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Differentiation of multiple system atrophy from idiopathic Parkinson's disease using proton magnetic resonance spectroscopy.

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Dfierentiation of Multiple Systern Atrophy
from Idiopathic Parhnson’s Disease Using
Proton Magnetic Resonance Spectroscopy
C. A. Davie, MRCP, G. K. Wenning, MD, G. J. Barker, PhD, P. S. Tofts, D Phil, €3. E. Kendall, FRCR,
N. Quinn, MD. W. I. McDonald, PhD, C. D. Marsden, DSc, and D. H. Miller, M D
Proton magnetic resonance spectroscopy, localized to the lentiform nucleus, was carried out in 7 patients with the
pure or predominantly striatonigral variant (SND) of multiple system atrophy (MSA), 5 patients with the olivopontocerebellar variant of MSA, 9 patients with a clinical diagnosis of idiopathic Parkinson’s disease (IPD), and 9 healthy
age-matched controls. The MSA group with predominantly striatonigral involvement showed a significant reduction
in the N-acetylaspartate (NAA)/creatine ratio (median, 1.19; range, 0.96-2.0; p < 0.02) compared with the NAA/
creatine ratio from the control group (median, 1.76; range, 1.61-2.0). In contrwt, the IPD group had a normal NAAl
creatine ratio (median, 1.82; range, 1.19-2.31; p > 0.5). The NAAlcreatine ratio was markedly reduced in 6 of the
SND patients and in only 1 IPD patient. The choline/creatine ratio was also significantly lower in the SND group
(median, 1.02; range, 0.91-1.23; p < 0.04) compared with the control group (median, 1.22; range, 1.05-1.65). The
IPD group showed a normal lentiform choline/creatine ratio (median, 1.13; range, 0.89-1.65; p = 0.25) compared
with controls. The olivopontocerebellar group also showed a significant reduction in the NAAicreatine ratio from
the lentiform nucleus (median, 1.47; range, 1.22-1.68; p < 0.01) compared with the controls as well as a nonsignificant
reduction in the choline/creatine ratio (median, 0.93; range, 0.85-1.27; p < 0.4). In vivo quantification of absolute
metabolite concentrations was possible in 7 MSA patients and 6 controls and confirmed an absolute reduction of
choline-containing compounds and NAA in the MSA group compared with controls with no significant difference
in the creatine concentrations between the MSA group and the controls. T h e reduction of the NAAlcreatine ratio
from the lentiform nucleus in the MSA groups probably reflects neuronal loss, occurring predominantly in the putamen. Proton magnetic resonance spectroscopy is a useful, noninvasive technique to help differentiate MSA from IPD.
Davie CA, Wenning GK. Barker GJ, Tofts PS, Kendall BE, Quinn N, McDonald WI, Marsden CD, Miller DH.
Differentiation of multiple system atrophy from idiopathic Parkinson’s disease using
proton magnetic resonance spectroscopy. Ann Neurol 1995;37:204-2 10
Multiple system atrophy (MSA) is a sporadic, degenerative disease of the nervous system. T h e condition encompasses a wide spectrum of clinical presentations
with various combinations of extrapyramidal, pyramidal, cerebellar, and autonomic signs and symptoms [ 11.
Pathologically, the condition is characterized by neuronal cell loss and gliosis particularly involving the
putamen, substantia nigra, pons, cerebellar cortex,
inferior olives, and Onuf‘s nucleus {a]. In addition,
characteristic glial cytoplasmic inclusions [3-51 are
present in these and other brain areas. These findings,
together with the absence of Lewy bodies (unless incidental), distinguish MSA from idopathic Parkinson’s
disease (IPD). Nevertheless, the two conditions may
be difficult to separate clinically, particularly in those
cases of the striatonigral (SND) variant of MSA
in which additional cerebellar and pyramidal signs
are absent, at least initially. Thus, in a review of
188 cases with pathologically proven MSA, 245; of
the patients with parkinsonism had neither pyramidal
or cerebellar signs [GI. Furthermore, in Parkinson’s
disease brain banks, between 5G and 22(;+ of brains
show the pathological changes of MSA at postmortem
I I , 73.
