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Correlation of isotopic cisternographic patterns in multiple sclerosis with CSF IgG values.

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Plasma Biotin Levels in Epileptics Receiving Single-Drug Therapy
No. of Patients
Biotin (ndL, mean 2 S D )
2 0 1 t 55
2 1 8 t 59
340 1 7 1
Sodium valproate
Correlation of Isotopic
Cisternographic Patterns
in Multiple Sclerosis
with CSF IgG Values
600 500LOO -
S. Bartolini, MD,* D . Inzitari, MD,"
A. Castagnoli, M D , t and L. Amaducci, MD"
3002 00
con trols
Plasma biotin levels in' epileptics receiving long-term anticonvulsant therapy (N = 264) and in controls (N = 93).
Supported by Grant Kr 65911 from the Deutsche Forschungsgemeinschaft.
The authors are indebted to Dr J. P. Vuilleumier, Department of
Vitamin and Nutrition Research, F. Hoffmann-LaRoche, for carrying out the biotin determinations.
1. Bonjour J-P: Biotin-dependent enzymes in inborn errors of
metabolism in humans. World Rev Nutr Diet 38:l-88, 1981
2. Charles BM, Hosking G, Green A, Pollit R, Bartlett K, Taitz
LS: Biotin-responsive alopecia and development regression.
Lancet 2:118-120, 1979
3. Cowan MJ, Wara DW, Packman S, Amman AJ, Yoshino M,
Sweetman L, Nyhan WL: Multiple biotin-dependent carboxylase deficiencies associated with defects in T-cell and Bcell immunity. Lancet 2:115-118, 1979
4. Frigg M, Brubacher G: Biotin deficiency in chicks fed a wheatbased diet. Int J Vitam Nutr Res 46:314-321, 1976
5. Krause K-H, Berlit P, Bonjour J-P: Erniedrigung des Biotins
als moglicher Faktor im Wirkmechanismus von Antiepileptika.
Arch Psychiatr Nervenkr 23 1:141-148, 1982
6. Patsalos PN, Lascelles FT:Changes in regional brain levels of
amino acid putative neurotransmitters after prolonged treatment with the anticonvulsant drugs diphenylhydantoin,
phenobarbitone, sodium valproate, ethosuximide, and sulthiame in the rat. J Neurochem 36:688-695, 1981
7. Sander JE, Malamud N , Cowan MJ, Packman S , Amman AJ,
Wara DW: Intermittent ataxia and immunodeficiency with
multiple carboxylase deficiencies: a biotin-responsive disorder.
Ann Neurol 8~544-547, 1980
8. Thoene J, Baker H, Yoshino M, Sweetman L Biotinresponsive carboxylase deficiency associated with subnormal
plasma and urinary biotin. N Engl J Med 304:817-820, 1981
T h i r t y - e i g h t patients with multiple sclerosis (MS)
were examined with isotopic c i s t e r n o g r a p h y (IC) in
order to s t u d y cerebrospinal fluid (CSF) dynamics. Cist e r n o g r a p h y was also performed in 15 patients with
a m y o t r o p h i c lateral sclerosis and in 14 with senile dementia of the A l z h e i m e r t y p e as controls. IC pattern of
"mixed" t y p e was found in 18 MS patients and all those
with A l z h e i m e r senile dementia examined, while the
IC examination did not show a b n o r m a l i t y in a n y of
15 patients with a m y o t r o p h i c lateral sclerosis. In
MS patients, the abnormal IC picture proved to be
significantly c o r r e l a t e d with the CSF IgG values as calculated b y Link's and Tourtelotte's formulas. The abnormal IC in MS ]may be due to altered CSF reabsorption or increased t r a n s e p e n d y m a l flow, or it m a y be
related to the a b n o r m a l concentration of IgG.
Bartolini S, Inzitari D, Castagnoli A, Amaducci L:
Correlation of isotopic cisternographic patterns in
multiple sclerosis with CSF I g G values.
A n n Neurol 12:486-489, 1982
In recent years, m a n y investigators have utilized
isotope c i s t e r n o g r a p h y (IC) to evaluate the formation
and absorption of cerebrospinal fluid (CSF) [2-41.
Attempts to correlate the results of isotope tests with
various disease st,ates have not always produced consistent associatioins. Nevertheless, certain patterns
have been a t t r i b u t e d to the presence of i n f l a m m a t o r y
From the *Department of Neurology and the +Nuclear Medicine
Service, University of' Florence, 50134 Florence, Italy.
Received May 12, 1981, and in revised form Feb 23, 1982. Accepted for publication Mar 15, 1982.
Address reprint requests to Dr Amaducci.
486 0364-5 134/82/110486-04$01.25 @ 1982 by the American Neurological Association
Results of Isotopic Cisternography i n Relation t o Clinical and Laboratoy Variables in Patients with Multiple Sclerosis and Controh
No. of Patients
IC Pattern
Mean Age (yr)
IgG Indexa
CNS IgG Synthesisb
18 (47%)
20 ( 5 3 % )
15 (100%)
14 (100%)
Abnormal “mixed”
Abnormal “mixed”
60.2 1
“IgG index calculated according to Link; normal values: 0.48
k 0.10.
b“Denovo” CNS IgG synthesis calculated according to Tourteilotte; normal values: G 3.3 mg per day.
