Superiority of BM over PBSC for recipients with pre-transplant lung dysfunction in HLA-matched allogeneic HCT.

BACKGROUND AIMS: Pre-transplant lung dysfunction is known to be a risk factor for non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). It is unclear which cell source gives better outcomes for patients with pulmonary dysfunction. METHODS: We analyzed 3289 adult patients with standard-risk disease who had received HLA-matched allo-HCT, and compared outcomes between those who received peripheral blood stem cell (PBSC) vs. bone marrow (BM) in two cohorts based on the presence of a lung score by the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI): the Lung-scored (LS) and non-LS cohorts. RESULTS: In the LS cohort, the 2-year overall survival (OS) in the BM group tended to be higher than that in the PBSC group (72.4% vs. 61.4%; P = 0.044). In the non-LS cohort, there was no significant difference between the two groups (71.7% vs. 73.2%; P = 0.13). Multivariate analyses confirmed that PBSC was significantly associated with inferior OS in the LS cohort (hazard ratio [HR], 1.66; 95% CI, 1.09-2.54; P = 0.019). On the other hand, the cell source did not affect OS in the non-LS cohort (HR, 0.92; 95% CI, 0.76-1.12; P = 0.41). We found that PBSC was associated with an increased risk of NRM in the LS cohort (HR, 2.17; 95% CI, 1.16-4.05; P = 0.016), while the cell source did not significantly affect NRM in the non-LS cohort. PBSC was not identified as a risk factor for relapse in either cohort. CONCLUSIONS: Our results suggest that BM might be beneficial for recipients with lung dysfunction in HLA-matched allo-HCT.

Impact of stem cell selection between bone marrow and peripheral blood stem cells for unrelated hematopoietic stem cell transplantation for hematologic malignancies: on behalf of the Donor/Source Working Group of the Japanese Society for Transplantation and Cellular Therapy.

BACKGROUND AIMS: This study aimed to comprehensively assess the impact of stem cell selection between bone marrow (BM) and peripheral blood (PB) in unrelated hematopoietic stem cell transplantation (HSCT) for hematological malignancies. Our objective was to identify specific factors associated with better transplant outcomes. METHODS: A retrospective analysis was conducted using data from the Japanese HSCT registry. Inclusion criteria were patients aged 0-70 years who underwent their first unrelated HSCT with BM or PB, with an 8/8 or 7/8 allele HLA match for hematological malignancies between 2010 and 2020. RESULTS: Among 10 295 patients, no significant difference was observed in overall survival, relapse, graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) or non-relapse mortality between the groups. Patients who received PB showed no clear difference in acute GVHD but had a greater rate of chronic GVHD, resulting in poor chronic GVHD-free, relapse-free survival (CRFS). Subgroup analyses highlighted the importance of patient-specific factors in source selection. Patients with non-Hodgkin lymphoma and a greater hematopoietic cell transplantation-comorbidity index showed better CRFS and GRFS when BM was the preferred source. Similar trends were observed among patients with standard-risk disease for CRFS. However, no such trends were evident among patients aged 0-24 years, indicating that both sources are viable choices for young patients. CONCLUSIONS: This real-world retrospective analysis showed similar basic outcomes for BM and PB in an unrelated setting. The results support that BM may still be preferred over PB, especially when the long-term quality of life is a major concern. A consideration of individual factors can further optimize transplant success. Further research is warranted to explore the long-term implications of stem cell source selection.

Improvement of early mortality in single-unit cord blood transplantation for Japanese adults from 1998 to 2017.

The major limitation of cord blood transplantation (CBT) for adults remains the delayed hematopoietic recovery and higher incidence of graft failure, which result in a higher risk of early mortality in CBT. We evaluated early overall survival (OS), non-relapse mortality (NRM), neutrophil engraftment, acute graft-vs-host disease, and cause of early death among 9678 adult patients who received single-unit CBT in Japan between 1998 and 2017. The probability of OS at 100 days was 64.4%, 71.7%, and 78.9% for the periods 1998 to 2007, 2008 to 2012, and 2013 to 2017, respectively (P < .001). The cumulative incidences of NRM at 100 days during the same period were 28.3%, 20.8%, and 14.6%, respectively (P < .001). The cumulative incidences of neutrophil engraftment were also improved during the same period (P < .001). The most common cause of death within 100 days after CBT was bacterial infection in 1998 to 2007 and primary disease in the latter two time periods. Across the three time periods, the proportions of deaths from bacterial and fungal infection, graft failure, hemorrhage, sinusoidal obstructive syndrome, and organ failure decreased in a stepwise fashion. Landmark analysis of OS and NRM after 100 days showed that OS did not change over time in the multivariate analysis. Our registry-based data demonstrated a significant improvement of early OS after CBT for adults over the past 20 years. The landmark analysis suggested that improvement of early mortality could lead to an improvement of long-term OS after CBT.

