[Proposals for the early diagnosis of late-onset hereditary ATTR amyloidosis in |nonendemic areas in Japan].

Late-onset hereditary ATTR (ATTRv) amyloidosis in nonendemic areas takes long periods of time to diagnose in many cases because the clinical symptoms are varied and nonspecific with the family history often unidentifiable. In recent years, disease-modifying therapies have been available for ATTRv amyloidosis, and early diagnosis is increasingly needed. The diagnosis of ATTRv amyloidosis usually requires histological confirmation of the amyloid deposition, although the amyloid detection rate largely depends on the experience, knowledge, and skill of the physician who performs the biopsy. It is important to consider ATTRv amyloidosis as a differential disease in idiopathic polyneuropathy. If ATTRv amyloidosis is strongly suspected, it is acceptable to perform TTR genetic testing prior to histological examination after a thorough differential diagnosis has been made.

Cerebral small vessel disease markers and long-term prognosis in spontaneous intracerebral hemorrhage: the HAGAKURE-ICH study.

We investigated the effects of individual and cumulative cerebral small vessel disease (SVD) markers on long-term clinical outcomes in spontaneous intracerebral hemorrhage (sICH) patients. This prospective, single-center cohort study was conducted from 2012 to 2019. SVD markers, including lacunae, cerebral microbleeds, white matter hyperintensity (WMH), and perivascular spaces in the basal ganglia, were assessed to calculate a summary SVD score. Patients were categorized into severe (score ≥3) and non-severe (score 0-2) SVD burden groups. Functional prognosis was defined as recovery, no change, or decline based on modified Rankin Scale changes at 2 years after discharge, excluding death. Associations of SVD burden and individual SVD markers with outcomes were evaluated using Cox proportional hazards modeling for recurrent stroke and all-cause mortality, and using ordinal logistic regression for functional prognosis. Among 155 sICH patients who underwent MRI, 98 showed severe SVD burden. Recurrent stroke and all-cause mortality rates were 2.2 and 8.3 per 100 patient-years, respectively, over a median 2.1-year follow-up. In terms of functional prognosis, 57 patients (51.8%) recovered, 32 (29.1%) showed no change, and 21 (19.1%) declined. A significant association was apparent between severe SVD burden and poorer functional prognosis (odds ratio [OR] 2.48, 95% confidence interval [CI] 1.04-6.04; p = 0.042), particularly with moderate-to-severe WMH (OR 2.54, 95%CI 1.02-6.54; p = 0.048). The cumulative effects of SVD markers inhibited long-term functional recovery in sICH patients. Severe SVD burden, as well as moderate-to-severe WMH, can be indicators of long-term prognosis after sICH.

Efgartigimod Successfully Ameliorated Acute Exacerbation of Myasthenia Gravis with Anti-muscle-specific Kinase Antibodies.

We herein report two patients with anti-muscle-specific kinase (MuSK) antibody-positive myasthenia gravis who experienced rapid deterioration of weakness, particularly respiratory muscle weakness, necessitating non-invasive positive pressure ventilation (NIPPV) and were treated with efgartigimod. After treatment initiation, a rapid reduction in IgG levels and recovery from clinical symptoms were observed. NIPPV was no longer required two to three weeks after the first infusion of efgartigimod. These findings suggest that the reduction of IgG levels using efgartigimod is a good treatment option in patients with myasthenia gravis positive for anti-MuSK antibodies, even during the acute phase of the disease.

Involvement of the nigrostriatal system in Gerstman-Sträussler-Scheinker disease with the PRNP-P102L mutation.

INTRODUCTION: Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal-dominant inherited prion disease most often associated with the human prion protein gene (PRNP)-P102L mutation. Although patients manifest considerable phenotypic heterogeneity, the involvement of the nigrostriatal system has not been well-studied. METHODS: We performed dopamine transporter single-photon emission computed tomography (DAT-SPECT) using 123I-ioflupane to investigate the nigrostriatal system function in nine patients with the PRNP-P102L mutation. We also examined the pathological findings in another patient whose predominant feature was ataxia and who died 5 years after disease onset. RESULTS: Striatum uptake of 123I-ioflupane indicated by specific binding ratio (SBR) values was significantly reduced in two patients. The DAT-SPECT examination was performed 6 months after disease onset in one of these patients who manifested rapidly developing cognitive decline mimicking Creutzfeldt-Jakob disease. DAT-SPECT was also performed 9 years after disease onset in another patient who manifested the conventional features of GSS involving ataxia and dementia in the initial phase but showed akinetic mutism at the examination time. Another patient examined 2 years after disease onset who predominantly manifested ataxia showed marginally abnormal SBR values. An autopsy case showed moderate neuronal loss in the substantia nigra, and the degree of neuronal loss was similar in most other parts of the brain. CONCLUSION: Nigrostriatal system involvement may occur in patients with GSS associated with the PRNP-P102L mutation, even though parkinsonism is not the predominant feature.

