Progressive supranuclear palsy phenotype mimicking synucleinopathies

Article (PDF Available)inJournal of the neurological sciences 329(1-2) · April 2013with92 Reads
DOI: 10.1016/j.jns.2013.03.008 · Source: PubMed
Abstract
BACKGROUND: Atypical parkinsonian syndromes are currently divided into two groups based on their pathological appearance: synucleinopathies and tauopathies. Based on recent clinico-pathological studies it is increasingly clear, that some pathological characteristics are shared by both groups. STUDY OBJECTIVE: To describe two pathologically proven cases of tauopathy manifesting in vivo in two typical synucleinopathy phenotypes: multiple system atrophy and dementia with Lewy bodies. PATIENTS AND METHODS: There were 67-year-old woman with a phenotype of multiple system atrophy and a 70-year-old man with a phenotype of dementia with Lewy bodies. The clinical diagnosis was based on the commonly used clinical diagnostic criteria. A detailed neuropathological examination of the brain was conducted post-mortem in both cases. RESULTS: The overall pathological picture corresponded with a rare combination of two neurodegenerative entities: 4R tauopathy (meeting the diagnostic criteria for typical progressive supranuclear palsy) and neocortical stage of Alzheimer's disease. CONCLUSION: The interesting feature in both our cases was the presence of dual pathology: diffuse tauopathy and Alzheimer's pathology. We believe, that our two unique cases should serve as an evidence that tauopathies such as CBS and PSP might mimic practically anything from the family of atypical parkinsonian syndromes, particularly when another concomitant neurodegenerative disease is present.
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Progressive supranuclear palsy phenotype mimicking synucleinopathies
Kateřina Menšíková
a,
, Radoslav Matěj
b
, Lucie Tučková
c
, Robert Rusina
d
,Jiří Ehrmann
c
, Petr Kaňovský
a
a
Department of Neurology, Palacky University Medical School, Olomouc, Czech Republic
b
Department of Pathology and Molecular Medicine, Thomayer Hospital, Prague, Czech Republic
c
Department of Pathology, Palacky University Medical School, Olomouc, Czech Republic
d
Department of Neurology, Thomayer Hospital, Prague, Czech Republic
abstractarticle info
Article history:
Received 21 November 2012
Received in revised form 18 February 2013
Accepted 12 March 2013
Available online 13 April 2013
Keywords:
Atypical parkinsonism
Synucleinopathies
Tauopathies
Multiple system atrophy
Dementia with Lewy bodies
Progressive supranuclear palsy
Alzheimer's pathology
Background: Atypical parkinsonian syndromes are currently divided into two groups based on their patholog-
ical appearance: synucleinopathies and tauopathies. Based on recent clinico-pathological studies it is increas-
ingly clear, that some pathological characteristics are shared by both groups.
Study objective: To describe two pathologically proven cases of tauopathy manifesting in vivo in two typical
synucleinopathy phenotypes: multiple system atrophy and dementia with Lewy bodies.
Patients and methods: There were 67-year-old woman with a phenotype of multiple system atrophy and a
70-year-old man with a phenotype of dementia with Lewy bodies. The clinical diagnosis was based on the
commonly used clinical diagnostic criteria. A detailed neuropathological examination of the brain was
conducted post-mortem in both cases.
Results: The overall pathological picture corresponded with a rare combination of two neurodegenerative
entities: 4R tauopathy (meeting the diagnostic criteria for typical progressive supranuclear palsy) and neocortical
stage of Alzheimer's disease.
Conclusion: The interesting feature in both our cases was the presence of dual pathology: diffuse tauopathy and
Alzheimer's pathology. We believe, that our two unique cases should serve as an evidence that tauopathies such
as CBS and PSP might mimic practically anything from the family of atypical parkinsonian syndromes, particu-
larly when another concomitant neurodegenerative disease is present.
© 2013 Elsevier B.V. All rights reserved.
