RESUMEN
PURPOSE: Intermittent claudication (IC) refers to leg pain that is induced by walking and relieved by rest. Neurogenic IC is usually associated with lumbar canal stenosis (LCS). We present rare findings from an autopsied patient who had neurogenic IC caused by vasculitis in the cauda equina. METHODS: We performed antemortem neurological and electrophysiological assessments, sural nerve biopsy, and post-mortem examination of the spinal cord and brain. RESULTS: A 61-year-old man noted sudden-onset leg pain that was not associated with any traumatic trigger. His leg pain consistently appeared when the patient walked and quickly faded on stopping. Spine surgery and cardiovascular departments both made a diagnosis of IC. However, magnetic resonance imaging (MRI) did not show LCS, and all ankle-brachial pressure indices were normal. He subsequently developed diffuse muscle weakness of the legs a month after disease onset. Myeloperoxidase antineutrophil cytoplasmic autoantibody was seropositive (140 IU/mL), and a sural nerve biopsy revealed axonal injury and angiitis. MRI showed multiple cerebral infarctions. He was diagnosed with microscopic polyangiitis (MPA) and underwent corticosteroid therapy. He died from complications two months after the onset. A post-mortem study revealed vasculitis in the subarachnoid space of the cauda equina, spinal cord, and brain parenchyma. The cauda equina showed a combined loss of small and large axonal fibres. The lumbar cord displayed central chromatolysis of the lower motor neurons. CONCLUSION: MPA is a rare cause of neurogenic IC when the symptom is acute and multimodal. Small-vessel vasculitis affecting the cauda equina may underlie MPA-associated IC.
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Cauda Equina , Estenosis Espinal , Vasculitis , Masculino , Humanos , Persona de Mediana Edad , Cauda Equina/diagnóstico por imagen , Cauda Equina/patología , Autopsia , Pierna , Claudicación Intermitente/diagnóstico por imagen , Claudicación Intermitente/etiología , Estenosis Espinal/complicaciones , Estenosis Espinal/diagnóstico por imagen , Constricción Patológica , Dolor/complicaciones , Vasculitis/complicaciones , Vasculitis/diagnóstico por imagen , Vasculitis/patologíaRESUMEN
Neurolymphomatosis is a neurological manifestation of lymphoma that involves the cranial or spinal peripheral nerves, nerve roots, and plexus with direct invasion of neoplastic cells. Neurolymphomatosis is rare among patients with low-grade lymphoma. We report an autopsied case of neurolymphomatosis that arose from follicular lymphoma. A 49-year-old woman who presented with pain of her neck and shoulder and numbness of her chin. Computed tomography revealed enlarged lymph nodes in her whole body, and biopsy from the axillary lymph node revealed grade 2 follicular lymphoma. Although the patient underwent chemotherapy, she gradually developed muscle weakness in the upper limbs and sensory disturbances of the trunk and limbs. 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed increased tracer uptake of the cervical nerve roots. Repeated FDG-PET after additional therapy revealed progression of disease within the nerve roots and brachial plexus, whereas gadolinium-contrast magnetic resonance imaging (MRI) showed weak enhancement of the cervical nerve roots without formation of mass lesions. She died after a total disease duration of 12 months. Postmortem observations revealed invasion of lymphoma cells into the cervical nerve roots, dorsal root ganglia, and subarachnoid spaces of the spinal cord. Neurolymphomatosis was prominent at the segments of C6-Th2. Combined loss of axons and myelin sheaths was observed in the cervical nerve roots and posterior columns. Lymphoma cells also invaded the cranial nerves. The subarachnoid and perivascular spaces of the brain demonstrated focal invasion of the lymphoma. Mass lesions were not observed in the central nervous system. The lymphoma cells did not show histological transformation to higher grades, and the density of the centroblasts remained at grade 2. Our report clarifies that low-grade follicular lymphoma can manifest as neurolymphomatosis and central nervous system invasion in the absence of transformation toward higher histological grades. FDG-PET may be more sensitive to non-mass-forming lesions, including neurolymphomatosis, than gadolinium-contrast MRI.
