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Immunoglobulin M neuropathy associated with anti-myelin-associated glycoprotein antibody (IgM/anti-MAG) neuropathy typically presents with chronic, distal-dominant symmetrical sensory or sensorimotor deficits. Ultrasonographic studies of IgM/anti-MAG neuropathy are limited, and were all performed on Western populations. We aimed to characterize the nerve ultrasonographic features of IgM/anti-MAG neuropathy in the Japanese population and evaluate whether they differ from the findings of the common subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP).In this cross-sectional study, we retrospectively reviewed medical records and extracted the cross-sectional areas (CSAs) of C5-C7 cervical nerve roots and median and ulnar nerves of 6 IgM/anti-MAG neuropathy patients, 10 typical CIDP (t-CIDP) patients, 5 multifocal CIDP (m-CIDP) patients, and 17 healthy controls (HCs).Cervical nerve root CSAs were significantly larger at every examined site on both sides in IgM/anti-MAG neuropathy than in m-CIDP and HCs but were comparable to those in t-CIDP. Peripheral nerve enlargements were greatest at common entrapment sites (ie, wrist and elbow) in IgM/anti-MAG neuropathy, a pattern shared with t-CIDP but not with m-CIDP. The degree of nerve enlargement at entrapment sites compared to non-entrapment sites was significantly higher in IgM/anti-MAG neuropathy than in t-CIDP.Our study delineated the ultrasonographic features of IgM/anti-MAG neuropathy in the Japanese population and observed similar characteristics to those of t-CIDP, with subtle differences. Further studies comparing results from various populations are required to optimize the use of nerve ultrasound worldwide.

A 43-year-old-woman developed paresthesia, weakness of limbs, dysphagia and deep sensory impairment 12 days after vaccination of Pfizer COVID-19 vaccine. Her deep tendon reflexes were absent and cerebrospinal fluid showed normal cell counts and protein level. Anti-ganglioside antibodies were negative, and F wave frequency was decreased in nerve conduction studies. We diagnosed her as immune mediated polyneuropathy caused by COVID-19 vaccine, and plasma exchange improved her symptoms. Compared with Guillain-Barré syndrome and polyneuropathy following COVID-19 infection and COVID-19 vaccination, deep sensory impairment was the most characteristic of this case. We supposed that non-antigen specific mechanism played an important role in the pathogenesis of this case.

We report the case of a 31-year-old man with a finger drop variant of Guillain-Barré syndrome (GBS). The patient visited a neurological clinic with complaints of difficulty in extending the fingers, which occurred seven days after he had fever and diarrhea. The physician who first saw the patient suspected posterior interosseous nerve palsy and referred him to our hospital. Neurological examination 35 days after the onset revealed distal weakness of the upper extremities, particularly in the bilateral extensor digitorum (Medical Research Council [MRC] scale 1/1 [right/left]). The left triceps surae muscle was also weak (MRC scale 5/4). Bilateral Achilles tendon reflexes were absent, but other neurological findings were normal. Cerebrospinal fluid examination showed albuminocytologic dissociation. Serum immunoglobulin G antibodies against GM1 were positive. Nerve conduction studies revealed reduced amplitude of compound muscle action potentials (CMAPs) without evidence of demyelination in the median, ulnar, radial, and tibial nerves. CMAP amplitude was most severely reduced in the radial nerve among the upper extremity nerves. We diagnosed the patient with acute motor axonal neuropathy. His symptoms gradually improved after treatment with intravenous immunoglobulin. When encountering acute finger drop, neurologists should consider the finger drop variant of GBS as a differential diagnosis.

A 75-year-old man with a history of hypertension developed weakness and sensory disturbance in the extremities 1 week after upper respiratory tract infection and faced difficulty walking. Screening at the time of hospital admission revealed an incidental positive SARS-CoV-2 PCR test, and COVID-19 was diagnosed. Neurological findings showed dysarthria, dysphagia, absence of deep tendon reflexes in the extremities, distal-dominant muscle weakness, sensory disturbance, urinary retention and constipation. Nerve conduction studies showed prolonged distal latency, decreased conduction velocity, and poor F-wave response, leading to a diagnosis of COVID-19-associated Guillain-Barré syndrome (GBS). The patient was treated with intravenous immunoglobulin, and his neurological symptoms improved without the need of a ventilator. Anti-ganglioside autoantibodies were negative. The patient developed GBS during the infectious period of SARS-CoV-2 and was treated in the isolation ward by clinical staff with personal protective equipment. Because COVID-19-associated GBS can develop during the infectious period of SARS-CoV-2, it is important for neurologists to consider GBS and other neurological disorders as being potentially COVID-19-related, and to treat patients with COVID-19 accordingly.

