close

Вход

Забыли?

вход по аккаунту

?

Cerebral fat embolism Usefulness of magnetic resonance spectroscopy.

код для вставкиСкачать
15. Zarranz JJ, Alegre J, Gómez-Esteban JC, et al. The new mutation, E46K, of ␣-synuclein causes parkinson and Lewy body
dementia. Ann Neurol 2004;55:164 –173.
16. Ishikawa A, Takahashi H, Tanaka H, et al. Clinical features of
familial diffuse Lewy body disease. Eur Neurol 1997;38(suppl
1):34 –38.
17. Wakabayashi K, Hayashi S, Yoshimoto M, et al. NACP/␣synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson’s disease brains. Acta Neuropathol
2000;99:14 –20.
18. Braak H, Braak E. Neuropathological staging of Alzheimerrelated changes. Acta Neuropathol 1991;82:239 –259.
19. McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines
for the clinical and pathologic diagnosis of dementia with Lewy
bodies (DLB): report of the consortium on DLB international
workshop. Neurology 1996;47:1113–1124.
20. Tomita T, Watabiki T, Takikawa R, et al. The first proline of
PALP motif at the C terminus of presenilins is obligatory for
stabilization, complex formation, and ␥-secretase activities of
presenilins. J Biol Chem 2001;276:33273–33281.
Cerebral Fat Embolism:
Usefulness of Magnetic
Resonance Spectroscopy
Rémy Guillevin, MD,1 Jean N. Vallée, MD, PhD,1
Sophie Demeret, MD,2 Romain Sonneville, MD,2
Francis Bolgert, MD,2 Francisco Mont’Alverne, MD,1
Charles Pierrot Deseilligny, MD,2
and Jacques Chiras, MD1
We report a case of cerebral fat embolism which occurred
in a 33-year-old man after a diaphyseal femoral fracture
without cranial traumatism. The initial examination
showed an incomplete picture of coma with tetrapyramidal
syndrome and cutaneomucous purpura. There was no respiratory damage. We present a magnetic resonance spectroscopy analysis of the cerebral lesions observed in the
initial phase of the embolism, as well as follow-up, which
has strengthened the clinical and imaging features for the
diagnosis.
Ann Neurol 2005;57:434 – 439
Fat embolism is a well-known occurrence in traumatology. It is usually suspected in the presence of a dis-
From the Departments of 1Neuroradiology and 2Neurology, Neurologic Resuscitation, Pitié-Salpêtrière hospital, Paris Cedex, France.
Received May 20, 2004, and in revised form Aug 17 and Dec 8.
Accepted for publication Dec 8, 2004.
Published online Feb 24, 2005, in Wiley InterScience
(www.interscience.wiley.com). DOI: 10.1002/ana.20388
Address correspondence to Dr Guillevin, Department of Neuroradiology Pr J. CHIRAS, Pitié-Salpêtrière hospital, 47-83 Bd de
l’Hôpital, 75651 Paris Cedex 13, France.
E-mail: remy.guillevin@psl.ap-hop-paris.fr
434
placed long bone fracture of the lower limbs and occurs in 0.5 to 3.5% of cases1,2 on the appearance of a
triad of respiratory, neurological, and cutaneomucous
signs after a symptom-free interval of 12 to 24 hours.
The neurological symptoms may vary considerably,
ranging from confusion to coma or even death. Neurological recovery usually takes a few weeks or
months.
Isolated forms of incomplete or neurological fat embolism are much rarer but are sometimes difficult to
diagnose. We report here the case of a 33-year-old patient who presented with cerebral fat embolism but no
respiratory damage or cardiac shunt, and for whom the
results of magnetic resonance spectroscopy (MRS) argued strongly in favor of a diagnosis of fat embolism.
As far as we know, this is a rare case, in which, thanks
to spectroscopy, the presence of lipids of extracerebral
origin could be demonstrated in vivo.
Case Report
Patient
A patient aged 33 years, with uneventful medical history, was hospitalized for an isolated traumatic femoral
diaphyseal fracture, without cranial traumatism or initial loss of consciousness. Initial Glasgow Coma Scale
score was 15, with no signs of hemodynamic shock or
respiratory distress. Traction was applied to the fracture
pending surgical reduction. Twelve hours after the accident, the patient was in a deep coma and was transferred to the resuscitation department under mechanical ventilation.
