This document summarizes the case of a 16-year-old male patient admitted to the neurology department for recurrent seizures. The patient has a history of Lennox-Gastaut syndrome diagnosed at NIMHANS. During his 3-day hospital stay, his vital signs and lab tests were monitored daily. He was treated with multiple antiepileptic drugs including injections of methylprednisolone, acetazolamide, pyridoxine, clobazam, phenytoin, levetiracetam and topiramate to control his seizures. His treatment appeared to show improvement in his condition before being discharged.

1. PRESENTED BY:
VISHNU.R.NAIR,
5TH YEAR PHARM.D,
NATIONAL COLLEGE OF PHARMACY(NCP).

2.  NAME: Mr.X
 AGE : 16 years
 SEX: Male
 WEIGHT: 45 kg
 HEIGHT: 150 cm
 BMI: 20
 IP NO: 202084/17
 DEPARTMENT: Neurology
 DOA: 2/08/2017
 DOD: 4/08/2017
 DURATION OF HOSPITAL STAY: 3 days.

3. REASON FOR ADMISSION:
- C/O recurrent seizures
PATIENT MEDICAL HISTORY:
- K/C/O LGS (Lennox-Gastaut Syndrome)
- Above condition  diagnosed at NIMHANS
SOCIAL HABITS:
- Non-smoker
- Non-alcoholic

4. KNOWN ALLERGIES: Nil
FOOD HABITS: Non-vegetarian
PATIENT MEDICAL HISTORY: Inj. Methylpred pulse
(every month)

5. LABORATORY INVESTIGATION:
DATE 2/8/17 3/8/17 4/8/17
TEMPERATURE(in
degree Fahrenheit)
N N N
B.P(in mm/Hg) 110/80 100/70 130/90
PULSE(in beats/min) 88 80 98
RR(in breaths/min) 20 20 20

6. HEMATOLOGICAL TESTS:
HEMATOLOGICAL PARAMETER VALUE OBSERVED
HEMOGLOBIN(in g/dl) 16.7
TLC (in cells/cumm) 9,500
PLATELET COUNT(in cells/cumm) 3,10,000
RBC COUNT(in cells/cumm) 5.18 million

7. URINALYSIS:
COLOUR Clear
PUS CELLS 1-2/hpf
CRYSTALS Nil
BACTERIA Present(few)
SUGAR Nil
WBC Nil
RBC Nil
CASTS Nil
EPITHELIAL CELLS 1-2/hpf

8. OTHER OBSERVATIONS:
SKIN Normal
BUILT & NOURISHMENT Normal
CVS S1S2(+)
RS NVBS
GIT Soft, non-tender
CNS WNL

9. DIAGNOSIS : “LENNOX-
GASTAUT SYNDROME”

11.  Definition
 Epidemiological statistics
 Etiology
 Pathophysiology
 Clinical manifestations
 Diagnosis
 Management strategies for LENNOX-GASTAUT SYNDROME.
 Bibliography/ Reference.

12. “Pediatric encephalopathy syndrome, characterized by
multiple seizure types, mental retardation & abnormal
findings on ECG”.

14. LENNOX-GASTAUT SYNDROME AWARENESS DAY: JANUARY 11, EVERY
YEAR!

15.  Occurs in 1-4% of patients, with childhood epilepsy
 More common in boys than in girls
 Prevalence in boys: 0.1 per 1,000 population
 Prevalence in girls: 0.02 per 1,000 population
 Age onset: 26-28 months.

16.  Mainly occurs due to the following causes:
1. IDIOPATHIC CAUSES
2. CRYPTOGENIC CAUSES
3. SYMPTOMATIC CAUSES:
- Encephalitis
- Meningitis
- Tuberous sclerosis
- Cortical dysplasia
- Hypoxia-ischemia injury

17. - Traumatic brain injury
- Infantile spasms.

18.  The exact mechanism behind this disease occurrence is not clearly defined,
though some theories exist
 According to one hypothesis  maturation of anterior parts of brain  increases
permeability of excitatory inter-hemisphere pathways in frontal areas
 Involvement of immunogenetic mechanisms in triggering LGS is also
reported(via an association between LGS & HLA-Class I Ag B7).

