Esther Sammler

ST4 in Neurology

Dundee

Oncology Foundation Doctors ‘ Lunchtime Teaching

Faints, Fits and Funny Turns

Background

• Seizures

Manifestation of an abnormal and excessive synchronized discharge of set of neurons

• Epilepsy

Brain disorder with an enduring predisposition to generate unprovoked epileptic seizures (in practice: < 2 more)

• Epidemiology

Lifetime prevalence of seizures is 1-5% Incidence of epilepsy in general population is 1%

ILAE* Classification of Seizures

ILAE* International League against Epilepsy

Causes of epilepsy / seizures

• Varies within age groups and geographical distribution

• Genetic and congenital conditions predominate in early

childhood

• Inherited predispositions, hippocampal sclerosis, alcohol & drug

abuse, trauma in older children and young adults

• Tumors and sporadic infections at all ages, but malignant brain

tumors >30

• Cerebrovascular and degenerative diseases in the elderly

Incidence of epilepsy depending on age

Precipitating causes

• Stress

• Sleep deprivation and fatigue

• Sleep / wake cycle

• Alcohol and alcohol withdrawal

• Metabolic disturbances

• Toxins and drugs

• Menstrual cycle

Prognosis of epilepsy

• 60 – 70% enter prolonged remission

• Predictors of an adverse outcome

– Early onset

– Symptomatic epilepsy

– Neurological deficit / learning disabilities

– Failure of Antiepileptic drug treatment

Burdens of Epilepsy on the Individual

• Physical morbidity (burns, fractures etc.)

• Psychological stress (e.g. loss of control, fear,

overprotection)

• Social stress (stigma, education, work, driving,

relationships, social life)

• Psychiatric illness (depression, anxiety)

• Co-morbidities

Healthcare Burden

Random series (n=1628) of pts on AED therapy

65% on montherapy, 35% on polytherapy

OVER LAST 12 MONTHS

• 28% attended specialist service

• 87% seen by GP

• 9% no contact

• 18% attended A&E (43% ever)

• 9% required hospital admission (47% ever)

Hart et al. The nature of epilepsy in the general population. Epilepsy Res 1995;21:43-9

Diagnosis of epilepsy

• Wide differential diagnosis

• Misdiagnosis is common

For example, 74 pts with dx of epilepsy were investigated with tilt-table, prolonged ECG, blood pressure monitoring and EEG monitored carotid sinus massage and an alternative cardiological cause was found in 31, including 13 on AED treatment)*

• Conditions most commonly mistaken are syncope and pseudoseizures

• Precise and detailed personal and witnessed accounts of prodrome, onset, evolution, and recovery period

• There is no shame in deferring a diagnosis if uncertain

Zaidi et al. Misdiagnosis of epilepsy: many seizure like attacks have a cardiovascular cause. J Am Coll Cardiol 2000; 36:1

Common reasons for misdiagnosis

• Incomplete history

• No eye witness account

• Not taking full clinical picture into account

• Over-interpretation of minor EEG abnormalities

Investigations in adult-onset epilepsy

• Classification of epileptic seizures and co-

morbidities will guide investigations

• The main role of investigations in new onset

epilepsy is to attempt to identify aetiology and

identify underlying cause in symptomatic seizures

– Cerebral Imaging– EEG– ECG– Blood tests

Management of first seizure

• Clear history of epileptic seizure

• Focal onset clinically (all patients > 25 years)– Detailed brain imaging in all– EEG

• Generalized onset clinically (all patients > 25 years)

– EEG– No need for imaging unless atypical

• ECG and bloods

• General safety and driving advice

• No AED treatment if first seizure event

• Refer to neurology

Management of pt with established epilepsy• Take careful and complete hx– Seizure semiology (witness!) and possible trigger factor– Previous seizure pattern in terms of frequency and clinical

presentation– AED: Any recent changes? Compliance? Previous AED?– AED serum levels: please don’t! possible exception phenytoin

• Investigate as appropriate

• Assure that AED are written up, available and appr. formulation!

• Neurology registrar on call (bleep 4968) always happy to discuss

• Safety and driving advice

DVLA – Medical rules for drivers

• First fit Group 1 liscence: 6 months off driving from the date

of the seizure if the licence holder has undergone

assessment by an appropriate specialist and no relevant

abnormality has been identified on investigation, for example

EEG and brain scan where indicated. Till 70 licence restored,

provided no further attack and otherwise well. (Special

consideration may be given when the epileptic attack is

associated with certain clearly-identified, non-recurring

provoking causes)

• Fit in established epilepsy: 12 months of driving

http://www.dft.gov.uk/dvla/medical.aspx

Seizures in oncological patients

• Epilepsy and malignancy are common conditions in the

general population and may co-exist

• New onset seizures in pt with known malignancy = “brain

metastasis”

• 4% of pts with epileptic seizures have intracranial malignancy

• 30-40% of pts with brain tumors present with fits

• 10-30% of pts with brain tumors will seize at some point

Seizures in oncological patients

• Primary CNS tumors

• Metastasis– 10x more frequent than primary CNS tumors

– Melanomas, lung, breast, kidney,ect

• Infiltrative Lesions– Meningeal carcinomatosis, Gliomatosis cerebri, Intravascular lymphomatosis

• Paraneoplastic syndromes (limbic encephalitis)

• Metabolic disorders and Infections

• Chemotherapy

• Radiotherapy

Investigations

• Tailored to patient

• Detailed imaging (MRI including gadolinium contrast)

• CSF analysis (up to 3 LP’s with up to 10-15ml CSF)

• Biochemistry (in particular Na, K, Ca, Mg, blood glucose)

• Infection screen

Treatment

• There is no evidence for prophylactic antiepileptic treatment

• Complex interactions between AED and chemotherapeutics– Enzyme inducing AED: phenytoin, phenobarbital, primidone, carbamazepine,

and to lesser extent, oxacarbamazepine and topiramate– Enzyme inhibiting AED: Valproate, Zonisamide, Felbamate

• Increased risk of adverse effects

• AED with beneficial pharmocokinetic profile: – Levetiraectam– Gabapentin– Pregabalin– Vigabatrin

• Other Tx (surgery, radiotherapy, ect)

AED potential for producing interactions

High Medium Low

CarbamazepinePhenotoinPhenobarbitalPrimidoneValproateFelbamate

LamotrigeneOxcarbazepineTiagabineTopiramateEthosuximideClonazepamClobazamZonisamide

VigabatrinGabapentinLevetiracetam*Pregabalin

Vecht et al., Lancet Neurol. 2003;2:404-409

Take home message

• Seizures in oncological patients is red flag and warrant

immediate assessment for underlying cause

• EEG only in special situations helpful (non-convulsive

status epilepticus, encephalopathy,…)

• Treatment of status epilepticus as in general population

• No prophylactic AED treatment

• Safety and driving advice

Thank you