Exacerbation of Thymoma-Associated Myasthenia Gravis Following Efgartigimod Treatment Related to Anti-acetylcholine Receptor Antibody Overshoot: A Report of Two Cases.

Myasthenia gravis (MG), a chronic, autoimmune disease affecting the neuromuscular junction, arises from various autoantibodies, including those against the acetylcholine receptor (AChR). Recently, efgartigimod, a human IgG1 antibody Fc fragment engineered to reduce the pathogenic IgG autoantibody level, was developed as a treatment for MG. However, the long-term effects of the treatment are still unclear. The present report describes two novel cases of thymoma-associated MG exacerbation following efgartigimod treatment related to anti-AChR antibody overshoot. Both cases shared certain characteristics, including anti-AChR antibody positivity and post-thymectomy status. After a few cycles of efgartigimod treatment, their MG deteriorated, and their anti-AChR antibody titer exceeded the level before efgartigimod therapy. Prior studies show that anti-AChR antibody titer does not correlate with the disease severity of MG. However, previous studies have reported antibody overshoot following plasma exchange, which, like efgartigimod, reduces the level of plasma IgG and autoantibodies. Thus, MG exacerbation with anti-AChR antibody overshoot may be an adverse effect of both efgartigimod and plasma exchange. When clinical symptoms in patients with thymoma-associated MG receiving efgartigimod deteriorate despite low IgG, assessing the anti-AChR antibody level can be important for reconsidering the treatment strategy.

Effects of oral care on prolonged viral shedding in coronavirus disease 2019 (COVID-19).

AIM: To assess the effects of oral care on prolonged viral shedding in coronavirus disease 2019 (COVID-19) patients. METHODS AND RESULTS: We evaluated the clinical course of eight COVID-19 patients, including their duration of viral shedding, by PCR testing of nasopharyngeal swabs. The average time from the onset of symptoms until the virus was no longer detectable was 31.6 ± 11.8 days (mean ± SD; range 17-53). Thus, it took 15.1 ± 14.7 (1-40) days from the time of clinical recovery for the virus to become undetectable. In two patients who had mental retardation and psychiatric disorders, the viral shedding period continued for 44 days or 53 days. These two patients did not voluntarily brush their teeth. When they were instructed on the importance of oral care, including tooth brushing and gargling, their tests for the coronavirus became negative. CONCLUSION: Most of the patients with COVID-19 had a viral shedding period of 30 days or less. In cases of prolonged viral shedding (≥44 days), noninfectious viral nucleic acid may have accumulated in uncleaned oral cavities and continued to be detected. We propose that tooth brushing and gargling remove such viral nucleic acid and improve the accuracy of PCR testing.

The Successful Treatment of Severe Trigeminal Neuralgia by a Single Mandibular Nerve Block and Subsequent Natalizumab Administration in a Patient with Multiple Sclerosis.

We report the case of a middle-aged woman who developed trigeminal neuralgia as a sequela of multiple sclerosis (MS). The trigeminal neuralgia was refractory to medications and persisted for two years. Eventually, it was resolved by a mandibular nerve block followed by natalizumab administration. The pain was controlled for 23 months, and additional nerve blocks were not required during this period. It has been previously reported that natalizumab therapy improves the Expanded Disability Status Scale (EDSS) scores and health-related quality of life in patients with MS. In the present case, natalizumab may have prolonged the effect of the mandibular nerve block and consequently improved the patient's quality of life.

Dimethyl Fumarate Was Ineffective but Not Harmful for a Patient with Myelin Oligodendrocyte Glycoprotein Antibody Disease.

We treated a myelin oligodendrocyte glycoprotein (MOG) antibody disease patient who had been prescribed dimethyl fumarate because she was thought to have been suffering from multiple sclerosis (MS). Mild optic neuritis relapsed at one year and four months after the administration of dimethyl fumarate. Therefore, dimethyl fumarate was ineffective for preventing relapse of MOG antibody disease. However, dimethyl fumarate for MOG antibody disease was not harmful compared with when disease-modifying drugs (DMDs) of MS were used for anti-aquaporin-4 antibody-positive neuromyelitis optica. If MS patients repeat relapses even after the start of DMDs, a differential diagnosis including MOG antibody disease should be made.

Inflammatory Cerebellar PML with a CD4/CD8 Ratio of 2.9 Showed a Favorable Prognosis in a Patient with Rheumatoid Arthritis.

The patient was a 74-year-old woman with rheumatoid arthritis who developed ataxia. MRI revealed T2-hyperintense lesions predominantly in the left middle cerebellar peduncle. Punctate or linear Gd enhancement was also observed on T1-weighted images. A brain biopsy was conducted and the pathology revealed a mild demyelinated lesion. Polymerase chain reaction (PCR) of biopsied brain tissues revealed the presence of JC virus (JCV) DNA, but JCV-infected oligodendroglia-like cells were not apparent on immunohistochemistry. Sensitive in-situ hybridization, however, detected three JCV-positive cells and the infiltration of CD4+ and CD8+ T cells and plasma cells was also observed. Immunosuppressants were tapered off and mirtazapine and mefloquine administered, resulting in a favorable outcome.

