overview of the various therapies used for epilepsy

1. Non Pharmacological therapies
in Epilepsy
Dr.Qamar Zaman
FCPS (Neurology),Specialty certified
Neurology(UK).

3. Intractable Epilepsy
• Disagreement over the definition of
intractable epilepsy.
• Seizure frequency of one seizure per month to
one per year or more have been proposed.
• Absolute seizure freedom is the only relevant
outcome consistently associated with
improvement in quality of life.

4. Comorbids linked to intractable seizure
• Patients with one or more seizures over the
past 2 years compared to those in remission
had higher levels of:
• Anxiety and depression.
• Greater perceived stigma and impact of
epilepsy.
• Lower employment.

5. Drug resistance
• Relative drug-resistant epilepsy: failure of two
past AEDs.
• Absolute drug resistance: failure of six AEDs.
• About 16.6% patients are rendered seizure-
free by addition of newly administered AEDs
even after failure of two to five past
antiepileptic drugs(2).

6. Drug responsiveness in Epilepsy
• About 2/3 are responsive to pharmacological
therapy while 1/3 were resistance.
• There was no difference in outcome between
patients with symptomatic and cryptogenic
epilepsy (58% vs 56%) seizure free
respectively)(3).

7. Options in Relative drug resistance
epilepsy
• Trial of medication changes.
• Newer drugs.
• Off label cannabinoids.

8. Drugs in trials
• Verapamil
• Atorvastatin
• NeuropeptideY
• Adenosine
• Thyrotropin-releasing hormone (TRH) and its
analogs(4)

9. Non Pharmacological therapies
• Surgical procedures
• Neurostimulation.
• Dietry therapies.
• Alternative medicine.

10. Surgery
• Resective surgery
• Palliative operations

11. Selection criteria for surgery
• a person should have tried at least 2–3 first
line antiepileptic drug treatments at
appropriate dosage over a period of 2 years.
• Whether to continue with trials of
antiepileptic drugs or to refer directly for
surgery depends upon the chance of surgical
success and the severity of the epilepsy.

12. Benefit vs risk
• The immediate risks of operation have to be
considered in relation to longer term benefits.
• The mortality of the operation may be offset
by the reduction in the chance of SUDEP.
• The loss of memory following an operation
may be offset by the risks to memory of
continued seizures.

13. Benefit vs risk
• Reducing the frequency or stopping the
seizures will result in a significant
improvement of quality of life.
• Less successful with severe psychiatric disease
or severe learning difficulties.
• It is paramount to ascertain the expectations
that care givers, family and the patient have of
surgery.

14. Presurgical assessment
• The presurgical assessment are to identify the
epileptogenic focus.
• Assessment of the risks associated with its
removal.
• It is a multidisciplinary process, involving the
neurologist, neurophysiologist,
neuropsychologist, neurosurgeon, psychiatrist
and radiologist.

16. • Presurgical investigations including clinical
history, seizure semiology, scalp EEG,
neuroimaging and neuropsychometry.
• Invasive EEG recordings.

17. Curative resective surgery
• Lesionectomy
• Surgery in temporal lobe epilepsy
• Extratemporal surgery
• Hemispherectomy

18. Lesionectomy
• Patients with dysembryoplastic neuro‐epithelial
tumors or discrete vascular lesion have a 50–80%
chance of seizure freedom following removal of
the lesion.
• Resections of focal cortical dysplasia have a 10–
50% chance of rendering a patient seizure free.
• The complications depend upon the location of
the lesion, and in particular its proximity to
eloquent cortex.

19. anterior temporal lobectomy or
selective amygdalo‐hippocampectomy.
• Approximately 50% of patients becoming
seizure free in the long term and 20% showing
significant improvement
• The overall mortality of temporal lobectomy is
less than 0.5%.
• A transient hemiparesis and The chance of
significant memory decline depends upon
baseline memory test, age and side of
operation.

