Ischemic Stroke During Daprodustat Therapy for Renal Anemia: A Report of Three Cases.

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are increasingly used to treat renal anemia. Ischemic stroke is a rare severe adverse event of HIF-PH inhibitor therapy, and its clinical characteristics have not been described to date. We report three cases of ischemic stroke during treatment with daprodustat, a HIF-PH inhibitor, for anemia associated with non-dialysis-dependent chronic kidney disease (CKD). In two patients, the hemoglobin level exceeded the target hemoglobin level of 13 g/dL for renal anemia. Two patients developed ischemic stroke within two months after the daprodustat administration. None of the three patients experienced a recurrence of ischemic stroke after daprodustat discontinuation. Daprodustat therapy is a risk factor for ischemic stroke, particularly during excessive elevation of hemoglobin levels or the early phases of treatment. Daprodustat should be discontinued to mitigate the risk of ischemic stroke recurrence.

Successful Childbirth During Satralizumab Treatment in Neuromyelitis Optica Spectrum Disorder.

A 40-year-old woman with neuromyelitis optica spectrum disorder (NMOSD) and anti-aquaporin 4 antibodies suffered three NMOSD episodes between 35 and 37 years of age. Despite treatment with prednisolone and azathioprine, her condition repeatedly relapsed. We introduced satralizumab, targeting interleukin-6 receptors, which stabilized her condition. At the age of 38, she became pregnant and delivered a healthy baby at 38 weeks. Post delivery, both mother and child stayed healthy with no NMOSD relapses. This case illustrates the efficacy and safety of satralizumab in managing NMOSD, especially for women in their reproductive years who are planning pregnancy.

Guillain-Barré syndrome after percutaneous coronary intervention and transcatheter aortic valve implantation.

Guillain-Barré syndrome (GBS) usually develops after preceding infection, but cardiac surgery can also occasionally cause GBS. Currently, cardiac catheterizations have already become common therapeutic options for heart diseases, but there have been no reports of GBS occurrence after that. Herein, we present a rare case in which GBS occurred following catheterization. An 85-year-old-man with sudden onset chest pain was rushed to our hospital and diagnosed with ST-elevated myocardial infarction. He underwent emergent percutaneous coronary intervention (PCI) to left anterior descending artery, but he still had exertional chest pain. Echocardiography revealed severe aortic stenosis (AS) and our heart team considered AS was the cause of symptom and decided to perform and transcatheter aortic valve implantation (TAVI), 11 days after the PCI. However, 5 days after the TAVI procedure, he presented with symmetrical muscular weakness of extremities. Cranial magnetic resonance imaging showed no significant lesion. Based on several signs including albuminocytologic dissociation in cerebrospinal fluid examination, demyelinating polyneuropathy in nerve conduction study, positive anti-ganglioside antibody, and the lack of preceding infection, he was diagnosed with GBS triggered by cardiac catheterizations. We administered high-dose intravenous immunoglobulin therapy and his motor strength gradually improved, finally discharged with full motor strength after 7 months rehabilitation. Learning objective: •Cardiac surgery has been already reported as a non-infectious risk factor of Guillain-Barré syndrome (GBS) in previous literatures, and cardiac catheterization such as percutaneous coronary intervention and transcatheter aortic valve implantation, which were relatively less invasive procedure, may be a potential risk factor for GBS occurrence as well.•If a patient complains of progressive, symmetrical neurological symptoms after cardiac catheterization, GBS should be considered as the possible cause, and nerve conduction study and cerebrospinal fluid examination may be helpful for the diagnosis.

Anti-nuclear matrix protein 2 antibody-positive dermatomyositis with gastrointestinal ulcers: A case report.

Gastrointestinal manifestations are a very rare complication of dermatomyositis (DM) and are much less frequent in adult cases than in juvenile cases. Only a few previous papers have reported adult patients who had DM with anti-nuclear matrix protein 2 (anti-NXP2) antibodies and who developed gastrointestinal ulcers. Herein, we report a similar case of a 50-year-old man who had DM with anti-NXP2 antibodies followed by relapsing multiple gastrointestinal ulcers. Even after the administration of prednisolone, his muscle weakness and myalgia deteriorated and gastrointestinal ulcers relapsed. In contrast, intravenous immunoglobulin and azathioprine improved his muscle weakness and gastrointestinal ulcers. Based on the parallel disease activity of the muscular and gastrointestinal symptoms, we considered that his gastrointestinal ulcers were a complication of DM with anti-NXP2 antibodies. We also propose that early intensive immunosuppressive therapy would be required for the muscular and gastrointestinal symptoms in DM with anti-NXP2 antibodies.

