neurophysiology lecture about hypsarrythmia and other variants

1. Messy!
Wafaa AL Shehhi
Pediatric Neurology Resident
Dr. Iftetah AL Homoud
Consultant, clinical neurophysiology.
April 2014

3. Case History
 Pre/post natal Hx:
 Uneventful pregnancy, full term, NSVD.
 Developmental assessment: He sat at the age of 1 year and started
walking at the age of 18 months and now he is walking and he is
prone to frequent fallings, poor or weak head control. The patient
has nonspecific babbling. He is only saying “bab and mom”
nonspecifically.

4. Case History
• Vaccination.
• Nutrition.
• Medical/surgical Hx.
• Allergy Hx.
• Drug Hx: clonazepam 0.25mg Q8hrs.

5. Case History
• Family Hx:
• No H/O consanguinity.
• No F/H/O same symptoms.

6. Physical Examination
 Vital sings: stable.
 Growth parameters: weight 11 kg 10th
– 25th
, Ht 90 cm 90th
,
HC 49 cm 50th
-75th
.
 No dysmorphic features.
 Cranial nerves: following objects and there is normal extraocular
movement.
 Motor exam: axial and appendicular hypotonia, DTR +1 all over.
 1 café au lait spot at his right hand measured 1.5 x 1.5 cm.
 systemic examination unremarkable.

7. DD
 Infantile spasms (west syndrome).
 HIE.
 Pyridoxine deficiency.
 Neurometabolic disorders.
 Biotinidase deficiency.
 Tuberous sclerosis.
 Congenital infections.

8. Work up
• Ammonia, lactate, tandem MS, G-CMS urine: Normal.
• Brain MRI: Unremarkable.
• EEG.

16. Management
 Started on vigabatrin 250mg Q12.
 With escalating the dose.
 Waiting for the next visit.

18. Infantile spasm
 Infantile spasms (IS) is an age-specific convulsive disorder of infancy
and early childhood.
 Infantile spasms were described first by West in 1841 (1)The triad
of spasms, arrest of psychomotor development, and hypsarhythmia
is known as West syndrome.
(1)West, WJ. On a peculiar form of infantile convulsions. Lancet 1841; 1:724.

19. Infantile spasm
 Age of onset — The majority (90 percent) of affected children present at less
than one year of age, with a range from one day to 4.5 years of age (2)
 Spasms — Spasms can involve the muscles of the neck, trunk, and
extremities [2]. They are usually symmetric and synchronous, but there can
be variant clinical patterns. (3)
 Three clinical types of spasms (3)
 In one report, 5042 seizures in 24 infants were classified as flexor, extensor,
and mixed flexor-extensor in 33.9, 22.5, and 42.0 percent, respectively [6].
Most infants have more than one type of spasm.
(2)Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: a U.S. consensus report. Epilepsia 2010; 51:2175.
(3)Kellaway P, Hrachovy RA, Frost JD Jr, Zion T. Precise characterization and quantification of infantile spasms. Ann
Neurol 1979; 6:214.

20. Infantile spasm
 Other clinical manifestations :
 Neurodevelopmental delay and/or regression with motor and cognitive
manifestations.
 Seizure types other than spasms occur in one-third to one-half of patients with
IS [4]. These include partial, myoclonic, tonic, and tonic clonic seizures.
(4)Koo B, Hwang PA, Logan WJ. Infantile spasms: outcome and prognostic factors of cryptogenic and
symptomatic groups. Neurology 1993; 43:2322.

21. Classification
 Symptomatic: (6) if an identifiable factor is responsible
for the syndrome.
 Virtually any disorder that can produce brain damage
can be associated with infantile spasms.
 Hydrocephalus.
 Microcephaly.
(6)http://www.uptodate.com/contents/clinical-features-and-diagnosis-of-
infantile-spasms?
source=search_result&search=infantile+spasms+children&selectedTitle=
1~47

22. Classification
 Tuberous sclerosis.
 HIE.
 Congenital infections.
 Meningitis /Encephalitis .
 Pyridoxine deficiency.
 Maple syrup urine disease.
 Phenylketonuria.
 Biotinidase deficiency.

23. Classification
 Cryptogenic: if no cause is identified but a cause is
suspected and the epilepsy is presumed to be
symptomatic.

24. Diagnosis
 Electroencephalography:
 Interictal patterns (5) :
 Hypsarrhythmia:“random high voltage slow waves and
spikes.These spikes vary from moment to moment, both
in duration and in location. At times they appear to be
focal,and a few seconds later they seem to originate
from multiple foci.
(5) *Peter Kellaway Section of Neurophysiology, Infantile Epileptic Encephalopathy with
Hypsarrhythmia, Journal of Clinical Neurophysiology 20(6):408–425,
choaticchoatic

26. Hypsarrythmia: Variations on the Theme
 24 hour study.
 1-4 months.
 67 patients: 6 cryptogenic, 61 symptomatic.
 Results:
 Variations from minute to minute.

