Different Complement Activation Patterns Following C5 Cleavage in MOGAD and AQP4-IgG+NMOSD.

OBJECTIVES: In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD. METHODS: CSF-C3a, CSF-C4a, CSF-C5a, and CSF-C5b-9 levels during the acute phase before treatment in patients with MOGAD (n = 12), AQP4+NMOSD (n = 11), multiple sclerosis (MS) (n = 5), and noninflammatory neurologic disease (n = 2) were measured. RESULTS: CSF-C3a and CSF-C5a levels were significantly higher in MOGAD (mean ± SD, 5,629 ± 1,079 pg/mL and 2,930 ± 435.8 pg/mL) and AQP4+NMOSD (6,017 ± 3,937 pg/mL and 2,544 ± 1,231 pg/mL) than in MS (1,507 ± 1,286 pg/mL and 193.8 ± 0.53 pg/mL). CSF-C3a, CSF-C4a, and CSF-C5a did not differ between MOGAD and AQP4+NMOSD while CSF-C5b-9 (membrane attack complex, MAC) levels were significantly lower in MOGAD (17.4 ± 27.9 ng/mL) than in AQP4+NMOSD (62.5 ± 45.1 ng/mL, p = 0.0019). Patients with MOGAD with severer attacks (Expanded Disability Status Scale [EDSS] ≥ 3.5) had higher C5b-9 levels (34.0 ± 38.4 ng/m) than those with milder attacks (EDSS ≤3.0, 0.9 ± 0.7 ng/mL, p = 0.044). DISCUSSION: The complement pathway is activated in both MOGAD and AQP4+NMOSD, but MAC formation is lower in MOGAD, particularly in those with mild attacks, than in AQP4+NMOSD. These findings may have pathogenetic and therapeutic implications in MOGAD.

Distal Chronic Inflammatory Demyelinating Polyneuropathy Following COVID-19 Vaccination in a Patient with Solitary Plasmacytoma: A Case Report and Literature Review.

We herein report a rare case of distal chronic inflammatory demyelinating polyneuropathy (CIDP) following coronavirus disease 2019 (COVID-19) vaccination. A 39-year-old woman with a solitary plasmacytoma developed general weakness 7 days after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine, which had progressed for 3 months. A neurological examination revealed limb weakness with areflexia. Serological tests identified the presence of IgG antibodies against anti-GM1 and anti-GM2 gangliosides. Comprehensive evaluations met the criteria of distal CIDP. Intravenous immunoglobulin, intravenous methylprednisolone, oral prednisolone, and plasma exchange were administered, and she gradually improved. Physicians should be aware of CIDP as a rare complication of COVID-19 vaccination.

First manifestation of AQP4-IgG-positive neuromyelitis optica spectrum disorder following the COVID-19 mRNA vaccine BNT162b2.

BNT162b2 is one of the effective COVID-19 vaccines. However, some researchers have also reported some neurological adverse events after the vaccination. Here, we present a case of a 52-year-old female who developed aquaporin (AQP) 4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) 14 days after the first dose of BNT162b2. She experienced the neck pain, weakness of the left arm and leg, numbness of the left hand, and impaired temperature sensation of the right leg. MRI showed T2WI hyperintense lesions in the area postrema and cervical spinal cord ranging from C1 to C6 level and Gd-enhanced lesions from C3 to C5 level; especially left lateral column was predominantly enhanced. Cell-based assays showed anti-AQP4 antibody (AQP4Ab) was positive. We diagnosed AQP4-IgG-positive NMOSD. After high-dose glucocorticoid therapy, she is showing improved symptoms. The present case was characterized by the findings that a Gd-enhanced lesion in the cervical cord localized dominantly at the left lateral column, consistent with the side of the shoulder where the vaccine was injected. Many studies suggested that AQP4-IgG-positive NMOSD development has multistep mechanisms following the blood-brain barrier (BBB) breakdown. We suspected that immune responses following vaccination lead to BBB disruptions. Through the limitedly damaged BBB, the plasma cells producing AQP4Abs might be recruited to CNS, and AQP4Abs might bind to the cervical cord and the area postrema. A population-based study revealed that neurological events following COVID-19 vaccination were less likely to be observed than COVID-19 infectious symptoms. Considering rare adverse events, clinicians need to observe any changes in patient condition.

Low frequency of cervicocranial artery involvement in Japanese with renal artery fibromuscular dysplasia compared with that of Caucasians.

BACKGROUND: Fibromuscular dysplasia (FMD), which usually affects the renal artery, also affects the carotid, vertebral, and intracranial arteries. Previous studies have shown a high prevalence of concomitant renal artery and cervicocranial lesions in FMD patients. However, the analyzed subjects were mostly Caucasians in Western countries. METHOD: We performed a retrospective analysis to examine the prevalence of cervicocranial vascular lesions in Japanese FMD patients with renal artery involvement at a single institution. The presence of cervicocranial lesions was evaluated by Doppler echography and magnetic resonance angiography. We compared this prevalence with that reported in the literature. RESULT: Thirty-one Japanese FMD patients with renal artery lesions were studied. The mean age was 30 ± 12 years, 71% were women, and 16% were smokers; all patients were Asians and had hypertension. Multifocal, tubular, and unifocal types of renal lesions were found in 52, 35, and 13% of patients, respectively. Bilateral renal lesions were found in 13% of patients. None of the patients had a cervical vascular lesion associated with FMD. Only two patients (8%) had a lesion in the intracranial artery, of which one was a known case of moyamoya disease. CONCLUSION: These findings suggest that cervical artery involvement and intracranial artery involvement are not common in renal FMD patients in Japan, which is in contrast to the data reported for Caucasian patients in Western countries. Ethnic differences could influence the occurrence of cervicocranial lesions. A study with a larger sample size should be performed to validate these findings.