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.

Pathogenic role of anti-cN1A autoantibodies in sporadic inclusion body myositis.

BACKGROUND: Sporadic inclusion body myositis (sIBM) is an intractable muscle disease that frequently affects elderly people. Autoantibodies recognising cytosolic 5'-nucleotidase 1A (cN1A) were found in the sera of patients with sIBM. However, the pathogenic role of the autoantibodies remained unknown. This study investigated the pathogenic properties of the autoantibodies using active cN1A peptides immunisation. METHODS: Wild-type C57BL6 mice were injected with three different mouse cN1A peptides corresponding to the previously reported epitope sequences of human cN1A. After confirming the production of autoantibodies to the corresponding cN1A peptides in each group, changes in body weight, exercise capacity by treadmill test and histological changes in mice injected with cN1A peptides or controls were investigated. RESULTS: Autoantibodies against cN1A were detected in serum samples from mice injected with cN1A peptide. Some groups of mice injected with cN1A peptide showed significant weight loss and decreased motor activity. The number of myofibres with internal nuclei increased in all the peptide-injected groups, with surrounding or invading CD8-positive T cells into myofibres, abnormal protein aggregates and overexpression of p62 and LC3. CONCLUSIONS: Active cN1A peptide immunisation partially reproduced the clinical and histological aspects of sIBM in wild-type mice. The murine model demonstrates the pathogenic properties of anti-cN1A autoantibodies to cause sIBM-like histological changes.

[Autoimmune Autonomic Ganglionopathy: Solving the 10 Assignments].

Autoimmune autonomic ganglionopathy (AAG) is a rare acquired immune-mediated neurological disease that causes various autonomic symptoms. AAG is induced by autoantibodies for the α3 and ß4 subunits of the ganglionic acetylcholine receptor (gAChR). gAChR antibodies mediate synaptic transmission in all autonomic ganglia, resulting in dysautonomia. Recent clinical and basic research topics in AAG include the following: 1)analysis of clinical features; 2)novel methods for gAChR antibody detection; 3)efficacy of combined immunotherapy; 4)novel experimental AAG; 5)COVID-19 and mRNA COVID-19 vaccination and its association with autonomic dysfunction; and 6)dysautonomia as an immune-related adverse event of immune checkpoint inhibitors in cancer therapy. The author and his collaborators have previously established "10 assignments" to understand the basic research and clinical issues of AAG. In this review, the author describes the current status of research on each of the "10 assignments," incorporating research trends over the last five years.

Immunotherapy for ocular myasthenia gravis: an observational study in Japan.

Background: Treatment for ocular myasthenia gravis (OMG) has not yet been well established. Few reports have been published on the clinical practice and outcomes of OMG. Objectives: We investigated treatment of OMG and its outcomes in Japan.We investigated treatment of OMG and its outcomes in Japan. Design: We performed a retrospective cross-sectional survey of OMG patients from eight hospitals in Japan. Methods: Clinical information, including sex, age at onset, initial symptoms, autoantibodies, clinical course, treatment history, complications, and outcomes, was obtained. In addition, we recorded the total number of patients with MG and OMG separately. Results: In total, 135 patients with OMG (67 men, 68 women) were included. Treatment of OMG was not simple and involved various immunotherapeutic strategies. Eight patients went into remission spontaneously without immunotherapy. A total of 117 patients showed improvements after treatment, whereas 10 patients showed refractory responses to treatment. Overall outcomes were good; however, symptoms persisted in 60.7% of patients even after treatment. Among 90 patients who received immunotherapy, only two showed a refractory response. Meanwhile, for 45 patients who did not receive immunotherapy, 8 were refractory. Thus, the rate of refractory disease in the group with immunotherapy was significantly lower (p = 0.001, u-test) than in the group without immunotherapy. The proportion of generalized MG patients among all MG cases was low in medical centers where immunotherapy for OMG was frequently performed. Conclusion: Although the overall prognosis for patients with OMG was good, symptoms remained in more than half of the patients. Immunotherapy, including corticosteroids, may be beneficial for patients with OMG. Plain language summary: Is immunosuppressive therapy beneficial for myasthenia gravis patients with ocular symptoms only? Patients with ocular myasthenia gravis (OMG) have only eye symptoms for more than 2 years. Whether this condition is an initial stage of the disease before eventually progressing to generalized myasthenia gravis (gMG) is still uncertain. Different from gMG, OMG is not life-threatening. But eye symptoms often cause troublesome problems in life. Doctors have treated OMG patients similarly to patients with gMG. There is no standard clinical practice for OMG. In this study, we examined how patients with OMG were treated at eight different specialist centers in Japan. In 135 patients with OMG, 8 patients became symptom free without treatment, 117 patients showed improvements after treatment, whereas 10 patients did not get well. Overall outcomes were good, but symptoms remained in 60.7% of patients even after treatment. Among 90 patients who received one or more immunotherapies, only 2 did not get well. Meanwhile, for 45 patients who did not receive immunotherapy, 8 remained ill. We found that treatment of OMG was not simple and often needed multiple immunotherapies. Administering immunotherapy, including corticosteroids, may be beneficial for patients with OMG.

