Subacute Spongiform Encephalopathies Research Articles

Psychiatric Presentation Revealing Creutzfeldt-Jakob Disease: A Case Report

Creutzfeldt-Jakob disease or subacute spongiform encephalopathy is a rare prion encephalopathy with a long incubation period and fatal outcome without remission. In this summary, we report a case of sporadic Creutzfeldt-Jakob disease consolidates by positive income CSF analysis of the 14.3.3 protein. This patient study report presents a 54 years old Moroccan male patient with no underlying disease. Whose history of the disease goes back to 04 months, by the admission at the department of psychiatry for the quickly progressive installation of a depressive syndrome, with behavioral disorders made up of anxiety and aggression towards, associated with a decline in visual acuity that the patient reported as very annoying and disabling, while the ophthalmologic examination without abnormalities, and the patient was able to walk alone and avoids obstacles while walking. With a strictly normal brain MRI, treatment by antidepressants and neuroleptics has been prescribed. The evolution was marked 3 months later by the appearance of significant memory disorders associated with hallucinations, impaired walking, and myoclonus in the upper limbs which are exerted by sounds in the arms and legs. A new brain MRI performed showed bilateral frontal and occipital cortical high signal, a visual evoked potential demonstrated a decrease in the activity of the visual pathways with alteration of the central macular vision, the electroencephalogram (EEG) revealed a slowing of the background activity with periodic activity and rapid rhythmicity, the study of Cerebrospinal fluid (CSF) was without abnormalities regarding CSF value of proteins and glucose but the dosage of the protein 14.3.3 came back positive. Following these clinical, biological, radiological, and electrophysiological elements, the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) was retained.

Report and literature review on two cases with different kinds of Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD), also known as corticostriate spinal degeneration, subacute spongiform encephalopathy or infectious spongiform encephalopathy, is a type of degenerative disease of the central nervous system caused by prion protein (PrP) infection, which is the most common type of human PrP disease. CJD is genetic and infectious, and is one of the most common causes of rapid progressive dementia with rare clinical occurrence. Herein, we report the clinical conditions of 2 cases of patients with different type of CJD we treated and followed up recently, and a review of relevant literature. The patient in case 1 was admitted due to ‘dizziness with hypomnesis, and mental and behavior disorder’. He was considered to suffer from a central nervous system infection - a viral encephalitis, but one month later, a repeated cranial MRI showed lace sign of bilateral frontotemporal parietal lobe in DWI sequence, an AEEG indicated periodic synchronous discharge, and the detection of cerebrospinal fluid 14-3-3 protein was positive. It was suggested to be diagnosed as the sporadic CJD. The patient in case 2 was admitted because of ‘progressive hypomnesis’. Cerebrospinal fluid 14-3-3 protein detection was negative, but the V203I-related mutation was found in the PRNP gene detection. The patient was suggested to be diagnosed as genetic CJD. Both patients died in a short time. An earlier diagnosis can provide a time window for treatment, and avoid unnecessary transmission in hospital, as well as doctor-patient dispute.

Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice.

Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population.

Comparison of the clinical course of Japanese MM1-type sporadic Creutzfeldt-Jakob disease between subacute spongiform encephalopathy and panencephalopathic-type

BackgroundApproximately half of Japanese sporadic Creutzfeldt-Jakob disease (sCJD) cases show panencephalopathic-type (PE-type) pathology, which is a rare subtype in North Americans and Europeans. Until now, the differences in the clinical course between subacute spongiform encephalopathy (SSE) cases and PE-type cases have been unclear. MethodsTo investigate the clinical course of both subtypes, clinical findings from 42 Japanese MM1-type sCJD cases (20 SSE cases and 22 PE-type cases) were retrospectively evaluated by statistical analysis. ResultsNo significant differences could be found regarding age at disease onset, the period between disease onset and first observation of myoclonus, the period between disease onset and the first observation of periodic sharp-wave complexes on electroencephalogram, or the period between disease onset and progression to the akinetic mutism state – whereas total disease duration and the period between the akinetic mutism state and death were significantly longer in PE-type cases. The prolonged disease duration was induced by the extended survival period in the akinetic mutism state. There was a statistically significant difference between the two series regarding performance of tube-feeding, but no statistically significant difference regarding performance of tracheotomy or gastrostomy. None of the cases received mechanical ventilation. ConclusionWe speculate that the most crucial factor of the prolonged survival period of Japanese sCJD cases, particularly in the PE-type, is that the introduction of tube-feeding in the akinetic mutism state leads to the stabilization of the patient's general condition.

