Tuesday, June 30, 2015

visual variant of Alzheimer’s disease VVAD vs Heidenhain Variant Creutzfeldt Jakob Disease hvCJD

Subject: visual variant of Alzheimer’s disease VVAD vs Heidenhain Variant Creutzfeldt Jakob Disease hvCJD


Research article


Visual signs and symptoms in patients with the visual variant of Alzheimer disease


Pierre-François Kaeser1, Joseph Ghika2 and François-Xavier Borruat1*


* Corresponding author: François-Xavier Borruat francois.borruat@fa2.ch


Author Affiliations


1 Department of Ophthalmology, University of Lausanne, Jules Gonin Eye Hospital, Avenue de France 15, Lausanne, CH-1004, Switzerland


2 Department of Neurology, University of Lausanne, CHUV, Lausanne, Switzerland


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BMC Ophthalmology 2015, 15:65 doi:10.1186/s12886-015-0060-9


The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2415/15/65


Received: 11 July 2014 Accepted: 19 June 2015 Published: 30 June 2015


© 2015 Kaeser et al.


This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.


Abstract Background


Prominent visual symptoms can present in the visual variant of Alzheimer’s disease (VVAD). Ophthalmologists have a significant role to play in the early diagnosis of VVAD.




We retrospectively reviewed the files of ten consecutive patients diagnosed with VVAD. All patients had a full neuro-ophthalmologic examination, a formal neurological and neuro-psychological testing, and cerebral MRI to confirm diagnosis. In addition, functional neuroimaging was obtained in seven patients.




The common primary symptom at presentation with all patients was difficulty with near vision (reading difficulty n = 8, “visual blur” in near vision n = 2), and difficulty writing (n = 3). Following assessment, impaired reading and writing skills were evident in 9/10 and 8/10 patients respectively. Median distance visual acuity was 20/25 and at near the median visual acuity was J6. Partial homonymous visual field defect was detected in 80 % (8/10) of the patients. Color vision was impaired in all patients when tested with Ishihara pseudoisochromatic plates, but simple color naming was normal in 8/9 tested patients. Simultanagnosia was present in 8/10 patients. Vision dysfunction corresponded with cerebral MRI findings where parieto-occipital cortical atrophy was observed in all patients. PET scan (5 patients) or SPECT (2 patients) revealed parieto-occipital dysfunction (hypometabolism or hypoperfusion) in all 7 tested patients




Visual difficulties are prominent in VVAD. Dyslexia, incomplete homonymous hemianopia, preserved color identification with abnormal color vision on Ishihara, and simultanagnosia were all symptoms observed frequently in this patient series. Ophthalmologists should be aware of the possibility of neurodegenerative disorders such as VVAD in patients with unexplained visual complaints, in particular reading difficulties.


Keywords: Alzheimer; Reading difficulty; Homonymous hemianopsia; Simultanagnosia



Journal of Neuro-Ophthalmology: March 2014 - Volume 34 - Issue 1 - p 4–9 doi: 10.1097/WNO.0b013e3182916155


Original Contribution


The Heidenhain Variant of Creutzfeldt-Jakob Disease—A Case Series


Parker, Sarah E. MD; Gujrati, Meena MD; Pula, John H. MD; Zallek, Sarah N. MD; Kattah, Jorge C. MD


Supplemental Author Material Collapse Box Abstract Background: To study the neuro-ophthalmologic characteristics of patients with the visual variant of Creuztfeldt-Jakob disease (CJD) predominantly affecting the occipital and parietal lobes, known as the Heidenhain variant (HvCJD). The initial symptoms and findings may overlap with other posterior cerebral degenerative disorders. We reviewed our experience with HvCJD including clinical course and results of neuroimaging, electroencephalography (EEG), and cerebrospinal fluid (CSF) studies. Neuropathological postmortem findings were reviewed when available to confirm the clinical impression.


Methods: Retrospective study of HvCJD patients examined in the past 15 years at a single tertiary referral university hospital. Rapid rate of visual and neurological deterioration and abnormal diffusion-weighted imaging (DWI) were characteristic for HvCJD.


Results: Three patients displayed abnormalities in DWI, EEG, and CSF and had rapid clinical progression, leading to a clinical diagnosis of HvCJD. None underwent diagnostic cerebral biopsy. In 2 patients, the diagnosis of sporadic CJD was confirmed by postmortem neuropathologic, immunohistochemical, and genetic studies.


