RESUMEN
Behçet's disease (BD) is a rare chronic inflammatory disease associated with systemic vasculitis. Involvement of the nervous system in BD is called neuro-BD (NBD). Epilepsy related to NBD is uncommon but responds well to anti-epileptic drugs. We present a case of NBD with drug-resistant mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS). The patient presented with headache, dizziness, disorientation, and generalized seizures. Magnetic resonance imaging (MRI) identified pontine lesions. Chronic inflammation was suspected, and steroid pulse therapy improved his symptoms. He relapsed 1 year after onset and was diagnosed with NBD. MRI revealed bilateral mesial temporal lesions, with the right being edematous and the left atrophic. NBD was controlled by steroid and immunosuppressive medication. Three years after the onset of NBD, the patient suffered MTLE, and MRI suggested left hippocampal atrophy. His seizures became drug-resistant and surgical therapy was considered 12 years after NBD onset. Pre-surgical MRI clearly showed left HS. After evaluations, the patient had left anterior temporal lobectomy (ATL) 13 years after NBD onset under stable NBD. The patient was seizure-free for > 2 years after surgery. Surgery will be an effective treatment for drug-resistant MTLE with HS even in patients with NBD, of course the effects of surgical intervention should be considered.
RESUMEN
In 2008, we reported a clinically and genetically new type of autosomal dominant disorder of motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough. To identify the nucleotide variant causative of this disease, we reanalyzed the linkage of the original Japanese pedigree including seven newly ascertained subjects with updated information. We assigned the locus of the disease to 1p13.3-q23 (maximum logarithm-of-odds score = 2.71). Exome sequencing for five patients and one healthy relative from the pedigree revealed 2526 patient-specific single-nucleotide variants (SNVs). By rigorous filtering processes using public databases, our linkage results, and functional prediction, followed by Sanger sequencing of the pedigree and 520 healthy Japanese individuals, we identified an intronic SNV in IQGAP3, a gene known to be associated with neurite outgrowth. Upon pathological examination of the sural nerve, moderate, chronic, mainly axonal neuropathy was observed. By histochemical analyses, we observed a patient-specific increase of IQGAP3 expression in the sural nerve. We concluded that the variant of IQGAP3 is associated with the disease in our pedigree.
Asunto(s)
Tos/complicaciones , Proteínas Activadoras de GTPasa/genética , Intrones/genética , Enfermedades del Sistema Nervioso Periférico/genética , Nervio Sural/patología , Enfermedades Urológicas/complicaciones , Adolescente , Adulto , Anciano , Tos/genética , Femenino , Genes Dominantes , Ligamiento Genético , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Atrofia Muscular/genética , Atrofia Muscular/patología , Linaje , Enfermedades del Sistema Nervioso Periférico/complicaciones , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Polimorfismo de Nucleótido Simple , Enfermedades Urológicas/genética , Secuenciación del ExomaRESUMEN
A 76-year-old woman showed a dramatic lowering of her tone of voice in October 2014, followed by muscle weakness of the left arm. The previous attending physician noticed remarkable left dominant frontotemporal lobe atrophy on cranial MRI. Her dysarthria, dysphagia and the muscle weakness of her extremities worsened, and a muscle biopsy revealed mitochondrial abnormality. The mitochondrial DNA from her muscle showed multiple deletions; the previous physician therefore diagnosed the patient with mitochondrial disease. The patient resembled amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD). No other cases of ALS-FTD with mitochondrial disease have been reported in Japan. We therefore consider the present case to be valuable.
