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in 2013 and a gadolinium‑enhancing lesion involving memory improvement after the immunotherapy.
the caudate and globus pallidus in a patient that we These sequelae further suggest the involvement of
described in 2013. When cognitive impairment a subcortical neuronal network in these patients.
[68]
is present, both unilateral and bilateral medial Furthermore, myoclonus was reported in 29%
temporal lobe and also caudate signal changes have of patients with positive VGKC complex‑IgG.
[12]
been described. [11,65] Interestingly, the basal ganglia The majority of the patients showed generalized
signal changes are controlateral to the facio‑brachial myoclonus, but segmental/multifocal, unilateral and
dystonic seizures in all the patient described focal cortical myoclonus have also been reported.
so far. [65,68] Electroencephalography shows ictal
epileptiform activity in a minority of patients with Epilepsy
a frontotemporal, frontal, or temporal focus. The In recent years, a number of studies have reported
[11]
LE following FBDS is clinically undistinguishable antibodies targeting neuronal cell surface antigens in
from the other VGKC‑LE with amnesia, confusion, patients with epilepsy, including antibodies against
hallucinations, sleep disturbances and other the VGKC‑complex and the N‑methyl‑D‑aspartate
nondystonic seizure types. The initial treatment glutamate receptor. [70‑72] The role of such antibodies
[11]
with antiepileptic drugs is ineffective in the majority in the pathogenesis of epilepsy has not been fully
[73]
of the patients, while the initiation of immunotherapy established, but they have been found more
with corticosteroids, intravenous immunoglobulin, likely to occur in patients with focal epilepsy of
and plasma exchange has proven to be useful in order undetermined cause rather than in patients with
[71]
to reduce the frequency of FBDS. [11,65] The cessation structural/metabolic focal epilepsy. In particular,
of FBDS after the immunotherapy is associated with VGKC‑complex antibodies are of interest in epilepsy,
a significant reduction in serum VGKC complex/ as they target VGKC that play an important role in
[73]
LGI‑1 antibody titers. Antiepileptic drugs are also regulating neuronal excitability. Lilleker et al.
[65]
responsible for adverse cutaneous reactions in a high found that in patients with unexplained adult onset
proportion of patients and the involvement of both epilepsy, VGKC‑complex antibodies were positive in
[65]
eyes and mouth has been reported in one patient, the 8% of cases and the 4.2% of the patients had titers
while the documented psychiatric side effects higher than 400 pM. Patients with VGKC‑complex
of steroids (including paranoia and hypomania) antibodies titers higher than 400 pM had focal seizures
generally improve by tapering steroids. In patients and in 4 out the 6 described cases the seizure focus
with persisting VGKC‑complex/LGI1‑antibodies, was diagnosed in the temporal lobe. These patients
relapses of FBDS have been described during the reported rising abdominal sensation, olfactory
steroid tapering period, and all the relapses showed an hallucination, piloerection, dejà vu, oromasticatory
absolute response, after increasing the corticosteroid automatism and depersonalization. Two patients
dose. had generalized tonic‑clonic seizures in addition to
focal seizures, and one patient had FBDS. No patient
The recognition of FBDS is critical because the had the clinical syndrome of LE, and no patient was
response to anti‑epileptic drugs is unsatisfactory diagnosed with cancer. The sera of all 6 patients
while response to immunotherapy is excellent, and were tested for LGI‑1 and Caspr‑2 antibodies. The
early initiation of immunosuppressant therapy offers serum of the patient who presented with FBDS tested
the chance to modify the course of this neurological positive for LGI‑1 antibodies; one patient was positive
disorder avoiding the development of full‑blown LE. for Caspr‑2 antibodies; all the other patients were
negative for both LGI‑1 and Caspr‑2 antibodies. Brain
Chorea and other movement disorders associated with MRI was normal in all patients except in one patient
VGPC complex‑IgG showing increased signal in the left hippocampus
Extrapyramidal involvement has been reported in and amygdala that was attributed to recent seizures.
21% of patients with positive VGKC complex‑IgG. Interestingly, all the patients improved with
The majority of these patients have tremor associated immunotherapy, although not all of them have been
with Parkinsonism, some patients experience tremor rendered seizure‑free. Furthermore, Iorio et al.
[72]
only while few patients have chorea. Tofaris et found that patients with neural antibodies not
[12]
al. described two patients in which chorea was responding to antiepileptic drugs may benefit from
[69]
the main symptom and anticipated by several weeks immunotherapy. They studied 81 patients (39 patients
the onset of LE. The involvement of the basal ganglia with epilepsy and other neurological symptoms and/
has been extensively demonstrated in patients with or autoimmune diseases responsive to antiepileptic
LGI‑1 antibodies [11,65,68] and it is worth noting that drugs and 42 patients with AED‑resistant epilepsy).
both the patients described by Tofaris et al. had Neural autoantibodies were detected in 22% of
[69]
residual executive dysfunction despite significant patients, mostly from the antiepileptic drug‑resistant

Neuroimmunol Neuroinflammation | Volume 3 | March 28, 2016 73