Angelman Syndrome and Epilepsy

Abstract

Twenty-six patients with Angelman syndrome (AS), of which 19 had 15ql 1-13 maternal deletion, were studied and followed at the University of San Paulo, Brazil, with particular reference to the prevalence and type of epilepsy and its response to antiepileptic drugs.

Full text

is
generated
in
the
nodules
or
in
the
adjacent
neocortex.
The
heterotopia
are
part
of
an
abnormal
circuitry involving
surrounding
cortex.
EEG-fMRI
studies
of
grey
matter
heterotopia
at
the
Montreal
Neurological
Institute
showed
metabolic
responses
in
the
heterotopia
while
spikes
were
generated
in
the
neocortex
(Kobayashi
Eet
al.
Brain
2006;129:366-374).
Activation
responses
reflected
excitation
involving
the
heterotopia
and
surrounding
cortex,
and
deactivation
also
reflected
a
distant,
extra-lesional
inhibition. EEG-fMRI
is
a
non-invasive
procedure
that
may
explain
the
epileptogenicity
of
neuronal
migration
disorders
and
the
involvement
of
areas
of
the
brain
distant
from
the
heterotopia.
ANGELMAN
SYNDROME
AND EPILEPSY
Twenty-six
patients
with
Angelman
syndrome
(AS),
of
which
19
had
15ql
1-13
maternal
deletion,
were
studied
and
followed
at
the University
of
San
Paulo,
Brazil,
with
particular
reference
to
the
prevalence
and
type
of
epilepsy
and
its
response
to
antiepileptic
drugs.
Epilepsy
occurred
in
22
patients
(85%),
19
with
deletion
and
3
without
positive
genetic
confirmation.
All
19
patients
with
deletion
had
generalized
seizures,
and
10
(53%)
had
partial
seizures.
Yideo-EEG
uncovered
atypical
absence
and
subtle
myoclonic
seizures,
often
missed
by
parents;
it
also
recorded
nonconvulsive
status
that
is
sometimes
prolonged
and
associated
with
cognitive
decline
in
7.
Mean
age
at
onset
of
seizures
was
1
year
1
month,
and
in
18
patients,
epilepsy
preceded
the
clinical
diagnosis
of
AS.
Five
(26%)
had
their
first
seizure
with
fever,
and
10
(53%)
had
epilepsy
aggravated
by
fever.
Sixteen
(84%)
had
status
epilepticus,
associated
with
hyperthermia
in
7.
Valproic
acid,
alone
or
in
combination
with
phenobarbital
or
clonazepam,
improved
seizure
control
while
carbamazepine,
oxcarbazepine,
and
vigabatrin
caused
aggravation
of
seizures.
Refractory
seizures
occurred
in
16
(84%)
during
infancy
and
early
childhood,
but
seizure
frequency
decreased
at
a
mean
age
of
5.3
years.
Improvement
in
seizure
frequency
and
severity
continued
through
late
childhood
and
puberty.
(Valente
KD,
Koiffmann
CP,
Fridman
C,
et
al.
Epilepsy
in
patients
with
Angelman
syndrome
caused
by
deletion
of
the
chromosome
15ql
1-13.
Arch
Neurol
January
2006;63:122-128).
(Respond:
Kette
D
Valente
MD
PhD,
Department
of
Psychiatry,
University
of
Sao
Paulo,
R
Jesuino
Arruda,
901/51,
04532-082
Sao
Paulo,
SP
Brazil).
COMMENT.
Angelman
syndrome
is
characterized
by
developmental
delay,
severe
mental
retardation,
paroxysmal
laughter,
ataxia
associated
with
hand
flapping,
seizures,
and
stereotyped
jerky
movements,
regarded
as
cortical
myoclonus
(Guerrini
R
et
al.
Ann
Neurol
1996;40:39-48).
Physical
signs
include
microcephaly,
prominent
jaw,
wide
mouth,
pointed
chin,
and
hypopigmentation.
Seizures
are
mainly
generalized,
frequently
partial,
atypical
absence,
myoclonic,
sometimes
included
as
a
cause
of
West,
or
Lennox-Gastaut
syndromes,
and,
as
shown
in
the
above
study,
often
febrile
in
type.
The
typical
interictal
EEG abnormality
shows
rhythmic
slow
waves
at
4-6
Hz
and
runs
of
2-3
Hz
slow
spike-wave
complexes
anteriorly.
Eye
closure
is
accompanied
by
spikes
and
2-4
Hz
slow
waves
posteriorly
(Robb
SA
et
al.
Arch
Dis
Child
1989;64:83-86;
Sugimoto
T
et
al.
Epilepsia
1992;33:1078-1082).
Status
epilepticus
is
a
frequent
complication,
sometimes
precipitated
by
hyperthermia,
and
often
recurrent.
Age-related
improvement
in
seizure
frequency
and
severity
is
an
additional
characteristic.
Pediatric
Neurology
Briefs
2006
10

