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
For all author emails, please log on.
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.
Methods
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.
Results
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
Conclusions
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
SNIP...
DISCUSSION
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
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*
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
No comments:
Post a Comment