20. Extratemporal surgery
• Performed less frequently and mainly consists
of frontal lobe surgery
• Overall, approximately 30–50% become
seizure free, depending on nature and extent
of the pathological basis of the epilepsy, but a
normal MRI reduces these odds(5).
• The risks of operation are related to the site of
resection.

21. Temporal and extratemporal surgery
• The likelihood of remaining seizure-free after
2 years of freedom from seizures was 86% for
10 years after FLE surgery and 90% for 16
years after TLE surgery.
• Etiology has an important role in the
prediction of long-term outcome after surgery.
(6).

22. Hemispherectomy
• Rasmussen’s encephalitis, SWS, and perinatal
infarction had better outcome (70% to 90%)
than those with CD and HME (60% to 80%) (7).
• Approximately 60% of patients with medically
refractory epilepsy who become seizure-free
after resective surgery remain so when AEDs
are withdrawn (8).

24. Palliative procedures
• Corpus callosotomy
• Multiple subpial transection

25. Corpus callosectomy
• Favorable outcome, (50% reduction of
seizures) reported in 60% to 80% of all
patients with atonic seizures and tonic
seizures resulting in falls.
• Favorable outcome for tonic–clonic seizures
varied from 40% to 80%.
• Complex and simple partial seizures were
significantly improved less often(9).

26. • These are disconnection procedure.
• therapeutic options in patients previously
rejected for more traditional resective surgery.
• Much of the success of both procedures
depends on the proper selection of patients
and the experience of the neurologic and
neurosurgical teams.

29. Neuro‐stimulation
• Vagal nerve stimulation (VNS)
• trigeminal nerve stimulation (TNS).
• DBS.
• transcranial magnetic stimulation.

30. VNS
• Response rates range from 50% to 59% .
• 51% reduction in mean monthly seizure
frequency(10) .

32. Criteria
• candidates should meet the following criteria:
(i) medically refractory seizures,
(ii) adequate trials of at least two AEDs,
(iii) exclusion of nonepileptic events,
(iv) ineligibility for epilepsy surgery.

33. • Earlier use produce a higher response rate, as
well as reduce the negative side effects
associated with long-term epilepsy and AED
therapy.
• Patients with history of non adherence to their
AED regimens, particularly those on
polypharmacy, may also be good candidates for
VNS therapy because of the assured compliance
and lack of further drug–drug interactions with
VNS therapy.

34. precaution
• Patients with existing pulmonary or cardiac
disease should be evaluated carefully before
implantation.
• chronic obstructive pulmonary disease may
increase the risk for dyspnea.
• A cardiologist’s evaluation should precede
implantation, with post procedural Holter
monitoring performed if clinically indicated.

35. • General anesthesia although local or regional
anesthesia has been used successfully as well.
• Rare cases of bradycardia, asystole, or both
mandate initial lead testing in the operating
room ; the anesthesiologist should be notified
immediately before this test.

36. • The patient can be discharged after the
procedure, which usually lasts for less than 1
hour, or can be observed overnight.

37. COMPLICATIONS AND ADVERSE
EFFECTS
• Surgical complications and difficulties are rare.
• Incisional infections.
• Fluid accumulation at the generator
• Unilateral vocal cord paralysis in most cases, it
remits completely over several weeks.
• hoarseness or a change in vocal quality and
tingling over the left cervical region on
delivery of the electrical pulse.

38. • Subjective dyspnea or a sensation of muscle
tightening in the neck may occur, without
changes on pulmonary function testing
• Cough or throat pain during stimulus delivery
sometimes necessitates a reduction in current
or pulse width.
• Pulmonary function does not change
significantly in patients without concomitant
lung disease (12)

39. ADVANTAGES AND DISADVANTAGES
• memory, alertness, mood, and communication
have been shown to improve.
• Improvements in QoL independent of treatment
effect on seizure frequency, as well as increased
daytime vigilance, have also been reported.
• without active patient participation, VNS therapy
may be an ideal treatment for the partially
compliant.
• Teratogenesis is not expected with VNS
therapy(13).

40. • The initial minimum cost is arounf $15,000 .
• Over the life time however, this cost
approximates that of many of the new AEDs
(14).

