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VV1 CJD, sporadic or variant or new variant another strain ?

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flounder

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----- Original Message -----
From: "Terry S. Singeltary Sr." <[email protected]>
To: <[email protected]>
Sent: Tuesday, October 18, 2005 9:46 AM
Subject: Re: sporadic CJD: Clinical and diagnostic characteristics of the rare VV1 type


> ##################### Bovine Spongiform Encephalopathy #####################
>
> looking further into this study, some very interesting aspects of VV1 sCJD
> cases;
>
>
> snip...
>
>
> Discussion
>
> Within the group of sporadic CJD patients, six subtypes have been identified
> by genetic
> and molecular analysis. Among those, the VV1 type represents the rarest one.
> In contrast to the classic disease type with rapid dementia at an old age,
> VV1 sCJD
> patients are young (typically under 50 years of age) and more frequently men
> (significant,
> p=0.039, one-sample test for binominal distribution): regarding the
> literature
> and our own cases only three out of 16 VV1 patients were women, which
> results in a
> men to women ratio of four to one.
> The disease duration of the VV1 cases in this study ranged from 17 to 49
> months.
> In the literature, the shortest disease duration in a VV1 patient has been
> reported as
> 10 months, the longest as 31 months (8), (1). The median disease duration of
> all VV1
> cases known to date is 18 months (10 - 49).
> It is important to note that two of our VV1 patients also clearly exceed the
> duration of
> dementia stipulated by the WHO criteria for possible and probable CJD (less
> than
> two years) and would have to be classified as “no case”, if they had not
> undergone
> neuropathological examination (11). Comparably long disease durations have
> only
> been reported for the MV2 type (median 17 months, 10 cases), the rare MM2
> type
> (median 14 months, three cases) as well as vCJD and genetic cases (1), (17).
> Of
> interest, some of the patients with MM2 type reported recently may show
> similiarities
> to the VV1 patients with respect to the cortical pattern of MRI signal
> increase, no
> PSWCs in the EEG and long duration of the disease (18).
> NEUROLOGY/2005/095190 Meissner 12
> As for the clinical disease course, VV1 patients typically develop slowly
> progressive
> dementia and behavioral disorders at the beginning of the disease. These
> symptoms
> mostly remain the only abnormalities for a long time (median seven months),
> compared
> to the classic CJD type, in which the cognitive decline is usually
> accompanied
> by further neurological symptoms after weeks, already.
> This prodromal phase is followed by further CJD symptoms such as ataxia
> (median
> seven months), rigidity (median nine months), myoclonus (median 10 months)
> and
> spasticity (median 12 months). The suspicion of CJD is thus only raised
> during a later
> disease stage (mostly with the onset of myoclonus).
> In the literature dementia has been described as the only leading clinical
> feature of
> VV1 types, probably because of the small number of patients known at the
> time (1),
> (2). We can now report personality changes as another characteristic found
> in all
> VV1 patients. The main psychiatric features were aggressive behavior (five
> cases), a
> regression to childish behavior (five cases) and fear (three cases).
> The early onset of cognitive decline and personality changes might be due to
> an
> early affection of the neocortex as well as the limbic system, which would
> be in line
> with the prominent neuropathological involvement of these areas and the
> frequent
> signal increase of the cortex and hippocampus seen on MRI. Interestingly,
> only those
> three patients who already displayed behavioral abnormalities at onset
> showed a
> strong signal increase of the hippocampus region on MRI.
> As another feature of VV1 patients, focal neurological deficits were seen in
> five out of
> nine patients, comprising hemiparesis, hemineglect, hemianopsia, Broca
> aphasia, as
> well as one-sided apraxia. Due to the longer overall disease duration with
> lesions
> slowly affecting various functional systems, focal signs may be seen more
> often in