Dysautonomia associated with immune checkpoint inhibitors.

OBJECTIVE: The purpose of this study is to report the clinical characteristics of dysautonomia associated with immune checkpoint inhibitors (ICIs). METHODS: We reported two patients with autoimmune autonomic ganglionopathy (AAG) occurring as immune-related adverse events (irAEs). We also performed a review of previous case reports presenting dysautonomia during ICI therapy. Moreover, we conducted pharmacovigilance analyses using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to investigate dysautonomia associated with ICI. RESULTS: Two patients in our care developed both AAG and autoimmune encephalitis following ICI therapy for lung cancers. We comprehensively reviewed 13 published cases (M:F = 11:2, mean onset age of 53 years) with ICI-associated dysautonomia including AAG (n = 3) and autonomic neuropathy (n = 10). Of these, ICI monotherapy was performed in seven and combination ICI use in six. In 6 of 13 patients, dysautonomia appeared within one month after the start of ICIs. Orthostatic hypotension was observed in 7 and urinary incontinence or retention in five. All patients except three showed gastrointestinal symptoms. Anti-ganglionic acetylcholine receptor antibodies were undetectable. All but two patients received immune-modulating therapy. Immuno-modulating therapy was effective in three patients with AAG and two patients with autonomic neuropathy, but ineffective in the others. Five patients died, of either the neurological irAE (n = 3) or cancer (n = 2). The pharmacovigilance analyses using FAERS showed that ipilimumab monotherapy and the combination of nivolumab and ipilimumab constituted significant risks for developing dysautonomia, consistent with the review of literature. CONCLUSION: ICIs can cause dysautonomia including AAG, and autonomic neuropathy is a neurological irAE.

Anti-ganglionic acetylcholine receptor antibodies in functional neurological symptom disorder/conversion disorder.

Objective: Autoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by autonomic failure associated with the presence of anti-ganglionic acetylcholine receptor (gAChR) antibodies; however, several studies have reported that individuals with anti-gAChR antibodies present with central nervous system (CNS) symptoms such as impaired consciousness and seizures. In the present study, we investigated whether the presence of serum anti-gAChR antibodies correlated with autonomic symptoms in patients with functional neurological symptom disorder/conversion disorder (FNSD/CD). Methods: Clinical data were collected for 59 patients presenting with neurologically unexplained motor and sensory symptoms at the Department of Neurology and Geriatrics between January 2013 and October 2017 and who were ultimately diagnosed with FNSD/CD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Correlations between serum anti-gAChR antibodies and clinical symptoms and laboratory data were analyzed. Data analysis was conducted in 2021. Results: Of the 59 patients with FNSD/CD, 52 (88.1%) exhibited autonomic disturbances and 16 (27.1%) were positive for serum anti-gAChR antibodies. Cardiovascular autonomic dysfunction, including orthostatic hypotension, was significantly more prevalent (75.0 vs. 34.9%, P = 0.008), whereas involuntary movements were significantly less prevalent (31.3 vs. 69.8%, P = 0.007), among anti-gAChR antibody-positive compared with -negative patients. Anti-gAChR antibody serostatus did not correlate significantly with the frequency of other autonomic, sensory, or motor symptoms analyzed. Conclusions: An autoimmune mechanism mediated by anti-gAChR antibodies may be involved in disease etiology in a subgroup of FNSD/CD patients.

