Prevalence and clinical profiles of anti-myelin-associated glycoprotein neuropathy in Japan: A nationwide survey study of 133 patients.

BACKGROUND AND PURPOSE: The aim of this study was to determine the prevalence of anti-myelin-associated glycoprotein (MAG) neuropathy and the current status of such patients in Japan. METHODS: We conducted a nationwide survey in 2021 using established epidemiological methods. Questionnaires were sent to all neurology and pediatric neurology departments throughout Japan to identify patients with anti-MAG neuropathy. An initial questionnaire was used to determine the number of patients, with a second one used to collect detailed clinical information. RESULTS: The estimated number of patients with anti-MAG neuropathy was 353, with a prevalence of 0.28 per 100,000 and an incidence of 0.05 per 100,000. The detailed clinical profiles of 133 patients were available. The median (range) age of onset was 67 (30-87) years, with a prominent peak in the age range 66-70 years, and the male-to-female ratio was 3.6. Most patients had distal sensory-predominant polyneuropathy, and neuropathic pain (50%), or sensory ataxia (42%), while 18% had Waldenström's macroglobulinemia or multiple myeloma. Intravenous immunoglobulin was the most frequently used treatment (65%), but the response rate was <50%, whereas rituximab was given in 32% of patients, and 64% of these showed improvement. At the last visit, 27% of patients could not walk independently. CONCLUSIONS: This study on anti-MAG neuropathy provides updated insights into the epidemiology of this disease, clinical profiles, and treatment approaches in Japan. Rituximab therapy, used for only one-third of the patients, demonstrated efficacy. During the final visit, a quarter of the patients were unable to walk independently. Further studies are warranted to determine the optimal management of this rare and intractable disorder.

Combined Therapy with Ixazomib, Lenalidomide, and Dexamethasone for Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes Syndrome.

Objective Immunomodulatory drugs and proteasome inhibitors are therapeutic options for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. This study aimed to evaluate the efficacy and safety of the combination of ixazomib, lenalidomide, and dexamethasone (IRd) for POEMS syndrome. Methods Six consecutive patients with POEMS syndrome who were treated with the IRd regimen at Chiba University Hospital between April 2018 and August 2021 were included. Serum M-protein and serum vascular endothelial growth factor (sVEGF) levels, overall neuropathy limitation scales (ONLS), clinical symptoms, and adverse events were assessed. Results Of the six patients, five had received prior treatments. Patients received a median of 5 cycles (range, 3-28 cycles) of IRd. Following treatment, serum M-protein disappeared in two patients, sVEGF levels returned to normal in two patients, two patients showed a reduction in the ONLS of 1, and clinical symptoms improved in four patients. The median level of sVEGF decreased from 2,395 pg/mL (range, 802-6,120 pg/mL) to 1,428 pg/mL (range, 183-3,680 pg/mL) in three months. Adverse events, including rash, neutropenia, sensory peripheral neuropathy, and nausea, were observed in three patients, which necessitated dose reduction or discontinuation of treatment. Conclusion IRd can be a therapeutic option for POEMS syndrome, albeit with careful monitoring of adverse events.

Temporal Changes in Brain Perfusion in a Patient with Myoclonus and Ataxia Syndrome Associated with COVID-19.

Myoclonus and ataxia, with or without opsoclonus, have recently been recognized as a central nervous system syndrome associated with coronavirus disease-2019 (COVID-19). A 52-year-old Japanese man developed myoclonus and ataxia 16 days after the onset of COVID-19. Brain single-photon emission computed tomography (SPECT) revealed hyperperfusion in the cerebellum and hypoperfusion in the cerebral cortices with frontal predominance during the acute stage, which improved over two months. This study indicates that brain perfusion SPECT can be effective in detecting functional alterations in COVID-19-related myoclonus and ataxia.

Recurrent Cerebral Infarcts Associated with Uterine Adenomyosis: Successful Prevention by Surgical Removal.

Hypercoagulability associated with malignant tumors causes thrombosis, termed Trousseau's syndrome, but is rarely associated with benign gynecological tumors, such as myoma and adenomyosis. We herein report a 47-year-old Japanese woman with uterine adenomyosis who developed multiple cerebral infarcts during menstruation. Edoxaban was initially used for prevention but failed to prevent recurrence of thrombosis. However, hysterectomy and bilateral salpingo-oophorectomy resulted in the successful prevention of recurrence of cerebral infarct for five years without antiplatelet or anticoagulant agents. In our patient, the surgical removal of adenomyosis was highly effective for preventing thrombosis in a patient with adenomyosis.

