Chiara Milano, Ezgi Saylam, Claudia Papi, Laura Marmolejo, Alexandra Sankovic, Raphael Reinecke, Jeroen Kerstens, Chiara Pizzanelli, Mistieri Mateus Simabukuro, Marie Benaiteau, Bastien Joubert, Matteo Gastaldi, Almeida Lívia Dutra, Frank Leypoldt, Mareike Jansen, Izumi Kawachi, Hisanao Akiyama, Nikolas Boy, Silvia Bozzetti, Broegger Peter Christensen, Pietro Businaro, Alessandro Dinoto, Tal Friedman-Korn, Urara Fujiwara, Tatsuya Fukumoto, Kenshiro Fuse, Ishmael Sam Hooshmand, Lauren Hurst, Raffaele Iorio, Isabelle Korn-Lubetzki, Lucchi André Filipe Rodrigues, Sara Mariotto, Johannes Michael, Yuko Morimoto, Frederik Rinze Neuteboom, L. Amanda Piquet, O. Andrea Rossetti, Sabine Rumpler-Kreiner, D. Jonathan Santoro, Florian Schwendinger, Brenda Shen, Steffen Syrbe, Johannes Troger, Ingrid Wagner, G. Christian Bien, Eugenia Martinez-Hernandez, Thais Armangue, Romana Höftberger, Takahiro Iizuka, J. Maarten Titulaer, Jerome Honnorat, Francesc Graus, O. Josep Dalmau, Setty Magaña and Marianna Spatola : Clinical Characterization and Long-Term Outcome in Children and Adults With Anti-AMPA Receptor Encephalitis, Neurology® Neuroimmunology & Neuroinflammation, 12, 5, e200453, 2025.
(Summary)
Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (anti-AMPAR) encephalitis manifests as limbic encephalitis in adults and is often associated with cancer. Although some reports suggest that it may occur in children, the clinical features in this population, as well as the prognostic factors and long-term outcomes in children and adults, are unknown. We performed a retrospective, international collaborative study of patients with anti-AMPAR encephalitis. Clinical information was reviewed, together with data from published pediatric patients. Clinical features of children and adults were compared with nonparametric tests. Survival rates (Kaplan-Meier curves) were compared using log-rank tests. Prognostic factors of poor outcome (modified Rankin Scale score >2) were identified using logistic regression models. A total of 115 patients were included, of whom 84 (71 adults, 13 children) had only AMPAR antibodies and 31 (27 adults, 4 children) had additional concurrent neural antibodies. Among patients with AMPAR antibodies alone, tumors were identified in 37 adults (56%) and none of the children (p < 0.0001). Children were more likely than adults to have behavioral/psychiatric symptoms (5/13, 39%, vs 8/71, 11%, p = 0.026) at onset, cerebellar dysfunction (6/13, 46%, vs 7/68, 10% p = 0.005) or movement disorders (5/13, 39%, vs 8/67, 12%, p = 0.032) during the disease course, and extratemporal brain MRI lesions (4/9, 44%, vs 5/44, 11%, p = 0.035). Among 34 patients with prolonged follow-up (>24 months), long-term neurocognitive sequelae were reported in 23 (68%), all adults. Failure to respond to first-line immunotherapy at multivariable analysis predicted a poor outcome (OR 8.0, 95% CI 1.1-59.2, p = 0.043). Among the 31 patients with concurrent neural autoantibodies, 22 (79%) had a tumor; those with high-risk antibodies had lower survival rates (p = 0.008). Children and adults with anti-AMPAR encephalitis show distinct clinical-radiologic features. At long-term follow-up, 68% of patients, all adults, have neurologic sequelae, with failure to respond to first-line immunotherapy being associated with worse outcomes.
Kenta Hanada, Yusuke Osaki, Koji Fujita, Tatsuya Fukumoto, Koji Fukushima, Hideki Kito and Yuishin Izumi : Segmental Zoster Paresis Accompanied by Horner's Syndrome., Internal Medicine, 62, 18, 2743-2746, 2023.
(Summary)
We herein report a 90-year-old immunocompromised woman who developed right upper limb weakness and right ptosis with a miotic pupil 1 week after oral therapy for zoster on the right T2 dermatome. The right pupil was dilated with instillation of 1% apraclonidine, indicating Horner's syndrome. The patient was treated with intravenous acyclovir and methylprednisolone. Focal weakness related to zoster, generally known as segmental zoster paresis, improved over five months, but Horner's syndrome remained. We suggest that aggressive intravenous treatment should be considered for rare cases of zoster that occur with a combination of these two neurological conditions.
(Keyword)
Aged, 80 and over / Female / Humans / Acyclovir / Blepharoptosis / Herpes Zoster / Horner Syndrome / Paresis
Progressive multifocal leukoencephalopathy (PML) is a fatal disease caused by John Cunningham virus (JCV) infection; however, a growing number of PML patients now survive longer and achieve remission, largely due to the advent of combination antiretroviral therapy. Several reports have suggested that the pathology in such patients presents only chronic demyelination without characteristic cellular changes, being referred to as "burnt-out" PML. On the other hand, our knowledge of "burnt-out" PML is still substantially limited, especially in patients with non-human immunodeficiency virus infection. Here, we report a case of PML associated with idiopathic CD4+ lymphocytopenia (ICL) who presented with spontaneous remission and survived for 11 years after onset. Notably, postmortem examination revealed surprisingly broad "burnt-out" lesions lacking the classic histopathological findings. However, pathogenic JCV-specific DNA sequences was still present in the autopsied brain tissue. This case suggests that complete remission can be achieved with a persistent presence of JCV-specific pathogenic sequences, even after a catastrophic infection. Considering that there have been a few reported cases of PML with ICL with long survival, the long-term survival of our case may share a favorable immunological response that is unique to a subgroup of ICL.
