ORIGINAL ARTICLE
Clinical and prognostic features of Heidenhain variant of Creutzfeldt−Jakob disease: A retrospective case series study
Shi-Lin Yang,Lin-Yuan Zhang,Shu-Fan Zhang,Miao-Yi Zhang,Ming Zhu,Qiang Dong,Qiao-Shu Wang,Xiang Han
First published: 03 May 2022 https://doi.org/10.1111/ene.15380
Shi-Lin Yang and Lin-Yuan Zhang contributed equally to this work.
Funding information:
This work was supported by grants from Shanghai Municipal Health Commission (20204Y0425), the National Natural Science Foundation of China (82001249), Shanghai Sailing Program (20YF1440200), and Natural Science Foundation of Shanghai (20ZR1445400).
Abstract
Background
Heidenhain variant of Creutzfeldt–Jakob disease (CJD) remains a diagnostic challenge in clinical practice. We aimed to describe the clinical and prognostic features of Heidenhain cases, through a case series study.
Methods
We retrospectively reviewed the definite or probable CJD cases admitted to two tertiary referral university hospitals over a decade to identify Heidenhain cases and investigated their survival status by telephone follow-up. Their clinical characteristics, neuroimaging features, electroencephalography (EEG) results, cerebrospinal fluid profiles, and PRNP gene mutations were also analyzed.
Results
Of a total of 85 CJD cases, 20 (24%) Heidenhain cases (11 women [55%]; median age, 64 years [range, 44–72 years]) were identified. The median survival time was 22 weeks (range, 5–155 weeks). The median duration of isolated visual symptoms was 3 weeks (range, 1–12 weeks). The most common early visual symptom was blurred vision (16/20, 80%), followed by diplopia (6/20, 30%). The prevalence significantly increased for complex visual hallucination (p = 0.005) and cortical blindness (p = 0.046) as the disease progressed. The positive rate of serial magnetic resonance images (20/20, 100%) was higher than that of serial EEGs (16/20, 80%). Two patients (2/10, 20%) had pathogenic PRNP mutations, E196A and T188K, respectively. Heidenhain cases with PRNP mutations had significantly longer survival time than those without PRNP mutations (p = 0.047).
Conclusions
Besides blurred vision (80%), diplopia (30%) was also a frequent early visual symptom among Heidenhain cases. Heidenhain phenotype can occur in genetic CJD cases. PRNP mutation status might be an important prognostic factor for Heidenhain cases.
***> We retrospectively reviewed the definite or probable CJD cases admitted to two tertiary referral university hospitals over a decade to identify Heidenhain cases and investigated their survival status by telephone follow-up.
***> Of a total of 85 CJD cases, 20 (24%) Heidenhain cases (11 women [55%]; median age, 64 years [range, 44–72 years]) were identified.
WOW!
SCIENCE NEWS NOV. 18, 2004 / 4:01 PM
Eye procedure raises CJD concerns
By STEVE MITCHELL, Medical Correspondent
snip...
Terry Singletary, whose mother died from a type of CJD called Heidenhain Variant, told UPI health officials were not doing enough to prevent people from being infected by contaminated medical equipment.
"They've got to start taking this disease seriously and they simply aren't doing it," said Singletary, who is a member of CJD Watch and CJD Voice -- advocacy groups for CJD patients and their families.
snip...
Singletary said CDC's assertion that no CJD cases from infected equipment or tissues have been detected since 1976 is misleading.
"They have absolutely no idea" whether any cases have occurred in this manner, he said, because CJD cases often aren't investigated and the agency has not required physicians nationwide report all cases of CJD.
"There's no national surveillance unit for CJD in the United States; people are dying who aren't autopsied, the CDC has no way of knowing" whether people have been infected via infected equipment or tissues, he said.
MONDAY, FEBRUARY 22, 2021
Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease: First Reported Case from East Africa
SUNDAY, NOVEMBER 04, 2018
Heidenhain variant of Creutzfeldt-Jakob disease in a patient who had bovine bioprosthetic valve implantation
WEDNESDAY, OCTOBER 31, 2018
PIG HEART VALVES and Potential Iatrogenic Transmissible Spongiform Encephalopathy TSE Prion Disease in Humans, what if?