[Modern Perspectives on Peripheral Neuropathology].

Recent advances in genetic and antibody testing have limited pathological examination of peripheral nerve specimens. However, when examining peripheral neuropathological findings from a modern perspective, there is often an opportunity to comprehend previously unnoticed observations upon re-examining the same specimen. For example, electron microscopy studies have suggested that the components that distinguish between nodal regions and internodes play a pivotal role in the behavior of macrophages that initiate myelin phagocytosis in the demyelinating form of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP). Conversely, some patients previously diagnosed with CIDP were found to possess distinctive mechanisms initiated by autoantibodies against paranodal junction proteins such as neurofascin 155 leading to the emergence of the concept of autoimmune nodopathy. In vasculitis, the roles of neutrophils in antineutrophil cytoplasmic antibody-associated vasculitis, eosinophils in eosinophilic granulomatosis with polyangiitis, and complements in nonsystemic vasculitic neuropathy in tissue damage have also been demonstrated when viewed from a modern perspective. Furthermore, mechanisms attributable to predominant small-fiber loss in hereditary transthyretin amyloidosis have been clarified at an ultrastructural level.

Subarachnoid iodine leakage on dual-energy computed tomography after mechanical thrombectomy is associated with malignant brain edema.

BACKGROUND: Dual-energy computed tomography (DE-CT) can differentiate between hemorrhage and iodine contrast medium leakage following mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We determined whether subarachnoid hemorrhage (SAH) and subarachnoid iodine leakage (SAIL) on DE-CT following MT were associated with malignant brain edema (MBE). METHODS: We analyzed the medical records of 81 consecutive anterior circulation AIS patients who underwent MT. SAH or SAIL was diagnosed via DE-CT performed immediately after MT. We compared the procedural data, infarct volumes, MBE, and modified Rankin scale 0-2 at 90 days between patients with and without SAH and between patients with and without SAIL. Furthermore, we evaluated the association between patient characteristics and MBE. RESULTS: A total of 20 (25%) patients had SAH and 51 (63%) had SAIL. No difference in diffusion-weighted imaging (DWI)-infarct volume before MT was observed between patients with and without SAH or patients with and without SAIL. However, patients with SAIL had larger DWI-infarct volumes 1 day following MT than patients without SAIL (95 mL vs 29 mL; p=0.003). MBE occurred in 12 of 81 patients (15%); more patients with SAIL had MBE than patients without SAIL (22% vs 3%; p=0.027). Severe SAIL was significantly associated with MBE (OR, 12.5; 95% CI, 1.20-131; p=0.006), whereas SAH was not associated with MBE. CONCLUSION: This study demonstrated that SAIL on DE-CT immediately after MT was associated with infarct volume expansion and MBE.

Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis.

Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of autoantibodies is important for distinguishing the disease from other neuropathies that present with autonomic dysfunction, other factors are important for accurate diagnosis. Here, we provide a comprehensive review of the clinical features of AAG, highlighting differences in clinical course, clinical presentation, and laboratory findings from other neuropathies presenting with autonomic symptoms. The first step in diagnosing AAG is careful history taking, which should reveal whether the mode of onset is acute or chronic, followed by an examination of the time course of disease progression, including the presentation of autonomic and extra-autonomic symptoms. AAG is a neuropathy that should be differentiated from other neuropathies when the patient presents with autonomic dysfunction. Immune-mediated neuropathies, such as acute autonomic sensory neuropathy, are sometimes difficult to differentiate, and therefore, differences in clinical and laboratory findings should be well understood. Other non-neuropathic conditions, such as postural orthostatic tachycardia syndrome, chronic fatigue syndrome, and long COVID, also present with symptoms similar to those of AAG. Although often challenging, efforts should be made to differentiate among the disease candidates.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

RNA Foci in Two bi-Allelic RFC1 Expansion Carriers.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, autosomal recessive neurodegenerative disorder caused by biallelic AAGGG/ACAGG repeat expansion (AAGGG-exp/ACAGG-exp) in RFC1. The recent identification of patients with CANVAS exhibiting compound heterozygosity for AAGGG-exp and truncating variants supports the loss-of-function of RFC1 in CANVAS patients. We investigated the pathological changes in 2 autopsied patients with CANVAS harboring biallelic ACAGG-exp and AAGGG-exp. RNA fluorescence in situ hybridization of the 2 patients revealed CCTGT- and CCCTT-containing RNA foci, respectively, in neuronal nuclei of tissues with neuronal loss. Our findings suggest that RNA toxicity may be involved in the pathogenesis of CANVAS. ANN NEUROL 2024;95:607-613.

