Paraneoplastic cerebellar degeneration with anti-Yo antibodies and an associated submandibular gland tumor: a case report.

BACKGROUND: As a debilitating syndrome, paraneoplastic cerebellar degeneration (PCD) remains challenging to treat. Further, anti-Yo antibody (directed against human cerebellar degeneration-related protein 2) detection in patients with PCD is associated with unsatisfactory responses to existing therapies. Here, we present the case of a 60-year-old woman who developed PCD with anti-Yo antibodies and a submandibular gland tumor. CASE PRESENTATION: A 60-year-old woman presented with a 5-day history of unsteadiness of gait and inadequate coordination of her extremities, along with truncal instability. Although walking without aid was possible, dysmetria of all four limbs, trunk, and gait ataxia was observed. While routine biochemical and hematological examinations were normal, the patient's blood was positive for anti-Yo antibodies. When the neurological symptoms deteriorated despite administration of intravenous methylprednisolone, fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) images with contrast enhancement were performed, which showed a tumor in the left submaxillary gland. She underwent total left submandibular gland resection, including the tumor; histological and immunohistochemical results revealed a salivary duct carcinoma. She was administered intravenous methylprednisolone, followed by 10 plasma exchange sessions, intravenous immunoglobulins, and cyclophosphamide therapy. Following treatment, her symptoms were not alleviated, even after the reduction of anti-Yo titers. CONCLUSIONS: Although tumor detection was delayed, early tumor detection, diagnosis, and PCD treatment are essential because any delay can result in the progression of the disorder and irreversible neurological damage. Therefore, we recommend that the possibility of a salivary gland tumor should be considered, and whole-body dual-modality CT, including the head and neck, and FDG-PET should be performed at the earliest for patients with well-characterized paraneoplastic antibodies when conventional imaging fails to identify a tumor.

Anti-myelin Oligodendrocyte Glycoprotein Antibody-positive Myelitis after Coronavirus Disease 2019.

We herein report a case of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-related myelitis caused by coronavirus disease (COVID-19) infection in 2021. A 22-year-old man with no history of any related illness contracted COVID-19. Eight days later, he developed bladder problems, paraplegia and sensory disturbances. Cervical spinal cord magnetic resonance imaging revealed extensive hyperintensity at T2 and spinal cord lesions extending from C4 to Th1. The patient was diagnosed with transverse myelitis and started on intravenous methylprednisolone, plasma exchange and intravenous immunoglobulin therapy. The symptoms improved only after intravenous methylprednisolone therapy. Anti-MOG antibodies were found in his serum and cerebrospinal fluid during routine screening. As this observation is unusual and could cause serious health problems, we wonder if COVID-19 triggered this autoimmune response.

Investigation of antiphosphatidyl-serine antibody and antiphosphatidyl-inositol antibody in ischemic stroke patients.

Antiphospholipid syndrome is characterized by arterial or venous thrombosis and the presence of antiphospholipid antibodies (aPL). We measured ß2-GPI aCL, IgGaCL, LA, antiphosphatidyl-serine antibody (PS), and antiphosphatidyl-inositol antibody (PI) in each patient at one month after the onset of stroke. In addition, carotid artery echography was performed in patients positive for PI or PS. Among the 250 patients, 13.6% (34/250) were positive for either PI or PS, and 6.8% (17/250) were positive for both. Carotid artery echography performed on these 34 patients showed that the frequencies of increased intimal-medial thickness (IMT) of 1.1 mm or more, plaque, and carotid artery stenosis of 50% or more were all significantly higher in patients positive for antinuclear antibody than those negative for the antibody (P < .05). PI and PS are associated with antinuclear antibody and precipitation of atherosclerosis. Ischemic stroke patients with SLE frequently showed a variety of antiphospholipid-protein antibodies.

Comparison between single antiplatelet therapy and combination of antiplatelet and anticoagulation therapy for secondary prevention in ischemic stroke patients with antiphospholipid syndrome.