1. Introduction
Atypical parkinsonian syndromes are currently divided into two
groups based on their pathological appearance: synucleinopathies and
tauopathies. The group of synucleinopathies consists of Parkinson's
disease (PD), Parkinson's disease dementia (PDD), dementia with
Lewy bodies (DLB), and multiple system atrophy in both parkinsonian
and cerebellar forms (MSA-P, MSA-C). The group of tauopathies is
formed by progressive supranuclear palsy (PSP) in all three pheno-
types: Richardson's syndrome (RS), PSP-parkinsonism (PSP-P), and
pure akinesia with gait freezing (PAGF); corticobasal degeneration syn-
dromes (CBS) are also tauopathies. Some pathological characteristics
are shared by both groups [1,2].
The clinical differential diagnosis of atypical parkinsonism is usually
difcult. There is an arbitrary difference between the clinical courses of
PDD and DLBD, based on the clinical diagnostic criteria [3,4]. Neverthe-
less, it is known that PSP and PD are commonly mistaken for one anoth-
er, as are PSP and CBS [5,6], furthermore, that PSP might manifest as a
CBS phenotype, and, nally, that CBS can mimic any of the others [7].
Their phenotypes and pathological substrates are usually intermixed
in a large clinico-pathological series [810]. On the other hand, the
misdiagnosis between PSP and MSA or DLB is rarely reported, probably
due to the presence of unique characteristics in the phenotypes of these
disorders. However, even this diagnostic challenge may appear. To doc-
ument that, we present two pathologically proven cases of tauopathy
manifesting in vivo in two typical synucleinopathy phenotypes: MSA
and DLB.
2. Case 1
A 67-year-old woman rst noticed impaired stability when walking
with a tendency to fall in all directions at the age of 60. These problems
had lasted 3 years when the patient was admitted to in-patient ward.
Except for the postural instability, the neurological examination was
normal; there were no signs of rigidity, bradykinesia, tremor or any
other extrapyramidal features. ENT examination also did not show
any signicant abnormality. The brain MRI results were near-normal,
and the brain stem auditory evoked potentials were registered with
normal responses. An X-ray of the cervical spine revealed advanced de-
generative changes, leading to a diagnosis of probable initial cervical
myelopathy. The patient was referred to the department of rehabilita-
tion medicine. Over the next six months, the impaired stability wors-
ened, and gait initiation disorder and impaired articulation appeared.
Journal of the Neurological Sciences 329 (2013) 34 37
Corresponding author. Tel.: +420 588443430.
E-mail address: katerina.mensikova@fnol.cz (K. Menšíková).
0022-510X/$ see front matter © 2013 Elsevier B.V. All rights reserved.
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The patient had a mild ataxia with intention tremor of both the upper
and lower limbs, and increased elementary postural reexes were
present as a rst sign of rigidity. Over the next 3 months, the impaired
articulation further progressed, and increased urinary frequency, subjec-
tive stiffness of the lower limbs, and repeated falls appeared. The patie nt
was referred to the in-patient ward of a tertiary movement disorders
centre and examined in detail. Parkinsonian syndrome with rigidity,
bradykinesia and hypokinesia, shufing gait with bilateral reduced
arm swing, and positive pull-test were present; brisk tendon reexes
and positive Babinski signs were present bilaterally. Neuropsychological
examination revealed a mild cognitive impairment (mild constructive
apraxia and a disorder of visuo-spatial orientation); the mini-mental
state examination (MMSE) score was 27 points, the overall results did
not meet the DSM-IV criteria for dementia. Brain MRI showed mild
non-specic white matter abnormalities in both hemispheres (Fig. 1).
The DaTSCAN examination did not reveal any signicant abnormality.
The bedside Thompson test revealed orthostatic hypotension; the
head-up tilt (HUT) test was positive, and a urodynamic study showed
an apparent detrusor hyperreexia. The biochemical, microbiological,
and immunological examinations of blood serum and cerebrospinal
uid were normal. Neurophysiological examinations (electroencepha-
lographic study, nerve conduction studies, electromyography, and mul-
timodal evoked potentials) did not show any signicant abnormality. A
diagnosis of probable MSA-P was made based on the clinical diagnostic
criteria published in 1999 [11], and L-DOPA treatment was initiated;
this did not improve the patient's symptoms. Over the next 12 months,
the gait progressively worsened and the falls became more frequent.