Although animal studies and studies on Parkinson’s disease (PD) suggest that dopamine deficiency slows the pace of the internal clock, which is corrected by dopaminergic medication, timing deficits in parkinsonism remain to be characterized with diverse findings. Here we studied patients with PD and progressive supranuclear palsy (PSP), 3–4 h after drug intake, and normal age-matched subjects. We contrasted perceptual (temporal bisection, duration comparison) and motor timing tasks (time production/reproduction) in supra- and sub-second time domains, and automatic versus cognitive/short-term memory–related tasks. Subjects were allowed to count during supra-second production and reproduction tasks. In the time production task, linearly correlating the produced time with the instructed time showed that the “subjective sense” of 1 s is slightly longer in PD and shorter in PSP than in normals. This was superposed on a prominent trend of underestimation of longer (supra-second) durations, common to all groups, suggesting that the pace of the internal clock changed from fast to slow as time went by. In the time reproduction task, PD and, more prominently, PSP patients over-reproduced shorter durations and under-reproduced longer durations at extremes of the time range studied, with intermediate durations reproduced veridically, with a shallower slope of linear correlation between the presented and produced time. In the duration comparison task, PD patients overestimated the second presented duration relative to the first with shorter but not longer standard durations. In the bisection task, PD and PSP patients estimated the bisection point (BP50) between the two supra-second but not sub-second standards to be longer than normal subjects. Thus, perceptual timing tasks showed changes in opposite directions to motor timing tasks: underestimating shorter durations and overestimating longer durations. In PD, correlation of the mini-mental state examination score with supra-second BP50 and the slope of linear correlation in the reproduction task suggested involvement of short-term memory in these tasks. Dopamine deficiency didn’t correlate significantly with timing performances, suggesting that the slowed clock hypothesis cannot explain the entire results. Timing performance in PD may be determined by complex interactions among time scales on the motor and sensory sides, and by their distortion in memory.

A 55-year-old man presented with recurrent brain infarction which had increased multifocally mainly in the cerebral white matter over the course of one year. Antibodies associated with antiphospholipid syndrome (APS) were initially negative. The patient was admitted to our department because of the thickened meninges shown on gadolinium enhanced brain MRI, mimicking hypertrophic pachymeningitis. However, blood and cerebrospinal fluid analysis revealed no significant inflammatory changes. On histopathological examination of the biopsied meninges, the arachnoid membrane was thickened with fibrosis, and arachnoidal microvessels were enlarged without significant inflammatory changes. The dura mater was not thickened, and no inflammation or microvessel enlargement were revealed. Finally, serum IgG anticardiolipin antibody testing was positive twice at an interval of more than 12 weeks, confirming the diagnosis of APS. Since initiating antithrombotic therapy with warfarin, brain infarction has not recurred. Without inflammation in the arachnoid membrane, the congestion of blood flow caused by thrombosis of microvessels in the arachnoid membrane might have increased the thickness of the arachnoid membrane.

Although serum IgG anti-ganglioside GQ1b antibody is the most specific biomarker for Fisher syndrome and its related disorders (FS-RD), 10%-30% of the patients are still negative in conventional assays ("GQ1b-seronegative") and the relationship between GQ1b-seropositive and -seronegative patients has been unclear. Some molecules require Ca(2+) cations to interact with their ligands (Ca(2+)-dependency). Here we have investigated whether Ca(2+)-dependency is also present in anti-GQ1b antibodies in FS-RD, especially in the GQ1b-seronegative patients and show that IgG antibodies against GQ1b-related antigens (isolated GQ1b and GQ1b-containing complexes) are detected Ca(2+)-dependently in the majority of GQ1b-seronegative patients with FS-RD. The Ca(2+)-dependent antibodies might react specifically with GQ1b-Ca(2+) conformation. This is the first demonstration of disease-related Ca(2+)-dependent antibodies in neurological field. GQ1b-related pathology would be involved in FS-RD more extensively than previously revealed.

