Lecture 11 - Chronic inflammatory & demyelinating diseases of virus origin (rev) (2025) (2)

Overview of Chronic Inflammatory and Demyelinating Diseases

Chronic inflammatory and demyelinating diseases can be caused by viruses. This document explores the characteristics and examples of these diseases, particularly focusing on slow virus infections and their impact on the central nervous system (CNS).

Introduction to Slow Virus Infections

The concept of slow virus infections was introduced in 1954 by Bjorn Sigurdsson, an Icelandic pathologist, during his lectures at the University of London. He described these infections as a category of diseases characterized by a prolonged initial period following the primary infection, which can last from several months to years. Once clinical signs appear, the disease often has a prolonged course, leading to severe health issues or death eventually.

Key Features of Slow Virus Infections

In defining slow virus infections, Sigurdsson suggested several criteria:

1. Prolonged Initial Period: There is a very long initial period after the primary infection.

2. Protracted Course: After clinical signs appear, the course is usually long and fraught with complications, often ending in serious disease.

3. Host Specificity: These infections tend to be limited to a single host species and affect specific anatomical systems, manifesting lesions in only one or a few organ systems.

Virus Persistence in the CNS

The central nervous system is a common site for virus persistence, as numerous viruses can reside within it. Factors contributing to this persistence include:

• Anatomical and Immunological Barriers: The CNS is relatively devoid of immune cells, and its unique barriers prevent effective clearance of viruses that enter.

• Immunoglobulin Levels: Immunoglobulin concentrations in the CNS are substantially lower than in serum.

• MHC Protein Expression: Low expression levels of MHC proteins on neurons inhibit the action of CD8+ T cells that would typically clear viral infections in other tissues.

• Immunological Tolerance: If the virus infects during critical developmental stages like in utero, it may provoke less of an immune response.

Other Factors Influencing Persistence

1. Deficits in Immune Function: Immunodeficiencies may allow viruses to persist without adequate immune response, leading to undetected infections.

2. Mutant Viruses: Mutations can lead to defective viruses that elude the immune system by being weakly virulent and thereby avoid rapid elimination.

Measles and Rubella: Key Diseases

Both measles and rubella are childhood diseases that can lead to severe neurological complications. They belong to different viral families but share similarities in their pathologies.

Measles Virus and Its Complications

Measles, once considered a common childhood disease, is caused by an enveloped RNA virus. It has historical significance due to its potential fatality and its resemblance to the Plague. The measles virus causes a range of complications, particularly in the nervous system, including:

• Acute Disseminated Encephalomyelitis (ADEM): An autoimmune condition occurring 1-2 weeks post-rash, leading to possible treatment resolution.

• Measles Inclusion Body Encephalitis (MIBE): Occurs in immunosuppressed individuals and leads to a severe prognosis due to inflammation and necrosis.

• Subacute Sclerosing Panencephalitis (SSPE): An extremely rare yet fatal variant characterized by a progressive neurological decline.

Pathogenesis of Measles

Measles virus transmission occurs via respiratory droplets, leading to initial infection in respiratory epithelial cells. After symptoms such as fever and cough appear, the virus spreads to lymph nodes and the bloodstream. Notable manifestations include:

• Koplik’s Spots: Characteristic oral lesions appearing before the rash.

• Rash Development: Indicates immune activation, coinciding with destruction of virus-infected skin endothelial cells.

The mortality rate for measles is about 1-3 deaths per 1,000 cases, with much higher rates in developing countries. Vaccination has drastically reduced measles incidence.

Rubella and Related Diseases

Rubella virus, or German measles, is also an RNA virus and can lead to severe congenital defects if a mother is infected during pregnancy. Complications following rubella include:

• Congenital Rubella Syndrome: Affects developing fetuses leading to serious abnormalities.

• Acute Disseminated Encephalomyelitis: Similar to measles, presenting within weeks post-rash onset.

• Progressive Rubella Panencephalitis (PRP): This slow infection leads to a gradual neurological decline, typically beginning during the second decade of life.

Vaccination and Public Health Impact

Vaccines for both measles and rubella, often combined as the MMR vaccine, significantly reduce incidence. The introduction of vaccines has led to a decline in cases and effectively eliminated these diseases in many regions. However, misinformation regarding vaccine safety has posed challenges in public health efforts to eradicate these diseases completely.

Conclusion

Chronic inflammatory and demyelinating diseases originating from viral infections remain a critical area of study. Understanding their complexities, particularly those associated with measles and rubella, highlights the importance of vaccination and ongoing research.