Case report of a child with hypothalamic hamartoma and refractory epilepsy, who improved with epilepsy surgery.

1. An Unusual Cause of Epilepsy
Dr. Pramod Krishnan
Consultant Neurologist
Manipal Institute of Neurological Disorders,
Manipal Hospital, Bangalore.

2. History
 15 month old boy, non-consanguinous parentage.
 Normal birth history.
 Polymorphic seizures since 8 months of age.
 Semiology:
1. Generalized tonic seizures.
2. Head drops.
3. Complex absences.
 10-15 seizures in a day, often in clusters, often on
awakening.
 Global developmental delay.

3. Treatment history
 Initially valproate.
 Later- trial of Vigabatrin, ACTH.
 At admission: Vigabatrin, Valproate, Levetiracetam
and phenobarbitone.
 No benefit with any of the anti-epileptic medications.
 Hormonal work-up was normal.

4. Examination
 Normal anthropometry.
 No neurocutaneous markers.
 Visual regards present. Looks to sound.
 Social smile, recognition of parents present.
 Does not talk, indicate needs or understand
commands.
 Cannot stand. No paucity of limb movements.

5. Impression
 Lennox Gastaut Syndrome phenotype.Lennox Gastaut Syndrome phenotype.
 To look for Symptomatic causes.To look for Symptomatic causes.
 Patient underwent ictal and inter-ictal EEGPatient underwent ictal and inter-ictal EEG

6. Inter-ictal awake and sleep EEG: Bilateral PHR spikes and slow waves noted.

7. Inter-ictal EEG: Spikes are predominantly occipital and temporo-occipital

8. Inter-ictal EEG: Poorly formed background. No generalized spikes/GPFA

9. EEG
 Bilateral PHR, mainly occipital/ temporo-occipital
spikes and slow waves.
 No features of generalized epilepsy.
 High IED burden, suggestive of an epileptic
encephalopathy.
 Ictal recording: unsuccessful due to poor cooperation.
Recorded seizures were marred by movement
artifacts.

10. Electroclinical diagnosis
 Symptomatic localization related epilepsy of probably
posterior head region origin.
 To look for perinatal hypoxic injury/ developmental
abnormalities.
 Patient underwent MRI brain.

23. Diagnosis
 Large hypothalamic hamartoma (HH) presentingLarge hypothalamic hamartoma (HH) presenting
as refractory epilepsy.as refractory epilepsy.
 Pleomorphic seizures are described in HH.Pleomorphic seizures are described in HH.
 Odd points:Odd points:
1.1. No gelastic seizures.No gelastic seizures.
2.2. EEG shows PHR spikes only.EEG shows PHR spikes only.
 Planned for surgery.Planned for surgery.

24. Left pterional craniotomy and Trans-sylvian approach
showing bifurcation of ICA adjoining the hamartoma.

25. Hamartoma visualized deep to ICA and adjoining the optic
nerve.

26. Extent of the hamartoma in relation to the ICA.

27. Extent of the hamartoma in relation to the ICA.

28. Pituitary stalk visualized. Hamartoma arising separate
from pituitary.

29. Excision of the hamartoma.

30. Post-excision.

31. Surgery and Post-operative period.
 Complete excision could not be done because of risk
of injury to hypothalamus, perforators.
 Patient had mild right sided paucity following surgery.
 AEDs were continued.
 No seizures noted following surgery.
 Post-op EEG done after one week showed good
improvement.

32. 1 week post-op EEG showed rare bilateral occipital spikes.

33. Diffuse slowing noted. No clinical or electrographic seizures
were noted.

34. HPE
 Hypothalamic hamartomaHypothalamic hamartoma

35. Follow-up after 2 months
 Seizure free for 6 weeks after surgery.
 Right sided weakness improved significantly.
 Improvement in motor milestones. Was able to walk
unassisted, play, manipulate toys.
 No improvement in language.
 Vigabatrin was discontinued. Continued on Valproate
and Clobazam..

36. Follow-up after 2 months.
 Recurrence of seizures 6 weeks after surgery.
 Semiology: brief gelastic seizures lasting 3-5 seconds.
 Gradual increase in frequency to 5-6/day.
 No regression of milestones.
 EEG showed excess beta activity related to Clobazam.
 3T MRI brain showed residual hamartoma.

37. Repeat EEG at 2 months showing predominance of beta activity.

38. No IEDs were noted. Ictal pattern was marred by artifacts.

39. Pre-op MRI Brain Post- op MRI Brain

40. Pre-op MRI Brain Post- op MRI Brain

41. One year later…..
 Still has gelastic seizures, 5-6/day.
 Probably also has CPS; no generalized seizures.
 On OXC and LEV.
 Walks independently, speaks a few words, plays with
toys, understands commands. No regression.
 Minimal residual right sided weakness.
 Has temper tantrums, crying spells, poor appetite.

