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INTRODUCTION: Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal-dominant inherited prion disease most often associated with the human prion protein gene (PRNP)-P102L mutation. Although patients manifest considerable phenotypic heterogeneity, the involvement of the nigrostriatal system has not been well-studied. METHODS: We performed dopamine transporter single-photon emission computed tomography (DAT-SPECT) using 123I-ioflupane to investigate the nigrostriatal system function in nine patients with the PRNP-P102L mutation. We also examined the pathological findings in another patient whose predominant feature was ataxia and who died 5 years after disease onset. RESULTS: Striatum uptake of 123I-ioflupane indicated by specific binding ratio (SBR) values was significantly reduced in two patients. The DAT-SPECT examination was performed 6 months after disease onset in one of these patients who manifested rapidly developing cognitive decline mimicking Creutzfeldt-Jakob disease. DAT-SPECT was also performed 9 years after disease onset in another patient who manifested the conventional features of GSS involving ataxia and dementia in the initial phase but showed akinetic mutism at the examination time. Another patient examined 2 years after disease onset who predominantly manifested ataxia showed marginally abnormal SBR values. An autopsy case showed moderate neuronal loss in the substantia nigra, and the degree of neuronal loss was similar in most other parts of the brain. CONCLUSION: Nigrostriatal system involvement may occur in patients with GSS associated with the PRNP-P102L mutation, even though parkinsonism is not the predominant feature.
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Deep brain stimulation (DBS) has emerged as an important therapeutic option for several movement disorders; however, the management of acute complications, such as acute subdural hematoma (ASDH), remains challenging. This is the case of a 71-year-old woman with Parkinson's disease who developed ASDH 12 years after bilateral DBS placement. On admission with altered consciousness, imaging revealed significant displacement of the DBS electrodes because of the hematoma. Emergent craniotomy with endoscopic evacuation was performed with preservation of the DBS system. Postoperatively, complete evacuation of the hematoma was confirmed, and the patient experienced significant clinical improvement. ASDH causes significant electrode displacement in patients undergoing DBS. After hematoma evacuation, the electrodes were observed to return to their proper position, and the patient exhibited a favorable clinical response to stimulation. To preserve the DBS electrodes, endoscopic hematoma evacuation via a small craniotomy may be useful.
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In middle-aged and older men, clinicians often suspect lumbar spine disease when gait is impaired with intermittent claudication, but spinal dural arteriovenous fistula (SDAVF) may be the etiology. An understanding of the key magnetic resonance imaging findings of SDAVF is necessary for early diagnosis, appropriate treatment, and minimization of complications.
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Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis. To clarify the overall profile of PML in Japan, patient data provided at the time of CSF-JCV testing over 10 years (FY2011-2020) were analyzed. PCR testing for 1537 new suspected PML cases was conducted, and 288 (18.7%) patients tested positive for CSF-JCV. An analysis of the clinical information on all individuals tested revealed characteristics of PML cases, including the geographic distribution, age and sex patterns, and CSF-JCV-positivity rates among the study subjects for each type of underlying condition. During the last five years of the study period, a surveillance system utilizing ultrasensitive PCR testing and widespread clinical attention to PML led to the detection of CSF-JCV in the earlier stages of the disease. The results of this study will provide valuable information not only for PML diagnosis, but also for the treatment of PML-predisposing conditions.
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Virus JC , Leucoencefalopatía Multifocal Progresiva , Humanos , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/epidemiología , Japón/epidemiología , Virus JC/genética , Reacción en Cadena de la Polimerasa , ADN ViralRESUMEN
Here, an overview of progressive multifocal leukoencephalopathy (PML) and its drug associations, especially the disease-modifying drug (DMD)-associated PML for multiple sclerosis (MS) were discussed. Additionally, along with presenting the current status of PML in MS caused by natalizumab, fingolimod, and dimethyl fumarate, the possibility of PML onset with siponimod and ofatumumab, the two newly proposed DMDs for MS, was provided. PML treatment in the era of DMD-associated PML, especially PML in MS, is an important issue. With respect to the treatment of PML, to date, there are no specific antiviral drugs against the JC virus; some drugs, that may have therapeutic potential reported recently, were also mentioned.