Syntheses of C2'-Fluorinated Analogs of Solamin.

The details of the total syntheses of C2'-fluorinated analogs of solamin, an antitumor annonaceous acetogenin, are described. Fluorine was enantioselectively introduced at the C2'-position by organocatalytic α-fluorination of the aldehyde according to a previously reported method. C2'-fluorinated solamin and its C2'-diastereomer were synthesized by the Sonogashira coupling of a tetrahydrofuran fragment and fluorine-containing γ-lactone fragments.

Myeloablative Unrelated Cord Blood Transplantation in Adolescents and Young Adults with Acute Leukemia.

Outcomes for adolescents and young adults (AYAs) with leukemia differ from other age groups and are still under-represented in clinical research. The aim of this study was to analyze outcomes of umbilical cord blood transplant (UCBT) in AYAs with acute leukemia reported to Eurocord/European Society for Blood and Marrow Transplantation. Patients (N = 504) had acute lymphoblastic (59%) or myeloid leukemia (41%), were aged 15 to 25 years, and received UCBT after myeloablative conditioning regimens between 2004 and 2016. The primary endpoint was 3-year overall survival (OS). Median follow-up was 3.9 years. Transplant was single in 58% and double UCBT in 42%. Three-year OS was 45% and leukemia free survival (LFS) was 41%. Cumulative incidence functions (CIFs) of nonrelapse mortality (NRM) and relapse were 31% and 28%, respectively. CIF of acute graft-versus-host disease (GVHD) grades II to IV at day 100 was 28%. Three-year CIF of chronic GVHD was 25%. In adjusted analysis, better disease status at UCBT (hazard ratio [HR], 2.74; P < .001) and more recent UCBT (HR, 1.43; P = .01) were associated with increased OS, and a similar effect of these factors was observed on LFS. Contrastingly, the use of antithymocyte globulin had a negative effect in LFS. The risk of acute GVHD grades II to IV increased with the use of double UCBT (HR, 1.65; P  = .02) and decreased with more recent transplant period (HR, .65; P = .02) and antithymocyte globulin use (HR, .55; P  = .01). Outcomes of AYA UCBT improved in more recent years, becoming comparable with pediatric results. Demonstrating the feasibility of UCBT in AYAs facilitates stem cell source selection and provides the basis for future prospective studies.

Glycyl-tRNA synthetase from Nanoarchaeum equitans: The first crystal structure of archaeal GlyRS and analysis of its tRNA glycylation.

This study reports the X-ray crystallographic structure of the glycyl-tRNA synthetase (GlyRS) of Nanoarchaeum equitans - a hyperthermophilic archaeal species. This is the first archaeal GlyRS crystal structure elucidated. The GlyRS comprises an N-terminal catalytic domain and a C-terminal anticodon-binding domain with a long ß-sheet inserted between these domains. An unmodified transcript of the wild-type N. equitans tRNAGly was successfully glycylated using GlyRS. Substitution of the discriminator base A73 of tRNAGly with any other nucleotide caused a significant decrease in glycylation activity. Mutational analysis of the second base-pair C2G71 of the acceptor stem of tRNAGly elucidated the importance of the base-pair, especially G71, as an identity element for recognition by GlyRS. Glycylation assays using tRNAGly G71 substitution mutants and a GlyRS mutant where Arg223 is mutated to alanine strengthen the possibility that the carbonyl oxygen at position 6 of G71 would hydrogen-bond with the guanidine nitrogen of Arg223 in N. equitans GlyRS.

