We reported an 81-year-old woman with metastatic melanoma, in whom myasthenia gravis and rhabdomyolysis developed after nivolumab monotherapy. The first symptom of myasthenia gravis was dyspnea. ...Ultrasonography detected hypokinesis of the bilateral diaphragm suggesting myasthenia gravis, although there was no abnormal finding of the lungs in computed tomography images. Acetylcholine receptor binding antibodies were low-titer positive in the preserved serum before administration of nivolumab, strongly suggesting that the myasthenia gravis was a nivolumab-related immune adverse event. Despite the remarkable clinical benefits of immune checkpoint inhibitors for patients with advanced melanoma, it is important to recognize unexpected immune-related adverse events.
We herein report the first case of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy after coronavirus disease 2019 (COVID-19). A 23-year-old man experienced fatigue, a fever, and ...headache 14 days after the resolution of COVID-19. He was severely disoriented and admitted to our hospital. On admission, the patient exhibited disorientation, headache, neck stiffness, myoclonus of both upper limbs, dysuria, and pyramidal signs. A blood examination revealed hyponatremia, and a cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis. The CSF test results were positive for anti-GFAPα antibodies. The patient was treated with methylprednisolone pulse therapy, followed by oral prednisolone, which quickly ameliorated his neurological abnormalities.
We encountered a 37-year-old Japanese man with KIF1A-associated neurological disorder (KAND) who exhibited motor developmental delay, intellectual disability, and slowly progressive cerebellar ...ataxia, hypotonia, and optic neuropathy. Pyramidal tract signs were evident late in this case. At 30 years old, the patient developed a neurogenic bladder. A molecular diagnosis revealed a uniallelic missense de novo variant (p.L278P) of KIF1A. Serial neuroradiological studies revealed atrophy of the cerebellum at an early age, and cerebral hemisphere atrophy progressed slowly over a 22-year observation period. Our study suggests that the primary etiology of KAND may be acquired, long-standing neurodegeneration rather than congenital hypoplasia.
A 49-year-old Japanese man had shown developmental delay, learning difficulties, epilepsy, and slowly progressive gait disturbance in elementary school. At 46 years old, he experienced repeated ...drowsiness with or without generalized convulsions, and hyperammonemia was detected. Brain magnetic resonance imaging detected multiple cerebral white matter lesions. An electroencephalogram showed diffuse slow basic activities with 2- to 3-Hz δ waves. Genetic tests confirmed a diagnosis of hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Leukoencephalopathy was resolved following the administration of L-arginine and lactulose with a decrease in plasma ammonia levels and glutamine-glutamate peak on magnetic resonance spectroscopy. Leukoencephalopathy in HHH syndrome may be reversible with the resolution of hyperammonemia-induced glutamine toxicity.
Taste disorder is a common symptom in the general population. Several studies have shown that patients with neurological disorders, such as amyotrophic lateral sclerosis and Parkinson's disease, ...develop taste disturbance. Facial onset sensory and motor neuronopathy (FOSMN) is a rare disease characterized by sensory disturbance and weakness spreading from the face to the limbs caudally. We describe a patient with FOSMN who showed taste disorder as the sole initial symptom.
A 49-year-old man who smoked cigarettes developed taste disturbance. Despite using zinc supplements, an herbal medication, and an ointment, his taste disorder worsened. 4 years later, a tingling feeling emerged at the tip of his tongue and gradually spread to his entire lips. At 55 years of age, he showed difficulty in swallowing, followed by facial paresthesia, muscle atrophy, and weakness in the face and upper limbs without apparent upper motor neuron sign. Cessation of smoking did not improve his taste disturbance, and he was unable to discriminate different tastes on the entire tongue. In an electrogustometric study, electrical stimulation did not induce any type of taste sensation. Blink reflex showed delayed or diminished R2 responses. Needle electromyography revealed severe chronic neurogenic changes in the tongue and masseter muscles. Mild chronic neurogenic changes were also observed in the limbs. In the thoracic paraspinal muscles, active neurogenic changes were detected. Findings of hematological and cerebrospinal fluid analyses, and magnetic resonance images of the brain and spinal cord were unremarkable. One cycle of intravenous immunoglobulin therapy did not improve his symptoms. We diagnosed him as having FOSMN with the sole initial symptom of taste disorder. Nine years after the onset of taste disorder, he developed impaired sensation of touch in the right upper limb and required tube feeding and ventilator support.
