[Heparin Resistance After Administration of Andexanet Alfa:Report of a Case].

The management of patients on direct oral anticoagulants (DOACs) who require an emergency cardiac surgery has been disputed in Japan. Recently, the use of andexanet alfa as an antidote for apixaban and rivaroxaban, is approved in the setting of life-threating or uncontrollable major bleeding. However, the efficacy and safety of andexanet alfa have been investigated. We report a case of 72-year-old man taking rivaroxaban who required the emergency coronary artery bypass grafting. He received andexanet alfa prior to the operation. Heparin resistance was noted before starting cardiopulmonary bypass. Consideration should be given to the use of andexanet alfa before or during cardiopulmonary bypass.

Paediatric brainstem encephalitis associated with glial and neuronal autoantibodies.

AIM: Central nervous system (CNS) autoantibodies have been reported in a range of neuroimmune diseases, but there has not been a systematic evaluation of autoantibodies in paediatric patients with brainstem encephalitis. METHOD: Serum samples from 57 children (40 male, 17 female, median age 12y, range 0.6-18y) with a diagnosis of brainstem encephalitis were tested retrospectively for antibodies to GQ1b, aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein (MOG), N-methyl-D-aspartate receptor, LGI1, CASPR2, glycine receptor (GlyR), DPPX, and the voltage gated potassium channel (VGKC)-complex. RESULTS: Disease localized to the brainstem was seen in 19 patients: Bickerstaff's brainstem encephalitis (n=14) and clinically isolated syndrome (n=5). Polyfocal presentation was seen in 38 children, with predominantly white matter disease in 18 patients and grey matter in 20 patients. CNS surface antibodies were found in 22/57 patients (two patients with double positivity): GQIb (n=6), NMDAR (n=7), GlyR (n=5), MOG (n=5), and one AQP4. Three patients were positive for VGKC-complex antibodies. All patients were negative for antibodies to DPPX and the VGKC-complex antigens LGI1, CASPR2, and contactin-2. Although there were some partial differences in the presentations, the clinical features and outcomes did not relate clearly to the presence or absence of specific antibodies. INTERPRETATION: As determined retrospectively, 39% of patients had cell surface antibodies. The results did not suggest any relationship with treatment or outcomes obtained but it is possible that specific antibody detection could be a helpful guide to more intensive immunotherapies in some cases.

Cytoalbuminologic dissociation in Asian patients with Guillain-Barré and Miller Fisher syndromes.

Cerebrospinal fluid (CSF) protein level, cell count, and its relationship to the timing of lumbar puncture were collected from patients with Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) from various Asian centers. A total of 507 patients with GBS were studied. Overall, 56% had elevated CSF protein level. This was significantly lower than that reported in a recent Dutch study (56% vs 64%). Cytoalbuminologic dissociation was also lower in the Asian cohort (55% vs 64%), with a significantly higher proportion of patients with mild pleocytosis (26% vs 15%). A lower proportion of the 164 patients with MFS had elevated CSF protein level (38% vs 56%), mild pleocytosis (11% vs 26%), and cytoalbuminologic dissociation (41% vs 55%) compared to patients with GBS. In both conditions, cytoalbuminologic dissociation was linked to the timing of lumbar puncture. Cytoalbuminologic dissociation was only observed in half of the Asian patients with GBS and MFS, and it is strongly dependent on the timing of the lumbar puncture.

Delayed traumatic aortic valve perforation after blunt chest trauma.

BACKGROUND: Aortic valve perforation is a rare complication of blunt chest trauma. We report a case of delayed aortic insufficiency presenting several months after trauma. CASE PRESENTATION: A 17-year-old male presented to the emergency department with traumatic brain injuries and blunt chest trauma, but no evidence of cardiac injuries. Three months later, he developed acute heart failure due to severe aortic valve regurgitation with left ventricular dysfunction. A sizable tear in the right coronary cusp caused aortic insufficiency. He was treated successfully by surgical replacement with an aortic bioprosthesis. CONCLUSION: We reported a successful surgical case of valve replacement for delayed aortic valve perforation. Delayed valve perforation should be kept in mind after blunt chest trauma.

Midterm Results of Mitral Valve Repair Using Loop Technique With Simple Height Reduction of the Large Posterior Leaflet.

