Neuroradiology (1990) 32:168-171

Neuro -radiology
9 Spfinger-Verlag 1990

Magnetic resonance imaging in MELAS syndrome
L. Rosen, S. Phillips, and D. Enzmann
Department of Diagnostic Radiology and Neurology,Stanford University School of Medicine, Stanford, California, USA
Received: 24 August 1989

Summary. MELAS syndrome is a distinct clinical entity
belonging to a group of mitochondrial encephalomyopathies characterized by the tetrad of myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Computed
tomography (CT) and magnetic resonance (MR) findings
are reviewed in a patient with MELAS. Serial CT studies
demonstrated multiple "migrating" infarcts in various
stages of evolution involving primarily the posterior temporal and occipital regions. MR was more sensitive than
CT in demonstrating the number and extent of cortical lesions in this disease entity.
Key words: MRT - MELAS syndrome

In 1984, Pavlakis et al. [1] described eleven patients with
a syndrome consisting of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
which he termed the MELAS syndrome. Additionally, a
large proportion of these patients exhibited short stature,
hemiparesis, hemianopsia, and the presence of ragged
red fibers in skeletal muscle when stained with Gomori
trichrome stain. MELAS is a distinct clinical entity belonging to a group of disorders known as mitochondrial
encephalopathies. These disorders, presumably stemming from a disorder in mitochondrial function, affect
both muscle and the central nervous system. Two closely
related but separate entities, the Kearns-Sayre syndrome
(KSS) and myoclonus epilepsy associated with raggedred fibers (MERFF syndrome) have also been described
[2, 3].
Only scattered descriptions of neuroradiological findings including computed tomography (CT) and cerebral
angiography have been described in MELAS syndrome
[5, 6, 11]. To our knowledge, to date there have been no
published reports of magnetic resonance imaging in these
patients. We report a patient with MELAS syndrome and
correlate the CT and MR findings.

Case report
A 27-year-old Hispanic right handed female was admitted
in November, 1984 with an acute onset of bitemporal
headache, left homonymous hemianopsia, and left sided
seizures. She had a previous history of recurrent headaches with visual symptoms. Her past medical history was
unremarkable except for small stature noted since early
childhood. Family history was negative except for a
mother with short stature. A C T scan at that time reportedly demonstrated a right parietal-occipital cortical low
density area consistent with infarct. Electroencephalogram (EEG) at that time revealed diffuse slowing without
epileptiform potentials. Cerebrospinal fluid (CSF) and
serum chemistry analysis were normal. A diagnosis of
complicated migraine was made, and the patient was
treated with phenytoin and propranolol with subsequent
resolution of her visual field deficit.
The patient was well until February, 1985 at which
time multiple grand mal seizures recurred which responded to restarting phenytoin. In May, 1985 she was admitted with an acute left hemiparesis and bilateral hearing
loss. CT reportedly demonstrated the previously noted
right parieto-occipital cortical lesion as well as a new left
superior temporal lucency. Echocardiogram, sedimentation rate, antinuclear antibody titers, treponemal antibody screen, and CSF analysis were normal. The patient
refused a cerebral angiogram. Her hemiparesis cleared
over several weeks, and she subsequently discontinued
anticonvulsant therapy.
In September, 1987, the patient presented with focal
right sided seizures which became generalized and the patient required endotracheal intubation. The seizures were
resistant to anticonvulsant therapy. Sequential arterial
blood gas monitoring at that time revealed a persistant
metabolic acidosis and serum lactic acid levels were noted
to be elevated. CT at that time (Fig. 1) revealed a new region of well-defined cortical low density in the left calcarine cortex with subtle adjacent cortical contrast en-

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Fig.la-c. Serial brain CT scans in
MELAS patient; a and b are with
intravenous contrast, a Scan
obtained during acute period of
seizure activity and metabolic
acidosis. A well-defined area of
lucency with minimal adjacent
cortical enhancement is seen in the
left calcarine cortex consistent
with a sub-acute infarct. Local
right parietal sulcal enlargement is
present, b Scan obtained
2 months after a demonstrates
resolution of the previously noted
left calcarine lesion. A subtle
ill-defined cortical low density
lesion is present in the left
posterior temporal lobe. Minimal
abnormal enhancement is noted.
c Scan obtained 1 month after
b demonstrated further definition
of left posterior temporal
cortical/sub-cortical low density
with mild associated mass effect
consistent with an evolving infarct

