Chronic myelitis associated with zoster sine herpete

Rationale: Neurological complications of varicella-zoster virus (VZV) infection include cerebral infarction, meningoencephalitis, segmental sensory disturbance, facial nerve palsy, and myelitis. Chronic myelitis is rarely reported. Diagnosis of VZV infection can be confirmed by elevated anti-VZV immunoglobulin G (IgG) antibody or detection of VZV DNA in the cerebrospinal fluid (CSF), the former reported to be superior. The detection rate of VZV DNA is generally thought to decrease with time after the onset of the condition. The utility of VZV DNA polymerase chain reaction (PCR) is thus thought to be limited to the acute phase of the disease. The presence of skin lesions also helps to render a diagnosis; however, cases of zoster sine herpete (ZSH), the occurrence of segmental symptoms without skin lesions, renders the diagnosis of VZV infection more difficult. Antiviral drugs, such as acyclovir, are the treatment of choice to resolve VZV infections.Patient concerns: A 65-year-old Japanese man felt heaviness and a throbbing pain on the ulnar side of the right forearm. He was previously diagnosed with cervical spondylosis, and received nonsteroidal anti-inflammatory drugs with little improvement. Contrast cervical magnetic resonance imaging showed a swelling and an increased signal intensity of the spinal cord, and an enhancing lesion, all of which were suggestive of myelitis.Diagnosis: We found no evidence for diagnoses of sarcoidosis, Behçet disease, multiple sclerosis, or neuromyelitis optica spectrum disorder. The CSF analysis revealed an elevation of the total protein concentration and that the patient was positive for VZV DNA, while anti-VZV IgG was not elevated. The patient was therefore diagnosed with ZSH myelitis.Interventions: We administered acyclovir and valaciclovir as the first therapy. At the time of recurrence, we used high-dose acyclovir, vidarabine, and high-dose methylprednisolone pulse therapy.Outcomes: The patient\u27s dysesthetic pain in the right upper limb improved following the first antiviral therapy. Two months later, he suffered a recurrence, but the second therapy significantly relieved his symptoms.Lessons: VZV infection should be regarded as an important differential diagnosis of chronic myelitis. VZV DNA PCR should be performed even in the chronic phase of the condition to introduce the possibility of antiviral therapy as a treatment option

Activation of MTK1/MEKK4 by GADD45 through Induced N-C Dissociation and Dimerization-Mediated trans Autophosphorylation of the MTK1 Kinase Domain▿ †

The mitogen-activated protein kinase (MAPK) module, composed of a MAPK, a MAPK kinase (MAPKK), and a MAPKK kinase (MAPKKK), is a cellular signaling device that is conserved throughout the eukaryotic world. In mammalian cells, various extracellular stresses activate two major subfamilies of MAPKs, namely, the Jun N-terminal kinases and the p38/stress-activated MAPK (SAPK). MTK1 (also called MEKK4) is a stress-responsive MAPKKK that is bound to and activated by the stress-inducible GADD45 family of proteins (GADD45α/β/γ). Here, we dissected the molecular mechanism of MTK1 activation by GADD45 proteins. The MTK1 N terminus bound to its C-terminal segment, thereby inhibiting the C-terminal kinase domain. This N-C interaction was disrupted by the binding of GADD45 to the MTK1 N-terminal GADD45-binding site. GADD45 binding also induced MTK1 dimerization via a dimerization domain containing a coiled-coil motif, which is essential for the trans autophosphorylation of MTK1 at Thr-1493 in the kinase activation loop. An MTK1 alanine substitution mutant at Thr-1493 has a severely reduced activity. Thus, we conclude that GADD45 binding induces MTK1 N-C dissociation, dimerization, and autophosphorylation at Thr-1493, leading to the activation of the kinase catalytic domain. Constitutively active MTK1 mutants induced the same events, but in the absence of GADD45

Late-onset Transthyretin (TTR)-familial Amyloid Polyneuropathy (FAP) with a Long Disease Duration from Non-endemic Areas in Japan

We herein report the case of an 84-year-old woman with transthyretin (TTR) Val30Met-associated familial amyloid polyneuropathy (FAP-ATTR Val30Met), representing a very old case. The patient had muscle weakness and sensory disturbances in her extremities caused by severe peripheral neuropathy. She also had vitreous opacity and orthostatic hypotension, and pyrophosphate scintigraphy showed a myocardial accumulation. Esophagogastroduodenoscopy revealed mucosal amyloid deposits, positive in anti-TTR antibody staining. A TTR gene analysis isolated the Val30Met mutation. More than a few cases of FAP-ATTR develop late, like our own, and their familial histories are often obscure in non-endemic areas, which might make a diagnosis difficult

Vestibular Impairment in Frontotemporal Dementia Syndrome

Background: No studies to date have attempted to evaluate frontotemporal lobar degeneration from the perspective of the vestibular system. Objective: The present study examined vestibular function in patients with frontotemporal dementia (FTD) clinical syndrome and evaluated whether vestibular disorders are involved in the clinical symptoms due to FTD. Methods: Fourteen patients with FTD syndrome, as well as healthy elderly controls without dementia, were included in the present study. All subjects underwent vestibular function tests using electronystagmography, such as caloric tests and visual suppression (VS) tests, in which the induced caloric nystagmus was suppressed by visual stimuli. The association between clinical symptoms and vestibular function in the FTD syndrome group was further examined. Results: In the FTD syndrome group, caloric nystagmus was not necessarily suppressed during VS tests. Furthermore, VS was observed to be significantly impaired in FTD syndrome patients with gait disturbance as compared to those without such disturbance. Conclusion: The present study revealed that impairment of VS in patients with FTD results in an inability to regulate vestibular function by means of visual perception, regardless of multiple presumed neuropathological backgrounds. This could also be associated with gait disturbance in patients with FTD syndrome