41. ADDENDUM
• Videotapes and information on the VNS
Therapy system are available free to patients,
nurses, and physicians from Cyberonics, Inc.

42. Trigeminal nerve stimulatiom
• Trigeminal nerve stimulation (TNS) has been
introduced.
• This has the advantage that it is carried out
with external electrodes and stimulator just at
night, removing the need for an operation and
not posing problems for MRI examination.

44. • bilateral stimulation of the ophthalmic branch
produced a mean reduction in seizure
frequency of 59% at 12 months (DeGiorgio et
al., 2009).
• active treatment group showed a significant
improvement in responder rate over the
treatment period, from 17.8% at 6 weeks to
40.5% at 18 weeks.

45. Repetitive transcranial magnetic
stimulation (rTMS)
• A noninvasive cortical stimulation method,
with variable results.
• RTMS modulates cortical excitability with
high-frequency rTMS enhancing and low-
frequency rTMS decreasing cortical excitability
in most individuals (Gangitano et al., 2002).

48. • Most studies used daily rTMS sessions for
about 1 week, then evaluated efficacy 2 to 4
weeks later.
• A meta-analysis deduced that low-frequency
rTMS is moderately beneficial, with more
improvement in subjects who have cortical
dysplasia or neocortical epilepsy (Hsu et al.,
2011).

49. DBS
• Stimulation of targets such as the thalamus,
subthalamic nuclei and the hippocampus are
still in the early stages of development.
• These methods are beginning to show
promise not only as palliation, but also as
potential cures.

52. • Reported results similar to those of VNS, with
approximately 50% of patients reporting a
>50% reduction in seizure frequency at 2
years.
• Around 10% of patients reporting periods of
seizure freedom of 3 months or more.

53. Radiosurgery
• Radiosurgery uses a stereotactic frame to
immobilize the head while radiation beams are
precisely directed from different angles to a
target.
• Regions within a few millimeters of the target
receive a substantially reduced radiation dose.
• Initially used for treatment of brain tumors and
AVMs not readily accessible to standard surgery,
with beneficial effect on seizure control.

54. • About 76.9% of patients randomized to the
high dose and 58.8% randomized to the low
dose were free of seizures for the prior 12
months (Barbaro et al., 2009).
• The degree of radiation-induced local vascular
insult and neuronal loss was dose dependent
and predicted long term seizure remission
(Chang et al., 2010).

55. • Neuropsychological testing showed no definite
change in cognitive measures from baseline at
2 years after radiosurgery (Quigg et al., 2011).
• Radiosurgery may have a place in the
treatment of drug resistant mesial temporal
epilepsy.
• However, the long-term risk/benefit ratio of
radio surgery needs better definition.

56. Dietry therapies
1. The Classical Ketogenic Diet
2. Medium Chain Triglyceride Ketogenic Diet
3. The Modified Atkins Diet (MAD)
4. Low Glycemic Index Diet

58. • The diet is the treatment of choice for children
with E1 deficiency and Glut1 deficiency.
• It is an effective and safe treatment for
children with refractory generalized
cryptogenic or symptomatic epilepsies.
• Recent work has suggested that it may be
equally effective in those with refractory
localization-related epilepsy

59. • In adults classic KD had efficacy rates of 22–
55% .
• The modified Atkins diet, and 12–67% .
• ketogenic diets offer promising new
adjunctive strategies for the treatment of
acute status epilepticus in the intensive care
setting.

