapid response/anaesthetic review and ITU transfer
