Identifying functional cortical plasticity after spinal tumour resection using navigated transcranial magnetic stimulation.

Our aim was to investigate the effectiveness of navigated transcranial magnetic stimulation (nTMS) brain mapping to characterise preoperative motor impairment caused by an intradural extramedullary (IDEM) tumour and postoperative cortical functional reorganisation. Preoperative and 1-year follow-up clinical, radiological and nTMS data from a case of thoracic spinal meningioma that underwent surgical resection of the lesion were collected and compared. A 67-year-old patient presented with severe progressive thoracic myelopathy (hypertonic paraparesis, clonus, insensate urinary retention) secondary to an IDEM tumour. Initial nTMS assessment showed bilateral upper limb representation with no positive responses for both lower limbs. He underwent successful surgical resection for his IDEM (meningioma WHO grade 1). At 1-year follow-up, the patient's gait was improved and his bladder function normalised. nTMS documented positive responses for both upper and lower limbs and a decrease in the area (right side: 1.01 vs 0.39cm2; left side: 1.92 vs 0.81cm2) and volume (right side: 344.2 vs 42.4uVcm2; left side: 467.1 vs 119uVcm2) of cortical activation for both upper limbs, suggesting a functional reorganisation of the motor areas after tumour resection. nTMS motor mapping and derived metrics can characterise preoperative motor deficit and cortical plasticity during follow-up after IDEM resection.

Intramedullary Spinal Epidermoid Cyst-A Rare Cause of Spastic Paraparesis.

Spinal intramedullary epidermoids are rare intramedullary lesions of the spinal cord. They may be congenital or acquired with the congenital type often associated with spinal dysraphism and other spinal anomalies. The clinical presentation depends on the level of the involvement of the spinal cord. Management of these lesions is surgical excision. We report a case of intramedullary spinal epidermoid who presented with spastic paraparesis.

Neurosarcoidosis: An under-diagnosed cause of myelopathy.

Sarcoidosis is a granulomatous disorder with multi-organ involvement, and etiology still remains unknown. Neurosarcoidosis is the involvement of the nervous system in sarcoidosis. Spinal cord involvement is usually intra-dural, but extra-dural involvement can also occur. Here, we report a case of 30 years old lady presenting with subacute onset paraparesis with bladder and bowel involvement, which was finally diagnosed as sarcoidosis-associated myelopathy with the longitudinally extensive transverse myelitis (LETM) phenotype.

Hepatic myelopathy neurological complication of chronic liver disease: two case reports.

BACKGROUND: Hepatic myelopathy is a very rare neurological complication of chronic liver disease. Patients habitually present with progressive pure motor spastic paraparesis. This neurological dysfunction is almost always due to cirrhosis and portocaval shunt, either surgical or spontaneous. CASES REPORT: We report two cases of a 57-year-old man and a 37-year-old woman with progressive spastic paraparesis linked to cirrhosis and portal hypertension. The two patients are of Tunisian origin (north Africa). Magnetic resonance imaging of the spinal cord of two patients was normal, while brain magnetic resonance imaging showed a T2 hypersignals of the pallidums. These signs, in favor of hepatic encephalopathy in the two patients with cirrhosis with isolated progressive spastic paraparesis without bladder or sensory disorders, help to retain the diagnosis of hepatic myelopathy. CONCLUSION: Hepatic myelopathy is a severe and debilitating neurological complication of chronic liver disease. The pathogenesis is misunderstood and seems to be multifactorial, including the selective neurotoxic role both of ammonia and other pathogenic neurotoxins. Usually a pathological brain magnetic resonance imaging showing a hepatic encephalopathy was documented, contrasting with a normal spinal cord magnetic resonance imaging that contributed to diagnosis of hepatic myelopathy. Conservative therapies such as ammonia-lowering measures, diet supplementation, antispastic drugs, and endovascular shunt occlusion show little benefit in improving disease symptoms. Liver transplantation performed at early stage can prevent disease progression and could probably allow for recovery.

HTLV-1/2 infection in Italy: a narrative review of epidemiological studies.