60. Classical Ketogenic Diet (4:1 or 3:1)
• Fat content makes up around 90% of the diet
with the rest coming from carbs and proteins
combined Strictest form of KD
• Generally started in a hospital environment
Can be achieved using food and tube feeds

61. Pros and Cons:
• Children or young adolescents
• Those with severe forms of epilepsy requiring rapid
improvement
• Families who need close supervision on meal planning
• Cons:
• Very strict
• Cumbersome
• Time consuming
• Precise food weighing required
• Requires in patient stay

62. MCT Ketogenic Diet
• Between 40-70% of energy needs comes from
MCT around 19% Rest comes from LCTs and
protein allowing high carbs.
• MCT needs to be included in every meal and
snack

63. Pros and cons
• Best suited for:
• Those who struggle with the carbohydrate
restriction
• Those who need a strict eating structure
• Cons:
• Can cause GI disturbances
• Precise food weighing required
• Requires in patient stay

64. • the efficacy of the Modified Atkins Diet (7).
53% of children reported a 50% seizure
reduction, with 15% achieving seizure
freedom.
• In adults around 30% reported a similar
reduction and only 3% became seizure free.

65. 4. Low Glycemic Index Diet
• The Glycemic Index (GI) is a measure of the
effect of carbohydrate on blood sugar levels.
Slower absorbing foods in the digestive tract
have a lower glycemic level.

66. • early myoclonic epilepsy,
• early infantile epileptic encephalopathy, and
• myoclonic absence epilepsy.
• severe epileptogenic myoclonic Lennox–Gastaut
syndrome,
• myoclonic–astatic epilepsy,
• severe infantile myoclonic epilepsy,
• and early infantile epileptogenic encephalopathy.
• West syndrome who are refractory to corticosteroids
and other medications (56).
• refractory absence epilepsy without myoclonus (57

67. Mechanism
• increased cerebral energy reserves and increased
GABA shunt activity may be important factors
bestowing an increased resistance to seizures in
ketotic brain tissue (30).
• antioxidant properties (31,32),
• altered purine metabolism due to enhanced
energy reserves (33), action of neuropeptides
(34),
• and alteration of mitochondrial uncoupling
protein (35).

68. ADVERSE EVENTS
• The ketogenic diet may be lethal in certain
circumstances in which cerebral energy
metabolism is deranged.
• pyruvate carboxylase deficiency. (37).
• Mitochondrial disorders or respiratory chain,
such as MERRF, MELAS ,cytochrome oxidase
deficiency (43).
• The diet is contraindicated in patients with
organic acidurias and porphyria (44).

69. Complications
• serious adverse events in 5 of 52 children
• reduced quantity of bone mass, which improves in
response to vitamin D supplementation (5000 IU/day)
• Renal calculi ,Lipemia retinalis .
• Bilateral optic neuropathy responsive to vitamin B
supplements.
• Thinning of hair and, rarely, alopecia may occur.
• severe hypoproteinemia , with lipemia and hemolytic
anemia renal tubular acidosis, and marked increases in
liver function tests

70. Alternative therapies
• Complementary and alternative medicine (CAM)
refers to a group of diverse medical and
healthcare systems, practices, and products that
are not generally considered part of conventional
medicine as practiced in the West.
• Such therapies are widely used by people in
Western countries in general and in particular by
individuals with neurological conditions, including
epilepsy.

71. • Yoga and epilepsy
• Pranayama or deep diaphragmatic breathing
• Asanas or postures
• Dhyana or meditation
• Ayurveda and epilepsy
• EEG Biofeedback and Epilepsy
• Botanicals and Epilepsy
• Acupuncture and Epilepsy
• music therapy studies.

72. • the limited evidence frequently due to a lack
of research funding and inadequate
practitioner training in evidence-based
medicine.
• The literature is clear; patients receiving
placebos do better than those who receive no
treatment at all.

73. • People with epilepsy will often consult their
neurologist about the advisability of adding
CAM therapies to their treatment regimen.
• they should have some awareness of the
dangers, interactions and possible benefits of
these treatments for their patients.

74. • different CAM interventions for epilepsy has
not been adequately studied or proven in
clinical trials.
• contrary to the popular belief that “natural is
safe,” these therapies can be harmful.
• some natural products and their constituent
compounds are under further preclinical
evaluation.

75. • The majority use CAM not for seizure control but
for general health purposes or for alleviation of
treatment-related adverse events or coexisting
conditions, such as depression.
• clinicians should specifically inquire about the use
of such therapies.
• it may uncover clinical needs to be further
investigated and overcome potential harm caused
by these products.