GABAB RECEPTOR ENCEPHALITIS:
UNEXPLORED ASSOCIATION WITH PULMONARY TUBERCULOSIS
Valerie SS, Chia YK, Ong AM Sheila
Neurology Department Queen Elizabeth Hospital, Kota Kinabalu, Sabah
Introduction :
GABAB receptor encephalitis refers to autoimmune encephalitis caused by autoantibodies to the Ƴ - aminobutyric acid receptor (subtype B).
Presentations may vary and include limbic encephalitis with seizures, status epilecticus, ataxia, or opsoclonus-myoclonus. It can be paraneoplastic
up to 35% of cases, most often associated with small-cell lung cancer and quite often in conjunction with another paraneoplastic antibody.
Objective:
The main novelty of this case is to demonstrate the relationship between tuberculosis and GABA B receptor encephalitis, which has never reported
before.
Case report:
A 34 year old lady was admitted to ICU for first episode of status epilepticus with
cognitive impairment. Otherwise she denied other neurological or systemic
symptoms. She had history of nasopharyngeal carcinoma, completed
radiochemotherapy 5 years ago, with no evidence of recurrence.
On examination, she was confused and had memory impairment. Other systemic
and neurological findings were insignificant.
Routine blood investigation were unrevealing. CSF revealed mild lymphocytic
pleocytosis (15 cells/mm3), normal glucose and protein, and GABAB receptor
antibody was positive. EEG showed moderate encephalopathy with
electrographic seizure. MRI brain showed bilateral hippocampal T2/FLAIR
hyperintensities. Otherwise no co-existing paraneoplastic antibody.
She was initially treated with IV methylprednisolone, followed by IV
Immunoglobulin and plasmapheresis. CT thorax, abdomen and pelvis was done
to look for malignancy, and revealed multiple lung nodules with cavitation
suggestive of PTB, which was confirmed with bronchoscopy and bronchial
washing (TB Genexpert positive). Hence she was started on antitubercular
treatment. Repeated CT after treatment showed improvement. She was then
discharged with oral steroid, antiepileptics and antitubercular medication.
She presented again 1 month after discharge for refractory seizures, requiring
second plasmapharesis. Subsequently she remained seizure free with
immunosuppressant and 3 antiepilectics.. However she is left with memory
disturbance and is still mildly encephalopatic.
EEG on presentation(left) showed background
slowing with electrographic seizure
EEG after treatment (right) showed
improvement in background rhythm and
absence of epilectic activities
MRI brain showed bilateral hippocampal
T2/FLAIR hyperintensities
Discussion:
GABAB encephalitis occurs relatively infrequently; however the
characterization of the antibody and clinical phenotype has occurred recently.
Interestingly, case serials of patients with anti- GABAB receptor encephalitis
emphasized the typical triad of clinical presentation, including memory
alternation, seizures, and SCLC. The mechanism of SCLC-associated
autoimmune responses remains to be elucidated. It may be related to
abnormal self-antigen expression in tumor cells, or the antigenic protein might
be mutated or modified to those foreign to the immune system. Neurological
symptoms often present before the cancer becomes symptomatic.
Our patient’s clinical presentation together with the positive CSF GABAB
autoantibodies and MRI findings was considered diagnostic of GABAB limbic
encephalitis. However chest imaging revealed lesions suggestive of pulmonary
tuberculosis which is consistent with bronchoscopy and bronchial washing
findings. Moreover, lung lesions improved after antitubercular treatment. Our
patient who has impaired cell mediated immunity has high risk of tuberculous
infection precipitated by high dose of steroid.
Tuberculosis has a high prevelence n Malaysia, especially the state of Sabah
which contains approximately 10% of the country’s total population, but a
disproportionally high burden of the country’s TB cases, estimated at 20-30%,
mainly due to large number of immigrants and long diagnostic delays.
On the other hand, tuberculous infection in our patient may be the induction
of brain reactive antibodies causing limbic encephalitis.
The CNS is an immune-privileged organ, protected by the blood–brain barrier.
Recognition of a specific antigen during immune surveillance results in the
activation of inflammatory cells and release of inflammatory cytokines and
chemokines that alter tissue barrier and initiate inflammation. Antigens such
as neuronal membrane antigens do not activate the immune system under
physiological conditions, but if activation is induced elsewhere, they can
become targets for an autoimmune attack, in which one of the mechanism
can be infection.
Cases had been reported where patient with GABAB encephalitis is associated
with non-malignant lung lesion, likely inflammatory in nature and showed
improvement during reassessment in chest lesion and neurological findings
without immunomodulatory treatment.
Conclusion :
It is unclear whether the relationship between tuberculosis and GABA B
encephalitis is of coincidence or causality.
Impaired cell mediated immunity with cumulative high dose of steroids in our
patient are known predisposing risk of tuberculosis infection, especially in
Sabah (TB endemic area).On the other hand, infection as trigger for limbic
encephalitis due to cross reactivity with neuronal antigen also remains a
possibility.
