Creutzfeldt—Jakob病的临床及病理分析

目的 探讨Creutzfeldt-Jakob病（CJD）的临床特点及诊断,提高生前确诊率。方法 对4例经病理证实的CJD患者的临床表现、光镜及电镜所见进行分析。结果 4例均具有典型的临床表现,病理可见神经细胞变性死亡,胶质细胞增生,无炎性改变,电镜除可见上述改变外,还可见部分髓鞘及轴索的肿胀、变性。结论 此病多为散发性,无特殊有效治疗,预后差。临床病理检查是确诊CJD的最佳检查方法。     

Serial EEG findings in sporadic and iatrogenic Creutzfeldt-Jakob disease.

OBJECTIVE: To study temporal and spatial development of EEG patterns in sporadic and iatrogenic Creutzfeldt-Jakob disease patients. METHODS: Temporal and spatial development of EEG patterns in 4 patients with sporadic Creutzfeldt-Jakob disease and 2 patients with iatrogenic Creutzfeldt-Jakob disease due to implantation of contaminated brain depth electrodes were investigated. A total of 56 EEGs were analyzed, over time spans ranging from 1272 to 3 days prior to death. RESULTS: Frontal intermittent rhythmical delta activity (FIRDA) was seen at early timepoints in 4/6 patients and might represent an early EEG pattern that is associated, with human prion diseases. EEG patterns associated with CJD are sensitive to midazolam. Initial EEG changes were seen at the site of prion exposure in iatrogenic Creutzfeldt-Jakob disease patients, before they could be observed at distant sites, suggesting that prion disease was initiated at the site of prion exposure. CONCLUSIONS: Serial EEG recordings are a valuable tool not only in the early diagnosis of sporadic CJD, but also in the determination of prion exposure in iatrogenic Creutzfeldt-Jakob disease. SIGNIFICANCE: FIRDA occur at an early stage of CJD and are progressively replaced by the classical PSWC. The EEG patterns of CJD are sensitive to midazolam. The initial EEG changes in iatrogenic CJD are seen at the site of prion exposure.     

Creutzfeldt-Jakob disease presenting as bulbar palsy

Creutzfeldt-Jakob disease (CJD) is a degenerative neurological disorder caused by a prion protein. The diagnosis may be challenging in unusual early presentations. A bulbar symptom as the initial complaint is a rare presentation for CJD, with only a few reports so far. These patients can be misdiagnosed with motor neuron disease or the Miller Fisher variant of Guillain-Barré syndrome. We describe a 69-year-old woman with CJD who presented with bulbar symptoms at the onset.     

The association of neuroleptic sensitivity in Lewy body disease with a false positive clinical diagnosis of Creutzfeldt-Jakob disease

BACKGROUND: Dementia with Lewy bodies (DLB) and Creutzfeldt-Jakob disease (CJD) share clinical features like cognitive decline, motor disturbances en psychiatric symptoms. Overlapping symptoms may cause physicians to mistake DLB for CJD. METHODS: Clinical data of 12 patients with autopsy-confirmed DLB who had been clinically suspected to suffer from CJD were analysed to investigate possible clinical features which led to misdiagnosis. RESULTS: There was an association in time between administering neuroleptics and rapid clinical deterioration in 8 out of 9 patients. CONCLUSION: It is suggested that the neuroleptic sensitivity in LBD fuelled the misdiagnosis of CJD in the presented series. Diagnostic confusion between CJD and DLB may have important clinical consequences and may lead to treatment restrictions.     