T h e need to differentiate MSA from IPD during life
is important for a number of reasons. First, MSA has
a less favorable prognosis with a median survival in
different series ranging from 5.5 to 9.5 years [6].Second, epidemiological studies attempting to establish
the etiologies of MSA and IPD are heavily dependent
o n correct diagnosis during life. Finally, pharmacological and nigral transplantation studies in IPD are less
likely to show significant and sustained benefit if MSA
patients are iriadvertently included {S].
From the Department of Clinical Neurology, Institute of Neurdogy.
London, UK.
Receivetl Mar 31, 1904, and in revised form Jun 2 0 and Aug 5.
Accepted for publication Aug 1 I , 1994.
AJJrcss correspvndencc co Dr hlillcr. NhlR Research Group, Instiof Neurology. Queen Square House, London W C I N 3BG.
Copyright (Q 1995 by the American Neurological Association
A number of imaging tools may help to differentiate
MSA from IPD. Brooks and co-workers [9-1 1) using
positron emission tomography (PET) examined striatal
uptake of the presynaptic dopminergic markers
["FF)Huorodopa and 3-["C]nomifensine. Putaminal uptake of both ligands was similarly reduced in MSA and
IPD, though in approximately half the MSA subjects,
caudate uptake was also markedly reduced, as opposed
to only moderate reduction in IPD. Studies with the
postsynaptic dopamine receptor ligand ["Clraclopride
have shown a greater reduction in striatal binding in
chronically levodopa-treated IPD patients than in a
group of patients with SND type MSA [ 12). However,
in a similar study of untreated patients, the 1 subject
who subsequently turned out to have MSA showed a
marked reduction of strbatal binding of raclopride relative to the remaining 8 with IPD [l.?]. Another study
of 38 patients with de novo parkinsonism used ["'I]iodobenzamide (IBZM) (a D2 receptor antagonist) as a
Iigand with single-photon emission computed tomography (SPECT) [14}. This showed good correlation between a good c h i d response to subcutaneous apomorphine (a D1 and D 2 receptor agonist), a good
subsequent response to dopamimetic therapy, and normal striatal IBZM binding. The use of other ligands
such as ["C]diprenorphine [ 151 and [18F)fluorodeoxyglucose [ 16, 17) in PET studies may also show mean
differences between the two groups.
Conventional magnetic resonance imaging (MRI)
with T,-weighted spin echo sequences at 1.5 T in pa-
I . 10
0 91
OPCA variant
1.3 1
S N D variant
tients with atypical parkinsonism has been reported to
show low signal in the putamen, which is thought to
be the result of increased iron content [lg]. However,
the specificity and sensitivity of this finding for MSA
remains unclear E19, 201.
Proton magnetic resonance spectroscopy (MRS) is a
noninvasive method that provides information about
the chemical pathology of conditions affecting the central nervous system. The largest peak visible with MRS
is derived principally from N-acetylaspartate (NAA),
an amino acid contained almost exclusively within neurons [2 1) and their processes in adult brain. Given that
loss of striatal neurons is a feature of MSA but not of
IPD, we have carried out an MRS study of the basal
ganglia to determine whether this technique is of use
in differentiating MSA from IPD.
Patients and Methods
Seven patients with clinically diagnosed pure ( n = 6) or
predominantly ( n = 1) srriatonigral MSA { l ] underwent
MRI and MRS. Their ages ranged from 41 ro 65 (mean 53)
years and mean clinical disease duration was 4.5 years. Their
clinical features and degree of dopamine sensitivity are shown
in the Table. W e were also able to study 5 patients who had
the pure ( n = 3 ) or predominantly ( n = 2) olivopontocerebcllar atrophy ( O P C A ) form of MSA (table). They ranged
in age from 47 to 65 (mean 5 7 ) years and had a mean disease
duration of 4 years. Nine patients with a clinical diagnosis of
IPD. age 4 2 to 66 (mean 50) years and with a mean disease
duration of 7.5 years, also underwent both MRI and MRS,
as did 9 healthy controls aged 4 2 to 62 (mean 53.3) years.