Objective: We aimed to analyze the clinical and histopathologic features of cancer-associated myositis (CAM) in relation to anti–transcriptional intermediary factor 1 γ antibody (anti-TIF1-γ-Ab), a marker of cancer association. Methods: We retrospectively studied 349 patients with idiopathic inflammatory myopathies (IIMs), including 284 patients with pretreatment biopsy samples available. For the classification of IIMs, the European Neuromuscular Center criteria were applied. Patients with CAM with (anti-TIF1-γ-Ab[+] CAM) and without anti-TIF1-γ-Ab (anti-TIF1-γ-Ab[−] CAM) were compared with patients with IIM without cancers within and beyond 3 years of myositis diagnosis. Results: Cancer was detected in 75 patients, of whom 36 (48%) were positive for anti-TIF1-γ-Ab. In anti-TIF1-γ-Ab(+) patients with CAM, cancers were detected within 1 year of myositis diagnosis in 35 (97%) and before 1 year of myositis diagnosis in 1. All the anti-TIF1-γ-Ab(+) patients with CAM satisfied the dermatomyositis (DM) criteria, including 2 possible DM sine dermatitis cases, and were characterized histologically by the presence of perifascicular atrophy, vacuolated fibers (VFs), and dense C5b-9 deposits on capillaries (dC5b-9). In contrast, 39 anti-TIF1-γ-Ab(−) patients with CAM were classified into various subgroups, and characterized by a higher frequency of necrotizing autoimmune myopathy (NAM). Notably, all 7 patients with CAM classified into the NAM subgroup were anti-TIF1-γ-Ab(−) and exhibited no dC5b-9 or VFs. Conclusions: CAM includes clinicohistopathologically heterogeneous disease entities. Among CAM entities, anti-TIF1-γ-Ab(+) CAM has characteristically shown a close temporal association with cancer detection and the histopathologic findings of dC5b-9 and VFs, and CAM with NAM is a subset of anti-TIF1-γ-Ab(−) CAM.

Background Guillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE) are a group of autoimmune neurological disorders (GBS spectrum disorder) that rarely recur. Recently, anti-ganglioside complex antibodies (GSC-Abs) were identified in patients with GBS spectrum disorder. However, there has been no case report describing GSC-Abs profiles in a recurrent case showing different phenotypes. Case presentation We report the case of a 33-year-old male patient with GQ1b-seronegative BBE-GBS after two prior episodes of MFS-GBS. Our patient showed ophthalmoplegia, ataxia, areflexia and a weakness of the extremities (MFS and GBS symptoms) in all episodes. In the episode reported here, our patient showed disturbed consciousness and an extensor response to cutaneous plantar stimulation was observed (BBE symptoms), with severe disability and requirement for artificial respiration management. GSC-Abs detected in previous episodes were also detected in the subsequent episodes, while new GSC-Abs emerged in each episode. Interestingly, whereas antibodies to GA1/GQ1b and GA1/GT1a, which are commonly identified in patients with GBS, MFS or BBE, appeared in all episodes, antibodies to GD1a/GD1b and GD1b/GT1b, which are predominantly associated with severe disability and the requirement for artificial respiration management in GBS, emerged for the first time in this episode. Conclusion This study reports novel phenomena about the GSC-Abs profiles and its relationship with clinical features in a case with recurrent GBS spectrum disorder, showing different phenotypes in different episodes. Further studies are required to reveal the significance of the GSC-Abs profiles in recurrent GBS spectrum disorder.

Anti-glycolipid antibodies are key to revealing the pathomechanisms of Guillain-Barré syndrome (GBS). There are correlations between the antigen specificities of the antibodies, clinical features, and preceding infectious agents. It has also been found that some glycoantigens are localized in human peripheral nervous tissues, corresponding to the clinical features. Antibody-detection methods are still evolving. The discovery of antibodies against glycolipid complexes expanded the horizon of anti-glycolipid research in GBS, which had started from isolated antigens. Recently, IgG antibodies against ganglioside GQ1b-related antigens that required Casup2+/supcations in the antigen-antibody reaction (Casup2+/sup-dependent anti-GQ antibody) have also been detected in patients with Fisher syndrome, or other related disorders, who were GQ1b-seronegative in conventional assays without adding Casup2+/sup. It is suggested that Casup2+/supinteracts with disialosyl groups [NeuAc (a2-8) NeuAc (a2-)] in gangliosides, and that the Casup2+/sup-dependent antibodies recognize the Casup2+/sup-bound conformation of GQ1b.

We report a 45-year-old man with motor axonal Guillain–Barre syndrome who developed left facial nerve palsy, right hypoglossal nerve palsy, and predominantly left-sided upper limb paresis and left lower limb paresis. Blood examination identified immunoglobulin G antibodies against gangliosides GD1a, GD1b and GQ1b, and GD1b/GD1a and GD1b/GT1b complexes. He was treated with intravenous immunoglobulin (400 mg/kg/day for 5 days) twice, and tongue deviation and facial palsy resolved in 3 months. Unilateral or asymmetric involvement of the cranial and limb nerves represent a variant form of axonal Guillain–Barre syndrome.