Glasgow Coma score was 6, and there was pyramidal
injury with hypertonia of the four limbs and a bilateral
Babinski sign. The pupils exhibited poorly reactive mydriasis, but the oculocephalic reflexes were intact. The
fundus was characterized by cotton wool spots and bilateral macular edema. There were no extraneurological
signs, apart from discrete petechiae of the trunk and
conjunctiva.
Standard biological tests, including blood gases,
were normal, and the search for toxic elements was
negative. An electroencephalogram showed diffuse
slowing down, with no paroxysmal signs. An emergency brain scan without contrast material injection
showed, in addition to the absence of intracranial
bleeding, small, aspecific hypodense areas less than a
centimeter wide in the subcortical white matter.
Transesophageal echocardiography was performed
twice, at admission and after extubation, with no
patent permeable oval foramen.
Thoracic tomodensitometry and bronchoalveolar lavage were normal, thus confirming the absence of infraclinical thoracic injury.
After extubation on day 15, evolution was characterized by slow partial neurological recovery, and two
© 2005 American Neurological Association
Published by Wiley-Liss, Inc., through Wiley Subscription Services
Fig 1. Magnetic resonance (MR) examination at day 1. (A) Diffusion-weighted MR axial image acquired 35 hours after shows
multiple focal area of increased signal with significant decrease of apparent diffusion coefficient (ADC). (B) Fluid-attenuated inversion recovery axial MR image shows the same aspect as diffusion-weighted image (DWI). Localizer of MRS (VOI 1) is positioned
on white matter location, with increased signal on MRI. (C, D) Probe press single voxel spectroscopy (TR ⫽ 1,500 milliseconds/
TE ⫽ 35 and 135 milliseconds). On short echo time (35 milliseconds) spectrum, a strong resonance of free lipids can be observed
which remains visible at long echo time. On long echo time (135 milliseconds) spectrum, there is no evidence of lactate, the ratio of
NAA/Cr is slightly reduced, and the ratio of Cho/Cr is slightly increased. (E) Fluid-attenuated inversion recovery axial MR image
shows the same aspect as DW image. Localizer of MRS (VOI 2) is positioned on gray matter location, without abnormalities on
MRI. (F, G) Probe press single voxel spectroscopy (TR ⫽ 1,500 milliseconds/TE ⫽ 35 and 135 milliseconds). As shown in C and
D, a strong resonance of free lipids can be observed (short echo time). There is no more evidence of lactate, and the ratios of
NAA/Cr and Cho/Cr are normal (long echo time).
sequelae: major tetrapyramidal syndrome and spastic
tetraparesis. Nevertheless, he was able to sit in an
armchair 3 months after the accident. From the neu-
ropsychological point of view, severe language and
memory disorders were noted, with persistent temporal and spatial disorientation. Five months after the
Guillevin et al: Cerebral Fat Embolism
435
accident, the patient was able to walk with assistance
and his language was virtually normal.
Table. Metabolites Quantitation
Magnetic Resonance Methods
Three successive MR examinations were performed
on the same GE 1.5T magnet at days 1, 8, and 70,
including standard imaging, as diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery
(FLAIR), T2*, T1-weighted images, before and after
intravenous gadolinium (DOTAREM, Guerbet,
France) administration. Single-voxel MRS (PROBE
PRESS sequence) had been performed systematically
on two locations: periventricular white matter (VOI
1) and occipital gray matter (VOI 2), with two echo
times on each voxel (TR ⫽ 1,500 milliseconds, TE ⫽
35/13 milliseconds). Placement of the VOI 2 have
been checked to avoid outer volume contamination
from the skull.
Quantitation of choline and N-acetylaspartase
(NAA) was assessed relatively to creatine peak on
135-millisecond TE spectrum, as well as the resonance of lactates (inverted from the baseline). Resonance of free lipids was assessed on 35-millisecond
TE spectrum.
VOI 1
Cho/Cr
NAA/Cr
Lactates
Lipids/Cr
VOI 2
Cho/Cr
NAA/Cr
Lactates
Lipids/Cr
Results
Day 1
Thirty-five hours after the onset of consciousness disorders, brain MR imaging (MRI) showed multiple hyperintense foci scattered over the FLAIR and diffusion
sequences, in the periventricular and juxtacortical white
matter, with apparent diffusion coefficient (ADC) diminished by 20 to 31% but no arterial systematization
of lesions (Fig 1A). T2* weighted images showed no
hemorrhagical areas. On T1-weighted postgadolinium
images, the signals for certain lesions were enhanced.