Cord Blood Unit Dominance Analysis and Effect of the Winning Unit on Outcomes after Double-Unit Umbilical Cord Blood Transplantation in Adults with Acute Leukemia: A Retrospective Study on Behalf of Eurocord, the Cord Blood Committee of Cellular Therapy, Immunobiology Working Party, and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Usually, after double umbilical cord blood transplantation (DUCBT), only 1 of the transplanted units persists in the long term. The characteristics of the winning cord blood unit (W-CBU) that determine unit dominance and how they influence the outcomes of DUCBT remain unclear. We retrospectively analyzed 347 patients with acute leukemia transplanted with a DUCBT (694 CBU) from 2005 to 2013 who had documented neutrophil engraftment and a W-CBU identified by chimerism analysis, to identify unit characteristics impacting on dominance. Median age at DUCBT was 40 years and median follow-up was 35 months. Among W-CBUs, 41% were ≥5/6 HLA matched to the recipient and 59% were ≤4/6. Multivariate analysis indicated that ≤4/6 HLA-matched W-CBUs led to lower leukemia-free survival (44% versus 56%; hazard ratio [HR], 1.5; P = .032) and overall survival (49% versus 62%; HR, 1.5; P = .028), increased nonrelapse mortality (26% versus 18%; HR, 1.9; P = .027), and acute graft-versus-host disease (46% versus 35%; HR, 1.7; P = .013). We were unable to predict unit dominance, but we demonstrated that outcomes were strongly influenced by the degree of HLA mismatch between W-CBU and recipient. Therefore, selection of both units with the lower number of HLA mismatches with the recipient is indicated.

Low Body Mass Index Is Associated with Increased Risk of Acute GVHD after Umbilical Cord Blood Transplantation in Children and Young Adults with Acute Leukemia: A Study on Behalf of Eurocord and the EBMT Pediatric Disease Working Party.

Body mass index (BMI) may influence outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of BMI on survival in children undergoing HSCT is not well defined, with conflicting results being reported on this issue. We analyzed 855 patients age 2 to 20 years with diagnosis of acute leukemia who underwent umbilical cord blood transplantation (UCBT) from 1990 to 2015. Patients were classified according to BMI as normal (fifth to 85th percentile), underweight (less than fifth percentile), overweight (85th to 95th percentile), and obese (>95th percentile) using growth charts for age and sex. All patients received single-unit UCBT after a myeloablative conditioning regimen. Diagnosis was acute lymphoblastic leukemia in 68% of the patients. Sixty-one percent of patients (n = 523) were in the normal BMI category, 11% (n = 96) were underweight, 16% (n = 137) overweight, and 12% (n = 99) obese. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was 35% (32% to 38%). According to pretransplantation BMI, aGVHD was 46% (33% to 59%) for underweight, 34% (31% to 42%) for normal, 36% (18% to 38%) for overweight, and 27% (15% to 37%) for obese (P = .04). In multivariate analysis, a BMI less than the fifth percentile was associated with higher incidence of acute grade II to IV GVHD compared with normal-BMI patients (hazard ratio, 1.61; 95% confidence interval, 1.15 to 2.26; P = .006). Our results show that being underweight at the time of transplantation is associated with an increased risk of aGVHD, highlighting the importance of nutritional status before UCBT.

[Peripheral neuropathy occurring soon after cord blood transplantation].

We experienced two cases of peripheral neuropathy in the early phase following cord blood transplantation. Case 1 was a 66-year-old man with recurrent T-ALL. On day 8, he experienced a sharp pain originating in both the palms and the soles, which worsened spreading to the knees, and was accompanied by muscle weakness. The neurological symptom progressed to the point of being unable to walk. A nerve conduction velocity test showed demyelination and axonopathy. In the CSF analysis, albuminocytologic dissociation and a rise in myelin basic protein were detected. These findings met the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). The symptoms improved with intravenous immunoglobulin (IVIG). He is now able to walk and continues to visit our department. Case 2 was a 42-year-old man with primary mediastinal large B-cell lymphoma. As the disease was refractory, he underwent reduced intensity cord blood transplantation (RICBT). Flare and numbness started in the palms and soles on day 26, with the symptoms progressing thereafter. A nerve conduction velocity test showed demyelination and axonopathy. The symptoms improved after IVIG administration. The diagnosis of peripheral neuropathy after transplantation is often difficult, but when an immunologic disorder is suspected to be the cause, early administration of IVIG may be effective.

