Friday, November 03, 2017

First case of V180I rare mutation in a Brazilian patient with Creutzfeldt-Jakob disease

First case of V180I rare mutation in a Brazilian patient with Creutzfeldt-Jakob disease

Ricardo Krause Martinez de Souza , MD, Nalini Drieli Josviak , PhD, Meire Silva Batistela , PhD, Paulo Sergio Faro Santos , MD, Michele Christine Landemberger , PhD & Ricardo Ramina , MDPhD Page 00 | Received 28 Aug 2017, Accepted 24 Oct 2017, Accepted author version posted online: 02 Nov 2017 Download citation http://dx.doi.org/10.1080/19336896.2017.1397869 

ABSTRACT

Here, we report the first case of V180I rare mutation in a Brazilian woman whose clinical condition started with memory impairment for recent events and insomnia with 2 months of evolution, without any other alterations in neurological examination. Both the electroencephalogram (EEG) and the routine biochemical examination of cerebrospinal fluid (CSF) were normal. CSF 14-3-3 protein search was positive. Magnetic resonance imaging (MRI) of the encephalon showed findings suggestive of Creutzfeldt-Jakob disease, confirmed by sequencing of PRNP gene that reveal V180I mutation also homozygosity for methionine at codon 129 (M129M).

KEYWORDS: Creutzfeldt-Jakob disease, V180I mutation, V180I/129M haplotype Disclaimer

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Author information

Ricardo Krause Martinez de Souza Dr. Ricardo Krause Martinez de Souza: ricardo.neurologia@gmail.com Nalini Drieli Josviak Dr. Nalini D. Josviak: drinaly@gmail.com Meire Silva Batistela Dr. Meire S. Batistela: mebatistela@gmail.com Paulo Sergio Faro Santos Dr. Paulo S. F. Santos: dr.paulo.faro@gmail.com Michele Christine Landemberger Dr. Ricardo Ramina: ramina@inc-neuro.com.br Ricardo Ramina Dr. Michele C. Landemberger: mchristine@cipe.accamargo.org.br




Case Report An autopsy case of Creutzfeldt-Jakob disease with a prion protein gene codon 180 mutation presenting with pathological laughing and an exaggerated startle reaction 

Authors Yasushi Iwasaki, Keiko Mori, Masumi Ito, Akio Akagi, Maya Mimuro, Tetsuyuki Kitamoto, Mari Yoshida First published: 13 July 2017Full publication history DOI: 10.1111/neup.12399 View/save citation Cited by (CrossRef): 0 articles Check for updates Citation tools Abstract

A 78-year-old Japanese woman presented with slow progressive disorientation and memory disturbances. Pathological laughing was observed at an early disease stage and continued for several months. Around the same time, the patient began to exhibit an exaggerated startle reaction and mild myoclonus. The pathological laughing and startle reaction disappeared before the patient reached an akinetic mutism state approximately 16 months after symptom onset. MRI showed extensive hyperintensity of the cerebral cortex and striatum on diffusion-weighted images, and swelling in the cerebral cortex on T2-weighted and fluid attenuated inversion recovery images. A prion protein (PrP) gene analysis revealed a V180I mutation with methionine homozygosity at codon 129. Neuropathological examination showed extensive spongiform changes with characteristic various-sized and non-confluent (VaSNoC) vacuoles in the cerebral neocortex and striatum. Gliosis and hypertrophic astrocytosis were generally mild in character. Neurons were relatively preserved in number. We believe that pathological laughing and an exaggerated startle reaction are possible pathognomonic findings of V180I genetic Creutzfeldt-Jakob disease. Based on the pathological findings of the present case, the presence of the VaSNoC-type spongiform changes with relative preservation of the neurons in the cerebral cortex and a lack of apparent brainstem involvement are associated at least in part with the pathological laughing and startle reaction.

A 78-year-old Japanese woman presented with slow pro-gressive disorientation and memory disturbances. Patholog-ical laughing was observed at an early disease stage andcontinued for several months. Around the same time, thepatient began to exhibit an exaggerated startle reactionand mild myoclonus. The pathological laughing and startlereaction disappeared before the patient reached an akineticmutism state approximately 16 months after symptom onset.MRI showed extensive hyperintensity of the cerebral cortexand striatum on diffusion-weighted images, and swelling inthe cerebral cortex on T2-weighted and fluid attenuatedinversion recovery images. A prion protein (PrP) gene anal-ysis revealed a V180I mutation with methionine homozygos-ity at codon 129. Neuropathological examination showedextensive spongiform changes with characteristic various-sized and non-confluent (VaSNoC) vacuoles in the cerebralneocortex and striatum. Gliosis and hypertrophicastrocytosis were generally mild in character. Neurons wererelatively preserved in number. We believe that pathologicallaughing and an exaggerated startle reaction are possible pa-thognomonic findings of V180I genetic Creutzfeldt-Jakobdisease. Based on the pathological findings of the presentcase, the presence of the VaSNoC-type spongiform changeswith relative preservation of the neurons in the cerebralcortex and a lack of apparent brainstem involvement areassociated at least in part with the pathological laughingand startle reaction