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Linfoma Folicular , Neurolinfomatosis , Autopsia , Femenino , Fluorodesoxiglucosa F18 , Gadolinio , Humanos , Persona de Mediana Edad , Neurolinfomatosis/patologíaRESUMEN
A 64-year-old man was admitted with acute onset disturbed consciousness. Cerebrospinal fluid analysis revealed pleocytosis and elevated protein, with negative cultures and PCR. Serum antibodies for autoimmune encephalitis were also negative. Brain magnetic resonance imaging (MRI) was unremarkable, but whole-body CT scan showed a tumor in the left lower lung lobe. Bronchial brush cytology demonstrated clusters of malignant cells, and 18 F-fluorodeoxyglucose positron emission tomography showed multiple lesions and increased uptake in the lung tumor. Clinically the patient had a stage IV lung carcinoma, graded as T3N3M1b (OSS). Steroid therapy had limited efficacy, but chemotherapy dramatically improved his neurological symptoms. Therefore, he was diagnosed with paraneoplastic autoimmune encephalitis based on the diagnostic criteria for paraneoplastic neurological syndromes. He died due to disease progression 14 months later. Subsequent postmortem examination revealed white ill-defined nodules in the left lung, with similar nodules in other organs. The brain weighed 1500 g before fixation, and a nodule was observed in the right precentral gyrus. Microscopically, the lung tumor was a pleomorphic carcinoma with an adenocarcinoma component. Multiple areas of micro-softening (≤500 µm) were identified in the cerebral cortex, gray-white matter junction and basal ganglia, and were distributed diffusely in both the limbic and non-limbic systems. Mild lymphocytic infiltrates were observed involving few intraparenchymal vessels. Few tumor metastases were observed in the right precentral gyrus. The multiple micro-softenings may reflect a chronic neuropathologic change of paraneoplastic autoimmune encephalitis. They were too small to be detected by brain MRI. However, these lesions may have the potential to cause the neurological symptoms in the acute phase because they were observed in many anatomical regions. We should pay attention to subtle findings such as micro-softenings when estimating the neuropathology of autoimmune encephalitis. Further investigations are needed to understand the characteristic neuropathology of this condition.
RESUMEN
Genetic and phenotypic heterogeneities are considerably high in adult-onset leukoencephalopathy, in which comprehensive mutational analyses of the candidate genes by conventional methods are too laborious. We applied exome sequencing to conduct a comprehensive mutational analysis of genes for autosomal dominant leukoencephalopathies. Genomic DNA samples from four patients of three families with autosomal dominantly inherited adult-onset leukodystrophy were subjected to exome sequencing. On the basis of the results, 21 patients with adult-onset sporadic leukodystrophy and one patient with pathologically proven HDLS were additionally screened for CSF1R mutations. Exome sequencing identified heterozygous CSF1R mutations (p.I794T and p.R777W) in two families. I794T has recently been reported as a causative mutation for hereditary diffuse leukoencephalopathy with spheroids (HDLS), and R777W is a novel mutation. Although mutational analysis of CSF1R in 21 sporadic cases revealed no mutations, another novel CSF1R mutation, p.C653Y, was identified in one patient with autopsy-proven HDSL. These variants were located in the PTK domain where the causative mutations cluster. Functional prediction of the mutant CSF1R as well as cross-species conservation of the affected amino acids supports the notion that these variants are pathogenic for HDLS. Exome sequencing is useful for a comprehensive mutational analysis of causative genes for hereditary leukoencephalopathies, and CSF1R should be considered a candidate gene for patients with autosomal dominant leukoencephalopathies.
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Predisposición Genética a la Enfermedad , Leucoencefalopatías/genética , Receptor de Factor Estimulante de Colonias de Macrófagos/genética , Adulto , Anciano , Análisis Mutacional de ADN , Exoma/genética , Familia , Femenino , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Linaje , Análisis de Secuencia de ADNRESUMEN
A 47-year-old woman presented with progressive limb weakness. A neurological examination revealed proximal dominant symmetrical muscle weakness in her limbs, and electromyography revealed complex repetitive discharges and short motor unit potentials with positive sharp waves in the biceps. We observed early recruitment in the quadriceps, and laboratory tests revealed normal creatine kinase. Serum protein electrophoresis showed monoclonal IgG-lambda, but the bone marrow aspiration specimen was normal. A muscle biopsy revealed nemaline rod accumulations in the muscle fibers; based on the results, we diagnosed the patient with sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance (SLONM-MGUS). We administered repeated intravenous immunoglobulin, but her limb weakness continued, and she developed a restrictive ventilatory defect. The patient received melphalan, followed by autologous stem-cell transplantation (ASCT). Her upper extremity strength and respiratory capability improved within one year after ASCT; however, it was not until six years after ASCT that her atrophied lower extremities strengthened. A discrepancy in the timeline of treatment response between the upper or respiratory muscles and the atrophied lower limb was characteristic in the patient, suggesting that the efficacy of ASCT on SLONM-MGUS should be evaluated in the long term, especially in severely atrophied muscles. In addition, this case showed that ASCT for SLOMN-MGUS is an effective treatment option in Asian populations.
