How good is the medical management of epilepsy

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How good is the medical management of epilepsy?

• June, 2006
• Peter L. Carlen MD FRCPC

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Neurologists trained in Epilepsy

• Most neurologists receive very little formal
  training in epilepsy and hence are usually not
  really adept in properly diagnosing and treating
  this specialized (albeit common) condition.

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Management

• Lifestyle
• pharmacotherapy
• surgery ablative
• surgery deep brain stimulation
• vagal nerve stimulation
• ketogenic diet
• Dynamic feedback and control

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Lifestyle

• Alcohol
• Sleep deprivation
• Stress management
• Photic stimulation
• With the ketogenic diet no sugar

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Early Identification of Refractory Epilepsy,
NEJM, Kwan and Brodie 342 (5) 314-319, 2000
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Pharmacoresistant Epilepsy is a Bad Disease

• low academic and job performance
• memory loss
• impaired psychosocial skills
• depression
• other multiple drug side effects and interactions
• increased risk of death including suicide

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Standard pharmacological targets

• Sodium channels
• Calcium channels
• GABA receptors chloride channels
• Glutamate receptors NMDA, AMPA/KAINATE

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Current Treatment Options
Partial
Generalized
Simple Complex Secondarily generalized
Tonic-clonic
Tonic
Myoclonic
Atonic
Infantile spasms
Absence
CBZ, PHT, PB, GBP, VGB
ACTH, VGB
ESX
VPA, LTG, TOP(FBM), LEV
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Classifying Side Effects of AEDs

• Adverse
• Dose-related (usually neurotoxicity)
• Acute (titration-related transient vs
  persistent)
• Chronic
• Idiosyncratic
• Allergic (mild severe, possibly
  life-threatening)
• Non-allergic
• Chronic
• Effects on organs or tissues
• Neurotoxicity (including cognitive)
• Teratogenicity
• Beneficial

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Some Less Common Side Effects of Newer AEDs

• Lamotrigine
• Insomnia
• Topiramate
• Kidney stones (lt 1.5)
• Especially with family history, males, dehydration

• Clobazam
• Weight gain
• Impotence
• Vigabatrin
• Hair loss
• visual field constriction
• Gabapentin
• Myoclonus
• Choreoathetosis

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Serious Side Effects of New Antiepileptic Drugs

• Vigabatrin
• Psychosis 2 - 4
• Peripheral retinal degeneration ? 1/3 (rarely
  symptomatic)
• Lamotrigine
• Severe skin reactions (e.g. Stevens-Johnson)
• 1/100 children
• 1/300 - 1/1,000 adults
• Felbamate
• Aplastic anemia 1/2,000 - 1/5,000
• Hepatic failure 1/5,000 - 1/10,000

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Lesser Used Treatments

• Amantadine
• Acetazolamide
• vitamin E
• IVIG
• Magnesium
• Mannitol

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Women and Epilepsy

• fertility, hyposexuality
• oral contraception (enzyme-inducing drugs)
• catamenial seizures (prometrium, acetazolamide,
  clobazam)
• pregnancy
• teratogenicity total population 3,
• single AC 7, two ACs 15 safest AC??
• folic acid supplementation (5mg)
• eclampsia
• labour
• puerperium
• breast feeding

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Novel pharmacological targets

• Potassium channels
• Chloride co-transporters
• Gap junctions
• Magnesium
• Glia neurotransmitter uptake and release,
  extracellular volume regulation, extracellular
  ion concentration regulation, glial ionic
  conductances
• Drug resistant proteins
• Antiepileptogenic (not anticonvulsant) processes
• Axons
• Inflammatory processes
• Neuropeptides
• Sex hormones
• Many others

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Ketogenic Diet A Novel AED Target

• Children with drug resistant epilepsy
• Diet (unpleasant) is administered for 2-3 years
  ketosis occurs in hours, AED effect in days
• 70 improved, 30 seizure free
• Unidentified secondary brain change has
  therapeutic effect
• NEED effective drug which avoids diet

The Atkins Diet new hope for (fat) adults with
seizures
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Seizure Alert Dogs - PAWS

• can and does train Service, Hearing and
  Combination Dogs to recognize and accept
  behaviors associated with an individual client's
  seizures. The dog can be trained to get help or
  stay with the person if needed during a seizure.
  The word "alert" has recently been used to
  identify all dogs who are trained to accept
  seizure behavior. Alert capability is a natural
  occurrence where the dog "alerts" the owner that
  a seizure is about to occur. Experience has shown
  PAWS trainers that true alerting behavior is the
  result of the dog and human developing a very
  close bond. That bond evolves as time passes and
  mutual trust develops.

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• Automated computer-based seizure warning systems
  /- dynamic interventions such as brain
  stimulation, drug ejection
• EEG-based biofeedback and psychological (operant)
  conditioning to prevent seizures

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• Medical inadequacies lack of good treatments
• lack of comprehensive epilepsy care centres
• lack of neurologists trained in epilepsy
• lack of properly trained neurosurgeons and the
• neurosurgical option
• lack of health care professionals trained in
  epilepsy
• including neuropsychologists, nurses, social
  workers,
• psychiatrists
• inadequate public education
• inadequate research

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Available Comprehensive Epilepsy Centres to
Ontario Citizens

• Hospital for Sick Children
• Partial (Embryonic) Centres with epilepsy surgery
  option
• University Health Network, Toronto
• University of Western Ontario, London
• Some epilepsy expertise available in Hamilton,
  Kingston, Ottawa
• Comment grossly inadequate for a population of
  12.5 million with an estimated 87,000 with
  epilepsy

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• No beds routinely available for long-term
  management of poorly controlled epileptics.
• For example, an intractable epileptic needing
  alterations in anticonvulsant regimen with or
  without major comorbidities such as psychosis or
  serious depression.

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Neurosurgeons trained in Epilepsy

• Also, most neurosurgeons receive very little
  formal training in epilepsy and hence are usually
  not comfortable in treating epileptic patients
• Furthermore there are only 2 centres in Ontario
  offering epilepsy surgery (Dr. Valiante to
  elaborate)

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Co-Morbidities Epilepsy

• The co-morbidities are disorders that go along
  with epilepsy. They may be more serious than the
  seizures themselves.
• Common co-morbidities include
• Cognitive
• Psychosocial / Psychiatric
• Behavioural
• Reproductive (adults)
• Sleep

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• Hence the need for greater awareness by
  neurologist to co-morbidities and the need for
  health care professionals trained in epilepsy
  including neuropsychologists, nurses, social
  workers, psychiatrists