Pediatric New Variant Creutzfeldt-Jakob Disease

Introduction to pediatric new variant Kreuzfeldt-Jacob disease The pathological changes and clinical outcomes of this disease are similar to Creutzfeldt-Jakobdisease (CJD, K-Ya disease) and bovine spongiform encephalopathy (BSE, commonly known as "mad cow disease"), and its appearance Closely related to BSE. In 1982, Prusiner named a group of diseases of chronic progressive degenerative diseases of the central nervous system as prion diseases. basic knowledge Sickness ratio: 0.0001% Susceptible people: children Mode of infection: non-infectious Complications: dementia

Pediatric new variant Kreuzfeldt-Jacob disease etiology

Causes:

New variant of Kreuzfeldt-Jacob disease (nvCJD): According to the definitions of Stewart and Ironside, nvCJD is characterized by clinical and neuropathological features due to exposure to bovine spongiform encephalopathy factors. New human prion diseases.

The current evidence strongly supports the causal relationship between nvCJD and BSE. Researchers generally accepted the conclusion that nvCJD is a pathogenic factor of BSE in humans, and the typing of experimental nvCJD factors identified the pathogen and nvCJD pathogens. The factors identified in the BSE are the same.

The English name of prion or scorpion venom is prion. From proteinaceous infectious particles, which are anti-protease-infective particles, PrP, the prion protein, is often used in research. Human PrP is composed of 253 amino acids. The protein consisting of the gene on the short arm of the 20th pair of chromosomes, PrP is expressed in different types of cells, but mainly expressed in neurons, its molecular weight is 27 ~ 30kD, the researchers expressed this in normal cells PrP is called Prpc, where c is a normal cell, normal Prpc has a protective neuron effect, and is protease sensitive, it does not cause disease, and abnormal prion protein is a post-translationally modified PrP of PrP. That is, PrPsc, where sc stands for scrapie, that is, pruritus, that is to say, PrPsc is the kind of PrP that causes pruritus in sheep. Prsc is partially resistant to protease, is a hydrophobic protein, it is inactivated by radiation, heat and Strong chemical treatment is highly resistant, PrPsc is a contagious protein, amino acid composition and sequence of PrPsc and PrPc in the same genus of animals The same, but the spatial configuration is different, which shows that the -helix and -sheet of the two PrPs account for different percentages of the length of the whole molecule, and the -helix and -sheet of PrPc are 42 respectively. % and 3%; but PrPsc is 30% and 43%, respectively, which shows that the spatial configuration is very different.

Pathogenesis:

In order to have a clear understanding of the disease, first briefly review CJD and BSE. 1. CJD and BSE: (1) Kreuzfeldt-Jacob disease (CJD): CJD is a sporadic disease in which the degeneration of the central nervous system becomes the main pathological change. 50 to 75 years old, mostly with mental decline (memory loss, emotional changes, judgment disorders, balance and movement disorders, etc.) onset, disease progression, hallucinations, disturbance of consciousness, paralysis, no desire, dementia, myoclonus, muscle Tonic, etc., most patients die within 6 months of onset.

The pathological changes of this disease are very special: the brain tissue has extensive vacuolization or spongy changes, brain atrophy, nerve cell loss, electron microscopy studies have found fibrils composed of amyloid protein in the brain, further studies found that patients with this disease There are protease-resistant proteins (PrP) in brain tissue. Studies on the physicochemical, immunological and molecular biological characteristics of these proteins suggest that these proteins are likely to be the same pathogens as prions that cause pruritus, from humans. The preparation of cadaveric brain tissue, or repair with human dura mater membrane, corneal transplantation and the like have caused iatrogenic transmission of the disease, but there is no evidence of spontaneously occurring infectious diseases for sporadic CJD, and it is likely to be PrP. As a result of mutations in the gene, in the case of a clear history of transmission, the incubation period of CJD is very long, up to 20 years, but blood transfusion and close contact with patients do not spread the disease, the incidence of this disease is in different countries and The area is very consistent, about 1 in 1 million.

(2) Bovine Spongiform Encephalopathy (BSE): BSE is a spongiform encephalopathy of cattle that was first identified in the UK in 1986. In the following years, the number of BSE-infected cattle in the UK was as many as 166,000. The prevalence of the disease in cattle reached its peak in 1993. Since then, the number of sick animals has decreased year by year and has been reduced to a very low level. The cause of the disease is the sheep infected with scrapie factor. The meat and bone are made from feed for cattle, and the pruritus is spongiform encephalopathy equivalent to sheep or goats. The infectious agent is prion or prion.

British scholars have studied BSE-producing cattle and a large number of experimental animals. The brains and spinal cords of BSE-infected animals are the most contagious, and lymph nodes and intestinal lymphoid tissues are contagious, while muscle, blood and milk are not measurable. Contagious.

The main clinical manifestations of BSE-bearing cattle are as follows:

1 behavioral changes: the most common are restlessness, madness and nervousness;

2 abnormalities in body position and movement: ataxia of the hind limbs, tremors and falls;

3 sensory changes: mainly expressed in the perception of sound and contact abnormalities, most (87%) sick animals have these three aspects of the nervous system performance, the course of the disease (from the earliest signs to death or slaughter) is usually several weeks to For a few months.

