叙利亚首例散发性克雅氏病的疑似病例

《International Medical Case Reports Journal》：First Suspected Case of Sporadic Creutzfeldt-Jakob Disease in Syria

首次确诊叙利亚散发克雅二氏病的72岁女性病例，揭示资源有限地区诊断困难及建立国家监测系统的必要性。

　　
Creutzfeldt-Jakob Disease (sCJD) Case Study from Syria: Diagnostic Challenges and Public Health Implications

Prion diseases represent a critical class of neurodegenerative disorders characterized by progressive neurological deterioration and eventual fatality. Among these conditions, sporadic Creutzfeldt-Jakob Disease (sCJD) accounts for over 85% of reported cases, yet remains largely understudied in low- and middle-income countries (LMICs). This report documents the first probable sCJD diagnosis in Syria, offering critical insights into the limitations of current diagnostic frameworks in resource-constrained settings.

The patient in question was a 72-year-old female presenting with a two-month history of depressive symptoms followed by rapid cognitive decline and motor dysfunction. Key clinical observations included disorientation, behavioral abnormalities (such as placing footwear in refrigerators), myoclonus (involuntary muscle jerks), and symmetrical neurological signs like Hoffman and Babinski reflexes. These symptoms alone warranted immediate consideration of prion diseases within the differential diagnosis.

Neuroimaging played a pivotal role in confirming the clinical suspicion. The MRI scan revealed cortical ribboning—a hallmark of prion-related neurodegeneration—across multiple brain regions, including the frontoparietal cortex and occipitotemporal lobes. Additionally, basal ganglia involvement with high signal intensity on diffusion-weighted imaging (DWI) was observed. Such MRI patterns are classically associated with sCJD and help distinguish it from mimicking conditions like autoimmune encephalopathy or frontotemporal dementia.

Diagnostic hurdles in this case were substantial. First, biochemical confirmatory tests such as cerebrospinal fluid (CSF) 14.3.3 protein assay or real-time quaking-induced conversion (RT-QuIC) were unavailable due to logistical and financial constraints. Second, postmortem neuropathological confirmation—considered the gold standard—was prohibited due to cultural and ethical barriers. Third, the absence of a dedicated national surveillance system in Syria limited the ability to track disease patterns or compare this case with regional data.

The clinical team systematically excluded alternative diagnoses. Blood tests revealed pyuria and granulocytosis, prompting antibiotic therapy for suspected urinary tract infection. However, this did not resolve the progressive neurological decline. thyroid function tests and vitamin B12 levels were normal, ruling out metabolic causes. The progression timeline—depressive symptoms preceding rapid dementia—aligns with typical sCJD presentations, which often begin with non-specific neuropsychiatric changes before advancing to motor dysfunction and fatal outcomes within 12 months.

A critical lesson from this case is the interplay between clinical acumen and resource availability. In LMICs, where specialized prion diagnostics are scarce, clinicians must rely on clinical criteria and imaging patterns. The World Health Organization (WHO) guidelines recommend a three-step approach: initial suspicion based on rapid dementia onset, exclusion of mimics through basic labs and neuroimaging, and confirmation (when possible) using CSF tests or RT-QuIC. However, in Syria and similar settings, even the first two steps are often compromised by delayed access to MRI and the unavailability of standardized diagnostic algorithms.

The patient’s treatment underscored another challenge—lack of effective therapies. Levetiracetam and levodopa were prescribed to manage myoclonus and rigidity, respectively, but these medications are primarily palliative and do not alter disease progression. Asymptomatic supportive care, such as antibiotics for secondary infections and physical therapy, remains the mainstay of management when definitive testing is impossible.

This case also highlights the limitations of existing surveillance systems. While high-income countries like the UK and Canada maintain robust prion disease registries, LMICs often lack the infrastructure to record or analyze such data. The global epidemiology atlas reveals that only 34 nations provide comprehensive surveillance figures for sCJD, with most LMICs relying on sporadic case reports. This gap not only obscures the true disease burden but also hinders research into causation and prevention strategies.