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Trasplante de Células Madre Hematopoyéticas , Gammopatía Monoclonal de Relevancia Indeterminada , Miopatías Nemalínicas , Femenino , Humanos , Persona de Mediana Edad , Músculo Esquelético , Resultado del TratamientoRESUMEN
Mutations in the valosin-containing protein (VCP) gene are known to cause various neurodegenerative disorders. Here, we report 8 Japanese patients [6 men, 2 women; median age at onset: 49.5 (range, 35-58) years] from 5 unrelated families with VCP missense mutations. Although 7 of 8 patients were diagnosed with either inclusion body myopathy or amyotrophic lateral sclerosis, 1 patient showed demyelinating polyneuropathy, which was confirmed by longitudinal nerve conduction studies. Sural nerve biopsy of the patient revealed intranuclear ubiquitin staining in Schwann cells. Three known pathogenic VCP mutations (p.Arg191Gln, p.Arg155Cys, and p.Ile126Phe) were detected. A novel mutation, c.293 A>T (p.Asp98Val), was also identified in a patient with amyotrophic lateral sclerosis and frontotemporal dementia. This mutation was predicted to be "deleterious" or "disease causing" using in silico mutation analyses. In conclusion, demyelinating polyneuropathy may be a novel phenotype caused by VCP mutations. The p.Asp98Val mutation was found to be a novel pathogenic mutation of VCP proteinopathy. We believe our cases represent a wide clinical spectrum of VCP mutations.
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Esclerosis Amiotrófica Lateral/genética , Enfermedades Desmielinizantes/genética , Mutación Missense/genética , Miositis por Cuerpos de Inclusión/genética , Polineuropatías/genética , Proteína que Contiene Valosina/genética , Adulto , Esclerosis Amiotrófica Lateral/diagnóstico , Pueblo Asiatico/genética , Análisis Mutacional de ADN/métodos , Enfermedades Desmielinizantes/diagnóstico , Familia , Femenino , Demencia Frontotemporal/diagnóstico , Demencia Frontotemporal/genética , Humanos , Japón , Masculino , Persona de Mediana Edad , Miositis por Cuerpos de Inclusión/diagnóstico , Linaje , Polineuropatías/diagnósticoRESUMEN
BACKGROUND: Although pure cerebellar ataxia is usually emphasized as the characteristic clinical feature of spinocerebellar ataxia type 6 (SCA6), parkinsonism has been repeatedly described in patients with genetically confirmed SCA6. METHODS: We conducted a positron emission tomography study using a combination of [18F]fluoro-L-dopa for dopamine synthesis and [11C]raclopride for dopamine D2 receptor function on six genetically confirmed SCA6 patients, both with and without parkinsonism. To the best of our knowledge, this is the first dopamine receptor imaging study of patients with SCA6. RESULTS: Most patients had somewhat decreased dopaminergic function, and this decrease was significant in the caudate nucleus. In addition, one SCA6 patient with parkinsonism had whole striatal dysfunction of both dopamine synthesis and dopamine D2 receptor function. CONCLUSIONS: The pathology of SCA6 may not be restricted to the cerebellum, but may also be distributed across various regions, including in both presynaptic and postsynaptic dopaminergic neurons to some degree. Patients with SCA6 may show apparent parkinsonism after the progression of neurodegeneration.
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Trastornos Parkinsonianos , Ataxias Espinocerebelosas , Dopamina , Humanos , Trastornos Parkinsonianos/diagnóstico por imagen , Tomografía de Emisión de Positrones , Racloprida , Ataxias Espinocerebelosas/complicaciones , Ataxias Espinocerebelosas/diagnóstico por imagenRESUMEN
Encephalitis is the most severe manifestation of central nervous system (CNS) infection by Varicella-Zoster-Virus (VZV). VZV associated encephalitis is now recognized to be a vasculopathy that affects large or small cerebral arteries. This report describes an autopsy case of an immunocompetent 66-year-old male who developed a progressive small vessel vasculopathy and clinically presented with a zosteriform rash and myelo-radiculoganglio-meningo-encephalitis followed by subarachnoid bleeding. This is an extremely rare manifestation of VZV vasculopathy associated with widespread CNS damage, and what is more, the spinal lesions were different from those of the cerebrum, brainstem and cerebellum, where the former were predominantly demyelinative changes and the latter were ischemic. To the best of our knowledge, few cases have been described pathologically in an immunocompetent individual. Further studies are needed to investigate the pathogenesis and treatment of VZV vasculopathy.
