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Changes in T-cell subpopulations in multiple sclerosis.

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10. NasraUah HA. The unintegrated right cerebral hemispheric
consciousness as alien intruder: a possible mechanism for
schneiderian delusions in Schizophrenia. Compr Psychiatry
1985;26:273-281
Reply
John OKusky, PhD,* Esther Strauss, PhD,?
Brenda Kosaka, MA,: Juhn Wada, MD,$$
David Li, MD, 11 Margaret Druhan, RN,$lI and
Julie Petrie, BAt
In view of our recent study El), Dr Nasrallah suggests that
enlargement of the corpus callosum in schizophrenic subjects
c2-41 may reflect a greater incidence of right-hemisphere
cerebral speech dominance. Furthermore, he speculates that
perinatal brain insult, resulting in the failure to elmnate
normally transient axons in the corpus callosum during postnatal development, may be an important factor in the pathogenesis of schizophrenia. We agree that these are interesting and testable hypotheses. However, we believe that the
potential results of this research would not warrant the use of
intracarotid injection of sodium amytal to determine cerebral
speech dominance in these subjects. A less invasive technique, such as neuropsychological assessment including a
verbal dichotic listening test (e.g., [5J), would be more suitable for this patient population.
The persistence of normally transient axons and synapses
has been implicated in the pathogenesis of several developmental disorders of the central nervous system. For example,
recent studies have demonstrated a failure to eliminate dendritic spines (and presumably their axospinous synaptic contacts) on developing brainstem neurons in sudden infant
death syndrome {G-7). In subjects with mental retardation,
the density of synapses in the cerebral cortex has been reported to be significantly grdater than in neurologically normal control subjects [S]. It is a distinct possibility that in
some types of schizophrenia the brain is characterized by an
excess of callosal axons and intracortical synapses. The extent
to which perinatal disease or injury can disrupt normal regressive events in the central nervous system during postnatal development remains an intriguing subject for future
developmental studies. Quantitative histological studies of
postmortem human brain are needed to test the validity of
these hypotheses.
'Department of Pathology, Division of Medical Microbiology
$Divisions of Neurological Sciences and $Neurology
Departments of IlDiagnostic Radiology and Wsychiatry
University of British Columbia
Vancouver, BC, Canada
?Department of Psychology
University of Victoria
Victoria,BC, Canada
References
1. OKusky J, Strauss E, Kosaka B, et al. The corpus callosum is
larger with right-hemsphere cerebral speech dominance. Ann
Neurol 1988,24:379-383
2. Rosenthal R. Bigelow LB. Ouantitative brain measurements in
chronic schizophrenia Br J Psychatry 1972;12 1 259-264
3 Bigelow LB,Nasrallah HA, Rauscher FP Corpus callosum thickness In chrotuc schtzophrenia Br J P~ychiatry1983,142 284-287
I
-
4. Nasrallah HA, Andreasen NC, Coffman JA, et al. A controlled
magnetic resonance imaging study of corpus callosum thickness
in schizophrenia. Biol Psychiatry 1986;2 1:274-282
5. Strauss E, Gaddes WH, Wada J. Performance on a free-recall
verbal dichotic listening task and cerebral speech dominance determined by the carotid amytal test. Neuropsychologia 1387;25:
747-753
6. Quattrochi JJ, McBride PT, Yates AJ. Brainstem immaturity in
sudden infant death syndrome: a quantitative rapid Golgi study of
dendritic spines in 95 infants. Brain Res 1985;325:39-48
7. Takashima S, Becker LE.Developmental abnormalities of medullary respiratory centers in sudden infant death syndrome. Exp
Neurol 1985;90:580-587
8. C r a g BG. The density of synapses and neurons in normal, mentally defective and aging human brains. Brain 1975;98:81-90
Changes in T-cell
Subpopulations in
Multiple Sclerosis
A. Achiron, MD, PhD," M. Mendel, MD,t G. Rechavi,
MD, PhD,? B. Ramot, MD,t and E. Melamed, MD*
Rose and colleagues {I J state in their study that patients wirh
remitting-relapsing multiple sclerosis (MS) frequently have
selective depletion of the CD45R+CD4+ T-cell subset during active phases of the disease. They found significant
changes in the ratio of two CD4+ T-cell subsets in 7 of 9
patients.