Dispersion of mean consecutive differences in single-fiber electromyography increases diagnostic sensitivity for myasthenia gravis.

INTRODUCTION: In this study we aimed to investigate the dispersion of mean consecutive difference (MCD) of concentric needle jitter studies of patients with myasthenia gravis (MG) and its effect on diagnostic sensitivity for MG. METHODS: One hundred fifty-three patients, including 76 patients with MG and 77 controls with possible MG who later received another diagnosis, underwent stimulated concentric needle jitter studies of the frontalis muscle. MCD mean, standard deviation (SD), and coefficient of variation (CV) were calculated. Diagnostic sensitivity and specificity were determined using receiver operating characteristic (ROC) analyses. RESULTS: MG patients showed a significantly greater MCD mean (MG: control, 26.3 µs; 13.5 µs [median]; P < .0001), MCD SD (MG: control, 12.8 µs; 5.1 µs [median]; P < .0001), and MCD CV (MG: control, 46.1; 37.5 [median]; P < .001) than those without MG. An ROC curve of SD showed a large area under the curve (0.88), and a cut-off value of 7.2 µs, which was calculated by maximum Youden index, exhibited high diagnostic sensitivity (86%) for MG. Combined MCD mean, outliers, and SD criteria showed higher sensitivity (88%) than conventional criteria alone (82%), at the expense of lower specificity. Five MG patients with normal MCD mean and abnormal MCD SD had only ocular symptoms. DISCUSSION: The dispersion of MCD as measured by MCD SD greater than 7.2 µs is significantly increased in patients with MG and may be a useful measure of abnormal jitter in the diagnosis of MG, especially for identifying patients with mild disease.

Postoperative Low Back Pain after Posterior Lumbar Interbody Fusion Surgery Using Cortical Bone Trajectory Screws.

STUDY DESIGN: Retrospective analysis of a case series of prospectively collected data. PURPOSE: To compare clinical and radiological outcomes between two posterior lumbar interbody fusion techniques: cortical bone trajectory (CBT) and traditional pedicle screw (PS). OVERVIEW OF LITERATURE: Biomechanical studies have revealed the benefits of the CBT technique. However, clinical evidence obtained from the direct comparison of outcomes between CBT and PS is limited. METHODS: We retrospectively investigated 104 patients who had undergone posterior lumbar interbody fusion using CBT or PS. Clinical symptoms were evaluated and compared between CBT and PS using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) and Visual Analog Scale (VAS) before and 1 year after surgery. Spinal fusion status was assessed by multiplanar reconstruction computed tomography at 1 year after surgery. RESULTS: The CBT and PS techniques were performed on 36 and 68 patients, respectively. Both CBT- and PS-treated patients exhibited improvement in each subdomain of the JOABPEQ and in the VAS. With regard to postoperative improvement of low back pain, the treatment effect, as assessed by the JOABPEQ, was greater for PS than for CBT. The spinal fusion rate was slightly lower for CBT than for PS, although the difference between them was not significant. The effect of treatment on postoperative low back pain was smaller for CBT than for PS, regardless of whether rigid spinal fusion was achieved. CONCLUSIONS: Clinical symptoms and spinal fusion efficiency were not significantly different between CBT and PS except for postoperative improvement in low back pain. The treatment effect on postoperative low back pain was smaller for CBT than for PS.

Treatment response and prognosis of POEMS syndrome coexisting with Castleman disease.

POEMS (polyneuropathy, organomegaly, endocrinopathy monoclonal gammopathy, and skin changes) syndrome is occasionally associated with Castleman disease (CD) and their prognosis is considered as poorer than that in POEMS alone patients. To elucidate recent prognosis of POEMS syndrome coexisting with CD, we reviewed clinical data of 102 patients with POEMS syndrome treated at our institution between 2000 and 2018 and compared clinical characteristics, response to treatment, and prognosis between POEMS patients with biopsy-proven CD (POEMS-CD) and those without it. Fourteen POEMS-CD patients and 56 POEMS alone patients were identified, and the remaining 32 patients with unbiopsied lymphadenopathy were excluded. POEMS-CD patients significantly showed earlier onset and less severe neuropathic symptoms. Most of the POEMS-CD patients were treated with thalidomide and dexamethasone (n = 10, 71%), and subsequently received autologous stem cell transplantation (n = 6, 43%). Response to thalidomide was better in patients with POEMS-CD than those with POEMS alone (90% vs 43% clinical response, [p = .012]; 80% vs 45% normalization of serum VEGF levels, [p = .079]). The 10-year overall survival (95% confidence interval) was 89% (50-98%) in POEMS-CD patients and 61% (42-77%) in those with POEMS alone. POEMS syndrome associated with CD constitutes a subgroup of POEMS syndromes characterized by earlier onset, mild polyneuropathy, and favorable response to treatment. Recognition of this subgroup is significant for determination of therapeutic strategy.

