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Efficacy of lorenzo oil in adrenomyeloneuropathy.

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cent report, cerebrospinal fluid specimens of PPS patients
were recorded positive in an assay designed to measure poliovirus-specific IgM antibodies {l). This finding could not be
reproduced by another group using a different type of IgM
assay {a]. The latter workers also failed to demonstrate enterovirus-specific genome sequences in cerebrospinal fluid
(CSF) by using a sensitive polymerase chain reaction (PCR).
Yet another group used PCR to search for enterovirusspecific nucleic acid sequences in muscle biopsy specimens
from patients with PPS, with negative results [3}.
The reason for the discrepant results is not known, but one
can speculate on differences in patient selection and methods
used. Therefore, we have reexamined the matter. Twentyone patients with PPS treated in Finnish hospitals were selected from the computerized register maintained by the National Board of Health. The study patients were enrolled
using strict preset criteria and examined for several clinical
and laboratory parameters (E. I n n u n e n , T. Hovi, A. Paetau,
et al, unpublished data). Seven of the patients were men and
14 were women. The mean age was 51 years (range, 33-68).
The mean age at onset of acute poliomyelitis was 7 years (6
mo to 24 yr). The period between the acute phase and onset
of PPS was 36 years (15-61 yr) and that between onset of
PPS and the present examination was 8 years (2-20 yr).
CSF specimens from the 21 PPS patients were collected
and stored at - 20°C until assay. Specimens were assayed at
a dilution of 1:10 for IgM-class antibodies specific for poliovirus using a highly sensitive p,-capture radioimmunoassay 141.
The virus strains used in the assays were poliovirus type l /
Mahoney, type 2IMEF-1, and type 3lSaukett. All specimens
were negative and yielded counts at the buffer background
level only. We do not believe that a putative protease in the
CSF [5, 61 could have destroyed IgM antibodies, if present,
in the tested specimens because the specimens were frozen
immediately after collection and, on the other hand, during
the development of our assay 141 we tested several CSF specimens repeatedly after varying time of storage at + 4°C without significant changes in the results. W e know that our test
is highly sensitive because of the pcapture principle and use
of radiolabeled virus as indicator of bound IgM. More than
85g1 of patients with clinically typical acute poliomyelitis
were shown to have IgM in their CSF during the first 2
weeks of disease. In contrast, positive results later than a
month from the onset were exceptional [4). A further indication of the sensitivity of our IgM assay is the observation
that a serum specimen from 1 of the present patients, who
had received a booster dose of inactivated poliovirus vaccine
6 months before sampling, was definitely positive for IgM
antibodies of both type 1 and type 3 poliovirus. Hence, our
conclusion from the present studies is that our data do not
support the idea that patients with PPS would have an ongoing intrathecal immune response to poliovirus suggesting
chronic infection.
’Enterovirus Laboratory
National Public Health lnstitute (KTL)
WHO Collaborating Centrefor Reference and Research on
Poliomyelitis for the European Region
Helsinki, $Department of Neurology
Hyvinkaa District Hospital
Hyvinkaa, Finland
116 Annals of Neurology
Vol 36 No 1 July 1994
References
1. Sharief MK, Hentges R, Giardi M. Intrathecal immune response
in patients with the post-polio syndrome. N Engl J Med 1991;
325:749-755
2. Melchers W, de Visser M, Jongen P, et al. The postpolio syndrome: no evidence for poliovirus persistence. Ann Neurol 1992;
32:728-732
3. Leon-Monzon M, Dalakas MC. Absence of persistent infection
with enteroviruses in muscles of patients with inflammarory myopathies. Ann Neurol 1992;32:219-222
4. Roivainen M, Agboanvalla M, Stenvik M, et al. Intrathecal immune response and virus-specific immunoglobulin M antibodies
in laboratory diagnosis of acute poliomyelitis. J Clin Microbiol
10033 1:2427-2432
5 . Sharief MK. Poliovirus persistence in the postpolio syndrome.
Ann Neurol 1993;34:415-416
6. Melchers W, de Visser M, Jongen P, et a]. Ann Neurol 1993;34:
416-417 (Reply)
Efficacy of Lorenzo Oil in
Adrenomyeloneuropathy
Ely Simon, M D
The important study by Kaplan and associates [ l ) to determine the efficacy of “Lorenzo oil” for altering the natural
history of the progressive spinal adult form of adrenoleukodystrophy (ALD) (i.e., adrenomyeloneuropathy [AMN]) is
important, especially given the inflated promises propagated
by the recent motion picture. The results showing no demonstrable benefit to the fatty acid manipulation, though, is
somewhat clouded. The authors note that after 1 year, only
2 1 of 70 patients achieved normal plasma C26 :0 levels. Their
explanation for the failure in most patients to achieve expected decreases, based on nutrition interviews, was noncompliance with the diet. If this is correct, then a subgroup analysis is in order to determine the effects of the therapy in those
patients known to be compliant, i.e., the 21 patients with
normal C26:O levels. Although the analysis of the entire
group is still interesting, it does not satisfactorily answer the
principal question of the study: Does glycerol trioleate and
glycerol trierucate alter the natural history of ALD or AMN?
Because, by the authors’ assessment, most patients were actually not taking or only partially taking the treatment, we may
not be able to evaluate the effects of the treatment in those
patients. Of course, it is possible that, in fact, they were
adequately compliant and that the dietary manipulations have
variable effects on an individual’s levels of C26 :0. Nonetheless, the data are available to the authors to do the appropriate subgroup analysis. As noted in the editorial by Moser
[2], the data supportive of a favorable effect of Lorenzo oil
are suggestive at best. More detailed analyses of clinical data
may yield substantive answers for physicians eagerly awaiting
effective, scientifically based therapies for ALD and other
degenerative diseases.
