Auteur(s) : Bruno Zanotelli Monnerat firstname.lastname@example.org, Tonicarlo
Rodrigues Velasco, Frederico Nakane Nakano, Alexandre Veriano
Júnior, Ana Paula Pinheiro Martins, Américo Ceiki Sakamoto
Centro de Cirurgia de Epilepsia, Hospital das Clínicas de
Ribeirão Preto, Ribeirão Preto/SP, Brazil
Bruno Z Monnerat
Centro de Cirurgia de Epilepsia,
Hospital das Clínicas de Ribeirão Preto,
CEP 14048-900, Brazil
In the last few years, awareness of autoimmune encephalitis has
increased, and in particular, voltage-gated potassium channel
(VGKC), N-methyl-D-aspartate receptor (NMDAR) and glutamic acid
decarboxylase (GAD) antibodies have been reported. Typically, the
clinical picture associated with these conditions is similar to
that of limbic encephalitis, of mainly complex partial seizures and
psychiatric comorbidities. We present a female found to have GAD
antibody (GADA)-associated encephalitis, presenting with opercular
myoclonic-anarthric status epilepticus (OMASE). Of note, this was
an adult patient with no history of diabetes. Brain MRI and seizure
semiology are presented.
A 23-year-old female was admitted to the epilepsy monitoring
unit for evaluation of refractory status epilepticus. The patient
was bedridden with a nasoenteral feeding tube. She was referred
from an intensive care unit in another city, as local treatment
protocols for status epilepticus were ineffective. On arrival,
there was continuous twitching of the right side of her face.
Eventually, twitching of the left side of the face was observed,
but was clearly much less frequent. She was torporous and presented
with significant laborious breathing, no gag reflex, and diffuse
hyperreflexia. No hemiparesis was found. She presented with
clinical status epilepticus for three months, and was recovering
from nosocomial pneumonia. Her speech was slow and dysarthric.
Her problems started four years before admission. As a
previously healthy girl, she had an unprovoked generalised
tonic-clonic seizure during sleep. After this event, treatment with
carbamazepine was started. Four months later, daily partial complex
seizures initiated and persisted, in spite of increasing doses of
carbamazepine. Two years later, she became pregnant. Even though
there was no increase in seizure frequency, she developed
post-partum depression, with rejection of the baby. Three months
before admission, after a generalised tonic-clonic seizure, she
developed continuous twitching in the right side of her face. She
was admitted to a local institution for treatment of focal status
epilepticus, reportedly with induced coma, but no improvement was
observed. There was no family history of epilepsy. She was referred
for evaluation and treatment.
Previous investigations revealed normal CSF results and
progressive lesions on brain MRI. The first scan obtained eight
months before admission demonstrated increased T2 signal changes in
the left hippocampal formation associated with decreased volume and
signs were interpreted as hippocampal sclerosis. A follow-up study
performed one month before admission demonstrated asymmetric
bilateral hippocampal sclerosis, more marked on the right side.
During long-term monitoring in the epilepsy unit, EEG was
obscured by muscle artefacts. The diagnosis of OMASE was suggested
by continuous and irregular twitching of the right side of the
lower face involving the tongue and dysphagia/dysarthria, which was
not associated with dysmetria. There was no propagation of muscle
twitching to other segments of the body and the patient could
easily follow commands, even though she appeared to be somewhat
somnolent. She demonstrated clear difficulty in pronouncing words,
but no weakness in the right arm (the patient was dextrous).
Infrequent twitching of the left side of the face was noted.
During the night, when the twitching was less intense, left and
right temporal and left frontal sharp waves were observed.
Continuous, 4-5-Hz focal myoclonic seizures of the right side of
her face and tongue were observed (see video sequence).
There was no ictal pattern on scalp EEG, which was, for most of the
time, obscured by movement artefact.
After two days of monitoring, CSF was obtained for analysis.
There was a high IgG index with suspicion of inflammatory disease.
Immunological investigation excluded lupus. Repeat brain MRI
revealed bilateral hippocampal sclerosis and multiple lesions with
hyperintensity on T2/FLAIR sequences, involving the temporal and
parietal lobes in both hemispheres, markedly in the left
perisylvian region (figure 1).
