Marked reduction in CSF lactate and
pyruvate levrels after C O Q t herapy in a
patient With mitochondria1
.thy
encephalopathy, lactic acidosis and
stroke-like episodes (MELAS)
9

Abe K, Fujimura H, Nishikawa Y, Yorifuji S, Mezaki T, Hirono N, Nishitani
N, Kameyama M. Marked reduction in CSF lactate and pyruvate levels
after CoQ therapy in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).
Acta Neurol Scand 1991: 83: 356-359.

Many CoQ trials for mitochondrial encephalomyopathy are reported,
however, the action of CoQ in the central nervous system is unknown.
We administered CoQ to a patient with MELAS, and decreasing CSF
lactate and pyruvate levels were revealed. This reduction in CSF lactate
and pyruvate may be evidence that CoQ acts directly on the CNS. There
have been no other descriptions of evidence of CoQ effective action in
the central nervous system, a finding unique to this report.

Mitochondria1 myopathy, encephalopathy, lactic
acidosis and stroke-like episodes (MELAS) is classified into “mitochondrial encephalomyopathy” (1-3).
No effective treatment for this syndrome has
been established, however, recent therapeutic trials
of coenzyme Q lO(CoQ) administration to patients
with Kerns-Sayre syndrome have demonstrated
clinical and biochemical improvement (4-8). We
experienced a MELAS patient who developed
marked reduction in CSF lactate and pyruvate levels
with clinical improvement.
Case report

A thirty-one-year-old male was admitted to our
hospital with untreatable seizures. Prenatal and perinatal histories were normal. He experienced the first
seizure at the age of twenty-one, as a college student.
He was then given an anticonvulsant drug. In spite
of regular medication, he continued to suffer two or
three seizures every year. In early 1989, as status
epilepticus he was transferred to hospital. Right
hemianopia and auditory agnosia were discovered.
MR imagmg revealed abnormal intensity lesions in
the left parietal and the left operculum, but they
diminished in two months. Cerebral angiography
was also performed, although there were no abnormal findings. He was referred to our hospital for
further examination.
356

K. Abe’, H. Fujimura’, Y. Nishikawa’,

S.Yorifuji’, T. Mezaki’, N. Hirono’,
N. Nishitani3, M. Kameyama’

’

Departments of Neurology, Osaka University
Medical School, Sumitorno Hospital, Second
Tanne Hospital, Japan

Key words: MELAS, CoQ, decreasing CSF lactate and pyruvate, fluctuating MR Images
Kazno Abe, Department of Neurology, Osaka
University Medical School, 1-1-50 Fukushima,
Fukushima-Ku, Osaka-530, Japan
Accepted for publication September 26, 1990

The patient was 159 cm in height, and had been
prescribed a major tranquilizer to prevent occasional
delirium. He seemed dull for his educational history.
On neurological examination, he presented right
hemianopia, auditory agnosia and slightly weak
muscle strength. Deep tendon reflexes were slightly
brisk, coordinative movements were normal. Laboratory data were in the normal range, except for an
abnormal elevation in CSF lactate (32 mg/dl, normal
control 4-16 mg./dl) and pyruvate (2.2 mg/dl, normal control 0.3-0.9 mg/dl) levels, but serum lactate
and pyruvate levels were normal. No acidosis was
demonstrated. The process of measurement of these
lactate and pyruvate levels was as follows: immediately after sampling, 2 m l CSF was added to the
same amount of 10% perchloric acid to move protein, and the supernatant was deep frozen until
needed. After neutralization with 3N potassium, the
CSF hydroxide lactate and pyruvate were analysed
using the standard enzymatic methods (4, 17).
Our patient had the following clinical features:
1) short stature, 2) normal prenatal and perinatal
histories, 3) seizures with hemianopia and auditory
agnosia, 4) muscle weakness, 5) headache with
nausea, and 6) increased C S F lactate and pyruvate
levels. These clinical features are compatible with the
criteria MELAS as described by Palvlaskis (9). To
confirm the diagnosis, a biopsy was performed in the
right quadriceps muscle; no ragged red fibers were