“Significance: p < 0.01.
IC = isotope cisternography; MS = multiple sclerosis; ALS = amyotrophic lateral sclerosis; SDAT = senile dementiaof the Alzheimer type.
illness. For this reason, we decided to evaluate IC in a
group of patients with multiple sclerosis (MS). The
results were compared with the findings in other patients with amyotrophic lateral sclerosis (ALS) and
senile dementia of the Alzheimer type (SDAT), respectively.
Material a n d Methods
Thirty-eight patients with definite MS, 14 male and 24 female, were examined. The diagnosis was assessed by clinical evaluation and laboratory investigation. In particular,
serum and CSF radial immunodiffusion (according to Mancini et a1 [8]) was performed in each case, and the IgG index
according to Link [7] and daily intrathecal production of
IgG [9]were calculated. The results of IC performed in 15
ALS patients and 14 patients with SDAT were compared as
IC was carried out with a routine lumbar puncture.
9Tc-DTPA solution, 20 to 30 pCi per kilogram of body
weight (total volume, 1 to 1.5 ml), was introduced into the
spinal subarachnoid space. Radiography was performed 1,
2, 6, and 24 hours after the injection. The cisternographic
pictures were classified according to recent literature [101
as follows:
Normal pattern: uninterrupted flow from the lumbar subarachnoid space into the basal cisterns, around the
brainstem, through the tentorial notch into the sylvian
cisterns, and over the convexities of the hemispheres to
the parasagittal regions. No ventricular activity is observed.
Mixed pattern: filling of the ventricular system 4 to 6 hours
after lumbar injection. At 24 hours ventricular activity
may still be seen, but normal flow over the hemispheric
convexities is also observed.
Ventricular pattern: ventricular influx both early and late as
long as radioactivity can be detected. Although there is
no flow of isotope above the tentorial notch, one or both
sylvian cisterns may occasionally be visualized; flow over
the hemispheres to the parasagittal regions is not observed.
The cisternographic patterns in the MS patients were
correlated with the clinical and laboratory variables of patient age, IgG index according to Link, and daily intrathecal
production of IgG according to Tourtellotte.
Computed tomographic (CT) studies were available for
15 of the patients with MS and all 14 with SDAT.
In 18 (47%) of the 38 MS patients examined, IC
showed an abnormal picture of mixed type. A mixed
pattern was also detected in all SDAT patients. None
of the 15 ALS patients showed an abnormal IC pattern. The four groups (MS with abnormal IC, MS
with normal IC, ALS, and SDAT) were compared according to patients’ mean age, mean IgG index, and
mean rate of IgG synthesis in the central nervous
system (Table). The group of MS patients with abnormal IC differed significantly from the others in
their IgG index and rate of IgG synthesis in the central nervous system.
CT scan of the brain was performed in 15 of the 38
MS patients and the findings compared with those
obtained by CT study of the 14 SDAT patients. CT
was carried out in 5 MS patients with an abnormal IC
picture. In 2, the scan showed enlargement of the
cerebral ventricles, mostly of the lateral. One of
these CT scan pictures is reproduced in Figure 1 and
is compared with the cisternogram, Figure 2, obtained in the same patient. In the other 3 MS patients
with abnormal IC only slight cortical and subcortical
atrophy was observable, similar to that seen in 3 of 10
MS patients with normal IC in whom CT was carried
out. In the other 7 patients no abnormality of the CT
picture was found. CT study in all SDAT patients
showed cortical and subcortical atrophy.
Some considerations should be pointed out in relation to the significance and diagnostic limits of the
technique of IC using @ T cas the marker. The abnormal patterns, particularly the so-called mixed
type, should no longer be considered of specific
diagnostic value [5, 61. It appears that an abnormal
pattern may be produced by different physiopathological mechanisms that are not yet completely
clarified. Moreover, similar pathological patterns
can be detected in different clinical conditions.
Brief Communication: Bartolini et al: Isotopic Cisternography in MS 487
F i g 1 . CT scan i n the MS patient whose cisternographicpictures are shown in Figure 2 demonstrates moderate dilatation
of the lateral ventricles and signs of mild subcortical atrophy.
We found an altered isotopic pattern of mixed type
in 47% of our MS patients and in all SDAT patients
subjected to this investigation. Among the possible
mechanisms of the altered IC in MS, the following
may be considered. First, the abnormal pattern may
be due to an inflammatory alteration of the subarachnoid spaces of the cerebral convexities. There is
pathological evidence of chronic inflammation of the
leptomeninges, localized mainly to the subarachnoid
spaces of the cerebral convexities, in the active forms
of MS [l]. These alterations may affect the normal
efflux of CSF from the ventricular system to the sites
of reabsorption in the cranial vault. And second, an
altered IC with a pattern of mixed type may be related to increased transependymal CSF reabsorption
as a consequence of alteration of the ependyma, the
periventricular white matter, or both. This abnormal
reabsorption may lead to inversion of the normal
flow gradient from the ventricles to the subarachnoid
space. The main periventricular distribution of demyelination in MS is well known [l].
