Sensory Ataxia Research Articles

Chronic Immune Sensory Polyradiculopathy (CISP): A Systematic Review of the Literature

Chronic immune sensory polyradiculopathy (CISP) is a rare inflammatory immune disorder affecting the nervous system, primarily targeting the proximal sensory nerve roots. The condition was first described by Sinreich in 2004. We conducted a systematic review of CISP cases published on PubMed to identify common clinical presentations, along with neurophysiological, radiological, cerebrospinal fluid (CSF), and other findings. Our review included a total of 22 patients from 8 articles. Many patients presented with gait difficulties and sensory ataxia and were found to have normal nerve conduction studies (NCS) and electromyography (EMG) but exhibited characteristic abnormalities in somatosensory evoked potentials (SSEP), elevated CSF protein levels, thickened nerve roots on contrast-enhanced lumbar spine MRIs, and histological changes on nerve root biopsies. Clinical improvement was observed following treatment with steroids and/or intravenous immunoglobulin (IVIG). The study concluded that while CISP is rare, it is an important clinical entity to consider, as accurate diagnosis and appropriate treatment can lead to significant improvements in neurological symptoms and disabilities.

A multiple animal and cellular models approach to study frataxin deficiency in Friedreich Ataxia.

Friedreich's ataxia (FA) is one of the most frequent inherited recessive ataxias characterized by a progressive sensory and spinocerebellar ataxia. The main causative mutation is a GAA repeat expansion in the first intron of the frataxin (FXN) gene which leads to a transcriptional silencing of the gene resulting in a deficit in FXN protein. The nature of the mutation (an unstable GAA expansion), as well as the multi-systemic nature of the disease (with neural and non-neural sites affected) make the generation of models for Friedreich's ataxia quite challenging. Over the years, several cellular and animal models for FA have been developed. These models are all complementary and possess their own strengths to investigate different aspects of the disease, such as the epigenetics of the locus or the pathophysiology of the disease, as well as being used to developed novel therapeutic approaches. This review will explore the recent advancements in the different mammalian models developed for FA.

Characteristics of anti-contactin1 antibody positive autoimmune nodopathies combined with membranous nephropathy

BackgroundAutoimmune nodopathy (AN) is a very rare new disease entity, especially when combined with membranous nephropathy (MN). MethodsAntibodies against nodal-paranodal cell adhesion molecules in the serum were detected using cell-based assays. Antibody subtypes against contactin-1 (CNTN1) were confirmed. Cases of anti-CNTN1 antibody-positive AN with and without MN were retrieved through a literature search to compare clinical and electrophysiological characteristics. ResultsA 65-year-old male patient with MN developed limb numbness and weakness, along with walking instability. Serum CNTN1 antibodies were positive, primarily those of the IgG4 subtype. Electromyography showed prominent demyelination patterns in both the proximal and distal segments of the nerves compared to the middle nerve trunk. Magnetic resonance imaging revealed enlargement of the bilateral brachial and lumbosacral plexuses and local hyperintensity of the right C5-C6 nerve roots. Thirty-five cases with anti-CNTN1 antibody-positive AN with MN and 51 cases with anti-CNTN1 antibody-positive AN without MN were compared. Furthermore, the proportion of patients with MN combined with AN presenting with acute or subacute onset was higher than that observed in the MN without AN group. Nevertheless, no substantial differences were noted between the two groups concerning the clinical and electrophysiological characteristics, which were mainly elderly men, manifested as sensory ataxia, IgG4 antibody subtype, electrophysiological demyelination, and a certain effect on immunotherapy. ConclusionIn cases of electrophysiological manifestation of demyelinating peripheral neuropathy, especially in distal and poximal segments of nerves, AN should be considered, and further screening for renal function should be performed. Concomitant MN does not aggravate or alleviate peripheral nerve symptoms.

Phenotypic variability related to dominant UCHL1 mutations: about three families with optic atrophy and ataxia.

