5- Neurology (Less acute: Epilepsy, Myasthenia Gravis, GBS, MND)) Flashcards
epilepsy background
- Umbrella term – tendency to have seizures
o Seizures: transient episodes of abnormal electrical activity in the brain
o EEG change, 2 unprovoked attackes
o Many types - Diagnosis: based on characteristic of the seizure episodes, MRI and EE`g
define epilepsy
Epilepsy is defined as having two or more unprovoked seizures.
secondary causes of seizures
- stroke.
- brain tumour
- severe head injury
- drug abuse or alcohol misuse
- encephalitis
- lack of oxygen during birth
- hypoglycaemia
secondary causes of seizures
- stroke.
- brain tumour
- severe head injury
- drug abuse or alcohol misuse
- encephalitis
- lack of oxygen during birth
- hypoglycaemia
investigations for epilepsy
- Electroencephalogram (EEG)
o Can show typical patterns in different forms of epilepsy and support diagnosis - MRI brain
o Visualise structures of the brain
o Diagnose structural problems e..g tumours - ECG to exclude problems with the heart
electrolyte disturbances which can cause seizures
hyponatremia, hypernatremia, hypoglycaemia, hyperglycaemia, hypocalcemia, and hypomagnesemi
management of epilepsy general
Aim: to be seizure free on minimum anti-epileptic medications. Ideally monotherapy with single anti-epileptic drug
main drug used for maintenance of epilepsy
Sodium Valproate
This is a first line option for most forms of epilepsy (except focal seizures).
pathophysiology of sodium valproate
works by increasing the activity of GABA, which has a relaxing effect on the brain.
side effects of sodium valproate
- Teratogenic so patients need careful advice about contraception (avoid in women of childbearing age unless no alternatives)
- Liver damage and hepatitis
- Hair loss
types of seizures
- Generalised Tonic-CLonic Seizures
- Focal seizures
- Abscence seizures
- Myoclonic seizures
- Infantile spasms (West syndrome)
Generalised Tonic-Clonic Seizures
These are what most people think of with an epileptic seizure. There is loss of consciousness and tonic (muscle tensing) and clonic (muscle jerking) episodes. Typically the tonic phase comes before the clonic phase. There may be associated tongue biting, incontinence, groaning and irregular breathing.
After the seizure there is a prolonged post-ictal period where the person is confused, drowsy and feels irritable or depressed.
Management of tonic-clonic seizures is with:
* First line: sodium valproate
* Second line: lamotrigine or carbamazepine
Focal Seizures
Focal seizures start in temporal lobes. They affect hearing, speech, memory and emotions. There are various ways that focal seizures can present:
- Hallucinations
- Memory flashbacks
- Déjà vu
- Doing strange things on autopilot
One way to remember the treatment is that they are the reverse of tonic-clonic seizures:
- First line: carbamazepine or lamotrigine
- Second line: sodium valproate or levetiracetam
Absence Seizures
Absence seizures typically happen in children. The patient becomes blank, stares into space and then abruptly returns to normal. During the episode they are unaware of their surroundings and won’t respond. These typically only lasts 10-20 seconds. Most patients (> 90%) stop having absence seizures as they get older.
Management is:
* First line: sodium valproate or ethosuximide
Atonic Seizures
Atonic seizures are also known as “drop attacks”. They are characterised by brief lapses in muscle tone. These don’t usually last more than 3 minutes. They typically begin in childhood. They may be indicative of Lennox-Gastaut syndrome.
Management is:
* First line: sodium valproate
* Second line: lamotrigine
Myoclonic Seizures
Myoclonic seizures present as sudden brief muscle contractions, like a sudden “jump”. The patient usually remains awake during the episode. They occur in various forms of epilepsy but typically happen in children as part of juvenile myoclonic epilepsy.
Management is:
* First line: sodium valproate
* Other options: lamotrigine, levetiracetam or topiramate
Infantile spasms
This is also known as West syndrome. It is a rare (1 in 4000) disorder starting in infancy at around 6 months of age. It is characterised by clusters of full body spasms. There is a poor prognosis: 1/3 die by age 25, however 1/3 are seizure free.