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Virus JC , Leucoencefalopatía Multifocal Progresiva , Esclerosis Múltiple , Antivirales/uso terapéutico , Dimetilfumarato/uso terapéutico , Clorhidrato de Fingolimod/uso terapéutico , Humanos , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Esclerosis Múltiple/tratamiento farmacológico , Natalizumab/efectos adversosRESUMEN
To understand tuberculous meningitis (TBM), its clinical features and standard therapy were briefly reviewed. In addition, to determine the therapeutic strategies for treatment-resistant TBM, several clinical cases, including those with paradoxical reaction, ventriculitis, cerebral tuberculoma, and human immunodeficiency virus (HIV) co-infection, are presented. Steroid pulse therapy and intrathecal isoniazid administration are discussed as specific therapeutic strategies. Immune reconstitution inflammatory syndrome in patients with TBM suffering from HIV co-infection and alternative drug selection for drug-resistant TBM cases are also introduced. Although TMB is a rare central nervous system infection, it remains a serious disease with high rates of mortality and neurological sequelae. Knowing therapeutic strategies for treatment-resistant TBM is necessary to prevent a devastating prognosis.
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Coinfección , Infecciones por VIH , Tuberculosis Meníngea , Coinfección/complicaciones , Infecciones por VIH/complicaciones , Humanos , Inflamación , Tuberculosis Meníngea/complicaciones , Tuberculosis Meníngea/tratamiento farmacológicoRESUMEN
A 58-year-old man was diagnosed with mycosis fungoides (MF) confirmed by skin biopsy for systemic erythema that appeared in 2006 and had been on psoralen plus ultraviolet A (PUVA) therapy and topical steroids. In September 2017, he had diffuse large B-cell lymphoma and received chemotherapy. Since March 2019, tumor stage MF with large cell transformation was observed, and chemotherapy containing brentuximab vedotin (BV) was performed, which yielded a remarkable response. During the preparation for allogeneic hematopoietic stem cell transplantation, bradykinesia, delayed response, and cognitive decline were observed. Head magnetic resonance imaging fluid-attenuated inversion recovery images showed hyperintensity in the deep white matter below the bilateral frontal cortex. The general cerebrospinal fluid test revealed no abnormalities and was below the sensitivity of JC virus (JCV) quantitative PCR. As progressive multifocal leukoencephalopathy (PML) was strongly suspected from clinical symptoms and radiographic signs, ultrasensitive JCV testing was performed. The test result was positive; hence, the patient was diagnosed with PML. Chemotherapy was discontinued, but his central nervous system symptoms worsened, and he died on the 135th day of illness. We considered that PML developed based on the underlying disease and immunodeficiency caused by chemotherapy such as BV.
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Virus JC , Leucoencefalopatía Multifocal Progresiva , Micosis Fungoide , Neoplasias Cutáneas , Brentuximab Vedotina , Humanos , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/etiología , Imagen por Resonancia Magnética/efectos adversos , Masculino , Persona de Mediana Edad , Micosis Fungoide/complicaciones , Micosis Fungoide/terapia , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
Here, progressive multifocal leukoencephalopathy (PML) and PML in systemic lupus erythematosus (SLE) are reviewed. Disease-modifying therapy (DMT) associated PML is an emerging condition, particularly in multiple sclerosis patients. Although PML is a rare adverse event in SLE, we should consider development of PML more carefully in not only conventional drug-induced PML but also DMT associated PML during SLE treatment in the era of DMT associated PML.
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Leucoencefalopatía Multifocal Progresiva/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Humanos , Inmunosupresores/efectos adversos , Leucoencefalopatía Multifocal Progresiva/inducido químicamenteRESUMEN
BACKGROUND: The clinical importance of ovarian teratoma in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been established, however investigations of ovarian teratoma in patients with anti-NMDAR encephalitis remain limited. OBJECTIVE: To clarify differences in NMDAR distribution and lymphocyte infiltration in ovarian teratoma between patients with and without anti-NMDAR encephalitis. METHODS: Participants initially comprised 26 patients with ovarian teratomas. NMDAR distribution and lymphocyte infiltration in ovarian teratomas were examined using immunopathological techniques. Clinical, laboratory, and radiological data were compared between patients showing the features of encephalitis. Anti-NMDAR antibodies in the serum and cerebrospinal fluid were also measured in encephalitis patients. RESULTS: Neuronal tissues were obtained from ovarian teratomas in 22 patients (after excluding 4 patients who did not satisfy the inclusion criteria), and the presence of NMDA receptor subunits was revealed in all patients. Lymphocyte infiltration was more frequent in the encephalitis group (n = 3) than in the non-encephalitis group. In particular, dense B-lymphocyte infiltration near neural tissues was observed in the encephalitis group. CONCLUSIONS: Differences in lymphocyte infiltration in ovarian teratomas between anti-NMDAR encephalitis and non-encephalitis patients suggest the immunological importance of the ovarian teratoma as the site of antigen presentation in anti-NMDAR encephalitis.