Ubiquitin C-terminal hydrolase L1 (UCHL1) has been associated with a severe, complex autosomal recessive spastic paraplegia (HSP79) [1] [2] [3][4]. More recently, UCHL1 loss of function (LoF) variants have been associated to an autosomal dominant disease characterized by late-onset spastic ataxia, neuropathy, and frequent optic atrophy [5]. Routine clinical care whole-genome (WGS) and exome (ES) sequencing. We present three families with autosomal dominant UCHL1-related disorder. The clinical phenotype mainly associated optic atrophy, mixed cerebellar and sensory ataxia, and possible hearing loss. We delineated two major phenotypes, even within the same family: (1) juvenile severe optic atrophy followed by a later-onset ataxia, or (2) late-onset ataxia with asymptomatic or mild optic atrophy. The families harboured three novel heterozygous variants in UCHL1: two loss of function (p.Lys115AsnfsTer40; c.171_174 + 7del11), and one missense (p.Asp176Asn) involving the catalytic site of the protein and potentially altering the adjacent splice site. We confirm the existence of dominantly inherited UCHL1 pathogenic variants. We describe a considerable intrafamilial phenotypic variability, with two main phenotypes. Optic atrophy was consistently present, but with varying degrees of severity. Neither delayed motor or intellectual development, nor dysmorphic features were part of the dominant phenotype in comparison with the autosomal recessive form. The molecular mechanism appears to be haploinsufficiency. UCHL1 monoallelic variants should therefore be considered in any case of early-onset optic atrophy or in late-onset complex ataxic syndrome with asymptomatic optic atrophy.

Decoding Multiple Antibody Positivity: Lessons from Paraneoplastic Sensory Ataxia.

Paraneoplastic neurologic syndromes are cancer-associated, immune-mediated neurologic manifestations that may involve any part of the nervous system. They usually present with characteristic neurologic features and should be considered in high-risk phenotypes such as limbic encephalitis, encephalomyelitis, rapidly progressive cerebellar syndrome, opsoclonus-myoclonus, sensory neuronopathy, enteric neuropathy, and Lambert-Eaton myasthenic syndrome. The diagnosis is made by antibody positivity in the serum or cerebrospinal fluid, in the presence of an appropriate clinical phenotype. Findings on antibody testing by immunoblot should always be verified by immunofluorescence. We report a rare case of sensory neuronopathy with triple paraneoplastic antibody positivity (anti-Hu, anti-collapsing response-mediator protein 5, and anti-amphiphysin) on immunoblot but only anti-Hu positivity on immunofluorescence. The presence of lower facial dyskinesias should raise the possibility of an immune-mediated neurologic syndrome in the appropriate clinical context.

Romberg's test revisited: Changes in classical and advanced sway metrics in patients with pure sensory neuropathy

ObjectivesThe Romberg test, undoubtedly a classical and well-established method in physical neurological assessment of patients with sensory ataxia, has long been suspected to be prone to several limitations. Here, we quantified upright stance before and after visual deprivation in a selected cohort of patients with pure sensory neuropathy. MethodsStatic balance was assessed in sensory neuropathy patients during quiet stance on a force platform under different visual and proprioceptive feedback conditions. Sural nerve neurography was employed to evaluate the severity of peripheral neuropathy. Conventional and advanced postural sway metrics were investigated to draw a quantitative analogy to the clinical Romberg test. ResultsPosturographic analyses showed that patients displayed Romberg and vestibular Romberg quotient values around 2, indicating an approximately twofold increase in body sway in the absence of vision. However, the diagnostic discrimination ability between patients and controls was only modest. Even less impactful were the diagnostic contributions of frequency domain and non-linear sway analyses. This was primarily attributed to the heightened body sway exhibited by patients with sensory neuropathy under 'eyes open' conditions, diminishing the contrast with the 'eyes closed' condition as assessed in the classical Romberg test. ConclusionWe conclude that the Romberg test, even in its quantitative form with the aid of an apparatus, had an unsatisfactory classification value in terms of distinguishing patients from healthy controls. Instead, it should be interpreted within the comprehensive context of the broader neurological examination and the electrodiagnosis of peripheral nerve function.