It can be difficult to treat but first line treatments are:
* Prednisolone
* Vigabatrin
carbamazepine
This is first line for focal seizures. Notable side effects are:
* Agranulocytosis
* Aplastic anaemia
* Induces the P450 system so there are many drug interactions
Phenytoin
Notable side effects:
* Folate and vitamin D deficiency
* Megaloblastic anaemia (folate deficiency)
* Osteomalacia (vitamin D deficiency)
Ethosuximide
Notable side effects:
- Night terrors
- Rashes
Lamotrigine
Notable side effects:
- Stevens-Johnson syndrome or DRESS syndrome. These are life threatening skin rashes.
- Leukopenia
when can antiepileptic medication be stopped
stop antiepileptics if seizure free for 2 years
which type of epilepsy will require lifelong antiepileptics even if seizure free for 2 years
if sezires caused by scarring of the brain e.g. due to stroke, tumour (if MRI abnormal)
Status epilepticus
Background
- Medical emergency
- Seizure lasting more than 5 minutes or more than 3 seizures in one hour
Management of status epilepticus
Management of status epileptics in the hospital:
Take an ABCDE approach:
- Secure the airway
- Give high-concentration oxygen
- Assess cardiac and respiratory function
- Check blood glucose levels
- Gain intravenous access (insert a cannula)
- IV lorazepam 4mg, repeated after 10 minutes if the seizure continues
- If seizures persist: IV phenobarbital or phenytoin
Medical options in the community:
* Buccal midazolam
* Rectal diazepam
myasthenia gravis background
- Autoimmune
- Causes muscle weakness that gets worse with activity and improves with rest
- FATIGUABILITY IS KEY WORD
What is the progression of juvenile myoclonic epilepsy?
JME typically begins in adolescence. Although the reported age of onset varies from 6 years up to 36 years, symptoms typically begin in adolescents, with a peak age most commonly of 12–18 years. Why the onset of this genetic disorder is delayed until adolescence is unclear
syndromes associated with epilepsy
West syndrome is a constellation of symptoms characterized by epileptic/infantile spasms, abnormal brain wave patterns called hypsarrhythmia and intellectual disability.
Rasmussen’s encephalitis (RE) is a very rare, chronic inflammatory neurological disease that usually affects only one hemisphere (half) of the brain. It most often occurs in children under the age of 10 but can also affect adolescents and adults.13
Progressive myoclonic (juvenile)
Angelman syndrome
pathophysiology of myasthenia gravis
- Motor neurones communicate with muscles at the NMJ
- Presynaptic neurones release NT (ACh) into the synapse
- ACh travels across the synapse and binds to receptors on the post-synaptic membrane -> causes initiation of cascade which produces muscles contraction
Two major types of MG
1) 85%- Acetylcholine receptor antibodies
- Blocks the receptor and prevents ACh from being able to stimulate the receptor and trigger muscle contraction
- Antibodies also activate complement system within NMJ – leading to damaged cells at the postsynaptic membranes -> worsens symptoms
2) 15%- Affect proteins (MuSK and LRP4) which are important for creation and organisation of ACh receptors-> therefore their destruction by autoantibodies causes symptoms of MG due to inadequate ACh receptors
- Muscle-specific kinase (MuSK) antibodies
- Low-density lipoprotein receptor-related protein 4 (LRP4) antibodies
Why are symptoms worse during muscle activity?
- As the receptors are used more during muscle activity, more of them become blocked up.
- This leads to less effective stimulation of the muscle with increased activity.
- There is more muscle weakness the more the muscles are used. This improves with rest as more receptors are freed up for use again.
Risk factors for MG
-
Thymoma
o 10-20% of patient with MG have a thymoma
o 20-40% of patients with thymoma develop MG -
Gender
o Interestingly myasthenia gravis affects men and women at different ages. Typical patients are either a woman under the age of 40 or a man over the age of 60.
presentation of MG
Severity varies dramatically from mild to life threatening.
Characteristic description: weakness that gets worse with muscle use and improve with rest e.g. minimal in the morning and worse at the end of the day.