NINDS
National Institutes of Health
Bethesda, M D 20892
References
1. Kaplan PW, Tusa RJ, Shankroff J, et al. Visual evoked potentials
in adrenoleukodystrophy:a trial with glycerol trioleate and Lorenzo oil. Ann Neurol 1993;34:169-174
2. Moser HW. Lorenzo oil therapy for adrenoleukodystrophy: a
prematurely amplified hope. Ann Neurol 1993;34:121-122
Reply
Peter W. Kaplan, MD, MB, BS, FRCP, Ronald Tusa, MD,
PhD, Jan Shankroff, MAS, JoEllen Heller, BA, and Hugo
Moser, M D
In adrenoleukodystrophy, there is a variable correlation of an
abnormally raised very long-chain fatty acid (VLCFA) level to
the degree of clinical abnormality. In consequence, when
trying to evaluate the effect of treatments aimed at lowering
the VLCFAs, there is uncertainty regarding the relative significance of a particular VLCFA level. Although clearly the
permanent normalization of such levels should be the goal
of these treatment modalities, it is unclear to what extent
duration of fall, absolute fall, o r relative fall (percent fall) are
therapeutically beneficial.
As noted in our results El], 21 of 70 patients achieved
normal plasma C26:O levels and an additional 29 patients
achieved at least some drop in C26:O. This variability of
biochemical response, the reason for which has not been
evaluated fully, provided the opportunity to correlate the
biochemical effect and clinical progression. Ely Simon suggests that a subgroup analysis should be done on compliant
patients, i.e., those with normalization of C26:O levels. This
subgroup analysis was performed and is given on page 17 1,
paragraph 1, line 10 where we examined dose-response with
correlations and found none. The grouped findings using x2
and odds ratios at baseline to the follow-up values obtained
at 7 year were analyzed with respect to success or failure in
normalization of the pattern-reversal visual evoked potential
PlOO latencies.
Because of the difficulties in obtaining normalization of
VLCFA levels or of the clinical abnormalities, evaluation of
therapeutic effect could be aimed at ranking degrees of success in lowering VLCFA and improvement in clinical state.
We are using such a graded approach to evaluate the effect
of Lorenzo’s oil on somatosensory evoked potentials.
Department of Neurotogy
Johns Hopkins University
School of Medicine
Baltimore, M D 21224
Reference
1. Kaplan PW, Tusa RJ, ShankroffJ, et al. Visual evoked potentials
in adrenoleukodystrophy:a trial with glycerol trioleate and Lorenzo oil. Ann Neurol 1993;34:169-174
4q35 Molecular Probes
for the Diagnosis and
Genetic Counseling of
Facioscapulohumeral
Muscular Dystrophy
G. C. Deidda, BS,’ S. Cacurri, BS,’ I. La Cesa, MD,f
C. Scoppetta, MD,? and L. Felicetti, MD*
Facioscapulohumeral muscular dystrophy (FSHD) is a degenerative disease of muscles that affects specific muscle groups
and displays a variety of phenotypic expressions. The inheritance pattern of FSHD is autosomal dominant, but patients
with a negative family history that is probably due to new
mutations have been frequently described. The gene for
FSHD has been localized to chromosome 4935 by linkage
studies, at 4 centimorgans distal to the linkage group
D4S 17 1-F 11-D4S 163-D4S 139 1-41, Recently W ijmenga
and co-workers [5] have described a probe, pl3E-11
(D4S810), that detects polymorphic D N A fragments in normal subjects, de novo D N A rearrangements of less than 28
kb in sporadic FSHD patients, and similar “small” fragments
in familial cases. The probe revealed a complex pattern of
bands ranging from 10 to 40 kb on standard agarose gel
electrophoresis because it recognizes two polymorphic loci
and a 10-kb Y-specific fragment. The rearranged fragments
are usually 14 to 28 kb in size, whereas the normal alleles
range between 30 and 300 kb. The association between de
novo D N A rearrangements and the development of FSHD
was demonstrated in 5 of 6 sporadic cases [5] and confirmed
by the transmission to the next generation in one family {6].
Here we report on an Italian sporadic FSHD family where
the propositus inherited two small pl3E-11 D N A fragments.
The larger is derived from D N A rearrangements within the
4935 region and is transmitted with the disease to the next
generation; the smaller is not 4q35 specific and does not
segregate with the disease. The Figure shows the pedigree
of the three generation FSHD family. Although the parents
did not have any symptoms of the disease, the proband (A)
is affected by a classical picture of FSHD disease, with weakness of facial muscles, proximal and distal weakness, scapular
winging, atrophy of the tibialis anterior, quadriceps, and
ileopsoas. Creatine kinase (CK) levels were slightly increased. Electromyographic studies and muscle biopsy were
consistent with myopathy. The daughter (C) showed an asymmetric smile, protruding lips, left scapular winging, and atrophy of the trapezius. The son (B) had weakness of the orbicularis oris, asymmetric scapular winging, slightly elevated CK
levels, and an electromyogram showing myopathic changes.
D N A analysis was performed by Southern blotting and hybridization with €32-labeled 4935 markers as described [3,
5). The proband (A) inherited from the mother (E) the chromosome characterized by the alleles 153-8.2-11.5 (4q35 haplotype) and two p13E-11 fragments, i.e., a “de novo” rearranged 23-kb fragment and a 13-kb smaller fragment. The
same haplotype was inherited by both affected children in
association with the 23-kb rearranged fragment. This indi-
Annals of Neurology
Vol 36 N o 1 July 1994
117
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