Burden of illness and mortality in men with Adrenomyeloneuropathy: a retrospective cohort study

BackgroundAdrenomyeloneuropathy (AMN) is a neurodegenerative disease phenotype of X-linked adrenoleukodystrophy (ALD), resulting in progressive myeloneuropathy causing spastic paraparesis, sensory ataxia, and bowel/bladder symptoms. We conducted a retrospective cohort study using two large administrative databases to characterize mortality and the burden of illness in adult men with AMN in the US.ResultsHealthcare resource use was assessed using a national commercial insurance claims database (2006–2021). Males with AMN ages 18–64 years and no evidence of cerebral ALD or other peroxisomal disorders were included and 1:4 matched on demographic characteristics to individuals without AMN. All study participants were followed for as long as observable. Patients with AMN were also identified in the Medicare Limited Dataset (2017–2022); mortality and age at death were compared with all Medicare enrollees. We identified 303 commercially insured men with AMN. Compared with non-AMN, individuals with AMN had significantly more inpatient hospital admissions (0.44 vs. 0.04 admissions/patient/year), outpatient clinic (8.88 vs. 4.1 visits/patient/year), outpatient hospital (5.33 vs. 0.99 visits/patient/year), and home healthcare visits (4.66 vs. 0.2 visits/patient/year), durable medical equipment claims (0.7 vs. 0.1 claims/patient/year), and prescription medication fills (18.1 vs. 5.4 fills/patient/year) (all p < 0.001). Average length-of-stay per hospitalization was also longer in AMN (8.88 vs. 4.3 days; p < 0.001). Rates of comorbidities were significantly more common in AMN compared to controls, including peripheral vascular disease (4.6% vs. 0.99%), chronic pulmonary disease (6.3% vs. 2.6%), and liver disease (5.6% vs. 0.88%), all p < 0.001. Among individuals age < 65 with Medicare disability coverage, mortality rates were 5.3x higher for adult AMN males (39.3% vs. 7.4%) and the age at death significantly younger (47.0 ± 11.3 vs. 56.5 ± 7.8 years), both p < 0.001. Among Medicare beneficiaries ages ≥ 65 mortality rates were 2.2x higher for men with AMN vs. those without AMN (48.6% vs. 22.4%), p < 0.001.ConclusionAMN imposes a substantial and underrecognized health burden on men, with higher healthcare utilization, greater medical comorbidity, higher mortality rates, and younger age at death.

Atypical presentations in an RTD patient and report of novel SLC52A3 and SLC52A2 mutations.

Riboflavin Transporter Deficiency (RTD) is a rare neurological disorder characterized by pontobulbar palsy, hearing loss, and motor cranial nerve involvement. SLC52A3 and SLC52A2 mutations are causes of RTD. SLC52A2 mutations are usually found in childhood onset cases. Fifteen Iranian RTD diagnosed patients without SLC52A2 mutations have been previously described. We aimed to identify causative mutations in two childhood cases. We recruited patients with diagnosis of BVVL. Comprehensive clinical evaluations were performed on the patients. SLC52A3 and SLC52A2 genes were PCR-amplified and Sanger sequenced. Candidate disease causing variations were screened for segregation with disease status in the respective families and control individuals. A novel homozygous SLC52A3 mutation (p.Met1Val) and a heterozygous SLC52A2 mutation (p.Ala288Val) were both observed in one proband with typical RTD presentations. The aggregate of presentations in the early stages of disease in the second patient that included weakness in the lower extremities, absence of bulbar or hearing defects, prominent sensory polyneuropathy as evidenced in electrodiagnostic studies, and absence of sensory symptoms including sensory ataxia did not prompt immediate RTD diagnosis. Dysarthria and decreased hearing manifested later in the disease course. A novel homozygous SLC52A2 (p.Val314Met) mutation was identified. A literature search found recent reports of other atypical RTD presentations. These include MRI findings, speech understanding difficulties accompanied by normal hearing, anemia, and left ventricular non-compaction. Knowledge of unusual presentations lessens the chance of misdiagnosis or delayed RTD diagnosis which, in light of favorable effects of riboflavin supplementation, is of immense importance.

