1 Introduction

Creutzfeldt-Jakob disease (CJD) is an extremely rare neurodegenerative disease. With an average life expectancy of about 6 ± 4 months, about 70% of CJD patients begin with rapidly progressive dementia [1]. Numerous studies have shown that microglia are activated by prion proteins (PrP^sc) in CJD and produce cytokines such as IL-8, IL-1β, IL-10, etc. [2, 3]. These inflammatory cytokines are related to progressive dementia in patients with CJD and play an important role in the Blood-Brain Barrier (BBB) impairment and apoptosis of neuronal cells [1, 4, 5]. Importantly, inflammatory cytokines overexpression is also found in neurodegenerative disease [6, 7]. They contribute to astroglial proliferation and astrogliosis, and inflammatory reactions lead to synaptic atrophy and eventually neuronal cell death [8]. These pathological changes are a direct contributor to cognitive decline in neurodegenerative diseases including CJD [9].

Although several data have indicated that inflammatory cytokines play a crucial role in CJD, most of these studies have been conducted on animals, and it is not clear enough the levels and effects of different cytokines, especially CSF, in human patients with CJD. To further determine the levels of expression of different cytokines in CJD we examined inflammatory cytokine levels in both blood and CSF in a CJD patient, and an epileptic encephalopathy patient's CSF and blood are examined as the control case.

2 Case Presentation

2.2 Investigations and Results

The DWI MRI scan shows that prominent diffusion restriction along the cortical ribbon (Figure 1A), and V-EEG indicates periodic release of sharp and three-phase waves (Figure 1B). Subsequently, the most important marker 14–3-3 protein showed positive in CSF. Finally, the patient was diagnosed with Probable CJD [10]. Firstly, we examined the CSF albumin and blood albumin of the patient (Table 1). Then, the different inflammatory cytokines in the CSF and blood of the patient were examined (Table 2).

TABLE 1. Cytokines levels in CSF and blood of patients with CJD and epileptic encephalopathy.

	CSF (pg/mL)		Blood (pg/mL)		Reference values (pg/mL)
	Case 1	Case 2	Case 1	Case 2
IL-6	1.25	2.48	12.20**	1.20	0–3.4
IL-8	51.90*	48.60	31.70**	4.20	0–14
TNF-α	5.02	6.04	14.40**	3.50	0–9.1
IL-10	4.50	4.20	3.70	3.90	0–9.1
IL-1β	8.89**	5.40	8.36**	3.60	0–5

• * p < 0.05.
• ** p < 0.01 vs. Case 2.

TABLE 2. Albumin levels in CSF and blood of patients with CJD and epileptic encephalopathy.

	Case 1	Case 2	Reference
Albumin (CSF) (g/L)	0.67**	0.34	0.15–0.45
Albumin (Blood) (g/L)	40.3	43.1	35–55
Albumin index of CSF/blood	16.7**	7.9	0–7.5

• ** p < 0.01 vs. Case 2.

3 Discussion

CJD is a rare neurodegenerative disease that presents with the rapid progression of cognitive dysfunction, ataxia, myoclonus, and death in less than 1 year. Early cognitive impairment is a prominent clinical feature, in which neuroinflammation plays a key role and elevated inflammatory factors accelerate cognitive impairment [11]. Our cases showed that IL-6, IL-8, IL-1β, and TNF-α levels were elevated in blood in the patient with CJD, but only IL-8 and IL-1β levels, especially IL-8, were significantly elevated in CSF.

IL-8 is a chemokine associated with immune response properties [12]. Several studies have shown that IL-8 levels are significantly higher compared to other inflammatory cytokines like IL-6, IL-1β, and TNF-α in various dementia diseases, such as Alzheimer's disease and vascular dementia et al. [6, 13]. Our cases also have shown that IL-8 levels obviously increased in the CSF of the CJD patient and the epileptic encephalopathy patient. In addition, IL-8 is significantly higher in the CSF of the CJD patient compared with the epileptic encephalopathy patient, which is roughly normal in the blood of the epileptic encephalopathy patient. Statistical analysis showed a marked difference in two cases (p < 0.05), which is different from a previous study [6]. Previous studies have shown that during the early stages of CJD, microglia are stimulated to secrete IL-8, and the action of IL-8 leads to apoptosis of neuronal cells, resulting in cognitive impairment [1]. Based on these results, we presume that IL-8 might be associated with the severity of cognitive impairment and suggest that IL-8 is the most sensitive inflammatory cytokine in the early stages of the inflammatory pathological reaction in CJD. Meanwhile, our cases have shown that IL-1β levels elevated in the CSF both in the CJD patient and the epileptic encephalopathy patient, but they were normal in the blood of the epileptic encephalopathy patient. Numerous studies have shown IL-1β could increase BBB permeability and participate in processes of cognition, learning, and memory [14]. In Table 1, results also showed that the C/B albumin index in the CJD patient is higher compared with the epileptic encephalopathy patient, indicating the BBB impairment. We considered that these results indicated that there is more obvious BBB damage in CJD than in the epileptic encephalopathy patient [15].

4 Conclusion

In summary, our observations showed that the levels of IL-8 and IL-1β notably increased in the CSF of CJD patients, suggesting that these two cytokines are closely related to cognitive impairment and BBB damage in CJD. Particularly, IL-8 might be a key target in early cognitive impairment in CJD. Furthermore, more studies are needed to study the role of these inflammatory factors in cognitive impairment in CJD.

Author Contributions

Liu GuoYan: data curation, writing – original draft. Zhan ShuQin: investigation. Qu HuiYang: data curation, investigation. Chen MengYing: formal analysis, writing – original draft. Ren HongWei: investigation, writing – original draft. Sun Hong: writing – review and editing.

Consent

Written consent was received from patients prior to the publishing of this case report and its related photographs.

Conflicts of Interest

The authors declare no conflicts of interest.