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Encefalitis Antirreceptor N-Metil-D-Aspartato/metabolismo , Encefalitis Antirreceptor N-Metil-D-Aspartato/patología , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Teratoma/inmunología , Teratoma/patología , Adolescente , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Autoanticuerpos/análisis , Linfocitos B/inmunología , Linfocitos B/patología , Femenino , Humanos , Inmunohistoquímica , Linfocitos/inmunología , Persona de Mediana Edad , Neuronas/inmunología , Neuronas/patología , Neoplasias Ováricas/complicaciones , Receptores de N-Metil-D-Aspartato/inmunología , Teratoma/complicaciones , Adulto JovenRESUMEN
A 57-year-old woman presented with motor and cognitive impairments under treatment for cryptogenic organizing pneumonia with immunosuppressive agents. Magnetic resonance imaging showed widespread signal abnormalities in the cerebral white matter. Susceptibility-weighted imaging showed attenuated contrast of the cerebral medullary vein in the lesions, and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) revealed decreased uptake at the same site and increased uptake in multifocal lung involvements. Lung biopsy findings were consistent with diffuse large B-cell lymphoma. Polymerase chain reaction for JC Virus DNA in cerebrospinal fluid yielded positive results. Based on these findings, the present case was given a diagnosis of progressive multifocal leukoencephalopathy (PML). The patient was treated with oral mefloquine, but her respiratory condition deteriorated and chemotherapy was required to prevent further deterioration. As a result, chemotherapy to treat lymphoma could not result in beneficial immune reconstitution, PML continued to progress despite mefloquine treatment, and the patient developed decorticate posture. The efficacy of mefloquine in patients with non-HIV-associated PML warrants further investigation.
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Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Linfoma de Células B/complicaciones , Mefloquina/uso terapéutico , Susceptibilidad a Enfermedades , Femenino , Fluorodesoxiglucosa F18 , Humanos , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Insuficiencia del TratamientoRESUMEN
A 39-year-old man suffering from progressive dysarthria, gait disturbance, and sensorineural deafness for 2 years was admitted to our hospital. He scored 28 points on the mini-mental state examination. He had previously undergone surgery at 24 years and 39 years of age for a cerebellar tumor (pilocytic astrocytoma). Superficial siderosis (SS) was diagnosed based on bloody cerebrospinal fluid (CSF) and the findings of T2-weighted head MRI that revealed marginal hypointensity of the surface of the cerebellum, brainstem, and cerebral cortex. After intravenous infusion and the oral use of hemostatic drugs (carbazochrome, tranexamic acid), the CSF became watery clear and his condition improved. Hemostatic drug therapy should be considered for SS.
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Hemostáticos/administración & dosificación , Siderosis/tratamiento farmacológico , Administración Oral , Adulto , Humanos , Inyecciones Intravenosas , MasculinoRESUMEN
A case of a small left pontine tegmental hemorrhage that presented as cheiro-oral syndrome with a bilateral perioral sensory disturbance is described. An 83-year-old man suddenly developed numbness in his bilateral perioral area and right hand. Head CT and MRI (T(2)*-weighted image) revealed a small left pontine tegmental hemorrhage. The patient was diagnosed as having cheiro-oral syndrome with bilateral perioral sensory disturbance, probably due to unilateral pontine tegmental hemorrhage. All residual symptoms disappeared within a month.In the present case, the following clinicopathological hypothesis was considered. The hematoma located in the left pontine tegmentum impaired the sensory fibers from the contralateral medial lemniscus (from the right hand) and the ventral trigeminothalamic tract (from the right perioral region). In addition, the ipsilateral trigeminothalamic tract (from the left perioral region) was also impaired. It is important to know that a small unilateral lesion in the brainstem (especially the pons) can cause cheiro-oral syndrome with a bilateral perioral sensory disturbance, and a small brainstem hematoma is the most frequent etiology of this disease.