Fig.2. Axial first echo (a, b) images from a T2 weighted sequence
(gated and flow compensation, TR = 2600 ms, TE = 30, 80 ms). Bilateral temporal and occipital high signal lesions consistent with infarcts are visualized. The abnormality involving the right calcarine
cortex is better visualized by MR (b, c). The left calcarine cortex lesion has apparently resolved by MR and CT criteria (compare to la
and lc). Unenhanced CT (c) shows cortical and subcortical low density in the !eft posterior temporal and left occipital regions as well as
ill-defined cortical low density in the corresponding location on the
right. Lesions do not adhere to vascular territories

hancement but without significant mass effect. Subtle sup
cal enlargement was all that remained of the previously
noted right parietal low density lesion. The focus of low
density in the left temporal cortex had completely resolved with no residua. A skeletal muscle biopsy demonstrated the presence of ragged red fibers and other
changes consistent with a mitochondropathy.
T h e patient was next admitted in N o v e m b e r , 1987 with
headaches, receptive aphasia, and a right visual field
deficit. CT at that time showed a new ill-defined cortical
and sub-cortical left posterior temporal lucency with local
sulcal effacement suggesting an acute infarct (Fig. 1). The
left calcarine cortex, in which a low density enhancing lesion had been seen a m o n t h earlier, now appeared normal.
An ill-defined subtle area of cortical low densitY with local
sulcal effacement was now present in the left posterior
temporal region (Fig.l). The patient was treated with
Coenzyme Q and subsequently recovered except for a

mild residual receptive aphasia. Since that time, she has
been admitted multiple times for severe headaches, vomiting, visual impairment, and fluctuating aphasia. CT
examination in January, 1988 showed the left temporo-occipital infarct to be much more well defined (Fig. 1). Local
atrophic changes in that region were now evident. A new
ill-defined right occipital lucency with local sulcal e f f a c e ment was seen.
A n M R scan was p e r f o r m e d in January, 1988 (General
Electric Signa at 1.5T), with T1 weighted and T2 weighted
pulse sequences. Multiple areas of cortical and subcortical
high signal on T2W images were seen in the right occipital,
left occipital, left posterior temporal, and right parietal regions which correlated with the areas of low density seen
on CT (Fig. 2). Additionally, high signal was noted in the
right medial temporal lobe which could not be appreciated on CT (Fig. 2). No posterior fossa, basal ganglia, or
brainstem abnormalities were seen.

Discussion
The patient described in this report meets the general
criteria for the diagnosis of M E L A S syndrome; that is,
there is evidence of myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. Short stature, seizures,
normal early development, as well as fluctuating m o t o r
and visual symptoms are additional diagnostic criteria
outlined by Pavlakis [1] which also pertain to our patient.
It is, therefore, a diagnosis to be entertained in young

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adult patients presenting with unexplained cerebral infarction, especially when the temporo-occipital regions
are involved.
The mitochondrial encephalomyopathies, to which
MELAS belongs, encompas a group of loosely related disorders characterized by neuromuscular clinical manifestations as well as proven or proposed defects in the
aerobic oxidative metabolic pathway presumably secondary to a structural or functional mitochondrial defect [4].
Kearns-Shy syndrome, Menke's syndrome, Alper's disease, Leigh's disease, myoclonus epilepsy with ragged red
fibers syndrome (MERFF), as well as MELAS belong to
this group.
Angiographic findings have been described in several
MELAS patients [1, 5, 6]. We are aware of seven patients
having undergone angiography described in the literature
to date [1, 5 9], of whom four had normal studies [7-9],
2 demonstrated findings of local infarction, i. e. focal areas
of capillary blush and early venous filling in the regions of
lucency seen on CT [6], and one was found to have extracranial carotid occlusion felt to be an angiographic complication. In no cases were findings of vasculitis or emboli
noted in these patients.
CT findings have included ventricular dilatation, basal
ganglia calcification, focal low-density cortical lesions,
and regions of cortical atrophy. Hasuo et al. [6] reported
foci of cortical enhancement on CT which did not correspond to vascular territories, but did correspond to areas
of capillary blush on angiography. Our patient is typical in
that CT demonstrated cortical infarcts of varying ages but
which did not correspond to vascular territories. The areas
of infarction typically involve the posterior temporal, parietal and occipital lobes. Our patient did not have ventriculomegaly or basal ganglia calcification seen in some
MELAS patients. MR demonstrated all areas of CNS involvement more dearly than CT. It showed abnormality
in areas that were previously abnormal on CT but had
reverted to a normal CT appearance. MR confirmed the
predominantly cortical location of the infarcts with less
white matter involvement. The posterior temporal and occipital predominance of the infarcts observed in this patient is typical of MELAS patients described previously
[6,11]. This correlates well with the visual symptoms these
patients frequently express.
Our patient demonstrated multiple infarcts of varying
ages which were seen to evolve on serial CT scanning.
New areas of acute infarction were seen on every followup
scan, with older lesions either progressing to focal areas of
cortical atrophy or, in some instances, normalizing. This
"migratory" nature of the lesions in MELAS is an observation which has been seen previously [6, 9, 11]. MR very
dramatically demonstrated the multiple cortical lesions in
our patient, and MR was more sensitive than CT in visualizing the full extent of the lesions present.
The mechanism for the cerebral infarcts seen in
MELAS patients remains unclear. The lesions frequently
tend to be in the parietal and occipital lobes, but often
they do not correspond to a defined vascular territory [1,
6, 10, 11]. The non-vascular nature of the infarcts suggests the ischemia may be cellular in origin, perhaps relating to the inability of the defective mitochondria to re-

