Neurology Flashcards
What is a seizure?
Transient occurrence of signs or symptoms due to abnormal excessive or synchronous neuronal activity in brain
Can be a disturbance of consciousness, behaviour, cognition, motor function or sensation
What is epilepsy?
Neurological disorder where person experiences recurring seizures
How is epilepsy defined?
At least 2 unprovoked seizures occurring >24h apart
Diagnosis of epilepsy syndrome
One unprovoked seizure and a probability of further seizures
RF for epilepsy
premature birth
complication febrile seizures
genetic conditions - tuberous sclerosis or neurofibromatosis
FHx of epilepsy or neurological illness
Head trauma, infections (meningitis/encephalitis) or tumours
Comorbid conditions: cerebrovascular disease and stroke
Dementia and neurodegenerative disorders (Alzheimers)
Aetiology of Epilepsy
Structural: abnormalities such as stroke, trauma or malformation of cortical development
Genetic
Infectious: TB, HIV, cerebral malaria, congenital infections
Metabolic: porphyria, pyrixodine deficiency
Immune: anti-NMDA receptor encephalitis and anti-LG11 encephalitis
PC for epilepsy/different types of seizure
Short-lived abrupt generalised muscle stiffening with rapid recovery = tonic seizure
Generalised stiffening and subsequent rhythmic jerks of limbs, urinary incontinence, tongue biting = generalised tonic-clonic seizure
Behavioural arrest = absence seizure
Sudden onset of loss of muscle tone = atonic seizure
Brief, shock-like involuntary single or multiple jerks = myoclonic seizure
Causes of seizure
Epilepsy
Vasovagal
Cardiac arrhythmias
Panic attacks with hyperventilation
NEAD
TIA
Migraine
Meds, alcohol, drug intoxication
hypoglycaemia
movement disorders
sleep disorders - narcolepsy, sleep apnoea
Delirium/dementia - altered awareness
Children: febrile convulsions, breath-holding attacks, night terrors, ritualistic behaviours
Triggers for seizures
Sleep deprivation
Stress
Light sensitivity
Alcohol use
Acute Mx of a tonic-clonic seizure <5m
Check for epilepsy identity card or jewellery
Protect for injury: cushion head, remove glasses
do NOT restrain them or put anything in mouth
When stops check airway and put in recovery position
Observe until recovered
Examine for any injuries
Call ambulance: if first seizure, another reoccurs shortly after first, person is injured, struggling to breathe or difficult to wake
Mx of tonic-clonic seizure >5m
OR >3 seizures in an hour
Buccal midazolam 1st line in community
Rectal diazepam if preferred or midazolam not available
IV lorazepam if IV access
Can an ambulance
When to call an ambulance for seizure?
If >5m
If first seizure
If seizure were prolonged to recurrent before treatment - status epilepticus
high risk of recurrence
hx of repeated seizures or status epilepticus
When can you stop prescribing AEDs?
Under specialist supervision if patient is seizure free >2y
Routine Mx for focal seizures
1st line = carbemazepine/lamotrigine
2nd line = levetiracetam, oxycarbazepine or sodium valproate
Mx of generalised tonic-clonic seizures
1st line = sodium valproate or lamotrigine
2nd line = carbemazepine, clobazam, levetiracetam or topiramate
Mx of absence seizures
1st line = sodium valproate or ethosiximide
2nd line = lamotrigine
Mx of myoclonic seizures
1st = sodium valproate
2nd = levetiracetam or topiramate
AVOID carbamazepine and oxycarbazepine as worsen seizures
Tonic or atonic seizures
sodium valproate or lamotrigine
Status epilepticus
Medical emergency
seizure lasting .5m
multiple seizures without regaining consciousness in interim
Mx of status epilepticus
ABCDE
Secure airway
giving high-flow oxygen
check CBG
Gain IV access
1st line = BDZs (buccal midazolam 10mg, rectal diazepam 10mg, IV lorazepam) repeat after 5-10mins if seizure continues
2nd = after 2 doses of BDZs are IV levetiracetam, phenytoin or sodium valproate
3rd = phenobarbital or GA
Causes of stroke
Small vessel occlusion/cerebral microangiopathy/thrombosis
Cardiac emboli (AF, endocarditis, MI)
Atherothromboembolism (e.g from carotids)
CNS bleeds (increased BP, trauma, aneurysm rupture, anticoagulation, thrombolysis)
What do cerebral infarcts look like clinically?