Autoimmune Nodopathy: When to Suspect and How to Treat?

Autoimmune nodopathy (AN) is a rare condition marked by autoantibodies that target specific proteins located within the node of Ranvier or paranodes. This disorder is distinctly different from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), with AN patients displaying unique clinical symptoms that include acute or subacute onset, primarily distal muscle weakness, sensory ataxia, tremors, and a significant increase in cerebrospinal fluid protein levels. Certain antibodies are linked to specific clinical manifestations; for instance, anti-contactin-1 neuropathy is often accompanied by nephrotic syndrome, whereas anti-pan-neurofascin neuropathy resembles fulminant Guillain-Barre syndrome. In contrast to CIDP patients, who usually experience substantial improvement with intravenous immunoglobulin (IVIG), those with AN may see poor or merely temporary benefits from IVIG therapy. Nonetheless, treatment with the anti-B cell therapy, rituximab, has shown promising results. These findings underscore the critical need for accurate identification of AN's clinical indicators, swift diagnosis of affected individuals, and the application of more effective, targeted treatments for this specific condition.

Autoimmune Nodopathy: When to Suspect and How to Treat?

Autoimmune nodopathy (AN) is a rare condition marked by autoantibodies that target specific proteins located within the node of Ranvier or paranodes. This disorder is distinctly different from chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), with AN patients displaying unique clinical symptoms that include acute or subacute onset, primarily distal muscle weakness, sensory ataxia, tremors, and a significant increase in cerebrospinal fluid protein levels. Certain antibodies are linked to specific clinical manifestations; for instance, anti-contactin-1 neuropathy is often accompanied by nephrotic syndrome, whereas anti-pan-neurofascin neuropathy resembles fulminant Guillain-Barre syndrome. In contrast to CIDP patients, who usually experience substantial improvement with intravenous immunoglobulin (IVIG), those with AN may see poor or merely temporary benefits from IVIG therapy. Nonetheless, treatment with the anti-B cell therapy, rituximab, has shown promising results. These findings underscore the critical need for accurate identification of AN's clinical indicators, swift diagnosis of affected individuals, and the application of more effective, targeted treatments for this specific condition.

Clinical, paraclinical and outcome features of 166 patients with acute anti-GQ1b antibody syndrome.

In this retrospective study, we aimed at defining the clinical, paraclinical and outcome features of acute neurological syndromes associated with anti-GQ1b antibodies. We identified 166 patients with neurological symptoms appearing in less than 1month and anti-GQ1b antibodies in serum between 2012 and 2022. Half were female (51%), mean age was 50years (4-90), and the most frequent clinical features were areflexia (80% of patients), distal upper and lower limbs sensory symptoms (78%), ophthalmoplegia (68%), sensory ataxia (67%), limb muscle weakness (45%) and bulbar weakness (45%). Fifty-three patients (32%) presented with complete (21%) and incomplete (11%) Miller Fisher syndrome (MFS), thirty-six (22%) with Guillain-Barre syndrome (GBS), one (0.6%) with Bickerstaff encephalitis (BE), and seventy-three (44%) with mixed MFS, GBS & BE clinical features. Nerve conduction studies were normal in 46% of cases, showed demyelination in 28%, and axonal loss in 23%. Anti-GT1a antibodies were found in 56% of cases, increased cerebrospinal fluid protein content in 24%, and Campylobacter jejuni infection in 7%. Most patients (83%) were treated with intravenous immunoglobulins, and neurological recovery was complete in 69% of cases at 1year follow-up. One patient died, and 15% of patients relapsed. Age > 70years, initial Intensive Care Unit (ICU) admission, and absent anti-GQ1b IgG antibodies were predictors of incomplete recovery at 12months. No predictors of relapse were identified. This study from Western Europe shows acute anti-GQ1b antibody syndrome presents with a large clinical phenotype, a good outcome in 2/3 of cases, and frequent relapses.

