Movement disorders and epilepsy Flashcards
Essential tremor
a) Diagnostic criteria - definite vs probable
b) vs. PD tremor
c) vs. dystonic tremor
d) Drugs/conditions that may cause physiological tremor
e) Treatment
a) Definite:
- Postural tremor of moderate amplitude is present in at least one arm
- Tremor of moderate amplitude is present in at least one arm during at least four tasks, such as pouring water, using a spoon to drink water drinking water, finger-to-nose manoeuvre, and drawing a spiral.
- Tremor must interfere with at least one activity of daily living.
- Medications, hypothyroidism, alcohol, and other neurological conditions are not the cause of tremor
Probable:
- Tremor of moderate amplitude is present in at least one arm during at least four tasks, or head tremor is present.
- Medications, hyperthyroidism, alcohol, and other neurological conditions are not the cause of tremor.
b) - Tends to be symmetrical (PD asymmetrical)
- Tends to worsen on action like handwriting or drinking cup of tea (PD may improve with action, worse with distractibility)
- Head tremor - “yes-yes” or “no-no” (head tremor rare in PD), and sometimes involvement of the voice
- Absence of extra-pyramidal signs
- Family history (50% cases are autosomal dominant)
- DAT scan normal in ET
- PD tremor improves with L-dopa
- Alcohol/beta-blockers improve ET. Anxiety/stress worsen it
- Archimedes spiral test assesses direction and amplitude of the tremor
c) - Dystonic tremors often have visible dystonia, e.g. cervical torticollis
- Dystonic tremors are ‘jerky’ rather than rhythmic
- Dystonic tremors often just affect one muscle group rather than ET which is usually bilateral
d) - β-agonists, valproate, thyroxine, TCAs, SSRIs, ciclosporin, lithium, alcohol
- Thyrotoxicosis, hypothermia, hypoglycaemia, phaeochromocytoma
e) β-blockers (e.g. propanolol), topiramate, or primidone (a barbiturate)
PD presentation - which is a worse prognostic feature as a presenting symptom, tremor or postural instability?
Postural instability carries a worse prognosis
Psychogenic tremor
- clinical features
- Abrupt onset, maximal at onset
- Likely has periods tremor-free and will terminate of its own accord
- Distractible
- Presence of other functional disorder/somatisation/mental health dx
O/E
- Entrainment - getting them to tap out rhythm that is different to frequency of tremor - results in tremor changing to this frequency as it is difficult to tap out 2 different frequencies
- Coactivation - during passive movement of the limb, there may be increased tone. Once the increased tone disappears, so too does the tremor
CJD
a) Diagnostic criteria for probable CJD (3 stages)
b) Causes
c) Investigations
d) Management
a) Must meet following criteria…
1) Progressive dementia, AND
2) At least two of:
- Myoclonus
- Visual or cerebellar disturbance
- Pyramidal/extra-pyramidal signs
- Akinetic mutism, AND
3) - Abnormal EEG, OR
- CSF positive for 14-3-3 protein and duration to death less than 2 years, OR
- High signal MRI abnormality in caudate nucleus/putamen on FLAIR, OR
- Positive brain biopsy
b) Prion disease, may be:
- Sporadic (80%) - no clear cause
- Variant (vCJD)* - same cause as mad cow disease (BSE), from ingesting meat of infected cows
- Familial - autosomal dominant
- Iatrogenic - most from growth hormone injections pre-1985 (extracted from pituitary glands of infected corpses. Nowadays, all GH is artificially manufactured), also risk from organ donation/blood transfusion
- A study published in October 2013 that tested random tissue samples suggested around 1 in 2,000 people in the UK population may be infected with vCJD, but show no symptoms to date
c) Routine bloods etc to r/o other cause
LP - for CSF 14-3-3, and for Real-time quaking-induced conversion (RT-QuIC)* to detect misfolded protein (prion)
MRI brain
Brain biopsy if diagnostic uncertainty
- Also used for other protein misfolding detection - e.g. alpha-synuclein in Parkinsons, tau in CTE and Alzheimers
d) Supportive
Antiepileptics in pregnancy
a) Which is the safest?
