RESUMEN
AIM: This study aimed to analyze two cases of marked hypo-high-density lipoprotein (HDL) cholesterolemia to identify mutations in ATP-binding cassette transporter A1 (ABCA1) and elucidate the molecular mechanism by which these novel pathological mutations contribute to hypo-HDL cholesterolemia in Tangier disease. METHODS: Wild type and mutant expression plasmids containing a FLAG tag inserted at the C-terminus of the human ABCA1 gene were generated and transfected into HEK293T cells. ABCA1 protein expression and cholesterol efflux were evaluated via Western blotting and efflux assay. The difference in the rate of change in protein expression was evaluated when proteolytic and protein-producing systems were inhibited. RESULTS: In case 1, a 20-year-old woman presented with a chief complaint of gait disturbance. Her HDL-C level was only 6.2 mg/dL. Tangier disease was suspected because of muscle weakness, decreased nerve conduction velocity, and splenomegaly. Whole-exome analysis showed compound heterozygosity for a W484* nonsense mutation and S1343I missense mutation, which confirmed Tangier disease. Cholesterol efflux decreased by a mixture of W484* and S1343I mutations. The S1343I mutation decreased the protein production rate but increased the degradation rate, decreasing the protein levels. This patient also had Krabbe disease. The endogenous ABCA1 protein level of macrophage cell decreased by knocking down its internal galactocerebrosidase.Case 2, a 51-year-old woman who underwent tonsillectomy presented with peripheral neuropathy, corneal opacity, and HDL-C of 3.4 mg/dL. Whole-exome analysis revealed compound heterozygosity for R579* and R1572* nonsense mutations, which confirmed Tangier disease. CONCLUSION: Case 1 is a new ABCA1 mutation with complex pathogenicity, namely, a W484*/S1343I compound heterozygote with marked hypo-HDL cholesterolemia. Analyses of the compound heterozygous mutations indicated that decreases in ABCA1 protein levels and cholesterol efflux activity caused by the novel S1343I mutation combined with loss of W484* protein activity could lead to marked hypo-HDL cholesterolemia. Galactocerebrosidase dysfunction could also be a potential confounding factor for ABCA1 protein function.
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GDF-15, a member of the transforming growth factor beta superfamily, regulates inflammatory and apoptotic pathways in various diseases, such as heart failure, kidney dysfunction, and cancer. We aimed to clarify potentially confounding variables affecting GDF-15 and demonstrate its utility as a mitochondrial biomarker using serum samples from 15 patients with mitochondrial diseases (MD), 15 patients with limbic encephalitis (LE), 10 patients with multiple sclerosis/neuromyelitis optica spectrum disorders (MS/NMOSD), and 19 patients with amyotrophic lateral sclerosis (ALS). GDF-15 and FGF-21 were significantly elevated in MD. GDF-15 and FGF-21 showed a good correlation in MD but not in LE, MS, and ALS. GDF-15 was potentially influenced by age in LE, MS/NMOSD, and ALS but not in MD. FGF-21 was not correlated with age in MS/NMOSD, ALS, LE, and MD. GDF-15 was not correlated with clinical features in LE or BMI or body weight in ALS. GDF-15 positively correlated with the Expanded Disability Status Scale (EDSS) in MS/NMOSD, while EDSS showed no correlation with age. In conclusion, the results revealed that GDF-15 may be influenced by EDSS in MS/NMOPSD and by age in LE, MS/NMOSD, and ALS but not in MD. Mitochondrial damage in MS/NMOSD is a potentially confounding variable affecting GDF-15.
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Factores de Crecimiento de Fibroblastos/sangre , Factor 15 de Diferenciación de Crecimiento/sangre , Enfermedades Mitocondriales/sangre , Esclerosis Múltiple/sangre , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/sangre , Biomarcadores/sangre , Evaluación de la Discapacidad , Femenino , Humanos , Encefalitis Límbica/sangre , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/sangre , Adulto JovenRESUMEN
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's 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.