Methotrexate-induced Subacute Encephalopathy That Showed No Abnormalities on Magnetic Resonance Imaging Soon after Symptom Appearance.

A 21-year-old woman was diagnosed with acute lymphoblastic leukemia. After the administration of intrathecal methotrexate (MTX), the patient experienced dysarthria and paralysis for one hour. Magnetic resonance imaging (MRI) performed one hour from the onset and just before symptoms disappeared revealed no abnormalities. The next day, the symptoms appeared again, and diffusion-weighed MRI revealed a high-intensity area in the left frontal lobe. The patient was diagnosed with MTX-induced encephalopathy. This case suggested that MRI performed as soon as symptoms appear might show normal findings in MTX-induced encephalopathy.

Orbital Intravascular Natural Killer/T-cell Lymphoma: An Unusual Cause of Ocular Symptoms.

Orbital intravascular lymphoma is rare and typically of B-cell lineage. In this study, we report a patient who developed orbital lesions of intravascular natural killer/T-cell lymphoma (IVNKL), an extremely rare lymphoma. An 88-year-old man presented with rapidly progressive right vision loss and double vision. A neurological examination revealed that he had decreased visual acuity and severe oculomotor impairment in the right eye. Magnetic resonance imaging showed right-dominant, nonmass lesions in both orbits. No lesions were found in the lymph nodes, skin, or brain. The patient received immunosuppressive and antifungal therapy, but his clinical condition rapidly deteriorated, and he died of multiple organ failure. Autopsy revealed natural killer/T-cell lymphoma proliferation within the lumina of small blood vessels in multiple organs, including the ocular adnexa of the right orbit. These findings show that he was ultimately diagnosed with IVNKL. IVNKL could initially cause ocular symptoms due to the involvement of the ocular adnexa. Ocular involvements have not been described previously. Even if patients initially present with only ocular symptoms, IVNKL should be considered.

Intravenous Immunoglobulin in the Treatment of Adalimumab-associated Optic Neuritis.

Optic neuritis (ON) is a rare complication of tumor necrosis factor (TNF)-α inhibitors. The autoantibody serostatus, treatment, and outcome of TNF-α inhibitor-associated ON remain unclear. We herein report a 50-year-old woman with ON following adalimumab therapy. The patient presented with decreasing visual acuity of the right eye, quickly diminishing to light perception. Anti-aquaporin-4 (anti-AQP4) and anti-myelin oligodendrocyte glycoprotein antibodies were negative. Adalimumab was discontinued, and intravenous methylprednisolone and intravenous immunoglobulin (IVIg) were administered. However, her visual acuity improved only up to counting fingers. IVIg may be ineffective depending on the pretreatment severity.

Prominent Prolongation of Cortical Silent Period Induced by Transcranial Magnetic Stimulation in Creutzfeldt-Jakob Disease.

The cortical silent period (CSP) induced by transcranial magnetic stimulation (TMS) has been reported to be prolonged in 2 Creutzfeldt-Jakob disease (CJD) patients who presented with periodic myoclonus. Herein, we will show a prominent prolongation of TMS-induced CSP in a patient with CJD who did not have periodic myoclonus. The patient was a 66-year-old woman who developed rapidly progressive dementia. No myoclonic jerks were observed. Brain magnetic resonance imaging showed high-intensity lesions in the cerebral cortex, basal ganglia, and thalamus on diffusion-weighted images. Electroencephalography (EEG) showed diffuse and continuous slow waves, but no periodic synchronous discharges (PSDs). A TMS study revealed that the duration of CSP was prominently prolonged: the duration of CSP (370 ms) equaled that of the mean + 6.5 SD of the normal value. One month after admission, the patient exhibited akinetic mutism and developed periodic myoclonus in her limbs. The clinical course was compatible with CJD. To date, CSP has been measured in only 2 CJD patients. The common findings in both cases were marked prolongation of CSP, periodic myoclonus, and PSD on EEG. In short, we demonstrated that TMS-induced CSP was prominently prolonged even at the early stage of CJD without periodic myoclonus or PSD. In other disorders, the CSP has not been reported to be comparably prolonged to that of CJD patients. Therefore, we conclude that TMS-induced CSP could be prominently prolonged even in the early stage of CJD. The marked prolongation of the CSP might be an early biomarker of CJD.