Asunto(s)
ADN Mitocondrial/genética , Eliminación de Gen , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/genética , Anciano , Esclerosis Amiotrófica Lateral , Arginina/administración & dosificación , Diagnóstico Diferencial , Resultado Fatal , Femenino , Demencia Frontotemporal , Humanos , Mitocondrias Musculares/patología , Enfermedades Mitocondriales/tratamiento farmacológico , Enfermedades Mitocondriales/patología , Músculo Esquelético/ultraestructuraRESUMEN
We describe the case of a 90-year-old woman who was hospitalized in July 2016 and subsequently experienced a sudden decline in consciousness level resulting in a state of deep coma. Involuntary movements were not observed, and bilateral Babinski signs were inconclusive. Diffusion-weighted MRI (DWI) of the brain showed bilateral hyperintensity in the thalamus and internal capsule, laboratory testing detected high levels of plasma ammonia, and an electroencephalogram showed delta waves and triphasic waves predominantly in the frontal lobe. Based on these results, treatment for hepatic encephalopathy was administered, which led to an improvement in consciousness level, a decrease in plasma ammonia levels, and a normalization in the DWI scan. Abdominal computed tomography scan showed no abnormality in the liver, but revealed an abnormal blood vessel leading from the ileocolic vein to the inferior vena cava; the patient was diagnosed with portal-systemic encephalopathy. In deep coma patients, acute encephalopathy with hyperammonemia is important for differential diagnosis when DWI shows high-density legions in the thalamus and internal capsule.
Asunto(s)
Imagen de Difusión por Resonancia Magnética , Encefalopatía Hepática/diagnóstico por imagen , Cápsula Interna/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Anciano de 80 o más Años , Diagnóstico Diferencial , Electroencefalografía , Femenino , Encefalopatía Hepática/complicaciones , Humanos , Hiperamonemia/etiología , Tomografía Computarizada por Rayos XRESUMEN
We report the case of a patient with bilateral blephaloptosis associated with a recurrence of diffuse large B-cell lymphoma (DLBCL) in the midbrain. A 70-year-old man experienced acute onset bilateral blephaloptosis; the other ocular movements, except for medial rectus muscle in the right eye, were not impaired. Pupils were isocoric and light reflexes were prompt. Other cranial nerves were intact. Gadolinium-enhanced MRI revealed abnormal enhancement in the midbrain and peri-ventricular regions. FDG-PET revealed an abnormal positive signal in the midbrain, similar to the distribution seen in the MRI scan. Cytology of the cerebrospinal fluid showed large atypical lymphocytes. These findings suggest that the recurrence of DLBCL in the midbrain caused bilateral blephaloptosis. The oculomotor fascicle is localized in the paramedian ventral midbrain. The fascicular fibers are divided topographically into four regions; the lateral, medial, rostral and caudal regions. In three-dimensional arrangement of the oculomotor fascicle, the fibers to the levator palpebrae superioris muscle and medial rectus muscles are located adjacently in caudal regions. Thus, we speculate that recurrence of DLBCL in the midbrain involving the right oculomotor fascicle caused blephaloptosis in the right eye, and then, infiltration of DLBCL to the left oculomotor fascicle subsequently caused blephaloptosis in the left eye. This is a valuable case to be documented in which neurological site of lesions consistent with those are found in radiological study.
Asunto(s)
Blefaroptosis/etiología , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Mesencéfalo/diagnóstico por imagen , Anciano , Humanos , Imagen por Resonancia Magnética , Masculino , Recurrencia Local de Neoplasia , Oftalmoplejía/etiología , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: OX40 is a member of the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells and promotes the development of effector and memory T cells. Although OX40 has been reported to be a target gene of human T-cell leukemia virus type-1 (HTLV-1) viral transactivator Tax and is overexpressed in vivo in adult T-cell leukemia (ATL) cells, an association between OX40 and HTLV-1-associated inflammatory disorders, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), has not yet been established. Moreover, because abrogation of OX40 signals ameliorates chronic inflammation in animal models of autoimmune disease, novel monoclonal antibodies against OX40 may offer a potential treatment for HTLV-1-associated diseases such as ATL and HAM/TSP. RESULTS: In this study, we showed that OX40 was specifically expressed in CD4+ T cells naturally infected with HTLV-1 that have the potential to produce pro-inflammatory cytokines along with Tax expression. We also showed that OX40 was overexpressed in spinal cord infiltrating mononuclear cells in a clinically progressive HAM/TSP patient with a short duration of illness. The levels of the soluble form of OX40 (sOX40) in the cerebrospinal fluid (CSF) from chronic progressive HAM/TSP patients or from patients with other inflammatory neurological diseases (OINDs) were not different. In contrast, sOX40 levels in the CSF of rapidly progressing HAM/TSP patients were higher than those in the CSF from patients with OINDs, and these patients showed higher sOX40 levels in the CSF than in the plasma. When our newly produced monoclonal antibody against OX40 was added to peripheral blood mononuclear cells in culture, HTLV-1-infected T cells were specifically removed by a mechanism that depends on antibody-dependent cellular cytotoxicity. CONCLUSIONS: Our study identified OX40 as a key molecule and biomarker for rapid progression of HAM/TSP. Furthermore, blocking OX40 may have potential in therapeutic intervention for HAM/TSP.