SND = srriatonigral degeneration; OPCA = olivopontocerebellar atrophv; Pa = parkinsonian; Ce = cerebellar signs; A u t = autonomic
features. Pyr = pyramidal signs; NAA = N-acrrylaspartate; Cho = choline-containing compounds; ( + ) = present; n.d. = not done; L - D o ~ ~
Response. I = poor response; 2 = moderate response; 3 = good response.
Davie et al: Differentiation by Proton MRS
The study was approved by the Joint Ethics Committee at
the Institute of Neurology and the National Hospital for
Neurology and Neurosurgery, London. Informed consent
was obtained from all patients prior to each study. MRI and
MRS were performed on a 1.5-T GE whole body scanner
using a standard quadrature head coil. A T,-weighted, fast
spin echo imaging sequence (TR, 5,000; Tch 13/78) with
3-mm slices and a l-mm interslice gap was used. Although
it was not a primary aim of this study, we also performed a
T,-weighted spin echo sequence (TR, 2,000; TE, 80) in 2
patients with the S N D variant of MSA, 4 with the OPCA
variant of MSA, 5 with IPD, and 5 controls to determine
whether any relationship existed between the spectroscopic
findings and the presence of hypointensity in the putamen.
These images were reported by an experienced neuroradiologist (B.E.K.) who was unaware in each case of the clinical
diagnosis and spectroscopic results.
Water-suppressed spectra were obtained from volumes of
interest (3.4-6 ml) centered on the putamen and globus pallidus (lentiform nucleus) using a STEAM sequence [ 2 2 ]
(Fig 1). In the IPD and MSA group, the basal ganglia contralateral to the most clinically affected side were studied. Acquisition parameters were TR, 2270 msec; TE, 270 msec;
TM, 12 msec. Data processing included 2-Hz line broadening, Fourier transformation, and zero-order phase correction.
No baseline correction was applied. Peak areas from creatine
and phosphocreatine, choline-containing compounds, and Nacetyl groups were calculated with the SAGE spectral analysis
program (GE Milwaukee). This was carried o u t by one of
the authors (C.A.D.) who at the time of analysis was unaware
Fig 1. T7-weightedspin tcbo (TR. 2,000 tllsec: TE, 80 rrrsec)
iniugf,fvom u bea1tb.y control shwing a spectroscopic volume of
iritemt reiiteved on the lefl pidamn? a i d globirs pallidus.
206 Annals of Neurology
Vol 37
No 2
February 1995
of the clinical diagnosis. The creatine/phosphocreatine resonance was used as an internal standard of reference and results are expressed as a ratio of metabolite to creatine.
In 7 MSA patients (5 S N D and 2 OPCA) and 6 controls
it was possible to calculate absolute concentrations for the
metabolites using the fully relaxed water signal as an internal
standard of reference E231. Metabolite concentrations [met]
were calculated from the following equation:
T, coII
x lDR
where so
and SoHrOdenote the signal intensities for metabolites and water respectively, { H,0] is the brain water
concentration in gray matter, T, coTT and T2(oTT are T, and T,
correction values based on published values for the metabolites studied [24], PI is the proton index and R = {(Rl
- (R1 + ~ ) w a e r l .
Statistical analysis was performed with a Mann-Whitney
confidence interval and test. Results are expressed as a rnedian value together with the range and p value.
In the MSA group with predominantly striatonigral
involvement (SND) there was a highly significant reduction of the NAAlcreatine ratio (median, 1.19;
range, 0.96-2.0; p < 0.02) compared with the control
group (median, 1.76; range, 1.61-2.0). In contrast, the
IPD group showed a normal NAAicreatine ratio (median, 1.82; range, 1.17-2.31; p > 0.5) (see Figs 2 and
3). The NAA/creatine ratio was markedly reduced (>3
SD) in 6 of the 7 S N D patients and in only 1 of the
9 IPD patients. The OPCA patients also showed a significant group reduction in the NAAlcreatine ratio
from the lentiform nucleus (median, 1.47; range,
1.22-1.68; p < 0.01) compared with the controls although there was overlap between these two groups.
