Although leuprorelin acetate, a luteinizing hormone-releasing hormone agonist, has been approved based on short-term clinical trials conducted in Japan, its long-term efficacy on physical function remains unclear. We aimed to evaluate the long-term therapeutic efficacy of leuprorelin acetate using real-world clinical data through a self-controlled trend-shift analysis. The analysis included 91 genetically confirmed patients with spinal and bulbar muscular atrophy, with follow-up data collected before and after treatment initiation. The functional outcomes assessed included the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) and modified Norris scales, grip power, and serum creatinine levels. Leuprorelin acetate significantly slowed disease progression. For instance, the annual ALSFRS-R decline rate improved from approximately 0.5 points pre-treatment to 0.2 points post-treatment. The subgroup analysis supported the potential benefit of early intervention. These findings highlight the value of leveraging patient registries and post-marketing real-world data to evaluate treatment efficacy in slowly progressive diseases, such as SBMA, where traditional randomized controlled trials are often limited by insufficient statistical power to detect therapeutic efficacy. They also underscore the need for innovative methodologies to assess post-approval drug performance, paving the way for improved clinical outcomes for neurodegenerative diseases.

Background Falls may cause elderly people to be bedridden, requiring professional intervention; thus, fall prevention is crucial. The use of electronic health records (EHRs) is expected to provide highly accurate risk assessment and length-of-stay data related to falls, which may be used to estimate the costs and benefits of prevention. However, no studies to date have investigated the extent to which hospital stays could be shortened through fall avoidance resulting from the use of prediction tools. Objective We first estimated the extended length of hospital stay caused by falls among elderly inpatients. Next, we developed a model that predicts falls using clinical text as input and evaluated its accuracy. Finally, we estimated the potentially shortened hospital stay that would be made possible by appropriate interventions based on the prediction model. Methods Patients aged 65 years or older were selected as subjects, and the EHRs of 1728 falls and 70,586 nonfalls were subjected to analysis. The extended-stay lengths were estimated using propensity score matching of 49 associated variables. Bidirectional encoder representations from transformers and bidirectional long short-term memory methods were used to predict falls from clinical text. The estimated length of stay and the outputs of the prediction model were used to determine stay reductions. Results The extended length of hospital stay due to falls was estimated to be 17.8 days (95% CI 16.6-19.0), which dropped to 8.6 days when there were unobserved covariates at an odds ratio of 2.0. The accuracy of the prediction model was as follows: area under the receiver operating characteristic curve, 0.851; F-value, 0.165; recall, 0.737; precision, 0.093; and specificity, 0.839. When assuming interventions with 25% or 100% effectiveness against cases where the model predicted a fall, the stay reduction was estimated at 0.022 and 0.099 days/day, respectively. Conclusions The accuracy of the prediction model using clinical text is considered to be higher than the prediction accuracy of conventional assessments. However, our model’s precision remained low at 9.3%. This may be due, in part, to the inclusion of cases in which falls did not occur because of preventative interventions during hospitalization. Nonetheless, it is estimated that interventions for cases when falls were predicted will reduce medical costs by 886 Yen/day (~US $6.50/day) of intervention, even if the preventative effect is 25%. Limitations include the fact that these results cannot be extrapolated to short- or long-term hospitalization cases, and that this was a single-center study.

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.