SUNDAY, JANUARY 17, 2016
Of Grave Concern Heidenhain Variant Creutzfeldt Jakob Disease
Thursday, December 24, 2015
Revisiting the Heidenhain Variant of Creutzfeldt-Jakob Disease: Evidence for Prion Type Variability Influencing Clinical Course and Laboratory Findings
Article type: Research Article
TUESDAY, JUNE 30, 2015
visual variant of Alzheimer’s disease VVAD vs Heidenhain Variant Creutzfeldt Jakob Disease hvCJD
SUNDAY, SEPTEMBER 25, 2011
Clinical Heidenhain Variant Of Sporadic Creutzfeldt-Jakob Disease (CJD) With Co-occurrence Of Prion Protein Types 1 and 2
Friday, August 20, 2010
Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease With the Co-Occurrence of Two Different Types of Prion Protein
FRIDAY, AUGUST 20, 2010
Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease With the Co-Occurrence of Two Different Types of Prion Protein
see also ;
> All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.
see full text ;
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
WEDNESDAY, SEPTEMBER 9, 2009
Co-existence of scrapie prion protein types 1 and 2 in sporadic Creutzfeldt-Jakob disease: its effect on the phenotype and prion-type characteristics
Co-existence of scrapie prion protein types 1 and 2 in sporadic Creutzfeldt-Jakob disease: its effect on the phenotype and prion-type characteristics.
by: Ignazio Cali, Rudolph Castellani, Amer Alshekhlee, Yvonne Cohen, Janis Blevins, Jue Yuan, Jan P. Langeveld, Piero Parchi, Jiri G. Safar, Wen-Quan Q. Zou, Pierluigi Gambetti Brain : a journal of neurology (4 September 2009)
ABSTRACT
Five phenotypically distinct subtypes have been identified in sporadic Creutzfeldt-Jakob disease (sCJD), based on the methionine/valine polymorphic genotype of codon 129 of the prion protein (PrP) gene and the presence of either one of the two protease K-resistant scrapie prion protein (PrP(Sc)) types identified as 1 and 2. The infrequent co-existence of both PrP(Sc) types in the same case has been known for a long time. Recently, it has been reported, using type-specific antibodies, that the PrP(Sc) type 1 is present in all cases of sCJD carrying PrP(Sc) type 2. The consistent co-occurrence of both PrP(Sc) types complicates the diagnosis and the current classification of sCJD, and has implications for the pathogenesis of naturally occurring prion diseases. In the present study, we investigated the prevalence of PrP(Sc) types 1 and 2 co-occurrence, along with its effects on the disease phenotype and PrP(Sc) strain characteristics, comparatively analysing 34 cases of sCJD, all methionine homozygous at codon 129 of the PrP gene (sCJDMM). To minimize overestimating the prevalence of the sCJDMM cases carrying PrP(Sc) types 1 and 2 (sCJDMM1-2), we used proteinase K concentrations designed to hydrolyse all fragments resulting from an incomplete digestion, while preserving the protease-resistant PrP(Sc) core. Furthermore, we used several antibodies to maximize the detection of both PrP(Sc) types. Our data show that sCJDMM cases associated exclusively with either PrP(Sc) type 1 (sCJDMM1) or PrP(Sc) type 2 (sCJDMM2) do exist; we estimate that they account for approximately 56% and 5% of all the sCJDMM cases, respectively; while in 39% of the cases, both PrP(Sc) types 1 and 2 are present together (sCJDMM1-2) either mixed in the same anatomical region or separate in different regions. Clinically, sCJDMM1-2 had an average disease duration intermediate between the other two sCJDMM subtypes. The histopathology was also intermediate, except for the cerebellum where it resembled that of sCJDMM1. These features, along with the PrP immunostaining pattern, offer a diagnostic clue. We also observed a correlation between the disease duration and the prevalence of PrP(Sc) type 2 and sCJDMM2 phenotypes. The use of different antibodies and of the conformational stability immunoassay indicated that the co-existence of types 1 and 2 in the same anatomical region may confer special conformational characteristics to PrP(Sc) types 1 and 2. All of these findings indicate that sCJDMM1-2 should be considered as a separate entity at this time.
http://www.citeulike.org/user/applebyb/article/5739998
> sCJDMM1-2 should be considered as a separate entity at this time.
Thank you very much !
