Transcript Management of seizures in Oncology patients

Esther
Sammler
ST4 in Neurology
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Background
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Seizures
Manifestation of an abnormal and excessive synchronized
discharge of set of neurons
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Epilepsy
Brain disorder with an enduring predisposition to generate
unprovoked epileptic seizures (in practice: < 2 more)
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Epidemiology
Lifetime prevalence of seizures is 1-5%
of epilepsy in general population is 1%
Incidence
ILAE* Classification of Seizures
Seizur
es
Partial
Simple
Complex
With 20 generalization
Generaliz
ed
Absence
Myoclonic
Atonic
Tonic
Tonic-Clonic
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 comorbidities 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
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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
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10x more frequent than primary CNS tumors
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Melanomas, lung, breast, kidney,ect
• Infiltrative Lesions
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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
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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
Carbamazepine
Phenotoin
Phenobarbital
Primidone
Valproate
Felbamate
Lamotrigene
Oxcarbazepine
Tiagabine
Topiramate
Ethosuximide
Clonazepam
Clobazam
Zonisamide
Vigabatrin
Gabapentin
Levetiracetam*
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