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Hemorragia Cerebral/complicaciones , Mano , Boca , Parestesia/etiología , Núcleo Tegmental Pedunculopontino , Trastornos de la Sensación/etiología , Enfermedades del Nervio Trigémino/etiología , Anciano de 80 o más Años , Hemorragia Cerebral/diagnóstico , Humanos , Imagen por Resonancia Magnética , Masculino , Síndrome , Tomografía Computarizada por Rayos XRESUMEN
It is unclear when and which neurologic deficits should be examined within 24 hours after intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute ischemic stroke. Relationships between serial changes in National Institutes of Health Stroke Scale (NIHSS) subscores and neurologic deterioration (ND) within the first 24 hours after therapy were investigated in 43 consecutive patients. The NIHSS score was measured by neurologists 28 times within 24 hours after therapy. Assessments of subscores associated with ND, defined as the first change 4 or more points from baseline, were performed at 15 minutes (most frequent time of the first ND), 120 minutes (median time of the first ND), and 24 hours after therapy. Seventeen of 43 patients (age range, 55-94 years) showed ND. Of the NIHSS subscores, increases in scores for loss of consciousness (15 minutes, P = .001; 120 minutes, P = .026; 24 hours, P = .018) and motor limbs total (15 minutes, P = .014; 120 minutes, P = .031) were related to deterioration. Items such as questions, gaze, visual fields, ataxia, language, dysarthria, and extinction/inattention were not related to deterioration at any time. In conclusion, ND of ischemic stroke patients treated with intravenous rt-PA therapy was frequently seen within 120 minutes after therapy. Items such as loss of consciousness and motor limbs total may be considered indices for monitoring neurologic deficits after therapy.
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Ataxia/etiología , Isquemia Encefálica/complicaciones , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/complicaciones , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Anciano de 80 o más Años , Ataxia/diagnóstico , Isquemia Encefálica/tratamiento farmacológico , Femenino , Fibrinolíticos/efectos adversos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Examen Neurológico , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Factores de Tiempo , Activador de Tejido Plasminógeno/efectos adversos , Resultado del Tratamiento , Inconsciencia/diagnóstico , Inconsciencia/etiologíaRESUMEN
Spinocerebellar ataxia 36 is caused by the expansion of the intronic GGCCTG hexanucleotide repeat in NOP56. The original article describing this condition demonstrated that patients with spinocerebellar ataxia 36 present with tongue atrophy, a finding that had not been seen in previous types of spinocerebellar ataxias. A total of 2121 patients with clinically diagnosed spinocerebellar ataxia participated in the study. We screened our patient samples for spinocerebellar ataxia 36 using the repeat-primed polymerase chain reaction method and also determined the clinical features of spinocerebellar ataxia 36. Of the ataxia cases examined, 12 were identified as spinocerebellar ataxia 36. Of these, 7 cases (6 families) were autosomal dominant, 4 cases (three families) had a positive family history but were not autosomal dominant, and 1 case was sporadic. The average age of onset was 51.7 years, and disease progression was slow. The main symptoms and signs of disease included ataxia, dysarthria, and hyperreflexia. Approximately half the affected patients demonstrated nystagmus, bulging eyes, and a positive pathological reflex, although dysphagia, tongue atrophy, and hearing loss were rare. Moreover, the observed atrophy of the cerebellum and brain stem was not severe. The patients identified in this study were concentrated in western Japan. The frequency of spinocerebellar ataxia 36 was approximately 1.2% in the autosomal dominant group, and the age of onset for this condition was later in comparison with other spinocerebellar ataxia subtypes.