Gut microbiota of Parkinson's disease in an appendectomy cohort: a preliminary study.

In patients with Parkinson's disease (PD), α-synuclein pathology is thought to spread to the brain via the dorsal motor nucleus of the vagus nerve. The link between the gut microbiome and PD has been explored in various studies. The appendix might play an important role in immunity by maintaining the microbiota as a reservoir. In recent times, appendectomy has been linked to a lower risk of PD, possibly owing to the role of the appendix in altering the gut microbiome. We aimed to elucidate whether the gut microbiota affects PD development in the appendectomy cohort. We analyzed the fecal microbial composition in patients with PD and healthy controls with and without a history of appendectomy. The abundance of microbes from the family Enterobacteriaceae was higher in feces samples from patients with Parkinson's disease compared to that in samples collected from healthy controls. Furthermore, there was a significant phylogenetic difference between patients with PD and healthy controls who had undergone appendectomy. There was a significant phylogenetic difference between patients with PD and HCs who had undergone APP. These results suggest the correlation between gut microbiota and PD in patients who have undergone APP.

A novel murine model of autoimmune dysautonomia by α3 nicotinic acetylcholine receptor immunization.

We aimed to establish a novel murine model of autoimmune autonomic ganglionopathy (AAG), which represents autoimmune dysautonomia, associated with MHC class II to understand its pathomechanism and the pathogenicity of nicotinic acetylcholine receptor (nAChR) antibodies. The amino acid sequence of the mouse nAChRα3 protein was analyzed using an epitope prediction tool to predict the possible MHC class II binding mouse nAChRα3 peptides. We focused on two nAChRα3 peptides in the extracellular region, and experimental AAG (EAAG) was induced by immunization of C57BL/6 mice with these two different peptides. EAAG mice were examined both physiologically and histologically. Mice with EAAG generated nAChRα3 antibodies and exhibited autonomic dysfunction, including reduced heart rate, excessive fluctuations in systolic blood pressure, and intestinal transit slowing. Additionally, we observed skin lesions, such as alopecia and skin ulcers, in immunized mice. Neuronal cell density in the sympathetic cervical ganglia in immunized mice was significantly lower than that in control mice at the light microscopic level. We interpreted that active immunization of mice with nAChRα3 peptides causes autonomic dysfunction similar to human AAG induced by an antibody-mediated mechanism. We suggested a mechanism by which different HLA class II molecules might preferentially affect the nAChR-specific immune response, thus controlling diversification of the autoantibody response. Our novel murine model mimics AAG in humans and provides a useful tool to investigate its pathomechanism.

Effectiveness of treatment for 31 patients with seropositive autoimmune autonomic ganglionopathy in Japan.