The
diagnosis
of
AS
should
be
considered
in
infants
with
developmental
delay
and
generalized
cryptogenic
seizures
resistant
to
medication.
Diagnosis
is
confirmed
in
85%
by
genetic
testing
and
deletion
of
chromosome
15ql
1-13.
In
rare
cases,
other
genetic
mechanisms
have been
uncovered,
and
in
15%
of
cases,
diagnosis
is
made
on
clinical
and
EEG
findings
alone.
Where
possible,
the
genetic
cause
should
be
determined
as
a
prelude
to
family
counseling.
RISK
OF
EMERGENCY
INTRACRANIAL
PATHOLOGY
AFTER
FIRST
COMPLEX
FEBRILE
SEIZURE
The
outcome
of
71
neurologically
normal
children
after
a
first
complex
febrile
seizure
(CFS)
was
determined
by
review
of
neuroimaging
findings,
telephone
interviews,
and
medical
records,
in
a
prospective
study
at
Columbia
University
College
of
Physicians
and
Surgeons,
New
York. During
the
study
period
March
1999-July
2002,
293
children
presented
to
the
ED
with
a
first
febrile
seizure
and
of
these,
79
(27%)
were
complex
in
type.
Complex
characteristics
(focal, multiple
episodes
in
a
24
hour
period,
and
prolonged
duration
>15
min)
were
single
in
51
(72%),
of
which
20
were
focal,
22
multiple
episodes,
and
9
prolonged
CFS.
Twenty
had
seizures
with
multiple
complex
features.
Lumbar
puncture
was
performed
in
10
(14%)
in
the
ED,
and
none
had
meningitis.
Emergency
cranial
CT
scans
were
obtained
in
the
ED
for
10
patients
(14%),
and
13
(18%)
patients
were
admitted.
A
total
of
46
(65%)
patients
had
emergency
CT
scans
in
the
ED
and/or
MRI
scans
within
1
week
after
the
ED
visit
and
were
followed
prospectively.
Outcome
was
determined
by
telephone
interview
within
the
subsequent
4
to
44
months
(median
22.4
months)
in
12
(17%)
patients
and
by
medical
record
review
in
13
(18%).
Of
the
71
patients studied,
none
had
intracranial
pathology
requiring
emergency
medical
or
neurosurgical
intervention
(95%
confidence
interval:
4%).
It
is
concluded
that
the
risk
of
emergency
intracranial
pathology
following a
CFS
is
low,
and
routine
emergency
neuroimaging
in
children
with
first
complex
febrile
seizures
is
probably
unnecessary.
(Teng
D,
Dayan
P,
Tyler
S,
et
al.
Risk
of
intracranial
pathologic
conditions
requiring
emergency
intervention
after
a
first
complex
febrile
seizure
episode
among
children.
Pediatrics
February
2006;117:304-308).
(Respond:
Dale
C
Hesdorffer
PhD,
Gertrude
H
Sergievsky
Center,
Columbia
University,
630
W
168th
St,
P&S
Unit
16,
New
York,
NY
10032).
COMMENT.
In
children
presenting
with
a
complex
febrile
seizure
(CFS),
each
patient
must
be
evaluated
clinically
to
exclude
possible
meningitis,
encephalitis
or
abscess,
and
routine
neuroimaging
in
the
ED
is
considered
unnecessary.
CT
scan
is
not
without
risk,
both
from
radiation
and the
need
for
sedation.
Risk
factors
for
subsequent
epilepsy
in
children
with
FS
include
the
CFS,
a
family history
of
epilepsy,
and
neurodevelopmental
abnormality
(in
Commentary
by
DiMario
FJ
Jr.
Pediatrics
2006;117:528-530);
adapted
from
Shinnar
S
et
al.
J
Child
Neurol
2002;17(suppl
1):S44-S52).
Earlier
studies
found
that
the
duration
of
the
FS
was
the
most
important
determinant
of
the
later
development
of
epilepsy
and
an
abnormal
EEG
(Millichap
JG
et
al.
Neurology
1960;10:643-653;
Maher
J
et
al.
Brain
1995;118:1521-1528).
Neuroimaging
should
be
considered
in
the
individual
patient
with
a
CFS
that
is
very
prolonged
or
is
followed
by
a
persistent
epileptiform
abnormality
in
the
EEG.
Pediatric
Neurology
Briefs
2006
11