Dr Paul TimmingsMBChB MD FRACP

Neurologist, Hamilton

Disclosures: Nil

Journey: Ongoing

Passion: Abundant

Fits and Faints: Syncope vs SeizureA few Thoughts and Tips

Dr Paul Timmings, MBChB MD FRACP

Neurologist

Waikato

Case 1

• Ms LC, age 17

• Fooling around on sofa w friends, Sunday am.

• Late night before (probably an early morning),

• Excess unaccustomed alcohol that night

• Sudden LOC, Back arched, Body briefly stiff.

• Quickly OK after ?transiently muddled

• To GP next day (Monday!)

Case 1

• O/E NAD, fully well, no tongue bite

• No PHx

• ECG; NAD, Bloods NAD

• Hx reviewed with boy-friend (eye witness)

• Advised no driving, no at risk activities (eg bathing)

• Diagnosis not entirely clear

• No Rx meantime

LOC - ?Cause

• A common presentation and question

– 6% of ED attendances & 3% of Medical admissions

– 15% under 18 have had “syncope”

– 25% of > 70 will have LOC ?cause in next 10yrs

• Huge capacity of Dr to influence QOL & DOL

• No substitute for a detailed and careful Hx

• Eye-witness accounts are vital

LOC ?Cause: Differential Dx• Seizure:

– Focal

– Generalised

• Syncope:

– Cardiac (arrhythmia, cardiomyopathy)

– Non-Cardiac (vasovagal, orthostatic, medication induced)

• Migraine

• Movement disorder (with paroxysmal events)

• Toxic / Metabolic (Hypo/Hyper-glycaemia, Alcohol, Drugs)

• Sleep disorder (Narcolepsy, Parasomnia)

• Cerebrovascular (TIA (rarely), Stroke)

• Psychogenic (Anxiety/Panic, Conversion (NEAD))McKeon et al Lancet Neurology 2006

LOC ?Cause: Differential Dx

• Differential is difficult & wide, - even huge

• 25-45% are undiagnosed at time of hosp Dx

• Investigative costs are large (e7756 in mid ‘90s review)

• Inappropriate investigations consume resources and choke waiting lists

• Incorrect or uncertain diagnoses add unnecessary social disability eg work/driving issues

McKeon et al Lancet Neurology 2006

How can we do better?

• Some features may help discriminate

Eg: prodrome, pallor, posturing, confusion

• 2/3 of blackouts are syncope

& ½ those are vasovagal

– Many episodes of LOC-?Cause are benign.

Sarasin et al Am J Med 2001

How can we do better?

• Some symptoms may help discriminate

Eg: prodrome, pallor, posturing, confusion

• 2/3 of blackouts are syncope & ½ those are vasovagal

• But – 9% of syncope cases are dead in 18 months &

30% with underlying cardiac disease are dead in 1 yr

• Correct triage and management of cardiac cases will save lives

Sarasin et al Am J Med 2001

Examples of Malignant Syncope

• LV or RV disease– AS, HOCM, Pul emboli, Pul hypertension

– Pump failure

– Ischaemia

• Rhythm problems– AF, PAT, PAF, AV node abn pathways eg WPW

– Heart block, VT, VF, Long QT

• Volume problems– Vasoactive drugs, autonomic neuropathy, volume

depletion

What about the Jerking?

What about the Jerking?

• Myoclonus occurs in 90 % of syncope patients

• Focal movements & automatisms also occur.

• Eyes open, shut, rolling, or moving side to side are not discriminatory either.

• The commonly held belief that jerking means epileptic seizure is WRONG.

Symptom Scoring is 94% Accurate

Sheldon et al J Am Col Cardiol 2002

LOC ?Cause: Investigations

• BioChem, BGL, CBC

• ECG

• Prolactin usually unhelpful

– Can be elevated in both syncope or seizure

– Usually normal in psychogenic sz – so may be useful

– Psycho-active drugs also elevate prolactin

Case 1

Case 1

• What key additional test(s) will help

EEG – 3 Hz spike&wave

LOC ?Cause: 2nd Tier Cardiac Investigations

• Holter monitor correctly identifies 10% of arrhythmias in 24hrs, repeat

gets another 10%.

