Seizure: European Journal of Epilepsy 64 (2019) 6–7

Contents lists available at ScienceDirect

Seizure: European Journal of Epilepsy
journal homepage: www.elsevier.com/locate/seizure

Clinical letter

Fixation-off sensitivity in mitochondrial encephalomyopathy, lactic acidosis,
and stroke-like episodes (MELAS) syndrome
Sangwon Lee, Dan-A Oh, Eun-Kee Bae

T

⁎

Department of Neurology, Inha University Hospital, Incheon, Republic of Korea

1. Introduction
Fixation-off sensitivity (FOS) is a rare phenomenon of electroencephalogrpahy (EEG) induced by elimination of central vision/fixation [1]. FOS is characterized by
posterior or generalized epileptiform discharges that consistently
occur after closing of the eyes and last as long as the eyes are closed for
more than 3 s [2,3]. It is differentiated from other “eye-condition” related visual sensitive phenomena, including eye closure sensitivity (just
immediately triggered by eye closure lasting for 3 s or less) and scotosensitivity (elicited by complete darkness; irrespective of eye opening
and closure) [2,3]. Although FOS has been reported in various epileptic
conditions representatively including idiopathic childhood occipital
epilepsies, it has never been reported in patients with mitochondrial
encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)
syndrome so far. Herein we report a unique case of FOS with or without
scotosensitivity presented with a new-onset seizure in genetically confirmed MELAS syndrome.
2. Case report
A 22-year old man visited our emergency department presenting
with a new-onset seizure while he was sleeping at night. The seizure
was assumed as a generalized tonic-clonic type and its duration was
about 2 min according to the witness of his parents. His initial vital
signs including blood pressure and body temperature were within
normal range. He was alert at the time of arrival and showed no focal
neurologic deficits. He had a few years of history of diabetes mellitus
(DM) being treated with oral hypoglycemic agents. He had no other
history of medical illness except DM. In his family history, his mother
has also been treated with oral hypoglycemic agents due to DM since
her first pregnancy. Other family members including his father and one
little brother did not report any specific medical illnesses and a history
of seizures or any neurologic symptoms. His initial laboratory data were
clinically insignificant except elevated levels of lactic acid
(10.40 mmol/L; normal range 0.50–1.50) and HbA1c (8.3%; normal
range 4.0–6.0). His brain magnetic resonance imaging (MRI) and
magnetic resonance angiography (MRA) were normal. EEG revealed

⁎

generalized spike-and-waves and polyspikes that consistently occur
after closing of the eyes and last as long as the eyes are closed, which is
suggestive of FOS (Fig. 1). Although he did not have any stroke-like
episodes, we examined a mitochondrially encoded tRNA leucine 1 (MTTL1) gene test from his peripheral blood in suspicion of MELAS syndrome because of young-age onset DM and his short stature (163 cm) in
addition to a seizure. The m.3243 A > G mutation was confirmed
through this test. Thereafter his mother with DM and one asymptomatic
little brother wanted to check the same genetic tests, both of them were
also confirmed to have m.3243 A > G mutation. He has been seizurefree with antiepileptic drugs (lamotrigine, levetiracetram) for more
than 6 months after the first seizure.
3. Discussion
Although various abnormal EEG findings can be encountered in
patients with MELAS syndrome, to our knowledge, FOS with or without
scotosensitivity has not been reported so far. FOS was first documented
in four children with occipital paroxysms (two had what is now known
as Panayiotopoulos syndrome, one had idiopathic childhood occipital
epilepsy of Gastaut and one had symptomatic occipital epilepsy) [1].
Since then it is most commonly encountered in patients with idiopathic
childhood occipital epilepsies, but may also be observed in cases of
symptomatic or cryptogenic focal and generalized epilepsies, as well as
in asymptomatic non-epileptic individuals [2]. Although FOS is rarely
seen in the adult population, it often represents the EEG expression of
symptomatic epilepsies (cortical malformations, celiac disease, calcified
vascular malformation, and stroke, etc.) [4]. Strictly speaking, we
should have differentiated FOS with scotosensitivity by the elimination
of central vision/fixation in the presence of light with the use of
modified Ganzfeld stimulation or Frenzel lenses. Although we didn’t
have a chance to perform this test, pure scotosensitivity is extremely
rare and specific characteristics of light sensitivity has also been rarely
studied in detail in the previous relevant literatures [3]. Besides, his
generalized spike-and-waves and polyspikes on EEG consistently occurred even during the photic stimulation, we think that this phenomenon is unlikely to be scotosensitivity. However we could not
completely rule out the possibility of combined scotosensitivity, we

Corresponding author at: Department of Neurology, Inha University Hospital, 27, Inhang-Ro, Jung-Gu, Incheon, Republic of Korea.
E-mail address: alchemist0210@gmail.com (E.-K. Bae).

https://doi.org/10.1016/j.seizure.2018.11.010
Received 13 September 2018; Received in revised form 7 November 2018; Accepted 20 November 2018
1059-1311/ © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Seizure: European Journal of Epilepsy 64 (2019) 6–7

S. Lee et al.

Fig. 1. Generalized epileptiform discharges that consistently occur after closing of the eyes and last as long as the eyes are closed.

used the term “FOS with or without scotosensivity” here. Although the
underlying mechanisms remain still uncertain due to its rarity, FOS is
thought to be modulated by α-rhythm generators and influenced by
cortical hyperexcitability [4]. In MELAS syndrome, epileptic seizures
occur primarily in association with stroke-like episodes, however, they
can happen in patient with normal brain MRI like our patient. The
underlying epileptogenic pathophysiology is quite obscure in this situation. Our case suggests that the occipital hyperexcitability associated
with FOS might have a pathophysiologic role in some patients with
MELAS syndrome. In addition, we propose that MELAS syndrome
should be considered as one of the rare but possible causes of adultonset FOS.

Acknowledgment
This work was supported by INHA UNIVERSITY Research Grant
(INHA56992).
References
[1] Panayiotopoulos CP. Inhibitory effect of central vision on occipital lobe seizures.
Neurology 1981;31:1330–3.
[2] Brigo F, Rossini F, Stefani A, Nardone R, Tezzon F, Fiaschi A, Manganotti P,
Bongiovanni LG. Fixation-off sensitivity. Clin Neurophysiol 2013;124:221–7.
[3] Karkare KD, Menon RN, Radhakrishnan A, Cherian A, Thomas SV. Electroclinical
characteristics and syndromic associations of "eye-condition" related visual sensitive
epilepsies-A cross-sectional study. Seizure 2018;58:62–71.
[4] Fattouch J, Casciato S, Lapenta L, Morano A, Fanella M, Lombardi L, Manfredi M,
Giallonardo AT, Di Bonaventura C. The spectrum of epileptic syndromes with fixation off sensitivity persisting in adult life. Epilepsia 2013;54(Suppl 7):59–65.

Conflict of interest
None.

7