Asunto(s)
Expresión Génica , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Paraparesia Espástica Tropical/patología , Receptores OX40/análisis , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores/líquido cefalorraquídeo , Líquido Cefalorraquídeo/química , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We report two patients with myotonic dystrophy type 1 (DM1) showing winged scapula in a single family. Genomic analysis revealed a marked expansion of CTG repeats in the 3' untranslated region; 1100 in patient 1 and 667 in patient 2. Muscle MRI revealed marked atrophy in the serratus anterior muscle in both patients. Muscle biopsy findings showed central nuclei and variations in fiber size. One of the patients showed ragged red fibers in muscles of the biceps brachii. To our knowledge, this is the first report of typical winged scapula in DM1.
Asunto(s)
Músculo Esquelético/patología , Distrofia Miotónica/patología , Escápula/patología , Adulto , Atrofia , Biopsia , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Distrofia Miotónica/diagnósticoRESUMEN
A 73-year old man was brought to our hospital because of acute onset of fever and consciousness disturbance. He had been hemodialyzed three times a week because of chronic renal failure since 13 years ago. Neurological examination revealed deteriorated consciousness and neck stiffness. A lumbar puncture yielded clouded fluid with a WBC 7,912/mm³ (polymorphonuclear cells 88%, mononuclear cells 12%), 786 mg/dl of protein and 4 mg/dl of glucose (blood glucose 118 mg/dl). Brain CT and MRI were unremarkable. He was treated with ceftriaxone and ampicillin. Streptococcus salivarius was isolated from the blood sample, but not from cerebrospinal fluid. The patient responded promptly to antibiotics therapy (ampicillin 3g/day, ceftriaxone 1g/day), and within several days he became lucid and afebrile. Isolated S. salivarius was sensitive for ampicillin and ceftriaxone. We diagnosed this case as S. salivarius bacteremia/meningoencephalitis. A gastrointestinal diagnostic workup revealed an asymptomatic gastric adenocarcinoma. S. salivarius is a common inhabitant of the oral mucosa that has been associated with infection in different sites. Meningeal infection by S. salivarius generally related to neoplasia of colon or iatrogenia, has been described on few occasions. This is the first report of S. salivarius bacteremia/meningoencephalitis associated with gastric neoplasm. Neurologist should be aware of the association of S. salivarius bacteremia/meningoencephalitis and gastrointestinal disease.
