RESUMO
SummaryThe common features of anti-N-methyl-d-aspartate (NMDA) receptor encephalitis are neuropsychiatric symptoms that are often challenging, treatment refractory and take years to recover. Electroconvulsive therapy (ECT) is effective in treating these symptoms in the acute phase, including catatonia and psychiatric issues.We describe the case of a man in his 30s with anti-NMDA receptor encephalitis characterised by neuropsychiatric features and treatment-refractory impulsivity, who was successfully treated with ECT. This case suggests that ECT use for behavioural symptoms can be associated with a significant response and may contribute to faster recovery from the disease.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Catatonia , Eletroconvulsoterapia , Masculino , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Catatonia/complicaçõesRESUMO
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disease that can affect multiple generations and cause complications with long-term prednisolone treatment. This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) in preventing NMOSD relapse while reducing prednisolone dosage. The trial involved nine patients with NMOSD who received MMF along with prednisolone dose reduction. MMF was effective in achieving prednisolone dose reduction without relapse in 77.8% of patients, with a significant decrease in mean annualized relapse rate. All adverse events were mild. The findings suggest that MMF could be a viable treatment option for middle-aged and older patients who require steroid reduction.Clinical trial registration number: jRCT, jRCTs051180080. Registered February 27th, 2019-retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs051180080.
Assuntos
Ácido Micofenólico , Neuromielite Óptica , Prednisolona , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imunossupressores/efeitos adversos , Imunossupressores/administração & dosagem , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/administração & dosagem , Neuromielite Óptica/tratamento farmacológico , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Prospectivos , Recidiva , Resultado do TratamentoRESUMO
We report two male patients who had a sensory seizure, which evolved into a focal impaired awareness tonic seizure, and after that, focal to bilateral tonic-clonic seizure. The first case, a 20-year-old man had been treated with steroids for anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive optic neuritis. His seizure started with abnormal sensation in the little finger of the left hand, which spread to the left upper and then to the left lower limb. The seizure then evolved into tonic seizures of the upper and lower limbs and he finally lost awareness. The second case, a 19-year-old man experienced floating dizziness while walking, followed by numbness and a pain-like electrical shock in the right upper limb. The right arm somatosensory seizure evolved into a right upper and lower limb tonic seizure, which spread to the bilateral limbs, and finally he lost awareness. Symptoms of both patients improved after the treatment with steroids. Both patients shared a similar high-intensity FLAIR lesion in the posterior midcingulate cortex. Both patients were diagnosed with MOG antibody-positive cerebral cortical encephalitis because of a positive titer of anti-MOG antibody in the serum. Several reports showed involvement of the cingulate gyrus in MOG antibody-positive cerebral cortical encephalitis, but only a few reported seizure semiology in detail. The semiology reported here is consistent with that of cingulate epilepsy or the findings of electrical stimulation of the cingulate cortex, namely, somatosensory (electric shock or heat sensation), motor (tonic posture), and vestibular symptoms (dizziness). Cingulate seizures should be suspected when patients show somatosensory seizures or focal tonic seizures. MOG antibody-positive cerebral cortical encephalitis should be considered as one of the differential diagnoses when the young patient shows the unique symptoms of an acute symptomatic cingulate seizure.
Assuntos
Encefalite , Imageamento por Ressonância Magnética , Humanos , Masculino , Autoanticorpos , Tontura , Encefalite/tratamento farmacológico , Glicoproteína Mielina-Oligodendrócito , Oligodendroglia , Convulsões/etiologia , Vertigem , Adulto JovemRESUMO
INTRODUCTION: Xeroderma pigmentosum (XP) is a rare intractable disease without a fundamental treatment, presenting with severe photosensitivity, freckle-like pigmented and depigmented maculae and numerous skin cancers before the age of 10 years without strict sun protection. About 70% of the patients exhibit extremely severe sunburn reactions and most of them develop neurological symptoms, including sensorineural hearing impairment and progressive peripheral and central nervous disorders beginning from childhood ages. In the preclinical study, we found that N-acetyl-5-methoxytryptamine was effective in suppressing skin tumour development in addition to improvement of auditory brainstem response in chronically ultraviolet-irradiated XP-A model mice. METHODS AND ANALYSIS: On the bases of the preclinical study, we conduct a clinical trial on the efficacy of NPC-15 for patients with XP with exaggerated sunburn reaction type by a multicentre, double-blinded placebo-controlled, two-group crossover study followed by a 52 weeks open study. ETHICS AND DISSEMINATION: Ethics approval is overseen by the Kobe University Institutional Review Board and Osaka Medical and Pharmaceutical University Institutional Review Board, and the study is conducted in accordance with the approved protocol. All participants will be required to provide written informed consent. Findings will be disseminated through scientific and professional conferences and peer-reviewed journal publications. The data sets generated during the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: jRCTs051210181.