1650 – Probable creutzfeld-jakob disease: a neuropsychiatric presentation

Creutzfeld-Jakob disease (CJD) is the commonest form of transmissible human subacute spongiform encephalopathy, with a worldwide distribution of 0.5 to 1.0 per million population. A retrospective review in 1998 from Singapore General Hospital revealed 5 possible cases over 2 years, in an island with a population of 4 million. We present a 76 year-old Chinese man, with a premorbid personality of an independent person who was neat and meticulous, admitted for a 3 month-history of progressive behavioural change, associated with memory impairment and unsteady gait. He had long-standing hypertension which was well-controlled. The abnormal behaviour included frequent complaints of people coming to his house to have meetings, frequent misplacing of his belongings, as well as decreased self-hygiene. This has affected his daily functioning. There were no other symptoms of dementia. Initial MMSE was 16/30, with impairment in 2-point orientation (place/person), the serial sevens, and delayed recall. There was marked inattention. There was no evidence of mood disorder. No perceptual disorder was elicited. The brain MRI revealed cortical hyperintensities (“cortical ribboning”) in right frontal, parietal, temporal, and caudate nucleus. Physical examination on the 5th day of admission revealed mild bradykinesia, mild hypertonia of all 4 limbs, mildly impaired proprioception, mildly unsteady gait, as well as occasional myoclonic jerks of the head. Electroencephalogram showed generalised fronto-central fairly rhythmical periodic complexes with triphasic morphology.Cerebrospinal fluid protein 14-3-3 were negative. Over the next 12 days, his Abbreviated Mental Test (AMT) decreased from 8/10 to 5/10. The clinical picture was highly suggestive of sporadic CJD.

Two Sequential Tc-99m ECD SPECT Studies in a Case of Sporadic Creutzfeldt–Jakob Disease Confirmed at Autopsy

Creutzfeldt-Jakob disease (CJD) is a subacute spongiform encephalopathy characterized by rapidly progressive dementia, hard to diagnose during life. We present a case of a patient with pathologically confirmed sporadic form of CJD in whom initial diagnostic tests were negative. Two sequential brain single-photon emission computed tomography with Tc-99m ethyl-cysteinate dimer were performed, the first one was performed few days after the admission into hospital and the second, 1 month later. Both studies revealed a decrease in regional cerebral blood flow indicative of neuronal dysfunction, more pronounced in the second study. Current radionuclide scintigraphy can be an useful tool for the investigation of CJD.

Can prion disease suspicion be supported earlier? Clinical, radiological and laboratory findings in a series of cases

The subacute spongiform encephalopathies are prion diseases characterized by acute and rapid neurodegeneration that lead to the death of the patient within months to a few years. The epidemiology of CJD is complicated and the frequency in Mexico is unknown. We aim to describe the cases of prion disease in Mexico. Consecutive patients who met the diagnostic criteria by the WHO were enrolled. We describe 26 patients with clinical manifestations, imaging and laboratory studies compatible with prion disease. The mean age at onset was 52 years old. The main clinical manifestations were cognitive alterations (69%) followed by extrapyramidal movements (50%), abnormal cerebellar function (46%), behavioral alterations (46%), myoclonus (46%), and mood depression (23%), among other features. Half of the patients progressed rapidly to a state of akinetic mutism (53%). Only 2 (7.6%) patients had a family history of a similar disease. Time interval between onset and diagnosis varied between 71 days to 24 months, with a median of 6 months. The classical bilateral basal ganglia hyperintensities were present in the very early stage of the disease. Protein 14-3-3 immuneassay in the CSF was positive in all measured cases. Bilateral basal ganglia hyperintensities was the most important early finding, while protein 14-3-3 was a late finding and the results were usually obtained after the patient was discharged. Around 1.5 cases of CJD cases per year are reported in our country. When suspected, MRI can support the diagnosis earlier than other studies.

