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From: TSS ()
Subject: Isolated visual symptoms at onset in sporadic Creutzfeldt-Jakob disease: the clinical phenotype of the ‘‘Heidenhain variant’’ [FULL TEXT]
Date: October 31, 2005 at 8:24 am PST

----- Original Message -----
From: Terry S. Singeltary Sr.
To: Bovine Spongiform Encephalopathy
Sent: Monday, October 31, 2005 10:35 AM
Subject: Isolated visual symptoms at onset in sporadic Creutzfeldt-Jakob disease: the clinical phenotype of the ‘‘Heidenhain variant’’


2005;89;1341-1342 Br. J. Ophthalmol.

S A Cooper, K L Murray, C A Heath, R G Will and R S G Knight

the "Heidenhain variant"

Creutzfeldt-Jakob disease: the clinical phenotype of

Isolated visual symptoms at onset in sporadic


Isolated visual symptoms at onset in sporadic Creutzfeldt-

Jakob disease: the clinical phenotype of the ‘‘Heidenhain


S A Cooper, K L Murray, C A Heath, R G Will, R S G Knight

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

See end of article for

authors’ affiliations

. . . . . . . . . . . . . . . . . . . . . . .

Correspondence to:

Dr Sarah Cooper, The

National Creutzfeldt-Jakob

Disease Surveillance Unit,

Western General Hospital,

Crewe Road, Edinburgh

EH4 2XU, UK; sarah.

Accepted for publication

15 July 2005

. . . . . . . . . . . . . . . . . . . . . . .

Br J Ophthalmol 2005;89:1341–1342. doi: 10.1136/bjo.2005.074856

Background: The Heidenhain variant of sporadic Creutzfeldt-Jakob disease (sCJD) is commonly

understood to represent cases with early, prominent visual complaints. The term is clarified to represent

those who present with isolated visual symptoms. This group may pose diagnostic difficulties and often

present to ophthalmologists where they may undergo needless invasive procedures.

Method: A retrospective review of 594 pathologically proved sCJD cases referred to the UK National CJD

Surveillance Unit over a 15 year period to identify Heidenhain cases.

Results: 22 cases had isolated visual symptoms at onset with a mean illness duration of 4 months. The

mean age at disease onset was 67 years. Most displayed myoclonus, pyramidal signs, and a delay in the

onset of dementia for some weeks. 17 (77%) were referred initially to ophthalmology. Two underwent

cataract extraction before diagnosis. All tested cases were homozygous for methionine at codon 129 of

the prion protein gene.

Conclusions: This rare, but clinically distinct, group of patients with sCJD may cause diagnostic difficulties.

Because ocular intervention carries with it the risk of onward transmission awareness of this condition

among ophthalmologists is important.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare and

uniformly fatal prion disease classically presenting as a

rapidly progressive dementia resulting in death usually

within 6 months.1 2

A subgroup of cases of sCJD present with isolated visual

symptoms. These can persist in the absence of cognitive

decline for some weeks.3 Historically, these are termed the

‘‘Heidenhain variant’’ of sCJD after work by Heidenhain in

1929.4 He described three cases of spongiform encephalopathy,

two of which had prominent, early visual symptoms.

The third presented with sensory complaints and athetosis.

Meyer et al described, in 1954, the case of a 38 year old man

who ‘‘became forgetful, experienced difficulty in concentrating…

suffered from headaches and his vision began to fail.’’

A right homonymous hemianopia was detected and death

occurred 6 months after the onset of symptoms.5

Subsequently, the term has been used rather imprecisely in

all cases where visual symptoms occur along with otherwise

characteristic early features. Visual symptoms are common in

sCJD and, in the early stages of the disease, have been

described in 20%.6 This study seeks to clarify Heidenhain

cases as a clinically distinct group where visual symptoms

occur initially in isolation. These cases may cause diagnostic

difficulty and raise particular public health concerns. They

are likely to present to ophthalmologists and may be subject

to needless ocular intervention, with risks of onward



A retrospective case file review was performed on all

pathologically proved cases of sCJD referred to the UK

National CJD Surveillance Unit (NCJDSU) between January

1990 and March 2005 inclusive. Case files comprised clinical

and epidemiological information collected by NCJDSU staff

and copies of hospital and general practitioner records. A

clinical assessment and interview with patients’ relatives was

conducted by a surveillance neurologist whenever possible

and usually while the patient was alive.