The human T-cell leukemia virus type 1 (HTLV-1) was first described in 1980. It is spread in highly endemic regions in the world, such as the Southwestern part of Japan, sub-Saharan Africa and South America, Caribbean, Middle East, and Australo-Melanesia regions. HTLV-1 causes adult T cell leukemia and is associated with many inflammatory conditions, most notably HTLV-1-associated myelopathy/tropic spastic paraparesis. HTLV-2, first isolated in 1982, was recognized as a common infection in intravenous drug users, but a clear association with disease remains elusive. The first estimate of HTLV-1-positive individuals worldwide, in 1993, was around 10-20 millions. Due to the lack of global population-based prevalence studies, this is considered an underestimate at the moment. Furthermore, HTLV-1 prevalence in Europe is impacted by changing migration flows. Particularly, no data on HTLV-1 prevalence in the general population in Italy are available. Here, we report a systematic literature review of studies conducted in Italy on HTLV-1/2 from 1980 to 2023. Based on the criteria we adopted a total of 426 publications were found (64 reviews, 99 epidemiological, and 263 translational studies). The contents of some representative publications are summarized and discussed. Moreover, an approximate estimation of about 26,000 HTLV-1 positive foreigners living in Italy was obtained from updated data of foreigners from each single country officially registered as resident in Italy and from data on HTLV-1 prevalence among the general population in the corresponding countries.

Novel insights into human T-lymphotropic virus type-1 (HTLV-1) pathogenesis-host interactions in the manifestation of HTLV-1-associated myelopathy/tropical spastic paraparesis.

Human T-lymphotropic virus type-1 (HTLV-1) was the first discovered human oncogenic retrovirus, the etiological agent of two serious diseases have been identified as adult T-cell leukaemia/lymphoma malignancy and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a debilitating chronic neuro-myelopathy. Despite more than 40 years of molecular, histopathological and immunological studies on HTLV-1-associated diseases, the virulence and pathogenicity of this virus are yet to be clarified. The reason why the majority of HTLV-1-infected individuals (∼95%) remain asymptomatic carriers is still unclear. The deterioration of the immune system towards oncogenicity and autoimmunity makes HTLV-1 a natural probe for the study of malignancy and neuro-inflammatory diseases. Additionally, its slow worldwide spreading has prompted public health authorities and researchers, as urged by the WHO, to focus on eradicating HTLV-1. In contrast, neither an effective therapy nor a protective vaccine has been introduced. This comprehensive review focused on the most relevant studies of the neuro-inflammatory propensity of HTLV-1-induced HAM/TSP. Such an emphasis on the virus-host interactions in the HAM/TSP pathogenesis will be critically discussed epigenetically. The findings may shed light on future research venues in designing and developing proper HTLV-1 therapeutics.

Lactococcus garviae in Lumbar Spondylodiscitis With Spinal Epidural Abscess Causing Paraparesis: A Case Report.

Spinal epidural abscess (SEA) can lead to a subacute onset of neurological deficits of the extremities and is commonly accompanied by spondylodiscitis if located anterior to the dura. Lactococcus garviae is a fish pathogen that is occasionally found in poultry, cattle, and swine. It is a rare cause of infection in humans. Most commonly it is associated with endocarditis. Until 2019, less than 30 cases of human Lactoccous garviae infection have been published. To the best of our knowledge, we present the second reported case of SEA with spondylodiscitis caused by Lactococcus garviae. How Lactococcus garviae caused SEA, remains unclear in this case.

Infective dermatitis associated with human T-cell lymphotropic virus type-1, an underdiagnosed disease.

Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood, although very rarely cases have been reported in adults. Most of the cases are from Jamaica and Brazil and occur in individuals with low socioeconomic status. IDH is always associated with refractory Staphylococcus aureus or beta-hemolytic Streptococcus infection of the skin and nasal vestibules. Patients with IDH may develop other even more severe HTLV-1-associated diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) of early or late appearance and adult T-cell leukemia/lymphoma. In the context of the Brazilian experience, it has been observed that 54% of IDH patients exhibit the juvenile form of HAM/TSP while the estimated incidence of adult HAM/TSP is 3%. As there are no curative treatments for HTLV-1 infection (or vaccines) or most of its associated diseases, prevention of infection is fundamental, mainly by vertical transmission, as it is responsible for the development of IDH, infantojuvenile HAM/TSP, and ATL. Public measures to reduce this transmission must be implemented urgently. Furthermore, it is recommended, mainly in HTLV-1 endemic areas, to search for HTLV-1 infection in all patients with infected eczema, even in adults.