Asunto(s)
Bacteriemia/microbiología , Meningoencefalitis/microbiología , Neoplasias Gástricas/diagnóstico , Infecciones Estreptocócicas , Anciano , Ampicilina/administración & dosificación , Antibacterianos/administración & dosificación , Bacteriemia/complicaciones , Bacteriemia/tratamiento farmacológico , Ceftriaxona/administración & dosificación , Diagnóstico Precoz , Gastroscopía , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Meningoencefalitis/complicaciones , Meningoencefalitis/tratamiento farmacológico , Diálisis Renal , Neoplasias Gástricas/etiología , Sulbactam/administración & dosificaciónRESUMEN
A 48-year-old woman presented with a 2-week history of headache. The headache was so severe in the standing position that she could hardly stand up. The results of general and neurological examination were unremarkable. MRI studies of the brain showed diffuse pachymeningeal gadolinium enhancement on the T(1) weighted images. The cerebrospinal fluid (CSF) opening pressure on lumbar puncture was 70 mm H(2)O. MR myelography and RI-cisternography disclosed leak of cerebrospinal fluid at the lumbar level. Then, we diagnosed her as headache associated with liquorrhea. Two weeks later, she noticed an inability to recognize familiar faces, including her own face in the mirror. The Cambridge Face Memory Test (CFMT) proved prospagnosia. Brain MRI revealed multiple subdural hematomas below the bilateral fusiform gyrus. SPECT demonstrated diffuse hypoperfusion in the brain including bilateral fusiform gyrus. Months later, she showed gradual improvement of prospagnosia. Follow-up brain MRI revealed disappearance of both subdural hematomas and diffuse pachymeningeal gadolinium enhancement. SPECT demonstrated marked improvement of cerebral blood flow in the whole brain including the right temporal-occipital lesion. This is the first report of acquired prospagnosia during the course of liquorrhea causing subdural hematomas. Subdural hematoma below a right fusiform gyrus may cause reversible prospagnosia.
Asunto(s)
Líquido Cefalorraquídeo/metabolismo , Hematoma Subdural/complicaciones , Prosopagnosia/etiología , Adulto , Femenino , Humanos , Lesiones por Latigazo Cervical/complicacionesRESUMEN
OBJECTIVES: Hyperthyroidism is often associated with various neuromuscular disorders, most commonly proximal myopathy. Peripheral nerve involvement in hyperthyroidism is very uncommon and has rarely been reported. We describe a 29-year-old woman with untreated hyperthyroidism who presented with chronic severe axonal sensory-motor polyneuropathy. Peripheral nerve involvement developed together with other symptoms of hyperthyroidism 2 years before presentation. She also had anorexia nervosa for the past 6 months, resulting in multivitamin deficiency. RESULTS: Electrophysiological and pathological findings as well as clinical manifestations confirmed the diagnosis of severe axonal polyneuropathy. Anorexia nervosa has been considered a manifestation of untreated hyperthyroidism. We considered hyperthyroidism to be an important causal factor in the polyneuropathy in our patient, although peripheral nerve involvement in hyperthyroidism is rare. To our knowledge, this is the first documented case of chronic severe axonal polyneuropathy ascribed to both hyperthyroidism and multivitamin deficiency. CONCLUSION: Our findings strongly suggest that not only multivitamin deficiency, but also hyperthyroidism can cause axonal polyneuropathy, thus expanding the clinical spectrum of hyperthyroidism.
Asunto(s)
Avitaminosis/complicaciones , Avitaminosis/fisiopatología , Hipertiroidismo/complicaciones , Hipertiroidismo/fisiopatología , Polineuropatías/etiología , Polineuropatías/fisiopatología , Adulto , Anorexia Nerviosa/complicaciones , Anorexia Nerviosa/fisiopatología , Enfermedad Crónica , Femenino , Humanos , Microscopía Electrónica , Neuronas Motoras/fisiología , Neuronas Motoras/ultraestructura , Células Receptoras Sensoriales/fisiología , Células Receptoras Sensoriales/ultraestructura , Índice de Severidad de la Enfermedad , Nervio Sural/fisiología , Nervio Sural/ultraestructuraRESUMEN
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by a deficiency of arylsulfatase A. MLD is a heterogeneous disease with variable age at onset and variable clinical features. We evaluated a 33-year-old female patient who developed manifestations of disinhibitory behavior. She was diagnosed with MLD by genetic analysis, which revealed compound heterozygous ARSA missense mutations (p.G99D and p.T409I). The same combination of mutations was previously reported in a Japanese patient with similar symptoms. We performed additional, detailed neuropsychological tests with functional imaging on the current patient that demonstrated frontal lobe dysfunction. These results indicate that the mutations have important implications for genotype-phenotype correlation in MLD.