Electroencephalogram (EEG) recordings and magnetic resonance

brain imaging (MRI) were reviewed at the NCJDSU.

Cases were identified whose first symptom was visual and

who exhibited no other cognitive, behavioural, or physical

symptoms for at least 2 weeks. The presence or absence of

cognitive decline was assessed by a review of case files,

including a detailed discussion with relatives and a questionnaire

completed by the NCJDSU neurologist. Patients

were excluded if there were any memory difficulties,

behavioural changes, episodes of confusion or disorientation,

speech problems, or other neurological symptoms or signs

within 2 weeks of the first symptom. Cases were identified

on a clinical basis without awareness of PRNP codon 129

genotype data. Genetic analysis was performed with

informed consent of the patient or the next of kin.


Twenty two patients out of 594 (3.7%) with pathologically

proved sCJD had clearly documented purely visual symptoms

for at least the first 2 weeks of the illness. The nature of these

initial symptoms is summarised in table 1.

Fourteen (64%) cases were women. Mean age at onset was

67 years (median 66 years, range 50–88 years). Mean duration

of illness was 4 months (median 3 months, range 1–

17 months). Seventeen patients (77%) lived for 3 months or


Clinical features

Throughout the illness myoclonus was observed in 21 (95%),

pyramidal signs in 19 (86%), cerebellar signs in 12 (55%),

psychiatric symptoms in seven (32%), other involuntary

movements in six (27%), sensory symptoms in four (18%),

Abbreviations: EEG, electroencephalogram; MRI, magnetic resonance

imaging; NCJDSU, National CJD Surveillance Unit; sCJD, sporadic

Creutzfeldt-Jakob disease


on 31 October 2005 Downloaded from

and extrapyramidal signs in one (5%). None had documented

seizures. A rapidly progressive dementia was observed in all

after the initial period of cognitive preservation which lasted

from 2–6 weeks.

Case 1

A 73 year old man complained of difficulty reading, with

blank spaces appearing in words. He also complained of

colours appearing abnormally enhanced. He was assessed by

an ophthalmologist when there was normal visual acuity but

dense scotomata lying to the right of fixation bilaterally. A

provisional diagnosis of an occipital infarct was made. Six

weeks after onset he developed myoclonus, followed by

ataxia and ultimately dementia. His vision deteriorated with

oculomotor apraxia and cortical blindness. He died 3 months

after disease onset.

Case 2

A 62 year old woman presented with deteriorating visual

acuity. She felt that her vision was ‘‘fogging up’’ and

complained of tunnel vision. She attended an optician but

no abnormality was identified. A week later she complained

that everything appeared green. An MRI brain scan was

ordered following referral to the ophthalmology department

but no diagnosis made. Over the next month her gait became

unsteady and she was increasingly forgetful. By the time she

developed myoclonus she could only perceive light. She died

in an akinetic and mute state 4 months after onset.

Investigation results

Twenty patients had at least one EEG. These were considered

typical for sCJD1 after review at the NCJDSU in seven cases

(35%). CSF 14-3-3 was analysed in five patients (positive in

all). Cerebral MRI was available for review in only six cases,

showing high signal in the basal ganglia in two (33%) and

being normal in four. Sixteen cases (73%) had PRNP gene

codon 129 genotype data. All of these were homozygous for

methionine. In nine the glycotype was known and was type 1

in all.1

Seventeen patients (77%) were initially referred to the

ophthalmology department. Two underwent cataract extraction

after the onset of symptoms and before a diagnosis of

sCJD. Thirteen (59%) were referred to the NCJDSU within

2 months of onset. Three cases were referred after death, one

of these after a necropsy revealed sCJD.


Although visual symptoms in sCJD are not uncommon they

often occur in the context of symptoms indicative of a more

widespread cortical involvement. These cases are distinct

because of the isolated visual symptoms at onset and the

striking early preservation of cognitive function. Aside from

the onset the cases are remarkably ‘‘typical’’ for sCJD. The

majority display an extremely rapid decline with associated

myoclonus once dementia has supervened. Nearly 60% of

these patients were referred to the NCJDSU within 2 months

of onset and only one case was referred as a result of

diagnosis at necropsy (compared to 19% of total cases of sCJD

referred in this way7). Two cases underwent cataract

extraction before the diagnosis of sCJD was considered.