Tubulovesicular structures in Creutzfeldt-Jakob disease

Summary By electron microscopy tubulovesicular structures (TVS) have been consistently observed in brain tissue of transmissible spongiform encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy and experimentally induced, but not naturally occurring, Creutzfeldt-Jakob disease (CJD). For the first time we report here the presence of TVS in human brains with CJD as detected by transmission electron microscopy. TVS were observed in all three CJD specimens (two biopsies, one autopsy), but they were rare and were found only in one or two location(s) per grid. TVS were seen in distended pre- and postsynaptic terminals and measured approximately 35 nm in diameter; they were smaller and of higher electron density than synaptic vesicles. Their occurrence in all types of transmissible spongiform encephalopathies irrespective of the affected host and the strain of the infectious agent suggests their biological significance.Supported by the Austrian Fund for the Advancement of Scientific Research (P8196-MED), and a grant from the Polish Academy of Science (VIII/40) (to P. P. L.)     

神经元特异性烯醇化酶及S-100蛋白对Creutzfeldt-Jakob病诊断价值的研究

目的　探讨早期诊断Creutzfeldt Jakob病 (CJD)的一种简便易行的检测方法。方法　采用ELISA及双抗体夹心方法检测 10例CJD、10例非CJD痴呆患者及 10名健康对照者的血清及CSF中神经元特异性烯醇化酶 (NSE)、S 10 0蛋白水平。同时对CJD患者血清中朊蛋白 (PrP)基因进行检测。结果　CJD组血清及CSF中NSE、S 10 0蛋白均较非CJD痴呆组升高 (均P <0 .0 5 ) ,血清中S 10 0蛋白明显升高 (P <0 .0 1)。CJD组血清中NSE及CSF中NSE、S 10 0蛋白较健康对照组明显升高 (均P <0 .0 1) ,血清中S 10 0蛋白较健康对照组升高(P <0 .0 5 ) ;非CJD痴呆组血清及CSF中NSE、S 10 0蛋白较健康对照组升高 (P <0 .0 5 )。 10例CJD中 8例为12 9密码子甲硫氨酸纯合子型 ,2例 12 9密码子甲硫氨酸和缬氨酸杂合型 ,无 12 9密码子缬氨酸纯合子型。结论　早期CSF中NSE及血清、CSF中S 10 0蛋白检测对CJD可以进行病情的判断及预后的评估。血清中S 10 0蛋白检测可用于CJD与非CJD痴呆的鉴别诊断。散发型CJD大部分为 12 9密码子甲硫氨酸纯合型 ,12 9密码子甲硫氨酸及缬氨酸杂合型CJD其临床表现与纯合型不同。     

Creutzfeldt-Jakob病的磁共振诊断

目的　探讨头部磁共振成像对Ｃｒｅｕｔｚｆｅｌｄｔ－Ｊａｋｏｂ病（ＣＪＤ）的诊断价值。方法　２例均经脑活检、免疫组化及实验鼠传递证实,分别于发病后２、１２个月进行头部磁共振检查。结果　２ 例双侧尾核、壳核于Ｔ２加权像均呈对称性均质高信号。结论　头部磁共振成像的异常信号对ＣＪＤ诊断虽非完全特异,但结合临床具有一定价值。     

实验动物传递证实密码子129甲硫氨酸纯合子Heidenhain型Creutzfeldt-Jakob病

】     

皮质-纹状体-脊髓变性病理与临床诊断☆(附5例临床分析)

目的　探讨皮质纹状体脊髓变性（ Ｃ Ｊ Ｄ） 的临床特点及诊断。方法　分析经病理证实的５ 例 Ｃ Ｊ Ｄ 的临床表现、光镜及超微检查结果。结果　５ 例均有典型 Ｃ Ｊ Ｄ 的临床表现,病理检查见神经细胞变性死亡,神经胶质细胞增生,无炎症性改变。超微检查除见上述改变外,还可见神经毡中膜性空泡内有卷曲的膜性碎片,部分髓鞘的轴突肿胀、空化。结论　本文５ 例 Ｃ Ｊ Ｄ 除引起中枢神经细胞胞体损害外,还可损害轴突,此病多为散发性,预后极差,目前无特效治疗。     

Autopsy case of sporadic Creutzfeldt–Jakob disease presenting with signs suggestive of brainstem and spinal cord involvement

