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)
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
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).
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
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
clinical course of GBS
acute
- Starts with radiculopathy (back ache) - before symptoms properly start
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
