Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease With the Co-Occurrence of Two Different Types of Prion Protein
Ignazio Cali1, Gianfranco Puoti1, Janis Blevins1, Adeela Alizai2, Pierluigi Gambetti1. 1Case Western Reserve University; 2Temple University Hospital
Sporadic Creutzfeldt-Jacob disease (sCJD) is a rare neurodegenerative disorder classified into five distinct phenotypes based on i) the polymorphic methionine (M)/valine (V) genotype at codon 129, and ii) detection of either type 1 or type 2 of the protease-resistant prion protein (PrPres) (Parchi et al., Ann Neurol 1999; Gambetti et al., Br Med Bull 2003). Sporadic CJDMM1, the most common CJD subtype, is the only CJD subtype that includes the Heidenhain variant (HsCJD), a condition characterized by early and prominent visual deficits associated with the preferential involvement of the occipital cortex (Kropp et al., Arch Neurol 1999). The histopathological phenotype of HsCJD is indistinguishable from that of sCJDMM1. Recently, we described a group of sCJD cases identified as sCJDMM1-2 in which both PrPres types were found to co-exist in the same brain (Cali et al., Brain 2009). In the present study, we investigated whether the Heidenhain clinical phenotype is present in sCJDMM1-2. To date, the screening of clinical histories from 59 sCJDMM1-2 patients that were received at the National Prion Disease Pathology Surveillance Center between 1998 and 2009 has led to the identification of 8 (14%) HsCJDMM1-2 subjects. The detailed study of two HsCJDMM1-2 cases shows that the immunohistopathological features as well as PrPres type determined in different brain locations are consistent with the features of the sCJDMM1-2 subtype (Cali et al., Brain 2009). The visual cortex is severely affected in both cases and is found to carry both PrPres types (Kropp et al., Arch Neurol 1999). To our knowledge, this is the first finding of HsCJD in sCJDMM1-2 and indicates that the presence of even relatively large amounts of PrPres type 2 does not impede the expression of HsCJD.
(Supported by, NIH AG-14359, CDC UR8/CCU515004 and Charles S. Britton Foundation; the CDC Foundation).
Subject: Creutzfeldt-Jakob Disease Presenting with Confusion and Visual Disturbance and hvCJD i.e. Heidenhain Variant CJD case report
Date: July 18, 2007 at 12:31 pm PST
TO The Editor-in-Chief,
Archives of Iranian Medicine, Editorial Office,
Academy of Medical Sciences of I.R.Iran,
P.O. Box: 19395-4655, Tehran, Iran.
TSS submission to the following study, comments and submission to follow ;
Arch Iranian Med 2007; 10 (3): 397 – 400 Archives of Iranian Medicine, Volume 10, Number 3, July 2007 397
Creutzfeldt-Jakob Disease Presenting with Confusion and Visual Disturbance
Masoud Nikanfar MD*, Mehdi Farhoudi MD•**, Monireh Halimi MD***, Fereidoon Ashrafian-Bonab MD***, Kaveh Mehrvar MD†
Creutzfeldt-Jakob disease is increasingly being reported in the last three decades as a result of increased awareness for the disease. Various studies have reported an annual incidence of 0.5 – 1.5 cases of Creutzfeldt-Jakob disease per million of general population. However, in our country, like other developing countries, the disease is still under-reported. Herewith, we described our clinical experience with an autopsy-proven case of Creutzfeldt-Jakob disease.
Archives of Iranian Medicine, Volume 10, Number 3, 2007: 397 – 400.
Introduction
Prions can cause neurodegenerative diseases that have long incubation periods and progress inexorably once the clinical symptoms appear. So far, five human prion diseases have been recognized including Kuru, Creutzfeldt-Jakob disease (CJD), variant Creutzfeldt-Jakob disease (vCJD also known as new variant CJD), Gerstmann-Straussler-Scheinker (GSS) syndrome, and fatal familial insomnia (FFI).1, 2 Bovine spongiform encephalopathy (BSE), one of prion infections affecting animals, was responsible for a more widespread public attention with its possible link to vCJD.3, 4 These human prion diseases share certain common neuropathologic features including neuronal loss, proliferation of glial cells, absence of an inflammatory response, and the presence of small vacuoles within the neutrophils, which produces a spongiform appearance. The current theory is that prion diseases are associated with the accumulation of an abnormal form of a host cell protein, the so-called “prion protein” (PrP).5 This paper describes the clinical experience with an autopsy-proven case of CJD managed at the Department of Neurology of Razi Hospital, Tabriz, North-West of Iran.
