Hepatitis B vaccine related‐myelitis?*

We present four incidental cases that developed partial myelitis following the administration of hepatitis B vaccine in 1998. The first two cases, a 33-year-old man and a 42-year-old woman developed progressive sensory symptoms without motor involvement within 4 weeks following the vaccination. Their magnetic resonance imaging (MRI) disclosed similar lesions consistent with myelitis at their cervical spinal cord. A comparable inflammatory lesion was seen at the T9-T10 levels of the spinal cord in the third case, who was a 40-year-old woman presenting with numbness in her legs and urinary retention following the vaccination. The fourth case who was a 42-year-old woman, presented with sensory symptoms in her left extremities, which developed 3 months after the vaccination. Her MRI showed a hyperintense lesion at C6. She also had two tiny lesions in her cranial MRI. In all cases, there was no history of preceding infections and no clinical evidence suggestive of any other disorders that may cause myelopathy. All patients recovered completely within 3 months with the exception of the third patient who developed new neurological symptoms after 12 months. Similar clinical and imaging presentation of myelitis following hepatitis B vaccination within a 1 year period with no other demonstrable clinical and laboratory evidence for any other disorder raise the probability of a causal link between these two events.     

Screening for Spinal Defects

Second-trimester diagnosis of most open neural tube defects has become clinically feasible in the past five years. Alpha fetoprotein is the common denominator in a two-stage screening program. Maternal serum analysis identifies high-risk pregnancies; amniotic fluid analysis is diagnostic. The biochemical basis for these tests and findings of clinical studies are reviewed.     

An Autopsied Case of Acute Hemorrhagic Leukoencephalitis

Abstract: This is a clinico-pathological study of one case of acute hemorrhagic leukoencephalitis occurring in a patient with lung cancer. The main changes observed by light microscopywere in the white matter. All of these changes were the result of hemorrhage and demyelination around the venous vessels. Glial mesenchymal reactions were minimal. In view of these findings, this case supports the hypothesis that immune mechanisms play a role in the pathogenesis of neuropsychiatric symptoms during malignant illnesses. Here we will discuss the problem of differential diagnoses of acute hemorrhagic leukoencephalitis and its close morphologic similarities to perivenous encephalitis. Acute hemorrhagic leukoencephalitis and perivenous encephalitis may be a single entity of a demyelinating disease.     

Complex interaction between mutant HNRNPA1 and gE of varicella zoster virus in pathogenesis of multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system causing axonal injury, neuronal loss, and atrophy of the central nervous system leading to permanent neurological and clinical disability. Presence of mutations in M9 domain of HNRNPA1 and detection of autoantibodies against this domain in HNRNPA1 qualifies it as a strong candidate for causing MS. These two aspects indicate the presence of a facilitator in associating them. Varicella zoster virus (VZV), known to cause chicken pox infection in humans, is a significant contender in sensitizing the infected people towards MS. Reactivation of latent herpes viruses by other infectious agents and cross-recognition of common viral antigens with antigens found in the myelin sheath induces molecular mimicry or superantigens. Mutations in HNRNPA1 cause mislocalization to the cytoplasm, and co-localize with stress granules (SG) causing cellular apoptosis, this creates the first step toward MS pathogenesis. Mutant HNRNPA1 accumulates in SG allowing the cells to display peptides of HNRNPA1 on surfaces of major histocompatibility complex (MHC) I triggering a cascade of immune reactions. Since glycoprotein E (gE) of VZV shares >62% amino acids sequence similarity with Prion-like domain (PrLD) of HNRNPA1, signifying the reason behind autoantibodies against M9 and PrLD of HNRNPA1. This review attempts to delineate the interactions of VZV, gE of VZV, with M9 domain and PrLD of HNRNPA1 in a step-by-step process. This supports the tripartite model that an environmental trigger in genetically susceptible individuals causes an autoimmune response to self-CNS antigens that result in the pathology observed in the brain and spinal cord of MS patients.     

实验性自身免疫性脑脊髓炎的视神经病理改变

目的 研究实验性自身免疫性脑脊髓炎(EAE)的视神经病理改变.方法 足垫皮下注射豚鼠脊髓匀浆和完全弗氏佐剂(CFA)混合物制作Wismr大鼠EAE模型,于发病后第6d将大鼠处死,取视神经、脑和脊髓,行HE和LFB染色,光镜和电镜下观察其病理改变.结果 病理检查发现EAE模型组大鼠脑、脊髓有不同程度的炎症反应和脱髓鞘改变;均有视神经病变,光镜主要表现为炎症反应和脱髓鞘,视神经髓鞘脱失重于炎症反应;电镜主要表现为髓鞘稀疏,少突胶质细胞数量减少、胞核固缩,其周围包裹的髓鞘板层松解,轴突髓鞘分离.结论 EAE大鼠存在明显的视神经病变,主要为视神经炎症反应和脱髓鞘改变.     