Satisfactory results have not yet been obtained in therapy for secondary prevention in ischemic stroke patients with antiphospholipid syndrome (APS). We therefore compared single antiplatelet therapy and a combination of antiplatelet and anticoagulation therapy for secondary prevention in ischemic stroke patients with APS.The subjects were 20 ischemic stroke patients with antiphospholipid antibody, 13 with primary antiphospholipid syndrome and 7 with SLE-related antiphospholipid syndrome. Diagnosis of APS was based on the 2006 Sydney criteria. Eligible patients were randomly assigned to either single antiplatelet therapy (aspirin 100 mg) or a combination of antiplatelet and anticoagulation therapy (target INR: 2.0-3.0; mean 2.4+/-0.3) for the secondary prevention of stroke according to a double-blind protocol. There was no significant difference between the two groups in age, gender, NIH Stroke Scale on admission, mRS at discharge, or rate of hypertension, diabetes mellitus, hyperlipidemia, or cardiac disease. We obtained Kaplan-Meier survival curves for each treatment. The primary outcome was the occurrence of stroke. The mean follow-up time was 3.9+/-2.0 years. The cumulative incidence of stroke in patients with single antiplatelet treatment was statistically significantly higher than that in patients receiving the combination of antiplatelet and anticoagulation therapy (log-rank test, p-value=0.026). The incidence of hemorrhagic complications was similar in the two groups. The recent APASS study did not show any difference in effectiveness for secondary prevention between single antiplatelet (aspirin) and single anticoagulant (warfarin) therapy. Our results indicate that combination therapy may be more effective in APS-related ischemic stroke.

Characteristics of Cerebral White Matter Lesions on MRI in Juvenile Patients with Migraine.

OBJECTIVE: Cerebral white matter lesions (WMLs) have been frequently observed on MRI in patients with migraine. We investigated characteristics of WMLs in migraine and tried to determine the relationship between its causal mechanism and arteriosclerosis. METHODS: A head MRI was performed in juvenile migraine patients. The distributions of deep and periventricular WMLs were separately studied in the anterior and posterior circulation. Grading was conducted according to the Fazekas classification. Arteriosclerotic risk factors were identified, and their effects on WMLs were investigated. RESULTS: WMLs were observed in 85 (40.5%) of 210 patients in our hospital. This is significantly higher than the 10 (19.2%) of 63 patients in the control group (p < 0.01). WMLs were significantly observed on the anterior territory of the deep white matter (p < 0.01) and the posterior territory of the periventricular white matter (p < 0.05). Multivariable analysis revealed that the occurrence of WMLs was not related to arteriosclerotic risk factors, while migraine (p < 0.01) and aging (p < 0.05) were significant risk factors. CONCLUSION: While migraine was a risk factor of WMLs, its relationship with arteriosclerotic factors was weak. Accordingly, a mechanism other than arteriosclerosis may be involved.

[Epidemiology of headache].

We discuss here the epidemiology of chronic headache. Headache is a widespread and costly public health problem. Few people do not experience headache: in men, the lifetime prevalence for headache of any kind is 93 %, and for women it is up to 99%. Approximately 8.4 million people in Japan suffer from migraine, and 22 million have tension-type headache. Despite the painful, costly, and disabling impact of headache, many patients with headache do not seek medical advice. It is important to recognize the incidence of various kinds of chronic headache, and to diagnose and treat them correctly. In this article, we review the incidence, precipitating factors, regional prevalence, and age dependence of the incidence of each type of chronic headache.

Examination of fluctuations in atmospheric pressure related to migraine.

BACKGROUND: Japan has four seasons and many chances of low atmospheric pressure or approaches of typhoon, therefore it has been empirically known that the fluctuation of weather induces migraine in people. Generally, its mechanism has been interpreted as follows: physical loading, attributed by atmospheric pressure to human bodies, compresses or dilates human blood vessels, which leads to abnormality in blood flow and induces migraine. We report our examination of the stage in which migraine tends to be induced focusing on the variation of atmospheric pressure. FINDINGS: Subjects were 34 patients with migraine, who were treated in our hospital. The patients included 31 females and three males, whose mean age was 32 ± 6.7. 22 patients had migraine with aura and 12 patients had migraine without aura. All of patients with migraine maintained a headache diary to record atmospheric pressures when they developed a migraine. The standard atmospheric pressure was defined as 1013 hPa, and with this value as the criterion, we investigated slight fluctuations in the atmospheric pressure when they developed a migraine. It was found that the atmospheric pressure when the patients developed a migraine was within 1003-1007 hPa in the approach of low atmospheric pressure and that the patients developed a migraine when the atmospheric pressure decreased by 6-10 hPa, slightly less than the standard atmospheric pressure. CONCLUSION: Small decreases of 6-10 hPa relative to the standard atmospheric pressure of 1013 hPa induced migraine attacks most frequently in patients with migraine.