Granuloma, vasculitis, and demyelination in sarcoid neuropathy.

BACKGROUND: Despite the suggestion that direct compression by granuloma and ischemia resulting from vasculitis can cause nerve fiber damage, the mechanisms underlying sarcoid neuropathy have not yet been fully clarified. METHODS: We examined the clinicopathological features of sarcoid neuropathy by focusing on electrophysiological and histopathological findings of sural nerve biopsy specimens. We included 18 patients with sarcoid neuropathy who had non-caseating epithelioid cell granuloma in their sural nerve biopsy specimens. RESULTS: Although electrophysiological findings suggestive of axonal neuropathy were observed, particularly in the lower limbs, all but three patients showed ≥1 abnormalities in nerve conduction velocity or distal motor latency. Additionally, a conduction block was observed in 11 of the 16 patients for whom waveforms were assessed; five of them fulfilled motor nerve conduction criteria strongly supportive of demyelination as defined in the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guideline for chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, sural nerve biopsy specimens revealed a mild to moderate degree of myelinated fiber loss. Fibrinoid necrosis was observed in one patient, and electron microscopy analysis revealed demyelinated axons close to granulomas in six patients. CONCLUSIONS: Patients with sarcoid neuropathy may meet the EAN/PNS electrophysiological criteria for CIDP due to the frequent presence of conduction blocks. Based on our results, in addition to the ischemic damage resulting from granulomatous inflammation, demyelination may play an important role in the mechanism underlying sarcoid neuropathy.

Clinicopathological features of graft versus host disease-associated myositis.

BACKGROUND AND OBJECTIVE: Chronic graft versus host disease (GVHD)-associated myositis targeting skeletal muscle is a relatively rare but potentially debilitating complication following allogeneic hematopoietic stem cell transplantation (HSCT). We reviewed the clinicopathological features of GVHD-associated myositis among patients receiving allogeneic HSCT to elucidate the cellular pathogenesis. METHODS: We retrospectively reviewed clinical data and muscle biopsy results from 17 consecutive patients diagnosed with GVHD-associated myositis at our institution between 1995 and 2019. Immunostaining findings of GVHD-associated myositis were compared to those of patients with anti-tRNA-synthetase antibody-associated myopathy (ASM) (n = 13) and dermatomyositis (DM) (n = 12). RESULTS: The majority of patients with GVHD-associated myositis showed subacute or chronic progression of mild to moderate limb weakness together with elevated serum creatine kinase. These patients also exhibited mild C-reactive protein elevation but were negative for myositis-related autoantibodies. Programmed death-1 (PD-1)-positive cells were observed in muscle interstitium adjacent to myofibers expressing human leukocyte antigen (HLA)-DR. The interstitium was also HLA-DR-positive, similar to biopsy samples from ASM patients but not DM patients. The proportions of HLA-DR-positive muscle fibers and PD-1-positive interstitial cells were significantly higher in GVHD and ASM samples than DM samples. The PD-1-positive cells were mostly CD-8-positive lymphocytes. DISCUSSION: GVHD-associated myositis is characterized by HLA-DR-positive myofibers and infiltration of PD-1-positive lymphocytes. These features distinguish GVHD-associated myositis from DM but not from ASM.

Optimal practices for the management of hereditary transthyretin amyloidosis: real-world experience from Japan, Brazil, and Portugal.