Clinicopathologic characteristics of five autopsied cases of dura mater‐associated Creutzfeldt‐Jakob disease

We present five cases of dura mater-associated Creutzfeldt-Jakob disease (dura-CJD) that were analyzed clinicopathologically and review previous reports. The average age at dura mater transplantation was 54.4 +/- 7.3 years, and the average age at CJD onset was 66.0 +/- 8.2 years, with an average latency period of 11.6 +/- 1.1 years. The average age at death was 67.6 +/- 8.7 years, with an average CJD disease duration of 16.8 +/- 10.4 months. Symptoms of CJD onset in four patients who received dura mater transplantation below the cerebellar tent reflected cerebellar or brainstem dysfunction, whereas symptoms of one patient who received transplantation above the cerebellar tent reflected cerebral cortical involvement. All patients showed rapidly progressive cognitive impairment, and both periodic sharp-wave complexes on electroencephalogram and myoclonus were observed in the early disease stage. Neuropathologic evaluation showed one case of subacute spongiform encephalopathy and four cases of panencephalopathic-type CJD. Widespread cerebral neocortical, subcortical gray matter and cerebellar cortical involvement were observed to varying degrees, and severity tended to be associated with CJD disease duration. There were no instances of kuru plaques or florid plaques. Prion protein (PrP) immunostaining showed widespread synaptic-type PrP deposition. No differences between our dura-CJD cases and typical cases of sporadic CJD were found with respect to clinicopathologic findings, except history of dura mater transplantation. Although a specific association between the dura mater graft site and neuropathologic observations was not evaluated in the present study, the initial symptoms appear to be closely related to the graft site, indicating a direct transmission of CJD from the graft site to the adjacent brain.

Creutzfeldt-Jakob Disease Presenting as Hyperparathyroidism and Generalized Tonic Status Epilepticus

Creutzfeldt-Jakob disease is the most common disorder among the very rare human transmissible subacute spongiform encephalopathies. Sporadic, familial or iatrogenic forms of the disease can be seen. The common presentations of the disease include rapidly progressive cognitive decline, behavioral changes, visual disturbances and cerebellar dysfunction. Hyperparathyroidism and toxicity of lithium and bismuth have been reported to induce similar symptoms and EEG findings, leading to a Creutzfeldt-Jakob like syndrome. We report a very rare case of Creutzfeldt-Jakob disease presenting with hyperparathyroidism and generalized tonic status epilepticus.

Pyramidal tract degeneration in sporadic Creutzfeldt‐Jakob disease

We investigated the neuropathologic features of pyramidal tract degeneration in 27 cases of sporadic Creutzfeldt-Jakob disease (sCJD). The present study included 13 cases of subacute spongiform encephalopathy (SSE), 13 cases of panencephalopathic-type (PE-type) sCJD and one case of thalamic-type sCJD. Pyramidal tract degeneration was observed in PE-type sCJD cases with disease duration of more than 13 months. Cases of SSE, PE-type sCJD of relatively short duration and thalamic-type sCJD showed no pyramidal tract degeneration. All cases with pyramidal tract degeneration showed severe cerebral neocortical involvement with widespread cerebral white matter degeneration. The loss of myelin and axons and macrophage infiltration and fibrillary gliosis seen in these pyramidal tract lesions is consistent with secondary tract degeneration due to cerebral neocortical involvement. Interestingly, some cases with pyramidal tract degeneration showed a distal-dominant pathology that we believe indicates retrograde degeneration or a "dying-back" phenomenon of the pyramidal tract. Our results indicate that pyramidal tract degeneration is a late pathologic event in sCJD. Investigation of pyramidal tract degeneration may help clarify the mechanisms underlying the development of sCJD white matter pathology, particularly that of PE-type sCJD.