The symptoms most affect the proximal muscles and small muscles of the head and neck. It leads to:
- Extraocular muscle weakness causing double vision (diplopia)
- Eyelid weakness causing drooping of the eyelids (ptosis)
- Weakness in facial movements
- Bulbar sympatoms- dysarthria, dysphagia, dysphonia
- Fatigue in the jaw when chewing ‘moving tongue around mouth’
- Slurred speech
- Progressive weakness with repetitive movement
Not affected
pupils affected
no sensory or reflex loss
Examination for MG
There are a few ways to elicit fatiguability in the muscles:
- Repeated blinking will exacerbate ptosis
- Prolonged upward gazing will exacerbate diplopia on further eye movement testing
- Repeated abduction of one arm 20 times will result in unilateral weakness when comparing both sides
Check for a thymectomy scar.
Test the forced vital capacity (FVC).
Investigations for MG
- Blood tests for specific antibodies: ACh-R, MuSK, LRP4
- CT or MRI thorax for thymoma
- EMG- reptitive nerve stimualtion- fatiguing the nerve electronically
- Edrophonium test (tensilon test- fatiguability test)
- ICE and rest test- ptosis
edrophonium test
- Facial weakness is provided by repeated facial movements (left)
- Edrophonium chloride (or neostigmine) dose given via IV
o **Short acting anticholinesterase- increases **conc of ACh in synaptic cleft by inhibiting cholinesterase (which breaks ACh down)
o Positive test-facial weakness will be rapidly relieved - Test should always be done in a hospital where there are resuscitation facilities and a drawn up syringe of atropine (a muscarinic receptor antagonist) present
management of MG
- Reversible acetylcholinesterase inhibitors (usually pyridostigmine (first line) or neostigmine (ITU)) increases the amount of acetylcholine in the neuromuscular junction and improve symptoms
Corticosteroids for Immunosuppression (e.g. prednisolone or azathioprine) suppresses the production of antibodies
–> steroid sparing - azothioprine - Thymectomy can improve symptoms even in patients without a thymoma
Monoclonal antibodies
* Rituximab is a monoclonal antibody that targets B cells and reduces the production of antibodies. It is available on the NHS if standard treatment is not effective and certain criteria are met.
* Eculizumab is a monoclonal antibody that targets complement protein C5. This could potentially prevent the complement activation and destruction of acetylcholine receptors. There is ongoing research and debate about whether the evidence is strong enough to offer it on the NHS. It is currently not recommended by NICE
severe complication of myasthenia gravis
myasthenic crisis
myasthenic crisis may look like
cholinergic crisis e.g. if given too much pyristigamine
myasthenic crisis
It can be life threatening. It causes an acute worsening of symptoms, often triggered by another illness such as a respiratory tract infection. This can lead to respiratory failure as a result of weakness in the muscle of respiration.
Presentation
- slack mouth
- weak neck
- unsafe swawllow
- frooling
- nasal speech
Do a FVC using bedisde spirometry and do a blood gas
Management
- Patients may require non-invasive ventilation with BiPAP or full intubation and ventilation.
- Medical treatment of myasthenic crisis is with immunomodulatory therapies such as IV immunoglobulins and plasma exchange.