The median reduction of NAA/creatine was greater in
the SND group compared with the OPCA patients,
though again there was some overlap (see Fig 2).
The chohdcreatine ratio was significantly lower in
the SND patients (median, 1.02; range, 0.86-1.23; p
< 0.04) compared with the control group (median,
1.22; range, 1.05-1.65). There was a reduction in the
cholinelcreatine ratio (median, 0.73; range, 0.85-1.27;
p < 0.4) from the OPCA group, though this did not
achieve significance. The IPD group showed a normal
choline/creatine ratio (median, 1.13; range, 0.89- 1.65;
p = 0.25) compared with controls.
The absolute creatine concentration in 6 controls
(median, 8.1 mM; range, 7.1-8.3) did not differ significantly from the 7 MSA patients (median, 9.1 mM;
range 5.9-7.5; p < 0.6). There was, however, a significant reduction in the absolute NAA cncentration in
the MSA group (median, 6.94 mM; range, 5.52-8.73)
compared with the controls (median, 10.61 mM; range,
8.9-11.1; p < 0.006). The concentration of choline-
8 2
/ I\
idiopathic Parkinson's disease
Column 1
F i g 2. Sl-LittKr graph N-acet?,laspat-tatelcreatine ratios from controfs and the patietit gror4ps. 1 = idiopathic Parkinson > disease
patieiit u h o bas IOU. signal in the piitamti o n magnetic resonance imaging: 2 = two oi,erlapping datu points: I # ) = the patient uho baA. pvedominand~~
rather thun pure striatonigral degeneration: l i X I = the patients uho hai'e predonzinaiztly rather
than pure nfit~opontocerebellartJpe of nidtipfr system atrophy.
I \
1 .o
pprn chemical shift
containing compounds showed a smaller, though still
significant reduction, in the MSA patients (median,
1.67; range, 1.0-1.93) compared with controls (median, 2.2; range, 1.79-2.4; p < 0.03).
Low signal in the putamen was seen in 1 of 2 S N D
patients imaged with the spin echo sequence. These
patients both showed significant reduction in the
NAAicreatine ratio. The 4 OPCA patients studied
with the spin echo sequence showed no evidence of
low signal from the putamen.
One of the 5 patients with IPD who underwent Tzweighted spin echo imaging showed low signal in the
putamen. This 45-year-old man was also the only IPD
patient to show a marked (>3 S D from the control
mean) reduction of the NAAicreatine ratio from the
lentiform nucleus (see Fig 2). He has a 7-year history
of predominantly right-sided parkinsonism with a mild
postural tremor and moderate akinesia and rigidity. He
has not yet received levodopa chronically but has derived moderate (about 2 5 9 ; ) benefit from combined
treatment with selegiline 10 mg in the morning, amantadine 100 mg tds, and pergolide 0.75 mg tds. He has
no autonomic symptoms, cerebellar or pyramidal signs.
A recent levodopa challenge with one tablet of Sinemet 251250 was negative.
None of 5 controls examined with T,-weighted spin
echo scans showed low signal in the putamen.
Fig 3. Magnetic- rrsr~nanrespectroscopy of lentiforin nucleriJ.
SND t w m s IPD zwsnI control (t'oluvw 4 ml: TR. 2 J'ec: TE.
270 nisei). Top .@ctrunz taken from the right kiitiform nucleus
of a 47-year-oldfeniale with striatonigral degenevatioii ( S N D I
u'ho has a 6-year histoty of parkinsotiism. uiorsc on the left,
and autonomicfailiire u i t b a drnen'ated urethral sphincter (patient 1i . ?'here is a reduction ofthe NAAlc-reatine ratio and
ihr cholinelcreatine ratio. Middle spectrunz takrii from the [dt
fentiJarm nucleus of a 47-yeur-old man uith an 8-year histoty
idioof prrdominantfy right-sided classic lei'od~pa-respansit,e
pathic. Parkinson*sdisease tlPD,. The NAAIcreatine ratio and
cho/itietcreatine rati0.r are nornial. Lower spectrum takefi from
the right fentifurnz nucleus of a 48-y~ar-oldhealthy c-ontrol.