Contralateral sensory loss or hemoplegia
Initially hypotonic progressing to hypertonic
Dysphasia
Homonymous hemianopia
Visuo-spatial deficit
What do brainstem infarcts look like clinically?
Quadriplegia
Disturbances of gaze and vision
Locked in syndrome
Clinical presentation of lacunar infarcts
infarcts in basal ganglia, internal capsule, thalamus and pons
ataxia hemiparesis
pure motor/sensory
sensorimotor
dysarthria/clumsy hand
cognition and consciousness are intact except thalamic stroke
Silent stroke
radiological or pathological evidence of an infarction without an attributable hx of acute neuro dysfunction
Cerebral venous thrombosis
more likely in patients with prothombotic tendence e.g pregnancy, infection, dehydration or malignancy
Carotid artery dissection
tends to occur in younger people and may be preceded by neck trauma
Vestibular stroke symptoms
nystagmus
N + V
head motion intolerance
new gait unsteadiness
Causes of stroke in younger patients
sudden BP drop by >/40mmHg
Carotid artery dissection
Vasculitis
SAH
venous sinus thrombosis
antiphospholipid syndrome
thrombophilia
Fabry disease
CADASIL (genetic disorder)
Modifiable risk factors for stroke
SMx
Alcohol misuse and drug abuse
Physical activity
poor diet
HTN
permanent and paroxysmal AF
valvular disease
carotid artery disease
Congestive HF
PVD
COCP
Hyperlipidaemia
DM
Hypercoagulable disorders
Non-modifiable RF for stroke
Infective endocarditis
Congenital or structural HD
Age
Gender - male
SCD
Antiphospholipid syndrome
CKD
OSA
Acute Mx of stroke
A-E
Admit to ASU
Exclude hypoglycaemia
NBM - SALT need to assess swallow
Immediate CT brain - exclude haemorrhage
Start aspirin 300mg for 2 weeks - if no haemorrhage
Thrombolysis - alteplase (tpa) may be given <4.5h - repeat CT after to check for haemorrhage
Thrombectomy - if proximal posterior circulation - <24h with IV thrombolysis
Should you manage BP in acute ischaemic stroke?
Lowering BP can worsen ischaemia - only given in HTN emergency or to reduce risks of thrombolysis
Primary prevention of stroke
Control RF
Treat HTN, DM, hyperlipidaemia, cardiac disease
Smoking cessation
Encourage exercise
Lifelong anticoagulation in AF and prosthetic heart valves
Secondary prevention of stroke
aspirin 300mg 2/52 then switch to:
Clopidogren 75mg OD OR if AF then apixaban
Atorvastatin 80mg (delayed until 48h)
BP and DM control
Address modifiable RF
Total anterior circulating stroke
Large cortical stroke affecting areas of brain supplied by both MCA and ACA
All 3 needed for TACS:
- unilateral weakness (and/or sensory deficit) of face, arm and leg
- homonymous hemianopia
- higher cerebral dysfunction (dysphasia, visuospatial disorder)
Partial anterior circulating stroke
Less severe form of TACs, only part of anterior circulation affected
Need 2 for diagnosis:
- unilateral weakness (and/or sensory deficit) in face, arm and leg
- homonymous hemianopia
- higher cerebral dysfunction (dysphasia, visuospatial disorder)
Posterior circulation syndrome (POCS)
Involves damage to area of brain supplied by posterior circulation (e.g cerebellum and brainstem)
Need one to be present:
- cranial nerve palsy and a contralateral motor/sensory deficit
- bilateral motor/sensory deficit
- conjugate eye movement disorder (e.g horizontal gaze palsy)
- cerebellar dysfunction (e.g vertigo, nystagmus, ataxia)
- isolated homonymous hemianopia
Lacunar strokes (LACS)
Subcortical stroke that occurs secondary to small vessel disease
No loss of higher cerebral functions (e.g dysphasia)
Need one:
- pure sensory stroke
- pure motor stroke
- sensori-motor stroke
- ataxia hemiparesis
What is the ABCD2 score for TIA?