b) Phenytoin - effects on foetus
c) Valproate - effects on foetus
a) Lamotrigine
- note also, that multiple antiepileptics are more dangerous than monotherapy
- also, that seizures during pregnancy can result in foetal death so patients should continue AEDs during pregnancy
b) Fetal Hydantoin Syndrome (FHS):
- Fingers, toes and nails are hypoplastic
- Heart defects
- Stunted growth, cleft palate/lip
c) Fetal valproate syndrome (1st trimester exposure)
- Neural tube defects
- Arachnodactyly
- Hypospadias
- growth defects
Frontal lobe epilepsy
a) Presentation
b) EEG
a) - Abnormal limb movements (e.g. cycling movements)
- Occurs mainly at night
b) EEG often normal, even during seizure
Especially due to poor coverage of the deep sulci of frontal lobes by the EEG electrodes
Myotonic dystrophy
a) What is myotonia, how is it elicited?
b) Other features
c) Age of onset
d) Inheritance
a) Inability of muscle to relax after use, may elicit through thenar eminence percussion or handshake/grip release
b) - Progressive muscle weakness, stiffness and wasting (more distal in type 1 and proximal in type 2 - like RTA), affects eyes commonly
- Cataracts
- Cardiomyopathy
- Type 2 diabetes
c) 20s - 30s
d) Autosomal dominant condition causing trinucleotide repeat expansions:
- Type 1 = DMPK gene (Ch 19)
- Type 2 = CNBP gene
Parkinson-plus syndromes (vs PD)
a) PSP
b) CBS
c) MSA
PSP: (the man from B6)
- Postural instability, frequent falls
- Speech problems (slow, dysarthric), swallow problems, spasticity, stiffness, cognitive problems are common
- Palsy of vertical gaze, rarely blink
Cortico-basal degeneration (cortical and basal signs):
- Cortical - cognitive problems, impulsivity, apathy, behaviour change, language problems (e.g. aphasic, may develop PFNA)
- Basal ganglia - ballismus (alien limb), myoclonus, dystonia, rigidity, bradykinesia
MSA: (basically fall into the room, then soil themselves)
- Muscle stiffness
- Symmetrical signs
- Autonomic issues (BP, syncope, bladder + bowel) / Ataxia (cerebellar signs)
- Can be Parkinsonian predominant (MSA-P) or cerebellar predominant (MSA-C)
- Usually have preserved cognitive function. Rapid decline with prognosis around 9 months and poor response to L-dopa
Huntingtons
a) CAG repeats - number in HD? number for early age of onset?
b) What is ‘anticipation’
a) >37 in HD
>60 leads to early age of onset
b) The number of repeats increases with successive generations, so children are likely to present earlier than their parents
Myoclonus post cardiac arrest
Lance Adams syndrome - within days-weeks, intention myoclonus, may have ataxia. Treated with valproate or clonazepam.
Status myoclonus- within 48h, generalised multi focal myoclonus with cognitive impairment and poor prognosis
Parkinsons medication side effects
a) Hallucinations
b) Impulsive behaviours
a) - Consider if dopaminergic meds need tapering down
- 1st line Rx: rivastigmine
- 2nd line: cautious use of atypical antipsychotics (clozapine and quetiapine have lowest rates of drug induced parkinsonism), antidepressants
b) - Reduce dose of any dopamine agonists and assess response
Drug-induced parkinsonism
a) Timescale and diagnostic criteria
b) Common culprit drugs
c) vs PD
d) Management
a) - Starts days-weeks after starting drug usually (can be more delayed)
- Usually resolves weeks-months after stopping the drug, but can last longer (if persisting or worsening, consider if they could be developing PD)
To diagnose DIP:
1) the presence of parkinsonism,
2) no history of parkinsonism before the use of the offending drug, and
3) onset of parkinsonian symptoms during use of the offending drug.