Assuntos
Neoplasias Cutâneas , Queimadura Solar , Xeroderma Pigmentoso , Animais , Camundongos , Xeroderma Pigmentoso/complicações , Queimadura Solar/complicações , Queimadura Solar/prevenção & controle , Estudos Cross-Over , Japão , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
We present a mild case of Cockayne syndrome that was referred to us with an extreme sunburn at the age of 3. In early teens, although her cutaneous symptoms alleviated without any medications, she developed tremor and dysarthria. Neurological examination and brain imaging suggested demyelination disorders. The patient's cells indicated a reduced recovery of RNA synthesis, which was partially restored by the introduction of CSB (Cockayne Syndrome B)-cDNA. In addition, her cells indicated a substantially reduced level of CSB protein. Despite the insidious progression of neurological symptoms, she gave birth to a child. Such mild cases of Cockayne syndrome may be misdiagnosed.
Assuntos
Síndrome de Cockayne , Reparo do DNA , Humanos , Feminino , Criança , Adolescente , Síndrome de Cockayne/complicações , Síndrome de Cockayne/diagnóstico , Síndrome de Cockayne/genéticaRESUMO
Background and Objectives: We describe 2 long-surviving siblings with a mild phenotype of Joubert syndrome (JBTS) harboring a novel compound heterozygous missense variant in the CPLANE1 gene. Methods: Targeted sequencing data of 2 middle-aged siblings (sister and brother) with JBTS were analyzed. Results: The patients were older than 60 years and presented with an inborn facial anomaly and ataxia, accompanied by a molar tooth sign on brain MRI. The male patient showed mild intellectual disability, abnormal eye movements, and progressive gait disturbance. Targeted sequencing revealed a compound heterozygous missense variant of CPLANE1 p.Arg1193Cys_Gln1223Pro; c.3577C>T_3668A>C. Multiple in silico assays predicted that the missense sites were pathogenic. Discussion: The phenotype-genotype correlation of CPLANE1 remains controversial, although many cases have been previously reported in children and young adults. Our study revealed a novel pathogenic variant of CPLANE1 in patients, confirming the role of this gene in JBTS, thus providing an opportunity for neurologists to recognize JBTS as a differential diagnosis for chronic progressive ataxia in an aging society.
RESUMO
BACKGROUND: Recessive mutations in SLC12A6 have been linked to hereditary motor sensory neuropathy with agenesis of the corpus callosum. Patients with early-onset peripheral neuropathy associated with SLC12A6 heterozygous variants were reported in 2016. Only five families and three variants have been reported to date, and the spectrum is unclear. Here, we aim to describe the clinical and mutation spectra of SLC12A6-related Charcot-Marie-Tooth (CMT) disease in Japanese patients. METHODS: We extracted SLC12A6 variants from our DNA microarray and targeted resequencing data obtained from 2598 patients with clinically suspected CMT who were referred to our genetic laboratory by neurological or neuropediatric departments across Japan. And we summarized the clinical and genetic features of these patients. RESULTS: In seven unrelated families, we identified one previously reported and three novel likely pathogenic SLC12A6 heterozygous variants, as well as two variants of uncertain significance. The mean age of onset for these patients was 17.5 ± 16.1 years. Regarding electrophysiology, the median motor nerve conduction velocity was 39.6 ± 9.5 m/sec. For the first time, we observed intellectual disability in three patients. One patient developed epilepsy, and her brain MRI revealed frontal and temporal lobe atrophy without changes in white matter and corpus callosum. CONCLUSIONS: Screening for the SLC12A6 gene should be considered in patients with CMT, particularly those with central nervous system lesions, such as cognitive impairment and epilepsy, regardless of the CMT subtype.