Cannabinoid receptors as new targets for HTLV-1 associated myelopathy (HAM/TSP) treatment.

BACKGROUND/AIM: The roles of endocannabinoids are described in immune modulation and neuroprotection. HTLV-1-associated myelopathy (HAM/TSP) is an inflammatory neurodegenerative disease. Therefore, in this study, the interactions of HTLV-1 regulatory factors and host cannabinoid receptors (CBRs) were evaluated in HAM/TSP. METHODS: Nineteen HAM/TSPs, 22 asymptomatic carriers (ACs), and 18 healthy controls (HCs) were enrolled. RNA was extracted from PBMCs and then reverse-transcribed to cDNA. The gene expression of CB1R and CB2R, as well as HTLV-1 proviral load (PVL), Tax and HTLV-1 basic leucine zipper factor (HBZ) were assessed by RT-qPCR. RESULTS: The mean expression of CB1R in ACs (8.51 ± 2.76) was significantly higher than HAMTSPs (1.593 ± 0.74, p = 0.05) and also HCs (0.10 ± 0.039, p = 0.001). The CB2R gene expression level in ACs (2.62±0.44) was significantly higher than HAM/TSPs (0.59 ± 0.15, p = 0.001) and HCs (1.00 ± 0.2, p = 0.006). Meanwhile there was a strong correlation between CB1R and CB2R gene expression levels in the HCs and HAM/TSPs (p = 0.001). HTLV-1-Tax expression in HAM/TSPs (386 ± 104) was higher than ACs (75 ± 32) and statistically significant (p = 0.003). While HTLV-1-HBZ was only expressed in three AC subjects and five HAM/TSPs, thus it cannot be analyzed. CONCLUSION: The up-regulation of CB2R has immunomodulatory effects in inflammatory reactions. While CB1R as a neuroprotective agent may suppress inflammatory reactions in ACs, preventing HAM/TSP. It seems that, like multiple sclerosis (MS), cannabinoid medications are beneficial in HAM/TSP.

Autoimmune Hemolytic Anemia Due to Spondyloenchondrodysplasia with Spastic Paraparesis and Intracranial Calcification due to Mutation in ACP5.

Spondyloenchondrodysplasia (SPENCD) is a rare spondylometaphyseal skeletal dysplasia with characteristic lesions mimicking enchondromatosis and resulting in short stature. A large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders. SPENCD is caused by loss of tartrate-resistant acid phosphatase activity, due to homozygous mutations in ACP5 , playing a role in nonnucleic-acid-related stimulation/regulation of the type I interferon pathway. In this article, we presented a 19-year-old boy with SPENCD, presenting with recurrent autoimmune hemolytic anemia episodes since he was 5 years old. He had short stature, platyspondyly, metaphyseal changes, intracranial calcification, spastic paraparesis, and mild intellectual disability. He also had recurrent pneumonia attacks. The clinical diagnosis of SPENCD was confirmed by sequencing of the ACP5 gene, and a homozygous c.155A > C (p.K52T) variation was found, which was reported before as pathogenic. In conclusion, in early onset chronic autoimmune cytopenias an immune dysregulation may often have a role in the etiology. Associating findings and immunologic functions should be carefully evaluated in such patients in the light of the literature. The present case shows the importance of multisystemic evaluation for the detection of SPENCD that has a monogenic etiology.

Neurological aspects of HTLV-1 infection: symptoms in apparently asymptomatic carriers.

Human T-lymphotropic virus type 1 (HTLV-1) is classically associated with the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although the mechanisms of this neurological disorder remain unclear. In addition, some patients who develop "minor" neurological signs that do not meet diagnostic criteria for HAM/TSP are classified as asymptomatic carriers. This study aims to demonstrate the neurological symptoms of Brazilian patients living with HTLV-1 classified as not-HAM.TSP. This observational study evaluated patients treated in an HTLV reference center in Bahia, Brazil, between February 2022 and July 2023. The data were obtained through the analysis of medical records and neurological consultation. Those individuals classified as HAM/ TSP were excluded from this study. 74 patients were submitted to a careful neurological evaluation: 23 HAM/TSP, 22 were classified with intermediate syndrome (IS), and 29 were oligosymptomatic. Self-reported symptoms were significantly more common in the IS group, including urinary symptoms such as nocturia, urgency, incontinence, dysuria, weakness, paresthesia, lumbar pain, xerostomia, and xerophthalmia. Physical examination findings consistent with reduced vibratory and tactile sensitivity were more common in the IS group (p = 0.017 and p = 0.013). Alterations in the V and VIII cranial nerves were present in both groups. HTLV-1 can lead to the development of important neurological signs and symptoms in apparently asymptomatic individuals. This data highlights the need for more research into the neurological aspects of HTLV-1 infection and emphasizes the importance of early diagnosis, treatment, and support for individuals living with this virus.