We describe an autopsy case of MM1‐type sporadic Creutzfeldt–Jakob disease (CJD), the duration of which was 93 days. The patient was a 59‐year‐old Japanese man with no family history of prion disease or known iatrogenic exposure to CJD. His first symptom was dysesthesia in the left arm, suggestive of cervical cord involvement, and he showed rapidly progressive neurologic signs, such as dysarthria, dysphagia, lethargy, sleep apnea and respiratory failure, suggestive of brainstem involvement. Progressive mental deterioration combined with episodes of myoclonic seizure and periodic synchronous discharges on the electroencephalogram were observed in the later disease stage. Autopsy showed typical spongiform change to be widespread in the cerebral and cerebellar cortices, thalamus and basal ganglia. Synaptic‐type PrP deposition was marked in the cerebral cortex, thalamus and basal ganglia. In the cerebellum, although the granular, molecular and Purkinje cell layers were well preserved from neuronal loss and gliosis, PrP deposition was marked in the molecular and granular cell layers. Spongiform degeneration and neuronal loss were not seen in the brainstem and spinal cord, but relatively marked PrP deposition was observed in the quadrigeminal body, substantia nigra, pontine nucleus, inferior olivary nucleus and posterior horn. Immunohistochemical staining for HLA‐DR showed proliferation of activated microglia in the cerebral and cerebellar cortices, pontine nucleus, inferior olivary nucleus and posterior horn. The mechanisms underlying the neurologic symptoms and signs were unclear, but we speculate that, in addition to widespread involvement of the cerebral cortex, PrP deposition and microglial activation in the brainstem and spinal cord were responsible.     

Presentation of Creutzfeldt-Jakob disease as acute corticobasal degeneration syndrome.

We provide a brief report with videotape documentation of a possible case of Creutzfeldt-Jakob disease.     

Immunohistochemical studies of the PrPCJD deposition in Creutzfeldt‐Jakob disease

The PrP^CJD deposition in eight brains of sporadic Creutzfeldt‐Jakob disease (CJD) was examined immunohistochemically using both hydrolytic autoclaving and formic acid pretreatment in order to understand the pathogenesis of CJD. Synaptic‐type PrP immunoreactivity was revealed in the gray matter in all cases and had a tendency to be weaker in devastated areas in cases with a longer duration of illness. However, in one particular case with numerous prion plaques, the degeneration was relatively mild while PrP^CJD immunoreactivity was intense despite the longest duration of illness among the examined cases. Deep layer accentuation of PrP^CJD immunoreactivity was observed in the cerebral cortices in most cases. This staining pattern, however, disappeared in a burnt‐out lesion exhibiting status spongiosus. The granular layer was damaged mostly in the cerebellum of the advanced cases. PrP^CJD and synaptophysin immunoreactivities decreased as the tissue degeneration progressed. Interestingly, the Purkinje cells had no positivity for PrP^CJD in all cases, although the neurons in relatively preserved cerebellum showed apparent positivity for synaptophysin. In the Ammon’s horn and subiculum the neurons were well preserved despite the marked immunoreactivity for PrP^CJD in all cases, although some cases demonstrated severe spongiform change. Approximately half of the cases showed intracytoplasmic inclusion body‐like immunoreactivity for PrP^CJD in neurons of the dentate nucleus. These findings suggest that PrP^CJD deposition may be an event that precedes neuronal degeneration evolving from deeper layers of the cerebral cortex. Although the Ammon’s horn and subiculum showed striking PrP^CJD deposition and spongiform change, neuronal loss did not take place, suggesting that deposited PrP^CJD itself seems not to be directly harmful to the neurons. Some investigators have assumed that microglia activated by PrP^CJD plays an important role in neuronal degeneration. Considering this, we speculate that microglia in the Ammon’s horn and subiculum may have a unique characteristic of not responding to PrP^CJD.     