Asunto(s)
Cerebrósido Sulfatasa/genética , Leucodistrofia Metacromática/genética , Mutación Missense/genética , Adulto , Encéfalo/patología , Femenino , Estudios de Asociación Genética , Heterocigoto , Humanos , Leucodistrofia Metacromática/patología , Imagen por Resonancia MagnéticaRESUMEN
A 64-year-old woman was referred to our hospital because of disturbance of consciousness. She had undergone distal gastrectomy for gastric carcinoma 17 years previously. General physical examination was unremarkable, neurologic examination disclosed hyperactive deep tendon reflexes in the upper limbs. Laboratory abnormalities included elevations of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and findings suggesting disseminated intravascular coagulation (DIC). Lumbar cerebrospinal fluid showed a protein concentration of 408 mg/dl and a glucose concentration of 82 mg/dl (blood: 110 mg/dl), as well as a cell count of 16/mm3. Cranial computed tomography indicated brain edema. Magnetic resonance imaging (MRI) of the brain showed diffuse thickening of the dura mater, with contrast enhancement upon gadolinium-DTPA administration. These findings suggested hypertrophic pachymeningitis. Magnetic resonance venography (MRV) showed occlusion of the left transverse sinus and attenuation of the straight sinus. MRI of the spine as well as gallium scintigrams demonstrated multiple areas of increased uptake in areas near the skull and spine. We therefore suspected tumor metastasis. The patient was given heparin as well as pulse therapy with methylprednisolone, but she died 7 weeks after symptom onset. At postmortem examination, the dura was thickened. Histopathologically, numerous tumor cell emboli in the dura were confined to the lumens of veins. The tumor cells were thought to have metastasized to the dura through the vertebral venous plexus (Batson's plexus). Immunostaining demonstrated immunoreactivity of tumor cells to epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). The primary origin of the carcinoma was not precisely identified by these findings. Widespread dural vein tumor emboli should be taken into consideration as a cause in cases that develop rapid deterioration of consciousness associated dura mater thickening.
Asunto(s)
Neoplasias de la Médula Ósea/patología , Duramadre/irrigación sanguínea , Duramadre/patología , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/secundario , Neoplasias Primarias Desconocidas , Células Neoplásicas Circulantes/patología , Autopsia , Trastornos de la Conciencia/etiología , Resultado Fatal , Femenino , Humanos , Persona de Mediana EdadRESUMEN
In an axonal variant of Guillain-Barré syndrome (GBS) associated with Campylobacter jejuni (C. jejuni) enteritis, the mechanism underlying axonal damage is obscure. We purified and characterized a DNA-binding protein from starved cells derived from C. jejuni (C-Dps). This C-Dps protein has significant homology with Helicobacter pylori neutrophil-activating protein (HP-NAP), which is chemotactic for human neutrophils through binding to sulfatide. Because sulfatide is essential for paranodal junction formation and for the maintenance of ion channels on myelinated axons, we examined the in vivo effects of C-Dps. First, we found that C-Dps specifically binds to sulfatide by ELISA and immunostaining of thin-layer chromatograms loaded with various glycolipids. Double immunostaining of peripheral nerves exposed to C-Dps with anti-sulfatide antibody and anti-C-Dps antibody revealed co-localization of them. When C-Dps was injected into rat sciatic nerves, it densely bound to the outermost parts of the myelin sheath and nodes of Ranvier. Injection of C-Dps rapidly induced paranodal myelin detachment and axonal degeneration; this was not seen following injection of PBS or heat-denatured C-Dps. Electron microscopically, C-Dps-injected nerves showed vesiculation of the myelin sheath at the nodes of Ranvier. Nerve conduction studies disclosed a significant reduction in compound muscle action potential amplitudes in C-Dps-injected nerves compared with pre-injection values, but not in PBS-, heat-denatured C-Dps-, or BSA-injected nerves. However, C-Dps did not directly affect Na(+) currents in dissociated hippocampal neurons. Finally, when C-Dps was intrathecally infused into rats, it was deposited in a scattered pattern in the cauda equina, especially in the outer part of the myelin sheath and the nodal region. In C-Dps-infused rats, but not in BSA-infused ones, a decrease in the number of sodium channels, vesiculation of the myelin sheath, axonal degeneration and infiltration of Iba-1-positive macrophages were observed. Thus, we consider that C-Dps damages myelinated nerve fibers, possibly through interference with paranodal sulfatide function, and may contribute to the axonal pathology seen in C. jejuni-related GBS.