Liver Transplantation Reverses Hepatic Myelopathy in the Decompensated Phase of Cirrhosis: Case Report and Literature Review.

Hepatic myelopathy (HM) is a rare neurological complication in the end stage of many liver diseases and is characterized by bilateral spastic paraparesis without sensory and sphincter dysfunction. It occurs owing to metabolic disorders and central nervous system dysfunction associated with cirrhosis. Without timely and effective clinical intervention, the prognosis of these patients is devastating. Although liver transplantation (LT) is an effective treatment for HM, the prognosis of these patients remains unsatisfactory. Early recognition and diagnosis of this disease are essential for improving patient prognosis. Here, we report a case of hepatitis B virus-associated decompensated cirrhosis with HM. The patient recovered well after LT. We also summarize the clinical characteristics and post-transplant outcomes of 25 patients with HM treated by LT through 2023, including this case.

Complete Rescue of HTLV-1p12KO Infectivity by Depletion of Monocytes Together with NK and CD8+ T Cells.

The transient depletion of monocytes alone prior to exposure of macaques to HTLV-1 enhances both HTLV-1WT (wild type) and HTLV-1p12KO (Orf-1 knockout) infectivity, but seroconversion to either virus is not sustained over time, suggesting a progressive decrease in virus expression. These results raise the hypotheses that either HTLV-1 persistence depends on a monocyte reservoir or monocyte depletion provides a transient immune evasion benefit. To test these hypotheses, we simultaneously depleted NK cells, CD8+ T cells, and monocytes (triple depletion) prior to exposure to HTLV-1WT or HTLV-1p12KO. Remarkably, triple depletion resulted in exacerbation of infection by both viruses and complete rescue of HTLV-1p12KO infectivity. Following triple depletion, we observed rapid and sustained seroconversion, high titers of antibodies against HTLV-1 p24Gag, and frequent detection of viral DNA in the blood and tissues of all animals when compared with depletion of only CD8+ and NK cells, or monocytes alone. The infection of macaques with HTLV-1WT or HTLV-1p12KO was associated with higher plasma levels of IL-10 after 21 weeks, while IL-6, IFN-γ, IL-18, and IL-1ß were only elevated in animals infected with HTLV-1WT. The repeat depletion of monocytes, NK, and CD8+ cells seven months following the first exposure to HTLV-1 did not further exacerbate viral replication. These results underscore the contribution of monocytes in orchestrating anti-viral immunity. Indeed, the absence of orf-1 expression was fully compensated by the simultaneous depletion of CD8+ T cells, NK cells, and monocytes, underlining the primary role of orf-1 in hijacking host immunity.

A Rare Presentation of Guillain-Barré Syndrome With Associated Horner Syndrome: A Case Report.

Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculoneuropathy involving the peripheral nervous system. Autonomic dysfunctions are well-known complications of GBS and are major contributors to mortality. Autonomic dysfunctions are classically described during the acute phase of illness. In the literature, Horner syndrome as a manifestation of GBS has been reported in very few cases. Here, we describe a case of GBS with an acute presentation of flaccid paraparesis associated with unilateral Horner syndrome. Detecting the cause of acute flaccid paraparesis with unilateral Horner syndrome poses a diagnostic challenge, making it crucial for clinicians to maintain a heightened awareness for distinguishing between GBS and its variants, as well as other potential mimics.

An Ultra-Rare Mixed Phenotype with Combined AP-4 and ERF Mutations: The First Report in a Pediatric Patient and a Literature Review.