Background: Autoimmune autonomic ganglionopathy (AAG) is characterized by serum autoantibodies against the ganglionic acetylcholine receptor (gAChR). Immunomodulatory treatments may alleviate AAG symptoms, but the most appropriate treatment strategy is unclear. Objective: This study aimed to confirm the effectiveness of treatments, particularly immunotherapy, in patients with seropositive AAG in Japan, as well as to determine the most effective treatment and the best assessment method for clinical response to treatment. Methods: We collected data from a previous cohort study of patients with seropositive AAG. The clinical autonomic and extra-autonomic symptoms were objectively counted and subjectively assessed using the modified Composite Autonomic Symptom Score. Post-treatment changes in the gAChR antibody level were evaluated. Results: Thirty-one patients received immunotherapy. Among them, 19 patients received intravenous methylprednisolone; 27, intravenous immunoglobulin; 3, plasma exchange; 18, oral steroids; 2, tacrolimus; 1, cyclosporine; and 1, mycophenolate mofetil. Patients who received immunotherapy showed improvements in the total number of symptoms (from 6.2 ± 2.0 to 5.1 ± 2.0) and modified Composite Autonomic Symptom Score (from 37.4 ± 15.3 to 26.6 ± 12.8). Orthostatic intolerance, sicca, and gastrointestinal symptoms were ameliorated by immunotherapy. Immunotherapy decreased the antibody levels (gAChRα3 antibodies, from 2.2 ± 0.4 to 1.9 ± 0.4, p = 0.08; gAChRß4 antibodies, from 1.6 ± 0.1 to 1.0 ± 0.2, p = 0.002), but antibody levels increased in 10 patients despite immunotherapy. The rate of improvement in the total number of symptoms was higher in patients with combined therapy than in patients with non-combined therapy (70.7% vs 28.6%). Conclusions: The scores in many items on the rating scale decreased after immunotherapy in patients with seropositive AAG, particularly in the combined immunotherapy group. However, more accurate assessment scales for clinical symptoms and multicenter randomized, placebo-controlled prospective studies are warranted to establish future treatment strategies.

FLAMES with Elevated Myelin Basic Protein Followed by Myelitis.

The pathophysiology of unilateral cortical fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (MOG)-associated encephalitis with seizures (FLAMES) is unclear. A 26-year-old man was referred because of a seizure. FLAIR showed an increased signal intensity and swelling of the right frontal cortex. His symptoms and imaging abnormalities were improved after intravenous methylprednisolone therapy. MOG antibody was detected both in serum and cerebrospinal fluid (CSF). Therefore, the patient was diagnosed with FLAMES. Myelin basic protein (MBP) was elevated in CSF. The high MBP value in the CSF in the present case suggested that demyelination as well as inflammation can occur in some FLAMES patients.

Intravenous cyclophosphamide treatment for systemic lupus erythematosus with severe autonomic disorders confirmed by head-up tilt table test: A case series.

Autonomic disorders are common in patients with systemic lupus erythematosus (SLE), but the therapeutic strategy and methods for evaluating the effects of therapy have not been established. We describe the three cases of SLE patients who developed severe autonomic disorders as demonstrated by the head-up tilt table test (HUT). All three patients were treated by intensive immunosuppressive treatments including intravenous cyclophosphamide (IVCY); their HUT results all became negative. Our cases suggest that IVCY treatment can be a good therapeutic option for severe autonomic disorders in SLE patients. The HUT is a useful objective method for the diagnosis of and the evaluation of longitudinal therapeutic effects on autonomic disorders in SLE patients with orthostatic intolerance.

Binasal hemianopia caused by bilateral optic perineuritis due to sarcoidosis.

•We describe the first case of binasal hemianopia due to bilateral optic perineuritis.•Bilateral optic perineuritis should be considered as a causative disease of binasal hemianopia.•Early diagnosis of optic perineuritis is crucial to avoid irreversible visual impairment.

[Yips in Kyudo (Japanese archery): prevalence, classification, and aggravating factors].

In Kyudo (Japanese archery), there are four disorders that hinder an archer's performance: Hayake (releasing the bow too early), Motare (unable to release the bow when intended), Biku (jerking when aiming), and Yusuri (shaking when drawing the bow, or aiming). These disorders are similar to Yips, a psycho-neuromuscular movement disorder, recognized in various sports, but few studies have examined yips in Kyudo. This study examined the frequency, classification, and risk factors of yips in Kyudo among medical students. The results showed that 41 of 65 students (63.1%) experienced at least one disorder. The frequency of Hayake was the highest (35 patients; 85.3%). An experience of playing was associated with the increased risk of yips in Kyudo. Motare was the only disorder that appeared on its own, and without complications from other disorders. Based on its characteristics, it was suspected that task-specific focal dystonia involved in Motare.

[A case of chronic postural tachycardia syndrome with positive anti-ganglionic acetylcholine receptor (gAChR) antibody].