In the acute phase, spectroscopic lesion analysis disclosed, in both the periventricular white matter (see Fig
1A–D) and occipital cortical regions (see Fig 1E–G),
the presence of marked long-chain lipid resonance but
no associated lactate resonance, whereas NAA/Cr is
high in VOI 2 and slightly decreased in VOI 1, but
not significantly (Table).
Day 8
MRI showed enhanced hyperintense areas of the white
matter, with the confluence of certain signals on the
diffusion- (Fig 2A) and FLAIR-weighted sequences,
whereas the MRS, showed a moderate increase in choline, a reduction of NAA, and lactate resonance that
persisted, whereas lipid resonance decreased considerably (see Table). The spectroscopic patterns arising
from the two VOI were still very similar (see Fig
2B–G).
436
Annals of Neurology
Vol 57
No 3
March 2005
Metabolite
EX 1
EX 2
EX 3
0.97
1.27
ND
1.95
1.05
0.85
Present
1.06
0.89
1.3
ND
ND
0.9
1.85
ND
1.05
1
0.8
Present
0.45
0.8
1.68
ND
ND
Ratios are determined on long echo time (TE ⫽ 135 millisecond)
for NAA and Cho (after normalization of baseline). Lactates and
lipids resonances are assessed on both short and long echo times.
ND ⫽ not detected; EX ⫽ examination.
Week 10
MRI showed regression of the encephalic lesions but
persistence of a slight FLAIR white matter hypersignal,
without any anomalies of the diffusion or T1 sequences, and MRS profile returned to normal in VOI
2, whereas NAA/Cr is slightly reduced in VOI 1 but
remaining in a satisfactory range (cf Fig 3A–F, Fig
3D–F, and the Table).
Five arguments in favor of cerebral fat embolism are
worth considering: (1) the patient exhibited a complex
fracture; (2) the onset of his “coma” was extremely
atypical; (3) the presence of a large early peak of lipid
resonance, in both the white and gray matter; (4) the
initial absence of any signs of acute cerebral ischemia
such as the presence of lactates and a strongly diminished NAA/creatine ratio, which might have explained
the cellular necrosis and therefore the release of free
lipids, and (5) the patient’s favorable clinical evolution
in view of his initial symptoms.
Discussion
The MRI anomalies usually visible in cerebral fat embolism already have been described and are not very
specific3–11: they consist of multiple scattered lesions in
the white matter, which are visible on long TR sequence images and are mainly located in the deep,
periventricular, and subcortical areas. Simon and colleagues12 reported a slight strengthening of the postgadolinium T1 signal that argues in favor of the rupture
of the blood–brain barrier. These lesions may or may
not be combined with focal hemorrhages.11 Some authors12–13 have suggested that the diffuse hyperintense
areas, with decreased ADC, observed on the DW images may reflect areas of ischemia induced by fat embolism. Thus, in the presence of such poorly specific
images, and given the patient’s incomplete clinical picture at admission, acute phase spectroscopic analysis
supplied important additional diagnostic evidence in
favor of fat embolism.
Fig 2. Magnetic resonance (MR) examination at day 8. (A) Diffusion-weighted MR axial image shows extensive lesions in the
periventricular, deep, and subcortical white matter, and (B, E) fluid-attenuated inversion recovery axial MR images, with VOI 1
(B) and VOI 2 (E). (C) Short echo time and (D) long echo time spectra from white matter location (VOI 1) show significant decreased of lipid resonance (C), resonance of lactate, reduced NAA/Cr and increased Cho/Cr (D). (F) Short echo time and (G) long
echo time spectra from gray matter location (VOI 2) show almost the same profiles.
First, a very high early peak of free lipids was detected in the white and the gray matter. This pattern,
as well as the absence of inverted signals between 0.9
and 1.4ppm argues against artifactual elevation of lipids. Other causes of pathological, large, broad, inphase resonances at 0.9 and 1.3 or 1.4ppm, mainly
visible at TE ⫽ 35 milliseconds include infections
such as cryptococcoma, toxoplasmosis and tuberculoma, inflammation, necrosis of tumor, lymphoma,
and stroke. All those diagnosis but stroke were ruled
out by clinical, biological, and MRI data.
Second, the same spectroscopic analysis disclosed
no evidence in favor of initial acute ischemia, in the
absence of early lactate resonance14 and of strong decrease of the NAA/Cr ratio (while lower in VOI 1
than in VOI 2). Conversely, the presence of large
quantities of lipids, because of their lower mobility
compared with water, would then be initially the
main factor of reducing the ADC. Those findings are
consistent with the absence of arterial systematization
of the signal anomalies on DWIs.