The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated trafficking of integral membrane proteins. Mutations affecting all subunits of the AP-4 complex have been linked to autosomal-recessive cerebral palsy and a complex hereditary spastic paraparesis (HSP) phenotype. Our report details the case of a 14-year-old boy born to consanguineous parents, presenting psychomotor delay, severe intellectual disability, microcephaly, and trigonocephaly. Despite a history of febrile seizures, subsequent years were devoid of seizures, with normal EEG. Exome sequencing revealed pathogenic variants in both the AP4B1 and ERF genes. Significantly, the patient exhibited features associated with AP4B1 mutations, including distinctive traits such as cranial malformations. The ERF gene variant, linked to craniosynostosis, likely contributes to the observed trigonocephaly. This case represents the initial documentation of a concurrent mutation in the AP4B1 and ERF genes, underscoring the critical role of exome analysis in unraveling complex phenotypes. Understanding these complex genotypes offers valuable insights into broader syndromic conditions, facilitating comprehensive patient management.

Hereditary spastic paraparesis type 18 (SPG18): new ERLIN2 variants in a series of Italian patients, shedding light upon genetic and phenotypic variability.

INTRODUCTION: Hereditary spastic paraparesis (HSP) is a group of central nervous system diseases primarily affecting the spinal upper motor neurons, with different inheritance patterns and phenotypes. SPG18 is a rare, early-onset, complicated HSP, first reported as linked to biallelic ERLIN2 mutations. Recent cases of late-onset, pure HSP with monoallelic ERLIN2 variants prompt inquiries into the zygosity of such genetic conditions. The observed relationship between phenotype and mode of inheritance suggests a potential dominant negative effect of mutated ERLIN2 protein, potentially resulting in a milder phenotype. This speculation suggests that a wider range of HSP genes could be linked to various inheritance patterns. PURPOSE AND BACKGROUND: With documented cases of HSP loci exhibiting both dominant and recessive patterns, this study emphasizes that the concept of zygosity is no longer a limiting factor in the establishment of molecular diagnoses for HSP. Recent cases have demonstrated phenoconversion in SPG18, from HSP to an amyotrophic lateral sclerosis (ALS)-like syndrome. METHODS AND RESULTS: This report highlights two cases out of five exhibiting HSP-ALS phenoconversion, discussing an observed prevalence in autosomal dominant SPG18. Additionally, the study emphasizes the relatively high incidence of the c.502G>A variant in monoallelic SPG18 cases. This mutation appears to be particularly common in cases of HSPALS phenoconversion, indicating its potential role as a hotspot for a distinctive SPG18 phenotype with an ALS-like syndrome. CONCLUSIONS: Clinicians need to be aware that patients with HSP may show ALS signs and symptoms. On the other hand, HSP panels must be included in genetic testing methods for instances of familial ALS.

[Medullary infarction secondary to endovascular treatment of thoracoabdominal aortic aneurysm] / Infarto medular secundario a tratamiento endovascular de aneurisma de aorta toraco-abdominal.

Medullary infarction is a severe and infrequent pathology, which represents 1% of all ischemic strokes, and is also a rare complication of different surgical procedures. It is caused by the acute interruption of the blood flow of the spinal cord, manifesting itself with clinical neurological deficits related to the affected vascular territory. Methods: We present the case of an 80-year-old patient, with cardiovascular risk factors, who is present on post-surgical day 13, after placement of a vascular endoprosthesis for a thoracoabdominal aneurysm, sudden appearance of paraparesis with progression to paraplegia and hypoesthesia in both lower extremities. CT angiography of the aorta rules out local complications in the endoprosthesis. Medullary MRI showed images compatible with acute dorsal medullary infarction from level D9. Results: On discharge, the patient presented paraplegia and hypoesthesia of both lower extremities with fecal and urinary incontinence. Conclusion: Spinal cord infarction may be limited to a vascular territory or be more extensive according to its pathogenesis. The affectation of the anterior spinal artery is the most common and is characterized by bilateral motor deficits and loss of thermoalgesic sensitivity, which could have a great impact on the quality of life of patients. Its etiology is varied, including aortic surgery within its causes. MRI is very useful for its diagnosis and currently there are no clinical guides for the optimal treatment.