Saturday, June 13, 2009
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009
http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html
by: Ignazio Cali, Rudolph Castellani, Amer Alshekhlee, Yvonne Cohen, Janis Blevins, Jue Yuan, Jan P. Langeveld, Piero Parchi, Jiri G. Safar, Wen-Quan Q. Zou, Pierluigi Gambetti Brain : a journal of neurology (4 September 2009)
ABSTRACT
Five phenotypically distinct subtypes have been identified in sporadic Creutzfeldt-Jakob disease (sCJD), based on the methionine/valine polymorphic genotype of codon 129 of the prion protein (PrP) gene and the presence of either one of the two protease K-resistant scrapie prion protein (PrP(Sc)) types identified as 1 and 2. The infrequent co-existence of both PrP(Sc) types in the same case has been known for a long time. Recently, it has been reported, using type-specific antibodies, that the PrP(Sc) type 1 is present in all cases of sCJD carrying PrP(Sc) type 2. The consistent co-occurrence of both PrP(Sc) types complicates the diagnosis and the current classification of sCJD, and has implications for the pathogenesis of naturally occurring prion diseases. In the present study, we investigated the prevalence of PrP(Sc) types 1 and 2 co-occurrence, along with its effects on the disease phenotype and PrP(Sc) strain characteristics, comparatively analysing 34 cases of sCJD, all methionine homozygous at codon 129 of the PrP gene (sCJDMM). To minimize overestimating the prevalence of the sCJDMM cases carrying PrP(Sc) types 1 and 2 (sCJDMM1-2), we used proteinase K concentrations designed to hydrolyse all fragments resulting from an incomplete digestion, while preserving the protease-resistant PrP(Sc) core. Furthermore, we used several antibodies to maximize the detection of both PrP(Sc) types. Our data show that sCJDMM cases associated exclusively with either PrP(Sc) type 1 (sCJDMM1) or PrP(Sc) type 2 (sCJDMM2) do exist; we estimate that they account for approximately 56% and 5% of all the sCJDMM cases, respectively; while in 39% of the cases, both PrP(Sc) types 1 and 2 are present together (sCJDMM1-2) either mixed in the same anatomical region or separate in different regions. Clinically, sCJDMM1-2 had an average disease duration intermediate between the other two sCJDMM subtypes. The histopathology was also intermediate, except for the cerebellum where it resembled that of sCJDMM1. These features, along with the PrP immunostaining pattern, offer a diagnostic clue. We also observed a correlation between the disease duration and the prevalence of PrP(Sc) type 2 and sCJDMM2 phenotypes. The use of different antibodies and of the conformational stability immunoassay indicated that the co-existence of types 1 and 2 in the same anatomical region may confer special conformational characteristics to PrP(Sc) types 1 and 2. All of these findings indicate that sCJDMM1-2 should be considered as a separate entity at this time.
http://www.citeulike.org/user/applebyb/article/5739998
> sCJDMM1-2 should be considered as a separate entity at this time.
Thank you very much !
Saturday, June 13, 2009
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009
http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html
Tuesday, July 29, 2008
Heidenhain Variant Creutzfeldt Jakob Disease Case Report
FINAL AUTOPSY DIAGNOSIS
I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.
Heidenhain Variant Creutzfeldt Jakob Disease Case Report
Thursday, January 29, 2009
***Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999–2008 (WARNING TO Neurosurgeons and Ophthalmologists)
Wednesday, August 20, 2008
***Tonometer disinfection practice in the United Kingdom: A national survey
TUESDAY, NOVEMBER 20, 2018
CDC Eyes of CJD patients show evidence of prions concerns for iatrogenic transmission
FRIDAY, SEPTEMBER 06, 2019
Disinfection of Multi-Use Ocular Equipment for Ophthalmological Procedures: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines
SATURDAY, SEPTEMBER 21, 2019
National Variability in Prion Disease–Related Safety Policies for Neurologic Procedures
Friday, September 27, 2019
Prion disease and recommended procedures for flexible endoscope reprocessing – a review of policies worldwide and proposal for a simplified approach
FRIDAY, SEPTEMBER 06, 2019
Disinfection of Multi-Use Ocular Equipment for Ophthalmological Procedures: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines
THURSDAY, SEPTEMBER 26, 2019
Veterinary Biologics Guideline 3.32E: Guideline for minimising the risk of introducing transmissible spongiform encephalopathy prions and other infectious agents through veterinary biologics
Wednesday, September 11, 2019
Is the re-use of sterilized implant abutments safe enough? (Implant abutment safety) iatrogenic TSE Prion
WEDNESDAY, DECEMBER 04, 2019
Three Cases of Creutzfeldt-Jakob Disease with Visual Disturbances as Initial Manifestation
Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM' my Mother
DIVISION OF NEUROPATHOLOGY
University of Texas Medical Branch 114 McCullough Bldg. Galveston, Texas 77555-0785
FAX COVER SHEET
DATE: 4-23-98
TO: Mr. Terry Singeltary @ -------
FROM: Gerald Campbell
FAX: (409) 772-5315 PHONE: (409) 772-2881
Number of Pages (including cover sheet):
Message:
*CONFIDENTIALITY NOTICE*
This document accompanying this transmission contains confidential information belonging to the sender that is legally privileged. This information is intended only for the use of the individual or entry names above. If you are not the intended recipient, you are hereby notified that any disclosure, copying distribution, or the taking of any action in reliances on the contents of this telefaxed information is strictly prohibited. If you received this telefax in error, please notify us by telephone immediately to arrange for return of the original documents.