Hereditary transthyretin (ATTRv) amyloidosis is a rare and autosomal dominant disorder associated with mutations in the transthyretin gene. Patients present with diverse symptoms related to sensory, motor, and autonomic neuropathy, as well as gastrointestinal, ocular, cardiac, renal and orthopedic symptoms, resulting from the deposition of transthyretin amyloid fibrils in multiple organs. The progressive nature of ATTRv amyloidosis necessitates pre- and post-onset monitoring of the disease. This review article is primarily based on a collation of discussions from a medical advisory board meeting in August 2021. In this article, we summarize the best practices in amyloidosis centers in three major endemic countries for ATTRv amyloidosis (Japan, Brazil, and Portugal), where most patients carry the Val30Met mutation in the transthyretin gene and the patients' genetic background was proven to be the same. The discussions highlighted the similarities and differences in the management of asymptomatic gene mutation carriers among the three countries in terms of the use of noninvasive tests and tissue biopsies and timing of starting the investigations. In addition, this article discusses a set of practical tests and examinations for monitoring disease progression applicable to neurologists working in diverse medical settings and generalizable in non-endemic countries and areas. This set of assessments consists of periodic (every 6 to 12 months) evaluations of patients' nutritional status and autonomic, renal, cardiac, ophthalmologic, and neurological functions. Physical examinations and patient-reported outcome assessments should be also scheduled every 6 to 12 months. Programs for monitoring gene mutation carriers and robust referral networks can aid in appropriate patient management in pre- to post-onset stages. For pre- and post-symptom onset testing for ATTRv amyloidosis, various noninvasive techniques are available; however, their applicability differs depending on the medical setting in each country and region, and the optimal option should be selected in view of the clinical settings, medical environment, and available healthcare resources in each region.

Impact of Vutrisiran on Quality of Life and Physical Function in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy.

INTRODUCTION: Hereditary transthyretin (ATTRv; v for variant) amyloidosis, also known as hATTR amyloidosis, is a progressive and fatal disease associated with rapid deterioration of physical function and patients' quality of life (QOL). Vutrisiran, a subcutaneously administered RNA interference (RNAi) therapeutic that reduces hepatic production of transthyretin, was assessed in patients with ATTRv amyloidosis with polyneuropathy in the pivotal HELIOS-A study. METHODS: The phase 3 open-label HELIOS-A study investigated the efficacy and safety of vutrisiran in patients with ATTRv amyloidosis with polyneuropathy, compared with an external placebo group from the APOLLO study of the RNAi therapeutic patisiran. Measures of QOL and physical function were assessed. RESULTS: At month 18, vutrisiran improved Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) total score (least squares mean difference [LSMD] in change from baseline [CFB]: -21.0; p = 1.84 × 10-10) and Norfolk QOL-DN domain scores, compared with external placebo. This benefit relative to external placebo was evident across all baseline polyneuropathy disability (PND) scores and most pronounced in patients with baseline PND scores I-II. Compared with external placebo, vutrisiran also demonstrated benefit in EuroQoL-Visual Analog Scale (EQ-VAS) score (LSMD in CFB: 13.7; nominal p = 2.21 × 10-7), 10-m walk test (LSMD in CFB: 0.239 m/s; p = 1.21 × 10-7), Rasch-built Overall Disability Score (LSMD in CFB: 8.4; p = 3.54 × 10-15), and modified body mass index (mBMI) (LSMD in CFB: 140.7; p = 4.16 × 10-15) at month 18. Overall, Norfolk QOL-DN, EQ-VAS, and mBMI improved from pretreatment baseline with vutrisiran, whereas all measures worsened from baseline in the external placebo group. At month 18, Karnofsky Performance Status was stable/improved from baseline in 58.2/13.1% with vutrisiran versus 34.7/8.1% with external placebo. CONCLUSION: Vutrisiran treatment provided significant clinical benefits in multiple measures of QOL and physical function in patients with ATTRv amyloidosis with polyneuropathy. Benefits were most pronounced in patients with earlier-stage disease, highlighting the importance of early diagnosis and treatment. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT03759379.

A Bioelectrical Impedance Analysis for the Assessment of Muscle Atrophy in Patients with Chronic Inflammatory Demyelinating Polyneuropathy.

Objective Muscle atrophy is observed in a subset of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Its manifestation is associated with a poor functional prognosis and poor response to immunomodulatory therapies. We evaluated muscle atrophy in patients with CIDP using a bioelectrical impedance analysis (BIA). Methods We enrolled 12 patients with CIDP for a BIA of muscle atrophy. Of these 12 patients, 10 were diagnosed with typical CIDP, 1 with multifocal acquired demyelinating sensory and motor neuropathy, and 1 with distal acquired demyelinating symmetric neuropathy. All 12 patients underwent a series of assessments and evaluations, including a BIA and computed tomography (CT). A correlation was found between the skeletal muscle mass determined by the BIA and that found using CT of the muscles. Results The BIA provided values for each patient's skeletal muscle mass index (SMI) ranging from 4.1 to 8.1 kg/m2. Four of the patients with CIDP had SMI values below the threshold for sarcopenia. CT of the patients' muscles provided scores indicating grades of muscle atrophy in the upper and lower extremities. A comparison of the outcomes from these two measures showed a good correlation between their muscle atrophy ratings (p<0.05). Conclusion We found that a BIA and muscle CT provided muscle atrophy assessments of equivalent accuracy. Therefore, a BIA can be a simple alternative to muscle CT that is suitable for regular use in daily clinical practice as a reliable tool for assessing muscle atrophy in patients with CIDP.

