Clinical Neurology最新文献

A 56-year-old male subject was presented with a two-month history of dysarthria and gait disturbance. T₂-weighted MRI revealed high signal intensity in the right cerebellar hemisphere, pons, and bilateral middle cerebellar peduncles. Suspecting brain-stem encephalitis, he was treated with steroid pulse therapy, which was ineffective. Subsequently, a qualitative PCR test was performed, confirming the diagnosis of progressive multifocal leukoencephalopathy (PML) with a high JC virus (JCV) load (273,857 copies/ml) in the cerebrospinal fluid (CSF). The JCV strain in the CSF was a prototype with a deletion in the regulatory region of its genomic DNA. Long-term untreated rheumatoid arthritis (RA) was identified as an underlying cause. Other potential immunodeficiency-related diseases, including idiopathic CD4 lymphocytopenia, malignant RA, systemic lupus erythematosus, chronic eosinophilic leukemia, malignant lymphoma, and congenital immunodeficiency, were ruled out based on various laboratory tests. Despite treatment with a combination of mefloquine and mirtazapine, the patient died on the 102nd day due to disease progression. RA with non-drug related immune abnormalities should be considered a potential underlying cause of PML.

The patient was a 41-year-old man with a history of diabetes mellitus since the age of 22 years and a family history of diabetes in his mother. He had repeated headaches, cerebellar symptoms, and bilateral cerebellar lesions on brain MRI (DWI, T₂ FLAIR hyperintensities). He was previously diagnosed with cerebellitis and treated with steroids at another hospital. Upon his third relapse, he was referred to our department. Clinical findings included short stature, diabetes, elevated CSF lactate and pyruvate levels, and increased lactate levels on aerobic exercise testing. Muscle biopsy revealed mitochondrial pathological abnormalities, and genetic testing of muscle tissue identified the mitochondrial DNA m.3243 mutation. These findings led to the diagnosis of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Stroke-like lesions in MELAS can involve not only the cerebrum but also the cerebellum. When cortical-predominant lesions with associated vascular dilatation are observed, MELAS should be considered in the differential diagnosis.

I had the honor of being awarded the 2021 Japan Neurological Society Award in the Clinical/Education category. The award theme was 'Efforts in Undergraduate and Specialist Training in Neurology,' and until the previous year, this category had been awarded to those who made significant contributions in clinical practice. This was the first time education had been recognized with an award in this category. It is believed that the publication of 'Neurology for Medical Students and Residents,' first published in 2008, played a crucial role in this honor due to its contribution to undergraduate and postgraduate education. I will discuss the background of the publication, its formation, the philosophy behind its creation, and what it aimed to convey.

A man in his 40s was transferred to our hospital due to headache, hearing loss, and altered consciousness, which developed several days after consuming a barbeque meal, including pork. Based on his clinical symptoms and various laboratory findings, he was diagnosed with bacterial meningitis caused by Streptococcus suis, and treatment was initiated with antibacterial agents and dexamethasone. After 3 weeks, his symptoms and laboratory results showed improvement, allowing for the discontinuation of the antibacterial therapy. However, a few days after stopping antibiotics, his symptoms and cerebrospinal fluid (CSF) findings worsened, prompting the resumption of antibacterial treatment. The therapy was ultimately terminated after 5 weeks, following confirmation of clinical and CSF improvement. Despite resolution of the meningitis symptoms, the patient was left with bilateral sensorineural hearing loss, predominantly affecting his right ear. Following systemic steroid administration and hyperbaric oxygen therapy, his left-sided hearing improved, but no improvement was observed in his right ear, and he continued to experience severe hearing loss.

We describe an autopsy case of spinal bulbar muscular atrophy (SBMA) concomitant with multiple system atrophy (MSA). A Japanese male patient developed gait disturbance in his twenties. His brother and niece also presented with similar clinical symptoms. His condition gradually worsened, and he became immobile at the age of 50 years. Genetic analysis revealed the expansion of CAG repeats of the SBMA gene. At 63 years of age, cerebellar ataxia symptoms emerged. Magnetic resonance images of the head showed a "hot cross bun sign" at the pontine basis and bilateral atrophy of the middle cerebellar peduncles and cerebellar hemispheres, suggesting MSA. He died of pneumonia at the age of 65 years, with a clinical illness of approximately 40 years. The neuropathological diagnosis was consistent with both SBMA and MSA. Neurons of the spinal anterior horn and brainstem motor nuclei were diminished. 1C2 (polyglutamine) immunoreactive intranuclear and intracytoplasmic inclusions were observed in the neurons in the substantia nigra, brainstem tegmentum, pontine nuclei, spinal anterior horn cells and Onuf's nucleus. These findings were suggestive of SBMA. Meanwhile, neurons of the inferior olivary nuclei, pontine nuclei, and Purkinje cells were nearly completely lost. The cerebellar white matter, pontine basis, and middle cerebellar peduncles showed a prominent loss of fibers. α-synuclein positive glial cytoplasmic inclusions were observed in widespread areas. These findings were suggestive of MSA. To the best of our knowledge, another case of SBMA accompanying MSA, similar to the present case, have been reported to date. Moreover, several cases of pathologically proven amyotrophic lateral sclerosis and MSA have been reported. The development of molecular biological techniques and accumulation of pathologically diagnosed patients may reveal common pathological mechanisms in SBMA and MSA.