Mucopolysaccharidosis IVA (Morquio A syndrome) and VI (Maroteaux-Lamy syndrome): under-recognized and challenging to diagnose.

OBJECTIVE: Mucopolysaccharidosis IVA (MPS IVA, or Morquio A syndrome) and VI (MPS VI, or Maroteaux-Lamy syndrome) are autosomal recessive lysosomal storage disorders. Skeletal abnormalities are common initial presenting symptoms and, when recognized early, may facilitate timely diagnosis and intervention, leading to improved patient outcomes. Patients with slowly progressing disease and nonclassic phenotypes can be particularly challenging to diagnose. The objective was to describe the radiographic features of patients with a delayed diagnosis of MPS IVA or VI. MATERIALS AND METHODS: This was a retrospective study. The records of 5 MPS IVA and 3 MPS VI patients with delayed diagnosis were reviewed. Radiographs were evaluated by a radiologist with special expertise in skeletal dysplasias. RESULTS: An important common theme in these cases was the appearance of multiple epiphyseal dysplasia (MED) with epiphyseal changes seemingly confined to the capital (proximal) femoral epiphyses. Very few patients had the skeletal features of classical dysostosis multiplex. CONCLUSIONS: Radiologists should appreciate the wide phenotypic variability of MPS IVA and VI. The cases presented here illustrate the importance of considering MPS in the differential diagnosis of certain skeletal dysplasias/disorders, including MED, some forms of spondylo-epiphyseal dysplasia (SED), and bilateral Perthes-like disease. It is important to combine radiographic findings with clinical information to facilitate early testing and accurate diagnosis.

FOXC2 mutations in familial and sporadic spinal extradural arachnoid cyst.

Spinal extradural arachnoid cyst (SEDAC) is a cyst in the spinal canal that protrudes into the epidural space from a defect in the dura mater. Most cases are sporadic; however, three familial SEDAC cases have been reported, suggesting genetic etiological factors. All familial cases are associated with lymphedema-distichiasis syndrome (LDS), whose causal gene is FOXC2. However, FOXC2 mutation analysis has been performed in only 1 family, and no mutation analysis has been performed on sporadic (non-familial) SEDACs. We recruited 17 SEDAC subjects consisting of 2 familial and 7 sporadic cases and examined FOXC2 mutations by Sanger sequencing and structural abnormalities by TaqMan copy number assay. We identified 2 novel FOXC2 mutations in 2 familial cases. Incomplete LDS penetrance was noted in both families. Four subjects presented with SEDACs only. Thus, SEDAC caused by the heterozygous FOXC2 loss-of-function mutation should be considered a feature of LDS, although it often manifests as the sole symptom. Seven sporadic SEDAC subjects had no FOXC2 mutations, no symptoms of LDS, and showed differing clinical characteristics from those who had FOXC2 mutations, suggesting that other gene(s) besides FOXC2 are likely to be involved in SEDAC.

Occurrence of central polydactyly, syndactyly, and cleft hand in a single family: report of five hands in three cases.

Central polydactyly, syndactyly, and cleft hand are categorized separately in the International Federation of Societies for Surgery of the Hand classification. However, some investigators have proposed that these malformations should be classified into a single category: abnormal induction of finger rays. In this article, we report 5 hands with central polydactyly, syndactyly, and cleft hand in 3 patients from the same family and discuss the phenotypes in each hand.

L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicism.

Long Interspersed Element 1 (L1) is a retrotransposon that comprises approximately 17% of the human genome. Despite its abundance in mammalian genomes, relatively little is understood about L1 retrotransposition in vivo. To study the timing and tissue specificity of retrotransposition, we created transgenic mouse and rat models containing human or mouse L1 elements controlled by their endogenous promoters. Here, we demonstrate abundant L1 RNA in both germ cells and embryos. However, the integration events usually occur in embryogenesis rather than in germ cells and are not heritable. We further demonstrate L1 RNA in preimplantation embryos lacking the L1 transgene and L1 somatic retrotransposition events in blastocysts and adults lacking the transgene. Together, these data indicate that L1 RNA transcribed in male or female germ cells can be carried over through fertilization and integrate during embryogenesis, an interesting example of heritability of RNA independent of its encoding DNA. Thus, L1 creates somatic mosaicism during mammalian development, suggesting a role for L1 in carcinogenesis and other disease.