Comparison of Allogeneic Transplant Outcomes Between Matched Sibling Donors and Alternative Donors in Patients Over 50 Years of Age with Acute Myeloid Leukemia: 8/8 Allele-Matched Unrelated Donors and Unrelated Cord Blood Provide Better Leukemia-Free Survival Compared with Matched Sibling Donors During Nonremission Status.

Acute myeloid leukemia (AML) is the most common indication for allogeneic hematopoietic cell transplantation (HCT). The increased availability of alternative donor sources has broadened donor types for older patients without HLA-matched sibling donors (MSD). It is uncertain if an MSD should be the first option for allogeneic HCT in patients with AML over 50 years of age. The objective of this study was to compare survival and other post-transplant outcomes between MSDs, 8/8 allele-matched unrelated donors (MUDs), 7/8 allele-MUDs, unrelated cord blood (UCB), and haploidentical donors for patients with AML over 50 years of age. We conducted a retrospective study to compare outcomes in 5704 patients with AML over 50 years of age and receiving allogeneic HCT between 2013 and 2021, using either MSD, 8/8 allele-MUD, 7/8 allele-MUD, UCB, or haploidentical donors in Japan. Complete remission (CR) and nonremission at HCT were analyzed separately for all analyses. In total, 3041 patients were CR, and 2663 patients were nonremission at the time of HCT. In multivariate analysis, donor type did not determine overall survival, irrespective of disease status at HCT. Leukemia-free survival (LFS) was significantly better for 8/8 allele-MUD (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.64 to 0.93; P = .005) and UCB (HR, 0.76; 95% CI, 0.65 to 0.88; P < .001), but not for 7/8 allele-MUD (HR, 0.97; 95% CI, 0.79 to 1.19; P = .794), and haploidentical donor (HR, 0.86; 95% CI, 0.70 to 1.05; P = .146) compared to the MSD group in nonremission status. However, donor type did not determine LFS among CR status. Relapse rates were significantly lower for 8/8 allele-MUD and UCB, whereas nonrelapse mortality was higher for UCB compared to the MSD group among both CR and nonremission status. Our registry-based study demonstrated that MSDs do not lead to superior survival compared to alternative donors for patients with AML over 50 years of age. Furthermore, 8/8 allele-MUDs and UCB provide better LFS compared with MSDs during nonremission status. Therefore, MSD is not necessarily the best donor option for allogeneic HCT in this population.

Development of an umbilical cord blood transplantation-specific nonrelapse mortality risk assessment score.

ABSTRACT: Higher rate of nonrelapse mortality (NRM) remains yet to be resolved in umbilical cord blood transplantation (UCBT). Considering that UCBT has some unique features compared with allogeneic hematopoietic cell transplantation from other graft sources, a UCBT-specific NRM risk assessment system is required. Thus, in this study, we sought to develop a UCBT-specific NRM Risk Assessment (CoBRA) score. Using a nationwide registry database, we retrospectively analyzed 4437 recipients who had received their first single-unit UCBT. Using the backward elimination method, we constructed the CoBRA score in a training cohort (n = 2687), which consisted of recipients age ≥55 years (score 2), hematopoietic cell transplantation-specific comorbidity index ≥3 (score 2), male recipient, graft-versus-host disease prophylaxis other than tacrolimus in combination with methotrexate, performance status (PS) 2 to 4, HLA allele mismatch ≥ 2, refined Disease Risk Index high risk, myeloablative conditioning, and CD34+ cell doses < 0.82 × 105/kg (score 1 in each). The recipients were categorized into 3 groups: low (0-4 points), intermediate (5-7 points), and high (8-11 points) groups according to the CoBRA score. In the validation cohort (n = 1750), the cumulative incidence of NRM at 2 years was 14.9%, 25.5%, and 47.1% (P < .001), and 2-year overall survival (OS) was 74.2%, 52.7%, and 26.3% (P < .001) in the low, intermediate, and high groups, respectively. In summary, the CoBRA score could predict the NRM risk as well as OS after UCBT. Further external validation will be needed to confirm the significance of the CoBRA score.

