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Key Points Cancer treatments are associated with substantial neurotoxicity, which is a diagnosis of exclusion Treatments affect both the central and peripheral nervous systems Biological and immunological therapies have different mechanisms of toxicity Recognition of neurotoxicity is important to prevent further neurological injury and to distinguish this toxicity from nervous system involvement of cancer Neurotoxicity caused by treatment is widely recognized in patients with cancer. This Review addresses the main neurotoxicities of cancer treatment with a focus on the newer therapeutics. Recognition of these patterns of toxicity is important because drug discontinuation or dose adjustment might prevent further neurological injury. Familiarity with the neurological syndromes associated with cancer treatments enables clinicians to use the appropriate treatment for the underlying malignancy while minimizing the risk of neurological damage, which might preserve patient quality of life. Neurotoxicity caused by traditional chemotherapy and radiotherapy is widely recognized in patients with cancer. The adverse effects of newer therapeutics, such as biological and immunotherapeutic agents, are less well established, and are associated with considerable neurotoxicity in the central and peripheral nervous systems. This Review addresses the main neurotoxicities of cancer treatment with a focus on the newer therapeutics. Recognition of these patterns of toxicity is important because drug discontinuation or dose adjustment might prevent further neurological injury. Knowledge of these toxicities also helps to differentiate treatment-related symptoms from progression of cancer or its involvement of the nervous system. Familiarity with the neurological syndromes associated with cancer treatments enables clinicians to use the appropriate treatment for the underlying malignancy while minimizing the risk of neurological damage, which might preserve patients' quality of life.

In the late nineteenth through the mid-twentieth centuries, the movementknown as Nichirenism sought to realize an ideal Japan based on the LotusSutra and the teachings of the medieval Buddhist figure Nichiren (1222–1282). In pursuing this goal, leaders within the movement sought to mobilizethe efforts of women. They formulated a female gender ideology that drewboth on Nichiren’s egalitarian reading of the dragon girl episode in the LotusSutra and on the contemporary discourse of “good wives, wise mothers” asexemplifying women’s proper social roles. This article has two major aims. One is to provide a preliminary overviewof women in Nichiren Buddhist history, considering women in Nichiren’searly community and introducing examples of women practitioners from latermedieval and early modern times. The second aim is to analyze how modernNichirenist advocates crafted and legitimated female gender norms, focusingon writings by the lay leader Tanaka Chigaku (1861–1939) and the elite nunMurakumo Nichijō (1896–1962). The ongoing influence of Nichirenist genderideology is also addressed. Finally, the article touches on the possibility ofalternative readings of Nichiren’s teaching with regard to women.

Between 1945 and 1951, the Nichiren Buddhist lay organization Soka Gakkai, which had disbanded during the Pacific War, regrouped and burgeoned in a massive proselytizing campaign led by its second president, Toda Jōsei. This effort intertwined three aims: to spread faith in the Lotus Sūtra as the basis for Japan’s postwar reconstruction; to establish an ideal government based on Buddhist principles; and to build a national ordination platform as Japan’s sacred center. Driving it was Toda’s conviction, inherited from his teacher, Makiguchi Tsunesaburō, that Japan was suffering a profound malaise and could only be saved by embracing Nichiren’s teaching. That message formed a powerful link between wartime and postwar Soka Gakkai organizations. It drew Makiguchi into conflict with wartime ideology, leading to his arrest; amid postwar hardships, it found eager reception and shaped what would become Japan’s largest religious movement.

Background High-dose methotrexate (HD-MTX) has broad use in the treatment of central nervous system (CNS) malignancies but confers significant toxicity without inpatient hydration and monitoring. Glucarpidase is a bacterial recombinant enzyme dosed at 50 units (u)/kg, resulting in rapid systemic MTX clearance. The aim of this study was to demonstrate feasibility of low-dose glucarpidase to facilitate MTX clearance in patients with CNS lymphoma (CNSL). Methods Eight CNSL patients received HD-MTX 3 or 6 g/m 2 and glucarpidase 2000 or 1000u 24 h later. Treatments repeated every 2 weeks up to 8 cycles. Results Fifty-five treatments were administered. Glucarpidase 2000u yielded > 95% reduction in plasma MTX within 15 min following 33/34 doses (97.1%) and glucarpidase 1000u yielded > 95% reduction following 15/20 doses (75%). Anti-glucarpidase antibodies developed in 4 patients and were associated with MTX rebound. In CSF, glucarpidase was not detected and MTX levels remained cytotoxic after 1 (3299.5 nmol/L, n  = 8) and 6 h (1254.7 nmol/L, n  = 7). Treatment was safe and well-tolerated. Radiographic responses in 6 of 8 patients (75%) were as expected following MTX-based therapy. Conclusions This study demonstrates feasibility of planned-use low-dose glucarpidase for MTX clearance and supports the hypothesis that glucarpidase does not impact MTX efficacy in the CNS. Clinical trial registration NCT03684980 (Registration date 26/09/2018).