Enhanced Aquaporin‐4 immunoreactivity in sporadic Creutzfeldt‐Jakob disease

Aquaporin-4 (AQP-4) is a water channel protein located on the plasma membrane of astrocytes and is regulated under various conditions. In the present study, a series of brains with sporadic Creutzfeldt-Jakob disease (sCJD) were investigated to determine the possible contribution of AQP-4 in the development of sCJD pathology. Six cases of subacute spongiform encephalopathy (SSE) and four cases of panencephalopathic (PE)-type sCJD were included. Increased AQP-4 immunoreactivity compared to that in controls was observed in all sCJD patients, particularly in the cerebral neocortex and cerebellar cortex. AQP-4 immunoreactivity was present in the cell bodies and processes of protoplasmic astrocytes in SSE and around cell bodies and processes of hypertrophic astrocytes in PE-type sCJD. Analysis of serial sections showed the development of sCJD pathology, particularly in neocortical lesions, as follows: PrP deposition; spongiform change and gliosis; enhanced staining for AQP-4; hypertrophic astrocytosis; and neuronal loss and tissue rarefaction. Strong AQP-4 immunoreactivity was present in burnt-out lesions such as those of status spongiosus. These results indicate that increased AQP-4 expression in sCJD is an early pathologic event and appears to remain until the late disease stage. We suggest that increased expression of AQP-4 is a pathologic feature of sCJD.

Clinicopathologic characteristics of sporadic Japanese Creutzfeldt–Jakob disease classified according to prion protein gene polymorphism and prion protein type

We analyzed neuropathologic features of 23 Japanese patients with sporadic Creutzfeldt-Jakob disease (sCJD) by means of prion protein (PrP) immunolabeling associated with codon 129 polymorphism of the PrP gene and western blot analysis of protease-resistant PrP (PrP type). Clinical features, particularly age at onset, disease duration, periodic synchronous discharge and presence of myoclonus, were also analyzed. This study included 11 cases of subacute spongiform encephalopathy (SSE), 10 cases of panencephalopathic (PE)-type sCJD and two cases of thalamic-type sCJD, classified according to cerebral pathology findings. According to PrP gene polymorphism and PrP type, 18 cases were classified as MM1-type, two as MV1-type, two as MM2-type and one as MM1 + 2-type sCJD. SSE and PE-type sCJD showed similar clinical features, with the exception of disease duration, codon 129 polymorphism and PrP type. Thalamic-type sCJD showed different clinical features and PrP type. We suggest that SSE and PE-type sCJD comprise the sCJD subtype and that PE-type sCJD is a prolonged pathologic phenotype of SSE. When we compare our results with those from a series of Caucasian sCJD patients, the percentages of codon 129 polymorphisms differed, as did classification based on PrP gene polymorphism and PrP type; our series included many PE-type sCJD cases and disease duration was relatively long and MM2-type cases showed clinicopathologic variability.

Perspectives immunoprophylactiques et immunothérapeutiques contre les maladies à prions

Prion diseases or transmissible subacute spongiform encephalopathies (TSSE) are fatal neurodegenerative conditions, for which there is so far no known treatment or prevention. Promising results achieved in the field of Alzheimer disease give however some reasons to hope that individuals with the disease or individuals at risk might benefit from similar immunoprophylactic or immunotherapeutic approaches. This article reviews current knowledge on the immunology of prion diseases. In the first section we describe the known routes of prion lymphoinvasion from the periphery to the sites of neuroinvasion. The second section focuses on the mediators of innate immunity mobilized within the central nervous system and on their ambivalent role in the pathogenesis of the disease. The final section describes the vaccine approaches aimed at stimulating adaptive immunity and at creating, in association with the mediators of the innate immune system, a defence barrier against prions.