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Arterias Cerebrales/patología , Encefalitis por Varicela Zóster/patología , Inmunocompetencia , Meningoencefalitis/patología , Enfermedades de la Médula Espinal/patología , Anciano , Linfocitos T CD8-positivos/patología , Linfocitos T CD8-positivos/virología , Encefalitis por Varicela Zóster/complicaciones , Humanos , Macrófagos/patología , Macrófagos/virología , Imagen por Resonancia Magnética , Masculino , Meningoencefalitis/complicaciones , Enfermedades de la Médula Espinal/complicaciones , Enfermedades de la Médula Espinal/virologíaRESUMEN
The patient was a 61-year-old woman with thyroid enlargement since her 20s. She began to fall down repeatedly towards the end of June 2015. She was admitted to our hospital in the middle of August because of difficulty in walking. Upon admission, she presented with neck tremor and was unable to maintain a sitting position due to ataxia of the trunk and limbs. We studied serum anti-neuronal antibodies and obtained a positive result for anti-amphiphysin antibody (AMPH-Ab). Cerebrospinal fluid analysis revealed elevated protein levels and IgG index. Other than the thyroid mass, a tumor was not detected. The resected thyroid specimen showed follicular adenoma. After performing immunotherapies, the cerebrospinal fluid protein levels and IgG index decreased, and her ataxia did not progress. When subacute cerebellar ataxia is suspected, studying AMPH-Ab should be considered.
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Adenocarcinoma Folicular/complicaciones , Autoanticuerpos/sangre , Ataxia Cerebelosa/diagnóstico , Ataxia Cerebelosa/etiología , Proteínas del Tejido Nervioso/inmunología , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Síndromes Paraneoplásicos del Sistema Nervioso/etiología , Neoplasias de la Tiroides/complicaciones , Enfermedad Aguda , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Ataxia Cerebelosa/terapia , Proteínas del Líquido Cefalorraquídeo/análisis , Femenino , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoterapia , Persona de Mediana Edad , Síndromes Paraneoplásicos del Sistema Nervioso/terapiaRESUMEN
Trousseau's syndrome is characterized by a cerebral or systemic thromboembolism caused by coagulation abnormalities in malignancy. We herein report a case of multiple ischemic strokes as the initial manifestation of anaplastic thyroid carcinoma (ATC). An 86-year-old man was admitted to our hospital due to a sudden-onset weakness of the left limbs. Brain magnetic resonance imaging revealed multiple ischemic lesions in the right middle cerebral artery territory and a mass in the left frontal lobe. Computed tomography revealed a thyroid mass and multiple lung tumors. A diagnosis of ATC was confirmed by a thyroid biopsy. Our case indicates that ATC should be considered as a cause of Trousseau's syndrome.
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Infarto Cerebral/etiología , Infarto Cerebral/terapia , Carcinoma Anaplásico de Tiroides/complicaciones , Carcinoma Anaplásico de Tiroides/patología , Anciano de 80 o más Años , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/patología , Infarto Cerebral/diagnóstico por imagen , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/patología , Humanos , Japón , Imagen por Resonancia Magnética , Masculino , Síndrome , Carcinoma Anaplásico de Tiroides/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
A 37-year-old man was hospitalized for an evaluation of acute bilateral multiple subcortical infarcts. There were no specific signal abnormalities in the temporal pole or external capsule. An abdominal skin biopsy showed granular, electron-dense, osmiophilic material (GOM) in the smooth muscle cells on electron microscopy. A direct sequencing analysis of NOTCH3 revealed a heterozygous c.986G>A substitution in exon 6, resulting in a Cys329Tyr amino acid replacement. According to these findings, the patient was diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencehalopathy (CADASIL). Thus, early phases of CADASIL can present as acute bilateral multiple subcortical infarcts without a characteristic temporal pole or any external capsule lesions.