> VV1 patients than in MM1 CJD cases who have a relatively rapid involvement
> of the
> whole brain.
> NEUROLOGY/2005/095190 Meissner 13
> The clinical diagnosis of CJD is based on EEG (PSWC, periodic sharp-wave
> complexes),
> CSF (finding of 14-3-3 protein) and MRI (hyperintense signal of the basal
> ganglia) together with a variety of clinical signs. Differences as to the
> sensitivity of
> diagnostic methods, depending on the underlying subtype of sCJD, have been
> reported
> (1), (19).
> As for VV1 patients, no useful paraclinical test - apart from the 14-3-3
> protein detection
> in CSF – could be offered, so far (1). It has been recently shown that the
> sensitivity of this test varies among the sCJD subtypes (20).
> The eight VV1 cases examined in this study were all positive for the 14-3-3
> protein in
> the CSF. Consistent with the literature findings (table (E)T-3), the 14-3-3
> protein was
> detected in the CSF of all tested patients but no typical EEG findings
> (PSWC) were
> found (although EEGs were performed repeatedly over a median time of seven
> months after onset). Focal slowing, however, seems to be a frequent finding
> of VV1
> patients (displayed by seven out of nine patients), and is consistent with
> the more
> focal neurological symptoms and main neuropathological affection of the
> cortex and
> basal ganglia.
> Signal increase on MRI was detected in all cortex areas of our VV1 patients.
> In the
> literature, cortical signal increase has been reported before in single VV1
> case reports.
> In our cases, the temporal cortex was affected most often (seven out of
> seven
> cases), followed by the hippocampus and insula (six out of seven cases,
> each).
> Signal increase of the hippocampus has not been described as a typical
> finding in
> sCJD and has only been reported twice (21), (22). The frequent occurrence of
> this
> abnormality in our VV1 cases suggests that it might be a specific feature of
> this rare
> CJD subtype.
> NEUROLOGY/2005/095190 Meissner 14
> Basal ganglia signal alterations have been reported as a typical MRI finding
> in 63%
> of sCJD cases (only T2-weighted MRIs included) (19). However, only two out
> of
> seven VV1 patients displayed this abnormality. In one case, these
> alterations were
> visible on a T2-weighted image four months after onset. The other patient
> showed
> only a slight signal increase of the right caudate (in relation to the left
> caudate) on a
> first scan three months after onset (T2, FLAIR) and a more prominent one in
> a
> FLAIR-weighted follow-up examination 3.5 months after onset. The reason for
> the
> rare occurrence of basal ganglia signal abnormalities might be that
> diffusionweighted
> images, the most sensitive technique, were only used in one of our cases
> (23).
> Hyperintense basal ganglia were reported to correlate with an early onset of
> dementia
> and shorter survival time in sporadic CJD (all subtypes) (19).
> Interestingly, our two
> VV1 cases displaying basal ganglia signal alterations were among those with
> the
> shortest disease duration (10 months and 18 months), which is in line with
> this observation.
> As on MRI, the temporal lobes were also most often affected on SPECT and
> PET.
> The earliest SPECT finding in one of our patients was a hypoperfusion of the
> temporal
> lobe three months after onset. Those patients who were examined after five
> months or later, showed a widespread cortical involvement. However, as
> stated before
> by other authors, no specific lesion pattern has been found for CJD so far
> (24),
> (25).
> A prolonged disease course, young age at disease onset, frequent psychiatric
> symptoms
> and comparably slowly progressive dementia are characteristics of both, VV1
> sCJD and vCJD. Differentiating these two patient groups may be difficult as
> the
> ranges concerning the disease age as well as the disease duration largely
> overlap
> (table (E)T-4). An absence of the 14-3-3 protein in the CSF and signal
> increase of the
> NEUROLOGY/2005/095190 Meissner 15
> pulvinar on MRI (pulvinar sign) may shift the diagnosis towards vCJD. In
> contrast, the
> presence of the 14-3-3 protein and hippocampal signal increase on MRI may
> speak
> for VV1 sCJD.
> The pulvinar sign – the most specific criterion for the diagnosis of vCJD -
> is clearly