Neuropathologic characteristics of spinal cord lesions in sporadic Creutzfeldt-Jakob disease

We investigated the neuropathologic features of spinal cord lesions in 23 patients with sporadic Creutzfeldt-Jakob disease (sCJD), paying particular attention to neuronal loss and gliosis, pyramidal tract degeneration and prion protein (PrP) deposition. The study included 9 cases of subacute spongiform encephalopathy, 13 cases of panencephalopathic-type sCJD and 1 case of sporadic fatal insomnia (sFI). In the spinal gray matter, although gliosis was present in some patients with disease of relatively long duration, the number of neurons, including large motor neurons, was well preserved regardless of disease duration. Pyramidal tract degeneration was observed in some patients with disease lasting more than 14 months but not in the patient with sFI. PrP deposition was present in the spinal cord of all sCJD patients, and was identified predominantly in the posterior horn, particularly in the substantia gelatinosa, regardless of disease duration or disease classification based on cerebral pathology. Relatively prominent PrP deposition was also observed in Clarke's column. The density of PrP deposition in the sCJD spinal cord was not associated with disease duration or neuronal degeneration. Our results indicate that PrP deposition in the spinal cord is an early pathologic event in sCJD and may remain to the end stage. Although no VV1, VV2 or MV2 cases were included in our study, we suggest that stereotypic accumulation of PrP is a consistent pathologic feature of sCJD and that the spinal cord remains relatively resistant to the pathologic process of sCJD, at least in patients with MM1 sCJD.

Subacute Spongiform Encephalopathies

Subacute spongiform encephalopathies are rare fatal diseases that affect the central nervous system, which is thought to be caused by prions, characterized clinically by a rapid progressive dementing course, along with generalized myoclonus. The prototype of these conditions in humans is Creutzfeldt-Jakob Disease (CJD). Although the final diagnosis depends on neuropathological examination, the presence of periodic sharp wave complexes on EEG and of the neuron-specific enolase, tau protein, S-100, and of the 14-3-3 protein in the cerebrospinal fluid, make the diagnosis of probable CJD. However, as these criteria are not completely accurate and the early diagnosis is extremely difficult, much interest has been focused recently on imaging methods. With the advent of diffusion-weighted imaging, MRI has shown high sensitivity and specificity, therefore being considered a useful method for the early diagnosis of this entity.

Méthodes de diagnostic des « maladies à prions » chez l'homme et chez l'animal

The potential existence of clinically silent cases of bovine spongiform encephalopathy (BSE) among cattle, and of humans incubating the new variant Creutzfeldt-Jakob disease (nvCJD) is still a major public health concern. Therefore, the development of screening tests for transmissible subacute spongiform encephalopathies (TSSE) in man and animals remains a priority. In the first part of this paper, we review the main methods used to diagnose generally clinical TSSE, such as brain imaging, electroencephalogram (EEG) analysis, and cerebrospinal fluid (CSF) analysis. In the second part, we present the post-mortem tests used to confirm a TSSE diagnosis, such as inoculation to laboratory animals, histological examination, and identification of abnormal prion protein (PrPres) using biochemical methods. Finally, the third part presents so-called rapid tests (Prionics, Bio-rad, Enfer), validated by the European Commission (EC) for post-slaughter BSE diagnosis in cattle. Now used on a large scale in Europe, these tests have helped assess the extent of the epizooty and eliminate from the food chain animals presenting a risk for human consumption. Since 2002, they have been used for the post-slaughter diagnosis of scrapie in small ruminants. New tests have recently been evaluated by the EC, but it is too soon to predict their role in the field.

Case Reports of Two Biopsy-proven Patients with Creutzfeldt-Jakob Disease in Singapore

Introduction: Creutzfeldt-Jakob disease (CJD) is the most common transmissible human subacute spongiform encephalopathy. There is limited literature on CJD in Southeast Asia. We describe the clinical course and diagnostic evaluation of 2 Singapore patients with biopsy-proven CJD. Clinical Picture: Two patients presented with non-specific symptoms such as withdrawal, forgetfulness, asthenia, giddiness and insomnia. Both patients had spontaneous myoclonic jerks and impairment of multiple neurologic systems (visual, pyramidal, cerebellar and neurocognitive systems). Magnetic resonance imaging and electroencephalography provided helpful supportive evidence. Diagnosis of CJD was established on brain biopsy. Histological features included spongioform degeneration, neuronal cell loss and astrocytosis. Treatment/Outcome: Treatment remains palliative. Deterioration in their clinical condition was relentless, progressing to a totally dependent state within 10 to 12 months. Conclusion: The early features of CJD can be varied and non-specific. It is important for physicians from different specialties to be cognisant of the clinical manifestations of CJD and the appearance of supportive and definitive investigations.