Introducción: El infarto medular es una patología severa e infrecuente, que representa el 1% del total de ictus isquémicos, siendo además una complicación rara de distintos procedimientos quirúrgicos. Es causado por la interrupción aguda del flujo sanguíneo de la médula espinal, manifestándose con déficits neurológicos clínicos relacionados con el territorio vascular afectado. Métodos: Presentamos el caso de un paciente de 80 años, con factores de riesgo cardiovascular, quien presenta en día postquirúrgico 13, tras colocación de endoprótesis vascular por aneurisma toraco-abdominal aparición brusca de paraparesia con progresión a paraplejía e hipoestesia en ambas extremidades inferiores.  Angio-TC de aorta descarta complicación local en la endoprótesis. RM medular mostró imágenes compatibles con Infarto agudo de médula dorsal desde el nivel D9. El paciente no fue subsidiario de tratamiento revascularizador. El tratamiento consistió en medidas de soporte. Resultados: Al alta el paciente presentaba paraplejia e hipoestesia de ambas extremidades inferiores con incontinencia fecal y urinaria. Conclusión: El infarto de la médula espinal puede estar limitado a un territorio vascular o estar más extendido según su patogenia. La afectación de la arteria espinal anterior es la más común y se caracteriza por déficits motores bilaterales y pérdida de la sensibilidad termoalgésica, pudiendo llegar a producir un gran impacto en la calidad de vida de los pacientes. Su etiología es variada, incluyéndose la cirugía aórtica dentro de sus causas. La RM es muy útil para su diagnóstico y actualmente no existen guías clínicas para el tratamiento óptimo.

HTLV in Sweden.

Sweden is a country with a low prevalence of human lymphotropic T-cell virus (HTLV) infection, estimated at < 0.005%, but the infection rate is notably higher in specific risk groups such as HTLV-2 among intravenous drug users (IVDU) and people originating from HTLV-1 highly endemic areas. Thus, in the most recent study from 2012, the prevalence of HTLV-2 among IVDU in Stockholm was 3.2%. However, much of the epidemiological data on HTLV in Sweden stems from studies conducted primarily between the 1990s and 2007, and the impact of migration to Sweden during the past 15 years has not been evaluated. Despite Sweden's status as a country with generally low prevalence of HTLV, it is prudent to anticipate and prepare for several potential challenges associated with HTLV infection in the future. Proactive measures to enhance awareness, alongside strategies to curtail transmission and mitigate complications, are crucial for addressing this relatively rare, but significant health issue. In this work, we review the current epidemiological knowledge about HTLV in Sweden and discuss future Swedish perspectives.

Multicenter, randomized, double-blind, placebo-controlled phase 3 study of mogamulizumab with open-label extension study in a minimum number of patients with human T-cell leukemia virus type-1-associated myelopathy.

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter, randomized phase 3 study evaluated the efficacy and safety of 0.3 mg/kg intravenous mogamulizumab, a monoclonal antibody targeting-CC chemokine receptor 4, every 12 weeks in HAM/TSP patients. This study comprised a 24-week double-blind, placebo-controlled period, 24-week open-label period, and extension treatment period. The primary endpoint was the proportion of patients with a ≥ 1-grade improvement in the Osame motor disability score (OMDS). Secondary endpoints were changes in HTLV-1 proviral load, 10-m timed walk, cerebrospinal fluid (CSF) neopterin levels, and safety. The exploratory endpoint was CSF chemokine C-X-C motif ligand 10 (CXCL10) levels. Thirty-four and 33 patients were randomized to mogamulizumab and placebo arms, respectively. At the end of the double-blind period, no significant difference was found in the OMDS improvement rate or other secondary efficacy endpoints assessing motor activities. However, the mogamulizumab arm showed a significant decrease in HTLV-1 proviral load (- 59.39 ± 29.91% vs. placebo 2.32 ± 36.31%) and CSF neopterin (p < 0.001)/CXCL10 levels (p = 0.004). The baseline OMDS pattern and the 60-80% HTLV-1 proviral load reduction were sustained through the open-label and extension treatment periods. Although a higher incidence of rash (69.2%) was reported, the safety profile was similar compared with a previous phase 1/2a study. We found no significant difference in clinical benefit; however, mogamulizumab may provide long-term clinical benefit by preventing disease progression, as CSF neopterin/CXCL10 levels are associated with long-term prognosis in HAM/TSP.Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).