Postural orthostatic tachycardia syndrome (POTS) is a form of orthostatic intolerance characterized by symptoms such as lightheadedness, fainting, and brain fog that occur with a rapid elevation in heart rate when standing up from a reclining position. The etiology of POTS has yet to be established. However, a growing body of evidence suggests that POTS may be an autoimmune disorder such as autoimmune autonomic ganglionopathy, an acquired, immune-mediated form of diffuse autonomic failure. Many patients have serum antibodies that bind to the ganglionic acetylcholine receptors (gAChRs) in the autonomic ganglia. Herein, we describe a 39-year-old female patient with an eight-year history of orthostatic intolerance. POTS was diagnosed based on the findings of a head-up tilt test, in which a rapid increase in the patient's heart rate from 58 bpm in the lying position to 117 bpm in the upright position without orthostatic hypotension was observed. The POTS symptoms were refractory to various medications except for pyridostigmine bromide, which resulted in a partial resolution of her symptoms. Her serum was found to be strongly positive for anti-gAChR (ß4 subunit) autoantibody (2.162 A.I., normal range: below 1.0). Based on these findings, a limited form of autoimmune POTS was diagnosed. After obtaining written informed consent, she was treated with intravenous immunoglobulin (IVIg) 400 mg/kg/day for five days, which led to clinical improvement by reducing her heart rate increase in the upright position. She was able to return to work with IVIg treatment at regular intervals. Our case provides further evidence of a potential autoimmune pathogenesis for POTS. Aggressive immunotherapy may be effective for POTS even in chronic cases.

[Therapeutic Strategies of Neuropsychiatric Systemic Lupus Erythematosus].

Damage of the central and peripheral nervous systems associated with systemic lupus erythematosus (SLE) is termed neuropsychiatric SLE (NPSLE). In this review, we have discussed SLE encephalopathy, which is associated with neurological symptoms in particular. At the time of diagnosis, disease severity should be evaluated based on clinical findings, imaging, laboratory tests, including cerebrospinal fluid tests and neurophysiological tests, of the patient. Subsequently, treatment involving both definitive therapy and symptomatic treatment is initiated. After introducing definitive therapy, it is further desirable to adopt an appropriate treatment approach by identifying the predominant type of pathogenesis (inflammatory or vascular). A collaborative approach involving specialists in collagen vascular disease, neurologists, and psychiatrists is important for appropriate management of NPSLE.

Very late onset neuromyelitis optica spectrum disorders.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) often presents in the elderly with an insidious onset of symptoms and aggressive progression. There have been anecdotal cases of very late onset (VLO)-NMOSD, but case series reports are rare. The aim of this retrospective study was to clarify the clinical features of VLO-NMOSD. METHODS: According to the age at onset, we classified patients with NMOSD into three subgroups: ≤49 years, early onset NMOSD (EO-NMOSD); 50-69 years, late onset NMOSD (LO-NMOSD); and ≥70 years, VLO-NMOSD. We evaluated the clinical characteristics, magnetic resonance imaging (MRI) findings, laboratory data, and immunotherapies of the groups. RESULTS: Overall, 12 men and 64 women with a median (interquartile range) age at onset and duration of disease of 42.0 (29.0-55.8) years and 70.0 (16.3-143.0) months, respectively, were included. Eight (11%) patients had VLO-NMOSD, 22 (29%) had LO-NMOSD, and 46 (61%) had EO-NMOSD. Patients with EO-NMOSD had a significantly longer interval between episodes as well as time between the first symptom and diagnosis of NMOSD than did those with VLO-NMOSD and LO-NMOSD (p = 0.046). Optic neuritis and nerve lesions on MRI were significantly less frequent in patients with VLO-NMOSD than in those with LO-NMOSD and EO-NMOSD (p = 0.002 and p = 0.028, respectively). In contrast, patients with VLO-NMOSD had higher nadir Expanded Disability Status Scale and Nurick scale scores and a significantly longer spinal lesion length than did those with LO-NMOSD and EO-NMOSD (p = 0.029, p = 0.049, and p = 0.032, respectively). CONCLUSIONS: Patients with VLO-NMOSD tend to develop severe myelitis with long cord lesions but not optic neuritis.

Association between neurosarcoidosis with autonomic dysfunction and anti-ganglionic acetylcholine receptor antibodies.