Age >60y
BP >/=140/90
Clinical features of TIA: unilateral weakness (2), speech disturbance without weakness (1)
Duration of symptoms: 10-59mins (1), >/=60mins (2)
History of DM: Yes (1)
What is a score that can be used to assess acute stroke?
NIH Stroke scale/score
Which patients should you use a HINTs test for?
Persistent vertigo over hours or days
Nystagmus
Normal full neuro exam
What is in in the HINTS test?
Head impulse test: positive test is eyes move with the head, then saccade quickly back to fixation point - indicates likely ipsilateral vestibulocochlear nerve
Nystagmus: bidirectional nystagmus specifies stroke
Test of skew: ask patient to look at your nose and cover one eye, move your hand to cover patients other eye - observe uncovered eye for any vertical/diagonal corrective movement - suggests central cause
What is a TIA and how do you manage it?
Episode of neuro dysfunction caused by focal brain, spinal cord or retinal ischaemia without evidence of acute ischaemia
Sx last <24h
Mx: Aspirin 300mg daily, referral for specialist assessment <24h, diffusion-weighted MRI
Extradural haemorrhage
bleeding between skull and dura mater
Subdural haemorrhage
bleeding between dura mater and arachnoid mater
Intracerebral haemorrhage
bleeding into brain tissue
RF for intracranial bleeds
head injury
HTN
aneurysms
ischaemic strokes (progression to bleeding)
brain tumours
thrombocytopenia
bleeding disorders
anticoagulants
PC for intracranial bleeds
Sudden onset headache
seizures
vomiting
reduced consciousness
focal neuro sx
Extradural haemorrhage (where, on CT, epidemiology)
between skull and dura mater
rupture of middle meningeal artery in temporoparietal region
associated with fracture of temporal bone
Bi-convex shape on CT
Do not cross sutures
Typically young patients w traumatic head injury and headache
Subdural haemorrhage
occurs between dura and arachnoid
rupture of bridging veins in outermost meningeal layer
CT: crescent shape
Crosses cranial sutures
Occurs in elderly and alcoholic patients - more atrophy in brains, vessels more prone to rupture
Intracerebral haemorrhage
bleeding in brain tissue
presents similarly to ischaemic stroke
sudden onset focal neuro sx - limb/facial weakness, dysphasia or vision loss
Spontaneously or secondary to ischaemic stroke, tumours or aneurysm rupture
Occurs anywhere: lobar ICH, deep ICH, IVH, basal ganglia haemorrhage, cerebellar haemorrhage
RF for SAH
Aged 45-70
women
black ethnic origin
HTN
SMx
Excessive alcohol intake
FHx
Cocaine use
SCD
CT disorders
Neurofibromatosis
PCKD
PC for SAH
sudden-onset occipital headache during strenuous activity (heavy lifting/sex)
Thunderclap headache
neck stiffness
photophobia
vomiting
neuro sx
Investigations for SAH
CT = first line
- hyper-attenuation in subarachnoid space
- normal CT does not exclude
- less reliable after >6h
LP - if normal CT
- wait >12h after sx onset
- takes time for Br to accumulate in CSF
- Will show: raised RCC, xanthochromia (yellow colour due to Br)
CTA - after diagnosis to locate source of bleeding
Mx of SAH
specialist neurosurgical unit
may need intubation and ventilation
Endovascular coiling - inserting a catheter into arterial system, platinum coils in aneurysm to seal from artery
Neurosurgical clipping - clip on aneurysm to seal it
Nimodipine: prevents vasospasm and therefore brain ischaemia
Mx of complications of SAH
Hydrocephalus - increased CSF - expansion of ventricles
- LP
- External ventricular drain (inserted into ventricles to drain CSF)
VP shunt - catheter connecting ventricles with peritoneal cavity
Treat seizures with AEDs
Mx of intracranial haemorrhage
Immediate CT to diagnose
Bloods: FBC (platelets) and a coag screen
Admit to ASU
Consider intubation, ventilation and ICU (if reduced consciousness)
Correct any clotting abnormality (e.g platelet transfusion or vit K for warfarin)
Correct severe HTN and hypoT
Smaller bleeds: conservative mx - close monitoring and repeat imaging
Surgical options for extradural or subdural haematoma:
- craniotomy - open surgery by removing a section of skull
- burr holes - small holes drilled in skull to drain blood
Gullian-Barre Syndrome: what is
Acute paralytic polyneuropathy affects peripheral nervous system
causes acute, symmetrical, ascending weakness and can also cause sensory sx
Cause of Guillain-Barre syndrome
Usually an infection: camplylobacter jejuni, CMV and EBV
Molecular mimicry
B cells create antibodies against antigens on triggering pathogen
these antibodies match proteins on peripheral neurons
May target proteins on myelin sheath or nerve axon
Presentation for Guillain-Barre syndrome
usually start <4w of triggering infection
Begin in feet and progress upwards
Sx peak 2-4w
Recovery lasts months-years
Symmetrical ascending weakness
reduced reflexes
peripheral loss of sensation
neuropathic pain
facial weakness
AN dysfunction - urinary retention, heart arrythmias
Investigations for Guillain-Barre syndrome
Clinically diagnosed using Brighton criteria
Nerve conduction studies - reduced signal through nerves
LP for CSF - raised protein with normal cell count and glucose
Management for Guillain-Barre syndrome
Supportive care
VTE prophylaxis (PE leading cause of death)
IVIG first line
Plasmapheresis alternative
Severe cases with resp failure may need intubation, ventilation and admission to ICU
Huntington’s Chorea: what is
Autosomal dominant
causes progressive neurological dysfunction
Trinucleotise disorder - genetic mutation in HTT gene on chromosome 4
Genetic anticipation - successive generations have more repeats in gene = earlier age onset + increased severity
Trinucleotide repeat disorders
repetitions of a sequence of 3 nucleotides
Huntingtons
Fragile X syndrome
Spinocerebellar ataxia
Myotonic dystrophy
Freidrich ataxia
Presentation for Huntington’s
Insidious progressive worsening of symptoms
Typically begins with cognitive, psychiatric or mood problems
Chorea (involuntary, random, irregular and abnormal body movements)
Dystonia (abnormal muscle tone - abnormal postures)
Rigidity (increased resistance to passive joint movement)
Eye movement disorders
Dysarthria
Dysphagia
Management for Huntingtons
No current options for slowing or stopping progression of disease
Genetic counselling for relatives, pregnancy and children
MDT - maintain QoL
PT - improve motility, maintain joint function and prevent contractures
SALT
Tetrabenazine - chorea sx
Antidepressants
Advanced directives
EoL care
Myasthenia gravis
Autoimmune disorder
Antibodies to nicotinic ACh receptors on post-synaptic side of NMJ
Peak incidence in 30s for women, 60/70s for men
Presentation for myasthenia gravis
slowly increasing or relapsing muscular fatigue
muscular groups affected in order (extraocular muscles, bulbar muscles, face, neck, limb gurdle, trunk)
Ptosis
Diplopia
Myasthenia snarl or smiling
“peek sign” - eyelids separate after manual opposition to sustained closure
Voice fading on counting to 50
muscles fatigue more readily after exercise
normal reflexes
no wasting/fasciculations
normal sensation
What is myasthenia gravis associated with?
Autoimmune disease (RA and SLE)
Thymic hyperplasia in females <50
Thymic atrophy or thymic tumours in men >50
Drugs to avoid in myasthenia gravis
beta blockers
antiarrhythmics (verapamil)
neuromuscular blocking agents
lithium
phenytoin
statins
prednisolone
some abx
Myasthenic crisis
worsening muscle weakness - resp failure needing intubation and mechanical ventilation
Difficult to differentiate from cholinergic crisis
Mx: plasmapharesis or IVIG and identify trigger for relapse
Investigations for myasthenia gravis
clinical diagnosis
increased AChR antibodies in 90%, MUSK antibodies
TFTs
EMG: decremental muscle response to repetitive nerve stimulation
Imaging: CT to exclude thymoma
Edrophonium test: IV edrophonium chloride
- normally cholinesterase enzymes in NMJ breakdown acetylcholine
- Edrophonium blocks enzymes - reducing breakdown of acetylcholine
- acetylcholine rises at NMJ temporarily reducing weakness
- +ve = myasthenia gravis