Neurogenic intermittent claudication caused by vasculitis in the cauda equina: an autopsy case report.

PURPOSE: Intermittent claudication (IC) refers to leg pain that is induced by walking and relieved by rest. Neurogenic IC is usually associated with lumbar canal stenosis (LCS). We present rare findings from an autopsied patient who had neurogenic IC caused by vasculitis in the cauda equina. METHODS: We performed antemortem neurological and electrophysiological assessments, sural nerve biopsy, and post-mortem examination of the spinal cord and brain. RESULTS: A 61-year-old man noted sudden-onset leg pain that was not associated with any traumatic trigger. His leg pain consistently appeared when the patient walked and quickly faded on stopping. Spine surgery and cardiovascular departments both made a diagnosis of IC. However, magnetic resonance imaging (MRI) did not show LCS, and all ankle-brachial pressure indices were normal. He subsequently developed diffuse muscle weakness of the legs a month after disease onset. Myeloperoxidase antineutrophil cytoplasmic autoantibody was seropositive (140 IU/mL), and a sural nerve biopsy revealed axonal injury and angiitis. MRI showed multiple cerebral infarctions. He was diagnosed with microscopic polyangiitis (MPA) and underwent corticosteroid therapy. He died from complications two months after the onset. A post-mortem study revealed vasculitis in the subarachnoid space of the cauda equina, spinal cord, and brain parenchyma. The cauda equina showed a combined loss of small and large axonal fibres. The lumbar cord displayed central chromatolysis of the lower motor neurons. CONCLUSION: MPA is a rare cause of neurogenic IC when the symptom is acute and multimodal. Small-vessel vasculitis affecting the cauda equina may underlie MPA-associated IC.

A Review of Anti-IL-5 Therapies for Eosinophilic Granulomatosis with Polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a systemic disorder characterized by asthma, eosinophilia, and vasculitis primarily affecting small vessels. Although this disease is classified as an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis along with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), observations suggest that eosinophils play a vital role in the pathophysiology of EGPA. Therefore, biopsy specimens derived from patients with EGPA demonstrated an increase in eosinophils within the vascular lumen and extravascular interstitium, especially in patients negative for ANCA. In addition, active secretion of eosinophil intracellular components by cytolysis and piecemeal degranulation occurs in the extravascular interstitium and bloodstream. Although the treatment for EGPA is described in the context of ANCA-associated vasculitis along with MPA and GPA, a therapeutic approach to suppress eosinophils is also considered. Monoclonal antibodies directed against interleukin-5 (IL-5) or its receptors are good therapeutic agents because IL-5 plays an important role in eosinophil growth, activation, and survival. Currently, mepolizumab (Nucala), reslizumab (Cinqair), and benralizumab (Fasenra) have been studied for use in patients with EGPA. These monoclonal antibodies were initially approved for use in patients with severe eosinophilic asthma. Mepolizumab is now approved for treating EGPA following the success of phase 3 randomized controlled trial. Therefore, further studies are needed to clarify long-term safety and efficacy of anti-IL-5 agents and establish indications of individual therapeutic agents tailored to individual conditions of patients with EGPA.

Demyelinating Neuropathy with Markedly Elevated Serum IgG4 Levels and Anti-Contactin 1 IgG4 Antibody.

We herein report a 77-year-old man with a 4-month history of progressive gait and sensory disturbances of the extremities. A nerve conduction study indicated demyelinating polyneuropathy. Serum IgG4 levels and anti-contactin 1 IgG4 antibodies were markedly increased. The sural nerve biopsy specimen showed IgG4-positive plasma cell infiltration in the epineurium. Treatment with steroids resulted in an amelioration of functional status, improvement of nerve conduction parameters, decreased serum IgG4 levels, and negative conversion of anti-contactin 1 antibody. Further studies are needed to clarify the significance of IgG4-positive plasma cell infiltration in anti-contactin 1 antibody-positive neuropathies.