Progressive cerebral atrophy in neuromyelitis optica.

We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients.

Two cases of acute myelitis with idiopathic hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome (IHES) is characterised by persistent eosinophilia and organ damage after ruling out other causes. IHES is clinically and pathologically heterogeneous, and several disease mechanisms have been described. Although neurological involvement with IHES is extremely rare, we report the first cases of acute myelitis with IHES, which are confirmed using MRI, fulfil the diagnostic criteria of IHES and pathologically reveal eosinophilic tissue infiltration in the liver and skin. Patient 1 had longitudinally extensive transverse myelitis, which developed in the absence of steroid therapy. Patient 2 developed acute myelitis with two short lesions during a 3 mg/day corticosteroid treatment. Both cases had eosinophilia (>1500/mm(3)) at the onset of myelitis. These findings suggest that earlier treatment and a sufficient dose of corticosteroids may prevent the lesional expansion in acute myelitis. Steroid therapy should be initiated early before organ involvement, because permanent neuronal damage with a larger lesion becomes more critical.

Abnormal nerve conduction study findings indicating the existence of peripheral neuropathy in multiple sclerosis and neuromyelitis optica.

OBJECTIVE: Chronic inflammatory demyelinating polyneuropathy (CIDP) has been reported in patients with multiple sclerosis (MS). However, there have been limited reports of peripheral neuropathy as a complication of neuromyelitis optica (NMO). In this paper, we showed the characteristics and differences between peripheral neuropathy as a complication of MS and NMO. METHOD: We analyzed a series of 58 MS and 28 NMO patients and evaluated nerve conduction studies (NCS) in 21 MS and 5 NMO patients. RESULTS: Six of the 58 MS and 3 of the 28 NMO patients revealed abnormal NCS findings. Three (5.2%) of the 58 MS patients fulfilled the criteria for CIDP. One (3.6%) of the 28 NMO patients showed peripheral neuropathy at the same time of NMO relapse, although CIDP was not seen in NMO. The other 5 (3 MS and 2 NMO) patients were complicated with neuropathy caused by concomitant diabetes mellitus and Sjögren's syndrome. CONCLUSION: Frequency of abnormal NCS findings might exhibit no significant difference between MS and NMO, although the cause and pathophysiology of peripheral neuropathy were different in MS and in NMO. There might be a group of NMO who were affected simultaneously in the central and peripheral nervous tissues.

Elderly-onset neuromyelitis optica which developed after the diagnosis of prostate adenocarcinoma and relapsed after a 23-valent pneumococcal polysaccharide vaccination.

We report a case of elderly-onset neuromyelitis optica (NMO) positive for the anti-aquaporin-4 (AQP-4) antibody; symptoms developed after the diagnosis of prostate adenocarcinoma and relapsed after a 23-valent pneumococcal polysaccharide vaccination. We suggest that activation of CD4-positive T cells and secretion of interferon-gamma induced by adenocarcinoma and complement activation induced by vaccination are responsible for the onset and relapse of NMO, even if a patient is positive for the anti-AQP-4 antibody. This case supports the previous experimental finding that the anti-AQP-4 antibody does not cause NMO-like lesions when injected alone, but does so after the induction of T cell-mediated experimental autoimmune encephalomyelitis or when co-injected with human complement.

Optic nerve and spinal cord are the major lesions in each relapse of Japanese multiple sclerosis.

For the purpose of predicting multiple sclerosis (MS) and neuromyelitis optica (NMO) relapses in Japanese population, we evaluated the localization and age of each demyelinating attack. We retrospectively analyzed the 78 medical records of Japanese MS and NMO patients. Then we identified 49 cases of relapsing-remitting-type patients and defined each of 116 demyelinating attacks. NMO had an older age at onset than MS, although the initial symptoms cannot predict the clinical phenotypes. Only 21.3% of demyelinating attacks were localized in the cerebrum and 78.7% were optic-spinal lesions, although MS comprised 70% and NMO comprised 30% of these 78 cases. Brainstem lesion had a relative male predominancy and a young age at attack. Our findings showed that optic nerve and spinal cord lesions are the major and critical lesions in each attack of Japanese CNS demyelinating diseases. There might be distinctive Japanese pathogenic features even in Western type MS.

The somatosensory cortex in multiple system atrophy.

In multiple system atrophy (MSA), it has been accepted that the motor-related cortical area may degenerate. However, there have been few investigations of the postcentral cortex of the somatosensory area. For this reason, we investigated the effects of MSA on both the precentral and the postcentral cortex and were able to demonstrate degenerative changes in each. Furthermore, our study showed that degeneration of the postcentral cortex preceded that of the precentral cortex. In addition, we showed that the Betz cells were not selectively lost, but merely depleted like other neurons of the deep cortical layers. Therefore, the effects of MSA are apparently related to selective loss of the small-sized myelinated fibers in the corticospinal tract.

