Creutzfeldt-Jakob disease presenting with bilateral hearing loss: A case report

lNTRODUCTlON

Sporadic Creutzfeldt-Jakob disease (sCJD) is a prion disease characterized as a fatal transmissible neurodegenerative disorder[1]. The key features of sCJD are rapidly progressive dementia and diverse symptoms including myoclonus, pyramidal and extrapyramidal symptoms, cerebellar disturbance,visual symptoms, and akinetic mutism. Among them, it is known that the most commonly reported presenting symptom is cognitive decline. In other presentations, dizziness is also often the first presenting symptom of sCJD, but hearing loss as an early manifestation is very rare[2]. Herein, we report a case of acute bilateral sensorineural hearing loss as the first manifestation of sCJD.

CASE PRESENTATlON

Chief complaints

A 76-year-old man presented with bilateral sudden hearing impairment and dizziness for 10 d.

History of present illness

The hearing impairment first developed on the left side and then rapidly progressed to bilateral. He also reported dizziness that was aggravated by positional changes and accompanied by a slight gait imbalance, but he could walk without assistance.

History of past illness

He was taking medications for hypertension and diabetes for over ten years. He denied any difficulty with activities of daily living or hearing impairment before the onset of symptoms.

Personal and family history

No special history of personal and family.

Physical examination

The patient revealed no spontaneous nystagmus or gaze-evoked nystagmus. The bedside head impulse test was unremarkable. The other cranial nerves were unremarkable, and there was no limb ataxia.

Laboratory examinations

Laboratory tests including routine blood tests, autoimmune studies, thyroid function tests, and antibodies of the paraneoplastic syndrome were unremarkable except for an HbA1c of 8.1% and hyperglycemia. Pure tone audiometry (PTA) showed bilateral severe hearing impairment (Figure 1).

Imaging examinations

Given his diagnosis of sudden sensory hearing loss, the patient received corticosteroid treatment(prednisolone 60 mg/d for 10 d and tapering) but it was ineffective. Two weeks later, however, he complained of aggravated gait impairment, word-finding difficulty, disorientation, and cognitive impairment. Repeat brain MRI showed high signal intensities in the frontal, temporal, parietal, and occipital cortices on diffusion-weighted imaging (Figure 2B). Cerebrospinal fluid (CSF) analysis revealed normal concentrations of protein and glucose without pleocytosis. However, the real-time quaking-induced conversion (RT-QuIC) assay was positive, and 14-3-3 protein was detected in the CSF by western blotting.

Further diagnostic work-up

Brain magnetic resonance imaging (MRI) was within normal limits (Figure 2A).

FlNAL DlAGNOSlS

Considering all the data, we diagnosed probable sCJD. The amended diagnostic criteria added that the combination of cognitive decline, positive CSF RT-QuIC, and one or more typical CJD symptoms can draw the diagnosis of probable sCJD[3]. Because he had never undertaken neurosurgery dealing with a dura mater and the genetic analysis revealed that there was no mutation or polymorphism of the prion gene, we excluded the possibility of familial CJD or iatrogenic CJD. Moreover, our patient revealed a positive RT-QuIC test and met the criteria of probable sCJD.

《“一帶一路”沿線資源環境與社會發展特征分析》采用信息融合和數據挖掘的方法對“一帶一路”沿線國家和區域的人文和自然等多源數據進行處理，對“一帶一路”沿線國家和地區的資源環境與社會發展特征進行了全面細致的分析.該書夯實了該方面的數據和信息基礎，同時為“一帶一路”相關科學研究提供支撐.但是，“一帶一路”倡議的實施是一個長期的過程，數據是基礎，但還需要完備的政策指導和合理的規劃設計，更依賴于自下而上的有效參與.單純的數據并不能高效的支撐“一帶一路”倡議的實施工作，接下來應基于多源數據，集成數據庫，建立地理信息服務平臺，以便可以更高效快速的為“一帶一路”相關工作的實施提供服務.

TREATMENT

Because of the characteristics of sCJD, the intractable rapidly progressive dementia[1], he received conservative care.

The patient’s symptoms rapidly progressed into akinetic mutism within only two months after the onset of bilateral hearing impairment.

OUTCOME AND FOLLOW-UP

整體來看，RJ版教科書與CM教科書有理數章節的例題素材選取具有一定的共性，即均是無背景的例題所占比重大，且無背景的例題均是有理數加減乘除運算等類的題目．另外，兩版教科書有背景的例題中，均有一小部分例題只是為了有背景”而創設背景，例題的背景素材無實際意義．

DlSCUSSlON

G組患兒家屬的滿意度為97.87%，明顯高于D組的85.1%，兩組相比，差異有統計學意義（P＜0.05）。見表3。

Hearing impairment as an early symptom of sCJD has been described in a few reports[5,6]. Those patients were elderly, older than 65 years, and first complained of only suddenly developed bilateral hearing impairment and subjective unsteadiness. Our patient’s hearing loss were also bilateral and unresponsive to steroid treatment. Postmortem studies in sCJD have revealed that the prion protein deposition in the brainstem is symmetrical and starts in the early stage of sCJD[7]. These neuropathologic characteristics account for the bilaterality of the hearing impairment in patients with sCJD.