spond adequately to periods of high metabolic demand.
Narrowing of the capillary lumen secondary to marked
swelling of capillary endothelial cells has been noted in
skeletal and smooth muscle biopsies in MELAS patients
[9]. It is unclear whether this degree of narrowing is sufficient to cause local tissue ischemia. Neuropathologically,
spongy degeneration with microcystic change focal cortical encephalomalacia are seen not only in MELAS syndrome but in Kearn's-Shy syndrome (KSS) and MERFF
as well [1].
The precise biochemical defect underlying the encephalomyopathies is not yet understood. In the original
patients described by Pavlakis [1], two of four demonstrated moderate reduction in cytochrome C oxidase activity. A defect in NADHCoQ reductase has also been
described in patients with MELAS [7, 12]. Interestingly,
Pavlakis [1] also found increased activity of citrate synthetase and carnitine palmatoyl transferase, two enzymes
located in the mitochondrial matrix. This may be a reflection of the increased number of mitochondria seen in
these patients. In a more general sense, the presence of
ragged red fibers seen in MELAS, KSS, and MERFF has
been associated with several other biochemical abnormalities as well, including abnormal function of cytochrome b, succinate- cytochrome c reductase, and
ATPase [1, 13, 14].
KSS and MERFF, although similar neuropathologically, have distinct clinical manifestations which would be
unlikely to be confused with MELAS. KSS is characterized by onset before age 20, opthalmoplegia, atypical
pigmentary degeneration of the retina, and one of the
following: heart block, CSF protein greater than
100 mg/dl, or a cerebellar syndrome [1, 6]. MERFF, described by Fukuhara et al. [2], is characterized by normal
early development, myoclonus, and a cerebellar syndrome. KSS and MERFF patients do not demonstrate
hemiparesis and hemianopia which are commonly seen
in MELAS patients.
There is evidence for familial transmission of
MELAS, although the exact mode of inheritance still remains unclear. The syndrome has been described in
siblings [8] as well as mother/child pairs [5, 11]. Maternal
mitochondrial inheritance, autosomal dominant, and Xlinked dominant patterns have all been proposed as
possible modes of inheritance [5], all of which could account for the transmission in families described to date.
Driscoll [5] reported a family in which the syndrome
spanned three generations, being present in three of
13 family members. He noted that several supposedly unaffected female family members had sensorineural hearing loss and short stature without stroke-like events, perhaps reflecting incomplete penetrance of a carrier state.
Additionally, he noted, as have others [1, 5, 6, 11], that
affected individuals have a markedly variable clinical
course. Some of those affected have an episodic course,
often with periods of nearly complete recovery of function, while others have a gradual, progressively worsening
clinical course.
MELAS should be considered in the differential diagnosis of cerebral infartion in young adults, especially if
they are fluctuating in nature, of varying ages, and do not

171
c l e a r l y c o r r e s p o n d to v a s c u l a r t e r r i t o r i e s . If clinical a n d
r a d i o l o g i c a l findings a r e suggestive, s e r u m p y r u v a t e a n d
l a c t a t e levels s h o u l d b e o b t a i n e d as well as s k e l e t a l m u s c l e
biopsy.

Acknowledgement. We gratefully thank Dr. Howard Slyter, Jr. for
providing valuable clinical information used in the preparation of
this manuscript.

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D. Enzmann, M. D.
Department of Diagnostic Radiology
and Nuclear Medicine
Stanford University School of Medicine
Stanford, CA 94305
USA