--------------------------
Patient Account: 90000014-518 Med. Rec. No.: (0160)118511Q Patient Name: POULTER, BARBARA Age: 63 YRS DOB: 10/17/34 Sex: F Admitting Race: C
Attending Dr.: Date / Time Admitted : 12/14/97 1228 Copies to:
UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report
FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858
Autopsy NO.: AU-97-00435
AUTOPSY INFORMATION: Occupation: Unknown Birthplace: Unknown Residence: Crystal Beach Date/Time of Death: 12/14/97 13:30 Date/Time of Autopsy: 12/15/97 15:00 Pathologist/Resident: Pencil/Fernandez Service: Private Restriction: Brain only
FINAL AUTOPSY DIAGNOSIS
I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.
please see full text here ;
TUESDAY, MARCH 29, 2022
***> OIE Agent causing chronic wasting disease (CWD) TSE Prion of Cervid <***
Tuesday, May 31, 2022
89th General Session of the World Assembly of OIE Delegates image for WOAH General Summit 2022 Chronic Wasting Disease CWD TSE Prion Discussions and Concerns
(this link is good and safe from my one of my tse prion blogs, My Norton has chosen wrongly to mark it as suspicious...terry)
TUESDAY, MAY 31, 2022
USA Bovine Spongiform Encephalopathy BSE: description of typical and atypical cases
SUNDAY, MAY 08, 2022
USA National Prion Disease Pathology Surveillance Center Surveillance Update April 11th, 2022
TUESDAY, MAY 24, 2022
Texas Creutzfeldt Jakob Disease CJD TSE Prion Update Singeltary FOIA Request Received May 23, 2022
TUESDAY, MAY 10, 2022
Concordance of CSF RT-QuIC across the European Creutzfeldt-Jakob Disease surveillance network
TUESDAY, APRIL 05, 2022
Incidence of Creutzfeldt-Jakob Disease in the United States 1993-2014
MONDAY, JANUARY 31, 2022
Validation of Revised International Creutzfeldt-Jakob Disease Surveillance Network Diagnostic Criteria for Sporadic Creutzfeldt-Jakob Disease Singeltary Comment Submission
Friday, March 11, 2022
Prevalence of Surgical Procedures at Symptomatic Onset of Prion Disease
WEDNESDAY, FEBRUARY 02, 2022
Understanding the nature of PrP found in Appendix tissues in the UK population
Friday, November 19, 2021
Safe laboratory management of prions and proteopathic seeds and Prion Poker, are you all in?
FRIDAY, DECEMBER 24, 2021
***> Creutzfeldt Jakob Disease CJD TSE Prion Update December 25, 2021 <***
TUESDAY, OCTOBER 26, 2021
Sporadic Creutzfeldt-Jakob Disease in a Very Young Person Singeltary Reply 2021
Saturday, December 18, 2021
Direct neural transmission of vCJD/BSE in macaque after finger incision
Tuesday, November 30, 2021
Second death in France in a laboratory working on prions
Second lab worker with deadly prion disease prompts research pause in France
A lab worker died of prion disease in 2019, nine years after a lab accident.
BETH MOLE - 7/29/2021, 5:16 PM
A 2020 paper published in the New England Journal of Medicine left little doubt that Jaumain had been infected on the job. She had variant CJD, but since Europe’s ‘mad cow’ outbreak ended after 2000 and the disease virtually disappeared, the paper said it was virtually impossible for someone her age in France to contract food-borne vCJD.
Science also said two independent reports – one by government inspectors – had found no safety violations at the lab where Jaumain worked. The press release also noted that the inspectors concluded there was “the presence of a risk control culture within the research teams”. The Jaumain family’s lawyer called the neutrality of the reports into question, however.
At the same time, the government inspectors’ report also revealed that there had been at least 17 accidents among the 100 or so scientists and technicians in France working with prions in the previous decade, raising concerns about how effective this risk control culture is. Five of these occurred when workers “stabbed or cut themselves with contaminated syringes or blades”.
Wednesday, July 28, 2021
France issues moratorium on prion research after fatal brain disease strikes two lab workers
Friendly fire, pass it forward, they call it iatrogenic cjd, or what i call 'tse prion poker', are you all in $$$
all iatrogenic cjd is, is sporadic cjd, before the iatrogenic event is discovered, traced back, proven, documented, put into the academic domain, and then finally the public domain, this very seldom happens, thus problem solved, it's all sporadic cjd...
SATURDAY, AUGUST 01, 2020
Sporadic Creutzfeldt-Jakob Disease among Physicians, Germany, 1993–2018 high proportion of physicians with sCJD were surgeons
SUNDAY, JULY 19, 2020
Joseph J. Zubak Orthopaedic surgeon passed away Monday, July 6, 2020, Creutzfeldt-Jakob Disease (CJD)
Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure
Variant Creutzfeldt–Jakob disease was identified in a technician who had cut her thumb while handling brain sections of mice infected with adapted BSE 7.5 years earlier. The long incubation period was similar to that of the transfusion-transmitted form of the disease.
THURSDAY, JULY 02, 2020
Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure
Terry S. Singeltary Sr.