Examination findings for myasthenia gravis
repeated blinking will exacerbate ptosis
prolonged upward gazing will exacerbate diplopia on further testing
repeated abduction of one arm 20x will result in unilateral weakness when complaining both sides
Mx for myasthenia gravis
Pyridostigmine (cholinesterase inhibitor) prolongs action of acetylcholine and improves sx
Immunosuppression - prednisolone or azathioprine suppresses production of antibodies - give osteoporosis prophylaxis
Thymectomy - improve sx, even if no thymoma
Rituximab when other treatments fail
UMNL: what is, signs and causes
UMN = neuron whose cell body originates in cerebral cortex or brainstem and terminates within brainstem or spinal cord
Signs: hypertonia, brisk reflexes, spasticity (clasp knife response, golgi tendon reflex), positive babinski sign, clonus
Causes: MND, TBI, Spinal cord injury, MS, Stroke, Hungtington’s
LMNL: what is, signs and causes
LMN = cell body lies within ventral horn of spinal cord or brainstem and terminates on muscle fibres
LMN signs = hyporeflexia/arereflexia, hypotonia/atonia, flaccid muscle weakness/paralysis, fasciculations, muscle atrophy
Causes: peripheral neuropathy, viruses, polio, CES, MND, C.Botulism, Guillain-Barre
Lambert-Eaton Myasthenic syndrome (LEMS)
Can be paraneoplastic (particularly small cell lung ca)
Antibodies are to voltage-gated calcium channels on pre-synaptic membrane
Less ACh released into synapse = weaker signal and reduced muscle contraction
Presentation for LEMS
Proximal muscle weakness - difficulty climbing stairs, standing from a seat or raising arms overhead
Autonomic dysfunction - dry mouth, blurred vision, impotence and dizziness
Reduced or absent tendon reflexes
S+S improve after muscle contraction (opposite to MG)
Mx for LEMS
- exclude underlying malignancy
- regular CXR/high resolution CT as sx can precede lung ca by >4y
- Amifampridine - blocks voltage-gated potassium channels in presynaptic membrane - prolongs depolarisation of cell membranes and assists calcium channels in carrying out action
Pyridostigmine (cholinesterase inhibitor)
Immunosuppressants
IVIG
Plasmapheresis
Multiple sclerosis
Chronic and progressive autoimmune condition
involves demyelination - affects electrical signals moving along neurons
RF for multiple sclerosis
Multiple genes
EBV
Low vit D
SMx
Obesity
Latitude - distance from equator increases risk
Presentation of MS
Onset typically in young adulthood
visual and sensory disturbances
limb weakness
gait problems
bladder and bowel sx
usually monosymptomatic
Sx may worsen with heat
optic neuritis
transverse myelitis
cerebellar related sx: ataxia, vertigo, clumsiness
Brainstem syndromes: ataxia, eye movement abnormalities, nystagmus, dysarthria or dysphagia
Optic neuritis
inflammation of optic nerve
partial or total unilateral visual loss developing over a few days
pain behind eye
loss of colour discrimination
fundoscopy often normal, disc may appear pale or swollen
Normally unilateral
Transverse myelitis
focal inflammation of spinal cord
sensory or motor sx below level of inflammation - develops over hours or days
Tight band sensation around trunk at level of inflammation, or shock like sensation radiating down spine induced by neck flexion
LUTS
patterns of disease in MS
Relapsing-remitting
Secondary progressive
Primary progressive
Relapsing-remitting MS
Most common
85% with MS have RRMS at onset
Episodes or exacerbations of sx are followed by recovery and periods of stability
Secondary progressive MS
Occurs when there is gradual accumulation of disability unrelated to relapses which become less frequent or stop completely
2/3s of people with RRMS to SPMS
Primary progressive MS
Steady progression and worsening of disease onset, without remissions
10-15% of people
Investigations for MS
Refer to neurology
MRI scans can show lesions - sensitive but not specific for plaque deterioration - exclude cord compression
LP - detect oligoclonal bands of Ig in CSF
What criteria is used for MS diagnosis?