Aetiopathogenesis of CNS Infections

Despite decades of dramatic progress in the prevention and treatment of infectious diseases (ID), it contineus to challenge the physicians diagnostic skill and remains a major cause of death and disability worldwide. Infectious agents are also increasingly recognized in the aetiology of non-infectious diseases. CNS infections include meningitis, Encephalitis, Myelitis, intracranial. Thrombophlebitis, brain abscess infected subdural hematoma as well as granulomatous disease due to TB, syphilis, fungal infections and plausibily sarcoidosis. In adults, pneumococcus, meningococcus and H.influenza account for about 80-90% of bacterial meningitis whilst in infants and children aged between 2 months to 7 years, H.influenza infeciton is common. Five viral syndromes are recognized and include myelitis/radiculitis; herpes zooster ganglionitis, acute aseptic meningitis, acute encephalitis or meingo-encephalitis and chronic infections due to “slow viruses”/unconventional agents simulating degenerative diseases. Conventional viruses cause sub-acute sclerosing pan-encephalitis, progressive rubella panencephalitis, and progressive multifocal leukoencephalopathy; while unconventional agents cause prion diseases which include kuru, sub-acute spongiform encephalopathy, Gestman Straussler sheinker (GSS) and familial fatal insominia. The clinical and pathological effects of these infections are diverse as the CNS is uniquely protected from pertubation by the blood brain barrier. The cerebral tissue is also resistant to infeciton, a necessary antecedant to susceptibility being infarction by arterial occlusion (embolism) or venous occlusion (thrombophlebitis). Nig. Medical Practitioner Vol. 45(1/2) 2004: 14-19

Encéphalopathie spongiforme mimant une dégénérescence corticobasale

The presentation of subacute spongiform encephalopathies is varied and includes various movement disorders such as parkinsonism, myoclonus, or dystonia. These signs, especially when asymmetrical, can lead to the diagnostic of corticobasal degeneration. We report the case of a 75-Year-old woman who developed clinical signs suggestive of corticobasal degeneration: asymmetric rigidity and apraxia, limb dystonia, and postural instability. The final diagnosis of spongiform encephalopathy was suspected because of rapid decline and confirmed by post-mortem examination. This case highlights the importance of considering subacute spongiform encephalopathy in patients with a clinical presentation compatible with corticobasal degeneration.

Encéphalopathies subaiguës spongiformes transmissibles ou maladies à prions

Prions are responsible for transmissible subacute spongiform encephalopathies (TSE) in humans and animals. Human transmissible spongiform encephalopathies are Creutzfeldt-Jakob Disease (CJD), Fatal Insomnia, Kuru and Gerstmann-Sträussler-Scheinker syndrome. In animals, TSE are natural scrapie in sheep and goats, bovine spongiform encephalopathy (BSE), feline spongiform encephalopathy, transmissible mink encephalopathy, and chronic wasting disease. Prions are thought to be composed of an abnormal isoform of a host-encoded protein, the prion protein (PrP). In vivo, raise in infectivity titre is always associated with a proportional accumulation of PrP. PrP from TSE-affected individuals resists proteinase K digestion and its accumulation is post-translational. Prions resist almost all the procedures generally used to inactivate conventional viruses. Due to their biophysical properties, prions behave differently depending upon the biophysical and biochemical characteristics of their environment. TSE agents are capable to cross the species barrier. In March 96, British epidemiologists reported the appearance of 10 cases of a new variant of Creutzfeldt-Jakob disease (vCJD), which is caused by the exposure of the human population to the BSE agent. Public health consequences are mainly depending upon the incidence of this emerging disease in UK and in continental Europe.