The mechanisms of electroconvulsive stimuli in BrdU-positive cells of the dentate gyrus in ACTH-treated rats.

In clinical studies, electroconvulsive stimuli have been associated with improvements in both depression and treatment-resistant depression. In a previous study, treatment with adrenocorticotropic hormone (ACTH) for 14 days decreased adult hippocampal cell proliferation. Furthermore, electroconvulsive stimuli significantly decreased the duration of immobility following repeated administration of ACTH for 14 days in rats. The present study was undertaken to further characterize the mechanism of treatmentresistant antidepressant effects of electroconvulsive stimuli by measuring cell proliferation, brain-derived neurotrophic factor (BDNF) levels, and phosphorylated and total cyclic adenosine monophosphate (cAMP) response element-binding protein (pCREB/CREB) levels in the hippocampus of ACTH-treated rats. Electroconvulsive stimuli increased cell proliferation in both saline-treated and ACTH-treated rats. Mature-BDNF protein levels showed a tendency to decrease in ACTH-treated rats. Electroconvulsive stimuli treatment increased mature-BDNF protein levels in the hippocampus of both saline-treated and ACTH-treated rats. Furthermore, electroconvulsive stimuli increased phospho-Ser133-CREB (pCREB) levels and the ratio of pCREB/CREB in both saline-treated and ACTH-treated rats. These findings suggest that the treatment-resistant antidepressant effects of electroconvulsive stimuli may be attributed, at least in part, to an enhancement of hippocampal cell proliferation.

Case report: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion: an autopsy case.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion is a clinicoradiological syndrome characterized by transient neuropsychiatric symptoms and hyperintensity of the splenium of the corpus callosum on diffusion-weighted MRI. Although intramyelinic edema and inflammatory cell infiltration can be predicted by MRI, the pathology of the splenium of the corpus callosum remains unknown. We encountered a case of clinically mild encephalitis/encephalopathy with a reversible splenial lesion and hypoglycemia in a patient who died of sepsis, and an autopsy was performed. The postmortem pathological findings included intramyelinic edema, myelin pallor, loss of fibrous astrocytes, microglial reactions, and minimal lymphocytic infiltration in the parenchyma. Based on these findings, transient demyelination following cytotoxic edema in the splenium of corpus callosum was strongly considered a pathogenesis of "clinically mild encephalitis/encephalopathy with a reversible splenial lesion" associated with hypoglycemia, and it could be generalized for the disease associated with the other causes. As cytotoxic edema could be the central pathology of the disease, the recently proposed term cytotoxic lesions of the corpus callosum may be applicable to this syndrome.

D-allose and D-psicose reinforce the action of metronidazole on trichomonad.

The effects of D-allose and D-psicose on Tritrichomonas foetus were examined. They were cultured in F-bouillon medium including glucose, but had never increased when glucose was substituted to those sugars. When cultured in a medium including a dose of ED(50) metronidazole and those sugars, trichomonad density was significantly less than that in a medium with metronidazole only. D-Allose remarkably reinforced the action of metronidazole. This means there are some interactions between metronidazole and those sugars. Although the mechanism is not clear, by using those sugars for treatment with metronidazole, the drug dosage could be lowered and the development of drug resistance of trichomonad parasites might be prevented.

The impact of GVHD on outcomes after adult single cord blood transplantation in European and Japanese populations.

The impact of GVHD and graft-versus-leukemia effect in unrelated cord blood transplantation (UCBT) is controversial. In the Eurocord/ALWP EBMT and JSTCT/JDCHCT collaborative study, we evaluated the impact of GVHD on UCBT outcomes in Japanese and European registries. A total of 3,690 adult patients with acute leukemia who received their first single UCBT were included. A multivariate analysis of overall survival (OS) revealed a positive impact of grade II acute GVHD compared with grade 0-I GVHD, in the Japanese cohort (hazard ratio (HR), 0.81; P = 0.001), and an adverse impact in the European cohort (HR, 1.37; P = 0.007). A negative impact of grade III-IV acute GVHD on OS was observed regardless of registries. In the analysis of relapse, a positive impact of grade II acutes GVHD compared with grade 0-I GVHD was observed only in the Japanese cohort, regardless of disease risk. The positive impact of limited chronic GVHD on OS was observed only in the Japanese cohort. In conclusion, a positive impact of mild GVHD after a single UCBT was observed only in the Japanese cohort. This could explain the ethnic difference in UCBT outcomes and might contribute to the preference usage of UCBT in Japan.