Assuntos
Doença de Charcot-Marie-Tooth , Simportadores , Adolescente , Adulto , Doença de Charcot-Marie-Tooth/genética , Criança , Pré-Escolar , Feminino , Heterozigoto , Humanos , Lactente , Japão , Mutação , Simportadores/genética , Adulto JovemRESUMO
BACKGROUND: In the current consensus criteria, onset after age 75 is considered as non-supporting for diagnosis of multiples system atrophy (MSA); however, some MSA patients present after age 75. Clinical and pathological characteristics of such later onset MSA (LO-MSA) compared to usual onset MSA (UO-MSA) remain poorly understood. METHODS: The clinical cohort included patients from Kobe University Hospital and Amagasaki General Medical Center Hospital, while the autopsy cohort was from the brain bank at Mayo Clinic Florida. We identified 83 patients in the clinical cohort and 193 patients in the autopsy cohort. We divided MSA into two groups according to age at onset: UO-MSA (≤ 75) and LO-MSA (> 75). We compared clinical features and outcomes between the two groups in the clinical cohort and compared the findings to the autopsy cohort. RESULTS: LO-MSA accounted for 8% in the clinical cohort and 5% in the autopsy cohort. The median time from onset to death or to life-saving tracheostomy was significantly shorter in LO-MSA than in UO-MSA in both cohorts (4.8 vs 7.9 years in the clinical cohort and 3.9 vs 7.5 years in the autopsy cohort; P = 0.043 and P < 0.0001, respectively). The median time from diagnosis to death was less than 3 years in LO-MSA in the clinical cohort. CONCLUSIONS: Some MSA patients have late age of onset and short survival, limiting time for clinical decision making. MSA should be considered in the differential diagnosis of elderly patients with autonomic symptoms and extrapyramidal and/or cerebellar syndromes.
Assuntos
Atrofia de Múltiplos Sistemas , Idoso , Autopsia , Encéfalo/patologia , Estudos de Coortes , Diagnóstico Diferencial , Humanos , Atrofia de Múltiplos Sistemas/diagnósticoRESUMO
A 62-year-old man showed abnormal behavior. Brain magnetic resonance imaging revealed multifocal lesions on T2-weighted images. Initial screening revealed that he was seropositive for antibodies against glutamate decarboxylase, which usually indicates treatment resistance to autoimmune encephalitis (AE). Intensive immunosuppressive therapies, however, improved the neurological symptoms. In line with this, we also detected seropositivity for antibodies against leucine-rich glioma-inactivated 1 and gamma-aminobutyric acid A receptor (GABAAR). Brain imaging and treatment responsiveness suggested that antibodies against GABAAR were the main cause of symptoms. Furthermore, the patient showed the presence of triple anti-neural antibodies in the absence of malignancy and had a favorable clinical course.
Assuntos
Encefalite , Doença de Hashimoto , Encefalite Límbica , Autoanticorpos , Encefalite/terapia , Humanos , Imunoterapia , Peptídeos e Proteínas de Sinalização Intracelular , Encefalite Límbica/terapia , Masculino , Pessoa de Meia-Idade , Receptores de GABA-ARESUMO
We report a 60-year-old woman who developed spinal cord infarction (SCI) with anti-aquaporin (AQP) 4 antibody seropositive. She was admitted to our hospital with acute onset of flaccid paraparesis and urinary disturbances that completed within a few minutes after acute pain in her lower back. Neurological examination revealed flaccid paraparesis, bladder and bowel dysfunction and dissociated sensory loss below the level of Th11 spinal cord segment. Diffusion weighted imaging (DWI) and T2-wighted imaging (T2WI) of thoracic spine MRI showed high signal intensity in the spinal cord between Th9 and Th12 vertebral levels with decreased apparent diffusion coefficient (ADC). We diagnosed her as having SCI. Thereafter the serum examination on admission was reported as positive for anti-aquaporin 4 (AQP4) antibody. Cerebrospinal fluid (CSF) analysis revealed pleocytosis, and the spinal cord lesions became enlarged in MRI on 12 days after the onset. We, therefore, suspected that the pathophysiology of neuromyelitis optica spectrum disorder (NMOSD) accompanied SCI. The patient underwent two courses of high dose intravenous methylprednisolone (IVMP) for three days (1â g/day). Her neurological symptoms did not improve significantly, but the size of T2WI MRI high signal lesion improved to that of the initial MRI scan. Anti-AQP4 antibody seropositivity may have modified the SCI pathology in the present patient.