Other complications
- DVT
- respitaotyr failure
- apsiration
- resp infection
Guillain Barre syndrome
Background
- Acute paralytic polyneuropathy triggered by infection -> affects peripheral nervous system
- Peripheral neuropathy related to the myelin sheath damage related to recent infection
- most commonly demyelinating
- potentially deadly
- commonest acute flaccid paralysis
can affect: motor, sensory and autonomic
causes of Guillain Barre syndrome
Post infectious:
- Epstein-Barr virus
- Campylobacter jejuni
- Cytomegalovirus
pathophysiology of Guillain Barre syndrome
- Occurs due to molecular mimicry
- B cells of the immune system create antibodies against the antigens on the pathogen that causes the preceding infection
- These antibodies also match proteins on nerve cells -> they may target proteins on the myelin sheath of the motor nerve cell or nerve axon
Typical story
- 1-2 wees after immune system stimulation
e.g. URTI, GI INFECTION, ALSO TRAUMA, SURGERY VACCINATION, PREGANCY
- Mimicry (cross reaction) with schwann cells
- T cell sensitisation damaging (myelin)
- impaired neurotransmission to the periphery
presentation of Guillain Barre syndrome
Acute, symmetrical, ascending weakness and can also cause sensory symptoms
FLACCID PARALYSIS
- Symmetrical ascending (not always) weakness (starting at the feet and moving up the body)
- Often starts with back pain due to radiculopathy before other symptoms start
- Reduced reflexes
- There may be peripheral loss of sensation or neuropathic pain
- It may progress to the cranial nerves and cause facial nerve weakness
- Can have autonomic dysfunction if affecting the ANS e.g. syncope
REQUIRED
- PROGRESSIVE WEAKNESS IN BOTH ARMS AND LEGS
- HYPOREFLEXIA
- Recovery must begin 2-4 weeks after progression ceases
clinical course of GBS
acute
- Starts with radiculopathy (back ache) - before symptoms properly start
investigations for GBS
- Clinical diagnosis
- Nerve conduction studies (reduced signal through nerves)
- Lumbar puncture for CSF (raised protein with normal cell count and glucose)
Management of GBS
- IV immunoglobulins- KEY
- Plasma exchange (alternative to IV IG)- plasmapheresis
- Supportive care e.g. nutrition and hydration
- VTE prophylaxis (pulmonary embolism is a leading cause of death)
In severe cases with respiratory failure patients may need intubation, ventilation and admission to the intensive care unit.
prognosis and complications for GBS
tell them most people make a fulll recoveyr, however some people may need some support breathing in ITU
- 80% full recovery
- 15% left with some neurological disability
- 5% die
Complications
Pain
DVT
SIADH
renal failure
hypercalcaemia (immobility
Motor neurone disease
Background
- Umbrella term that encompasses a variety of specific diagnoses
- Key features
o Progressive
o Fatal condition
o Where motor neurones stop functioning
o No affect on sensory neurones , therefore no sensory symptoms
Types of MND
1) Amyotrophic lateral sclerosis (ALS)
- Most common
- Specific motor neurone disease
- Stephen Hawking
2) Progressive bulbar palsy
- Primarily affects muscles of talking and swallowing
3) Progressive muscular atrophy
4) Primary lateral sclerosis
Pathophysiology of MND
- There is a progressive degeneration of both upper and lower motor neurones.
- The sensory neurones are spared.
- The exact cause is unclear although several mechanisms have been considered.
risk factors for MND
- Typical presentation
o Late middle aged (e.g. 60) man
o With affected relative - There is a genetic component and many genes have been linked with an increased risk of developing the condition.
o Taking a good family history is important as around 5-10% of cases are inherited. - There also seems to be an increased risk with
o Smoking
o Exposure to heavy metals
o Certain pesticides
Presentation of MND
Does not affect mental functioning or the senses (such as seeing or hearing)
- Progressive weakness of muscles throughout the body affecting the limbs, trunk, face and speech
- Weakness often first noticed in upper limbs
- Increased fatigue when exercising
- Clumsiness, dropping things, tripping over
- Dysarthria
- UMN and LMN signs
signs of lower motor neurone disease
- muscle wasting
- reduced tone
- fasciulations
- reduces reflexes
signs of upper motor neurone disease
- increased tone or spasticity
- brisk reflexes
- upgoing plantar responses
investigations for MND
- Clinical diagnosis
- Diagnosis only made by specialist when there is certainty
management of MND
No effective treatments for halting or reversing progression of the disease
Drug
-
Riluzole
o Can slow progression and extend survival by a few months in ALS -
Edaravone
o Used in US and not UK
o Potential to slow progression of disease
Supportive
- Non-invasive ventilation at night
- Palliative
Prognosis
- Patient will die between 2-3 years after diagnosis
complications of both MG and GBS
type 2 respiratory failure
driving laws UK after seizures
- Secondary seizure (proveds) – stop driving for 6 motnhs
- Unprovoked (e.g. epilepsy)– 12 months