Conclusions: The gold standard for establishing the diagnosis of HvCJD is based on the characteristic histopathologic findings and molecular confirmation. Concern with potential iatrogenic CJD, related to surgical instrumentation or operating room prion contamination, has limited the availability of confirmatory brain biopsy. Our case series illustrates how the combination of clinical neuroimaging and EEG studies and 14:3:3 protein and other neuronal protein marker levels can lead to the diagnosis of HvCJD. Immunohistochemical analysis and genetic testing at a specialized prion research center will assist in identifying the sporadic variant and genetic forms of CJD.


© 2014 by North American Neuro-Ophthalmology Society






In 1998, Benson et al (11) described PCD as an unusual neurodegenerative disorder involving the posterior parietal and occipital lobes. Neuropathologic findings in PCD include senile plaques and neurofibrillary tangles, typical for Alzheimer disease in the majority of cases (7–9). Less frequently, subcortical gliosis as a variant of Pick disease and spongiform changes, neuronal loss and gliosis due to prion infection were reported (9). However, epidemiologic data are lacking. Clinical findings in PCD and HvCJD include combinations of visual field defects, cortical blindness, dyschromatopsia, visual agnosia, alexia, prosopagnosia, palinopsia, optical anosognosia, Balint and Gertsmann syndrome (12–16). Between 1998 and 2012, we evaluated 10 patients with PCD; 3 had sporadic HvCJD who were followed until their death. We are uncertain about the etiology in the remaining 7 patients who developed either a slowly progressive dementia (evolving over several years) and are still alive or were lost to follow-up. The largest published series of the HvCJD included 34 pathologically confirmed cases over a 51-month period (6). This study from the University of Göttingen in Germany is the geographic base of the “German National Creutzfeldt-Jakob Disease Surveillance Study.” Clinical findings were available in 25 cases and consisted of a combination of visual loss and higher visual deficits as found in previous studies. The rate of neurological deterioration was faster in the HvCJD group compared with other CJD variants and did not correlate with location or extent of neuropathologic findings. Homozygosis for methionine in codon 129, identified in 2 of our patients, was noted as a possible genetic indicator of an aggressive clinical course. We evaluated our patients by applying the diagnostic criteria used by Kropp et al (6) and endorsed by the World Health Organization (Table 1). Neuroimaging findings showed subtle increased intensity in the parieto-occipital region on T2 and FLAIR images only in case 2. Yet all 3 patients had striking visual deficits on examination. Therefore, HvCJD should be considered in any patient with visual field loss and a normal MRI or when imaging abnormalities fail to explain the clinical findings (15). Our imaging protocol included diffusion-weighted imaging (DWI) sequences (12,16). Restricted diffusion involving the gyri of the parieto-occipital cortex was observed in 2 of our cases (Fig. 3). The third patient (Case 2) was evaluated before the incorporation of DWI sequences in the MRI protocol at our institution. DWI was the most helpful ancillary test supporting the diagnosis of HvCJD, and to our knowledge, other PCD variants usually are not associated with DWI changes. Graphic Table 1


Initial EEG results showed nonspecific focal or generalized slowing, but follow-up EEG showed periodic sharp waves (Fig. 2) characteristic of CJD in later stages, correlating with the presence of myoclonus. SPECT scanning confirmed occipital hypoperfusion in one of our cases and should be part of PCD evaluation. SPECT largely has been replaced by PET that demonstrates focal cerebral hypometabolism in PCD (13,17). An important characteristic observation suggesting HvCJD in our patients was rapid clinical deterioration. The initial HvCJD diagnosis in Case 1 was supported by progressive neurological deterioration over 10 weeks after the onset of visual symptoms. Our other 2 patients were evaluated at an earlier stage of disease and were scheduled for additional testing over several days. Both patients failed to keep their 2-week follow-up appointments, and contact with their families revealed that they experienced rapid neurological deterioration with inability to perform activities of daily living. This prompted us to perform house calls to complete neurological evaluation and discussion with the family. Markers of massive neuronal loss (14:3:3 protein and neuronal-specific enolase) were elevated in 2 of our cases. These markers are deemed highly specific and sensitive (1). Their value must be interpreted with caution in individual cases, as increased neuronal protein levels (false positives) may be found in other rapidly progressive dementias and potential PCD mimics including autoimmune and paraneoplastic encephalitis, nonconvulsive status epilepticus, intravascular lymphoma, and vasculitis (2,5). Although characteristic histopathology of CJD remains the gold standard in establishing the diagnosis, the risk of instrument or surgical suite prion contamination during brain biopsy has limited the availability of brain biopsy (10). Until a specific serum or CSF prion marker is available, the premortem diagnosis of HvCJD in a patient with PCD continues to rely on close clinical monitoring, neuroimaging testing, serial EEG, and elevated CSF markers (18,19). We strongly recommend that specimens be sent to the National Prion Research Center at Case Western Reserve University in Cleveland, OH, and similar prion research centers for confirmatory, cerebral histopathology, immunohistochemical staining of abnormal protease-resistant prion protein, and genetic testing. This testing protocol establishes the diagnosis of sporadic, variant, and genetic forms of CJD and hopefully will prevent delay in establishing the correct diagnosis (20). In vitro, anti-prion agents have been found effective in controlling prion growth and progression. Unfortunately, these agents have failed to cure or slow CJD infection in humans (21–23).