The transient appearance of lactate resonance and
drastic decrease of NAA/Cr on the spectroscopy done
on day 8 (see Table) rather suggests a hypoxic-
Guillevin et al: Cerebral Fat Embolism
437
Fig 3. Magnetic resonance (MR) examination at week 10. (A, D) Fluid-attenuated inversion recovery axial MR image shows a
significant regression of white matter (VOI 1) focal lesions, and still no lesion on gray matter (VOI 2). (B) Short echo time and
(C) long echo time spectra (VOI 1) also show significant regression of previous anomalies (NAA/Cr ratio is slightly reduced). (E)
Short echo time and (F) long echo time spectra (VOI 2) show normal metabolite ratios on gray matter.
ischemic mechanism secondary to fat embolism. Kamenar and Burger,15 Kim and colleauges,16 and Drew
and colleagues17 published a microscopic description
of fat globules, essentially located in the cortical microvascularization of gray matter, which is usually
spared because of its greater vascular anastomotic potential. This implies that the mechanism responsible
then might be secondary venous ischemia of the white
matter.15
The second advantage of early spectroscopic analysis
may be prognostic. Thus, the absence of patent signs
of tissular ischemia on the initial spectroscopy at day 1
seemed suggestive of a favorable prognosis, given the
initial neurological picture. Several authors have indeed
stressed the correlation between the functional prognosis and the levels of lactate and NAA,18 –20 as well as
the higher sensitivity of MRS than conventional MRI
for the detection of ischemic lesions. MR detection of
intracerebral lactates constitutes a sensitive marker of
metabolic stress,14 –19 even if increase of lactate and
further depletion of NAA are both potentially reversible,19 with still controversial relationship between
them, especially in irreversible ischemia.19,20 Therefore,
the initial absence of detectable lactate resonance or
strongly reduced NAA argues in support of a favorable
outcome despite the highly disturbed initial neurological picture. The fact that the patient’s spectroscopic
438
Annals of Neurology
Vol 57
No 3
March 2005
profiles had returned to almost normal at 3.5 months
strengthens this argument.
Conclusion
MRS may improve the specificity of MR examination
for the study of cerebral fat embolism especially in its
incomplete forms. It is totally innocuous and directly
confirms the abnormal presence of free lipids, in
the absence of any other significant initial spectral
anomaly.
Last, the absence of initial ischemic signs suggests
that the initial spectroscopy may have prognostic value
that could be assessed from the results of a future prospective study.
References
1. Johnson MJ, Lucas GL. Fat embolism syndrome. Orthopedics
1996;19:41– 48; discussion, 48 – 49.
2. Gurd AR. Fat embolism: an aid to diagnosis. J Bone Joint Surg
Br 1970;52:732–737.
3. Bardana D, Rudan J, Cervenko F, Smith R. Fat embolism syndrome in a patient demonstrating only neurologic symptoms.
Can J Surg 1998;41:398 – 402.
4. Finlay ME, Benson MD. Case report: magnetic resonance imaging in cerebral fat embolism. Clin Radiol 1996;51:445–
446.
5. Kawano Y, Ochi M, Hayashi K, et al. Magnetic resonance imaging of cerebral fat embolism. Neuroradiology 1991;33:72–74.
6. Takahashi M, Suzuki R, Osakabe Y, et al. Magnetic resonance
imaging findings in cerebral fat embolism: correlation with clinical manifestations. J Trauma 1999;46:324 –327.
7. Chrysikopoulos H, Maniatis V, Pappas J, et al. Case report:
post-traumatic cerebral fat embolism: CT and MR findings.
Report of two cases and review of the literature. Clin Radiol
1996;51:728 –732.
8. Kamano M, Honda Y, Kitaguchi M, Kazuki K. Cerebral fat
embolism after a nondisplaced tibial fracture: case report. Clin
Orthop 2001:206 –209.
9. Cheatham ML, Block EF, Nelson LD. Evaluation of acute
mental status change in the nonhead injured trauma patient.
Am Surg 1998;64:900 –905.
10. Citerio G, Bianchini E, Beretta L. Magnetic resonance imaging
of cerebral fat embolism: a case report. Intensive Care Med
1995;21:679 – 681.
11. Erdem E, Namer IJ, Saribas O, et al. Cerebral fat embolism
studied with MRI and SPECT. Neuroradiology 1993;35:
199 –201.
12. Simon AD, Ulmer JL, Strottmann JM. Contrast-enhanced MR
imaging of cerebral fat embolism: case report and review of the
literature. AJNR Am J Neuroradiol 2003;24:97–101.