19. A. TONIC SEIZURES:
- Frequency: 17-95%
- More common during NON-REM SLEEP
B. ATYPICAL ABSENCE SEIZURES:
- Frequency: 17-100%
- Associated with incomplete loss of consciousness
- Eye myoclonias may occur

20. C. ATONIC/ MASSIVE MYOCLONIC/ MYOCLONIC+ ATONIC SEIZURES:
- Frequency: 10-50%
- May lead to a sudden fall, causing injuries
D. OTHER TYPES :
Include:
1. GTCS(15%)
2. Complex partial seizures(5%)
3. Absence Status Epilepticus(SE)
4. Tonic SE
5. Non-convulsive SE

21. E. GENERAL SYMPTOMS:
Include:
1. Abnormalities in mental status functions
2. Abnormalities in levels of consciousness
3. Mood instability
4. Personality disturbances
5. Acute psychotic episodes(in older children)
6. Social isolation(in older children)
7. Memory impairment.

22. A. ELECTROENCEPHALOGRAPHY:
- Here  both waking & sleeping EEG is recorded
- Helps to capture & classify different seizure types in the patient
- Video/EEG Telemetry is also helpful
B. INTERICTAL EEG:
- Helps to detect prognosis of the disease
- Used to check spikes pattern observed in an EEG

23. C. NEUROIMAGING STUDIES:
- MRI is preferred over CT-Scan
- Used to detect:
a. Brain malformations
b. Tuberous sclerosis
c. Hypoxia-ischemia injury
- PET/SPECT scan is not commonly used.

24.  Includes:
a. Goals of therapy
b. Treatment guidelines
c. Pharmacotherapy
d. Non-pharmacotherapy.

25.  To avoid complications
 To focus on reducing/eliminating seizure frequency
 To focus on minimum ADRs, with maximal drug effectiveness
 To focus on using minimum number of drugs
 To focus on ameliorating symptoms
 To improve HRQoL.

26.  Usually, 3 categories of drugs can be used:
1. FIRST-LINE AGENTS
2. SECOND-LINE AGENTS
3. THIRD-LINE AGENTS.

27. 1. FIRST-LINE AGENTS:
- Based on clinical experience
- Drugs include:
a. Valproic acid
b. Benzodiazepines(Clonazepam, clobazam, nitrazepam)
- NOTE: NITRAZEPAM is not FDA-APPROVED for treatment of LGS, yet, it is
used in some Western Countries
2. SECOND-LINE AGENTS:
- These are treatments, that are believed to be effective, based on OPEN-LABEL
CONTROLLED STUDIES
- Drugs include:
a. Vigabatrin
b. Lacosamide.

28. 3. THIRD-LINE AGENTS:
- They are treatments, that are believed to be effective, based on DOUBLE-BLIND
PLACEBO-CONTROLLED STUDIES
- Include:
a. Lamotrigine
b. Topiramate
c. Felbamate
d. Rufinamide.

29.  Drugs include:
1. Valproic acid 10. Clobazam
2. Lamotrigine
3. Topiramate
4. Felbamate
5. Zonisamide
6. Vigabatrin
7. Levetiracetam
8. Rufinamide
9. Clonazepam

30. 1. VALPROIC ACID:
- Considered as 1st line choice for treating LGS(for the past 2 decades)
- More effective in CRYPTOGENIC LGS
- Used mainly as DIVALPROEX
- Use in children, greater than 10 years of age
- ADRs:
a. Hepatotoxicity(if used in children < 3 years of age)
b. Weight gain
c. Alopecia
d. Tremors.
- DOSE: 60 mg/kg/day(Max. dose).

31. 2. LAMOTRIGINE:
- Useful for LGS patients, in spite of high risk of IDIOSYNCRATIC
DERMATOLOGICAL REACTIONS
- Use other anticonvulsant medications along with it, cautiously
- Start with a low dose, and then titre slowly
- ADRs:
a. life-threatening hypersensitivity(skin rashes)
b. SJS
c. TEN.

