THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
3
,4
fulfilled criterion 2 and 4. Four patients did not have myopathy,
neither clinically nor on muscle biopsy, but they all fulfilled
criteria 1 and 4.
In the majority of the cases, the LST was carried out during
the diagnostic work-up. In a few patients the LST was carried out
after the diagnosis had been established. Individual values of the
serum lactate at R1, S5, S10, S15 and R2 are given in the Figure.
Mean (SD) serum lactate levels at rest and during exercise are
given in the Table. Resting lactate was normal in 114 patients (74
protocol, and the applied criteria for abnormality. The
abnormal LST in a patient with Refsum’s disease might be due
to a special diet this patient had to follow. In the patient with
oculopharyngeal muscular dystrophy the abnormal LST was
attributed to the catabolic state this patient was in at the
beginning of hospitalization.
11,13
Contrary to previous reports,
serum lactate was normal at
rest before the exercise in three-quarters of the included patients
with MCP. This might be due to the test protocol, demanding a
rest of 10 minutes before the test and the selection bias. That
two-thirds of the MCP patients with abnormal LST had normal
resting lactate, stresses the importance of measuring serum
lactate not only at rest, but also during slight exercise when MCP
%
) and increased in 41 (26 %). Among the patients with
increased R1 value, three had a normal LST. In nine patients
6%) the R2 value further increased compared to the highest
(
value during exercise. The LST was abnormal in 103 patients
4
,21
(67%). Among these, resting lactate was normal in 64 patients
62%). In three patients without myopathy the LST was
is suspected. Additionally, the LST should be carried out in
patients with normal electrophysiological findings but having
(
4
abnormal. In patients with abnormal LST, the EMG was
myogenic in 47 (46%), neurogenic in 16 (16%), unspecifically
abnormal in 13 (13%), and normal in 27 patients (26%). Forty-
six patients with abnormal LST (45%) showed ragged-red fibers
clinical evidence of MCP. Particularly in patients who refuse
muscle biopsy, the LST may be helpful to support the
3
,4,10
diagnosis.
However, a normal LST does not exclude MCP.
Increased resting lactate but normal LST in three of the
investigated patients remains unexplained. Further increase of
serum lactate at R2 in nine patients may be due to a prolonged
wash-out of serum lactate.
>
5%, 98 patients (95%) reduction of cytochrome-c oxidase
activity on muscle biopsy, and 80 patients (78%) abnormally
shaped and structured mitochondria.
Usually there is a good relation between the LST and the
degree of muscle affection on histopathological findings. In
some cases, however, an abnormal LST may not be associated
2
1
DISCUSSION
Despite great progress in the diagnostic procedures,
particularly molecular genetic techniques, the LST has defended
its role as a screening method in the diagnostic work-up of
MCPs. This might be due to the fact that the LST is cheap, quick
and easy to perform, even by unskilled technicians, and is
2
1
with a reduction of the oxidative enzyme stainings. In such
cases, the heteroplasmy rate in the skeletal muscle may be low.
The close relation between the LST and the muscle pathology in
the present investigation is supported by the fact that the organ
most often affected was the skeletal muscle. In only four patients
there was no evidence of myopathy. That the LST was abnormal
in three of these patients favors the LST also as a screening test
for subclinical myopathy in MCP. The low frequency of
abnormal biochemical findings in the present investigation might
be due to the low heteroplasmy rate and the fact that there was
only a checkerboard reduction of oxidative enzymes in most
4,8
applicable to the majority of the MCP patients. Unfortunately,
there is still no consensus about the protocol the LST should
follow in the daily routine. Among various protocols to perform
the LST, the most frequently applied is the one proposed by Zierz
8,11,16
et al
which follows a similar procedure as in the present
investigation but regards an individual result abnormal only if
serum lactate exceeded 1.5 mmol/l at rest and 2.0 mmol/l during
exercise. In several other studies subjects were stressed
according to a protocol different from the one applied in the
2
,4
cases. That not all patients with abnormal EMG, ragged-red
fibers >5%, reduced oxidative enzyme staining, abnormal
mitochondria or proven mtDNA mutation also had an abnormal
LST, supports the view that the diagnosis of MCP requires a
multiprofessional effort and the synopsis of clinical, serological,
electrophysiological, histopathological, biochemical and genetic
6
,10,12,13,16-20
present investigation.
Generally, a disadvantage of
protocols which require an absolute workload is that differences
in muscle mass and physical conditioning are not considered,
although it is well-known that the lactate increase under a fixed
workload may be due to deconditioning and reduced body
2
data.
In conclusion, this study showed that the LST was abnormal
in two-thirds of the patients with MCP. The specificity of the test
is high. The test supplements clinical, bioptical and genetic
investigations. The test is easy to perform, cheap and reliable.
The test is particularly helpful in patients with strong clinical
evidence of a MCP, but who refuse muscle biopsy, or in whom
genetic screening is not informative.
1
7,21
mass.
Although a workload relative to the maximal is
assumed to give a higher sensitivity and specificity, particularly
if the maximal workload is reached stepwise, results of a recent
investigation show that cycling with 30% of the maximal
2
2
workload does not increase the diagnostic yield of the LST.
This unexpected finding might be due to the determination of the
maximal workload by an “all work-out exercise”. Another
modification of the LST, which relies on the calculation of the
difference between resting lactate and the maximal lactate value
during exercise, does not increase the diagnostic yield of the LST
either (unpublished data). In previous studies, on smaller groups
of patients, the sensitivity of the test ranged between 66 and
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1. DiMauro S, Bonilla E, Zeviani M, Nakagawa M, DeVivo DC.
Mitochondrial myopathies. Ann Neurol 1985: 17: 521-538.
2
.
Morgan-Hughes JA. The mitochondrial myopathies. In: Engel AG,
Franzini-Armstrong C, eds. Myology. Basic and Clinical. New
York: McGraw-Hill, 1994: 1610-1651.
3
,8-14
100%,
being thus in line with our Figure. Why the sensitivity
of the present investigation to detect MCP was not higher than
previously reported, might be due to the selection bias, the test
3. Finsterer J, Shorny S, Capek J, et al. Lactate-stress test in the
diagnosis of mitochondrial myopathy. J Neurol Sci 1998: 159:
1
76-180.
5
2
Schrauth
