First Suspected Case of Sporadic Creutzfeldt-Jakob Disease in Syria

Introduction

Prion diseases are rare and fatal neurodegenerative diseases caused by the buildup of a misfolded prion protein, leading to neural apoptosis and spongiform degeneration of brain tissue. Sporadic Creutzfeldt–Jakob Disease (sCJD), which has an unknown cause, represents more than 85% of CJD cases, with an incidence of 1.5 to 2 per million worldwide annually.¹ However, a recent global epidemiology atlas indicates that formal surveillance data are only available from 34 countries worldwide Figure 1.² On the other hand, data from low- and middle-income countries (LMICs) primarily rely on case reports or case series.^3–9 This lack of data is particularly concerning for LMICs, where underreporting is common due to limited diagnostic capacity.¹⁰ Less frequent forms include: genetic CJD (gCJD) due to inherited disease-causing mutations in the prion protein gene PRNP, iatrogenic CJD (iCJD) from medical procedures, and variant CJD (vCJD) from consuming contaminated beef.¹ CJD progresses rapidly, with nearly 90% of patients dying within a year of symptom onset. The clinical presentation is nonspecific and includes myoclonus, cognitive impairment, rapidly progressive dementia, hallucinations, and cerebellar signs.¹¹ While sCJD may not be initially suspected, it should be considered in cases of rapid cognitive decline. This paper discusses a case of probable sCJD, which is, to our knowledge, the first in Syria. We address diagnostic difficulties in low-income countries, where biochemical confirmation is costly, making clinical findings and neuroimaging crucial. We also highlight the need for surveillance protocols to document future cases and prevent outbreaks.

Figure 1 Heatmap showing the global annual mortality rate (AMR) of sporadic Creutzfeldt–Jakob Disease illustrated as color gradients (cases per million).

Figure 2 Timeline of the progression of the disease detailing major signs and symptoms divided into three periods: prehospitalisation, hospitalisation, and posthospitalisation.

Case Report

History

A 72-year-old woman presented to our hospital after rapid deterioration of consciousness level and motor function. The patient was a life-long nonsmoker and abstained from alcohol. Medical history included hypertension. A detailed history was taken from family members and revealed inattention, failure to perform daily activities, apathy, disorientation to time and place, notable personality changes, and altered speech patterns starting two months before presentation Figure 2. The patient then developed visual hallucinations, behavioral abnormalities (placed her shoes in the refrigerator), and poorly defined involuntary movements that subsided during sleep. Notably, she exhibited depressive symptoms for several months preceding the neurocognitive decline. The patient was examined by several neurologists who excluded thyroid function abnormalities and vitamin B12 deficiency, however, the diagnosis remained inconclusive.

Admission

A local neurologist referred the patient to our hospital upon worsening consciousness level and motor function. Physical examination upon admission revealed positive Hoffman and Babinski signs bilaterally, and rigidity in all four limbs. Further testing revealed pyuria and blood granulocytosis. The patient was hospitalized for supportive care and case study, during which she developed myoclonic jerks and hyperreflexia, and received a brain magnetic resonance imaging (MRI) scan from a nearby private facility showing multiple abnormalities. Table 1 and Figure 3 detail the patient’s significant work-up results and key examination findings.

Table 1 Outline of Significant Clinical, Chemical, and Neuroimaging Findings During Hospitalisation

Figure 3 Serial axial diffusion-weighted magnetic resonance images (DWI) demonstrating cortical hyperintensity (cortical ribboning) and basal ganglia involvement. (a): Fronto-parietal cortex. (b–e): Occipito-temporal cortex. (f): Temporal cortex. (c and d): Note the characteristic high signal intensity in the heads of the caudate nuclei and putamen.

Diagnosis

Given the patient’s history of rapidly progressive neuropsychiatric disorder, clinically evident myoclonus, and extrapyramidal and pyramidal signs, along with the characteristic brain MRI findings, a diagnosis of probable sCJD was established based on the CDC diagnostic criteria,¹² which require: (1) Progressive dementia; and (2) At least two of the following clinical features: myoclonus, visual or cerebellar signs, pyramidal/extrapyramidal signs, or akinetic mutism; along with (3) A typical MRI finding of high signal in the caudate nucleus and putamen or at least two cortical regions on Diffusion-Weighted Imaging (DWI) or Fluid-Attenuated Inversion Recovery (FLAIR). As noted in Figure 3, the DWI abnormalities are present in almost all cortical regions with thalamic and striatal involvement. This pattern is more indicative of CJD and excludes other types of rapidly progressive dementia such as autoimmune encephalopathy.^13–15 The symmetrical abnormalities observed on the DWI also indicates a later stage of the disease, aligning with the patient’s clinical presentation.¹³ Several CJD-mimicking diseases were excluded based on clinical reasoning and biochemical findings Table 2.¹⁶ Real-time quaking-induced conversion (RT-QuIC) and cerebrospinal fluid (CSF) 14.3.3 were unavailable.