NAA. N-acetylaspartate: Cr. creatine: Cho, i-holirie-io)itaiiiiiig
The most striking finding in this study was the significant reduction in the NAAIcreatine ratio and choline/
creatine ratio from the putamen and globus-pallidus in
patients with the pure or predominantly striatonigral
variant of MSA and the preserved NAAIcreatine and
choline/creatine ratios in the patients with classic IPD.
The patients with the OPCA variant of MSA also
showed a significant, but less marked, group reduction
of the NAAIcreatine ratio.
In this study we have used creatine/phosphocreatine
(creatine) as an internal standard of reference since
these two compounds are in chemical equilibrium and
Davie et al: Differentiation by ProtonMRS
their total concentration should accordingly remain
constant. If there was an elevation of creatine in the
MSA group, this could have resulted in the reduced
NAAicreatine and cholineicreatine ratios that we observed in the MSA patients. However, this does not
appear to be the case since absolute quantitation of
metabolites in 7 of the MSA patients and 6 controls
showed no significant difference in the concentration
of creatine between the MSA patients and controls,
although there was a significant reduction of N A A and
choline-containing compounds in the MSA group. W e
are therefore satisfied that the reduced NAAicreatine
and cholineicreatine ratios observed in the MSA group
are due to an absolute reduction in the concentration
of N A A and choline-containing compounds rather
than an increase in the concentration of creatineiphosphocreatine.
N A A is an amino acid that, in adult brain, is almost
exclusively contined to neurons and their processes
[Z 1, 251. A reduction in NAAicreatine has been demonstrated in many conditions in which there is neuronal and/or axonal loss [26-29} although in some
disorders this abnormality may partly reverse, suggesting that neuronal dysfunction alone may contribute
to a reduced ratio [j0, 311. T h e reduction of N A A i
creatine, we have shown in the striatonigral variant of
MSA, may well reflect neuronal loss occurring predominantly in the putamen and, to a lesser extent, the
globus pallidus I?}. Such neuronal loss is more evident
pathologically in MSA patients with predominantly
parkinsonian features. However, as in the original case
of MSA, described by Graham and Oppenheimer C321,
that had cerebekar, autonomic, and pyramidal signs but
not parkinsonism, neuronal loss may also be found in
the putamen despite the lack of extrapyramidal features during life. This is consistent with our finding in
the present study of a Significant reduction in the median NAAicreatine ratio in the O P C A group. W e were
unable to demonstrate a group reduction of the N A A /
creatine ratio or cholineicreatine ratio in the I P D
group, which is in keeping with the findings from a
large multicenter spectroscopic study of patients with
I P D [331. It is also in keeping with pathological studies
in I P D that reveal neuronal preservation in the lentiform nucleus C341. In our present study, the l I P D
patient who did show a dramatic reduction of N A A /
creatine also showed low signal in the putamen, a feature more commonly reported in MSA. Although we
have not yet observed his response to chronic treatment with levodopa, there are still no features after 7
years of parkinsonism to suggest anything other than
IPD. It is still, however, possible that this patient belongs to the recognized group of S N D patients who
phenotypically mimic classic IPD, particularly in view
of his subsequent negative response to a single-dose
levodopa challenge test.
208 Annals of Neurology
No 2 February 1005
There was also 1 S N D patient with a normal N A A i
creatine ratio from the lentiform nucleus. This 59-yearold man has a 6-year history of parkinsonism. An initial
good response to levodopa subsequently waned and
he developed pyramidal signs, respiratory stridor, impotence, postural faintness with abnormal autonomic
function tests, and urinary incontinence with a pathological anal sphincter electromyography. Despite
marked parkinsonian features, it is still possible that
this patient has preservation of neurons within the striatum, a finding that has recently been described in 2
SND patients at postmortem 135).