The authors of a previous report conducted a brain MRI at the initial presentation, and it was within normal limit[5]. Our patient showed imaging findings that reflected his complaints and symptoms of sCJD. At his first visit when he complained of only hearing impairment and vague dizziness, the brain MRI was unremarkable. After other symptoms developed, however, repeat brain MRI revealed characteristic high signal intensities of the bilateral cerebral cortices, which were a clue for the diagnosis of sCJD.

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他說：“你換購到機票沒有？我是第一次賣里程呢，做一下售后調查，不知道會不會有什么問題。”粒粒回答：“沒有問題，我已經在云南騰沖。”

CONCLUSlON

The patient presented with sudden onset hearing impairment and dizziness, followed by progressive cognitive impairment and confusion. Repeat brain MRI revealed characteristic findings of sCJD, and the RT-QuIC test was positive. For patients with abrupt bilateral hearing impairment, especially in the elderly, various differential diagnoses, including sCJD, should be considered. Moreover, when sCJD is suspected, close follow-up with thorough history taking and neurologic examinations and repeated workups that include brain diffusion-weighted imaging and CSF analysis will be helpful.

This patient presented with an abrupt onset of bilateral hearing impairment and dizziness as the first manifestation of sCJD. Although he only complained of otologic symptoms and was diagnosed initially with bilateral sensorineural hearing loss, the patient then developed additional neurologic symptoms including cognitive decline and prominent gait imbalance, which rapidly progressed. The amended diagnostic criteria of sCJD area that the combination of positive CSF RT-QuIC and progressive cognitive impairment or any of typical CJD symptoms can draw the diagnosis of probable sCJD[3]. Our patient revealed a positive RT-QuIC test and met the criteria of probable sCJD. The possibilities of familial or iatrogenic CJD were excluded because there was no mutation or polymorphism of the prion gene and he had no history of epidemiological evidence. Although the etiology of sCJD has been unknown, many researchers assumed that the prion disease might be initiated by the stochastic misfolded cellular prion protein or mutations in the prion protein gene at ongoing neurogenesis areas[4].

FOOTNOTES

Lee ES conceived and designed the study; Lee TK provided supervision; Lee ES and Lee collected the data; Lee SN wrote the first draft of the manuscript; Lee SA and Lee JD edited and contributed to critical revision; and All authors read and approved the final version of the manuscript for submission.

National Research Foundation of Korea, No. 2019R1C1C1006539.

在此基礎上初步設計出幾套不同風格的界面用于備選。同時要做到以下幾點：①把用戶想象成計算機初學者；②盡量用易于識別的圖示表達，少用文字；③能夠用鼠標點選的絕不做成填寫；④讓用戶感覺不到技術的存在；⑤做到一個沒有“幫助”的軟件。

The authors declare that this single case report has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

The authors declare that they have no conflict of interest.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

“中央空調主機智能節電管理系統”是通過采集末端和室外的溫、濕度變化信號，經過服務器AS4N分析和運算，給出控制信號到控制器GCRE，控制器控制主機按原廠自有的邏輯調節空調負載。把空調主機和末端直接、統一管理，實現了中央空調系統的協調、即時運行和綜合性能優化。智能節電管理系統的核心就是數據庫和策略庫。如圖3所示。

Among the presenting symptoms of our patient, the dizziness was nonspecific and vague, but the hearing impairment was abrupt and very severe. Furthermore, the hearing difficulty was broad, from low to high frequency. When a patient with cognitive decline is suspected of having hearing difficulty,an appropriate evaluation is difficult because laboratory tests, such as pure tone audiometry, cannot be obtained without patient cooperation, and an accurate history of onset time and the pattern of the hearing impairment is needed. In sCJD, the most common presenting symptom is cognitive decline[3].Thus, even if hearing impairment occurs in the early stage of sCJD, evaluations for the presence of hearing symptoms and otologic function under rapidly progressive cognitive decline are difficult. In our patient, however, the history of hearing impairment and the result of PTA were reliable because the patient did not complain of cognitive impairment at presentation.

3.大數據管理決策能力。 “互聯網+”時代，政府治理主體和對象數據信息呈爆發式增長，局限于傳統的監測、管理、應對手段無法摸清經濟社會發展及政府行政真實情況，更難做出科學有效的治理決策，只有借助大數據技術獲取、處理和分析海量信息，支撐經濟管理、政務服務和社會關系塑造等治理活動，才能夠保障政府行為的精確度和科學性。

South Korea

Seunghee Na 0000-0001-8578-8578; Se A Lee 0000-0002-6263-1903; Jong Dae Lee 0000-0003-2866-9841;Eek-Sung Lee 0000-0003-3517-8207; Tae-Kyeong Lee 0000-0001-6913-4689.

Korean Neurological Association.

Ma YJ

A

在農業解決方案中，頗具前景的是創新型數字農業業務，能夠通過數字技術帶來最佳用戶體驗并增加效率。數字技術的應用在每個地區的需求不一樣，數字農業平臺涉及的氣候數據采集、病害診斷、解決方法推薦等，將會幫助農戶更好種植，逐步達到可持續農業發展的愿景。

(2)對于識別樣本,若不滿足式(13)條件則說明高壓開關柜為異常狀態。此時,計算R幀語料的特征和其關于所有訓練模型的似然值p(X/GMMn)。

Ma YJ