Clinical efficacy of haematopoietic stem cell transplantation for adult adrenoleukodystrophy.

Accumulated experience supports the efficacy of allogenic haematopoietic stem cell transplantation in arresting the progression of childhood-onset cerebral form of adrenoleukodystrophy in early stages. For adulthood-onset cerebral form of adrenoleukodystrophy, however, there have been only a few reports on haematopoietic stem cell transplantation and the clinical efficacy and safety of that for adulthood-onset cerebral form of adrenoleukodystrophy remain to be established. To evaluate the clinical efficacy and safety of haematopoietic stem cell transplantation, we conducted haematopoietic stem cell transplantation on 12 patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy in a single-institution-based prospective study. Through careful prospective follow-up of 45 male adrenoleukodystrophy patients, we aimed to enrol patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy at early stages. Indications for haematopoietic stem cell transplantation included cerebral form of adrenoleukodystrophy or cerebello-brainstem form of adrenoleukodystrophy with Loes scores up to 13, the presence of progressively enlarging white matter lesions and/or lesions with gadolinium enhancement on brain MRI. Clinical outcomes of haematopoietic stem cell transplantation were evaluated by the survival rate as well as by serial evaluation of clinical rating scale scores and neurological and MRI findings. Clinical courses of eight patients who did not undergo haematopoietic stem cell transplantation were also evaluated for comparison of the survival rate. All the patients who underwent haematopoietic stem cell transplantation survived to date with a median follow-up period of 28.6 months (4.2-125.3 months) without fatality. Neurological findings attributable to cerebral/cerebellar/brainstem lesions became stable or partially improved in all the patients. Gadolinium-enhanced brain lesions disappeared or became obscure within 3.5 months and the white matter lesions of MRI became stable or small. The median Loes scores before haematopoietic stem cell transplantation and at the last follow-up visit were 6.0 and 5.25, respectively. Of the eight patients who did not undergo haematopoietic stem cell transplantation, six patients died 69.1 months (median period; range 16.0-104.1 months) after the onset of the cerebral/cerebellar/brainstem lesions, confirming that the survival probability was significantly higher in patients with haematopoietic stem cell transplantation compared with that in patients without haematopoietic stem cell transplantation (P = 0.0089). The present study showed that haematopoietic stem cell transplantation was conducted safely and arrested the inflammatory demyelination in all the patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy when haematopoietic stem cell transplantation was conducted in the early stages. Further studies are warranted to optimize the procedures of haematopoietic stem cell transplantation for adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy.

[A 64-year-old male with recurrence of herpes simplex encephalitis after suffering from severe pneumonia and sepsis].

The case is a 64-year-old male who had a past history of herpes simplex virus encephalitis (HSE) two years prior to his admission. He was admitted to our hospital due to severe pneumonia and sepsis. Several days later, he developed HSE again. It has been known that immunosuppressive state called immune paralysis occurs in the patient with sepsis due to the amplification of anti-inflammatory responses after the initial hyper-inflammatory phase, which increases the susceptibility to various latent viruses including herpes simplex virus. In the present case, we consider that the severe infection may trigger the recurrence of HSE through the viral reactivation due to immune paralysis. When we see a patient suffering from severe infection who had a past history of HSE, we should keep in mind that such a patient may have a risk of the recurrence of HSE.

[Anti-Hu antibody positive sensory neuronopathy causing painful legs and moving toes (PLMT) in a 75-year-old female with small cell lung cancer (SCLC)].

The case is a 75-year-old female. She had dysesthesia in the distal extremities and truncal ataxia, and they had progressed in two months. Neurological examination revealed the findings of segmental dysesthesia in the distal extremities, impaired deep sensations in the trunk and four limbs, and painful legs and moving toes (PLMT). After workup, she was diagnosed with small cell lung cancer and her blood sample was positive for anti-Hu antibody. We concluded that her neurological symptoms were attributable to sensory neuronopathy associated with paraneoplastic syndrome. No cases with PLMT caused by paraneoplastic syndrome have been reported so far. She had chemotherapy to lung cancer and Duloxetine without improvement of PLMT. On the other hand, intravenous immunoglobulin treatment improved lightening pain in the toes without improvement of moving toes.