• External loop recorder correctly identifies 25%

• Implantable recorders identify arrhythmias in 25-46% and prove Sinus

Rhythm during Syx in 24-42%. Giving overall yield of 50-88%

• Echocardiogram helpful if cardiac Hx (otherwise low yield)

– If systolic dysfunction on echo, is highly predictive of arrhythmia

• Tilt table testing (35-70% yield)

• Cardiac EP studies (up to 80% yield in selected cases)

Seizure

Spontaneous Seizure

Repeated Spontaneous

SeizuresEpilepsy

Focal

Symptomatic

Treat Cause

Single

Wait, no Rx Gen

EEG+/- Imaging

LOC ?Cause: 2nd Tier Neuro Investigations

• EEG

– Routine EEG within 24hrs has 50% yield, after that only 25-30%

• Sleep during the EEG adds 25%

• Sleep deprivation adds 25%

– Sleep deprived EEG with sleep sensitivity = 85%

• Imaging: CTB or MRB

– 2% yield if primary generalised seizure (on Hx & EEG)

– 17% yield if focal onset seizures or focal Ep activity on EEG

• Video EEG may alter diagnosis in 24-58% especially in psychogenic / non-epileptic events

Roupakiotus et al Seizure 2000King et al Lancet 1998

EEG: What Use is It?

• A normal EEG will not exclude Seizure/Epilepsy(due to technique dependent false negative rate)

• A normal EEG (in a patient who had a seizure)

implies 20-30% chance of second seizure by 2 yrs

• An abnormal EEG that shows interictal

epileptogenic activity means 60-75% chance of a

second seizure by 2 yrs

Risk Factors for Seizure

• Febrile convulsion

• Perinatal insult / abnormal gestation / delivery

• CNS infection

• CNS mass lesion

• Family Hx of epilepsy

• TBI with LOC > 30min or penetrating brain injury

• Dev delay / “IHC”

• Stroke

LOC ?Cause: Syncope vs Seizure: Distinguishing the Clinical Features

Seizure: Investigative and Management Algorithm

McKeon et al Lancet Neurology 2006

GeneralisedFocal or

Focal then Gen? NEAD Provoked

EEG sleep deprived w

sleep

EEG routine and

MRB or CTB

Wait for 2nd Szbefore starting

Rx.EEG gives prognostic

information.

Focal EEG IED’s & focal brain

lesion = Epilepsy.

Video EEGMay need

monitoring

Treat cause.

Arrange psychiatry / psychology

help.

Syncope: Investigative and Management Algorithm

McKeon et al Lancet Neurology 2006

Typical prodromeNormal examNormal ECG

Cardiac Red FlagsChest pain, No warning Abn Cardiac exam/ECG. FHx Sudden death

Cough, Pain, Micturition, Defaecation

Orthostatic

Neurallymediated.

Cardiogenic.?Carotid sinus

Cardiac work up:Telem/Holter/Echo/Angio

Situational

DrugsVolume lossAutonomic failure

Diabetes MSA

Syncope: Investigative and Management Algorithm

McKeon et al Lancet Neurology 2006

Typical prodromeNormal examNormal ECG

Cardiac Red FlagsChest pain, No warning Abn Cardiac exam/ECG. FHx Sudden death

Cough, Pain, Micturition, Defaecation

Orthostatic

Neurallymediated.

Cardiogenic.?Carotid sinus

Cardioinhibitoryor Vasodepressor

Conservative Rx.HUTT if atypical

Midodrine/ Fludrocort/?Pacemaker

Cardiac work up:Telem/Holter/Echo/Angio

May need implantable recorder

Treat Cardiac Disease

Situational

Manage Situation or other disease.

May need Neurology review

DrugsVolume lossAutonomic failure

Diabetes MSA

Case 2• 47 yr old tanker driver

• Sent by employer. Had put truck though fence off highway. No injuries. Just after taking a break & PU’ing @ Tirau.

• No recall of event, no witness.

• No PHx

• Single, non smoker, 24-48 stubbies per wkend.

• O/E NAD, wt 103kg, BMI 32,ECG NAD, Bloods NAD

Case 2• 47 yr old tanker driver

• Sent by employer. Had put truck though fence off highway. No injuries. Just after taking a break & PU’ing @ Tirau.