We report a 65-year-old woman with neuromyelitis optica spectrum disorder manifesting acute cerebellar ataxia, and intractable nausea and vomiting. She tested positive for anti-aquaporin 4 antibodies and had a lung adenocarcinoma simultaneously. She underwent partial pulmonary resection, and tumor cells of the lung adenocarcinoma were stained with an anti-aquaporin 4 antibody. By administering intravenous methyl prednisolone and plasma exchange, aquaporin 4 antibody titer was reduced, and neurological deficits and the lesion status on magnetic resonance imaging markedly improved. Paraneoplastic neuromyelitis optica spectrum disorder in conjunction with lung adenocarcinoma was a reasonable diagnosis.

A-waves are intermediate components that are observed between the compound muscle action potential (CMAP) and the F-waves. We recently suggested that abundant A-waves in Guillain-Barre syndrome (GBS) can be a novel marker of demyelination because they were strongly correlated with the acute inflammatory demyelinating polyneuropathy (AIDP) subtype and the absence of anti-glycolipid antibodies.1 Hiraga et al 2 reported that patients with AIDP without anti-ganglioside antibodies showed progressive prolongation of the distal motor latency (DML) of the median nerve, whereas the DML of patients with AIDP with anti-ganglioside antibodies may initially be prolonged but rapidly return to normal, suggesting an essentially axonal pathology. These results imply the possibility that the time course of DML of the median nerve (median DML) can be used as another marker of demyelination. In this report, we reanalysed the data collected in our previous study1 and compared the A-waves with other parameters, using the time course of the median DML as a gold standard. The data of 30 patients with GBS (21 men and 9 women, 43.7±19.5 years old) were reanalysed. The abundant A-waves were defined as three or more identifiable peaks between the CMAP and F-waves, observed in the median or ulnar nerves at least once during weeks 3–6 from onset.1 Clinical features of patients with abundant A-waves were compared with those without. Patients were classified into two groups using three different criteria, which were already determined in the preceding study.1 The first criterion was the abundant A-waves, which were positive in 9 and negative in 21patients. The second was Ho's criteria,3 applied …

Serum antibodies against glycolipids, mainly gangliosides, are detected in about 60% of patients with Guillain-Barré syndrome (GBS) and its variants. Anti-glycolipid antibodies play a crucial role in the pathogenic mechanisms of GBS. The antibody titer is the highest in the acute phase and decreases gradually. Molecular mimicries occur between the glycolipids and surface molecules on the infectious agents. Clinical subtypes of GBS are related to the antigenic specificities of the antibodies. The distribution of gangliosides in peripheral nervous tissues could explain the different clinical manifestations. The anti-GQ1b antibody is detected in 80-90% of patients with Fisher syndrome characterized by ophthalmoplegia. GQ1b is localized in the paranodes of the human cranial nerves innervating the extraocular muscles. This is consistent with the clinical association between the anti-GQ1b antibody and ophthalmoplegia. The anti-GM1 antibody is associated with acute motor axonal neuropathy, whereas the anti-GD1b antibody is detected in acute sensory ataxic neuropathy. GBS animal models sensitized by gangliosides, such as GM1 or GD1b, develop monophasic peripheral neuropathies. In the animal models, disruption of molecule clusters and deposition of complement products were observed in the nodal and paranodal regions. Clinical and experimental data suggest complement-mediated pathogenic mechanisms triggered by anti-glycolipid antibodies in GBS.

Introduction We report the case of a patient who developed symptoms of acute cerebellar ataxia (ACA) after administration of the human papilloma virus (HPV)-16/18 vaccine. Patient and Method This patient developed symptoms of ACA, including nausea, vertigo, severe limb and truncal ataxia, and bilateral spontaneous continuous horizontal nystagmus with irregular rhythm, 12 days after administration of the HPV-16/18 AS04-adjuvanted cervical cancer vaccine. After this, the patient received methylprednisolone pulse and intravenous immunoglobulin (IVIG) therapies as well as immunoadsorption plasmapheresis. Results Severe ACA symptoms did not improve after methylprednisolone pulse and IVIG therapies, but the patient recovered completely after immunoadsorption plasmapheresis. Conclusion This temporal association strongly suggests that ACA was induced by the vaccination.

Guillain-Barré syndrome (GBS) is a heterogeneous disease, and has a various clinical course and outcome. Despite the use of standard therapies, such as plasma exchange or intravenous immunoglobulin therapy, some patients still have residual neurological sequelae. New therapies and treatment modalities may improve outcome in patients with poor recovery in the current standard therapies, if the patients with poor prognosis could be identified in early disease phase. In recent years, prognosis and potential determinants of clinical outcome in GBS have been investigated by various methods. The clinical prediction models using selected predictors (high age, preceding diarrhea, and low Medical Research Council sum score, and their combined scoreing systems, etc.) were advocated.

