Transmissible spongiform encephalopathies (TSES), also known as prion diseases, are rare and fatal neurodegenerative disorders caused by misfolded prion proteins. These diseases, including Creutzfeldt-Jakob Disease (CJD) and fatal familial insomnia (FFI), offer unique challenges in diagnosing TSEs due to their subtle early symptoms and rapid progress. Accurate diagnosis is important for continuing patient care, public health and research efforts.  This article explores the equipment, biomarkers and obstacles associated with early detection of TSE.

Diagnostic Tools for TSEs

Diagnosis of TSE depends on clinical assessment and combination of special tests. Since TSEs share symptoms with other neurological disorders, doctors use clinical equipment to identify the unique properties of prion diseases.

• Electroencephalogram (EEG): EEG measures brain activity and can uncover specific abnormal wave patterns that are often associated with occasional sporadic Creutzfeldt-Jakob Disease (SCJD). In some cases, EEG may not always detect changes in early stages.

• Magnetic resonance imaging (MRI): MRI scans provide wide images of brain tissue. Specific patterns, such as hyperintensity, may be a sign of TSE in the basal ganglia or thalamus. Advanced imaging technology continues to improve clinical accuracy.

• Cerebrospinal fluid (CSF) test: Analysis of cerebrospinal fluid helps identify biomarkers associated with prion diseases. Tests for 14-3-3 protein, rope protein and other markers are often used. Although these biomarkers are not very specific to TSEs, they are valuable to support a diagnosis.

• Genetic Testing: For hereditary TSE, the genetic test of the prion protein gene (PRNP) identifies familial insomnia (FFI) and Gerstmann-Sträussler-Scheinker syndrome (GSS). Genetic counseling is necessary for risk families.

Despite the use of these devices, many evidence must often be put together to diagnose TSE, as no test is safe.

The Role of Biomarkers in Diagnosis

Biomarkers play an important role in the diagnosis of TSE, especially in cases where clinical properties are not clear. Many biomarckers have been identified, providing insight into the disease process:

• 14-3-3 Protein: The presence of 14–3-3 proteins in cerebrospinal fluid is associated with neuronal injury and is often detected in patients with occasional CJDs. Although it is not exclusive to TSEs, it is a useful indicator of neurodegeneration.

• Tau protein: The elevated level of tau protein in cerebrospinal fluid may indicate the presence of pioneer diseases. Tau is also associated with other neurodegenerative energy disorders, making it an aid, but fruitless biomarker.

• RT-QuIC Assay: real-time quaking-induced conversion (RT-QuIC) assay analysis is a groundbreaking technique that detects high-sensitivity protein interactions with high sensitivity and uniqueness. In vitro, by increasing the writing set, RT-QuIC has emerged as one of the most promising clinical units for TSE.

• Genetic mutation: The PRNP gene has fixed markers for the hereditary forms of TSE. Identifying these mutations provides clarity in family matters and guides the risk assessment.

Biomarkers help doctors separate TSE from other conditions, but the challenge is to develop biomarkers that definitely detect the disease in its early stages.

The Challenge of Early Detection

Early detection of TSE is particularly challenging due to many factors:

• Subtle early symptoms: Early symptoms of TSE, such as mild memory loss, mood or fatigue, often mimic other neurological or psychiatric conditions. This delays to requirement for medical treatment and performing special tests.

• Rapid progress: When the symptoms become clear, the TSE goes fast, leaving a narrow window for diagnosis. Patients may already be in advanced stages at testing time.

• TSEs Rarity: Rarity of Prion Diseases means that many doctors have limited experience in diagnosing them. It can contribute to incorrect diagnosis or delayed recognition.

• Overlap with other disorders: TSE symptoms overlap with Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders, which complicate the diagnosis.

Emerging Advances in Detection

Research runs innovation in preliminary detection methods for TSE. Promising progress includes:

• High-sensitivity biomarker: Attempting to identify the new biomarker who quickly and especially detects prion diseases continues in clinical technology with  RT-QuIC.

• Non-invasive technology: searching for blood-based or urine-based analyses can make TSE diagnosis less aggressive and more accessible.

• Machine learning models: Artificial intelligence is used to analyze complex data from imaging and biomarker tests, which improves clinical accuracy and speed.

Conclusion

An approach to multiple discourse is necessary to combine clinical assessment, biomorker and advanced test units. Although important advances have been made, early identity is still a challenge due to the subtle outbreak and rapid progress of these diseases. Continuous research in biomarker and diagnostic technologies provides hope for better detection and management of TSE. Currently, consciousness and vigilance are important to identify these rare but devastating disorders.