OBJECTIVE: Systolic anterior motion (SAM) is one of the most serious problems in mitral valve repair. Height reduction is a key procedure to solve SAM, and there are limited data on the surgical results of height reduction procedure. This study is to assess the effectiveness and midterm results of simple height reduction procedure for SAM in patients with severe mitral regurgitation (MR). METHODS: From 2008 to 2022, 50 patients underwent loop technique with an additional simple height reduction procedure for prevention of SAM. We examined the midterm results of patients with simple height reduction regarding recurrent MR and reoperation. The follow-up period ranged from 171 to 3,816 days (median, 883 days). RESULTS: There were 338 patients (87%) who underwent loop technique without height reduction and 50 patients (13%) who underwent loop technique with height reduction. After the height reduction procedure, SAM was prevented in 44 patients, and 6 patients needed volume loading to suppress SAM. Freedom from recurrence of moderate to severe or severe MR at 1, 3, and 5 years was 98%, 88%, and 88% in the height reduction group versus 98%, 96%, and 94% in the group with loop technique alone (P = 0.074). Receiver operating characteristic curves showed that a systolic dimension of 26 mm had a sensitivity of 75% and a specificity of 83% for predicting SAM after height reduction. CONCLUSIONS: Loop technique with simple height reduction was a simple, secure, and effective procedure to prevent SAM and recurrent significant MR in the midterm periods.

Serologic marker of acute motor axonal neuropathy in childhood.

Guillain-Barré syndrome is divided into two subtypes: acute inflammatory demyelinating polyneuropathy, and acute motor axonal neuropathy. Autoantibodies to gangliosides GM1, GM1b, GD1a, or GalNAc-GD1a were proposed as serologic markers of acute motor axonal neuropathy in adults. In a previous study of Japanese children with Guillain-Barré syndrome, acute motor axonal neuropathy was associated with anti-GM1 immunoglobulin G antibodies. Larger, comprehensive studies are required to confirm this finding. The present study revealed that immunoglobulin G antibodies were against GM1 (34%), GM1b (22%), GD1a (25%), GalNAc-GD1a (13%), and any of these (44%) in 32 Japanese children with Guillain-Barré syndrome. Patients who had the autoantibodies more often manifested previous diarrhea (71% vs 11%, P = 0.001), acute motor axonal neuropathy (64% vs 11%, P = 0.003), and slower recovery (healthy at final follow-up: 29% vs 78%, P = 0.011; able to run with minor signs, 64% vs 11%, P = 0.003) than patients who did not. The clinical features were consistent with those in adults carrying anti-ganglioside antibodies. Anti-ganglioside antibody testing may help predict outcomes in pediatric patients with Guillain-Barré syndrome who prefer not to undergo repeated nerve-conduction studies.

Leukocyte and complement activation by GM1-specific antibodies is associated with acute motor axonal neuropathy in rabbits.

Acute motor axonal neuropathy (AMAN) in humans is associated with the presence of GM1-specific antibodies. Immunization of rabbits with GM1-containing ganglioside mixtures, purified GM1, or Campylobacter jejuni lipo-oligosaccharide exhibiting a GM1-like structure elicits GM1-specific antibodies, but axonal polyneuropathy only occurs in a subset of animals. This study aimed to dissect the molecular basis for the variable induction of AMAN in rabbits. Therefore, we analyzed the pro-inflammatory characteristics of GM1-specific antibodies in plasma samples from ganglioside-immunized rabbits with and without neurological deficits. GM1-specific plasma samples from all rabbits with AMAN were capable of activating both complement and leukocytes, in contrast to none of the plasma samples from rabbits without paralysis. Furthermore, GM1-specific IgG-mediated activation of leukocytes was detected before the onset of clinical signs. These data suggest that AMAN only occurs in rabbits that develop GM1-specific antibodies with pro-inflammatory properties.

Various immunization protocols for an acute motor axonal neuropathy rabbit model compared.

Various ganglioside immunization protocols were examined to refine the procedure for establishing an animal model of acute motor axonal neuropathy. The most effective was subcutaneous injection of an emulsion of 2.5mg of bovine brain ganglioside mixtures, keyhole lympet hemocyanin, and complete Freund's adjuvant to Japanese white rabbits, repeated at 3-week intervals. Under that protocol, all the rabbits developed marked flaccid paralysis associated with plasma anti-GM1 IgG antibody. This acute motor axonal neuropathy rabbit model also could be reproduced by the use of incomplete Freund's adjuvant, methylated bovine serum albumin, and New Zealand white rabbits. These results provide useful information for the confirmation of and further research on the model.

[Intravenous immunoglobulin therapy for Guillain-Barré syndrome in Japan: changes in treatment after its inclusion in health insurance coverage].