Regional comparisons further emphasize diagnostic disparities. For instance, Peru and India have reported cases of probable sCJD using similar clinical and imaging criteria, yet their national surveillance systems remain underdeveloped. In contrast, countries with advanced healthcare infrastructure have achieved 95%+ diagnostic accuracy through standardized protocols combining clinical evaluation, MRI, and CSF testing. The Syrian case mirrors these challenges but also serves as a catalyst for change.

Key recommendations emerge from this experience:
1. **National Surveillance Systems**:LMICs must establish dedicated prion disease registries to document cases, track progression, and monitor geographic or temporal clusters. Such systems would not only improve local awareness but also feed into global databases critical for public health planning.
2. **Imaging Infrastructure Development**:MRI accessibility in Syria is currently limited to private facilities, creating significant delays and cost barriers. Public hospitals in LMICs require targeted investments in neuroimaging equipment and training programs to interpret prion-specific MRI patterns.
3. **Education and Training**:Physicians in resource-limited settings need regular updates on prion disease clinical features and diagnostic algorithms. Multidisciplinary workshops involving neurologists, radiologists, and public health officials could bridge knowledge gaps.
4. **Cost-Effective Diagnostic Tools**:Research into low-cost, rapid diagnostic tests for prion diseases is urgent. For example, simplified CSF testing protocols or portable MRI units could democratize access to critical diagnostics.
5. **Ethical and Cultural Considerations**:Postmortem brain biopsy, while definitive, is often inaccessible due to cultural taboos or logistical hurdles. Alternative confirmatory methods, such as CSF 14.3.3 testing, should be prioritized even in resource-constrained environments.

The case also reveals systemic healthcare weaknesses in LMICs. Limited budgets often prioritize treatable conditions over rare diseases, leading to underinvestment in prion research. For instance, the Syrian healthcare system struggles to balance routine services with niche neurological disorders. This imbalance necessitates advocacy for equitable funding mechanisms and international partnerships to share diagnostic expertise.

Global implications are equally significant. The WHO estimates that sCJD incidence in LMICs is underreported by a factor of 10–20 due to diagnostic delays. This means the true global burden could be twice the current 1.5–2 cases per million estimate. Accurate data is crucial for understanding disease distribution, risk factors, and potential transmission pathways. For example, regions with high beef consumption or medical tourism might see elevated sCJD rates, but such correlations are difficult to establish without robust surveillance.

The video abstract accompanying this report underscores the importance of visualizing complex neurological cases. Through animations, it demonstrates how MRI findings correlate with disease progression stages—initially affecting the caudate nuclei and putamen before spreading to cortical regions. This visual guidance can be particularly valuable for clinicians unfamiliar with prion neuroimaging patterns.

Keywords and themes:
- **Epidemiology**: Underreporting in LMICs leads to inaccurate disease prevalence data.
- **Neuroimaging**: Cortical ribboning and basal ganglia involvement are key MRI indicators.
- **Diagnostic Barriers**: Lack of access to CSF testing and RT-QuIC hinders confirmation.
- **Public Health Strategy**: Surveillance systems and cross-border collaborations are essential for outbreak prevention.

This case report is not merely a documentation of an individual’s experience but a call to action for healthcare systems worldwide. By addressing diagnostic gaps, improving surveillance, and fostering international collaboration, LMICs can contribute meaningfully to global prion disease research. The Syrian case exemplifies both the fragility of current diagnostic frameworks and the potential for transformative change through targeted investments in healthcare infrastructure and education.

最终，这一病例研究为全球卫生政策制定者提供了重要参考。在叙利亚这样的国家，建立以临床评估和MRI为核心的诊断流程，同时推动低成本检测工具的研发，将成为遏制神经退行性疾病蔓延的关键。通过整合国际资源与本土需求，LMICs有望在提升疾病诊断率的同时，为全球神经退行性疾病防控贡献独特经验。