32. - DOSAGE REGIMEN:
a. With Valproate: 0.5-5 mg/kg/day; PO
b. Without Valproate: 5-10 mg/kg/day; PO
c. With enzyme-inducing AEDs: 5-15 mg/kg/day; PO
d. Maximum dose: 400 mg/day; PO.

33. 3. TOPIRAMATE:
- Safe & effective as adjunctive therapy for LGS
- ADRs:
a. Nephrolithiasis
b. Weight loss
- DOSE : 6 mg/kg/day; PO.

34. 4. FELBAMATE:
- Effective in LGS patients
- High risk of APLASTIC ANEMIA  Mandates this drug to be used as 3rd/4th line
choice for LGS
- ADRs:
a. URTI
b. Aplastic anemia
c. Purpura
- DOSE:
a. Use in patients> 2 years of age
b. Max. dose: 45 mg/kg/day
c. Reduce concomitant dose of CBZ, phenytoin, valproate by 20%.

35. 5. ZONISAMIDE:
- Effective as long-term adjuvant therapy in LGS patients
- ADRs:
a. Somnolence
b. Dizziness
c. Nephrolithiasis
- Avoid usage in children < 16 years
- DOSE: 600 mg PO daily(Max. dose).

36. 6. VIGABATRIN:
- Approved by US-FDA in 2009, as:
a. Monotherapy for WEST SYNDROME(in patients, aged 1 month-2 years)
b. Adjuvant treatment for adults with refractory complex partial seizures.
- ADRs:
a. Somnolence
b. Weight gain
c. Irreversible visual field defects, due to retinal atrophy.
- Avoid usage in patients, below 1 month of age
- DOSE : For patients, aged 1 month-2 years: 150 mg/kg/day(Max. dose).

37. 7. LEVETIRACETAM:
- Mainly FDA-approved for partial seizures
- May be used for a number of seizure types in LGS
- ADRs:
a. Sedation
b. Increased B.P(in children <4 years)
c. Dizziness.
- DOSE:
a. For patients, aged 4-12 years: 30 mg/kg/day(Max.dose)
b. For patients, aged >12 years: 1.5 g, BD(Max.dose).

38. 8. RUFINAMIDE:
- Drug  modulates sodium channel activity  prolongs its inactivated state
- Used as adjunct therapy in adults & children aged 1 year or older with LGS
- ADRs:
a. Dizziness
b. SJS
- DOSE : 3,200 mg/day(Max.dose).

39. 9. CLONAZEPAM:
- Effective 1st line AED for LGS
- DEMERITS :
a. ADRs, with long-term usage
b. Development of tolerance
- Since there is risk of development of tolerance  it is advised to:
a. Use on alternative days, OR
b. Use alternate 2 BZDs daily.

40. 10. CLOBAZAM:
- Drug  binds to GABA-A receptor  potentiates GABA-ergic neurotransmission
- Drug  has an active metabolite(N-DESMETHYL CLOBAZAM)  shows long
duration of action
- Used for LGS in patients, older than 2 years
- ADRs:
a. Sedation
b. Weight gain
c. URTI
- DOSE: 40 mg/day(Max.dose).

41. Includes:
a. Corpus callostomy
b. Vagus nerve stimulation
c. Focal cortical resection
d. Ketogenic diet
e. Patient counselling tips.

42. A. CORPUS CALLOSTOMY:
- Only effective to reduce DROP ATTACKS
- Considered PALLIATIVE than CURATIVE
B. VAGAL NERVE STIMULATION:
- Done by means of a surgically-implanted programmable device
- Approved by FDA, as adjunct treatment for reducing seizure frequency in LGS
- Requires follow-up period within 5 years
C. FOCAL CORTICAL RESECTION:
- Used in rare cases
- Resection of localized lesion(vascular lesion, tumor)  improves seizure control
in LGS

43. D. KETOGENIC DIET:
- Consists of high ratio of FATS to PROTEINS and CARBOHYDRATES
- Ratio is usually in between 2:1 to 4:1
- Benefits include:
a. Fewer seizures
b. Reduced drowsiness
c. Better behavior
d. Requires fewer number of concomitant AEDs.