Design and synthesis of C35-fluorinated solamins and their growth inhibitory activities against human cancer cell lines.

The convergent synthesis of C35-fluorinated analogues of solamin, a mono-THF Annonaceous acetogenin, has been achieved by the Sonogashira coupling of the THF ring fragment and the fluorinated γ-lactone fragment. It was revealed that the number of fluorine atoms on the γ-lactone moiety affects the growth inhibitory activities against human cancer cell lines.

Prognostic factors for adult single cord blood transplantation among European and Japanese populations: the Eurocord/ALWP-EBMT and JSHCT/JDCHCT collaborative study.

Large differences in patient and transplant backgrounds make it difficult to identify consistent prognostic factors of unrelated cord blood transplantation (UCBT) among different populations. Thus, we performed a collaborative study between Eurocord/ALWP-EBMT and JSHCT/JDCHCT. Adults with acute leukaemia who underwent a single UCBT were eligible. In total, 3764 and 1027 patients of the JSHCT/JDCHCT and Eurocord/ALWP-EBMT registries, respectively, were included. The median ages of the Japanese and European cohorts were 51 and 38 years, respectively. Three or more HLA mismatches were more frequently observed in the Japanese cohort. The median total nucleated cell (TNC) counts were 2.58 and 3.51 × 107/kg in the Japanese and European cohorts, respectively. Anti-thymocyte globulin was used in only 2% of the Japanese cohort compared with 65% of the European cohort. The 3-year overall survival (OS) was 41% in JSHCT/JDCHCT and 33% in Eurocord/ALWP-EBMT. In the multivariate analysis, TNC dose and HLA matching had no significant effect on OS in either cohort, whereas year of transplantation, age, and refined disease risk index affected OS in both cohorts. Despite considerable differences in characteristics between the Japanese and European cohorts, we observed similar prognostic factors affecting UCBT outcomes in adult patients with acute leukaemia in both registries.

Synthesis of C4-fluorinated solamins and their growth inhibitory activity against human cancer cell lines.

C4-Fluorinated analogues of solamin, an antitumor acetogenin, were synthesized and investigated for their antitumor activities against 39 tumor cell lines. C4-Fluorinated solamins showed more potent growth inhibitory activity against cancer cell lines than solamin.

[Verification of multifocal electroretinogram Veris III system for clinical problems].

PURPOSE: To verify the usefulness of the Veris III system, which is said to be problematic in clinical applications for recording multifocal electroretinograms (mfERG) by an ophthalmologist. METHODS: A test wave was input to the system and the data were analyzed using Veris Science software. The items tested were overlapping, spatial averaging, combination procedures, and emission properties of the cathode ray tube (CRT) monitor (B 4). RESULTS: Overlapping was not observed under the standard stimulus conditions. The data resulting from both spatial averaging and combination procedures coincided with the theoretical calculated data defined by both procedures. Analysis of the emission properties of the CRT monitor showed that it took 85 mu seconds from the beginning to the end of the bright emission. CONCLUSIONS: No clinical problems were found in the M-sequence program, the spatial averaging procedure, or the combination procedure using several test waves. It is necessary to pay attention to the configuration of pattern stimulation on the CRT monitor (B 4), because it has a very steep emission during a very short time.

A case of cerebral reversible vasoconstriction syndrome triggered by repetition transcranial magnetic stimulation.

A 75-year-old man was admitted for combined low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy. Five days after the initiation of rTMS, he developed hypotension and temporary exacerbation of the right hemiplegia with thunderclap headache. MRA showed segmental stenosis of the left middle cerebral artery, which findings were improved at 9 days after the onset of the headache. He was diagnosed as having the reversible cerebral vasoconstriction syndrome (RCVS). The rTMS was recognized as safe rehabilitation treatment. However, it is necessary to recognize that RCVS can become one of the precipitants. This is the first report of RCVS triggered by rTMS.