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Brief treatment with dichloroacetate does not modify suspected subacute necrotizing encephalomyelitis.

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dure can be performed easily because patients in question
would be maintained on respiratory support. Neuromuscular blocking agents are devoid of central nervous system
effects [GI.
EKG contamination is so common in high-sensitivity
EEG recordings that its absence should alert the technologist to examine the integrity of the recording system.
Baseline irregularity is often exaggerated by ballistocardiographic sffects that are identifiable by a regular relationship to the QRS complex of the EKG.
At the sensitivity employed, electrical noises generated
within the amplifiers may b e substantial. They are often
unevenly distributed between EEG channels, and adequate
calibrations should be provided. Further, electromagnetic
field characteristics are highly variable and unstable at settings used in portable EEG recording and can contribute
both intermittent and continuous wave activity resembling
cerebral electrical potentials.
EEG Laboruzory
Department of Neurology
University of Utah College of Medicine
Salt Luke City, U T 84132
1. American ElectroencephalographicSociety: Minimum technical standards for EEG recording in suspected cerebral death. In
Klass DW, Daly DD (eds): Current Practice of Clinical Electroencephalography. New York, Raven, 1979, pp 492-496
2. American Neurological Association: Statement regarding
method for determining that the brain is dead. Trans Am
Neurol Assoc 101:322-323, 1976
3. Ashwal S, Schneider S: Failure of electroencephalography to
diagnose brain death in comatose children. Ann Neurol
6512-517, 1979
4. Knott JR: Identification of EKG-related artifacts in very low
voltage EEG records. Am J EEG Techno1 16:129-130, 1976
5. Radberg C, Soderlundh S: Computer tomography in cerebral
death. Acta Radio1 [Suppl] (Stock) 346: 119-129, 1975
6. Toman JE, Davis JP: The effects of drugs upon the electrical
activity of the brain. Pharmacol Rev 1:425-492, 1949
Brief Treatment with
Does Not Modify
Suspected Subacute
Owen B. Evans, MD, and Peter W. Stacpoole, MD, P h D
Subacute necrotizing encephalomyelitis (SNE) is a neuropathological diagnosis often associated with disordered
pyruvate metabolism. Inhibition of thiamine triphosphate
synthesis [4] and, recently, defective regulation of the
pyruvate dehydrogenase complex (PDHC) 131 have been
reported in patients with SNE. DeVivo et a1 [31 suggested
the use of dichloroacetate (DCA) in treatment of these
disorders. W e report a brief trial of DCA in a child with
suspected SNE.
A 51/2-year-old girl had presented at 11/2 years with
ataxia and tremor. She subsequently developed progressive ataxia, dysmetria, ophthalmoplegia, bulbar paresis,
polyneuropathy, growth retardation, persistent tachycardia, episodic fever, and hypertension. Laboratory studies
showed mildly elevated urine catecholamines and hyperlactatemia that was exacerbated by a glucose challenge. Inhibition factor for thiamine pyrophosphateadenosine triphosphate phosphotransferase was demonstrated in the urine (courtesy of Dr J. R. Cooper).
Biochemical studies showed normal P D H C , pyruvate
decarboxylase, a-ketoglutarate dehydrogenase, and lipoamide dehydrogenase activity in muscle, fibroblasts, and
platelet-enriched plasma. Muscle histochemistry study
was normal for cytochrome c oxidase. Modifying the
platelet P D H C assay [l] by using 10 m M phosphate buffer
and shortening the incubation period to 5 minutes showed
activation of P D H C following preincubation with 20 mhf
magnesium chloride and 2 m M calcium chloride. T h e patient showed reduced basal P D H C activity (99 pmol/
minimg protein) compared to 5 healthy controls (221
93.1) but higher activated P D H C (357 versus 278
The value of (PDHC activated - P D H C basal)/(PDHC
basal) x 100 [3] was 26196, compared with 120
in controls; this difference was not statistically significant.
Because platelet isolation favors activation, the finding of
low basal PDHC activity in isolated platelet-enriched
plasma preparations is similar to the abnormalities of
PDHC regulation in the child reported by DeVivo et al [3].
The relationship of thiamine triphosphate synthesis inhibition to possible defective PDHC regulation is not known.
When the patient was 3 years old, before her biochemical defect had been identified and before the discovery of
chronic D C A neurotoxicity [ 5 ] , she was hospitalized for a
therapeutic trial of DCA for hyperlactatemia. Informed
consent was obtained from the child’s parents. The drug
was given as a single daily oral dose. The mean blood lactate level 10 days before treatment was 3.46 mMol per liter
t 29 SEM (normal, <2.10). During the continuous 10-day
Notes and Letters
treatment period, blood lactate decreased to 2.64 & 0.22
o n a DCA regimen of 20 mg/kg/day for 7 days and to 1.90
& 0.10 with 30 mg/kg/day for 3 days ( p < 0.05). The child
showed no complication or clinical improvement during
drug therapy.
Ours is the first report of D C A in the treatment of a
P D H C disorder. This and other studies 121 have shown the
efficacy of DCA in treating hyperlactatemia. However, because of the complexjty of P D H C regulation, hyperlactatemia may result from other biochemical disturbances
which secondarily affect P D H C activation. Therefore, reduction of blood lactate per se may not affect the primary
disease process. Longer treatment periods would b e necessary to determine if DCA can arrest the progression of
SNE. Animal studies are under way to study the cause of
DCA neurotoxicity and to investigate less toxic analogues
of therapeutic potential. At present, chronic administration
of the drug cannot be recommended.
Supported in part by agrant from the Muscular Dystrophy Association.
Department of Neurology and Division of Endocrinology,
Department of Medicine
Vanderbih University Medical Center
Nashville. T N 3 7232
1. Blass JP, Cedarbaum SD, Kark RAP: Rapid diagnosis of pyruvate and keroglutarate dehydrogenase deficiencies in plateletenriched preparations from blood. Clin Chim Acta 75:2 1-30,
2. Coude FX, Saudubray JM, DeMaugie F, et al: Dichloroacetate
as treatment for congenital lactic acidosis. N Engl J Med
299:1365-1366, 1978
3. DeVivo DC,Haymond M W , Obert KA, et al: Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (Leigh disease). Ann Neurol
6:483-494, 1979
4. Pincus JH:Subacute necrotizing encephalomyelopathy (Leigh’s
disease): a consideration of clinical features and etiology. Dev
Med Child Neurol 14:87-101, 1972
5. Stacpoole PW, Moore GW, Kornhauser DM: Toxicity of
chronic dichloroacetate. N Engl J Med 300:392, 1979
Failure to Include
Coauthor of Paper
Hugo W. Mnser, M D
D u e to an oversight on my part, D r Aubrey Milunsky’s
name failed to b e included in the paper entitled “Adrenoleukodystrophy : elevated C-26 fatty acid in cultured
skin fibroblasts,” by Moser HW, Moser AB, Kawamura N ,
Murphy J, Milunsky A, Suzuki K, Schaumburg H, Kishimoto Y (Ann Neurol 7:542, 1980). That this was indeed an oversight is evidenced by the fact that the Eunice
Kennedy Shriver Center had been listed as one of the
places of origin, and none of the other authors is associated
with that center. D r Milunsky’s name has been added to all
the reprints of the paper. I take full responsibility for chis
unintended oversight and apologize for it.
TheJohn F . Kennedy Initiiute
707 hTBroadway
Baltimore, M D 21205
648 Annals of Neurology Vol 8 No 6 December 1980
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treatment, subacuta, suspected, modify, brief, necrotizing, encephalomyelitis, dichloroacetate
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