44. - Diet includes:
a. HIGH FAT(Nuts, cream, butter)
b. LOW CARBOHYDRATES (Starchy fruits, bread, pasta, grains, sugar)
c. ADEQUATE PROTEINS(Pulses, soyabeans)
E. PATIENT COUNSELLING TIPS:
1. Avoid consuming artificial sweeteners/additives
2. Avoid skipping meals, especially breakfast
3. Avoid all “white products”, like:
a. White flour
b. White sugar
c. Table salt
d. White rice.

45. 4. Do not skip taking medicines, without doctor’s approval
5. Get enough sleep(since sleep deprivation can trigger seizures)
6. Manage stress, and avoid stressful situations.

46. TREATMENT GIVEN:
T. NAME G. NAME DOSE ROUTE DURATION 2/3 3/3 4/3
Inj.
Methylpred
nisolone
Methylpred
nisolone
1 g i.v OD Y Y Y
T. Dianox Acetazolami
de
250 mg P/O 1-0-1 Y Y Y
T.
Benadone
Pyridoxine 40 mg P/O 1-0-1 Y Y Y
T. Shelcal Ca + Vit.D3 500 mg P/O 0-1-0 Y Y Y
T. Frisium Clobazam 7 mg P/0 ½-0-½ Y Y Y
T. Lamotrigine Lamotrigin
e
100 mg P/O 1-0-2 Y Y Y
T. Eptoin Phenytoin 100 mg P/O 1-0-2 Y Y Y
T. Levipil Levetiracet
am
1 g P/O 1-0-1 Y Y Y
T. Topaz Topiramate 10o mg P/O 0-0-1 Y Y Y

47. PROGRESS CHART + ASSESSMENT OF CURRENT
THERAPY:
1. DAY 1(2/3/2017):
- Patient was admitted with c/o recurrent seizures
- k/c/o LGS(diagnosed at NIMHANS)
- The following treatment strategy was initiated:
A. INJ.METHYLPREDNISOLONE:
- Due to various etiologies  a SIGNIFICANT STRESS RESPONSE is
experienced by the developing brain  results in LGS
- Methylprednisolone (steroid) has potential to reset the deranged homeostatic
mechanisms of the brain  results in:
i. Reduced convulsive tendency
ii. Improved developmental trajectory(www.annalsofian.org)

48. B. T. DIANOX(ACETAZOLAMIDE):
- Acetazolamide has been shown to be effective in the treatment of some types of
epileptic seizures
- Drug  shows the following actions:
i. Increases seizure threshold
ii. Minimizes seizure frequency via its effects on the amount of CO2 in brain fluids
iii. Inhibits chemical pathways that play significant role in seizures.
C. T. BENADONE(PYRIDOXINE):
- Usually indicated for PYRIDOXINE-RESPONSIVE SEIZURES
- Here, it is indicated to reduce seizure frequency & also helps to prevent
exacerbation of clinical seizures &/ encephalopathy during an acute illness.

49. D. T. SHELCAL(VITAMIN D3+ CALCIUM CARBONATE):
- Long-term use of AEDs  can result in loss of bone mass & increased risk of
OSTEOPOROSIS
- Calcium & Vitamin D3 supplementation  improves BMD in patient taking
AED!(https://www.wiley.com)
E. T. FRISIUM(CLOBAZAM):
- Novel 1,5-benzodiazepine, approved by the US-FDA for the treatment of LGS in
2011
- Confers less sedative properties compared to other benzodiazepines(Marius
Pernea, Alastair G.Sutcliffe. “Clobazam and its use in Epilepsy”).

50. F. T. LAMOTRIGINE:
- Addition of lamotrigine to other anti-seizure drugs resulted in improved seizure
control (Motte et al.,1997)  this shows that lamotrigine is an effective & well-
tolerated drug for this treatment-resistant form of epilepsy.
G. T. EPTOIN(PHENYTOIN):
- Drug  shows the following actions, that results in anti-epileptic effects:
i. Drug  promotes Na+ efflux / reduces its influx from membranes in motor
cortex neurons
ii. Drug  slows conduction velocity.