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Ataxias Espinocerebelosas/genética , Adulto , Edad de Inicio , Pueblo Asiatico/genética , Tronco Encefálico/patología , Cerebelo/patología , Progresión de la Enfermedad , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Examen Neurológico , Reacción en Cadena de la Polimerasa , Ataxias Espinocerebelosas/epidemiología , Ataxias Espinocerebelosas/patología , Expansión de Repetición de TrinucleótidoRESUMEN
A 62-year-old man was admitted to our hospital because of rapidly progressive dysarthria, truncal ataxia, and gait disturbance. High titers of the ProGRP and anti-P/Q-type VGCC antibody were detected in the serum. High accumulation of [18F] was detected at the hilus of the left lung on [18F]-FDG-PET scan. A high-frequency repetitive stimulation test of the median nerve yielded an incremental response. On the basis of these findings, a diagnosis of paraneoplastic cerebellar degeneration (PCD) and Lambert-Eaton myasthenic syndrome (LEMS) associated with small cell lung carcinoma (SCLC) was diagnosed. After intravenous immunoglobulin therapy (IVIg), methylprednisolone (m-PSL) pulse therapy, and other multidisciplinary concurrent treatments, a partial regression of the SCLC and a significant improvement in neurological symptoms were observed. However, ataxia relapsed and brainstem encephalitis developed 6 months later. A marginal improvement in neurological symptoms was observed with IVIg, m-PSL pulse therapy, and intravenous cyclophosphamide pulse therapy (IVCY). SCLC also recurred later. We hypothesized that VGCC of the brainstem was damaged by anti-P/Q-type VGCC antibody.
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Autoanticuerpos/sangre , Biomarcadores de Tumor/sangre , Tronco Encefálico , Canales de Calcio Tipo P/inmunología , Canales de Calcio Tipo Q/inmunología , Encefalitis/etiología , Síndrome Miasténico de Lambert-Eaton/etiología , Neoplasias Pulmonares/complicaciones , Degeneración Cerebelosa Paraneoplásica/etiología , Carcinoma Pulmonar de Células Pequeñas/complicaciones , Terapia Combinada , Encefalitis/diagnóstico , Encefalitis/terapia , Humanos , Síndrome Miasténico de Lambert-Eaton/diagnóstico , Síndrome Miasténico de Lambert-Eaton/terapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Degeneración Cerebelosa Paraneoplásica/diagnóstico , Degeneración Cerebelosa Paraneoplásica/terapia , Fragmentos de Péptidos/sangre , Tomografía de Emisión de Positrones , Proteínas Recombinantes/sangre , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Carcinoma Pulmonar de Células Pequeñas/inmunología , Carcinoma Pulmonar de Células Pequeñas/terapia , Resultado del TratamientoRESUMEN
OBJECTIVE: To clarify the incidence and clinical significance of HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) showing T2 hyperintensity in the spinal cord on magnetic resonance images (MRI). PATIENTS AND METHODS: We reviewed the spinal cord MRI of 38 HAM/TSP patients and analyzed them in relation to clinical and laboratory findings. Analyzed data were: age at onset, disease duration, disability status, responsiveness to interferon therapy, brain abnormalities on MRI, serum anti-HTLV-I titers, and cerebrospinal fluid (CSF) findings. RESULTS: MRI findings of the spinal cord were classified into 3 types, "normal" (n=22, 57.9%), "atrophy" (n=13, 34.2%) and "T2-hyperintensity" (n=3, 7.9%). Patients in the normal and atrophy types showed slowly progressive paraparesis. Significant differences were not found between the normal and atrophy types in any clinical or laboratory data, including disease duration, disability status and responsiveness to interferon-alpha therapy. Meanwhile, all patients showing T2-hyperintensity had severe paraparesis of a rapid progressive nature, with CSF IgG elevation. CONCLUSION: HAM/TSP with T2-hyperintensity on spinal MRI shows a rapid progressive clinical course with severe motor impairment. The incidence of this malignant form of HAM/TSP is estimated to be around 7.9%.
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Infecciones por HTLV-I/epidemiología , Virus Linfotrópico T Tipo 1 Humano , Imagen por Resonancia Magnética/métodos , Enfermedades de la Médula Espinal/epidemiología , Médula Espinal/patología , Médula Espinal/virología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Infecciones por HTLV-I/líquido cefalorraquídeo , Infecciones por HTLV-I/patología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Enfermedades de la Médula Espinal/líquido cefalorraquídeo , Enfermedades de la Médula Espinal/patologíaRESUMEN
OBJECTIVE: To examine the long-term effects of tacrolimus in steroid-dependent myasthenia gravis (MG) patients. PATIENTS AND METHODS: We administered tacrolimus at 3 mg/day to 10 generalized MG patients presented with clinical worsening by a reduction in dose of prednisolone. The effects of tacrolimus were assessed by using the MG activities of daily living (MG-ADL) profile and the post-intervention status criteria provided by the Myasthenia Gravis Foundation of America (PSC-MGFA). RESULTS: Seven patients were able to use tacrolimus without serious adverse effects for 1.0-5.1 years (mean 3.1 years). Further, its administration improved myasthenic symptoms to the level of pharmacologic remission or minimal manifestations of PSC-MGFA in 5 patients and made it possible to discontinue prednisolone administration in 4 of those 5. However, despite improvements caused by tacrolimus, the reduction in dose of prednisolone caused worsening of symptoms in another 2 patients. In addition, blood trough levels of tacrolimus lower than the recommended range were effective to maintain long-term improvements in 2 patients. CONCLUSIONS: Administration of tacrolimus induced long-term improvements and enabled replacement of prednisolone in patients with intractable steroid-dependent MG.