Taste disorder can be the initial manifestation of FOSMN and might involve the solitary nucleus.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A 61-year-old Japanese man presented with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. NR1 antibodies were detected in his cerebrospinal fluid. Chest computed tomography revealed lung ...tumor. The patient was diagnosed with paraneoplastic anti-NMDAR encephalitis associated with lung cancer and treated with two cycles of intravenous high-dose methylprednisolone and one cycle of intravenous immunoglobulin. However, he died one year later without improvement. An autopsy confirmed small-cell lung cancer (SCLC). Immunohistochemistry revealed the expression of NR1 subunits in the tumor cells, suggesting that SCLC may trigger NR1 autoimmunity though the expression of NR1 subunits as onconeural antigens, expanding the phenotypic spectrum of paraneoplastic neurological syndrome associated with SCLC.
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slow-progressing multisystem neurodegenerative disorder. Biallelic AAGGG repeat expansion in RFC1 has been ...identified as causative of this disease, and repeat conformation heterogeneity (ACAGG repeat) was also recently implied. To molecularly characterize this disease in Japanese patients with adult-onset ataxia, we accumulated and screened 212 candidate families by an integrated approach consisting of flanking PCR, repeat-primed PCR, Southern blotting and long-read sequencing using Sequel II, GridION or PromethION. We identified 16 patients from 11 families, of whom seven had ACAGG expansions (ACAGG)exp/(ACAGG)exp (ACAGG homozygotes), two had ACAGG and AAGGG expansions (ACAGG)exp/(AAGGG)exp (ACAGG/AAGGG compound heterozygotes) and seven had AAGGG expansions (AAGGG)exp/(AAGGG)exp (AAGGG homozygotes). The overall detection rate was 5.2% (11/212 families including one family having two expansion genotypes). Long-read sequencers revealed the entire sequence of both AAGGG and ACAGG repeat expansions at the nucleotide level of resolution. Clinical assessment and neuropathology results suggested that patients with ACAGG expansions have similar clinical features to previously reported patients with homozygous AAGGG expansions, although motor neuron involvement was more notable in patients with ACAGG expansions (even if one allele was involved). Furthermore, a later age of onset and slower clinical progression were implied in patients with ACAGG/AAGGG compound heterozygous expansions compared with either ACAGG or AAGGG homozygotes in our very limited cohort. Our study clearly shows the occurrence of repeat conformation heterogeneity, with possible different impacts on the affected nervous systems. The difference in disease onset and progression between compound heterozygotes and homozygotes might also be suspected but with very limited certainty due to the small sample number of cases in our study. Studies of additional patients are needed to confirm this.
Background : Hereditary transthyretin (ATTRv) amyloidosis, a disorder accompanied by axonal polyneuropathy, is often misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). ...Prolongation of distally evoked compound muscle action potential duration (DCMAPD), an electrophysiological parameter of heterogeneous conduction delay at the distal part of the motor nerve suggesting demyelinating neuropathies, is included in an index of diagnostic criteria for CIDP. However, DCMAPDs are strongly influenced by low-frequency filtering (LFF) settings, which differ across hospitals worldwide. Aim : To analyze DCMAPD in patients with ATTRv amyloidosis with polyneuropathy (ATTRv-PN). Methods : DCMAPs of the median, ulnar, tibial, and peroneal nerves were recorded under LFF settings of 2, 10, and 20 Hz in 50 patients with ATTRv-PN. The changes of DCMAPD accompanied with the changes of LFF settings were analyzed. The appropriateness of the cut-off values of the DCMAPD in the latest criteria for CIDP, which defined under various LFF settings, was also validated in ATTRv-PN patients. Results : The DCMAPD was shorter with increasing LFF settings. Less than 10％ of patients with ATTRv-PN demonstrated prolonged DCMAPD of the ulnar, tibial, and peroneal nerves. In contrast, ten patients demonstrated prolonged DCMAPD in the median nerve under LFF settings of 2, 10, and/or 20 Hz. Nine of the ten cases were complicated with carpal tunnel syndrome (CTS). Conclusion : Prolongation of DCMAPDs in the ulnar, tibial, and peroneal nerves is rare in ATTRv-PN patients. DCMAPD analysis of the median nerve in patients with ATTRv-PN requires caution, because they frequently develop CTS and those with CTS may demonstrate prolonged DCMAPD.
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