Asunto(s)
Campylobacter jejuni/metabolismo , Proteínas de Unión al ADN/farmacología , Vaina de Mielina/efectos de los fármacos , Fibras Nerviosas Mielínicas/efectos de los fármacos , Fibras Nerviosas Mielínicas/metabolismo , Canales de Sodio/efectos de los fármacos , Canales de Sodio/metabolismo , Animales , Anticuerpos Monoclonales/farmacología , Axones/efectos de los fármacos , Campylobacter jejuni/química , Cromatografía en Capa Delgada , Ensayo de Inmunoadsorción Enzimática , Gangliósidos/metabolismo , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Vaina de Mielina/patología , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/patología , Fibras Nerviosas Mielínicas/patología , Conducción Nerviosa/efectos de los fármacos , Técnicas de Placa-Clamp , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/metabolismo , Ratas , Ratas Endogámicas Lew , Proteínas Recombinantes/farmacología , Nervio Ciático/efectos de los fármacos , Nervio Ciático/patologíaRESUMEN
Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive, inflammatory disease of the central nervous system (CNS). We report a patient with transverse myelitis, who exhibited acute onset and rapid progression of the disease and whose symptoms resembled those observed in multiple sclerosis with spinal cord presentation. During neurological exacerbation of the condition, the HTLV-I proviral load in the cerebrospinal fluid (CSF) increased to 10 times that in the peripheral blood. This suggests that the accumulation of HTLV-I-infected cells in the CNS contributes to neurological exacerbation. Based on the increased proviral load in the CSF, we diagnosed the disease as acute progressive HAM/TSP. The measurement of the HTLV-I proviral load in the CSF is useful for the diagnosis of HAM/TSP and for monitoring its progression.
Asunto(s)
ADN Viral/líquido cefalorraquídeo , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Paraparesia Espástica Tropical/líquido cefalorraquídeo , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/virología , Carga Viral , ADN Viral/aislamiento & purificación , Femenino , Infecciones por HTLV-I/líquido cefalorraquídeo , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/fisiología , Humanos , Persona de Mediana Edad , Esclerosis Múltiple , Enfermedades de la Médula Espinal/líquido cefalorraquídeo , Enfermedades de la Médula Espinal/virologíaRESUMEN
OBJECTIVE: This study was to clarify the roles of midkine (MK) in the brain. METHODS: We determined cerebrospinal fluid MK levels in patients with neurological disorders by enzyme-linked immunoassay and immunostained autopsied brain samples in patients with meningitis. RESULTS: MK levels were 0.37+/-0.21 ng/ml in controls (n=46, mean +/- S.D.), 0.67+/-0.19 ng/ml in patients with cerebral infarction (n=8), 1.78+/-1.32 ng/ml in patients with meningitis (n=25; ANOVA and post-hoc Fisher's PLSD test, p<0.0001), 0.31+/-0.25 ng/ml in patients with human T-lymphotrophic virus type I-associated myelopathy/tropical spastic paraparesis (n=29), and 0.42+/-0.17 ng/ml in patients with amyotrophic lateral sclerosis (n=8). The regression equations were Y=0.005X+0.498 (Y, CSF MK level; X, cell number) and Y=0.007X+0.326 (Y, MK level; X, protein level) for all CSF samples. Autopsy brain samples from patients with meningitis expressed MK weakly in mononuclear cells on immunohistochemical examination. Western blot and polymerase chain reaction analyses showed that leukocytes were MK positive. CSF MK levels were not high in patients with cerebral infarction but were increased in patients with meningitis. CSF MK levels were high in normal controls, compared to those of other cytokines. MK was expressed in choroid plexus of normal brain and released there. CONCLUSION: Our findings suggested that MK may maintain normal adult brain as a neurotrophic factor, and that MK may be released from leucocytes in brain of patients with meningitis as an immunological mediator.