The patient's ability to walk and stand required the use of walkers;
within the next 6 months she required a wheelchair. Over the next
12 months, the rigidity and postural instability further progressed,
followed by the development of severe dystonic contractions of both
the upper and lower limbs bilaterally; anterocollis also appeared.
Dystonia was treated with botulinum toxin type A; however, only
mild improvement was achieved. Severe dysphagia, which appeared
3 months later, required a percutaneous endoscopic gastrostomy with
tube feeding. As a result of the overall disease progression (mainly of
the rigidity, postural instability, and dystonia) the patient gradually
became immobile and bedridden; nevertheless, her cognition was still
fairly good (MMSE score 26). The patient died due to bronchopneumo-
nia after (approximately) 7 years of the disease course.
3. Case 2
A 70-year-old male with history of ischaemic heart disease, hyperten-
sion, diabetes, and a minor stroke with transitory left-sided hemiparesis
was rst consulted after a 4-year history of relatively slowly progressive
memory disturbance, which was followed by a progressive gait disorder
with falls, together with visual hallucinations, and dysarthria. His wife
reported at the time of consultation recent increasing personality
changes, with agitation, social disinhibition, and dressing apraxia, at
the same time, he developed paranoid delusions and emotional incon-
tinence with spasmodic laughter. The condition progressively wors-
ened; however, considerable uctuations in the disease course were
observed by the patient's family.
Neurological examina tion showe d apathy with conside rable psych o-
motor slowing, marked reduction in verbal uency, and important laten-
cies in answering even simple questions. Parkinsonian features included
hypomimia and mild symmetric rigidity with marked akinesia but no
tremor. Slowed hypometric oculomotor saccades (usually present in
DLB), dysarthria, hyperreexia, and slurred gait completed the clinical
presentation. There was also positive evidence from spouse and family
that the patient suffered from REM-sleep behavioural disorder (RBD).
A neuropsychological assessment revealed alterations in episodic
and visual memory in both memorization and retrieval (free recall 2/
10 items; recognition 12/20; very restricted learning curve 3-2-2-1
from a list of 10 words). Visuospatial functions were impaired with al-
terations in complex gure copy and recall; the drawing was dispropor-
tionate and without a clear conception, and important details were
missing, although the clock drawing test was normal. In Repeatable Bat-
tery for the Assessment of Neuropsychological Status (RBANS), the total
measured index score was 60. Executive dysfunction included markedly
reduced verbal uency, with de
cits in conceptualization, problem
solving, and concentration. Speech was dysarthric and effortful, but rep-
etition and comprehension were preserved. The patient had no signs of
depression. The MMSE score was 20. MRI scans revealed slight sym-
metric cerebellar atrophy and rare, small, nonspecic (probably post-
ischaemic) white matter lesions (Fig. 2). The DaTSCAN examination
revealed only non-signicant reduction of tracer uptake bilaterally.
Total tau, phosphotau, and beta-amyloid levels in the cerebrospinal
uid were normal. Our diagnostic conclusion, based on the clinical diag-
nostic criteria [3], was probable DLB. We started treatment with L-DOPA
up to 750 mg daily and donepezil 10 mg daily. Over the following
months, the cognitive performance partially improved (MMSE raised
to 22) and behavioural and psychotic symptoms regressed, but akinesia
with rigidity increased, and falls became more frequent. The falls
described by the patient's family were such as those seen in postural
instability with gait disorder or orthostatic hypotension; there were
no signs or descriptions of sudden, unexpected falls typical for PSP.
Subsequently, patient's gait considerably worsened, and urinary
incontinence developed. The previously reported uctuating course
changed into a more steady progression. About 16 months after the
initial assessment, the patient was bedridden with severe rigidity de-
spite 1000 mg L-DOPA daily, and memory and cognitive performance
worsened as well (the MMSE dropped to 17). The behavioural features
re-emerged, and so memantine was added. Nevertheless, the patient's
condition continued to worsen and he died from terminal broncho-
pneumonia 1 year later, i.e., 6 years after the initial signs manifested.
