| Abstract|| |
Sporadic Creutzfeldt-Jakob disease (CJD) is the most common prion disease. It is a rare, fatal neurodegenerative disease caused by an infectious protein called prion. The diagnosis can be confirmed only by histological examination of brain tissue. Because of the transmissible nature of the disease, autopsy or brain biopsy cannot be performed at many institutions. Histology shows spongiform changes, neuronal loss, reactive astrocytic proliferation, accumulation of pathologic protein occurring in three general forms: Sporadic, familial, and acquired form, including a variant form of CJD. It clinically presents as predominantly progressive dementia with a rapid onset, myoclonus, cerebellar, pyramidal, extra pyramidal and visual signs. Occurrence of periodical spikes in electro-encephalogram, observation of cortical signal alterations in magnetic resonance imaging (MRI) studies, and detection of protein 14-3-3 in cerebrospinal fluid substantiate diagnosis. Autopsy case is presented of a 50 year old woman with progressive dementia, typical neurological symptoms, MRI findings and confirmation of CJD on histology and immunostaining.
Keywords: Autopsy, infective prion, sporadic Creutzfeldt-Jakob disease, spongiform encephalopathy
|How to cite this article:|
Gadgil NM, Chaudhari CS, Gohil SD, Kalgutkar AD. Creutzfeldt-Jacob disease: An autopsy case report in tertiary care hospital. Indian J Pathol Microbiol 2012;55:97-9
|How to cite this URL:|
Gadgil NM, Chaudhari CS, Gohil SD, Kalgutkar AD. Creutzfeldt-Jacob disease: An autopsy case report in tertiary care hospital. Indian J Pathol Microbiol [serial online] 2012 [cited 2020 Feb 21];55:97-9. Available from: http://www.ijpmonline.org/text.asp?2012/55/1/97/94871
| Introduction|| |
Creutzfeldt-Jakob disease More Details (CJD) is a rarely seen neurodegenerative disease among the infectious spongiform encephalopathies. It has four subtypes as sporadic, familial, iatrogenic, and variant forms.  Mean age at the onset is 60 years, with incidence of 1/1.000.000. Firstly in 1982, Prusiner hypothetically proposed prions as causative infectious agents of CJD. In fact, normally a prion (PrPC) is a glycoprotein found in normal cells of humans and animals. Infective prion (PrPSc) is a posttranslational product.  Prion diseases have generated increasing public concern since the identification of the relationship between bovine spongiform encephalopathy and new variant CJD.  Sporadic CJD remains the most common prion related neurodegenerative disease in humans. In this article, an autopsy case with a sporadic CJD, in which diagnosis was based on medical history, clinical presentation, findings of magnetic resonance imaging (MRI), electro-encephalogram (EEG), autopsy brain histology, and immunostaining for infected prion protein, in accordance with clinical diagnostic criteria of World Health Organization and Masters et al.  is presented. 
| Case Report|| |
A 50 year old female, housewife presented with altered sensorium without any history of trauma. She had symptoms of akinetic state, mutism, rapid progressive dementia, and myoclonic jerks with duration of three months. She had mixed diet habits with meat consumption. Patient had no surgical or invasive procedure history in past with no similar symptoms in any members of the family. On clinical examination, she was drowsy with flexor posturing of upper limbs on painful stimulus. No signs of decerebrate and decorticate rigidity were detected. She had a low-grade fever, pulse at 80 beats/min, respiration at 20 breaths/min, and normal blood pressure. The rest of the physical examination was unremarkable. Magnetic resonance imaging (MRI) of the brain revealed mild cerebral atrophy, increase in signal intensity in putamen, caudate nucleus, and cerebral cortex (cortical ribboning). Cerebro spinal fluid (CSF) analysis showed elevated protein of 45 mg/dl, normal glucose, and no pleocytosis. Analysis for CSF protein 14-3- 3 was not performed `due to unavailability. An EEG obtained one week later revealed bilateral synchronous periodic epileptiform discharges characteristic of spongiform encephalopathy. The possibility of sporadic CJD was considered. Patient became progressively unresponsive to verbal commands and developed breathlessness and was put on ventilatory support. After a week, patient could not be revived and died.
Autopsy was performed and the histological examination of brain revealed marked spongiform changes and gliosis predominantly involving the cerebral and cerebellar cortices [Figure 1]. Immunostaining studies for PrSc performed with the use of antiprion protein monoclonal antibodies revealed a synaptic pattern of staining, which is characteristic of CJD [Figure 2]. and [Figure 3].