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative dis-ease that can be classified as sporadic (idiopathic), genetic(hereditary) or acquired (inherited).1–3Genetic CJD(gCJD) can be further classified based on mutation of theprion protein (PrP) gene.2,3Individual PrP mutations showvariable geographic distribution and frequency.3Although5–10% of CJD cases show an autosomal-dominantinheritance pattern,3some gCJD variants occur sporadicallyin patients without relevant family history because of denovo mutations, incomplete genetic penetrance, or the mis-diagnosis of affected family members.3A majority ofsporadic CJD cases exhibit characteristic clinical findingsincluding rapid progressive dementia, myoclonus andperiodic sharp wave complexes (PSWCs) on electroenceph-alography (EEG);1,2,4–6in contrast, gCJD cases frequentlyfail to exhibit one or more of these hallmarks dependingon the type of mutation.2,6CJD with point mutation ofvaline to isoleucine at codon 180 of PrP (V180I gCJD) isthe most frequent form of gCJD in Japan,7whereas thisvariant is extremely rare in Europe and North America.3According to several previous reports,1,8–10the clinicalfeatures of V180I gCJD are relatively uniform but differfrom those of sporadic CJD as follows: (i) an older ageof onset; (ii) prolonged disease duration with a slowercourse of progression; (iii) cerebral cortical symptomssuch as aphasia, apraxia and hemiparesis in the earlystage of disease; (iv) a lower positive rate of brain-specificproteins such as neuron-specific enolase, total tau protein,and 14–3-3 protein in cerebrospinal fluid (CSF); (v) theabsence of PSWCs on EEG throughout the disease... 

Correspondence: Yasushi Iwasaki, M.D., Ph.D., Department ofNeuropathology, Institute for Medical Science of Aging, AichiMedical University, 1-1 Yazakokarimata, 480-1195 Nagakute, Japan.Email: iwasaki@sc4.so-net.ne.jpReceived 04 March 2017; revised 16 June 2017 and accepted17 June 2017.© 2017 Japanese Society of Neuropathologydoi:10.1111/neup.12399Neuropathology 2017; 








TUESDAY, SEPTEMBER 27, 2016 

Classical Scrapie Diagnosis in ARR/ARR Sheep in Brazil 

Acta Scientiae Veterinariae, 2015. 43(Suppl 1): 69.
 

MONDAY, MAY 5, 2014 

Brazil BSE Mad Cow disease confirmed OIE 02/05/2014


WEDNESDAY, JANUARY 29, 2014

Another Suspect case of Creutzfeldt-Jakob disease investigated in Brazil


THURSDAY, SEPTEMBER 26, 2013 

Brazil evaluate the implementation of health rules on animal by-products and derived products SRM BSE TSE PRION aka MAD COW DISEASE


Friday, December 07, 2012 

ATYPICAL BSE BRAZIL 2010 FINALLY CONFIRMED OIE 2012 


Wednesday, December 19, 2012 

Scientific Report of the European Food Safety Authority on the Assessment of the Geographical BSE Risk (GBR) of Brazil 


Terry S. Singeltary Sr.

SATURDAY, MARCH 11, 2017 

Are Brazilian cervids at risk of prion diseases?



MONDAY, OCTOBER 02, 2017 

Creutzfeldt Jakob Disease United States of America USA and United Kingdom UK Increasing and Zoonotic Pontential From Different Species


THURSDAY, AUGUST 17, 2017 

*** Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States revisited 2017

Singeltary et al


FRIDAY, AUGUST 11, 2017 

Infectivity in bone marrow from sporadic CJD patients

Bioassays in transgenic mice expressing the human prion protein revealed the presence of unexpectedly high levels of infectivity in the bone marrow from seven out of eight sCJD cases. These findings may explain the presence of blood-borne infectivity in sCJD patients. They also suggest that the distribution of prion infectivity in peripheral tissues in sCJD patients could be wider than currently believed, with potential implications for the iatrogenic transmission risk of this disease. 


*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery *** 

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. 

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them. 


THURSDAY, AUGUST 10, 2017 

*** Minimise transmission risk of CJD and vCJD in healthcare settings Updated 10 August 2017


National Prion Center could lose all funding just as concern about CWD jumping to humans rises

SATURDAY, JULY 15, 2017 

*** National Prion Center could lose all funding just as concern about CWD jumping to humans rises



Terry S. Singeltary Sr.

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