Classification of spongiform encephalopathies
This group of infections affects both humans and various animal species. The pathological process leads to specific changes in brain tissues, giving them a characteristic spongiform structure.
The main nosological forms occurring in humans include:
- Creutzfeldt-Jakob disease;
- Kuru disease;
- Gerstmann-Sträussler-Scheinker syndrome;
- Fatal familial insomnia;
- Amyotrophic leukospongiosis.
Prion infections also circulate among animals. The best known are scrapie (scrapie), which affects sheep and goats, as well as bovine spongiform encephalopathy (infamously known as "mad cow disease"). In addition, transmissible mink encephalopathy, feline spongiform encephalopathy, and chronic wasting disease, which occurs in captive deer and elk, are distinguished.
Creutzfeldt-Jakob disease (CJD)
This is the most well-known human prion pathology, with an incubation period that can stretch up to 20 years. The clinical picture is dominated by rapidly progressive dementia, various movement disorders, as well as visual and cerebellar impairments.
The disease occurs in two main forms:
- Classic variant. Affects primarily elderly individuals (average age of onset is 68 years). It is characterized by a lightning-fast course: death occurs just 4–5 months after the manifestation of symptoms.
- New variant. Occurs in younger patients (average age is about 28 years). The disease lasts somewhat longer, and death is recorded after 13–14 months.
Routes of infection and causes:
- Alimentary route: infection occurs through the consumption of the brain or meat of cows suffering from spongiform encephalitis, especially if the products have undergone insufficient heat treatment.
- Iatrogenic (medical) route: associated with medical procedures. Infection can be transmitted through blood transfusions, corneal transplants, the use of surgical sutures (catgut), or insufficiently sterilized instruments. Mortuary procedures and the administration of biologically active substances of animal origin (e.g., hormones) to patients pose a hazard.
- Spontaneous and genetic mechanisms: the development of the disease is provoked by the hyperproduction of the normal PrP protein or the stimulation of its transition into the pathological form PrPsc against the background of insertions and mutations in the prion gene (familial cases occur).
Kuru ("Shivering")
A historically important disease whose epidemiology is closely linked to the island of New Guinea, where the infection massively affected Papuan tribes. The infectious nature of this disease was first proven by researcher D. Carleton Gajdusek.
The mechanism of transmission of infection is alimentary. Infection occurred during the process of ritual cannibalism: tribe members ate the brains of their deceased relatives, which were not subjected to sufficient heat treatment.
The clinical picture of Kuru includes:
- Pronounced cerebellar disorders (gross disturbances of gait and coordination of movements);
- Mental and autonomic symptoms: severe chills and inappropriate euphoria, for which the pathology was dubbed "laughing death".
The prognosis for Kuru is absolutely unfavorable — patient death occurs within 1 year.
Inherited prion syndromes
In addition to acquired forms, there are prion diseases that are inherited and have a strict familial character.
Gerstmann-Sträussler-Scheinker syndrome is an inherited pathology with an incubation period from 5 to 30 years. Symptomatology includes dementia, pronounced muscle hypotonia, and bulbar syndrome (severe swallowing disorders, dysarthria). After the appearance of the first symptoms, the disease inexorably progresses, leading to death in 4–5 years.
Fatal familial insomnia is inherited in an autosomal dominant manner. A key manifestation is progressive insomnia and a total disruption of circadian rhythms. The condition is accompanied by sympathetic hyperreactivity: patients exhibit tachycardia, hypertension, hyperthermia, and hyperhidrosis. Later, severe neurological manifestations join in — myoclonus, ataxia, tremor, and hallucinations. The direct cause of the patient's death is progressive cardiovascular failure.
Briefly: answers to topical questions
What is the structural difference between the pathological prion PrPsc and the normal PrPc protein?