• No recall of event, no witness.

• No PHx

• Single, non smoker, 24-48 stubbies per wkend.

• O/E NAD, wt 103kg, BMI 32,ECG NAD, Bloods NAD

• EEG no abnormal activity

Case 2

• EEG: Prominent snoring noted, & occasional gasping

• Epworth score =8

• OPSG: Prominent snoring, several respiratory pauses with O2 desaturation & arousals.

• Likely diagnosis

Case 2

Case 2• OSA & Sleep attack leading to MVA

• Sleep episodes may be abrupt & intrusive!?Due to fragmented night sleep & fatigue.

• Should not drive until managed CPAP

• Untreated OSA:

– Increased risk of: Accidents, BP, AF, cardiac events, stroke, sudden death.

• High Epworth score not always noted(Usually a marker of excessive daytime sleepiness)

Case 3

• Mr L. J. Age 65

• BIBA

• Found sitting bemused by letter box

• Had grazed hand and knee

• Disoriented to time & place

• Pulse 80, reg. BP 136/82, BGL@ scene 6.2

• Admitted w confusion ? cause

Case 3

• ECG: NSR. Urine non-infected. Bloods normal

• Other Hx:

– Lives with mildly demented wife

– 2 yrs ago in hosp with “minor stroke”, - good recovery but slight L limb weakness persists

• CTB: small old R cortex infarct, widespread white matter ischaemic changes

Case 3

• Remained confused for 24hrs (in hospital)– Then “came right” & anxious to get home to wife.

So, was D/C’d but no Rx Δ. Dx ?TIA

• 2 similar spells over next 3 months1. Found by daughter sitting muddled on sofa.

2. Slumped briefly @ church, then confused.

• Neurology review: EEG R temporal sharp & slow waves

• Dx: Likely, post stroke epilepsy

Case 4

• Ms P.S. age 72

• C/O repeated episodes of vaudeville music

– Definite onset, not related to any conscious thought

– All were songs that she knew as a young woman

– Like torture, - very intrusive. Even wake her from sleep

• Normal exam & Normal imaging

• EEG posterior temporal theta

– Dx: simple partial seizures

– All episodes ceased with VPA 400mg/day

Epilepsy in th Elderly

• The young “fit fitters” come to clinic,

but

• The older “funny turners” are trapped in the corners at their (rest) homes.

• Epilepsy in older people is now their 3rd

commonest condition

– exceeded only by stroke & dementia

Incidence & Prevalence Vs. Age

• Incidence & Prevalence of epilepsy in elderly is now the highest of any age group

Brodie 2005Hauser 2007

Epilepsy Incidence in Infants & Children is Decreasing & Increasing in Elderly

Hauser 2007

Epilepsy in Elderly:Cerebrovascular Disease is Main Cause

• Stroke risk rises with age

• 50% of new epilepsies are 20 to vascular events

Kramer 1999

Type of “Stroke” Affects Seizure Risk

• By 5 yrs post event

– 10% of ischaemic infarcts will have seizures

– 25-30% of haemorrhages will have seizures

Burn 1997

Diagnosis

• In the elderly “New Onset Epilepsy” is often manifest with vague complaints:

• confusion

• altered mental status

• memory difficulty

• Eye witness descriptions of onset, or the instant of “state change” are often unavailable

• Symptom scoring strategies don’t work!

Diagnostic Difficulties• Many seizures are brief & may be un-noticed

• Almost all epileptic events in elderly are focal onset (i.e. Partial epilepsy)

– Caused by focal brain disease

• Seizures often leave elderly confused or disoriented for a day or longer

• Elderly are more prone to post ictal confusion & Todd’s paresis

• Post ictal confusion typically lasts longer

Differential Diagnosis is Challenging

• Need to consider

– Syncope

– Cardiac arrhythmia

• e.g. transient cardiac stand still, unsustained VT, or PAT/F

– TIA

– TGA

– Episodic vertigo

– Metabolic disturbances eg

• Low sodium

• Low glucose

– Drug interactions and adverse effects

Causes of Seizures in Elderly:The Top 4

• Previous vascular event(s) 50-70%

• Metabolic / toxic 10%

• Tumour (primary or met) 10-20%

• Dementia(s) & degenerations 10-18%

Management

• Diagnose correctly – Think of it!