44. Ictal rhythm: diffuse attenuation

45. EEG
 Slow BGA.
 Independent right and left temporal, fronto-temporal
spikes (Lt>Rt).
 No generalized spikes or PHR spikes.
 Ictal: diffuse attenuation.
 PET-CT: left temporal hypometabolism.

46. Plan…?
 ? Medical management.
 ? Repeat surgery.

47. Discussion

48. Hypothalamic hamartoma
 Hypothalamic hamartomas are ectopic masses of
neuronal and glial tissue, which may be small and
pedunculated or sessile and relatively large.
 Histology resembles grey matter with varying
proportions of neurons, glia and fiber bundles.
 They are not true tumors. They grow at approximately
the same rate as the rest of the encephalon.
 Do not produce symptoms or signs of nerve tissue
compression.

49. Gelastic seizures
 Gelastic seizures are usually the presenting seizures in
patients with hypothalamic hamartoma.
 51/60 patients reported by Tassinari et al and 6/6 by
Alexis et al had gelastic seizures as the presenting
seizures and 16/19 patients reported by Mullatti et al
had gelastic seizures.
 Adult onset patients were less likely to have gelastic
seizures.

50. Clinical presentation
 Age of onset is 1 day to 15 years (mean is 2.8 years).Age of onset is 1 day to 15 years (mean is 2.8 years).
 Multiple seizure types are common (gelastic, tonic,Multiple seizure types are common (gelastic, tonic,
tonic-clonic, atypical absences, complex partialtonic-clonic, atypical absences, complex partial
seizures, secondary GTCS, drop attacks).seizures, secondary GTCS, drop attacks).
 Seizures and EEG may mimic temporal or frontal lobeSeizures and EEG may mimic temporal or frontal lobe
involvementinvolvement depending on whether the HH connects
to the mamillary bodies or medial hypothalamus.

51. Clinical presentation
 Cognitive deficits are almost universal (80-100%).
 Behavioral problems (PDD, ADHD) occur in 30-40%.
 Correlates with severity of epilepsy.
 Less of a problem in HH without epilepsy.
 Precocious puberty is common with mean age of
onset of 5-6 years.

52. EEG
 EEG is usually abnormal and suggests diffuse or lobar
involvement.
 Lobar features suggest frontal, fronto-temporal or
temporal involvement and is usually bilateral.
Posterior head region abnormalities are not reported.
 Rarely, usually in adults, EEG may be normal.

53. Management
 The high seizure frequency and the severity of the
behavioral and cognitive decline permits its inclusion
as a surgically remediable, catastrophic epilepsy of
childhood, in which extremely frequent seizures,
result in epileptic encephalopathy.
 Mechanisms of plasticity cannot drive functional
compensation unless the lesion is resected.
 Evidence suggest that early intervention results in a
better final developmental outcome.

54. Medical management
 Rare patients, usually adults, have seizures that are
well controlled with AEDs.
 Few patients have transient control with AEDs.
 Most eventually have intractable epilepsy.
 Choice of AEDs depends on the dominant seizure
type and EEG findings.
 Behavioral problems: Typical/ atypical neuroleptics.

55. Surgical management
 Seizures in HH either originate in the HH (gelastic
seizures) or in cortical structures that have a close
relationship to the HH (frontal/ temporal lobes).
 When refractory, they are controlled only by resection,
destruction or disconnection of the hamartoma.
 Resection of HH alleviating generalized seizures
suggest secondary epileptogenesis in the cortex.
 Surgery targeting cortical areas have failed.

56. Surgical management
 Extent of resection or disconnection is the major
determinant of the surgical outcome.
 Surgical resection has a far greater impact on the
major seizures than on minor ones.
 Minor gelastic seizures and CPS may still occur if any
amount of hamartomatous tissue is left in place.
 This is a common occurrence in the face of the lack of
a clear anatomical plane between the hamartoma and
the hypothalamic tissue.

57. Surgical outcome
 11/13 patients in a series had 90% or more reduction11/13 patients in a series had 90% or more reduction
in major seizures. They continued to have minorin major seizures. They continued to have minor
seizures (brief gelastic, CPS) at reduced frequency.seizures (brief gelastic, CPS) at reduced frequency.
 2/13 were totally seizure free.2/13 were totally seizure free.
 4/13 developed deficits which recovered well.4/13 developed deficits which recovered well.
 5/13 required re-surgery.5/13 required re-surgery.
 All had good improvement in cognition and behavior.All had good improvement in cognition and behavior.

58. Importance of the present case
 Hamartomas are rare, especially large ones.
 No gelastic seizures prior to surgery, but appeared
following surgery.
 Unusual EEG findings.
 Challenges related to surgery.
 Early surgery.
 Good seizure outcome.

59. THANK YOU