Marked reduction in CSF lactate

Fig. l.a,b MR imaging (Shimazu 1.5 Tesla superconducting system, TR/TE = 2500/120) MR imaging reveals high intensity lesions
in the left occipital, but these diminish on subsequent MR imaging.

observed. However, ragged red fibers are not always
found in MELAS patients, and these histological
findings are not contrary to the diagnosis of MELAS.
We then began high dosage CoQ administration.
After a week, his hemianopia and state of delirium
began to improve. The doses of major tranquilizer
were tapered. After three weeks, a lumber puncture
was performed, to reveal markedly decreased CSF
levels of lactate and pyruvate. IMP-SPECT images
demonstrated improved IMP-uptakes in the whole
brain. Until now, no seizures have occurred and
muscle weakness has gradually improved. Admission of high doses of CoQ is being continued.
(Fig. 2).
Discussion

Our patient demonstrated elevated CSF lactate and
pyruvate levels without lactic acidemia. CSF lactate
and pyruvate levels do not parallel those in serum,
and elevation of those levels has been considered to
imply mitochondrial metabolic failure (9). Patients
with such alternative diseases as diabetes mellitus or

inflammatory diseases not infrequently demonstrate
elevation in CSF lactate and pyruvate levels, but our
patient had no such disorders. Patients with cerebral
infarction are also known to demonstrate elevated
CSF lactate and pyruvate levels, but such change is
transient (1 1-13). In our patient, impaired mitochondrial metabolism in the central nervous system
is considered the possible cause for elevation in CSF
lactate and pyruvate levels (14-16).
The most singular feature of our patient is a marked
reduction in CSF lactate and pyruvate levels after
CoQ administration. This reduction is unique,
because CoQ therapy for mitochondrial encephalomyopathy has been tried previously, without, however, any reduction being reported. Ogasahara et al.
( 6 ) reported that cardiac conduction defect and
abnormally elevated serum lactate and pyruvate
levels were improved after daily administration of
60-120 mg of CoQ for three months. They postulated that exogenous CoQ is incorporated into the
mitochondrial inner membrane and increases mitochondrial enzyme activities. Goda et al. (7) reported
a MELAS patient who had normal enzyme activity
357

Abe et al.

seizure

t

$1 t

t

hemianopsia
auditory
agnosia

muscle
weakness

- serum
x pyruvate --CSF
lactate

30- 3.0-

\

20- 2.0-

10-

1.0X
'

/

X

OL

0-

41 1
Fig. 2. Progress chart of this case. After CoQ administration, CSF lactate and pyruvate levels decrease and clinical symptoms are

improved simultaneously.

in the electron transport system and normal lactic
acidosis, and demonstrated a reduction in serum
lactate and pyruvate levels, although, no changes in
CSF levels. If CSF lactate and pyruvate levels reflect
mitochondrial metabolism, reduction in those levels
could be accompanied by clinical improvement. We
believe the reduction in CSF lactate and pyruvate
levels in our patient may indicate effective action of
CoQ in the central nervous system. Although exogenous CoQ is known not to be able to pass the
blood brain barrier, our patient had a broken blood
brain barrier, so CoQ could pass relatively freely
through it and into the brain tissue.
The mechanism of CoQ function in our patient is
unknown, however, the reported reduction in CSF
lactate and pyruvate levels is enough to rationalize
CoQ administration.