Management

Myoclonic jerks and rigidity were managed via Levetiracetam (500 mg/12 hours) and Levodopa/Carbidopa (100/25 mg/8 hours), respectively. The patient also received proper hypertensive therapy and antibiotic therapy (Ceftriaxone 1000mg/24 hours and Levofloxacin 750 mg/24 hours) for urinary tract infection. She was discharged to receive care at home as requested by her family.

Follow-Up

Three months later, follow-up examination revealed a right-sided palmomental reflex and palmar grasp reflex. The patient also exhibited severe cervical dystonia. A few days later, she developed aspiration pneumonia, which led to her death.

Discussion

The presented case report highlights a probable sCJD in a 72-year-old woman, which to our knowledge, is the first case to be documented in Syria. Given the estimated annual global incidence of 1.5–2 cases per million,¹ the absence of prior reports from Syria, a country with a population of approximately 20 million, suggests a significant surveillance gap and profound underdiagnosis. The case underscores the need for a national prion disease registry to monitor future cases, including iCJD and vCJD, and aid in outbreak prevention. Additionally, the patient’s nonspecific symptoms emphasize the importance of considering CJD in differential diagnoses, as delayed diagnosis may stem from not considering prion diseases in the first place.

This report has several limitations, primarily the lack of CSF 14.3.3 testing and advanced diagnostic tools such as RT-QuIC. Consequently, diagnosis relied heavily on clinical examination, exclusion of other conditions, and brain MRI findings. The patient was referred to a private facility to quickly obtain an MRI scan, however, the majority of patients normally face long MRI waitlists in affordable public hospitals, reflecting the broader difficulties of accessing advanced imaging in LMICs.¹⁰ Cultural considerations did not allow for performing post-mortem brain biopsy, which prevented the histological, ie gold standard, confirmation of the diagnosis. Furthermore, as noted in Table 2, the lack of specific ancillary tests means we could not definitively exclude all CJD mimics. However, as detailed in the case discussion, it is unlikely that this case is a CJD mimic as it fits the criteria for a probable CJD diagnosis.

Table 2 Diagnostic Rationale Behind Excluding Various Sporadic Creutzfeldt–Jakob Disease Mimics

The economic realities of healthcare in resource-limited countries are another limitation. In such contexts, the economic value of pursuing extensive diagnostic procedures for currently untreatable diseases such as CJD can be questioned, especially when resources are needed for managing treatable conditions. Hence, CJD registries are limited to high income countries, which renders case reports from LMICs essential to better understand the global burden. Collaborative initiatives between research institutions and LMIC healthcare systems could provide cost-effective screening strategies that improve CJD surveillance.

A review of the experiences in other developing nations reveals a consistent challenge in obtaining definitive diagnoses for CJD which limits the comprehensiveness of global epidemiological understanding.² Surveillance is often either non-existent or inadequate in many LMICs, contributing to underreporting and frequently relying on clinical criteria rather than pathological confirmation.^2,17 For example, in a series of six cases reported from Peru, all patients were discharged with a probable diagnosis of prion disease because necropsy, the gold standard for definitive confirmation, was not performed.⁶ Furthermore, key supportive tests like the 14-3-3 protein assay in CSF were often not performed due to the high cost of extra-institutional private testing.⁶ Recent reports from Morocco, Romania, and Saudi Arabia were largely established as probable CJD, relying heavily on clinical criteria, MRI, and sometimes EEG, due to the unavailability or financial constraint of definitive confirmatory tests.^3–5 Similarly, reports from various Asian countries underscore the provisional nature of many diagnoses, often classifying cases as probable or possible sCJD.¹⁷ For instance, Chinese surveillance data, despite being extensive, still categorized the vast majority of sCJD cases reported between 2010 and 2016 as probable or possible rather than definite.¹⁷ In India, a lack of applicable diagnostic techniques meant earlier reports included a significant number of probable cases.¹⁷ Even in more recent Indian case reports, the ability to perform highly specific tests like CSF 14-3-3 and RT-QuIC was not possible due to financial and logistic constraints.⁷ Earlier studies in India (2011–2013) and Kenya (1990–2004) also described numerous probable and possible cases.^8,9 The abundance of probable and possible reports from LMICs reflects similar logistical conditions and underscores the critical need for national surveillance systems in LMICs to track the global burden of prion diseases and improve early detection.

Raising awareness among clinicians about prion diseases is essential to overcome difficulties in diagnosis, mitigate diagnostic delays, and improve case detection rates. Education through workshops, seminars, and accessible resources like clinical guidelines can aid early recognition and enhance understanding and preparedness, ultimately improving diagnosis and patient management in the region.

Conclusion

This case highlights the pressing need to raise awareness of prion diseases among healthcare professionals in resource-limited countries. It underscores the importance of including CJD in the differential diagnosis of rapidly progressive dementia, suggesting the need for prion disease surveillance and registries in LMICs. Despite limitations such as diagnostic resource scarcity and economic constraints, this report serves as a foundational step toward recognizing and addressing prion diseases in Syria and similar regions.