2. There are two possible mechanisms of human disease caused by PrPc:

(1) One is the conversion of the original PrPc to PrPsc: Studies have shown that when a mutation occurs in the PrPc gene, the expressed PrPc can be converted to PrPsc, and the already occurring PrPsc encounters with PrPsc in the cell or on the cell surface. , the formation of heterodimers or trimers, the conversion of PrPc to PrPsc, this process seems to be an autocatalytic reaction, without the need for chemical modification, can increase the PrPsc exponentially, because PrPsc on the intracellular lysosome The protease in the protease is resistant and will not be destroyed. When it accumulates to a certain extent, it causes spongiform lesions of the brain tissue. The mutation of the PrPc gene can be familial, which can explain familial prion diseases such as familial CJD. And fatal familial insomnia (FFI).

(2) Damage of brain tissue: Another possible mechanism is that exogenous PrPsc can reach brain tissue cells after infection, and if it is large, it may directly cause damage to brain tissue, but the more likely mechanism may be this. When exogenous PrPsc is encountered with endogenous PrPc, it may also transform a large amount into PrPsc to cause lesions.

Pediatric new variant Kreuzfeldt-Jacob disease prevention

The control of this disease consists in taking measures to prohibit the addition of ruminant tissue to ruminant feed, taking measures to ensure the inactivation of all infected prions in slaughter or refining procedures, and controlling nvCJD also includes the ban on eating animals. Various organizations to reduce exposure to BSE factors, national and worldwide monitoring of BSE and nvCJD are also beneficial to limit the disease, the World Health Organization (WHO) European Union (EU) related agencies to prevent BSE transmission to humans, A series of guidelines and requirements have been developed, including the above measures, as well as the classification of different tissues of cattle. According to the main points, it can be considered that eating milk, dairy products, beef, etc. does not cause the disease, but in the past Condiments made from bovine bones (including vertebrae, and possibly spinal cords) without high temperature treatment have been used on the market, and such foods may spread the disease, although to date there is no evidence of bovine central nervous tissue. Pharmaceutical products prepared from tissues other than outside cause nvCJD to occur, but when manufacturing pharmaceutical products from different tissues of cattle, it should be highly restricted Source material (ie, cattle should be drawn from the BSE-free countries), the production process should eliminate prions or similar pathogens measures.

Pediatric new variant Kreuzfeldt-Jacob disease complications Complications dementia

Dementia and movement disorders appear later.

Pediatric new variant Kreuzfeldt-Jacob disease symptoms Common symptoms Ataxia involuntary movement Depression and dementia

The incubation period of the disease is about 9 years. Zeidler et al. analyzed 21 cases of nvCJD in the UK. The average age of the patients was 29 years (range, 16 to 48 years). The median duration of the disease was 14 (9 to 35 months). In the first month, all patients had psychiatric symptoms in the early stages of the disease (most commonly depression), 13 patients visited the psychiatrist at an early stage; 8 patients developed sensory symptoms at an early stage, and all cases showed ataxia And involuntary movement, most patients near the end of the disease when there is no dynamic dumb, most cases have EEG abnormalities, brain imaging can show non-specific abnormalities.

The clinical features of nvCJD are psychosis, paresthesia and ataxia, and later manifestations of dementia and other symptoms of advanced CJD progression, but the patient's age is small and the course of disease is relatively long.

Pediatric new variant Kreuzfeldt-Jacob disease check

The following tests have an auxiliary diagnostic significance:

1. Cerebrospinal fluid examination of cerebrospinal fluid neuron-specific enolase 35ng / ml, glial protein S-100 8ng / ml, and the so-called 14-3-3 protein and tau protein positive, when the clinical manifestations are consistent with the disease, Very supportive of the diagnosis of this disease.

2. The tonsil biopsy has reported that the Western blotting of monoclonal antibodies against PrPsc in the tonsil biopsy specimens can make early diagnosis of BSE, but whether this method can be used to diagnose nvCJD has not been determined.

Brain CT and EEG should be checked.

1. EEG examination of EEG abnormalities, but in any case did not see the typical periodic integrated wave of CJD.

2. Imaging examination of the brain The imaging examination of the brain is usually normal or non-specific abnormality. Although it has been reported that the single-photon emission computed tomography (SPECT) technique is helpful for the diagnosis of nvCJD, it is not specific to this disease.

Diagnosis and differential diagnosis of pediatric new variant Kreuzfeldt-Jacob disease

The diagnosis of this disease and the identification of sporadic CJD rely on histopathological examination of brain tissue, but it is difficult to do brain biopsy in clinical cases. Other laboratory tests can not confirm the diagnosis, but it is important for diagnosis. The meaning of the reference.

The main difference between nvCJD and sporadic CJD identification is the following:

1. Most cases of age at onset of nvCJD are diagnosed before the age of 40, while the CJD of sporadic hair is only 1% or less.

2. Clinical manifestations The clinical manifestations of nvCJD in the early stage of the disease were mainly behavioral changes, while early-stage CJD dementia was performed.

3. EEG examination The electroencephalogram of nvCJD cases lacks three-phase slow waves, but most of the sporadic CJD cases have this wave.

4. Neuropathological changes In most cases of nvCJD neuropathology, brain tissue plaques have been stained for prion protein, but this phenomenon is rare in sporadic CJD.

The material in this site is intended to be of general informational use and is not intended to constitute medical advice, probable diagnosis, or recommended treatments.