In December 2000, health insurance in Japan was instituted for the use of intravenous immunoglobulin (IVIg) therapy for the acute phase of Guillain-Barré syndrome (GBS) that required aid to walk or worse. A nation-wide questionnaire survey was made to investigate the changes in treatment. In September 2002, a letter of inquiry was sent to experienced physicians in 620 teaching hospitals associated with the Societas Neurologica Japonica and 417 associated with the Societas Paediatrica Japonica. Totally, 356 neurologists (57%) and 223 pediatricians (53%) responded. After the introduction of IVIg health insurance coverage, more than 90% thought that GBS patients should be hospitalized and given treatment. The frequency of hospitals with an intensive care unit, however, was 70%. Before IVIg therapy's inclusion in health insurance coverage, many neurologists selected plasmapheresis (88%) rather than IVIg (4%) therapy, whereas pediatricians preferred IVIg (49%) to plasmapheresis (12%). After its inclusion, 75% of neurologists selected IVIg rather than plasmapheresis (21%), whereas pediatricians selected IVIg (86%) over plasmapheresis (5%). In March 2003, new payment system based on Diagnosis Procedure Combination was introduced into 82 large hospitals, and leads to difficulties to select IVIg in the hospitals. The payment system should be revised.

[Outcome after Guillain-Barré syndrome: comparison of motor function status and changes in social life].

Effects on the motor function and social life of the patients after Guillain-Barré syndrome (GBS) were studied. A letter of inquiry was sent to the patients in November 2001; 98 patients responded validly. The questionnaire had questions with 3 possible answers related to situations at work, at home, and about leisure activities. The Hughes functional grade, which evaluates physical conditions, and arm disability scale scores were assessed. Although the assessments showed good recovery in most patients who had had a job, 31% had to quit work, and 17% had to discontinue their leisure activities. These physical assessments accurately reflected the severity of the conditions of the patients given in-home care (8%) because daily life activities depend on muscle strength. Of the 75 patients who had no, or minimal, neurological symptoms or signs in both assessments, 53% reported one or more changes in their social lives. We conclude that the questionnaire answers show that GBS patients may have serious psychosocial outcomes that are not measurable by the usual physical assessments. These findings may be a help when considering the rehabilitation of GBS patients and their return to social life.

[Details about the first medical examinations of patients with Guillain-Barré or Fisher syndromes].

Randomized controlled trials have shown beneficial responses to plasma exchange and intravenous immunoglobulin in Guillain-Barré syndrome (GBS), but details about the first medical examination of patients with GBS and Fisher syndrome (FS) have not been reported. We investigated the period from first consultations to treatment after the onset of patients with GBS and FS. A questionnaire was used to collect informations on 247 patients with GBS and 125 with FS, all of whom had been referred to our neuroimmunological laboratory informations between January 2001 and October 2001 for serum anti-ganglioside antibody tests. A letter of inquiry was sent to the primary physicians; 150 (61%) patients with GBS and 72 (58%) with FS responded validly. Patients with GBS generally consulted an internist [58%, neurologist (21%)] or orthopedist (17%), those with FS an internist [52%, neurologist (26%)] or ophthalmologist (25%). Consultation with a neurologist usually came after one with a physician. We conclude that physicians should be aware that patients may have GBS or FS, and that such recognition is useful for early diagnosis and treatment of these syndromes.

Acute motor axonal neuropathy rabbit model: immune attack on nerve root axons.

Macrophages in the periaxonal space and surrounding intact myelin sheath are the most prominent pathological feature of acute motor axonal neuropathy (AMAN). We describe this characteristic in nerve roots from paralyzed rabbits immunized with bovine brain ganglioside or GM1. IgG was deposited on nerve root axons. Distal nerve conduction was preserved, and late F wave components were absent during the acute phase. Initial lesions were located mainly on nerve root axons, as in human AMAN. This study thus provides supportive evidence that the rabbits constitute a model of AMAN.

Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain-Barre syndrome.

Molecular mimicry between microbial and self-components is postulated as the mechanism that accounts for the antigen and tissue specificity of immune responses in postinfectious autoimmune diseases. Little direct evidence exists, and research in this area has focused principally on T cell-mediated, antipeptide responses, rather than on humoral responses to carbohydrate structures. Guillain-Barré syndrome, the most frequent cause of acute neuromuscular paralysis, occurs 1-2 wk after various infections, in particular, Campylobacter jejuni enteritis. Carbohydrate mimicry [Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-] between the bacterial lipooligosaccharide and human GM1 ganglioside is seen as having relevance to the pathogenesis of Guillain-Barré syndrome, and conclusive evidence is reported here. On sensitization with C. jejuni lipooligosaccharide, rabbits developed anti-GM1 IgG antibody and flaccid limb weakness. Paralyzed rabbits had pathological changes in their peripheral nerves identical with those present in Guillain-Barré syndrome. Immunization of mice with the lipooligosaccharide generated a mAb that reacted with GM1 and bound to human peripheral nerves. The mAb and anti-GM1 IgG from patients with Guillain-Barré syndrome did not induce paralysis but blocked muscle action potentials in a muscle-spinal cord coculture, indicating that anti-GM1 antibody can cause muscle weakness. These findings show that carbohydrate mimicry is an important cause of autoimmune neuropathy.