Autoimmune Nodopathy

Autoimmune nodopathy (AN), a newly established category of autoimmune disease, refers to an immune-mediated neuropathy associated with development of autoantibodies against membrane proteins, including neurofascin 186, neurofascin 155, contactin-1, and contactin-associated protein 1 located in the nodes of Ranvier or paranodes. Subclass analysis of these autoantibodies reveals predominant elevation of immunoglobulin (G4. Patients with AN show clinical and laboratory characteristics such as distal-predominant sensorimotor disturbance, sensory ataxia, poor response to intravenous immunoglobulin, and highly elevated cerebrospinal fluid protein levels. B cell-depletion therapy using an anti-CD20 monoclonal antibody is effective for patients with AN. Autoantibody measurement is beneficial not only for diagnosis but also for deciding treatment strategies for AN.

A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy.

Despite linkage to chromosome 16q in 1996, the mutation causing spinocerebellar ataxia type 4 (SCA4), a late-onset sensory and cerebellar ataxia, remained unknown. Here, using long-read single-strand whole-genome sequencing (LR-GS), we identified a heterozygous GGC-repeat expansion in a large Utah pedigree encoding polyglycine (polyG) in zinc finger homeobox protein 3 (ZFHX3), also known as AT-binding transcription factor 1 (ATBF1). We queried 6,495 genome sequencing datasets and identified the repeat expansion in seven additional pedigrees. Ultrarare DNA variants near the repeat expansion indicate a common distant founder event in Sweden. Intranuclear ZFHX3-p62-ubiquitin aggregates were abundant in SCA4 basis pontis neurons. In fibroblasts and induced pluripotent stem cells, the GGC expansion led to increased ZFHX3 protein levels and abnormal autophagy, which were normalized with small interfering RNA-mediated ZFHX3 knockdown in both cell types. Improving autophagy points to a therapeutic avenue for this novel polyG disease. The coding GGC-repeat expansion in an extremely G+C-rich region was not detectable by short-read whole-exome sequencing, which demonstrates the power of LR-GS for variant discovery.

Superior oblique palsy as the initial manifestation of anti-contactin-1 IgG4 autoimmune nodopathy: A case report

Autoimmune nodopathy (AN) is a group of peripheral neuropathies caused by antibodies targeting the nodes of Ranvier or paranodes. It typically presents with sensory ataxia, distal limb weakness, and tremor, and often has a subacute onset, with limited response to immunoglobulin or corticosteroids. We report a case of anti-contactin-1 neuropathy initially manifesting as isolated superior oblique palsy, aiming to broaden the clinical spectrum of the disease. A 68-year-old male with well-controlled diabetes, hypertension, and hyperlipidemia developed acute binocular vertical diplopia, progressing over two months to include distal paresthesia, sensory ataxia, ageusia, and dysarthria. Concurrent nephrotic syndrome was identified. Nerve conduction studies supported demyelination. Despite treatment with intravenous methylprednisolone followed by long-term immunosuppression, some disability persisted. Serum archived during his admission tested positive for anti-contactin-1 IgG, with IgG4 as the predominant subclass, in the flow cytometry assay for AN. This case extends the clinical spectrum of AN. Some cases of isolated cranial nerve palsies, especially in the relevant context like nephrotic syndrome, may be attributed to AN. Prompt initiation of more effective therapies, such as rituximab, could significantly improve outcomes.