外周神经损伤诱发异常传入性活动的动力学变化

外周神经受到损伤的初期,损伤区传递冲动能力减弱和速度减慢,随后发生传导阻滞和神经髓鞘膜脱落的形态学病变。此时可记录到不同类型的传入神经纤维的异常传入放电活动,粗纤维产生规则的高频的异位放电,细纤维有不规则的阵发性放电。对脱髓鞘膜区进行逆行性刺激可引起放电频率增加,单次脉冲的逆行性刺激可使部分C类纤维产生多次的异位放电。脱髓鞘膜区对K~ 通道阻断剂以及外源性的去甲肾上腺素异常敏感,提示异常电活动是受伤神经区轴突膜上离子通道和介质受体发生变化的结果。     

Focal Perivascular Alterations of White Matter in Herpes Simplex Encephalitis —A Histological and Immunocytochemical Study—

Abstract: Several cases of human herpes simplex encephalitis treated with Vidarabin have been investigated with the histological and immunocytochemical techniques. Cases with a subacute evolution revealed areas of focal perivascular myelin destruction in the white matter. The distribution of herpes simplex antigen did not show any preferential localization of the virus in perivascular oligoglia! cells. In contrast, a spatial and temporal relationship has been found between the appearance of immunoglobulin-bearing cells around the vessels and that of areas of focal perivascular myelin damage. Therefore, it is postulated that the areas of focal destruction of myelin are not related to the cytotoxic effect of the virus but are rather dependent on the immune response of the host.     

The cuprizone model for demyelination

Background –  Important advances in multiple sclerosis (MS) research have been made as a direct or indirect result of experiments in animal models for the disease, although MS is a disease only affecting humans. The cuprizone model is a model for toxic demyelination. In this model, young mice are fed with the copper chelator cuprizone, leading to oligodendrocyte death and a subsequent reversible demyelination. Spontaneous remyelination can be seen as early as 4 days after withdrawal of cuprizone.
Materials and methods –  This article reviews previous research on this model and discusses the potential of the model for future application in MS research.
Discussion –  The cuprizone model correlates with newer histopathological data in MS and is a valuable tool for studies on de- and remyelination. The use of the C57BL/6 strain offers the potential for future studies on transgene and knockout mice.     

Implications of progressive multifocal leukoencephalopathy and JC virus for the etiology of MS

JCV infects oligodendrocytes and, to a lesser extent, astrocytes in the brain and spinal cord and causes the demyelinating disease known as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals. The possibility exists that this opportunistic infection reactivates from a latent state in the brain. It is proposed that the pathogenetic immune response in a multiple sclerosis (MS) brain may be directed predominantly toward antigens of a DNA virus, such as JCV, which is latent in glial cells. The target antigens could be synthesized only during transient viral reactivation or could persist, thus explaining the two basic patterns of neurological symptoms in MS. It is further proposed that the viral genome as a minichromosome becomes focally distributed in glial cells following vertical passage in dividing progenitor cells after infection early in life. The concept that the host response to a single agent can evoke two distinct pathologies (PML and MS) derives from a chronic mycobacterial infection of peripheral nerves-leprosy.     

A double antibody radioimmunoassay for myelin basic protein in cerebrospinal fluid

Levels of myelin basic protein (MBP) in cerebrospinal fluid (CSF) are useful in assessing the extent of demyelination which has occurred, or is occurring, in a variety of human problems associated with demyelination. Thus, an accurate, specific, simple, and consistent test for detecting MBP in CSF is needed. We describe such a test herein. The radioimmunoassay (RIA) described is a double antibody RIA using human MBP, and rabbit anti-MBP as reagents. The test can be done using only 200 microL of unconcentrated CSF. The test was sensitive to 0.1 microgram MBP/L. Recovery of known amounts of MBP was 97-105%, the within-assay and between-assay reproducibility were excellent. The "normal range" for our MBP-RIA was less than 2 micrograms/L, with a "grey area" between 2.0 and 3.0 micrograms/L.