McDonald criteria
Presentation for PD
Unilateral features - become bilateral as progresses
Bradykinesia
Hypokinesia - reduced facial expression, arm swinging or blinking
Slow, shuffling gait
small cramped handwriting
Hypertonia: stiffness or rigidity
Tremor: resting
Autonomic dysfunction: constipation, postural hypoT, urinary frequency/urgency
Depression, anxiety, fatigue
reduced sense of smell
Mx for PD
1st line:
- Levodopa,
-Dopamine agonists (Ropinirole/Pramipexole),
- MAO_B inhibitors (Selegiline/rasagiline/safinamide)
Adjuvant treatment: COMT inhibitors - entacapone/opicapone
Oral amantadine
Apopmorphine (when advanced and optimal oral treatment, even out end-of-dose effects)
MND
Cluster of neurodegenerative diseases
more common in males
Selective loss of neurons in motor cortex of brain, loss of cranial nerve nuclei and loss of anterior horn cells
Upper and lower motor neurons can be effected
No sensory loss or sphincter disturbance (separates from MS and polyneuropathies)
Never affects eye movements (distinguish from MG)
4 clinical patterns of MND
Amyotrophic lateral scelorsis (ALS)
Progressive bulbar palsy
Progressive muscular atrophy
Primary lateral sclerosis
ALS
most common MND
loss of motor neurons in motor cortex and in anterior horn of cord
Combined UMN and LMN signs
Worse prognosis if there is a bulbar onset (sx occurring in face or neck) increased age or decreased FVC
Progressive bulbar palsy
Only affects cranial nerves IX to XII
signs = LMNL of tongue and muscles of talking and swallowing, flaccid, fasciculating tongue, normal or absent jaw jerk, unprovoked crying or inappropriate laughter
Progressive muscular atrophy
affects <10%
anterior horn cell lesion
LMN signs only
Affects distal muscle groups before proximal muscle groups
Better prognosis than ALS
Primary lateral sclerosis
rare
loss of Betz cells in motor cortex
Mainly UMN signs
Marked spastic leg weakness
No cognitive decline
Diagnostic criteria for ALS
Definite ALS: LMN + UMN signs in 3 regions
Probable ALS: LMN + UMN signs in 2 regions
Probable with lab support: LMN + UMN signs in 1 region or UMN signs in >/= 1 region. EMG shows acute denervation in >/=2 limbs
Possible: UMN + LMN in 1 region
Suspected: UMN or LMN signs in 1 region
Presentation for MND
Median onset 60
>40 with a stumbling, spastic gait, foot drop +/- proximal myopathy, weak grip and shoulder abduction or aspiration pneumonia
look for LMN signs: spasticity, brisk reflexes, upgoing plantars
LMN signs: wasting, fasciculation of tongue, abdomen, back and thigh
Speech and/or swallowing affected
Frontotemporal dementia
Mx of MND
MDT approach
Riluzole (ALS) - inhibitor of glutamate release and NMDA receptor antagonist - only med that improves survival
Excess saliva: positioning, oral care and suctioning, antimuscarics
Dysphagia: blend foods, gastrostomy, peg feeding? discuss early
Spasticity: exercise, othortics
Communication difficulties: augmentative and alternative communication equipment
End of life care: involve palliative care team from diagnosis, opioids to relieve breathlessness, discuss NIV
Friedreich’s ataxia: what is
Most common inherited ataxia in UK
Degenerative disease that primarily affects nervous system and heart
Associated with cardiomyopathy or DM
Aetiology of Friedreich’s ataxia
Mutation of Frataxin gene on chromosome 9
GAA repeat expansion of Frataxin gene
decreased synthesis of frataxin (mitochondrial protein)
Presentation for Freidreich’s ataxia
unsteadiness of gait
clumsiness or deterioration in athletic performance
Ataxia
Cranial nerve involvement - dysarthria, visual loss, hearing loss and dysphagia
extensor plantar responses
areflexia
pyramidal weakness in lower limb
loss of joint position and vibration disturbance
scoliosis
symmetrical pes cavus
hypertrophic cardimyopathy
DM
peripheral cyanosis, oedema and cold feet
Investigations for Freidreich’s ataxia
Nerve conduction studies show motor velocities >40 in arms, absent sensory action potentials
genetic analysis
ECG - VH and T wave inversion
Exclude vit E deficiency
ECHO - VH, septal hypertrophy and hypertrophic cardiomyopathy
MRI brain and spinal cord - atrophic changes, particularly cervical spinal cord
Genetic counselling and tests
Mx for Freidreich’s ataxia
MDT approach
Annual review - assess neurology, cardiac function, MSK problems, comprehensive systems review and blood tests
Supportive treatments
Prognosis for Freidreich’s ataxia
average life expectancy is 40-50y
loss of ability to walk typically occurs 15y after diagnosis
most common cause of death are cardiac failure and arrhythmias