Interferon-gamma release assay (IGRA) using specific tuberculous antigens is a rapid, specific and sensitive method for the detection of tuberculous infection, and usually done in peripheral blood sample. We examined IGRA in cerebrospinal fluid (CSF) in a patient strongly suspected of having tuberculous meningitis. A 53-year old woman had a month history of headache and fever with meningeal sign. Routine systemic bacterial, tuberculous and viral analyses all resulted in negative study except for increase of adenosine deaminase in CSF. Neither of antibacterial or antiviral treatments were effective, but she was successfully treated with antituberculous agents. In IGRA, the interferon-gamma concentration in her CSF was high in the background level and increased further after the antigen stimulation, suggesting theoretically that tuberculous antigen-specific T cells were presented in her CSF. IGRA of CSF in combination with peripheral blood-IGRA could be a useful and rapid method for diagnosing active tuberculosis in the central nervous system.

A 38-year-old man developed dysesthesia, diplopia, and an unsteady gait following an upper respiratory infection. IgG anti-GQ1b antibody was detected in his serum and he was diagnosed as Fisher syndrome. The patient also complained of loss of taste sensation, and it resolved along with improvement of other neurological manifestations. In Guillain-Barré syndrome, cranial nerve involvement is very common, though taste disturbance is a rare complaint. Impairment of taste has been reported in association with severe facial nerve involvement, but taste disturbance developed without facial nerve palsy in the present case and taste sensation was diminished in the area of all four nerves involved in taste sensation. These findings suggest that the impaired taste sensation in the present patient was not a complication of facial nerve palsy as in previous cases, but rather due to taste sensory specific involvement.

The authors found serum immunoglobulin M (IgM) autoantibody in a patient with typical acute cerebellar ataxia (ACA) and identified the antigen molecule as triosephosphate isomerase (TPI). TPI antigenicity to the patient's antibody was the highest in the cerebellar tissue. Eight of 23 patients with ACA had increased IgM anti-TPI antibody titers vs those of healthy controls. Preceding Epstein-Barr virus infection was confirmed serologically in all 8 patients. Anti-TPI antibody decreased with clinical improvement.

A 27-year-old man presented with subacute progressive left hemiparesis and hemi-sensory loss. Laboratory examinations revealed CD4 count at 14/microl, the HIV antibody positive, and HIV-RNA at 4.3 x 10(4) copies. Brain CT showed hypodence areas without contrast enhancement or mass effect in the right parietooccipital white matter and the right external capsule. On MR imaging, the lesion in the parietooccipital area showed hypointensity without enhancement on T1-weighted images and hyperintensity on T2-weighted images. On FLAIR images, the lesion showed hypointensity surrounded by hyperintensity. Meanwhile, diffusion-weighted images revealed three layers of different intensity. The area that demonstrated hypointensity on FLAIR images showed also hypointensity, while that in the area that demonstrated hyperintensity on FLAIR was divided into two parts; an area of isointense that encircles an hypointense area and a hyperintense area in the margin. The isointense and hypointense areas on diffusion-weighted images showed hyperintensity on apparent diffusion coefficient map. As JCV DNA was detected from his CSF, the diagnosis of PML was made. Based on comparative assessment of these MR images, it was speculated that the PML lesion appeared to be constituted of three parts from the margin to the center: cytotoxic edema, vasogenic edema, and liquefied lesion such as necrosis.

A 46-year-old woman with a nine-year history of diabetes mellitus (DM) without treatment had an acute onset of right hemiballism. For the treatment of hyperglycemia (random blood sugar 588 mg/dl) conventional insulin therapy was started, and HbA1c rapidly decreased from 16.3% to 8.8% over the first two months. During this period, there were no hypoglycemic symptoms or episodes, though amnesia appeared just after the insulin therapy was started. T1-weighted MRI showed hyperintensity in the left basal ganglia, which has been reported in many cases of chorea or ballism associated with DM. In addition, there were unique changes in the left temporal lobe, including transient contrast enhancement along the cortex followed by transient hyperintensity in the cortical-subcortical area on T2 weighted and FLAIR images, and then hyperintensity along the cortex on T1 weighted images and atrophy. These findings were thought to indicate a consecutive process, i.e., capillary hyperlucency followed mainly by vasogenic edema and then laminar necrosis. Similar MR findings were reported in hypoglycemic coma. MRA also revealed a transient vasospasm in the left MCA M1-M2 portions in this patient. These signal changes may have been related to the prolonged hyperglycemic state as well as blood sugar control that was too rapid.