[Diagnosis and potential treatment of antiphospholipid syndrome-related mainly on ischemic stroke].

Antiphospholipid syndrome (APS) was defined in 2006 by an international consensus as an autoimmune disease that manifests clinically as recurrent thrombotic complications or fetal loss and serologically as elevated plasma levels of antiphospholipid antibodies (aPLs). aPLs are a heterogeneous group of antibodies directed against anionic phospholipids, phospholipid-binding plasma proteins, and phospholipid-protein complexes. Standard ELISA for anticardiolipin (aCL) and anti-ß2-glycoprotein I antibodies and clotting assays for lupus anticoagulant (LA) are recommended for detecting aPLs. Phosphatidylserine-dependent anti-prothrombin antibody (aPS/PT) assay may also be useful as a confirmatory test for APS. aPLs are an independent risk factor for initial occurence of ischemic stroke, especially in young adults. APS patients with thrombotic stroke frequently have other, often conventional, vascular risk factors. Guidelines issued in 2011 by the American Heart Association and American Stroke Association recommended antiplatelet therapy for patients with cryptogenic ischemic stroke or TIA and who test positive for aPL. In contrast, oral anticoagulants with a target international normalized ratio (INR) of 2.0-3.0 are recommended for patients with ischemic stroke who meet all the criteria for APS. Recently, 3 new anticoagulants for stroke prevention, dabigatran, rivaroxaban, and apixaban, have been studied in phase 3 clinical trials in patients with atrial fibrillation. However, optimal treatment for catastrophic APS is unknown. Current treatment guidelines emphasize the importance of early diagnosis and recommend aggressive therapies to avoid a fatal outcome. Combinations of high doses of intravenous heparin, steroids, and immunoglobulins and/or repeated plasma exchanges can be considered as treatments of choice for this severe condition.

Preventive effect of cyproheptadine hydrochloride in refractory patients with frequent migraine.

Cyproheptadine hydrochloride (CH) is rarely used to treat adult patients with migraine in Japan because it causes sleepiness. In this study, we investigated the preventive effect of CH in 12 patients who had failed to respond to conventional preventive treatments among 103 migraine patients treated at our hospital. These 12 subjects had all received unsuccessful migraine prophylaxis with lomerizine, valproic acid and topiramate, or had discontinued these treatments due to adverse reactions. Initially, the subjects were given 4 mg CH before sleeping. In those who experienced no clinically significant sleepiness following the treatment, the drug was orally administered at 4 mg after breakfast as well (8 mg per day in total). Drug efficacy was evaluated by examining the frequency of migraine at one month and three months after the start of treatment. The frequency of migraine was dramatically reduced in all patients within 7 to 10 days after starting treatment. The average frequency of migraine during the three-month period was 2.6 episodes per month, representing a significant (p < 0.01) reduction from the pretreatment frequency of over 10 per month. Our results indicate that CH may be effective as a migraine-preventive treatment for patients in whom conventional drugs have been ineffective or have caused side effects. But this study is not a double blind randomized trial, and an open study with no control group.

Hemiplegic peripheral neuropathy accompanied with multiple cranial nerve palsy.

A 32-year-old man experienced double vision around January, 2010, followed by weakness of his left upper and lower extremities. Articulation disorders and loss of hearing in his left ear developed, and he was admitted to our hospital on February 14, 2010. Physical examination was normal, and neurological examination showed clear consciousness with no impairment of cognitive function, but with articulation disorders. Olfactory sensation was reduced. Left ptosis and left gaze palsy, complete left facial palsy, perceptive deafness of the left ear, and muscle weakness of the left trapezius muscle were observed. Paresis in the left upper and lower extremities was graded 4/5 through manual muscle testing. Sensory system evaluation revealed complete left-side palsy, including the face. Deep tendon reflexes were slightly diminished equally on both sides; no pathologic reflex was seen. No abnormality of the brain parenchyma, cerebral nerves or cervicothoracolumbar region was found on brain magnetic resonance imaging. On electroencephalogram, alpha waves in the main frequency band of 8 to 9 Hz were recorded, indicating normal findings. Brain single photon emission computed tomography (SPECT) scan showed reduced blood flow in the right inner frontal lobe and both occipital lobes. Nerve biopsy (left sural nerve) showed reduction of nerve density by 30%, with demyelination. The patient also showed manifestations of multiple cranial nerve disorder, i.e., of the trigeminal nerve, glossopharyngeal nerve, vagus nerve, and hypoglos-sal nerve. Whole-body examination was negative. Finally, based on ischemic brain SPECT images, spinal fluid findings and nerve biopsy results, peripheral neuropathy accompanied with multiple cranial nerve palsy was diagnosed.