W e were unable to demonstrate a correlation between the presence of levodopa responsiveness in the
MSA group and the degree of reduction in the N A A /
creatine ratio. If N A A represents a marker of neuronal
integrity one perhaps would have expected better preservation of N A A in those MSA patients with dopa
responsiveness. Fearnley and colleagues [36} showed
relative neuronal preservation in 4 S N D patients (of a
series of 10) who benefited from dopa. However,
other pathological studies have shown the relationship
between putaminal cell loss and dopa responsiveness
to be less clear. A recent clinicopathological study of
35 cases of MSA 137) showed no significant correlation
between the extent of pathological damage in the putamen and levodopa response, though there was a trend
for the degree of the last, but not best, recorded levodopa response to be inversely associated with the degree of putaminal damage. O n e MSA patient with
marked parkinsonian features described by the same
authors [ 3 5 ] showed only a very modest response to
levodopa and yet pathologically had no cell loss in the
putamen at death. Despite the lack of neuronal dropout, oligodendroglial cytoplasmic inclusions (which
may contribute to neuronal dysfunction) were plentiful
in the putamen in this case. It may be, then, that striatal
cell loss is neither necessary nor sufficient to explain
reduced dopaminergic responsiveness in MSA. This
view is supported by the relatively mild loss of striatal
D2 receptor density in levodopa-treated patients with
SND studied by PET using ["Clraclopride [ 121.
These observations suggest that degeneration of downstream pallidal and brainstem connections may be
more important than loss of dopamine receptor bearing striatal neurons.
In the present study, a systematic evaluation of putaminal hypointensity using T,-weighted spin echo sequences was not performed in all patients. Nevertheless, it is of interest that 3 MSA patients ( 1 S N D and
2 O P C A ) showed a markedly low NAAlcreatine ratio
with normal putaminal intensity, suggesting that MRS
may prove to be a more sensitive diagnostic tool than
MRI in evaluating patients with suspected MSA. It is
also noteworthy that the MSA patient with the lowest
NAA/creatine ratio (0.96) and the 1 I P D patient with
a marked reduction of the NAA/creatine ratio both
showed putaminal hypointensity. It has been postulated that iron deposition (the putative cause of signal
loss) in the striatum in MSA leads to neuronal loss by
promoting the formation of cytotoxic free radicals
{ZO]. However, the observed reduction of the N A A /
creatine ratio in 3 MSA patients in the absence of putaminal hypointensity suggests that the relationship between neuronal loss and iron deposition is not clear
cut. It is also theoretically possible that iron deposition,
by affecting the relaxation times of the metabolites,
could produce the reduction in NAA/creatine ratio
seen in the MSA group. Again, the poor relationship
we have observed between the NAA/creatine ratio
and putaminal hypointensity makes this unlikely.
T h e other finding in this study was the mean reduction of cholindcreatine ratio in the MSA group with
S N D . Choline-containing compounds are abundant in
all cell membranes r38) and play an important role in
membrane synthesis and turnover. A large increase
in the choline/creatine ratio can be produced by the increased membrane turnover, for example, in association with inflammatory cellular infiltration 1391. It may
be that a reduction in the choline/creatine ratio indicates reduced membrane turnover in the lentiform nucleus in MSA, perhaps as a result of cell loss, although
further experimental studies are necessary to clarify
this finding.
In conclusion, this study has shown that proton MRS
in the basal ganglia is a useful, noninvasive technique
to help differentiate MSA from IPD. T h e specificity
of these findings must be evaluated by studying other
parkinsonian conditions such as the Steele Richardson
Olszewski syndrome, which o n occasion may also be
difficult to differentiate clinically from IPD E40).
The N M R Research Group is supported by a generous grant from
the Multiple Sclerosis Society of Great Britain and Northern Ireland.
G.K.W. is supported by the Parkinson’s Disease Society of the
United Kingdom.