Assuntos
Neuromielite Óptica/etiologia , Isquemia do Cordão Espinal/complicações , Aquaporina 4/imunologia , Autoanticorpos , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Líquido Cefalorraquidiano/citologia , Imagem de Tensor de Difusão , Feminino , Humanos , Leucocitose/líquido cefalorraquidiano , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico , Isquemia do Cordão Espinal/diagnósticoRESUMO
A 74-year-old man, who received pembrolizumab for the treatment for non-small cell lung cancer, developed quadriparesis 10 days after the first course of treatment accompanied by gait disturbance. Dysesthesia was observed in the distal extremities, and tendon reflexes were absent. Neurological examination and peripheral nerve conduction study supported the diagnosis of Guillain-Barré syndrome-like acute inflammatory demyelinating polyneuropathy caused by pembrolizumab. The administration of pembrolizumab was discontinued. Moreover, he was initially treated with intravenous immunoglobulin therapy, followed by intravenous methylprednisolone therapy and oral prednisolone. The limb weakness improved to a degree that he could walk alone on discharge. Pembrolizumab, which is an immune checkpoint inhibitor with a high anti-tumor effect, is reported to cause various adverse events. However, neuromuscular complications following cancer treatment with immune checkpoint inhibitors are relatively rare. Treatment with corticosteroids is considered to be effective for treating immune-related adverse events. Corticosteroids were effective in treating peripheral neuropathy caused by immune checkpoint inhibitors in this patient. Thorough treatment should be considered with a combination of corticosteroids and immunoglobulin therapy, in addition to discontinuation of immune checkpoint inhibitors, for this rare entity, which differs from that for idiopathic Guillain-Barré syndrome.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome de Guillain-Barré/induzido quimicamente , Síndrome de Guillain-Barré/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoglobulinas Intravenosas/administração & dosagem , Metilprednisolona/administração & dosagem , Idoso , Humanos , Imunoterapia , Infusões Intravenosas , Masculino , Prednisolona/administração & dosagem , Pulsoterapia , Resultado do TratamentoRESUMO
BACKGROUND: In this study, we aimed to investigate the progression of peripheral nervous system involvement in xeroderma pigmentosum group A (XP-A). METHODS: We performed nerve conduction studies in 17 genetically confirmed XP-A patients and conducted follow-ups. Of these patients we also analyzed gray matter volume (GMV) using brain MRI and assessed the severity score of clinical and skin manifestation. RESULTS: We found significant reduction in the motor and sensory nerve action potential amplitude and mild reduction in conduction velocity. These findings were predominant in sensory nerves and the lower limbs, were observed since early childhood, and gradually deteriorated with age. CONCLUSIONS: The electrophysiological characteristics of XP-A patients are consistent with length-dependent axonal polyneuropathy and there is progressive deterioration from early childhood.
Assuntos
Encéfalo/fisiopatologia , Condução Nervosa/fisiologia , Xeroderma Pigmentoso/fisiopatologia , Adolescente , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Índice de Gravidade de Doença , Xeroderma Pigmentoso/diagnóstico por imagem , Adulto JovemRESUMO
A 42-year-old woman diagnosed with multiple sclerosis (MS) at the age of 37 was initially treated with interferon-ß IM. The frequency of clinical relapses was twice in 4 years. At the age of 41, due to difficulty in administering muscle injections, an oral medication fingolimod was started. However, it was discontinued after a month due to decreased lymphocyte count, following which natalizumab was administered. The number of relapses increased 3 times in eleven months, and the number of T2 lesions on the MRI increased from 12 to 23. Natalizumab was discontinued because the test for the anti-natalizumab antibody was positive. It was suspected that both, the rebound syndrome caused by fingolimod cessation and the drug neutralization by anti-natalizumab antibodies, were associated with the exacerbation of disease activity. Thus, careful attention should be paid to potential occurrence of these events post switching between disease-modifying drugs for treating MS with high activity.