13. Parizel PM, Demey HE, Veeckmans G, et al. Early diagnosis of
cerebral fat embolism syndrome by diffusion-weighted MRI
(starfield pattern). Stroke 2001;32:2942–2944.
14. Lai ML, Hsu YI, Ma S, Yu CY. Magnetic resonance spectroscopic findings in patients with subcortical ischemic stroke.
Zhonghua Yi Xue Za Zhi (Taipei) 1995;56:31–35.
15. Kamenar E, Burger PC. Cerebral fat embolism: a neuropathological study of a microembolic state. Stroke 1980;11:477– 484.
16. Kim HJ, Lee CH, Lee SH, et al. Early development of vasogenic edema in experimental cerebral fat embolism in cats: correlation with MRI and electron microscopic findings. Invest
Radiol 2001;36:460 – 469.
17. Drew PA, Smith E, Thomas PD. Fat distribution and changes
in the blood brain barrier in a rat model of cerebral arterial fat
embolism. J Neurol Sci 1998;156:138 –143.
18. Graham GD, Kalvach P, Blamire AM, et al. Clinical correlates
of proton magnetic resonance spectroscopy findings after acute
cerebral infarction. Stroke 1995;26:225–229.
19. Wardlaw JM, Marshall I, Wild J, et al. Studies of acute ischemic stroke with proton magnetic resonance spectroscopy: relation between time from onset, neurological deficit, metabolite
abnormalities in the infarct, blood flow, and clinical outcome.
Stroke 1998;29:1618 –1624.
20. Barker PB, Gillard JH, van Zijl PC, et al. Acute stroke: evaluation with serial proton MR spectroscopic imaging. Radiology
1994;192:723–732.
Interaction of ␣-Synuclein
and Tau Genotypes in
Parkinson’s Disease
Catherine E. Mamah, BSc,1 Timothy G. Lesnick, MS,2
Sarah J. Lincoln, BSc,3 Kari J. Strain, BS,2
Mariza de Andrade, PhD,2 James H. Bower, MD,1
J. Eric Ahlskog, PhD, MD,1
Walter A. Rocca, MD, MPH,1,2 Matthew J. Farrer, PhD,3
and Demetrius M. Maraganore, MD1
To determine whether the microtubule-associated protein
tau (MAPT) and ␣-synuclein (SNCA) genes interact to
confer Parkinson’s disease (PD) susceptibility, we conducted a study of 557 case–control pairs. There was an
increased risk of PD for persons with either SNCA 261/
261 or MAPT H1/H1 genotypes as compared with persons with neither (odds ratio, 1.96; 95% confidence interval, 1.34 –2.86; p ⴝ 0.0003). However, the combined
effect of the two genotypes was the same as for either of
the genotypes alone (separate and equal). These findings
are consistent with in vitro experiments that revealed taumediated fibrillization of ␣-synuclein protein at low concentrations (dose threshold effect).
Ann Neurol 2005;57:439 – 443
Aggregation and fibrillization of the ␣-synuclein protein may represent key events in the pathogenesis of
Parkinson’s disease (PD).1 Mutations in the
␣-synuclein gene (SNCA) that promote its aggregation
and fibrillization are causal in families.2– 4 Although
these mutations are rare, allelic variability within the
SNCA promoter may confer PD susceptibility via a
mechanism of gene overexpression and protein aggregation.5,6
At low protein concentrations, the fibrillization of
␣-synuclein is promoted by the interacting
microtubule-associated protein tau,7 and ␣-synuclein
and tau pathology may co-occur in PD.8 Haplotype
variability within the microtubule-associated protein
From the Departments of 1Neurology and 2Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN; and the
3
Department of Neuroscience, Mayo Clinic College of Medicine,
Jacksonville, FL.
Received Aug 17, 2004, and in revised form Dec 8. Accepted for
publication Dec 8, 2004.
Published online Feb 24, 2005, in Wiley InterScience
(www.interscience.wiley.com). DOI: 10.1002/ana.20387
Address correspondence to Dr Maraganore, Professor of Neurology,
Department of Neurology, Mayo Clinic College of Medicine,
200 First Street SW, Rochester, MN 55905.
E-mail: dmaraganore@mayo.edu
© 2005 American Neurological Association
Published by Wiley-Liss, Inc., through Wiley Subscription Services
439
Документ
Категория
Без категории
Просмотров
0
Размер файла
253 Кб
Теги
spectroscopy, magnetic, usefulness, fat, resonance, embolism, cerebral
1/--страниц
Пожаловаться на содержимое документа