Previous work has highlighted the incidence of ocular surgery

in sCJD cases with visual symptoms8. Although there have

not been any reports of CJD transmission following cataract

surgery, it has been reported after corneal grafting. Abnormal

prion protein has been isolated from ocular tissue.9 It is

important that ophthalmologists are aware of the condition

despite its rarity as onward transmission through ocular

surgical intervention remains a concern.

All tested cases were homozygous for methionine at codon

129 of the PRNP gene. This genotype is associated with a

clinically typical disease course10 rather than isolated visual

symptoms themselves. The methodology in this study differs

from that previously employed as unselected, consecutive

cases from surveillance in one country were obtained by

applying a careful definition of a ‘‘Heidenhain’’ case. We have

shown that 22 cases have been identified over 15 years out of

a population of approximately 58 million in the United

Kingdom. The more defined inclusion criteria for visual onset

cases used here compared to those employed in the past6 may

have identified a distinct subgroup of cases as reflected in the

genotype findings.

Defining a group of cases with isolated visual symptoms at

onset may aid future recognition of similar cases. By

clarifying the definition of Heidenhain cases we have

identified a group who generally exhibit short illness

duration, myoclonus, and a PRNP codon 129 MM genotype.

As well as aiding diagnosis these findings may contribute to

the understanding of the how abnormal prion protein causes

disease within the central nervous system.


We would like to thank the referring clinicians and the patients and

relatives of patients with CJD for their assistance with the

surveillance work.

Authors’ affiliations

. . . . . . . . . . . . . . . . . . . . .

S A Cooper, K L Murray, C A Heath, R G Will, R S G Knight, The

National Creutzfeldt-Jakob Disease Surveillance Unit, Western General

Hospital, Crewe Road, Edinburgh EH4 2XU, UK

Competing interests: none declared


1 Knight R, Collins S. Human prion diseases: cause, clinical and diagnostic

aspects. In: Rabenau HF, Cinatl J, Doerr HW, eds. Prions. a challenge for

science, medicine and public health systems. Basle: Karger, 2001;68–92).

2 Brown P, Cathala F, Sadowsky D, et al. Creutzfeldt-Jakob disease in France:

II. Clinical characteristics of 124 consecutive verified cases during the decade

1968–1977. Ann Neurol 1979;6:430–7.

3 Vargas ME, Kupersmith MJ, Savino PJ, et al. Homonymous field defect as the

first manifestation of Creutzfeldt-Jakob disease. Am J Ophthalmol


4 Heidenhain A. Klinische und anatomische Untersuchungen u¨ber eine

eigenartige organische Erkrankung des Zentralnervensystems im Praesenium.

Zeitschrift fu¨r die gesamte Neurologie und Psychiatrie 1928;118:49–114.

5 Meyer A, Leigh D, Bagg CE. A rare presenile dementia associated with

cortical blindness (Heidenhain’s syndrome). J Neurol Neurosurg Psychiatry


6 Kropp S, Schulz-Schaeffer WJ, Finkenstaedt M, et al. The Heidenhain variant

of Creutzfeldt-Jakob disease. Arch Neurol 1999;56:55–61.

7 National UK Creutzfeldt-Jakob Disease Surveillance Unit, 2005. Unpublished


8 S-Juan P, Ward HJT, De Silva R, et al. Ophthalmic surgery and Creutzfeldt-

Jakob disease. Br J Ophthalmol 2004;88:446–9.

9 Head MW, Northcott V, Rennison KA, et al. Prion protein accumulation in

eyes of patients with sporadic and variant Creutzfeldt Jakob disease. Invest

Ophthalmol Vis Sci 2003;44:342–6.

10 Parchi P, Giese A, Capellari S, et al. Classification of sporadic Creutzfeldt-

Jakob disease based on molecular and phenotypic analysis of 300 subjects.

Ann Neurol 1999;46:224–33.