The structural difference between the pathological prion PrPsc and the normal PrPc protein lies in a conformational change and a decrease in molecular weight.
| Characteristic | Normal protein (PrPc) | Pathological prion (PrPsc) |
|---|---|---|
| Proportion of $\beta$-sheet structures | 3% | More than 40% |
| Molecular mass | — | Decreased: 27–30 kDa |
| Properties | — | Hydrophobic, prone to the formation of amyloid fibrils/plaques |
The pathological isoform arises as a result of post-translational modifications and accumulates in plasma vesicles.
What laboratory diagnostic methods are used for ante-mortem confirmation of prion diseases?
For ante-mortem definitive confirmation of prion diseases, CNS tissue biopsy is used.
Also used in diagnostics are:
- Pathohistology — detection of spongiform changes in brain tissue, astrocytosis/gliosis, staining for amyloid; an important sign is the absence of inflammatory infiltrates.
- Immunochemical methods — detection of protein markers of brain disorders in cerebrospinal fluid using ELISA and immunoblotting with monoclonal antibodies.
- Molecular genetic methods — genetic analysis of the prion gene and PCR for the detection of PrP.
What is the resistance of prions to standard sterilization and disinfection methods?
Prions possess extreme resistance to standard sterilization and disinfection methods. Conventional decontamination regimens, including formalin treatment and standard autoclaving, do not reduce their infectivity.
Strict conditions are required for inactivation:
- Autoclaving — at 134 °C for 30 minutes or at 121 °C for 4 hours (with the addition of 1N NaOH).
- Chemical treatment — use of bleach with 1N NaOH with a 1-hour exposure.
- Physical method — incineration of materials.
Also, pathological proteins are resistant to proteolysis, high temperature, radiation, and $\beta$-propiolactone.
What pathomorphological changes in brain tissue are characteristic of transmissible spongiform encephalopathies?
Transmissible spongiform encephalopathies are characterized by spongiform changes in brain tissue, a decrease in the number of neurons, gliosis/astrocytosis, amyloid plaques, and the absence of inflammatory infiltrates.
- Spongiosis — appearance of multiple oval vacuoles in the neuropil and neurons; fusion of vacuoles leads to microcyst formation and disruption of cortical cytoarchitecture.
- Neuronal changes — progressive vacuolar degeneration, reduction in the number of neurons; surviving neurons are shrunken and hyperchromic.
- Glia — proliferation of glial elements, progressive astrocytosis/gliosis.
- Amyloid plaques — prion protein amyloid plaques; in Gerstmann–Sträussler–Scheinker syndrome, a large number of plaques containing PrP-Sc are described, predominantly in the cerebellum.
- Inflammation — an important differential diagnostic feature: absence of inflammatory infiltrates.
Macroscopically, prion encephalopathies are characterized by atrophy of the cerebral convolutions; in Creutzfeldt–Jakob disease, diffuse cerebral cortical atrophy with spongiform changes is observed.
To remember the three main mechanisms of Creutzfeldt-Jakob disease development, use the acronym «MEATS»: Medical (iatrogenic), Evident Spontaneous (mutations), and Alimentary (contaminated food).
Class and exam questions
What is the main difference between the classic variant of CJD and the new variant?
The classic variant affects older individuals (average age 68) and leads to death within 4–5 months. The new variant occurs in younger people (around 28 years old), and the disease duration is 13–14 months.
How can one contract a prion infection in a medical facility?
The iatrogenic pathway occurs through the use of insufficiently sterilized instruments, catgut, blood transfusions, tissue transplants (cornea), as well as the administration of animal hormones and during autopsy procedures.
What is the cause of death in fatal familial insomnia?
Despite severe neurological disorders, the immediate cause of death in such patients is progressive cardiovascular failure.
What else to study on this topic
- Pathogenesis of PrP protein transformation into the pathological PrPsc form
- Sympathetic hyperreactivity in fatal familial insomnia
- Amyotrophic leukospongiosis: clinical features
- Specifics of spongiform encephalopathies in various animal species (scrapie, mad cow disease)
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