A 75-year-old woman with multiple myeloma was admitted due to an acute disturbance of consciousness and aphasia two months after administration of daratumumab, lenalidomide and dexamethasone combination therapy (DLd therapy). Brain MRI on admission showed no acute ischemic changes. She was treated with antiepileptic drugs, and DLd therapy was discontinued, but her consciousness deteriorated, and follow-up brain MRI showed progressive FLAIR high-signal intensity lesions in the cerebral deep white matter bilaterally. Though methylprednisolone pulse therapy and high-dose intravenous immunoglobulin were ineffective, plasma exchange improved her consciousness, and she began to speak. In addition, her MRI findings improved. Progressive multifocal leukoencephalopathy induced by drugs for multiple myeloma has been reported, but, in this case, leukoencephalopathy associated with daratumumab was suspected because JC virus DNA was not detected in her cerebrospinal fluid.

A 54-years-old Japanese man visited local hospital with six-month history of progressive numbness and muscle weakness in his lower limbs. He was diagnosed with POEMS syndrome based on positive serum M-protein, elevated serum VEGF, and splenomegaly. MRI showed multiple cerebral infarcts in the watershed area, and MRA showed complete vascular occlusion of the right internal carotid artery and severe vascular stenosis of the left common carotid artery, suggesting hemodynamic cerebral infarction. He was referred to our department and treated with three courses of Daratumumab-Bortezomib-Dexamethasone (DBd) therapy. After normalization of VEGF was confirmed, right superficial temporal artery-middle cerebral bypass surgery was performed. He has been kept in good condition with improved muscle strength and walking ability, and normalized VEGF level under the maintenance Daratumumab-Lenalidomide-Dexamethasone (DLd) therapy. Because POEMS syndrome-associated vasculopathy can develop even in the very early stage of the disease, intensive evaluation of craniocervical vessels before treatment initiation is very important for treatment selection and risk assessment.

A woman in her 50s. Since October of X-1, she had been suffering from lower back and occipital pain. Despite undergoing medical evaluations at multiple hospitals, no discernible abnormalities were identified. As her symptoms worsened, she presented to our department in January of X, reporting severe pain in the left occipital to posterior neck that increased with both neck flexion and extension. A neurological examination revealed a left-sided deviation of the tongue (left hypoglossal nerve paralysis). A head MRI revealed signal abnormalities in the left occipital condyle and multiple nodules with contrast effects in the brain parenchyma. A computed tomography (CT) scan revealed a mass in the left lung, multiple intrahepatic masses, and bone destruction in the spine and left occipital condyle. In light of these findings, a diagnosis of lung cancer with metastasis to multiple organs and occipital condyle syndrome due to metastasis to the left occipital condyle was suspected. Subsequent cytological analysis of bronchoalveolar lavage fluid and liver biopsy substantiated the diagnosis of adenocaricinoma. The subsequent administration of osimertinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, led to a reduction in the size of the tumor, as well as improvements in the hypoglossal nerve palsy and occipital pain. It is imperative to note that occipital condyle syndrome signifies the metastasis of a malignancy to the base of the skull, necessitating meticulous observation and management.

We report a 54-year-old woman previously healthy who developed acute fever, headache, and impaired consciousness. We administered corticosteroid therapy as autoimmune mediated meningoencephalitis, which improved her symptoms and reduced cerebrospinal IL-6 level, but her cognitive impairment persisted. Contrast-enhanced MRI showed diffuse meningeal enhancement lesion, which led us to the possibility of leptomeningeal amyloidosis (LA). We performed transthyretin gene analysis identified heterozygosity for the c.265T>C, p.Y89H (Y69H) variant, which is known as one of the causative mutations of familial LA. Given the responsiveness to steroid treatment, it is possible that the inflammatory pathology related to amyloid deposition in leptomeninges with encephalitis-like symptoms contributed to the prolonged duration of symptoms lasting from hours to days.

Benign adult familial myoclonus epilepsy (BAFME) is an autosomal dominantly inherited disease characterized by infrequent seizures and tremorous myoclonus. The disease is also called familial adult myoclonic epilepsy (FAME) or familial cortical myoclonic tremor with epilepsy (FCMTE). Although the causes of BAFME had been unknown for a long, we identified TTTCA and TTTTA repeat expansions in intron 4 of SAMD12 as a cause of BAFME type 1. We also found TTTCA and TTTTA repeat expansions in TNRC6A and RAPGEF2 also cause the disease (BAFME types 6 and 7, respectively), thus proposing a concept of repeat motif-phenotype correlation. After that, TTTCA and TTTTA repeat expansions in STARD7, MARCHF6, YEATS2, and RAI1 have been identified as causes of BAFME types 2, 3, 4, and 8. The findings further supported the concept. The involvement of RNA-mediated toxicity, particularly of UUUCA repeats, is assumed to be the pathomechanism of this disease. The next step will be understanding the molecular pathomechanism of BAFME and identifying molecular targets of more efficient therapeutic approaches.