Asunto(s)
Infarto Cerebral/metabolismo , Líquido Cefalorraquídeo/química , Plexo Coroideo/metabolismo , Citocinas/líquido cefalorraquídeo , Citocinas/metabolismo , Meningitis/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Estudios de Casos y Controles , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Midkina , RatasRESUMEN
The authors herein describe a case of multifocal peripheral neuropathy with HTLV-I-associated myelopathy (HAM) in a patient with chronic adult T-cell leukemia (ATL). The clinical features included subacute progressive sensory-motor neuropathy in the bilateral upper limbs, and bilateral pyramidal tract involvement with bladder dysfunction. An MRI with (67)gadolinium enhancement revealed enlargement of the affected peripheral nerves. (8)FDG positron emission tomography (PET) disclosed increased uptake in the affected nerves, suggesting neurolymphomatosis or inflammation. Anti-HTLV-I antibody was positive in both the serum and CSF. The HTLV-I proviral load in the peripheral blood mononuclear cells was high. Chemotherapy for ATL resulted in marked improvement of motor functions in the upper limbs. This is the first case of multifocal upper limb neuropathy with HAM in a patient with chronic ATL.
Asunto(s)
Leucemia Prolinfocítica de Células T/complicaciones , Paraparesia Espástica Tropical/complicaciones , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/patología , Extremidad Superior/patología , Recuento de Células Sanguíneas , Medios de Contraste , Femenino , Fluorodesoxiglucosa F18 , Gadolinio , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Examen Neurológico , Nervios Periféricos/patología , Nervios Periféricos/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico por imagen , Tomografía de Emisión de Positrones , Extremidad Superior/diagnóstico por imagen , Extremidad Superior/inervaciónRESUMEN
We report a 36-year-old patient with 46XY pure gonadal dysgenesis (GD), who manifested a syndrome of progressive motor-sensory neuropathy. Sural nerve biopsy showed severe axonal neuropathy. Since reported cases of chronic motor-sensory neuropathy and pure gonadal dysgenesis have been characterized by nerve biopsy evidence of minifascicle formation, we suggest that this clinical association may be a new type of hereditary motor-sensory neuropathy, not necessarily associated with minifascicle formation.
Asunto(s)
Axones/patología , Disgenesia Gonadal 46 XY/complicaciones , Neuropatía Hereditaria Motora y Sensorial/complicaciones , Neuropatía Hereditaria Motora y Sensorial/patología , Adulto , Biopsia , Femenino , Disgenesia Gonadal 46 XY/genética , Proteínas Hedgehog/genética , Neuropatía Hereditaria Motora y Sensorial/genética , Humanos , Nervio Sural/patologíaRESUMEN
The objective of this study was to investigate the association of human T-lymphotropic virus-type I (HTLV-I) infection with sporadic inclusion body myositis in 11 patients from an endemic area in Japan. The clinical features were consistent with sporadic inclusion body myositis, and anti-HTLV-I antibodies were present in the sera of all patients. Their muscle biopsies showed the diagnostic features of inclusion body myositis, including endomysial T-cell infiltration, rimmed vacuoles, deposits of phosphorylated tau, and abnormal filaments in the nuclei and cytoplasm of the myofibers. The fibers expressed major histocompatibility complex class I antigens and were invaded by CD8 and CD4 cells. In a single human leukocyte antigen-A2-positive patient, in situ human leukocyte antigen-A*0201 / Tax11-19-pentamer staining showed pentamer-positive cells surrounding the muscle fibers. Double-immunogold silver staining and polymerase chain reaction in situ hybridization revealed that HTLV-I proviral DNA was localized on helper-inducer T cells, but not on muscle fibers. Human T-lymphotropic virus-type I proviral loads in peripheral blood mononuclear cells from each patient were similar to those in HTLV-I-associated myelopathy/tropical spastic paraparesis. This study suggests that HTLV-I infection may be one of the causes of sporadic inclusion body myositis, as has been reported in human immunodeficiency virus type-1 infection.