51. H. T.LEVIPIL(LEVETIRACETAM):
- Mainly FDA-approved for partial seizures
- May be used for a number of seizure types in LGS
I. T.TOPAZ(TOPIRAMATE):
- Safe & effective as adjunctive therapy for LGS
- Demonstrated to be effective for LGS(Sachdeo et al., 1999)

52. 2. DAY 2(03/08/2017):
- Patient is conscious & oriented
- No fresh complaints noted
3. DAY 3(04/08/2017):
- No fresh complaints
- Patient was found to be symptomatically better, & was discharged appropriately.
. .

53. DISCHARGE SUMMARY:
- A 16-year old male patient was admitted, with H/O multiple episodes of atonic,
absent & myoclonic seizures
- He was evaluated in detail in NIMHANS, & was diagnosed to have LGS
- Patient was advised to have Inj. Methylpred pulse every month
- He was treated with Inj. Methylprednisolone(1 g) for 5 days, along with other
antiepileptics
- He was advised to review after 1 month, for the next dose of METHYLPRED
PULSE.

54. DISCHARGE ADVICE:
Patient was prescribed the following medications upon discharge:
1. T. TOPAZ 50 mg(1-0-0)
2. T. LEVIPIL 1 g (1-0-1)
3. T. EPTOIN 100 mg (1-0-2)
4. T. LAMOTRIGINE 100 mg (1-0-1)
5. T. FRISIUM 10 mg (1-0-1)
6. T. DULCOLAX (2 * HS)
7. T. WYSOLONE 40 mg (1-0-0) [For 2 weeks]
FOR 1 MONTH

55. POINTS TO PHYSICIAN:
1. Concomitant administration of TOPIRAMATE & CLOBAZAM  increased risk
of CNS effects  monitor for increased sedation, respiratory depression!
2. Concomitant administration of TOPIRAMATE & ACETAZOLAMIDE  high
risk of NEPHROLITHIASIS!

56. DRUG-BASED COUNSELLING TIPS:
1. T.TOPAZ(TOPIRAMATE):
- Report to physician if there is change in visual field(visual field defects)!
2. T.LEVIPIL(LEVETIRACETAM):
- Can be taken with/without food
- Increase intake of Vitamin B6 rich foods
3. T. EPTOIN(PHENYTOIN):
- Patient should be advised to maintain good dental hygiene

57. 4. T.LAMOTRIGINE:
- Although drug can be taken with/without food  taking drug with food/plenty of
water is advised(to prevent gastric distress)
6. T.DULCOLAX(BISACODYL):
- Oral tablet should not be taken WITHIN 1 HOUR OF CONSUMING MILK/ANY
DAIRY PRODUCTS
- For rapid effect  drug should be taken with a glass of water on an empty
stomach
7. T.WYSOLONE(PREDNISOLONE):
- Should be taken after meals/with food/milk to reduce GI effects
- An increase in the dietary intake of Pyridoxine, Vitamin C, Vitamin D, Folate,
Calcium & Phosphorus is recommended

58. DISEASE-RELATED COUNSELLING TIPS:
1. EPSOM SALT:
- EPSOM SALT  Contains magnesium sulphate  changes psychochemical cell
relationships in the brain  reduces frequency of seizures and convulsions
- Use in the form of:
a. Epsom salt bath (2-3 times/ week)
b. Add half tsp of salt to orange juice / water  drink every morning
2. LIME:
- Popular Ayurvedic remedy
- Lime  helps improve blood circulation to brain
- Also normalizes excess calcium that may hamper brain functionality
- Use in the form of:
a. (2 tsp. lime juice + half tsp. baking soda + water)  drink daily before going to bed
b. Apply lime juice on head  massage thoroughly for a few mins.  do daily before
taking a shower

59. 3. GET ENOUGH SLEEP, AS SLEEP DEPRIVATION TRIGGERS SEIZURES
4. MANAGE STRESS AND AVOID STRESSFUL SITUATIONS
5. FOLLOW A KETOGENIC DIET, COMPRISING:
a. High fat(nuts, cream, butter)
b. Low carbohydrate (starchy fruits, bread, pasta, grains, sugar)
c. Adequate protein (pulses, soybean etc.)
d. Helps treat DIFFICULT TO CONTROL (REFRACTORY) EPILEPSY in
children……………..

60. THANK YOU!!!!!!