Table 1 Visual symptoms at onset (n = 22)

Visual symptom

Number of patients

(n = 22)*

Decreased visual acuity 8

Blurred vision 6

Peripheral visual field defect 2

Visual distortions 3

Impaired colour vision 2

Palinopsia 1

Tunnel vision 1

*One patient experienced both impaired colour vision and visual

distortions at onset.

1342 Cooper, Murray, Heath, et al

on 31 October 2005 Downloaded fromtss



##################### Bovine Spongiform Encephalopathy #####################

Animal Prion Diseases Relevant to Humans (unknown types?)
Thu Oct 27, 2005 12:05

About Human Prion Diseases /
Animal Prion Diseases Relevant to Humans

Bovine Spongiform Encephalopathy (BSE) is a prion disease of cattle. Since 1986, when BSE was recognized, over 180,000 cattle in the UK have developed the disease, and approximately one to three million are likely to have been infected with the BSE agent, most of which were slaughtered for human consumption before developing signs of the disease. The origin of the first case of BSE is unknown, but the epidemic was caused by the recycling of processed waste parts of cattle, some of which were infected with the BSE agent and given to other cattle in feed. Control measures have resulted in the consistent decline of the epidemic in the UK since 1992. Infected cattle and feed exported from the UK have resulted in smaller epidemics in other European countries, where control measures were applied later.

Compelling evidence indicates that BSE can be transmitted to humans through the consumption of prion contaminated meat. BSE-infected individuals eventually develop vCJD with an incubation time believed to be on average 10 years. As of November 2004, three cases of BSE have been reported in North America. One had been imported to Canada from the UK, one was grown in Canada, and one discovered in the USA but of Canadian origin. There has been only one case of vCJD reported in the USA, but the patient most likely acquired the disease in the United Kingdom. If current control measures intended to protect public and animal health are well enforced, the cattle epidemic should be largely under control and any remaining risk to humans through beef consumption should be very small. (For more details see Smith et al. British Medical Bulletin, 66: 185. 2003.)

Chronic Wasting Disease (CWD) is a prion disease of elk and deer, both free range and in captivity. CWD is endemic in areas of Colorado, Wyoming, and Nebraska, but new foci of this disease have been detected in Nebraska, South Dakota, New Mexico, Wisconsin, Mississippi Kansas, Oklahoma, Minnesota, Montana, and Canada. Since there are an estimated 22 million elk and deer in the USA and a large number of hunters who consume elk and deer meat, there is the possibility that CWD can be transmitted from elk and deer to humans. As of November 2004, the NPDPSC has examined 26 hunters with a suspected prion disease. However, all of them appeared to have either typical sporadic or familial forms of the disease. The NPDPSC coordinates with the Centers for Disease Control and state health departments to monitor cases from CWD-endemic areas. Furthermore, it is doing experimental research on CWD transmissibility using animal models. (For details see Sigurdson et al. British Medical Bulletin. 66: 199. 2003 and Belay et al. Emerging Infectious Diseases. 10(6): 977. 2004.)

SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM 1997 TO 2004. SPORADIC CJD CASES TRIPLED, and that is with a human TSE surveillance system that is terrible flawed. in 1997 cases of the _reported_ cases of cjd were at 54, to 163 _reported_ cases in 2004. see stats here;

p.s. please note the 47 PENDING CASES to Sept. 2005

p.s. please note the 2005 Prion D. total 120(8) 8=includes 51 type pending, 1 TYPE UNKNOWN ???

p.s. please note sporadic CJD 2002(1) 1=3 TYPE UNKNOWN???

p.s. please note 2004 prion disease (6) 6=7 TYPE UNKNOWN???


AS implied in the Inset 25 we must not _ASSUME_ that
transmission of BSE to other species will invariably
present pathology typical of a scrapie-like disease.




#################### ####################

STEADY INCREASE IN sCJD in other Countries as well;



MOMS AUTOPSY REPORT DOD 12-14-97 Heidenhain Variant CJD 'confirmed'

Moms death from hvCJD



CJD/BSE aka madcow disease in the U.S., please let me count the Ways$$$

please note, old urls with LYMAN in it, change the word lyman to MADCOW, leave everything else the same.





[[PART 6]]

Subject: Re: 60% of US CJD never tested per Gambetti


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