A CASE OF SENSORY ATAXIA AND ITS MANAGEMENT THROUGH PANCHAKARMA

Sensory ataxia is both a symptom and a sign in neurology. It is a form of ataxia (loss of coordination) caused not by cerebellar dysfunction but by loss of sensory input into the control of movement. Sensory ataxia is dis-tinguished from cerebellar ataxia by the presence of near-normal coordination when the patient visually observes the movement but marked worsening of coordination when the eyes are shut, indicating a positive Romberg's sign. Sensory ataxia also lacks the associated features of cerebellar ataxia, such as pendular tendon reflexes, scanning dysarthria, nystagmus and broken pursuit eye movements. Sensory ataxia can manifest in sensory large fibre peripheral neuropathies and conditions causing dysfunction of the spinal cord's dorsal columns due to vari-ous disorders: infectious, auto-immune, metabolic, toxic, vascular and hereditary diseases. There is no direct correlation to sensory ataxia in Ayurvedic classics; based on pathology, it is nearer to Kaphavrita vyana vata. Objectives--By considering sensory ataxia as Kaphavrita vyana vata, the present study has attempted to evalu-ate the efficiency of Ayurvedic formulation in the conservative management of sensory ataxia. Met hod-A case of sensory ataxia, initially patient was treated with Dashamoola kaya seka followed by Shastika shalipindasweda, followed by Balavarnakara niruha basti1 and Anuvasana basti with ksheera bala taila as per Kala Basti schedule (modified), followed by Shaman aushadhi. Result-Patient was observed for symptomatic improvement based on the questionnaire over graded signs &amp; symptoms, also observed for clinical examination before &amp; after treatment. Conclusion: The study has shown that conservative management of sensory ataxia can be managed effectively through the Ayurvedic principle and improve quality of life.

Development of a functional outcome measure for riboflavin transporter deficiency.

Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised clinically by pontobulbar palsy, sensory ataxia, sensorineural deafness, muscle weakness, optic atrophy and respiratory failure. A robust and responsive functional outcome measure is essential for future clinical trials of disease-modifying therapies including genetic therapies. The Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS) is a well-validated outcome measure for CMT and related neuropathies, and might have utility for measuring disease progression in individuals with RTD. However, the CMTPedS requires modifications to account for phenotypic differences between children with CMT and RTD. The aim of this study was to develop a functional outcome measure based on the CMTPedS for specific use in individuals with RTD. The CMTPedS data collected over the last 10 years in individuals with RTD attending the Peripheral Neuropathy Management Clinic at the Children's Hospital at Westmead (Sydney, Australia) were reviewed to evaluate each item within the CMTPedS. A literature review of articles published until September 2021 for functional outcome measures generated an item pool for pilot testing. The results of this pilot testing, alongside analysis of existing CMTPedS item scores in the RTD cohort, informed the modification of the CMTPedS. CMTPedS data were reviewed for eight individuals over the past 10 years. Two items were identified as requiring modification or removal and additional items of proximal strength and function needed to be considered. Six studies were identified in the literature review, and five items were selected for pilot testing. 'Shoulder internal rotation' and the '30-s sit to stand test' were added as proximal measures of strength and function. The composite balance item comprising nine tasks in the CMTPedS showed a ceiling effect and was replaced with the single 'Feet apart on a line eyes open' balance item. 'Pinprick sensation' was removed due to a floor effect. This study provides preliminary evidence that the Riboflavin Transporter Deficiency Pediatric Scale (RTDPedS) is a functional outcome measure covering strength, upper and lower limb function, balance and mobility for individuals with RTD to assess disease severity and progression in clinical trials and cohort studies.

Autoantibodies Against Dihydrolipoamide S-Acetyltransferase in Immune-Mediated Neuropathies.