Study of phosphatidylserine-dependent anti-prothrombin antibody in cerebral infarction.

PURPOSE: This study was carried out to clarify the relationship of IgG phosphatidylserine-dependent anti-prothrombin antibody (aPS/PT), IgG beta 2 glycoprotein I-dependent anticardiolipin antibody (beta 2-GPI aCL), and lupus anticoagulant (LA) to cerebral infarction, using data from 93 patients who visited our hospitals. MATERIALS AND METHODS: We computed the positive rates for each of IgG aPS/PT, beta 2-GPI aCL, and LA in the 93 patients with cerebral infarction, and carried out logistic regression analysis with IgG aPS/PT as the outcome variable and with beta 2-GPI aCL, LA, and each risk factor as predictor variables in order to assess the relationship of IgG aPS/PT with each factor. RESULTS: IgG aPS/PT was more highly correlated with LA than beta 2-GPI aCL in IgG aPS/PT-positive patients with cerebral infarction. IgG aPS/PT itself appears to have high specificity as a marker for antiphospholipid syndrome (APS), because there were patients who were IgG aPS/PT-positive but both beta 2-GPI aCL- and LA-negative. CONCLUSION: In IgG aPS/PT-positive patients with cerebral infarction, IgG aPS/PT is more highly correlated with LA than beta 2-GPI aCL. It is also strongly associated with APS. Measurement of IgG aPS/PT in patients with cerebral infarction could be of diagnostic value.

A case of hypertrophic pachymeningitis with prolonged headache, attributable to Epstein-Barr virus.

Hypertrophic pachymeningitis is a condition characterized by significant chronic inflammatory thickening of the cranial dura mater, frequently presenting with symptoms such as headache and cranial neuropathy. In this report, we describe a very rare case of hypertrophic pachymeningitis, considered to be attributable to Epstein-Barr virus (EBV), which was diagnosed in a patient who visited our hospital with a complaint of ongoing severe headaches. The diagnosis was based on positive specific serum EBV antibody titers, with VCA-IgM levels of less than 1:10, VCA-IgG levels of 1:160, and EBNA levels of 1:40, as well as on the results of magnetic resonance imaging of the head with contrast media.

Clinical efficacy of rizatriptan for patients with migraine: efficacy of drug therapy for migraine accompanied by tension headache-like symptoms, focusing on neck stiffness.

According to an epidemiological study in Japan, there are as many as 22 million patients with tension headache and 8.4 million with migraine. Furthermore, patients suffering from both types of headache concurrently are estimated to account for more than 50% of headache patients. We studied the efficacy of drug therapy for migraine accompanied by tension headache-like symptoms, focusing principally on neck stiffness. We evaluated the efficacy of rizatriptan by comparison of findings before and after therapy in 34 migraine patients, consisting of 16 without neck stiffness (migraine without neck factor: WONF) and 18 with it (migraine with neck factor: WNF), who received treatment at our neurology/internal medicine department from 1 March 2004 to 31 May 2005. In the study, all the patients were asked to keep a record of their migraine status. The severity of migraine was classified by physicians according to the International Headache Society diagnostic criteria, based on which drug efficacy was evaluated. We selected rizatriptan for migraine treatment in our study based on Dr. Ferrari's report. In the efficacy study of rizatriptan, in the group of 34 migraine patients, the pain relief rate (79.4%) and pain-free rate (41.2%) at two hours after treatment were as high as those reported in the meta-analysis performed by Ferrari et al., indicating high efficacy of rizatriptan. In the efficacy comparison between the WONF and WNF groups, the painfree rates were 56.3% and 27.8%, and cumulative pain relief rates were 100% and 61.1%, respectively, with better results in the WONF group. A test result was also significantly better (p=0.0076) in the WONF group. Rizatriptan was proved effective in treating migraine patients accompanied by tension headache-like symptoms. Comparison of efficacy rates between patient groups with and without tension headache-like symptoms showed that the pain relief rate in the group without neck stiffness was higher.