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CADASIL/diagnóstico , Adulto , CADASIL/fisiopatología , Infarto Cerebral/diagnóstico , Infarto Cerebral/fisiopatología , Diagnóstico Diferencial , Exones/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Microscopía Electrónica , Miocitos del Músculo Liso/patología , Piel/patologíaRESUMEN
A 56-year-old man who underwent a tooth extraction in the previous year presented with weakness of the right upper extremity. Brain CT and MRI scans showed subcortical hemorrhage in the left frontal lobe. His body temperature was 37.5°C. Blood examination revealed anemia, elevated levels of C-reactive protein, and a positive result for PR3-ANCA. Aggregatibacter segnis was identified in the incubated blood cultures, and transesophageal echocardiograms showed infectious growth in the anterior mitral leaflet. He was diagnosed with infectious endocarditis. After treatment with ceftriaxione, the clinical symptoms were improved. We concluded that infectious endocarditis caused cerebral hemorrhage and that the positive result for PR3-ANCA was a false positive. Infectious endocarditis can mimic ANCA-associated vasculitis. When ANCA-associated vasculitis is suspected, infectious endocarditis must be ruled out.
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Aggregatibacter segnis , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Endocarditis Bacteriana/diagnóstico , Infecciones por Pasteurellaceae/diagnóstico , Aggregatibacter segnis/aislamiento & purificación , Hemorragia Cerebral/etiología , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a familial neurodegenerative disease clinically characterized by progressive cognitive and motor dysfunction. Mutations in the colony-stimulating factor 1 receptor (CSF1R) gene have recently been identified in HDLS patients. The presence of diffuse axonal spheroids, myelin loss, and pigmented microglia in the white matter are pathologic hallmarks of HDLS; however, early pathologic findings have not been described in HDLS patients. We report a Japanese family with HDLS. A novel heterozygous c.653 C>Y mutation in the CSF1R gene was identified in the female proband who died at the age of 63 years; postmortem findings were compatible with HDLS. We also autopsied her sister who was considered to be neurologically asymptomatic and died of tuberculosis at the age of 44 years. Postmortem studies revealed patchy axonal degeneration and myelin loss, predominantly in the subcortical white matter. Pigmented microglia were distributed diffusely throughout the cerebral white matter and expressed CSF1R poorly. In conclusion, our observations suggest that the pathology of HDLS may initially be characterized by multifocal lesions in subcortical white matter regions. Moreover, pigmented microglia poorly express CSF1R and are distributed diffusely throughout the white matter at the early disease stage, preceding axonal damage and myelin loss.
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Adulto , Diagnóstico Precoz , Femenino , Humanos , Leucoencefalopatías/genética , Leucoencefalopatías/patología , Persona de Mediana EdadRESUMEN
BACKGROUND: Infantile neuroaxonal dystrophy (INAD) is a rare autosomal-recessive neurodegenerative disorder. Patients with INAD usually show neurological symptoms with infant onset and die in childhood. Recently, it was reported that mutations in the PLA2G6 gene cause INAD, but neuropathological analysis of genetically confirmed individuals with neuroaxonal dystrophy has been limited. RESULTS: Here, we report a Japanese individual with neuroaxonal dystrophy associated with compound heterozygous mutations in the PLA2G6 gene. A novel splice-site mutation resulting in skipping and missense mutations (p.R538C) in exon 9 was identified in the patient. This patient initially presented with cerebellar ataxia at the age of 3 years, which was followed by symptoms of mental retardation, extrapyramidal signs, and epileptic seizure. The patient survived until 20 years of age. Neuropathological findings were characterized by numerous axonal spheroids, brain iron deposition, cerebellar neuronal loss, phosphorylated alpha-synuclein-positive Lewy bodies (LBs), and phosphorylated-tau-positive neurofibrillary tangles. In particular, LB pathology exhibited a unique distribution with extremely severe cortical involvement. CONCLUSIONS: Our results support a genetic clinical view that compound heterozygous mutations with potential residual protein function are associated with a relatively mild phenotype. Moreover, the severe LB pathology suggests that dysfunction of the PLA2G6 gene primarily contributes to LB formation.