Due to the supposed inflammatory nature of the disease, a workup
for autoimmune antibodies was conducted, revealing 7,990 U/mL
serum anti-GAD65 antibodies (normal range: <0.90 U/mL).
Tests for other autoantibodies were negative. Antibody testing for
HIV in serum was negative. Further immunological investigation
excluded lupus and vasculitis, primarily based on negative tests
for ACA and ANA antibodies and normal inflammatory markers such as
VHS and C-reactive protein.
The patient was placed on a five-day regimen of intravenous
methylprednisolone at 1 g/day. She regained independence, but
continued to present with facial myoclonia, even though it was much
improved. She had no history of diabetes and her glycaemic levels
remained normal, except for brief periods during the corticosteroid
treatment. Finally, no evidence of ovarian teratoma was found.
Here, we report a patient with OMASE. Due to the multitude of
T2/FLAIR hyperintense lesions on brain MRI, the decision to
investigate probable encephalitis was taken. Rasmussen's
encephalitis was not considered due to the presence of bilateral
lesions and the absence of progressive brain atrophy and
hemiparesis. An increased CSF IgG index raised the suspicion of
autoimmune encephalitis and a diagnosis of GADA-associated
encephalitis was made.
Anti-GAD autoantibodies are increasingly being recognised as an
aetiology for encephalitis. GAD is the rate-limiting enzyme for the
synthesis of γ-aminobutyric acid (GABA), the major inhibitory
neurotransmitter in the CNS (Liimatainen et al., 2009). Most
reports associate anti-GAD autoantibodies with limbic encephalitis
(Olson et al., 2002; Saiz et al., 2008; Korff et
al., 2011; Mirabelli-Badenier et al., 2012) or temporal
lobe epilepsy (Stagg et al., 2010). However no complex
partial seizures were recorded in our patient during long-term
video-EEG monitoring. Moreover, most patients had diabetes mellitus
type I, which was not evident in our patient.
Treatment consists mainly of immunotherapy using
glucocorticoids, plasmapheresis, intravenous immunoglobulin, and
cyclophosphamide (Olson et al., 2002; Saiz et al.,
2008; Kanter et al., 2008; Korff et al., 2011) with
variable results. In our patient, methylprednisolone IV
significantly improved the opercular syndrome during
hospitalisation. No further treatment was offered, and the patient
regained independence at home, even though minor myoclonic seizures
persisted in the right side of her lower face.
The few reported cases of OMASE in the literature (Thomas et
al., 1995) are associated with stroke or tumour. Patients
presented with facial twitching and fluctuating cortical dysphasia
which improved with treatment for status epilepticus. The myoclonia
also involved the tongue and palate. As in our case, the EEG may
not be suggestive of cortical ictal epileptic activity (figure 2), which
can be seen in 80% of patients with simple partial seizures
(Devinsky et al., 1988). The presence of bilateral motor
expression in a strictly unilateral epileptiform discharge was
attributed to the bilateral projections of the inferior
corticonuclear pathways. This presentation of non-convulsive status
epilepticus was recognised in a recent review (Sutter and Kaplan,
An adult patient presenting with pseudobulbar syndrome and
anarthria was previously diagnosed with Foix-Chavany-Marie
opercular syndrome (FCMS) due to non-convulsive status epilepticus
(Steiner-Birmanns et al., 2006), possibly caused by
oxycodone use. A third report related FCMS with chronic herpes
simplex encephalitis (Sasaguri et al., 2002), and extensive
bilateral damage was observed on brain MRI, including atrophy.
Neither had myoclonia.
In conclusion, OMASE can occur when the inferior rolandic areas
are involved in epileptogenic lesions associated with epilepsia
partialis continua, such as GADA-associated encephalitis.
Acknowledgements and disclosures
This study was not funded by any supporting body and is reported
without any financial interests.
The authors have no conflicts of interests to declare.
Legends for video sequences Myoclonia in the right side of the
face during sleep Key words for video research on
www.epilepticdisorders.com Syndrome: Epilepsia partialis
continua Etiology: encephalitis Phenomenology:
status epilepticus (non convulsive); myoclonic seizure
Localization: Operculum (left)