W e thank Professors P. K. Thomas, A. E. Harding, and C. Mathias
and D r S. D. Shorvon for kindly allowing study of patients under
their care. We also acknowledge G E (Milwaukee. W I ) for providing
spectroscopy software for data analysis. Assistance with statistical
analysis was kindly provided by Ms A Petruckevitch.
1. Quinn N . Multiple system atrophy-the
nature of the beast. J
Neurol Neurosurg Psychiatry 1989;52(spec suppl):78-89
2 Daniel SE. The neuropathology and neurochemistry of multiple
system atrophy. In: Bannister R, Mathias C, eds. Autonomic
failure. A textbook of clinical disorders of the autonomic nervous system. 3rd ed. Oxford: Oxford University Press, 1992:
3. Papp MI, Kahn JE, Lantos PL. Glial cytoplasmic inclusions in
the C N S of patients with multiple system atrophy (srriatonigral
degeneration. olivopontocerebellar atrophy and Shy Drager syndrome). J Neurol Sci 1989;91:79-100
4. Papp M I , Lantos PL. Accumulation of tuhular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. J Nrurol Sci 1992;1O7:172-182
5. Papp MI, Lantos PL. Cellular pathology of multiple system atrophy: a review. J Neurol Neurosurg Psychiatry 1994;57: 129-
0. Quinn N P , Marsden CD. The motor disorder of multiple system atrophy. J Neurol Neurosurg Psychiatry 1993;56.12391242
7. Rajput A H , Rozdilsky B, Rajput A. Accuracy of clinical diagnosis in parkinsonism-a
prospective study. Can J Neurol Sci
8. Redmond DE, Leranth C, Spencer DD. et al. Feral neural graft
survival. Lancet 1990;2:820-822
9. Brooks DJ, lbanez V, Sawle G V , et al Differing patterns of
striatal 18F-Dopa uptake in Parkinson’s disease, multiple system
atrophy and progressive supranuclear palsy. Ann Neurol 1990;
10. Brooks DJ, Salmon EP, Mathias CJ, et al. T h e relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure and Parkinson’s
disease, studied with PET. Brain 1990;113:1539-1552
11. Burn DJ, Sawle G V , Brooks DJ. Differential diagnosis of Parkinson’s disease, MSA and Steele kchardson Olszewski’s syndrome: discriminant analysis of striaral “F-dopa PET data. J
Neurol Neurosurg Psychiatry 1994;57:278-284
2 . Brooks DJ, lbanez V, Sawle GV, et al. Striatal D2 receptor
status in patients with Parkinson’s disease, striatonigral degeneration and progressive supranuclear palsy. measured with 11Craclopride and positron emission tomography. Ann Neurol
-3. Sawle G V , Playford ED, Brooks DJ, et al. Post synaptic changes
in the striatal dopamine projection in dopa naive parkinsonism.
Diagnostic implications of the D 2 receptor status. Brain 1993;
1.1. Schwarrz J, Tatsch K, Arnold G, et al. 123-iodobenzamideSPECT predicts dopaminergic responsiveness in patients with
de novo parkinsonism. Neurology 1992;42:556-561
15. Burn DJ, Mathias CJ, Quinn N, et al. Striatal opiate receptor
binding in Parkinson’s disease and MSA: 11C diprenorphine
study. Neurology 1993;13:4545 (Abstract)
16. De Volder AG, Francart J, Laterre C, et al. Decreased glucose
utilization in the striarum and frontal lobe in probable srriatonigral degeneration. Ann Neurol 1989;26:239-247
17. Eidelberg D. Takikawa S, Moeller S, et al. Striatal hypometabolism distinguishes striatonigral degeneration from Parkinson’s
disease. Ann Neurol 1993;33:5 18-527
1X. Drayer BP, Olanow W. Burger P, et al. Parkinson plus syndrome: diagnosis using high field imaging of brain iron. Radiology 1986;159:493-498
10. Stern MB. Braffman B H , Skolnick BE. et al. Magnetic resonance imaging in Parkinson’s disease and parkinsonian syndromes. Neurology 1989;39:1524- 1520
LO. Olanow CW. Magnetic resonance imaging in parkinsonism.