|Figure 1: (a, b) The cortical ribbon showed spongy change; with mild gliosis and fairly well preserved neurons with multiple coalescing vacuoles of variable sizes. (A-hematoxylin and eosin, ×100, B- hematoxylin and eosin, ×400). (c) Cerebellum showed spongiform change in the molecular layer, with preserved white matter and purkinje cells (hematoxylin and eosin, ×400)|
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|Figure 2 (a,b): Cerebellum: Immunostaining control (arrow points to depsotion of Prion Protein in the granular layer as small multiple plaques) (IHC, x 400). (c,d): Cerebellum: The positive immunostaining in case showed synaptic (granular, diffuse) pattern of Prion Protein staining in the molecular layer and around vacuoles|
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|Figure 3: Basal ganglia, Caudate nuclei: Positive immunostaining in case showed synaptic pattern (immunostained with mouse monoclonal antibody (IgG-2) recognizing 140-184 amino acid component of PrPsc, the antigen being from cow's brain)|
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| Discussion|| |
CJD accounts for more than 85% of all cases of prion disease. The worldwide annual incidence is approximately one per one million people. The disease occurs sporadically in 90% of cases, is inherited in less than 15% of cases, and is transmissible in less than 5% of cases. In sporadic cases, age at onset ranges from 16 to 86 years, with an average of 61.5 years with rapidly progressive dementia and myoclonus manifesting as a response to auditory and tactile stimuli. In late stages, patient develops akinetic mutism. The disease is always fatal, with a mean interval of 8 months and a median interval of 4.5 months between onset and death. Eighty percent of the patients die from infection, cardiac, and respiratory failure within the first year.
Familial CJD is associated with a relatively early onset (40- 50 years of age) and a prolonged course. Typical EEG findings are not seen, and genetic studies revealed nearly 20 genes mutations. Usually, iatrogenic form occur secondary to duramater graft implantation, corneal transplantation, and surgical operations performed with contaminated instruments. 
New variant, CJD (nvCJD), has been reported since the middle of 90's. The mean age at the onset of the disease is 29 years and its mean survival is 16 months. Typical features of sporadic CJD could not be observed. The protein 14-3-3 could not be detected in CSF. This variant leads to cerebral prion plaques, contrary to spongiform alterations, in the brain tissue.
Recently, significant progress has been made in establishing the ante mortem diagnosis in suspected cases of CJD. These include MRI and 14-3-3 protein immunoassay in CSF. MRI has been shown to be a valuable tool in CJD diagnosis with bilateral areas of increased signal intensity, predominantly affecting the basal ganglia (caudate nuclei, putamen), with sensitivity of 67% and specificity of 93%.  Periodic biphasic or triphasic, synchronized sharp wave EEG complexes occurring during middle or late stages of disease are typical and found in 90% of the patients. Steinhoff in his series of 150 cases reported 64% sensitivity and 91% specificity for EEG examinations. ,
Our patient met Masters et al.'s  criteria for probable CJD, such as inappropriate behavior, ataxia, myoclonic jerks, akinetic mutism, and rapid decline in cognitive function, during a three-month period. T-2 weighted magnetic resonance imaging of the brain revealed mild cerebral atrophy, increase in signal intensity in putamen, caudate nucleus, and cerebral cortex (cortical ribboning). Unfortunately, 14-3-3 protein analysis was not performed because of the lack of availability of the test at the hospital. However, characteristic findings of bilateral synchronous epileptiform periodic activity seen on EEGs supported the clinical diagnosis in this case.
Autopsy was performed with disposable, protective clothing, and a face visor, protecting eyes and nose. Instruments were decontaminated by immersing in 1N NaOH for one hour followed by autoclaving at 121°C for one hour. Contaminated surface was flooded with 2N NaOH for one hour, mopped up and rinsed with water. Before processing, formalin fixed tissue sections were treated with 95% formic acid for an hour and then transferred to fresh formalin for another two days. Sections were cut on routine microtome with disposable blade. Processing fluid and other waste decontaminated by incineration. ,
The histological examination revealed marked spongiform changes and gliosis predominantly involving the cerebral and cerebellar cortices. Immunostaining studies for PrSc performed with the use of antiprion KG9 protein monoclonal antibodies revealed a synaptic pattern of staining, which is characteristic of CJD. Eventually, the diagnosis of sporadic CJD with unknown source was confirmed at autopsy on the basis of histologic and immunostaining studies.
Conclusion: Prion diseases are transmissible and invariably fatal. Because of its transmissible nature, care of patients with CJD is challenging and a cause of concern among family physicians, surgeons, pathologists, and nursing staff. Patients with CJD might be refused of care because of clinicians' lack of knowledge and their concern about contracting the disease. Autopsies cannot be performed at many institutions because of the transmissible nature of the disease. Increased educational efforts, specific protocols, and additional testing sites are needed to address these obstacles, because enormous efforts are currently required to arrange for an autopsy to confirm the diagnosis.
| Acknowledgment|| |
- CJD Registry, Dept of Neuropathology, NIMHANS, Bangalore.
- Sunder Uma MD,Professor, Dept of Medicine, Lokmanya Tilak Medical College and Municipal General Hospital, Sion, Mumbai - 400 022, India.
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Chetan S Chaudhari
Department of Pathology, Lokmanya Tilak Medical College and Municipal General Hospital, Sion, Mumbai - 400 022
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]