Two subtypes of optic-spinal form of multiple sclerosis in Japan: clinical and laboratory features.

Seventy-seven cases of the optic-spinal form of multiple sclerosis (OSMS) were collected from 6 institutes in 3 cities of Japan, and the clinical and MRI features were analyzed. Two-thirds of the OSMS patients had longitudinally extensive spinal cord MRI lesions (LESL), and had clinical features similar to those of relapsing neuromyelitis optica which often causes severe disability. In contrast, OSMS patients without LESL tended to have milder disease and had some feature commonly seen in the conventional form of MS. The percentage of OSMS without LESL in total OSMS has recently been increasing. The present study suggests that LESL is crucially important for distinguishing the two subtypes of OSMS.

Interferon beta-1b exacerbates multiple sclerosis with severe optic nerve and spinal cord demyelination.

To evaluate the effect of interferon beta-1b (IFNB-1b) on multiple sclerosis (MS) with severe optic nerve and spinal cord demyelination, we examined the relationship between IFNB-1b treatment outcome and the clinical and genetic characteristics of three types of demyelinating diseases of the central nervous system, i.e., neuromyelitis optica (NMO), MS and MS with severe optic-spinal demyelination. Japanese MS frequently carried HLA DPB1*0501, which is associated with NMO. MS with DPB1*0501 showed severe optic-spinal demyelination represented by longitudinally extensive spinal cord lesion, blindness and CSF pleocytosis. IFNB-1b treatment did not succeed in these patients because of the increase of optic nerve and spinal cord relapse and other severe side effects. IFNB-1b should not be administered to demyelinating patients with genetic and clinical characteristics mimicking NMO such as HLA DPB1*0501 allele, longitudinally extensive spinal cord lesion, blindness and CSF pleocytosis even if they have symptomatic cerebral lesions as typically seen in MS. The present study strongly suggests that these patients should be diagnosed as having NMO.

[Transcortical sensory aphasia due to extensive infarction of left cerebral hemisphere].

We report a case of transcortical sensory aphasia occurred after extensive infarction of left cerebral hemisphere. A 68-year-old, right-handed man with atrial fibrillation suddenly developed cerebral embolism of left middle cerebral artery. He was treated conservatively, and the right hemiplegia, aphasia, apraxia in a slight degree and right hemispatial neglect in a slight degree consequently existed. MRI showed a large cortical and subcortical infarct lesion including the left Broca's area, central region, perisylvian area with Wernicke's area and temporal lobe. In contrast, neuropsychological evaluation using the Western Aphasia Battery (WAB) demonstrated transcortical sensory aphasia, e.g., fluency 8, auditory comprehension 1. repetition 10 and object naming 2.4. In addition to preserved repetition, both linguistic prosody and affective prosody were well preserved. Most cases with transcortical sensory aphasia are known to occur with the lesion including temporo-parieto-occipital junction of dominant hemisphere. Our patient and a few other reported cases of transcortical sensory aphasia had a lesion in perisylvian area including Wernicke's area. Therefore, it is possible that their minor hemisphere worked selectively for repetition. Furthermore, we suggest that this patient presented dissociative aphasia that all the process of repetition and the function of linguistic and emotional prosody were represented in the right hemisphere and the other functions including comprehension of word meanings were existed in the left hemisphere. We believe that our case of transcortical sensory aphasia with dissociative aphasia gives a suggestion about the mechanism and localization of repetition and prosody in the whole system of language.

Characterization of the T cell receptor repertoire in the Japanese neuromyelitis optica: T cell activity is up-regulated compared to multiple sclerosis.

To characterize T cell immunity in Japanese neuromyelitis optica (NMO), we examined the T cell receptor (TCR) repertoire in NMO patients with complementarity-determining region 3 (CDR3) spectratyping and compared the results with those from multiple sclerosis (MS) patients and healthy subjects. Both NMO and MS patients had a larger number of clonally expanded Vbeta genes than healthy subjects. Moreover, NMO patients had a significantly larger number of expanded Vbetas than MS patients. The detailed analysis revealed that Vbeta1 and Vbeta13 were significantly activated in NMO than MS. These results reflected unique pathophysiology of Japanese NMO, which is distinguishable from that of MS. Furthermore, longitudinal examinations of the TCR repertoire demonstrated that the number of clonally expanded Vbetas in NMO correlates with the Kurtzke Expanded disability status scale (EDSS). Although the activation pattern of the TCR repertoire in relapsing-remitting MS (RRMS) was similar to that in NMO, secondary progressive MS (SPMS) patients with longer disease durations and higher EDSS scores consistently had a smaller number of clonally expanded Vbetas than RRMS patients. Detailed TCR investigations will provide useful information to evaluate the clinical and immunological status of NMO and MS and to develop effective immunotherapies.