4. Neuropathology
A detailed neuropathological examination of the brain was
conducted in both cases. Formalin-xed, parafn-embedded blocks
from the following regions were examined: frontal, temporal, parietal
and occipital cortices, hippocampus and p arahippocampal region, basal
ganglia, brain stem at the level of substantia nigra, oblongata at the
level of lower olives, and cerebellum (Fig. 3). For immunohistochemistry,
5 μm-thick sections of formalin-xed and parafn-embedded tissue
Fig. 1. Case 1: Sagittal T1-weighted MRI showing the normal shape of the brain stem
and rare small nonspecic (probably post-ischaemic) white matter lesions.
35K. Menš íková et al. / Journal of the Neurological Sciences 329 (2013) 3437
Author's personal copy
were incubated with primary antibodies against the following antigens:
α-synuclein(1:5000,Signet,Dedham,MA,USA,4D6);tauAT8(1:200,
Pierce Biotechnology, Rockford, IL, USA, pS202/pT205); tau, 3-repeat iso-
form DR3 (1:500, Upstate Biotechnology, Lake Placid, NY, USA, 8E6/C11);
tau, 4-repeat isoform DR4 (1:200, Upstate Biotechnology, Lake Placid,
NY,USA,1E1/A6);β-amyloid peptide (1:100, Dako, Glostrup, Denmark,
6F/3D).
The immunohistochemical examination excluded clinical diagnoses
of synucleinopathy in both cases. Prominent positivities were seen in
reaction to the hyperphosphorylated form of tau protein (clone AT8)
and the isoform of tau protein DR3 and DR4. In response to the
monoclonal antibody against tau protein (clone AT8) there were evi-
dent numerous pretangles and tangles in the hippocampus and
parahippocampal region; further there were tufted astrocytes, glial
and cytoplasmic neuronal inclusions, and tangles and threads in all
previously mentioned areas, particularly in the substantia nigra, in the
cerebellar dentate nucleus, in the pons, and in the motor and premotor
cortex. Tau-positive inclusions of different types were present in differ-
ent degrees in the basal ganglia, in the midbrain, and in the cerebellum.
The most signicant antibody reaction against the isoform of tau pro-
tein DR4 was present only in the midbrain, while in the temporal lobe
in some areas the DR3 isoform predominated. The intensity of these
changes in both cases was very similar, with a slightly higher accentua-
tion in the midbrain area in case 2. Both cases reached a score of 6 to 7
according to the Williams scoring system [12]. A positive antibody
reaction against ß-amyloid peptide demonstrated various numbers of
different types of amyloid plaques in case 1, where amyloid plaques of
different types were seen in the basal ganglia as well (Fig. 3A). Neuro-
pathological changes in both cases were consistent with the neocortical
stage of Alzheimer's disease, as dened by the newly published consen-
sual NIA criteria for diagnosis of Alzheimer's disease; they reached the
high level in ABC scoring system [13].
The overall pathological picture corresponded to a rare combina-
tion of two neurodegenerative entities: 4R tauopathy (meeting the
diagnostic criteria for typical progressive supranuclear palsy) and a
neocortical stage of Alzheimer's disease.
5. Discussion
In their clinico-pathological study, Williams and Lees stated that
Neurologists could not correctly diagnose PSP early in most patients
and instead recorded a diagnosis of PD [10]. In contrast, the mistaken
diagnosis of PSP in a case of pathologically conrmed Parkinson's dis-
ease was the least frequent in their retrospective study. Their study
Fig. 2. Case 2: Sagittal T1-weighted MRI, showing near-normal shape of the brain stem
with slight atrophy of the cerebellum. Courtesy of J. Keller, Department of Radiology,
Na Homolce Hospital, Prague, Czech Republic.
Fig. 3. Different morphologies of amyloid plaques and cerebral amyloid angiopathy in positive immunohistochemical reaction with monoclonal antibody against amyloid-ß-peptide
in case 1 (A), and neurobrillary degenerative structur es stained with monoclonal antibody against hyperphosphorylated tau protein in case 2 (B) showing Alzheimer's
disease-related neuropathology. Numerous deposits of hyperphosphorylated tau protein (C) positive with monoclonal antibody against DR4 subtype of tau protein (D) in
substantia nigra proved PSP. Original magnication: 200×.