358

References
Y, CEDERBAUM
SD, CANCILLA
PA, NIELSEND,
1. SHAPIRA
LIPPEBM. Familial poliodystrophy, mitochondrial myo-

pathy, and lactate acidemia. Neurology 1975: 25: 614-621.
RR. Reversible alexia, mitochondrial myopathy,
2. SKOGLUND
and lactic acidemia. Neurology 1979: 29: 717-720.
PL, CLIMIEARW, GILROYJ, MAHMUDMZ.
3. HOLLIDAY
Mitochondria1 myopathy and encephalopathy: a deficiency
of NADH-CoQ dehydrogenase? Neurology 1983: 33:
1619-1 622.
4. OGASAWARA
S, YORIFUJI
S, NISHIKAWA
Y, TAKAHASHI
M,
WADAK, HAZAMA
T, NAKAMURA
Y, HASHIMOTO
S, KONO
N, TARUIS. Improvement of abnormal cardiac conduction
defect with coenzyme QlO in Kerns-Sayer syndrome.
Neurology 1985: 35: 372-377.
S, TAKAHASHI
M, TARUIS.
5. YORIFUJIS, OGASAWARA
Decreased activities in mitochondrial inner membrane electron transport system in muscle from patients with
Kearns-Sayre syndrome. J Neurolo Sci 1985: 71: 65-75.
S, NISHIKAWA
Y, YORIFUJIS , SOGA F,
6. OGASAWARA
NAKAMURA
Y, TAKAHASHI
M, HASHIMOTO
S , KONON,

Marked reduction in CSF lactate
TARUIS. Treatment of Kearns-Sayre syndrome with
coenzyme QlO. Neurology 1986: 36: 45-53.
T, ISHIMOTO
S,KOBAYASHI
T, GOTOI,
7. GODAS, HAMADA
KUROlWA Y. Clinical improvement after administration of
coenzyme QlO in a patient with mitochondrial encephalomyopathy. J Neurology 1987: 234: 62-63.
JS,
8. HARTZH, CHANGCH, PERRINEVD, NEERUNJUN
AYYAR R. Familial poliodystrophy, mitochondria1
myopathy, and lactate acidemia. Child Neurology 1977: 34:
180-185.
SG, PHILLIPS
PC, DIMAURO
S, DE VIVO DC,
9. PALVLASKIS
ROWLAND
LP. Mitochondrial myopathy, encephalopathy,

lactic acidosis, and strokelike episodes: a distinctive clinical
syndrome. Ann Neurol 1984: 16: 481-488.
10. ZUPPINGR, KASSIKAE, RAUDAM
E. Cerebrospinal fluid
metabolic acidosis and brain oxygen supply. Arch Neurology
1971: 25: 33-38.
11. POSNERJB, PLUMF. Independent of blood and cerebrospinal fluid lactate. Arch Neurology 1967: 16: 492-496.
12. KURIYAMA
M, UMEZAKIH, FUKUDA
Y, OSAMEM, KOIKE
K, TATEISHI
J, IGATAA. Mitochondrial encephalomyo-

pathy with lactate-pyruvate elevation and brain infarction.
Neurology 1984: 34: 72-77.
S,NISHIMURA
Y, FUJIIK, OSHIMAM,
13. YAOH, SADOSHIMA
ISHITSUKA
T, FUJISHIMAM. Cerebrospinal fluid lactate in
patients with diabetes mellitus and hypoglycemic coma. J.
Neurology, Neurosurgery, and Psychiatry 1989: 52:
372-375.
14. EGGERJ, KENDALLE. Computed tomography in mitochondrial cytopathy. Neuroradiology 1981: 22: 73-78.
T. Mitochondrial
15. YAMAMOTOT, BEPPU H, TSUBAKI
encephalomyopathy: fluctuating symptoms and CT. Neurology 1984: 34: 1456-1460.
S, YASUMORI
K, UCHINOA, GODAS,
16. HASUOK, TAMURA
ISHIMOTO
S, WAKUTAY, KISHIM, MASUDA
K. Computed
tomography and angiography in MELAS (mitoshondrial
myopathy, encephalopathy, lactic acidosis and stroke-like
episodes); reported of 3 cases. Neuroradiology 1987: 29:
393-397.
17. Enzymatic determination of I-lactate concentration in blood
or serum, no. 15792; bulletin, C.F. Boehringer and Sons
Chemical CO., Mannheim, Germany, September 1963.

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