OBJECTIVE: To determine whether autonomic dysfunction in neurosarcoidosis is associated with anti-ganglionic acetylcholine receptor (gAChR) antibodies, which are detected in autoimmune autonomic ganglionopathy. METHODS: We retrospectively extracted cases of sarcoidosis from 1787 serum samples of 1,381 patients between 2012 and 2018. Anti-gAChR antibodies against the α3 and ß4 subunit were measured by luciferase immunoprecipitation to confirm the clinical features of each case. We summarized literature reviews of neurosarcoidosis with severe dysautonomia to identify relevant clinical features and outcomes. RESULTS: We extracted three new cases of neurosarcoidosis with severe dysautonomia, among which two were positive for anti-gAChR antibodies: Case 1 was positive for antibodies against the ß4 subunit, and Case 2 was positive for antibodies against both the α3 and ß4 subunits. We reviewed the cases of 15 patients with neurosarcoidosis and severe dysautonomia, including the three cases presented herein. Orthostatic hypotension and orthostatic intolerance were the most common symptoms. Among the various types of neuropathy, small fiber neuropathy (SFN) was the most prevalent, with seven of nine cases exhibiting definite SFN. Six of eight cases had impaired postganglionic fibers, of which the present three cases revealed abnormality of 123I-MIBG myocardial scintigraphy. Of the 11 cases, 10 were responsive to immunotherapy, except one seropositive case (Case 2). CONCLUSIONS: The presence of gAChR antibodies may constitute one of the mechanisms by which dysautonomia arises in neurosarcoidosis.

gAChR antibodies in children and adolescents with acquired autoimmune dysautonomia in Japan.

OBJECTIVE: Patients with acquired autonomic dysfunction may have antibodies specific to the ganglionic nicotinic acetylcholine receptor (gAChR). However, the clinical features of children and adolescents with acquired autonomic dysfunction (AAD) remain unclear. This study aimed to determine the clinical features of pediatric patients with acquired autonomic dysfunction. METHODS: This study retrospectively examined a series of patients of AAD with serum gAChR antibodies who were referred to our laboratory for antibody testing between January 2012 and April 2019. The study included 200 patients (<20 years, 20 cases; ≥20 years, 175 cases) with clinical features of AAD. RESULTS: Upon comparing pediatric and adult patients, we found that antecedent infection and autonomic symptoms at onset with gastrointestinal symptoms occurred more frequently in children with AAD. We confirmed that four children (20.0%) met the diagnostic criteria for postural orthostatic tachycardia syndrome (POTS). A significantly higher number of children than adults had POTS (P = 0.002). In addition, upper GI dysfunction was more prevalent in children than in adults (P = 0.042). In particular, nausea and vomiting occurred in 60.0% of children with AAD and in 21.1% of adults (P < 0.001). The frequency of paralytic ileus was significantly higher in children with AAD (20.0%) relative to adults (6.3%) (P = 0.030). Regarding extra-autonomic manifestations, encephalopathy was more frequent in children (15.0%) than in adults (1.1%) (P < 0.001). INTERPRETATION: Pediatric AAD patients have their own clinical characteristics, and these features may be unique to children and adolescents.

Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM)-like Symptoms Associated with Anti-ganglionic Acetylcholine Receptor Antibodies.

This report describes a 59-year-old woman who presented with progressive encephalomyelitis with rigidity and myoclonus (PERM)-like symptoms and severe dysautonomia, including orthostatic hypotension, sinus bradycardia, dysuria, and prolonged constipation. Her neurological symptoms improved after immunotherapy, but the dysautonomia persisted. Anti-ganglionic acetylcholine receptor (gAChR) α3 subunit antibodies, which are frequently identified in patients with autoimmune autonomic ganglionopathy, were detected in the pre-treatment serum. The central distribution of the nicotinic acetylcholine receptors, a target of anti-gAChR antibodies, and immunotherapeutic efficacy observed in this case indicate that anti-gAChR α3 subunit antibodies are associated with the PERM-like features accompanied by autonomic manifestations.