36 K. Menš íková et al. / Journal of the Neurological Sciences 329 (2013) 3437
Author's personal copy
involved the primary referral pattern of PD patients who were diag-
nosed post-mortem with atypical parkinsonism. In our situation, the
initial diagnoses of synucleinopathy in two patients (MSA and DLB
respectively, made according to the clinical diagnostic criteria) were un-
changed until their deaths, and the pathological diagnosis of tauopathy
was a surprise.
The variability of initial symptoms of neurodegenerative parkin-
sonism is a well-known feature [14], and a precise initial diagnosis
may be a challenge despite the use of instrumental assessments
[15,16]. The fact that corticobasal degeneration can mimic practically
any other atypical parkinsonian syndromes is also seen as a useful
paradigm [7,17]. A recent retrospective study showed that PD might
mimic PSP in some cases, including eye movement abnormalities
and subcortical cognitive dysfunction; the authors concluded that
this is an advantage for the correct diagnosis of PSP, and in particular
in the identication of cases of PSP-P. They also stated that the pa-
tients with the clinical syndromes of DLB and underlying Lewy body
pathology are unlikely to be confused with PSP-P because of the
early cognitive decline and visual hallucinations that are major com-
ponents in the clinical diagnostic criteria of DLB [18]. We had a differ-
ent experience. We had to manage patients in whom the diagnoses of
typical synucleinopathies (probable MSA-P and probable DLB) were
made on the basis of current and validated clinical diagnostic criteria.
Despite the relatively long course of disease in both patients (7 and
6 years), there were never any reasons to change the diagnosis that
was made in the rst year after disease onset. MR imaging in either
case did not bring any important diagnostic information. In case 1,
one should expect on MR images atrophy of putamen, peduncles or
cerebellum. However, the absence of these signs is not an exclusion
criterion for the diagnosis of MSA. This fact has been conrmed in
the recent clinico-pathological study, in which the atrophy of puta-
men was present in 50% cases, cerebellar atrophy in 38% of cases,
and the peduncular or pontine atrophy in only 33% of cases [19].On
the other hand, the presence on non-specic white matter lesions
has been frequently reported in MSA cases in the recent years, and
has been conrmed in a more recent double-blind MRI study [20].
All these facts make, in our opinion, another argument in support of
the discussion of the usefulness of any rigid clinical diagnostic criteria
for atypical parkinsonian syndromes, as it appears periodically in the
literature [2,7]. We are aware of the necessity to have consensual diag-
nostic criteria for any given nosological entity for the purpose of trans-
lational and pharmacological research. However, these criteria should
be seen as a secondary tool in the differential diagnosis of parkinsonian
syndromes, since they only reect the state of knowledge at the time.
Gilman's (et al.) MSA criteria can serve as a shining example, since
they were changed over the course of 8 years [11,21].
The interesting feature in both our cases was the presence of dual
pathology: diffuse tauopathy and Alzheimer's pathology in the limbic
stage. There is a report of a PSP patient mimicking synucleinopathy of
MSA-P type, but without any signs of cognitive decline and without
the presence of Alzheimer's pathology [22]. Dual pathology was de-
scribed in a patient with the PSP-P phenotype of atypical parkinson-
ism; the tauopathy and alpha-synucleinopathy co-occurred in this
case [23]. From this point of view, our two unique cases should
serve as an evidence that CBS and PSP might mimic practically any-
thing from the family of atypical parkinsonian syndromes, particular-
ly when another concomitant neurodegenerative disease is present.
Conict of interest
The authors report no conict of interest.
Acknowledgement
Supported by the grants IGA LF UP 2012-013, IGA MZ CR NT-12221,
NT-12094-5/2011, and the Institutional Support from the Ministry of
Health, Czech Republic.
References
[1] Galpern WR, Lang AE. Interface between tauopathies and synucleinopathies: a
tale of two proteins. Ann Neurol 2006;59:44958.
[2] Wenning GK, Colosimo C. Diagnostic criteria for multiple system atrophy and pro-
gressive supranuclear palsy. Rev Neurol 2010;166:82933.
[3] McKeith I, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, et al. Diagnosis
and management of dementia with Lewy bodies: third report of the DLB consor-
tium. Neurology 2005;65:18637.
[4] Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, et al. Clinical
diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord
2007;22:1689707.