Asunto(s)
Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/epidemiología , Virus Linfotrópico T Tipo 1 Humano , Miositis por Cuerpos de Inclusión/complicaciones , Miositis por Cuerpos de Inclusión/epidemiología , Anciano , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Linfocitos T CD8-positivos/virología , Femenino , Productos del Gen tax/metabolismo , Infecciones por HTLV-I/patología , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/metabolismo , Humanos , Hibridación in Situ/métodos , Japón/epidemiología , Masculino , Microscopía Electrónica de Transmisión/métodos , Persona de Mediana Edad , Músculo Esquelético/patología , Músculo Esquelético/ultraestructura , Músculo Esquelético/virología , Miositis por Cuerpos de Inclusión/patología , Miositis por Cuerpos de Inclusión/virología , Estudios Retrospectivos , Tinción con Nitrato de Plata/métodosRESUMEN
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) cleaves the phosphodiester bond between a covalently stalled topoisomerase I (Topo I) and the 3' end of DNA. Stalling of Topo I at DNA strand breaks is induced by endogenous DNA damage and the Topo I-specific anticancer drug camptothecin (CPT). The H493R mutation of Tdp1 causes the neurodegenerative disorder spinocerebellar ataxia with axonal neuropathy (SCAN1). Contrary to the hypothesis that SCAN1 arises from catalytically inactive Tdp1, Tdp1-/- mice are indistinguishable from wild-type mice, physically, histologically, behaviorally, and electrophysiologically. However, compared to wild-type mice, Tdp1-/- mice are hypersensitive to CPT and bleomycin but not to etoposide. Consistent with earlier in vitro studies, we show that the H493R Tdp1 mutant protein retains residual activity and becomes covalently trapped on the DNA after CPT treatment of SCAN1 cells. This result provides a direct demonstration that Tdp1 repairs Topo I covalent lesions in vivo and suggests that SCAN1 arises from the recessive neomorphic mutation H493R. This is a novel mechanism for disease since neomorphic mutations are generally dominant.
Asunto(s)
Hidrolasas Diéster Fosfóricas/metabolismo , Ataxias Espinocerebelosas/genética , Animales , Antineoplásicos/farmacología , Axones , Bleomicina/farmacología , Encéfalo/metabolismo , Camptotecina/análogos & derivados , Camptotecina/farmacología , Células Cultivadas , Ensayo Cometa , Embrión de Mamíferos/citología , Etopósido/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Genes Recesivos , Humanos , Irinotecán , Ratones , Ratones Noqueados , Mutación , Hidrolasas Diéster Fosfóricas/deficiencia , Hidrolasas Diéster Fosfóricas/genética , Polineuropatías/genética , Polineuropatías/metabolismo , ARN Mensajero/metabolismo , Ataxias Espinocerebelosas/metabolismo , Topotecan/farmacologíaRESUMEN
This study investigated the role of human T-cell lymphotropic virus type I HTLV-I infection in 11 patients who developed slowly progressive myelopathy with abnormal spinal cord lesions. The authors performed clinical and neuroradiological examinations and calculated the odds that an HTLV-I-infected individual of a specific genotype, age, and provirus load has HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Anti-HTLV-I antibodies were present in both the serum and cerebrospinal fluid in all of the patients. Abnormal magnetic resonance imaging (MRI) lesions were classified as cervical to thoracic type (CT type), cervical type (C type), and thoracic type (T type). In each type, there was swelling of the spinal cords with high-intensity lesions, which were located mainly in bilateral posterior columns, posterior horns, or lateral columns. Virological and immunological analyses revealed that all patients showed a high risk of developing HAM/TSP. These 11 patients may have developed HAM/TSP, as manifested by spinal cord abnormalities shown on MRI. These MRIs implicate clinical variability of HAM/TSP, which may indicate active-early stages of HAM/TSP lesions.