References :
1. B. Diamond, G. Honig, S. Mader, L. Brimberg, and B.T.Volpe: Brain-Reactive
Antibodies and Diseases, Annu Rev Immunol. 2013; 31: 345-385
2. Wysota B, Teare L. Karim A, et al AUTOIMUNE GABAB ANTIBODY
ENCEPHALITIS ASSOCIATED WITH NON-MALIGNANT LUNG LESION. J Neurol
Neurosurg Psychiatry 2013;84:e2
3. Liu KQ, Yan SQ, Lou M. Gamma-aminobutyric-acid-B receptor antibodies
in limbic encephalitis with small cell lung cancer. Neuroimmunol
Neuroinflammation 2015;2(3):187-9
4. Höftberger R (2015) Neuroimmunology: an expanding frontier in
autoimmunity. Front. Immunol. 6:206. doi: 10.3389/fimmu.2015.00206
5. William et al. BMC Infectious Diseases (2015) , Pulmonary tuberculosis in
 GABAB RECEPTOR ENCEPHALITIS:UNEXPLORED ASSOCIATION WITH PULMONARY
TUBERCULOSIS
Neurology Department Queen Elizabeth Hospital, Kota Kinabalu, Sabah
Introduction :
GABA B receptor encephalitis refers to autoimmune encephalitis caused by autoantibodies to the Ƴ - aminobutyric acid receptor (subtype B). Presentations
may vary and include limbic encephalitis with seizures, status epilecticus, ataxia, or opsoclonus-myoclonus. It can be paraneoplastic up to 35% of cases,
most often associated with small-cell lung cancer and quite often in conjunction with another paraneoplastic antibody.
Objective:
The main novelty of this case is to demonstrate the relationship between tuberculosis and GABAB receptor encephalitis, which has never reported before.
Case report:
A 34 year old lady was admitted to ICU for
first episode of status epilepticus with
cognitive impairment. Otherwise she denied
other neurological or systemic symptoms.
She had history of nasopharyngeal
carcinoma, completed radiochemotherapy 5
years ago, with no evidence of recurrence.
On examination, she was confused and had
memory impairment. Other systemic and
neurological findings were insignificant.
Routine blood investigation were unrevealing.
CSF revealed mild lymphocytic pleocytosis (15
cells/mm3), normal glucose and protein, and
GABAB receptor antibody was positive. EEG
showed moderate encephalopathy with
electrographic seizure. MRI brain showed
bilateral hippocampal T2/FLAIR
hyperintensities. Otherwise no co-existing
paraneoplastic antibody.
She was initially treated with
methylprednisolone, followed by
Immunoglobulin and plasmapheresis. CT
thorax, abdomen and pelvis was done to look
for malignancy, and revealed multiple lung
nodules with cavitation suggestive of PTB,
which was confirmed with bronchoscopy and
bronchial washing (TB Genexpert positive).
Hence she was started on antitubercular
treatment. Repeated CT after treatment
showed improvement. She was then
discharged with oral steroid, antiepileptics and
antitubercular medication.
She presented again 1 month after discharge
for refractory seizures, requiring second
plasmapharesis. Subsequently remained
seizure free with immunosuppressant and 3
antiepilectics. however she remained mildly
encephalopatic, and still having memory
disturbance.
Chia YK , Valerie SS, Ong AM Sheila
Discussion:
GABA B encephalitis occurs relatively infrequently;
however the characterization of the antibody and
clinical phenotype has occurred recently.
Interestingly, case serials of patients with anti-
GABA-B receptor encephalitis emphasized the
typical triad of clinical presentation, including
memory alternation, seizures, and SCLC. The
mechanism of SCLC-associated autoimmune
responses remains to be elucidated. It may be
related to abnormal self-antigen expression in
tumor cells, or the antigenic protein might be
mutated or modified to those foreign to the
EEG on presentation(left)
showed background slowing immune system. Neurological symptoms often
with electrographic seizure present before the cancer becomes symptomatic.
EEG after treatment (right) Our patient’s clinical presentation together with
showed improvement in
the positive CSF GABA B autoantibodies and MRI
background rhythm and
absence of epilectic activities findings was considered diagnostic of GABA B
limbic encephalitis. However chest imaging
revealed lesions suggestive of pulmonary
tuberculosis which is consistent with
bronchoscopy and bronchial washing findings.
Moreover, lung lesions improved after
antitubercular treatment. Our patient who has
impaired cell mediated immunity has high risk of
tuberculous infection precipitated by high dose of
steroid.
IV Tuberculosis is a disease of major public health
IV significance in Malaysia, with a current estimated
incidence of 80 new cases annually per 100,000
population. The state of Sabah in eastern
Malaysia on the island of Borneo contains
approximately 10% of the country’s total
population, but a disproportionally high burden of
the country’s TB cases, estimated at 20-30%. The
case notification rate for Sabah has been sustained
Bronchoscopy
showed hyperemia MRI brain showed at higher levels of 144 to 217 per 100,000
population during recent decades while rates have
of left main bilateral hippocampal
bronchus and left T2/FLAIR hyperintensities fallen in other parts of Malaysia mainly due to
large number of immigrants and long diagnostic
lower lobe
delays.
On the other hand, tuberculous infection in our
patient may be the induction of brain reactive
antibodies causing limbic encephalitis.
The CNS is an immune-privileged organ, protected
by the blood–brain barrier. Recognition of a
specific antigen during immune surveillance
results in the activation of inflammatory cells and
release of inflammatory cytokines and
chemokines that alter tissue barrier and initiate
inflammation. Antigens such as neuronal
CT Thorax (before ATT) showed membrane antigens do not activate the immune
multiple lung nodules, CT Thorax (after ATT)
confluence at left lung base with showed resolving lung system under physiological conditions, but if
air bronchogram, subcentimeter nodules activation is induced elsewhere, they can become
mediastinum nodes targets for an autoimmune attack, in which one of