> defined as bilateral hyperintensity of the pulvinar of the thalamus in
> relation to the
> anterior putamen (26). To our knowledge, only one case of VV1 sCJD has been
> reported
> presenting MRI findings according to that definition (10). Thus, to avoid
> false
> diagnoses of vCJD, special attention should be paid to the relation between
> the signal
> increases in the individual brain regions.
> A further and simple method to rule out a diagnosis may be the determination
> of the
> patient’s molecular type. As, until today, all cases of vCJD have been
> reported to be
> methionine homozygous at the codon 129 of the prion protein gene, a genetic
> analysis
> may be the fastest way to differentiate vCJD from the valine homozygous VV1
> sCJD (27). This is, however, only valuable as long as no vCJD patients of
> other molecular
> types are reported.
> NEUROLOGY/2005/095190 Meissner 16
> Acknowledgements
>
> snip...end..................TSS
>
> ----- Original Message -----
> From: "Terry S. Singeltary Sr." <[email protected]>
> To: <[email protected]>
> Sent: Monday, October 17, 2005 10:14 AM
> Subject: sporadic CJD: Clinical and diagnostic characteristics of the rare
> VV1 type
>
>
> ##################### Bovine Spongiform Encephalopathy
> #####################
>
> From: TSS ()
> Subject: sporadic CJD: Clinical and diagnostic characteristics of the rare
> VV1 type
> Date: October 17, 2005 at 7:59 am PST
>
> Published online before print October 12, 2005
> (Neurology 2005, doi:10.1212/01.wnl.0000184674.32924.c9)
>
> Received February 24, 2005
> Accepted August 24, 2005
>
> Sporadic Creutzfeldt-Jakob disease: Clinical and diagnostic characteristics
> of the rare VV1 type
> B. Meissner MD, I. M. Westner MD, K. Kallenberg MD, A. Krasnianski MD, M.
> Bartl MD, D. Varges , C. Bösenberg , H. A. Kretzschmar MD, FRCPath, M.
> Knauth MD, W. J. Schulz-Schaeffer MD, and I. Zerr MD*
>
> From the Departments of Neurology (Drs. Meissner, Krasnianski, Bartl, Zerr,
> D. Varges and C. Bösenberg), Neuroradiology (Drs. Kallenberg and Knauth),
> and Neuropathology (Dr. Schulz-Schaeffer), Georg-August-Universität
> Göttingen; and Center for Neuropathology and Prion Research (Drs. Westner
> and Kretzschmar), Ludwig-Maximilians-Universität München, Germany.
>
>
>
> * To whom correspondence should be addressed. E-mail:
> [email protected] .
>
>
> Abstract-- Background: Recently, six molecular subtypes of sporadic CJD
> (sCJD) have been identified showing differences regarding the disease
> course, neuropathologic lesion patterns, and sensitivity to diagnostic
> tools. Only isolated cases of the rare VV1 type have been reported so far.
> Objective: To describe the clinical characteristics and neuropathologic
> lesion profiles in nine cases. Methods: In the years 1993 until late 2003,
> 571 definite neuropathologically confirmed cases of sporadic CJD were
> identified in Germany. Of these, nine were homozygous for valine and
> displayed type 1 of the pathologic PrPSc in the brain (VV1 type). Results:
> The authors describe eight men and one woman belonging to the VV1 type. All
> patients were relatively young at disease onset (median 44 years vs 65 years
> in all sCJD) with prolonged disease duration (median 21 months vs 6 months
> in all sCJD). During the initial stages, their main clinical signs were
> personality changes and slowly progressive dementia as well as focal
> neurologic deficits. None of the nine VV1 patients had periodic sharp-wave
> complexes (PSWCs) in the EEG. Only two out of seven displayed the typical
> signal increase of the basal ganglia on MRI, whereas signal increase of the
> cortex was seen in all patients. The 14-3-3 protein levels were elevated in
> CSF in all cases tested. Conclusions: The clinical diagnosis of the VV1 type
> of sCJD can be best supported by the 14-3-3 test and cortical signal
> increase on MRI. Because of the young age at onset vCJD is sometimes
> suspected as a differential diagnosis. MRI plays an important role in
> differentiating these two disease types and should be performed early during
> the disease course.
>
>
> http://www.neurology.org/cgi/content/abstract/01.wnl.0000184674.32924.c9v1
>
>
> TSS
>
> #################### https://lists.aegee.org/bse-l.html
> ####################
>
> #################### https://lists.aegee.org/bse-l.html ####################
>