Assuntos
Substituição de Medicamentos/efeitos adversos , Cloridrato de Fingolimode/administração & dosagem , Cloridrato de Fingolimode/efeitos adversos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Natalizumab/administração & dosagem , Natalizumab/efeitos adversos , Adulto , Anticorpos , Progressão da Doença , Feminino , Humanos , Injeções Intramusculares , Interferon beta/administração & dosagem , Contagem de Linfócitos , Natalizumab/imunologia , RecidivaAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Diafragma/fisiopatologia , Miosite/induzido quimicamente , Nervo Frênico/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Autoanticorpos/imunologia , Conectina/imunologia , Diafragma/diagnóstico por imagem , Eletromiografia , Humanos , Canal de Potássio Kv1.4/imunologia , Masculino , Miosite/complicações , Miosite/imunologia , Condução Nervosa , Ventilação não Invasiva , Respiração com Pressão Positiva , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Ultrassonografia , Capacidade VitalRESUMO
OBJECTIVE: To identify mutations in vacuolar protein sorting 13A (VPS13A) for Japanese patients with suspected chorea-acanthocytosis (ChAc). METHODS: We performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis of the VPS13A gene, and chorein Western blotting of erythrocyte ghosts. As the results of the analysis, 17 patients were molecularly diagnosed with ChAc. In addition, we investigated the distribution of VPS13A gene mutations and clinical symptoms in a total of 39 molecularly diagnosed Japanese patients with ChAc, including 22 previously reported cases. RESULTS: We identified 11 novel pathogenic mutations, including 1 novel CNV. Excluding 5 patients with the unknown symptoms, 97.1% of patients displayed various neuropsychiatric symptoms or forms of cognitive dysfunction during the course of disease. The patients carrying the 2 major mutations representing over half of the mutations, exon 60-61 deletion and exon 37 c.4411C>T (R1471X), were localized in western Japan. CONCLUSIONS: We identified 13 different mutations in VPS13A, including 11 novel mutations, and verified the clinical manifestations in 39 Japanese patients with ChAc.
RESUMO
Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease caused by deficiency in repair of DNA lesions generated by ultraviolet radiation and other compounds. Patients with XP display pigmentary change and numerous skin cancers in sun-exposed sites, and some patients show exaggerated severe sunburns even upon minimum sun exposure as well as neurological symptoms. We conducted a nationwide survey for XP since 1980. In Japan, the frequency of the XP complementation group A is the highest, followed by the variant type; while in the Western countries, those of groups C or D are the highest. Regarding skin cancers in XP, basal cell carcinoma was the most frequent cancer that afflicted patients with XP, followed by squamous cell carcinoma, and malignant melanoma. The frequency of these skin cancers in patients with XP has decreased in these 20 years, and the age of onset of developing skin cancers is higher than those previously observed, owing to early diagnosis and education to patients and care takers on strict prevention from sunlight for patients with XP. On the other hand, the effective therapy for neurological XP has not been established yet, and this needs to be done urgently.
Assuntos
Xeroderma Pigmentoso/patologia , Xeroderma Pigmentoso/terapia , Idade de Início , Reparo do DNA , Replicação do DNA , Genótipo , Humanos , Japão/epidemiologia , Fenótipo , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/epidemiologia , Protetores Solares/administração & dosagem , Inquéritos e Questionários , Xeroderma Pigmentoso/complicações , Xeroderma Pigmentoso/epidemiologiaRESUMO
Several genes related to mitochondrial functions have been identified as causative genes of neuropathy or ataxia. Cytochrome c oxidase assembly factor 7 (COA7) may have a role in assembling mitochondrial respiratory chain complexes that function in oxidative phosphorylation. Here we identified four unrelated patients with recessive mutations in COA7 among a Japanese case series of 1396 patients with Charcot-Marie-Tooth disease (CMT) or other inherited peripheral neuropathies, including complex forms of CMT. We also found that all four patients had characteristic neurological features of peripheral neuropathy and ataxia with cerebellar atrophy, and some patients showed leukoencephalopathy or spinal cord atrophy on MRI scans. Validated mutations were located at highly conserved residues among different species and segregated with the disease in each family. Nerve conduction studies showed axonal sensorimotor neuropathy. Sural nerve biopsies showed chronic axonal degeneration with a marked loss of large and medium myelinated fibres. An immunohistochemical assay with an anti-COA7 antibody in the sural nerve from the control patient showed the positive expression of COA7 in the cytoplasm of Schwann cells. We also observed mildly elevated serum creatine kinase levels in all patients and the presence of a few ragged-red fibres and some cytochrome c oxidase-negative fibres in a muscle biopsy obtained from one patient, which was suggestive of subclinical mitochondrial myopathy. Mitochondrial respiratory chain enzyme assay in skin fibroblasts from the three patients showed a definitive decrease in complex I or complex IV. Immunocytochemical analysis of subcellular localization in HeLa cells indicated that mutant COA7 proteins as well as wild-type COA7 were localized in mitochondria, which suggests that mutant COA7 does not affect the mitochondrial recruitment and may affect the stability or localization of COA7 interaction partners in the mitochondria. In addition, Drosophila COA7 (dCOA7) knockdown models showed rough eye phenotype, reduced lifespan, impaired locomotive ability and shortened synaptic branches of motor neurons. Our results suggest that loss-of-function COA7 mutation is responsible for the phenotype of the presented patients, and this new entity of disease would be referred to as spinocerebellar ataxia with axonal neuropathy type 3.