Case Report
A 71-year-old woman referred to our hospital on May 3, 2004 with a one and a half-month history of visual symptoms accompanied by transient confusion and disorientation and dystonic posture in her right arm. Her family members reported that she had transient attacks of agitation, hallucinations, and confusional state with a duration of about 15 minutes. After each attack, she became normal without any memories of attacks. Gradually, the frequency of these attacks increased. Meanwhile, she complained of transient visual problems such as macropsy, micropsy, blurred vision, and color vision disturbance. She had also transient dystonic posture in her right arm. Before admission, she also developed a mild left-sided hemiparesis. She was visited by a psychiatrist who prescribed haloperidol and clonazepam with no beneficial effect; her condition became worse progressively. On admission, she had mild confusion, and headache, and vertigo. General examination was normal. In neurologic examination, she had a left hemiparesis, left central hemifacial weakness, no in her right arm. All biochemical laboratory tests of plasma and urine were normal. Cerebrospinal fluid analysis was normal. In brain computed tomography (CT) and magnetic resonance imaging (MRI), multiple lacunar infarctions and senile atrophy were reported. In her first electroencephalogram (EEG), generalized slow sharp waves appeared in all montages (Figure 1A). The patient’s general condition and level of consciousness progressively deteriorated during hospitalization. After 15 days, she developed myoclonie seizures — first in her right arm and then generalized. In the next EEG, there was progressive slowness and periodic sharp waves. In her last EEG, slow and disorganized background activity that was interrupted by repetitive discharges of large sharp waves in all montages — about one cycle per second — were recorded (Figure 1B, C). She was intubated and finally on June 9, 2004, she died of sepsis. In pathologic study performed two days after death, the spongiform encephalopathy was documented. Histopathologic examination revealed no Kuru plaque in Congo red and PAS staining. No inflammatory infiltration was present (Figure 2). Discussion
snip...full text ;
Greetings Editor-in-Chief et al Archives of Iranian Medicine, Editorial Office,
I kindly wish to submit the following to the Authors of the above study, and to the Archives of Iranian Medicine, Editorial Office, Academy of Medical Sciences of I.R.Iran.
THESE symptoms are very similar of which my mother had i.e. Heidenhain Variant Creutzfeldt Jakob Disease. I can remember her and her right arm, and she would stretch her arm against the wall, ...... strange reading this. also, clinical onset of disease to death similar, approx. 12+ weeks, and of course my mother went blind at onset, again, with similar symptoms. ODD, they don't even mention the Heidenhain Variant of CJD, one of six documented phenotypes of the sporadic CJDs to date, with 'unknown' phenotype of Sporadic CJD growing in USA (14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins). ...TSS
The Heidenhain Variant of Creutzfeldt-Jakob Disease
Stefan Kropp, MD; Walter J. Schulz-Schaeffer, MD; Michael Finkenstaedt, MD; Christian Riedemann, MD; Otto Windl, PhD; Bernhard J. Steinhoff, MD; Inga Zerr, MD; Hans A. Kretzschmar, MD; Sigrid Poser, MD
Arch Neurol. 1999;56:55-61.
Objective To investigate whether typical neuropathological and radiological findings can be identified in patients with the clinical diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease (CJD).
Design Case study. The clinical symptoms, neuropathological findings, electroencephalograms, magnetic resonance images, and cerebrospinal fluid samples of 14 Heidenhain cases were evaluated. Neuropathological changes were compared with those in a group of 14 patients with ataxia as the leading clinical sign.
Setting A university hospital, base of the German National Creutzfeldt-Jakob Disease Surveillance Study.
Patients Medical records of 169 neurologically examined patients with prospectively classified and neuropathologically confirmed CJD were analyzed.
Main Outcome Measure Difference in neuropathological and radiological findings between patients with the Heidenhain variant and other patients with CJD.
Results Of 169 patients with confirmed CJD, 20% showed characteristic clinical findings such as blurred vision, visual field restriction, metamorphopsia, or cortical blindness. Disease course of the Heidenhain group, as compared with the group of all patients with definite CJD, was significantly shorter (5.7 months vs 7.5 months; P=.02, t test). Neuropathological examination of patients with the Heidenhain variant showed most pronounced changes in the occipital lobe but less damage in the cingulate gyrus and basal ganglia compared with 14 patients with CJD who had ataxia as the leading clinical sign. Eleven (92%) of 12 genetically analyzed Heidenhain cases were homozygous for methionine at codon 129 of the prion protein gene (PRNP). In 9 of 9 cases, the 14-3-3 protein was present. In 7 (78%) of 9 cases, the level of neuron-specific enolase was elevated, with a concentration above 35 ng/mL. Periodic sharp-wave complexes were observed in 11 (78%) of the 14 cases. In 7 (63%) of 11 patients, magnetic resonance images showed symmetric hyperintensities in the basal ganglia in the T2- and proton-weighted sequence. In 4 of 11 cases the T2- and proton density–weighted images showed a pronounced signal increase confined to the gray matter of the occipital and visual cortex. Isolated atrophy of the visual cortex was noticeable in 2 of 11 cases.
Conclusions The clinical presentation of the Heidenhain variant of CJD was shown to correlate with the neuropathological findings of gliosis and nerve cell loss. In patients with visual disorders of unclear origin and signs of dementia, the differential diagnosis of a Heidenhain variant of CJD must be taken into consideration.
From the Departments of Neurology (Drs Kropp, Riedemann, Zerr, and Poser), Neuropathology (Drs Schulz-Schaeffer, Windl, and Kretzschmar), Neuroradiology (Dr Finkenstaedt), and Clinical Neurophysiology (Dr Steinhoff), Georg-August-University Göttingen, Göttingen, and the MR/CT Institute Hamburg, Hamburg (Dr Finkenstaedt), Germany.
Creutzfeldt-Jakob Disease Presenting with Visual Blurring, Diplopia and Visual Loss: Heidenhain’s Variant
K E Lee,*MBBS, MRCP (UK), N K Loh,**MBBS, MRCP (UK), M Med (Int Med), A K Y Tan,***FAMS, MBBS, MRCP (UK), W L Lee,† MBBS (Hons), MRCP (UK), M Med (Paed), H T L Tjia,‡ FAMS, MBBS, M Med (Int Med)
http://www.annals.edu.sg/pdf_nov98/leeke.pdf
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 ;
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
(hmmm, this is getting interesting now...TSS)
Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,
see also ;
All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
<< Home