Background. Central nervous system (CNS) histoplasmosis is a life-threatening condition and represents a diagnostic and therapeutic challenge. Isolation of Histoplasma capsulatum from cerebrospinal fluid (CSF) or brain tissue is diagnostic; however, culture is insensitive and slow growth may result in significant treatment delay. We performed a retrospective multicenter study to evaluate the sensitivity and specificity of a new anti-Histoplasma antibody enzyme immunoassay (EIA) for the detection of IgG and IgM antibody in the CSF for diagnosis of CNS histoplasmosis, the primary objective of the study. The secondary objective was to determine the effect of improvements in the Histoplasma galactomannan antigen detection EIA on the diagnosis of Histoplasma meningitis. Methods. Residual CSF specimens from patients with Histoplasma meningitis and controls were tested for Histoplasma antigen and anti-Histoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody using assays developed at MiraVista Diagnostics. Results. A total of 50 cases and 157 controls were evaluated. Fifty percent of patients with CNS histoplasmosis were immuno-compromised, 14% had other medical conditions, and 36% were healthy. Histoplasma antigen was detected in CSF in 78% of cases and the specificity was 97%. Anti-Histoplasma IgG or IgM antibody was detected in 82% of cases and the specificity was 93%. The sensitivity of detection of antibody by currently available serologic testing including immunodiffusion and complement fixation was 51% and the specificity was 96%. Testing for both CSF antigen and antibody by EIA was the most sensitive approach, detecting 98% of cases. Conclusions. Testing CSF for anti-Histoplasma IgG and IgM antibody complements antigen detection and improves the sensitivity for diagnosis of Histoplasma meningitis.

The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-β-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF BDG level was 85 pg/ml for cases, compared to <31 pg/ml for all controls (P < 0.05) and 82 pg/ml for controls with other causes of fungal meningitis (P = 0.27). The sensitivity for detection of BDG in CSF was 53.2%, whereas the specificity was 86.9% versus all controls and 46% versus other CNS fungal infections. CSF BDG levels of ≥80 pg/ml are neither sensitive nor specific to support a diagnosis of Histoplasma meningitis.

Background: Advances in whole exome sequencing (WES) provide us not only candidate variants potentially pathogenic for muscular dystrophy, but also numerous variants of unknown significance. To confirm the pathogenicity of variants, protein analyses with conventional 3,3-diaminobenzidine (DAB) immunohistochemistry or western blot of biopsied muscle are helpful for confirming the diagnosis, when the protein amount is markedly reduced. However, utility of such analyses is limited, when the amount of the protein is comparable between controls and subjects.

A complete loss of merosin, which is encoded by LAMA2, causes congenital muscular dystrophy with leukoencephalopathy. Partial merosin deficiency can be caused not only by primarily LAMA2 mutations, but also secondarily by dystroglycanopathy. Although it can be molecularly diagnosed based on a genetic analysis, this method is labor-intensive because of its huge genome size. A 26-year-old male patient presented with mild muscular weakness, joint contractures, and epilepsy. Double immunofluorescence staining of a muscle biopsy specimen showed mislocalization of merosin, and a genetic analysis revealed a homozygous c.818G>A (p.Arg273Lys) mutation in LAMA2. Double immunofluorescence staining and whole exome sequencing were useful for the diagnosis of partial merosin deficiency.

A 20-year-old woman suffered from anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and was treated with removal of an ovarian teratoma and retroperitoneal ganglioneuroma in addition to immunotherapy. She was incapable of face recognition, had difficulty with object recognition, and lacked color sensation and stereo perception during recovery. These symptoms were transient and completely resolved over 4 months. Our report documents additional aspects of visual impairment associated with anti-NMDAR encephalitis and suggests that the disease can lead to diffuse cerebral dysfunction including the cortical visual system.

To report the clinical, radiological, and immunological association of demyelinating disorders with anti–N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis.

Inflammatory myofibroblastic tumor (IMT) is a disease characterized by tumorous lesions consisting of myofibroblastic spindle cells and inflammatory cells that occur primarily in the soft tissues and viscera of children and young adults. Total excision is the most effective therapy. Steroids have been used to treat unresectable lesions with some success. We herein report a case of IMT involving the frontal bone accompanied by pachymeningitis. The tumor was characterized by an aggressive clinical course that was refractory to prednisolone. Performing total excision seemed difficult. Celecoxib and methotrexate were effective treatments. Our experience suggests the efficacy of celecoxib and methotrexate as alternatives for treating unresectable IMT.