b) - Typical antipsychotics most commonly
- atypical antipsychotics - risperidone, olanzapine and aripiprazole (quetiapine and clozapine safer in PD)
- antiemetics - metoclopramide, domperidone*
- antiepileptics - valproate, phenytoin
- antidepressants - SSRIs, lithium
*Domperidone has theoretically lower risk as doesn’t really cross BBB; so often used for N&V in PD
c) - PD is most common cause of Parkinsonism; DIP is second most common
- PD is more commonly unilateral, although 50% DIP is also unilateral
- PD affects pre-synaptic and post-synaptic neurons whereas DIP only affects post-synaptic (which is evident on DAT scan - normal symmetrical uptake in striatum in DIP vs asymmetric reduced uptake in PD)
d) - Stop offending medication
- If they require antipsychotics, consider quetiapine or clozapine
Stopping AEDs - risk of recurrence
In GTC epilepsy, if seizure free for 2 years, there is a 40% chance of further seizure within 2 years on stopping AED vs 10% if AEDs continued
Risks of recurrence increased if:
- CT or EEG abnormality
- Older age of onset of seizures
- Requiring multiple AEDs
Status epilepticus.
a) Define SE, RSE and SRSE
b) T 0-5 mins
c) T 5-15 mins
d) T 15-30 mins
e) T 30 mins+
f) Choice of antiepileptic in 2nd line management
a) - SE - seizures lasting longer than 5 mins or recurrent seizures without break
- RSE - seizures lasting longer than 30 mins despite 2nd line treatment
- SRSE - seizures lasting longer than 24h despite 3rd line treatment (will almost certainly have precipitating factor - structural, metabolic, infective, etc.)
b) - Semi-prone position, no restraining, head protection
- Airway - consider if adjunct needed
- Administer high flow oxygen
- Establish IV access
- Send bloods + VBG
- Take BM
- Treat any treatable causes
c) If lasting >5 mins…
- Administer benzodiazepine (4mg lorazepam IV or 10mg buccal midazolam)
- If no response to 1st benzo dose after 5 mins, give 2nd dose
- Consider possibility of non-epileptic seizures
- 12-lead ECG, regular observations
- Call ICU
d) If lasting >15 mins despite 2 doses of benzodiazepines…
- Ensure IV or IO access.
- Give 2nd line AED
–> keppra 60mg/kg (max dose 4500mg)
–> valproate 40mg/kg (max dose 3000mg)
–> phenytoin 20mg/kg (max dose 2000mg)
- If no response after infusion of 2nd line AED, consider a different second line AED or phenobarbital
e) If lasting >30 mins despite 2nd line AED loading dose…
- Need anaesthetics/ ICU support
- Propofol OR midazolam OR ketamine OR thiopentone (or combination)
- Continuous EEG monitoring ideally
- Maintenance doses of 2nd line AEDs needed 12h after loading dose
f) - Keppra preferred unless coexisting mood disorder
- Valproate preferred if underlying mood disorder but risks in pregnancy/childbearing age, liver disease, pancreatitis or other metabolic/mitochondrial disease
- Phenytoin needs cardiac monitoring and large-bore IV access. Generally avoided as risks of bradycardia, hypotension, heart block, phlebitis, worse outcomes in drug overdose/withdrawal, porphyria and genetic epilepsies
Antiepilepetics: mechanism of action
- Benzodiazepines
- Keppra
- Valproate
- Lamotrigine
- Phenytoin
- Phenobarbital
- Benzos - GABA agonists
- Keppra - modulates synaptic vesicle protein, SV2A, which is believed to impede nerve conduction across synapses
- Valproate - Sodium channel inhibitor, calcium channel inhibitor, GABA transaminase inhibitor, NMDA
receptor antagonism - Lamotrigine - unknown, thought to be sodium channel blocker
- Phenytoin - sodium channel blocker
- Phenobarbital - GABA agonist
- Propofol - GABA agonist and NMDA antagonist
- Ketamine - NMDA antagonist
- Thiopentone - GABA agonist