This study aimed to identify disease-related autoantibodies in the serum of patients with immune-mediated neuropathies including chronic inflammatory demyelinating polyneuropathy (CIDP) and to investigate the clinical characteristics of patients with these antibodies. Proteins extracted from mouse brain tissue were used to react with sera from patients with CIDP by western blotting (WB) to determine the presence of common bands. Positive bands were then identified by mass spectrometry and confirmed for reactivity with patient sera using enzyme-linked immunosorbent assay (ELISA) and WB. Reactivity was further confirmed by cell-based and tissue-based indirect immunofluorescence assays. The clinical characteristics of patients with candidate autoantibody-positive CIDP were analyzed, and their association with other neurologic diseases was also investigated. Screening of 78 CIDP patient sera by WB revealed a positive band around 60-70 kDa identified as dihydrolipoamide S-acetyltransferase (DLAT) by immunoprecipitation and mass spectrometry. Serum immunoglobulin G (IgG) and IgM antibodies' reactivity to recombinant DLAT was confirmed using ELISA and WB. A relatively high reactivity was observed in 29 of 160 (18%) patients with CIDP, followed by patients with sensory neuropathy (6/58, 10%) and patients with MS (2/47, 4%), but not in patients with Guillain-Barré syndrome (0/27), patients with hereditary neuropathy (0/40), and healthy controls (0/26). Both the cell-based and tissue-based assays confirmed reactivity in 26 of 33 patients with CIDP. Comparing the clinical characteristics of patients with CIDP with anti-DLAT antibodies (n = 29) with those of negative cases (n = 131), a higher percentage of patients had comorbid sensory ataxia (69% vs 37%), cranial nerve disorders (24% vs 9%), and malignancy (20% vs 5%). A high DLAT expression was observed in human autopsy dorsal root ganglia, confirming the reactivity of patient serum with mouse dorsal root ganglion cells. Reactivity to DLAT was confirmed in patient sera, mainly in patients with CIDP. DLAT is highly expressed in the dorsal root ganglion cells, and anti-DLAT antibody may serve as a biomarker for sensory-dominant neuropathies.

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

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. 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. 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. 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.

Hereditary Ataxias: From Bench to Clinic, Where Do We Stand?

Cerebellar ataxias are a wide heterogeneous group of movement disorders. Within this broad umbrella of diseases, there are both genetics and sporadic forms. The clinical presentation of these conditions can exhibit a diverse range of symptoms across different age groups, spanning from pure cerebellar manifestations to sensory ataxia and multisystemic diseases. Over the last few decades, advancements in our understanding of genetics and molecular pathophysiology related to both dominant and recessive ataxias have propelled the field forward, paving the way for innovative therapeutic strategies aimed at preventing and arresting the progression of these diseases. Nevertheless, the rarity of certain forms of ataxia continues to pose challenges, leading to limited insights into the etiology of the disease and the identification of target pathways. Additionally, the lack of suitable models hampers efforts to comprehensively understand the molecular foundations of disease's pathophysiology and test novel therapeutic interventions. In the following review, we describe the epidemiology, symptomatology, and pathological progression of hereditary ataxia, including both the prevalent and less common forms of these diseases. Furthermore, we illustrate the diverse molecular pathways and therapeutic approaches currently undergoing investigation in both pre-clinical studies and clinical trials. Finally, we address the existing and anticipated challenges within this field, encompassing both basic research and clinical endeavors.

Clinical Features of Autoimmune Nodopathy With Anti-Neurofascin-155 Antibodies in South Koreans.

Anti-neurofascin-155 (NF155) antibody is one of the autoantibodies associated with autoimmune nodopathy. We aimed to determine the clinical features of South Korean patients with anti-NF155-antibody-positive autoimmune nodopathy. The sera of 68 patients who fulfilled the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) were tested for anti-NF155 antibodies using a cell-based assay (CBA) and enzyme-linked immunosorbent assay (ELISA). The anti-NF155-positive sera were also assayed for NF155 immunoglobulin G (IgG) subclasses, and for anti-NF186 and NF140 antibodies. The clinical features of the patients were reviewed retrospectively. Among the 68 patients, 6 (8.8%) were positive for anti-NF155 antibodies in both the CBA and ELISA. One of those six patients was also positive for anti-NF186 and anti-NF140 antibodies. IgG4 was the predominant subclass in four patients. The mean age at onset was 32.2 years. All six positive patients presented with progressive sensory ataxia. Five patients treated using corticosteroids presented a partial or no response. All six patients were treated using intravenous immunoglobulin (IVIg). Among them, five exhibited a partial or poor response and the other exhibited a good response. All three patients treated using rituximab showed a good response. The clinical characteristics of the patients were consistent with those in previous studies. Anti-NF155 antibody assay is necessary for diagnosing autoimmune nodopathy and its appropriate treatment, especially in young patients with CIDP who present with sensory ataxia and poor therapeutic responses to corticosteroids and IVIg.