Brain monoamine abnormalities in the two types of Creutzfeldt-Jakob disease

Analysis of monoamine concentrations in brain tissue was carried out on the two types of Creutzfeldt-Jakob disease (CJD). The results showed decreased levels of catecholamines compared to control cases in a number of areas, and the reductions were most pronounced for dopamine. In general, the case classified as the amyotrophic form of CJD showed a greater degree of a monoamine loss than the case with spongiform encephalopathy, which is the typical transmissible form of CJD. These findings support the scarce available data indicating disturbances in the catecholaminergic systems in these types of brain diseases, and may have therapeutic implications.     

Review: contribution of transgenic models to understanding human prion disease

Transgenic mice expressing human prion protein in the absence of endogenous mouse prion protein faithfully replicate human prions. These models reproduce all of the key features of human disease, including long clinically silent incubation periods prior to fatal neurodegeneration with neuropathological phenotypes that mirror human prion strain diversity. Critical contributions to our understanding of human prion disease pathogenesis and aetiology have only been possible through the use of transgenic mice. These models have provided the basis for the conformational selection model of prion transmission barriers and have causally linked bovine spongiform encephalopathy with variant Creutzfeldt-Jakob disease. In the future these models will be essential for evaluating newly identified potentially zoonotic prion strains, for validating effective methods of prion decontamination and for developing effective therapeutic treatments for human prion disease.     

Chorea-acanthocytosis presenting as motor neuron disease

Introduction: Chorea‐acanthocytosis (ChAc) is a rare autosomal recessive disease characterized by involuntary movements, seizures, cognitive changes, myopathy, and axonal neuropathy. Methods: We report a patient who presented with gait impairment and dysarthria. Clinical and neurophysiological assessment disclosed upper and lower motor neuron signs suggestive of motor neuron disease (MND). Results: Later observation of involuntary movements prompted further investigation. Acanthocytes were identified, and the patient's chorein level was low. Genetic studies identified a novel double heterozygous mutation of the chorein gene involving an exon‐stop mutation associated with another mutation that can affect the normal splicing of the RNA. Conclusions: We speculate that this genetic mutation could cause the atypical presentation. ChAc should be included in the differential diagnosis of atypical MND. Muscle Nerve, 2012     

Creutzfeldt-Jakob disease presenting with alien limb sign.

Creutzfeldt-Jakob disease is a fatal spongiform encephalopathy, which typically presents with a rapidly progressing dementia and additional neurological findings that can be quite variable and diverse. Here we report the unusual case of a patient who presented with left alien limb sign without overt cognitive impairment and was ultimately diagnosed with pathologically confirmed Creutzfeldt-Jakob disease.     

Miliary brain metastases presenting as rapidly progressive dementia

We report the case of a 79‐year‐old woman who developed a rapidly progressive dementia (RPD) with severe memory impairment, early visual hallucinations and extrapyramidal signs. Symptoms started suddenly after hip replacement surgery following an accidental fall. Motor epileptic seizures appeared at the end of the illness. Dementia worsened gradually leading to akinetic mutism. She died five and a half months after the onset of symptoms. MRI showed cerebral atrophy but failed to detect any other lesion. Results of all laboratory tests performed were negative. After the most frequent treatable diseases were excluded, the diagnosis of dementia with Lewy bodies was initially considered. CJD was also suggested based on the rapid evolution of the disease and the positivity of 14‐3‐3 protein in CSF. Neuropathological examination revealed an extensive miliary metastatic dissemination from an unknown primary adenocarcinoma. Pulmonary origin was suggested according to the immunohistochemical profile. Histopathological changes of Alzheimer's disease were also observed in the cerebral cortex and hippocampus. Neither Lewy bodies nor PrP deposits were found. The sudden onset of the dementia just after the hip replacement surgery raises the possibility of a pathological fracture with secondary tumoral microembolic dissemination. Despite its rarity, this entity should be included in the differential diagnosis of RPD. This case illustrates the definite importance of neuropathological post‐mortem examination in order to elucidate the different types of dementia.