Introduction We investigated the long-term effects of leuprorelin on leg-muscle strength in spinal and bulbar muscular atrophy (SBMA). We hypothesized that testosterone suppression by leuprorelin would prevent the progression of muscle weakness. Methods In a prospective, long duration, open trial, 16 SBMA patients underwent medical castration with leuprorelin for 3.5 years. Chlormadinone was coadministered initially to prevent a testosterone surge. The strength of knee extension and flexion were quantitated using a torque machine. Results Our hypothesis was rejected. The leg strength measures decreased significantly with the mean reduction of 22.327.8%. In a post hoc analysis, the leg strength of 4 patients with higher pretreatment baseline total testosterone levels and short disease duration of 16 years were stronger at baseline and decreased by only 12.315.7% after treatment. Conclusions Leuprorelin was not effective in this small long-term treatment trial in SBMA. The possibility that earlier treatment might be beneficial may deserve further study. Muscle Nerve 47: 816822, 2013

and chronic inflammatory demyelinating polyneuropathy (CIDP). Case report: A 78-year-old man presented with a 2-week history of ataxia, progressive weakness, and numbness of both hands and feet. His weakness was such that he was unable to ambulate. He has a history of well-controlled diabetes and refractory Crohn’s disease treated with infliximab for 1 year. He had marked distal muscles and mild proximal muscles weakness. He was areflexic throughout and had loss of proprioception below his wrists and knees with preservation of pain sensation. Initial nerve conduction studies (NCSs) of the median, ulnar, peroneal, and tibial motor nerves showed markedly prolonged distal latencies, decreased amplitudes, temporal dispersion, and absent F waves. His sensory NCSs were unresponsive. It was concluded that his CIDP was secondary to infliximab after ruling out other causes. He received intravenous (IV) Solu-Medrol 1 g daily for 3 days and IV immunoglobulin (IVIg) for 5 days with marked improvement. NCSs 6 weeks later showed shortened latencies, shortened F waves, and increased amplitudes. Conclusion: Infliximab is a TNF-alpha inhibitor used in the treatment of Crohn’s disease. It has been rarely linked to MS and CIDP. In this report the patient achieved significant clinical and electrodiagnostic improvement with a combination of IVIg and Solu-Medrol treatment.

Introduction: Contamination by far-field potentials (FFPs) may interfere with motor unit number estimation (MUNE) in the ulnar nerve. Methods: Surface motor unit potentials (SMUPs) from 29 spinal and bulbar muscular atrophy (SBMA) patients and 27 control subjects were classified into SMUPs from the abductor digiti minimi muscle (ADM SMUPs) or non-ADM SMUPs, based on the waveform patterns from 3-channel recordings. Results: The mean areas of the ADM SMUPs and non-ADM SMUPs in control subjects were 219.0 +/- 131.3 and 63.7 +/- 48.5 Vms, respectively. In SBMA patients they were 1988.9 +/- 999.4 and 222.7 +/- 125.7 Vms, respectively. The percentages of non-ADM SMUPs were 68 +/- 22% in controls and 84 +/- 15% in SBMA patients. Conclusions: Non-ADM SMUPs generated mainly by FFPs often had a negative onset in the routine lead and were indistinguishable from ADM SMUPs. More frequent exclusion of smaller non-ADM SMUPs in controls by size criteria would reduce the diagnostic yield of MUNE.

Introduction: A reliable electrophysiological marker for clinical trials is increasingly needed in spinal and bulbar muscular atrophy (SBMA). We previously developed a quantitative analysis method for surface electromyography (SEMG), the clustering index (CI) method. Our purpose was to test the utility of the CI method for evaluating lower motor neuron involvement in SBMA patients. Methods: Subjects included 29 SBMA patients and 27 healthy controls. The recording electrode was placed over the abductor digiti minimi (ADM) muscle with a proximal reference. The Z‐score, based on the CI method, was compared with compound muscle action potential (CMAP) amplitude and motor unit number estimation (MUNE), with regard to sensitivity. Results: The Z‐scores of the CI method, CMAP amplitude, and MUNE were abnormal in 100%, 72%, and 93% of the patients, respectively. Interrater reliability of the CI method was sufficiently high. Conclusion: The CI method is promising as a non‐invasive electrophysiological marker in SBMA. Muscle Nerve, 2011