Background Post-traumatic headaches (PTH) are a common sequelae of traumatic brain injury (TBI) and greatly impact patient function and quality of life. Post-traumatic greater occipital neuralgia (GON) is a type of post-traumatic headache. Conventional treatment includes steroid/anesthetic injections which typically alleviate pain but have a short duration of effect. Platelet-rich plasma (PRP) is an emerging biological treatment for numerous degenerative disorders, including peripheral nerve disorders. The primary aim of this pilot study is to evaluate whether a randomized control trial of PRP for the treatment of GON in patients with post-traumatic headaches is feasible in regard to recruitment, adherence, retention, and adherence and adverse events. Exploratory aims include improvement in pain, function, and quality of life in patients with post-traumatic GON receiving PRP compared to steroid/anesthetic and normal saline injections. Methods Thirty adults (over 18 years of age) with post-traumatic GON will be randomized into one of three groups: (1) autologous PRP injection, (2) steroid/anesthetic injection (standard care), or (3) placebo injection with normal saline. Injections will be performed to the greater occipital nerve under ultrasound guidance by a trained physician. Daily headache intensity and frequency data will be collected pre-injection and for the duration of the study period. Feasibility will be defined as greater than 30% recruitment, 70% completion of intervention, 70% retention, and less than 2 minor adverse events. Exploratory outcomes will be explored using the Headache Impact Test-6 (HIT-6, a valid and reliable 6-item questionnaire for assessment of the impact of headaches across different diagnostic groups of headaches) and the quality of life in following brain injury questionnaire (QOILIBRI). Discussion This pilot study will be the first to evaluate the feasibility of PRP as a potential treatment of GON in patients with post-traumatic headache. Trial registration ClinicalTrials.gov - NCT04051203 (registered August 9, 2019).

The yield of echocardiography in cancer patients with acute ischemic stroke is unknown. We identified adult patients with active systemic cancer diagnosed with acute ischemic stroke at a tertiary-care cancer center from 2005 through 2009 who underwent transthoracic (TTE) or transesophageal echocardiography (TEE). Two neurologists independently reviewed all clinical data, including TTE and TEE reports, and adjudicated whether echocardiographic studies revealed a definite or possible source of stroke according to pre-defined criteria. Patients were classified as having suspected cardioembolic strokes if imaging showed embolic-appearing infarcts in more than one vascular territory. Among 220 patients with cancer and ischemic stroke who underwent echocardiography, 216 (98 %) had TTE and 37 (17 %) had TEE. TTE revealed a definite source in 15 (7 %, 95 % CI 4–10 %) patients and a possible source in 42 (19 %, 95 % CI 14–25 %), while TEE revealed a definite source in 10 (27 %, 95 % CI 12–42 %) patients and a possible source in 14 (38 %, 95 % CI 21–54 %). In 92 patients with suspected cardioembolic strokes who underwent TTE, 6 (7 %, 95 % CI 1–12 %) had a definite source, including 4 with marantic endocarditis, and 20 (22 %, 95 % CI 13–30 %) had a possible source. Twenty-one of these patients also underwent TEE, which demonstrated a definite or possible source in 16 (76 %, 95 % CI 56–96 %) patients, including marantic endocarditis in 4 (19 %). The yield of TTE for detecting marantic endocarditis and other cardiac sources of stroke in cancer patients is low, but TEE may provide a higher yield in targeted patients.

In the late nineteenth through the mid-twentieth centuries, the movementknown as Nichirenism sought to realize an ideal Japan based on the LotusSutra and the teachings of the medieval Buddhist figure Nichiren (1222–1282). In pursuing this goal, leaders within the movement sought to mobilizethe efforts of women. They formulated a female gender ideology that drewboth on Nichiren’s egalitarian reading of the dragon girl episode in the LotusSutra and on the contemporary discourse of “good wives, wise mothers” asexemplifying women’s proper social roles. This article has two major aims. One is to provide a preliminary overviewof women in Nichiren Buddhist history, considering women in Nichiren’searly community and introducing examples of women practitioners from latermedieval and early modern times. The second aim is to analyze how modernNichirenist advocates crafted and legitimated female gender norms, focusingon writings by the lay leader Tanaka Chigaku (1861–1939) and the elite nunMurakumo Nichijō (1896–1962). The ongoing influence of Nichirenist genderideology is also addressed. Finally, the article touches on the possibility ofalternative readings of Nichiren’s teaching with regard to women.

In 1279, twenty peasants who were lay followers of the Buddhist teacher Nichiren were summarily arrested at Atsuhara in the Fuji district of Suruga province and were sent for trial to Kamakura, where three of them were beheaded. This incident is known in the history of Nichiren Buddhism as the Atsuhara persecution. The first part of this article outlines the circumstances of the persecution and the political and religious tensions that fueled it and considers how Nichiren was able to persuade his followers to remain steadfast in the face of a grave threat. The second part examines links between Nichiren's interpretation of the persecution and larger themes in his teaching of exclusive devotion to the Lotus Sutra, especially that offering one's life for the sutra's sake guarantees one's attainment of buddhahood. Lastly, the article touches on how later accounts of the Atsuhara persecution shaped a normative ideal within the Nichiren tradition of how Lotus devotees should meet opposition from those in power.