Neurol Clin 1992;10:405-420
2 1. Urenjak J, Williams SR, Gadian D G , Noble M. Proton nuclear
magnetic resonance spectroscopy unambiguously idenrihes different neural cell types. J Neurosci 1993;1 3 9 8 1-989
22. Frahm J, Michaelis T. Mcrboldt KD. et al. Improvements i n
localised proton N M R spectroscopy of human brain, water suppression, short echo times and 1 ml resolution. J Magn Reson
1?nO;90:46/1-d7 3
2 3 . Christiansen P. Henriksen 0,Stubgaard M, et al. In vivo quantification of brain metabolites by ‘H-MRS using water as an internal standard. Magn Reson Imaging 1993;11:107-118
2 i. Frahm J. Bruhn H, Gyngell ML, et al. Localised proton N M R
Davie et al: Differentiation by Proton MRS 209
spectroscopy in different regions of the human brain in vivo:
relaxation times and concentrations of cerebral metabolites.
Magn Reson Med 1989;11:47-63
Birkrn DL, Oldendorf WH. N-Acetyl-aspartic acid: a literature
review of a compound prominent in 1 H N M R spectroscopic
studies of brain. Neurosci Biobehav Rev 1989;13:23-31
Matthews PM, Francis G, Antel J, Arnold DL. Proton magnetic
resonance spectroscopy for metabolic characterisation of
plaques in multiple sclerosis. Neurology 1991;41:125 1-1256
Chong WK, Sweeney B, Wilkinson ID, et al. Proton spectroscopy of the brain in HIV infection: correlation with clinical,
immunologic and MR imaging findings. Radiology 1993; 188:
Gideon P, Henriksen 0, Sperling B, et al. Early time course of
N acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. A
proton magnetic resonance spectroscopy study. Stroke 1992;2S:
Shino A, Matsuda M, Morikawa S, et al. Proton magnetic resonance spectroscopy with dementia. Surg Neurol 1993;39:143147
Arnold DL. Reversible reduction of N-acetylaspartate after
acute central nervous system damage. In: Proceedings of the
eleventh annual meeting of the Society for Magnetic Resonance
in Medicine. 1992;1:643 (Abstract)
Davie CA, Hawkins CP, Barker GJ, e t al. Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions.
Brain lW4;117:49-58
Annals of Neurology
Vol 37
No 2
February 1995
32. Graham JG, Oppenheimer DR. Orthostatic hypotension and
nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiatry 1969;32;28-34
33. Holshouser B, Komu M, Moller H , et al. Single volume proton
MR spectroscopy on patients with Parkinson’s disease. Proceedings of the twelfth meeting of the Society of Magnetic Resonance in Medicine 1993;1:235 (Abstract)
34. Oppenheimer DR, Esiri MM. Diseases of the basal ganglia, cerebellum and motor neurons. In: Hume Adam J, Dochen LW,
eds. Greenfield’s neuropathology. 5th ed. London, Melbourne:
Edward Arnold, 1992:988-997
35. Wenning GK, Quinn NP, Magalhaes M, eta]. “Minimal change”
multiple system atrophy. Mov Disord 1994;9:161-166
S6. Fearnley JM, Lees AJ. Striatonigral degeneration. A clinicopathological study. Brain 1990;113:1823-1842
37. Wenning GK, Ben-Shlomo Y , Magalhaer M, et al. A clinicopathological study of 35 cases of multiple system atrophy. J
Neurol Neurosurg Psychiatry (in press)
38. McIlwain H, Bachelard HS. In: Biochemistry and the central
nervous system. London: Churchill Livingstone 1985;282
39. Brenner RE, Munro PMG, Williams SCR, e t al. The proton
N M R spectrum in acute EAE: the significance of the change in
the Cho:Cr ratio. Magn Reson Med 1993;29:737-745
40. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical
diagnosis of idiopathic Parkinson’s disease: a clinicopsthological
study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:
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