Our results indicated a significant correlation between abnormal IC patterns and IgG produced in
situ. However, this finding also suggests that CSF
IgG levels may be influenced by CSF dynamics and
F i g 2. CisternoRraphtcpictures ( A )2 hours, (B)6 hours, and
(C) 24 hours after tracer injection i n 1 of the MS patients
studied. This pattern was classzjied as mixed type.
may correlate with the reabsorption rate of CSF
proteins at drainage sites.
Further studies in MS, using more sensitive
isotopic techniques and CT with metrizamide together with determination of IgG turnover with
isotope-marked IgG, seem necessary in order to
confirm and clarify our data in MS patients.
T h e authors wish to express their gratitude to Prof R. D. A d a m
for his critical review of the manuscript.
488 Annals of Neurology Vol 12 No 5 November 1082
1. Adams CW: Pathology of multiple sclerosis: progression of
lesions. Br Med Bull 33:15-21, 1977
2. Di Chiro G, Ashburn WL, Bunier WH: Technetium Tc 99m
serum albumin for cisternography. Arch Neurol 19:218-227,
3. Farrel K, Hill A, Chuang S: Papilledema in Guillain-Barre
syndrome. A case report. Arch Neurol 38:55-57, 1981
4. James
De Land
FH, WagnerAm
J Cerebral
Ther Nucl Med 110:74-87, 1970
5. Kieffer SA, Wolff .JM, Prentice WB, Loken M K Scinticisternography in individuals without known neurological disease. Am J Roentgenol Radium Ther Nucl Med 112:225236, 1971
6. Kieffer SA, Wolff M, Westreich G: The borderline scinticisternogram. Radiology 106: 133-140, 1973
7. Link H: The value of cerebrospinal fluid immunoglobulin
analysis in clinical neurology. Riv Patol Nerv Ment 97:323344, 1976
8. Mancini G, Carbonara AD, Heremans JF: Immunochemical
quantitation of antigens by single radial immunodiffusion.
Immunochemistry 2:235, 1956
9. Tourtellotte WW, Booe IM: Multiple sclerosis: the bloodbrain-barrier and the measurement of de novo central nervous
system IgG synthesis. Neurology (Minneap) 28 (suppl):
76-83, 1978
10. Wolinsky J, Barnes BB, Margolis MT: Diagnostic test in normal pressure hydrocephalus. Neurology (Minneap) 23:706713, 1973
Intravascular Malignant
Histiocytosis Mimicking
Central Nervous
System Vasculitis:
An Immunopathological
Diagnostic Approach
c. C i e g e r , MD,* y. Robitaille, m,”
S. Jothy,
and G. Elleker, MDX
A 53-year-old man presented with a lumbosacral
polyradiculoneuropathy and developed fluctuating
encephalopathy suggestive of multifocal small vessel
disease. Postmortem examination demonstrated multifocal vascular occlusions by undifferentiated cells
confined to the intravascular space. Extravascular
spread was found only in spleen and liver. The presence of lysozyme and absence of factor VIII in the
cytoplasm of the malignant cells confirmed their histiocytic nature. This patient had an unusual intravascular form of malignant histiocytosis that must be
included in the differential diagnosis of multifocal
vascular disease.
Krieger C, Robitaille Y ,Jothy S, Elleker G:
Intravascular malignant histiocytosis mimicking
central nervous system vasculitis: an
immunopathological diagnostic approach.
Ann Neurol 12:489-492, 1982
Widespread vascular occlusion by malignant cells is
not often considered in the diagnosis of multifocal
nervous system disease. Rare examples of neoplastic
angioendotheliosis [2, 12, 14, 181 and tumor emboli
[6] have been considered to produce signs by this
A patient with progressive polyradiculoneuropathy
and fluctuating encephalopathy was found at autopsy
to have multiple small vessel occlusions by malignant
histiocytes. Malignant cells were found within vascular lumens without parenchymal involvement of any
organ except the spleen and liver.
Case Report
A 53-year-old man developed progressive leg weakness,
numbness, and gait difficulty over four months. O n admisFrom the *Montreal Neurological Institute, and the +Department
of Pathology, McGill University, Montreal, Quebec, Canada.
Received Jan 4, 1982, and in revised form Mar 25. Accepted for
publication Mar 26, 1982.
Address reprint requests to Dr Robitaille, Department of
Neuropathology, Montreal Neurological Institute, 3801 University St, Montreal, Que, Canada H3A-2B4.
0364-5134/82/ 110489-04$01.25 @ 1982 by the American Neurological Association
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correlation, patterns, igg, cisternographic, values, sclerosis, csf, multiple, isotopic
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