Tatsuya Fukumoto, Ryosuke Miyamoto, Koji Fujita, Masafumi Harada and Yuishin Izumi : Gait apraxia as a presenting sign of Gerstmann-Sträussler-Scheinker disease, Neurology and Clinical Neuroscience, 9, 4, 339-341, 2021.
Kohei Muto, Ryosuke Miyamoto, Yuka Terasawa, Yoshimitsu Shimatani, Keijiro Hara, Takumi Kakimoto, Tatsuya Fukumoto, Yusuke Osaki, Koji Fujita, Masafumi Harada, Hisanori Uehara, Yasushi Takagi and Yuishin Izumi : A novel COL4A1 variant associated with recurrent epistaxis and glioblastoma., Human Genome Variation, 8, 1, 18, 2021.
(Summary)
COL4A1-related disorders are characterized by a higher incidence of cerebral hemorrhage than other hereditary cerebral small vessel diseases. Accumulating data have shown broad phenotypic variations, and extracerebral hemorrhages have been linked to these disorders. Moreover, the coexistence of neural tumors has been described. Here, we report a Japanese family with a novel COL4A1 variant, including a patient with recurrent epistaxis and glioblastoma.
Tatsuya Fukumoto, Ryosuke Miyamoto, Koji Fujita, N Murakami, Naoko Matsui and Yuishin Izumi : Reversible mixed perfusion on 123 I-IMP SPECT in anti-AMPA receptor encephalitis: A case report, Journal of the Neurological Sciences, 421, 117306, 2021.
Thomas Cezar Suratos, Naoko Takamatsu, Hiroki Yamazaki, Yusuke Osaki, Tatsuya Fukumoto, Hiroyuki Nodera and Yuishin Izumi : Utility of phrenic nerve ultrasound in amyotrophic lateral sclerosis, Acta Neurologica Belgica, 121, 1, 225-230, 2020.
(Summary)
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons causing progressive weakness. It eventually involves the diaphragm which leads to respiratory paralysis and subsequently death. Phrenic nerve (PN) conduction studies and diaphragm ultrasound has been studied and correlated with pulmonary function tests in ALS patients. However, PN ultrasonography has not been employed in ALS. This study aims to sonographically evaluate the morphologic appearance of the PN of ALS patients. Thirty-eight ALS patients and 28 normal controls referred to the neurophysiology laboratory of two institutions were retrospectively included in the study. Baseline demographic and clinical variables such as disease duration, ALS Functional Rating Scale-Revised score, and ALS region of onset were collected. Ultrasound was used to evaluate the PN cross-sectional area (CSA) of ALS and control subjects. The mean PN CSA of ALS patients were 1.08 ± 0.39 mm on the right and 1.02 ± 0.34 mm on the left. The PN CSA of ALS patients were significantly decreased compared to controls (p value < 0.00001). The PN CSA of ALS patients was not correlated to any of the demographic and clinical parameters tested. This study demonstrates that ALS patients have a smaller PN size compared to controls using ultrasonography.
Yuki Yamamoto, Nobuaki Yamamoto, Koji Fujita, Tatsuya Fukumoto, Nagahisa Murakami, Hideo Mure, Yasuhisa Kanematsu, Yasushi Takagi and Yuishin Izumi : Cerebral venous thrombosis: An unexpected complication with cerebrospinal fluid leaks after a fall in a patient with spinocerebellar ataxia type 6, Internal Medicine, 59, 14, 1749-1753, 2020.
(Summary)
A 65-year-old woman with spinocerebellar ataxia presented with generalized seizures due to subcortical hemorrhaging. Magnetic resonance imaging (MRI) revealed obstruction of the superior sagittal sinus. Despite treatment, she became comatose. MRI newly revealed subdural fluid collection and descent of the brainstem. Her history indicated a recent fall, prompting additional studies, which revealed lumbar fracture and cerebrospinal fluid (CSF) leaks. We performed an epidural blood patch, and her consciousness was fully restored in one month. This is the first report of cerebral venous thrombosis with CSF leaks in the lumbar region due to a fall injury.
Tatsuya Fukumoto, Fumiaki Katada, Susumu Sato, Hidehiro Shibayama, Shigeo Murayama and Toshio Fukutake : A case of acute leukoencephalopathy induced by a combination of 5-fluorouracil and metronidazole, Clinical Neurology, 58, 2, 118-123, 2018.
(Summary)
We describe a 66-year-old woman who received folinic acid, leucovorin, fluorouracil and oxaliplatin for advanced rectal carcinoma. These drugs were initiated on day 1, and a pelvic abscess was identified on day 7. Piperacillin-tazobactam was initially administered, but was changed to ceftriaxone and metronidazole on day 14 on the basis of antimicrobial susceptibility testing. On the following day, the patient reported blindness, and MRI of the brain showed signal abnormalities in the splenium of the corpus callosum on DWI, suggestive of metronidazole encephalopathy. Although the total body exposure was 2 g, metronidazole was discontinued. The patient developed coma a few days later, and MRI of the brain on day 26 showed high signal intensity extensively involving the white matter in the cerebrum as well as the brainstem and cerebellum. She died 37 days after the initial administration of the chemotherapy. Pathological studies demonstrated decreased staining intensity in the myelin sheath and multiple vacuolar alterations, consistent with toxicity induced by metronidazole and fluorouracil. Care should be taken when administering a combination of these drugs, even if the total body exposure to each drug is limited.