• Cardiac disease is also more common.

• Address co-morbidities & poly-pharmacy

• AED’s (Anti-Epileptic-Drugs) are effective

• Review safety issues (re seizures/falls/confusion)

– Living arrangements

– Supervision / support

• Educate

– Spouse / family / carers

Pk-Pd issues in Elderly• Absorption

• Distribution

• Metabolism and excretion

• Decreased absorption

• Delayed oesophageal emptying

• Altered gastric pH

• Delayed gastric emptying

• Increased intestinal transit time

• Decreased albumin and degree of protein binding

(Albumin reduces by 2.5%/decade)

• Decreased body fat

• Decreased hepatic metabolism

• Decreased renal clearance

(Renal clearance reduces by 1%/yr)

Net metabolic capacity might be 50% of a younger adult

Effect of Doubling Half-Life

Choosing an AED: Special Considerations in Elderly

• Choose a Rx that works best in focal onset epilepsies

• Carbamazepine CR or Lamotrigine

– Equally effective

– Equally well tolerated

• Levetiracetam may be a good alternative

– (few interactions, inert metabolites)

Choosing an AED: Special Considerations in Elderly

• Carbamazepine– Hyponataremia - if co-administered with diuretics– Enzyme inducer so many interactions

• Lamotrigine– Needs slow titration– Anti-depressant, alerting (slight)

• Levetiracetam– No important interactions– Depression– GI upset

• Valproate– Metabolic inhibitor, so possible interactions– Tremor, Parkinsonian symptoms, Encephalopathy (rare)

Epilepsy in Elderly: Summary• Epilepsy in elderly is a growing but under-

recognised problem

– Seizures are now their 3rd commonest condition

• 50-70% are post stroke

– 10% of stroke patients have epilepsy by 5yrs

• Most seizures are atypical & have focal onset

– Many leave prolonged confusion in their wake

– Correct diagnosis can be tricky

• AED therapy is effective. But be mindful of interactions, odd adverse effects & reduced metabolic capacity (Go Low & Slow)

Discussion?

Paul Timmings

Neurologist

Hamilton

Extras

EPILEPSY in OLDER PEOPLE: KEY POINTS

•Elderly have the highest incidence of seizures of any age group.

•Nearly half of acute symptomatic seizures in the elderly and 30% to 50% of all epilepsy cases in this age group are associated with stroke.

•In elderly, new onset of epilepsy is often associated with vague complaints such as confusion, altered mental status, or memory problems.

•The differential diagnosis of seizures in the elderly should rule out spells due to other causes, such as syncope (cardiac disease), transient ischemic attack, transient global amnesia, or episodic vertigo.

•In treating epilepsy, the choice of antiepileptic drug (AED) is usually dictated by seizure type and tolerability but will be complicated by co-morbidities or age-associated differences in AED pharmacokinetics.

•Older and newer AEDs are both effective.

•Newer AEDs generally have better overall tolerability, fewer drug interactions, more predictable kinetics, and a broader spectrum of activity; but they also have slower titration schedules and cost considerably more than older AEDs.

EEG

• So, what use for EEG?

• A test of function vs a view of structure

• Useful in assessment of altered mental status– syncope /LOC ?cause

– Epilepsy management

– Non-convulsive status epilepticus (NCSE)

– Metabolic & encephalopathic disease

– Drug effects also often reflected in EEG

EEG – Who needs it?

• Patients with poor or worsening Ep control,

- re ? new changes in EEG

• Investigation of toxic / metabolic

encephalopathies

• Some coma patients

• Some cerebral infections (eg Herpes, CJD, SSPE)

EEG – Who needs it?

• LOC ? Cause with suspicion of seizure

• Altered mental status ?cause ?NCSE, – must include atyp. dementias and some psychoses (re ?NCSE)

• Single Sz patients (prognostic data)

• Can help define the Epilepsy Syndrome

• Well controlled Ep. Pts. re ? to stop Rx

EEG

• Get more from an EEG test, after you

– Define your question

– Use the test appropriately

– Understand the result and its limitations

Dr Paul TimmingsNeurologist Hamilton

Syncope: Investigative and Management Algorithm

McKeon et al Lancet Neurology 2006