IN light of Asante/Collinge et al findings that BSE transmission to the
129-methionine genotype can lead to an alternate phenotype that is
indistinguishable from type 2 PrPSc, the commonest _sporadic_ CJD;

-------- Original Message -------- Subject: re-BSE prions propagate as

either variant CJD-like or sporadic CJD Date: Thu, 28 Nov 2002 10:23:43

-0000 From: "Asante, Emmanuel A" To:
"'[email protected]'"

Dear Terry,

I have been asked by Professor Collinge to respond to your request. I am

a Senior Scientist in the MRC Prion Unit and the lead author on the

paper. I have attached a pdf copy of the paper for your attention. Thank

you for your interest in the paper.

In respect of your first question, the simple answer is, yes. As you

will find in the paper, we have managed to associate the alternate

phenotype to type 2 PrPSc, the commonest sporadic CJD.

It is too early to be able to claim any further sub-classification in

respect of Heidenhain variant CJD or Vicky Rimmer's version. It will

take further studies, which are on-going, to establish if there are

sub-types to our initial finding which we are now reporting. The main

point of the paper is that, as well as leading to the expected new

variant CJD phenotype, BSE transmission to the 129-methionine genotype

can lead to an alternate phenotype which is indistinguishable from type

2 PrPSc.



I hope reading the paper will enlighten you more on the subject. If I

can be of any further assistance please to not hesitate to ask. Best wishes.



Emmanuel Asante

<> ____________________________________

Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial

College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG

Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email:

[email protected] (until 9/12/02)

New e-mail: [email protected] (active from now)

____________________________________

snip...

full text ;

http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm


AND the new findings of BASE in cattle in Italy of Identification of a
second bovine amyloidotic spongiform encephalopathy: Molecular
similarities with sporadic

Creutzfeldt-Jakob disease


http://www.pnas.org/cgi/content/abstract/0305777101v1


Adaptation of the bovine spongiform encephalopathy agent to primates
and comparison with Creutzfeldt- Jakob disease: Implications for
human health

THE findings from Corinne Ida Lasmézas*, [dagger] , Jean-Guy Fournier*,
Virginie Nouvel*,

Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp [Dagger

] , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce [||] , Dominique

Dormont*, and Jean-Philippe Deslys* et al, that The agent responsible
for French iatrogenic growth hormone-linked CJD taken as a control is
very different from vCJD but is similar to that found in one case of
sporadic CJD and one sheep scrapie isolate;

http://www.pnas.org/cgi/content/full/041490898v1

Characterization of two distinct prion strains
derived from bovine spongiform encephalopathy
transmissions to inbred mice

http://vir.sgmjournals.org/cgi/content/abstract/85/8/2471


Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.



http://jama.ama-assn.org/cgi/content/full/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=dignosing+and+reporting+creutzfeldt+jakob+disease&searchid=1048865596978_1528&stored_search=&FIRSTINDEX=0&journalcode=jama



BRITISH MEDICAL JOURNAL



SOMETHING TO CHEW ON



BMJ



http://www.bmj.com/cgi/eletters/319/7220/1312/b#EL2



BMJ



http://www.bmj.com/cgi/eletters/320/7226/8/b#EL1



ALL animals for human/animal consumption must be tested for TSE.

ALL human TSEs must be made reportable Nationally and Internationally, OF ALL AGES...


TSS
 

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