Assuntos
Complexo IV da Cadeia de Transporte de Elétrons/genética , Neuropatia Hereditária Motora e Sensorial/complicações , Neuropatia Hereditária Motora e Sensorial/genética , Mutação/genética , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/genética , Adolescente , Animais , Animais Geneticamente Modificados , Encéfalo/diagnóstico por imagem , Células Cultivadas , Drosophila , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Saúde da Família , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Predisposição Genética para Doença/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HeLa , Neuropatia Hereditária Motora e Sensorial/diagnóstico por imagem , Humanos , Discos Imaginais/metabolismo , Discos Imaginais/ultraestrutura , Locomoção/efeitos dos fármacos , Locomoção/genética , Masculino , Pessoa de Meia-Idade , Neurônios Motores/patologia , Junção Neuromuscular/genética , Junção Neuromuscular/patologia , Junção Neuromuscular/ultraestrutura , Desempenho Psicomotor/fisiologia , Interferência de RNA/fisiologia , Medula Espinal/diagnóstico por imagem , Ataxias Espinocerebelares/diagnóstico por imagem , Adulto JovemRESUMO
A 40-year-old woman with renal dysfunction for 2 years was admitted to our hospital suffering from a headache. Family history revealed that her mother had a headache, renal dysfunction, and brain infarction in younger age. She had a retinal hemorrhage, a retinal atrophy, pitting edema in her lower extremities. Her neurological findings were unremarkable. Brain imaging showed multiple white matter lesions accompanied with calcifications and slightly enhancement. Kidney biopsy showed the thrombotic microangiopathy, Gene analysis demonstrated a causative mutation in three-prime repair exonuclease-1 (TREX1) gene, c.703_704insG (p.Val235GlyfsX6), thereby we diagnosed her as retinal vasculopathy with cerebral leukoencephalopathy (RVCL). RVCL is an autosomal dominant condition caused by C-terminal frame-shift mutation in TREX1. TREX1 protein is a major 3' to 5' DNA exonuclease, which are important in DNA repair. While TREX1 mutations identified in Aicardi-Goutieres syndrome patients lead to a reduction of enzyme activity, it is suggested that mutations in RVCL alter an intracellular location of TREX1 protein. There are no treatments based evidences in RVCL. We administered cilostazol to protect endothelial function, and her brain lesions and renal function have not become worse for 10 months after. It is necessary to consider RVCL associated with TREX1 mutation if a patient has retinal lesions, white matter lesions accompanied with calcifications, and multiple organ dysfunction.
Assuntos
Cérebro/patologia , Exodesoxirribonucleases/genética , Leucoencefalopatias/diagnóstico , Leucoencefalopatias/genética , Mutação , Fosfoproteínas/genética , Vasculite Retiniana/diagnóstico , Vasculite Retiniana/genética , Administração Oral , Adulto , Calcinose , Cérebro/diagnóstico por imagem , Cilostazol , Humanos , Leucoencefalopatias/complicações , Leucoencefalopatias/dietoterapia , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Vasculite Retiniana/complicações , Vasculite Retiniana/tratamento farmacológico , Tetrazóis/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
There is no reliable objective indicator for upper motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). To determine the clinical significance and potential utility of magnetic resonance (MR) signals, we investigated the relationship between clinical symptoms and susceptibility changes in the motor cortex measured using susceptibility-weighted MR imaging taken by readily available 3-T MRI in clinical practice. Twenty-four ALS patients and 14 control subjects underwent 3-T MR T1-weighted imaging and susceptibility-weighted MR imaging with the principles of echo-shifting with a train of observations (PRESTO) sequence. We analysed relationships between relative susceptibility changes in the motor cortex assessed using voxel-based analysis (VBA) and clinical scores, including upper motor neuron score, ALS functional rating scale revised score, and Medical Research Council sum score on physical examination. Patients with ALS exhibited significantly lower signal intensity in the precentral gyrus on susceptibility-weighted MR imaging compared with controls. Clinical scores were significantly correlated with susceptibility changes. Importantly, the extent of the susceptibility changes in the bilateral precentral gyri was significantly correlated with upper motor neuron scores. The results of our pilot study using VBA indicated that low signal intensity in motor cortex on susceptibility-weighted MR imaging may correspond to clinical symptoms, particularly upper motor neuron dysfunction. Susceptibility-weighted MR imaging may be a useful diagnostic tool as an objective indicator of upper motor neuron dysfunction.