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Fosfolipasas A2 Grupo VI/genética , Distrofias Neuroaxonales/fisiopatología , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismo , Edad de Inicio , Pueblo Asiatico/genética , Western Blotting , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Análisis Mutacional de ADN , Resultado Fatal , Humanos , Japón , Imagen por Resonancia Magnética , Masculino , Mutación Missense , Distrofias Neuroaxonales/genética , Distrofias Neuroaxonales/patología , Tomografía Computarizada de Emisión de Fotón Único , Adulto JovenAsunto(s)
Hipofosfatemia/etiología , Desnutrición/terapia , Nutrición Parenteral Total/efectos adversos , Enfermedades del Sistema Nervioso Periférico/etiología , Ataxia/etiología , Colitis Ulcerosa/complicaciones , Complicaciones de la Diabetes , Diarrea/complicaciones , Disartria/etiología , Humanos , Masculino , Desnutrición/complicaciones , Persona de Mediana Edad , Debilidad Muscular/etiología , Infarto del Miocardio/complicaciones , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológicoAsunto(s)
Enfermedad de Parkinson/complicaciones , Síndrome de las Piernas Inquietas/etiología , Anciano , Anciano de 80 o más Años , Eszopiclona/uso terapéutico , Humanos , Hipnóticos y Sedantes/uso terapéutico , Masculino , Enfermedad de Parkinson/diagnóstico por imagen , Síndrome de las Piernas Inquietas/diagnóstico por imagen , Tomógrafos Computarizados por Rayos XRESUMEN
Intravenous glucose administration is the most common cause of hypophosphataemia in hospitalised patients. While most of these cases are asymptomatic, severe hypophosphataemia, when combined with phosphorus depletion, can cause acute neuropathy that mimics Guillain-Barré syndrome. A malnourished patient who received intravenous hyperalimentation (IVH) without intravenous phosphate (IP) developed hypophosphataemia and acute sensorimotor neuropathy. F waves in the peripheral nerve trunk were absent or diminished, while nerve conduction velocities were nearly normal. The sural nerve biopsy revealed the presence of some subperineurial oedema and mild axonal atrophy. Prompt IP administration reversed the patients' neurological symptoms and normalised F waves. Our data suggest that hypophosphataemia plays a role in the pathogenesis of neuropathy that develops in patients following IVH without IP.
RESUMEN
INTRODUCTION: Miliary dissemination is a rare form of brain metastasis. The clinical and pathologic features of this form are unclear. METHODS: We report a 66-year-old man with miliary brain metastases from adenocarcinoma of the lung, describing MRI and neuropathologic findings in the context of previously reported cases. RESULTS: Initial disorientation progressed to an apallic state within 6 months. Although, CT with administration of contrast agent failed to demonstrate any lesions, MRI with Gd-DTPA administration showed multiple enhancing miliary nodules in the cerebral cortex, basal ganglia, thalamus, cerebellum, and brainstem. Some of those nodules also could be seen on T2-weighted imaging without Gd-DTPA, but were difficult to identify conclusively. A histopathologic examination at autopsy disclosed diffusely distributed miliary tumor nodules in a perivascular distribution without surrounding focal edema or reactive gliosis. Notably, this patient with miliary brain metastases developed disorientation followed by unconsciousness, which overshadowed other focal neurologic signs at that time. CONCLUSION: We should consider this pattern of brain dissemination when a cancer is associated with unexplained disturbance of consciousness.
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Adenocarcinoma Papilar/patología , Adenocarcinoma Papilar/secundario , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/secundario , Neoplasias Pulmonares/patología , Adenocarcinoma Papilar/psicología , Autopsia , Neoplasias Encefálicas/psicología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
Immunological diagnostic methods have been widely performed and showed high performance in molecular and cellular biology, molecular imaging, and medical diagnostics. We have developed novel methods for the fluorescent labeling of several antibodies coupled with fluorescent nanocrystal QDs. In this study we demonstrated that two bacterial toxins, diphtheria toxin and tetanus toxin, were detected simultaneously in the same view field of a cover slip by using directly QD-conjugated antibodies. We have succeeded in detecting bacterial toxins by counting luminescent spots on the evanescent field with using primary antibody conjugated to QDs. In addition, each bacterial toxin in the mixture can be separately detected by single excitation laser with emission band pass filters, and simultaneously in situ pathogen quantification was performed by calculating the luminescent density on the surface of the cover slip. Our results demonstrate that total internal reflection fluorescence microscopy (TIRFM) enables us to distinguish each antigen from mixed samples and can simultaneously quantitate multiple antigens by QD-conjugated antibodies . Bioconjugated QDs could have great potentialities for in practical biomedical applications to develop various high-sensitivity detection systems.