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Mielitis/etiología , Zoster Sine Herpete/complicaciones , Zoster Sine Herpete/diagnóstico , Anciano , Antivirales/uso terapéutico , ADN Viral/análisis , Antebrazo , Herpesvirus Humano 3/aislamiento & purificación , Humanos , Imagen por Resonancia Magnética , Masculino , Mielitis/diagnóstico por imagen , Reacción en Cadena de la Polimerasa , Recurrencia , Zoster Sine Herpete/líquido cefalorraquídeo , Zoster Sine Herpete/tratamiento farmacológicoRESUMEN
Trigeminal nerve disorder is an important neurological sign that is often seen with multiple sclerosis (MS). We investigated eye movements in three MS patients with trigeminal disorder due to pontine lesions near the trigeminal root entry zone (REZ). Upbeat nystagmus was observed in all MS patients with trigeminal REZ lesions. We conjecture that trigeminal nerve disorder and upbeat nystagmus appeared due to simultaneous damage to both the trigeminal nerve and the vestibulo-ocular reflex pathway. If upbeat nystagmus appears in MS patients exhibiting a trigeminal nerve disorder, such as trigeminal neuralgia, and paralysis, pontine lesions near the trigeminal REZ should be considered. Upbeat nystagmus can be understood as a useful sign for the clinical regional diagnosis of trigeminal nerve disorder.
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Esclerosis Múltiple/diagnóstico , Nistagmo Patológico/diagnóstico , Puente/patología , Enfermedades del Nervio Trigémino/diagnóstico , Adulto , Femenino , Humanos , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Nistagmo Patológico/etiología , Enfermedades del Nervio Trigémino/etiología , Neuralgia del Trigémino/complicaciones , Neuralgia del Trigémino/diagnóstico , Adulto JovenRESUMEN
Glutamate receptor δ2 (GluRδ2) is expressed in the neuronal postsynaptic densities at the junctions between the Purkinje cells and the parallel fibers. Recent reports have described patients with opsoclonus who possess anti-GluRδ2 antibodies. We report the case of a 53-year-old man with opsoclonus whose cerebrospinal fluid was positive for anti-GluRδ2 antibodies. Electronystagmography revealed abnormal sinusoidal eye movements, which were definitively identified as opsoclonus. The frequency and amplitude of saccadic oscillations diminished after plasmapheresis (PE). The patient's opsoclonus was altered after PE, suggesting that anti-GluRδ2 antibodies may act on the saccade generator in the brainstem via the cerebellum and that they may be involved in the onset of opsoclonus.
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Trastornos de la Motilidad Ocular/inmunología , Trastornos de la Motilidad Ocular/terapia , Plasmaféresis/métodos , Receptores de Glutamato/inmunología , Animales , Autoanticuerpos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Central nervous system graft-versus-host disease can present quite a diagnostic challenge. We herein present a case of histologically-confirmed chronic graft versus host disease (GVHD) involving the central nervous system that occurred at 19 months after peripheral blood stem cell transplantation. Cranial magnetic resonance imaging showed areas of confluent hyperintensity in the deep/subcortical white matter with multiple punctate and curvilinear gadolinium enhancements, suggesting the disruption of the blood-brain barrier. A brain biopsy revealed perivascular CD3-positive T cell infiltration around the small vessels. We propose that the detection of punctate-enhanced lesions by magnetic resonance imaging may be a useful finding that facilitates the early diagnosis of chronic GVHD involving the central nervous system.
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Encéfalo/diagnóstico por imagen , Encéfalo/patología , Enfermedad Injerto contra Huésped/diagnóstico por imagen , Enfermedad Injerto contra Huésped/patología , Angiografía por Resonancia Magnética/métodos , Biopsia , Medios de Contraste , Femenino , Humanos , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Trasplante de Células Madre de Sangre PeriféricaRESUMEN
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.