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Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Miastenia Gravis/tratamiento farmacológico , Prednisolona/uso terapéutico , Tacrolimus/uso terapéutico , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
It has been reported that antibodies (Abs) against heterogeneous nuclear ribonucleoproteins (hnRNPs) are associated with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). However, these studies were done under nonmasked conditions. In order to determine whether Abs against hnRNPs associate with HAM/TSP and MS, the authors assayed Abs against two major hnRNPs, hnRNP A1 and A2/B1, in 105 cerebrospinal fluid (CSF) samples under fully masked conditions. Samples included 40 cases of HAM/TSP, 28 of MS, and 37 of other neurological diseases. Anti-hnRNP A1 Abs, and especially anti-hnRNP A2/B1 Abs, were found significantly more often in the CSF of MS patients than in other groups. However, there was no difference in the incidence of anti-hnRNP A1 Abs between HAM/TSP and other disease groups.
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Autoanticuerpos/líquido cefalorraquídeo , Ribonucleoproteínas Nucleares Heterogéneas/líquido cefalorraquídeo , Ribonucleoproteínas Nucleares Heterogéneas/inmunología , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/inmunología , Formación de Anticuerpos , Autoanticuerpos/biosíntesis , Encéfalo/metabolismo , Anticuerpos Anti-HTLV-I , Virus Linfotrópico T Tipo 1 Humano/inmunología , Humanos , Esclerosis Múltiple/sangre , Paraparesia Espástica Tropical/inmunología , Distribución AleatoriaRESUMEN
A 55-year-old man with chronic alcoholism was first referred to us in 1992 because of spastic quadriparesis. T2-weighted images of MRI showed pontine and extracapsule lesions as central pontine and extrapontine myelinolysis (CPM/EPM). He had macrocytic anemia with normal serum level of vitamin B12 (B12). Gait disturbance was progressively worsened from the end of 2004 and dysuria appeared from June, 2005. Neurological examination on admission in November, 2005, showed mild impairment of recent memory, spastic paraparesis with hyperreflexia in all limbs, loss of deep sensations in lower limbs and urinary disturbance. The low serum level of B12 with marked macrocytic anemia was noted. On MRI. the pontine lesion extended to the midbrain but no abnormality was found in the spinal cord. We intramuscularly administered B12, resulting in marked improvement of both anemia and neurological symptoms. The brainstem lesion on MRI, however, was unchanged. We assume that B12 deficiency was involved in the formation of CPM/EPM and the neurological symptoms in our patient.
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Alcoholismo/complicaciones , Mielinólisis Pontino Central/etiología , Deficiencia de Vitamina B 12/complicaciones , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mielinólisis Pontino Central/diagnósticoRESUMEN
Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower limbs. HSP is caused by failure of development or selective degeneration of the corticospinal tracts, which contain the longest axons in humans. The most common form of HSP is caused by mutations of the spastin gene (SPAST), located on chromosome 2p21-p22, which encodes spastin, one of the ATPases associated with diverse cellular activities (AAA). In this study, we detected four causative mutations of SPAST among 14 unrelated patients with spastic paraplegia. Two missense mutations (1447A-->G, 1207C-->G) and two deletion mutations (1465delT, 1475-1476delAA) were located in the AAA cassette region. Three of these four mutations were novel. Previous reports and our results suggest that the frequency of SPAST mutations is higher among Japanese patients with autosomal dominant HSP, although SPAST mutations are also observed in patients with sporadic spastic paraplegia.