27. Hypsarrythmia: Variations on the Theme
 “ Modified” hypsarrythmia patterns:
 Interhemispheric Synchronization.
 Asymmetry (hemi or unilateral hyps).
 Consistent focus of abnormal discharge.
 Episodes of attenuation-focal,regional,generalized.
 High voltage bilateral asynchronous slowing.
 Change in pattern between a wake and sleep states.
 Relative normalization.

28. Interictal patterns
 Hypsarrhythmia with Increased Interhemispheric Synchronization:
 Multifocal spike and sharp wave activity and the diffuse
asynchronous slow wave activity are replaced or intermixed with
activity that exhibits a significant degree of interhemispheric
synchrony and symmetry.

30. Interictal patterns
 Asymmetric Hypsarrhythmia:
 Hemihypsarrhythmia or unilateral hypsarrhythmia and is characterized by
the presence of hypsarrhythmia, with a consistent amplitude asymmetry
between hemispheres.
 Always associated with underlying structural abnormalities of the brain.

32. Interictal patterns
 Hypsarrhythmia with a Consistent Focus of Abnormal Discharge:
 A distinct focus of spike or sharp wave activity is superimposed on a
typical hypsarrhythmic background.

34. Interictal patterns
 Hypsarrhythmia with Episodes of Voltage Attenuation:
 A hypsarrhythmic pattern that is interrupted by episodes of
generalized, regional, or localized voltage attenuation that typically
persist from 2 to 10 seconds.
 These episodes most commonly are seen during nonrapid eye
movement (NREM) sleep.

36. Interictal patterns
 Hypsarrhythmia with Little Spike or Sharp Activity:
 This is a rare variant and consists of high-voltage,asynchronous, and
synchronous slow activity with little or no spike/sharp wave
components.

38. Interictal patterns
 Transient alterations occur in the hypsarrhythmic pattern
throughout the day in relation to the sleep states.(5)
 During NREM sleep, the voltage of the background activity typically
increases, and there is a tendency for grouping of the multifocal
spike and sharp wave activity, often resulting in a pattern with a
periodic appearance.
(5)Peter Kellaway Section of Neurophysiology, Infantile Epileptic
Encephalopathy with Hypsarrhythmia, Journal of Clinical Neurophysiology
20(6):408–425,

39. Interictal patterns
 Attenuations or electrodecremental episodes frequently occur
during NREM sleep.
 Usually the hypsarrhythmic pattern is markedly reduced or
completely absent during rapid eye movement (REM) sleep.
 On arousal from NREM sleep,there is also typically a reduction in
amplitude or complete disappearance of the hypsarrhythmic
pattern that may persist for a few seconds to many minutes.

41. Interictal patterns
 Hypsarrhythmia characteristically disappears with increasing age.
 Hypsarrhythmia disappeared in 94% of patients by age 5 years and
in 100% by age 7.

42. Other Interictal Patterns
 Focal or multifocal spikes and sharp waves.
 A bnormally slow or fast rhythms.
 Diffuse slowing.
 Focal slowing.
 Focal depression.
 Paroxysmal slow or fast bursts.
 A slow spike and wave pattern or continuous spindling.

43. Ictal patterns
(!) A high-voltage,frontal-dominant, generalized slow wave transient
followed by a period of attenuation. (5).
(2) A generalized sharp and slow wave complex.
(3) A generalized sharp and slow wave complex followed by a period of
voltage attenuation.
(4) A period of voltage attenuation only.
(5) A generalized slow transient only.
(5) *Peter Kellaway Section of Neurophysiology, Infantile Epileptic Encephalopathy
with Hypsarrhythmia, Journal of Clinical Neurophysiology 20(6):408–425,

44. Ictal patterns
(6) A period of attenuation with superimposed fast activity.
(7) A generalized slow wave transient followed by a period of voltage
attenuation with superimposed fast activity.
(8) A period of attenuation with rhythmic slow activity.
(9) Fast activity only.

45. Ictal patterns
(10) A sharp and slow wave complex followed by a period of voltage
attenuation with superimposed fact activity.
(11) A period of voltage attenuation with superimposed fast activity
followed by rhythmic slow activity.

46. Treatment
 Hormonal therapy: (2) (6)
 ACTH.
 Corticosteroids.
(2)Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: a U.S. consensus report. Epilepsia 2010;
51:2175.
(6)Go CY, Mackay MT, Weiss SK, et al. Evidence-based guideline update: medical treatment of
infantile spasms. Report of the Guideline Development Subcommittee of the American
Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology
2012; 78:1974.

47. Treatment
 Antiepileptic drugs:
 Vigabatrin.
 Other AEDs:
a. Valproic acid.
b. Zonisamide.
c. Topiramate.

48. Treatment
 OTHER MEDICAL THERAPIES
 Pyridoxine.
 Ketogenic diet.
 Others.

49. Prognosis

50. Thank you