[5] Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ. The accuracy of diagnosis of parkinso-
nian syndromes in a specialist movement disorder service. Brain 2002;125:86170.
[6] Testa D, Monza D, Ferrarini M, Soliveri P, Girotti F, Filippini G. Comparison of natural
histories of progressive supranuclear palsy and multiple system atrophy. Neurol Sci
2001;22:24751.
[7] Ling H, O'Sullivan S, Holton JL, Revesz T, Massey LA, Williams DR, et al. Does
corticobasal degeneration exist? A clinicopathological re-evaluation. Brain 2010;133:
204557.
[8] Litvan I, Grimes DA, Lang AE, Jankovic J, McKee A, Verny M, et al. Clinical features
differentiating patients with postmortem conrmed progressive supranuclear
palsy and corticobasal degeneration. J Neurol 1999;246(Suppl. 2):15.
[9] O'Sullivan SS, Massey LA, Williams DR, Silveira-Moriyama L, Kempster PA, Holton
JL, et al. Clinical outcomes of progressive supranuclear palsy and multiple system
atrophy. Brain 2008;131:136272.
[10] Williams DR, Lees AJ. How do patients with parkinsonism present? A clinicopath-
ological study. Int Med J 2009;39:712.
[11] Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, et al. Consensus
statement on the diagnosis of multiple system atrophy. J Neurol Sci 1999;163:948.
[12] Williams DR, Holton JL, Strand C, Pittman A, de Silva R, Lees AJ, et al. Pathological tau
burden and distribution distinguishes progressive supranuclear palsy-parkinsonism
from Richardson's syndrome. Brain 2007;130:156676.
[13] Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carillo MC, et al. National
Institute of Aging-Alzheimer's Association guidelines for the neuropathological
assessment of Alzheimer's disease. Alzheimers Dement 2012;8:113.
[14] Caslake R, Moore JN, Gordon JC, Harris CE, Counsell C. Changes in diagnosis with
follow-up in an incident cohort of patients with parkinsonism. J Neurol Neurosurg
Psychiatry 2008;79:12027.
[15] Tang CC, Poston KL, Eckert T, Feigin A, Frucht S, Gudesblatt M, et al. Differential
diagnosis of parkinsonism: a metabolic imaging study using pattern analysis. Lancet
Neurol 2010;9:14958.
[16] Haller S, Badoud S, Nguyen D, Barnaure I, Montandon ML, Lovblad KO, et al. Differ-
entiation between Parkinson disease and other forms of Parkinsonism using sup-
port vector machine analysis of susceptibility-weighted imaging (SWI): initial
results. Eur Radiol 2013 Jan;23(1):129.
[17] Wadia PM, Lang AE. The many faces of corticobasal degeneration. Park Relat
Disord 2007;13:S33640.
[18] Williams DR, Lees AJ. What features improve the accuracy of the clinical diagnosis of
progressive supranuclear palsy-parkinsonism (PSP-P)? Mov Disord 2010;25:35762.
[19] Massey L, Micalef C, Paviour D, O'Sullivan S, Ling H, Williams D, et al. Conventional
magnetic resonance imaging in conrmed progressive supranuclear palsy and
multiple system atrophy. Mov Disord 2012;27:175562.
[20] Umoto M, Miwa H, Ando R, Kajimoto Y, Kondo T. White matter hyperintensities in
patients with multiple system atrophy. Park Relat Disord 2012;18:1720.
[21] Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, et al.
Second consensus statement on the diagnosis of multiple system atrophy. Neurology
2008;71:6706.
[22] Compta Y, Marti MJ, Rey MJ, Ezquerra M. Parkinsonism, dysautonomia, REM
behaviour disorder and visual hallucinations mimicking synucleinopathy in a
patient with progressive sup ranuclear palsy. J Neurol Neurosurg Psyc hiatr
2009;80:5789.
[23] Mooney T, Tampiyappa A, Robertson T, Grimley R, Burke C, Ng K, et al. Dual
pathology of corticobasal degeneration and Parkinson's disease in a patient with
clinical features of progressive supranuclear palsy. Neurol India 2011;59:88790.
37K. Menš íková et al. / Journal of the Neurological Sciences 329 (2013) 3437
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