It was stated by the authors that some of the MS patients
were treated with corticosteroids after a major relapse and
were given prednisone, 80 mgiday, with tapering of the drug
over 40 days. According to the results, 3 patients received
this treatment and also showed changes in CD4+ T-cell subsets.
To our knowledge, corticosteroids can induce T-cell subset changes. In our laboratory we study T-cell subsets only in
steroid-free patients. Chofflon and associates 121, in their
work on T-cell subpopulations published in the same issue,
emphasized that their MS patients had received no steroids
for one month before entering the study. Compston and coworkers [3} found an increase in OKT8 and OKT4 in MS
patients treated with high doses of methylprednisolone.
Other authors E4, 5) also reported similar effects of corticosteroids on T-cell subpopulations.
The finding of Rose and colleagues [l) may reflect a state
of ongoing lymphocyte activation induced by corticosteroids,
and not necessarily an abnormal Auctuanon related to disease
activity. T o define changes in lymphocyte subpopulations,
we recommend that they be analyzed during a corticosteroidfree period.
*Departmentof Neurology
center
Petah Tiqva. Israel
Unit
fMo'ecular
Hematology Instrtute
Cham Sheba Medzcal Center
Tel Hashomer, Israel
Annals of Neurology Vol 26 No 2
August 1989 291
References
Lynn M. Rose, PhD,' Arthur H. Ginsberg, MD,t
Ted L. Rothstein, MD,? Jeffrey A. Ledbetter, PhD,$
and Edward A. Clark, PhD'
study. Three of the nine patients studied received corticosteroid therapy, and in all three the steroids were administered
after blood was drawn for subset analysis. All 3 patients had
been corticosteroid-free for at least six months prior to their
relapses. Thus, the subset fluctuations observed prior to relapse cannot be attributed to corticosteroid treatment. It is
possible that the prednisone given as therapy affected the
absolute numbers of CD45R+ and CD45R- C D 4 + T-cell
subsets in the two to three month period following the relapses; however, our data do not support this conclusion. We
found no consistent paetern of subset fluctuation as a result
of treatment. Furthermore, the subset fluctuations observed
in untreated patients and the lack of similar changes in normal controls support our hypothesis that these changes are
related to disease activity.
In addition, there is no evidence to suggest that corticosteroids can differentially affect the expression of the CD45R
glycoprotein on T-cell subsets. This undoubtedly needs to be
tested and would certainly help clarify questions about the
effects of steroids on lymphocyte subsets. In the meantime,
we would like to stress that subset fluctuations occur in the
absence of corticosteroid treatment and appear to be related
to an ongoing disease process.
W e are pleased to respond to D r Achiron and colleagues
concerning our study of fluctuations of CD4' T-cell subsets
in multiple sclerosis. First, we agree that lymphocyte subset
changes should be studied during corticosteroid-free periods.
We made every attempt to adhere to this principle in our
"Department of Microbioloa
University of Washington
fNorthwest Hospital
$Oncogen Corporation
Seattle, WA
1. Rose LM, Ginsberg AH, Rothstein TL, et al. Fluctuations of
CD4 ' T-cell subsets in remitting-relapsing multiple sclerosis.
Ann Neurol 1988;24:192-199
2. Chofflon M, Weiner HL, Morimoto C, Hafler DA. Loss of functional suppression is linked to decreases in circulating suppressor
inducer (CD4 2H4 +) T cells in multiple sclerosis. Ann Neurol
1988;24:185-191
3. Compston DA, Milligan NM, Hughes PJ, et al. A double-blind
controlled trial of high dose methylprednisolone in patients with
multiple sclerosis: 2. Laboratory results. J Neurol Neurosurg Psychiatry 1987;50:517-522
4. Bertoglio JH, LeRoux E. Differential effects of glucocorticoids
on the proliferation of a murine helper and a cytolytic T cell
clone in response to IL-2 and IL-4. J Immunol 1988;141:1191-
+
1196
5. Pfeffer PF, Hirschberg H . Effect of methylprednisolone on human lymphucytes primed to alloantigens. J Clin Lab Immunol
1983;10:19-24
Reply
292
Annals of Neurology
Vol 26 No 2
August 1989
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