P07 Behavioral Neurology: Aging and Dementia MRI More Useful Than PET for Diagnosis of Heidenhain Variant Creutzfeldt-Jacob Disease (P07.163)


Jonathan Beary1 and Edward Manno2 1 General Neurology, Neurological Institute Cleveland Clinic Cleveland OH 2 Cerebrovascular Neurology, Neurological Institute Cleveland Clinic Cleveland OH


OBJECTIVE: To demonstrate that MRI detection of subtle focal cortical abnormalities can prove more useful than positron emission tomography (PET) in the diagnosis of Heidenhain variant Creutzfeldt-Jakob Disease (hvCJD).


BACKGROUND: hvCJD is a rare neurodegenerative, spongiform encephalopathy with an aggressive clinical course. PET brain imaging has been reported to detect focal cortical abnormalities in hvCJD with greater sensitivity than MRI. However, because PET is both more costly and less accessable than MRI, early diagnosis of this disease and subsequent prognostication may be unnecessarily delayed. The reliability of MRI over PET in detecting isolated occipital cortical changes suggestive of hvCJD has not been well studied.


DESIGN/METHODS: This is a case report with relevent neuroimaging review.


RESULTS: A 70 year-old right-handed male experienced visual hallucinations and visuospatial disorientation with worsening ataxia followed by progressive anterograde amnesia and cortical blindness. Six weeks later he was comatose with startle myoclonus. A sharply-contoured periodic pattern was evident posteriorly on continuous EEG monitoring with brain MRI revealing subtle bilateral occipital cortical diffusion restriction. PET brain imaging showed diffuse non-focal cortical hypometabolism. Both cerebrospinal fluid (CSF) 14-3-3 and tau protein studies were positive. EEG progressed to refractory status epilepticus and the patient died four days later. ***The presence of abnormal brain protease-resistant prion protein and MM1 genotype at autopsy supported the diagnosis of hvCJD.


CONCLUSIONS: hvCJD should be considered in patients with rapid-onset idiopathic visual disturbance and dementia. When combined with EEG and CSF analysis, isolated MRI visual cortex diffusion restriction is suggestive of this ultra-aggressive prion variant. MRI is able to efficiently facilitate valuable prognostication early in hvCJD and can be more useful than costly PET imaging.


Disclosure: Dr. Beary has nothing to disclose. Dr. Manno has nothing to disclose.



Resident and Fellow Section


Mystery Case:


Heidenhain variant of Creutzfeldt-Jakob disease


Matthew Kalp, MD, PhD and Christopher H. Gottschalk, MD


A 75-year-old woman complained of a “scrambled brain” for 1 month. She endorsed poor depth perception and an inability to construct “mental maps” of her home and the grocery store. Examination revealed impaired delayed recall, ocular apraxia, optic ataxia, and simultanagnosia (Bálint syndrome). Diffusion-weighted MRI demonstrated cortical hyperintensities in the occipital lobes extending into the right parietal lobe, suggesting spongiform encephalopathy (figure). The 14-3-3 protein and elevated neuron-specific enolase were detected in the CSF. The patient was diagnosed with the Heidenhain variant of Creutzfeldt-Jakob disease.1 Early in the disease, this subgroup of patients with prion disease have isolated visual, not cognitive, symptoms and may be referred to an ophthalmologist.2


© 2014 American Academy of Neurology



Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'


DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114 McCullough Bldg. Galveston, Texas 77555-0785




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):






Saturday, June 27, 2015


A Naturally Occurring Bovine Tauopathy Is Geographically Widespread in the UK


Research Article



Singeltary Comment;


IBNC Tauopathy or TSE Prion disease, it appears, no one is sure


Posted by flounder on 27 Jun 2015 at 16:29 GMT




Thursday, January 2, 2014


CWD TSE Prion in cervids to hTGmice, Heidenhain Variant Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ???


kind regards, terry

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