Migraine is a common and often disabling disease with a prominent genetic basis. There are many comorbidities associated with migraine which have been identified as risk factors for progression to chronic migraine. Each of these has its own genetic load and shares some common characteristics with migraine. The identification of migraine comorbidities may help clarify common underlying genetic and biological mechanisms of diseases. The treatment of migraine should involve a multifaceted approach, aimed at identifying and reducing possible risk and comorbidity factors. This may prevent the evolution toward a chronic form and then toward pharmacological resistance.
Background: Autoimmune cerebellar ataxia (AICA) is a general term for diseases in which the cerebellum is damaged by an autoimmune mechanism. For the diagnosis of the AICA, anti-thyroid antibodies (anti-thyroid peroxidase antibody and anti-thyroglobulin antibody), anti-glutamic acid decarboxylase (GAD) antibodies, and anti-gliadin antibodies are measured. Immunotherapy is known to be effective for AICA, but some patients with effective immunotherapy lack autoantibodies associated with cerebellar ataxia. The purpose of this study was to clarify whether the effectiveness of immunotherapy in patients with suspected AICA could be predicted by anti-mouse cerebellar tissue-derived antigen antibody tests. Methods: This study was conducted on 25 patients with idiopathic cerebellar ataxia (excluding multiple system atrophy, hereditary spinocerebellar degeneration, cancer-bearing patients, and patients taking phenytoin) who received immunotherapy from 2005 to 2016 at Tokyo Medical University Hachioji Medical Center. The patients were suspected of having AICA because they were positive for cerebellar ataxia-related autoantibodies (anti-thyroid antibody, anti-GAD antibody, anti-gliadin antibody, or anti-transglutaminase 6 antibody) or other autoantibodies. Antibodies that bind to mouse cerebellar tissue-derived antigens were defined as “anti-mouse cerebellar tissue-derived antigen antibodies” in this study, and their IgG-class antibodies were comprehensively measured using a slot blot. Results: Anti-mouse cerebellar tissue-derived antigen antibody test results were correlated with immunotherapy efficacy. Furthermore, the combination of anti-mouse cerebellar tissue-derived antigen and anti-GAD antibody tests could predict the effectiveness of immunotherapy with 83% sensitivity and 100% specificity, while the combination of the anti-mouse cerebellar tissue-derived antigen, anti-GAD, and anti-gliadin (IgA class) antibody tests could predict the effectiveness of immunotherapy with 94% sensitivity and 86% specificity. Conclusion: Anti-mouse cerebellar tissue-derived antigen antibody tests could help to provide useful information for immunotherapy administration to patients with idiopathic cerebellar ataxia suspected to be AICA.
A 16-year-old male was brought to the emergency room with fever and status epilepticus, and was diagnosed with febrile infection-related epilepsy syndrome (FIRES). Seizure control was not achieved and the patient developed multiple complications. Ketamine infusion therapy and intrathecal dexamethasone therapy were administered, in addition to other anti-seizure treatment and immunotherapy for super-refractory status epilepticus (SRSE). The patient was weaned from the ventilator on day 170 and was able to live at home, although he continued to experience monthly focal motor seizures and moderate motor impairment. This case suggests that more aggressive treatment might be an option in FIRES with prolonged SRSE.
A 42-year-old male had intractable hyperkinetic seizure since childhood. Bottom-of-sulcus dysplasia was shown by MRI to be most likely an ictal focus, whereas ictal semiology suggested possible focus in the left frontal cortex. Scalp-recorded EEG could not delineate ictal EEG change at all partly because of violent hyperkinetic seizure, and thus intracranial EEG study by epidural electrodes was conducted as the best procedure for the safety concern. It showed ictal focus over the bottom-of-sulcus dysplasia and thus it was completely resected with seizure free more then 20 years until now. It was concluded that epidural electrodes are regarded as safe invasive recording method especially for violent hyperkinetic seizure, and that can provide us with essential information before epilepsy surgery.
A 69-year-old man visited our hospital complaining of fatigue in the lower extremities while walking. The patient had a two-year history of congestive heart failure and received a permanent artificial pacemaker implantation for sick sinus syndrome. Physical examination revealed proximal muscle weakness and exaggerated lumbar lordosis. Serum creatine kinase level was 1,455 U/l. The atrophies of the paraspinal muscles at thoracic to lumbar spine levels, rectus abdominis and soleus muscles were detected on computed tomography. Muscle biopsy showed mild to moderate variability in muscle fiber size with regenerating and necrotic muscle fibers. Mononuclear cell infiltration was not found. HLA-ABC expression was minimum. After anti-mitochondrial M2 antibody was detected, administration of oral prednisolone resulted in improvements in muscle strength and serum creatine kinase level. Based on the clinical course, examination and clinical findings, the patient was diagnosed as anti-mitochondrial M2 antibody positive myositis. Anti-mitochondrial M2 positive myositis is not only difficult to diagnose by muscle biopsy, but can also be preceded or complicated by fatal cardiac complications.
This case involved a 72-year-old woman. From the day after mitral annuloplasty, a fever over 37°C and ballismus-like involuntary movements of the right upper and lower limbs appeared. A few month later, involuntary movements spread throughout the body, and she developed impairment of consciousness and difficulty speaking and eating. Levels of protein in cerebrospinal fluid were high. Positive results were seen for serum mumps immunoglobulin G and M antibody. Because steroid pulse therapy proved effective, we suspected autoimmune encephalitis associated with mumps virus infection.
A 75-year-old female had a history of prior ischemic stroke with aphasia and right hemiplegia. Magnetic resonance angiography showed left internal carotid artery occlusion. She was successfully treated with intravenous recombinant tissue plasminogen activator (IV t-PA) and underwent endovascular thrombectomy (EVT). She was diagnosed with cardioembolic stroke due to the presence of atrial fibrillation and mitral valve stenosis, and warfarin was administered. However, she experienced large vessel occlusion twice within 2 years. Upon further analysis, transesophageal echocardiography revealed a mobile hyperechoic structure on the aortic valve, which was assumed to be an embolic source. Thus, we decided to perform mitral and aortic valve replacement. The excised aortic valve structure was suggested to be an example of Lambl’s excrescence, histopathologically. After surgery, the patient had no recurrence for 3 years. Several cases of ischemic stroke associated with Lambl’s excrescence have been reported, but definitive guidelines for managing patients with Lambl’s excrescence do not currently exist. Surgical intervention for Lambl’s excrescence with recurrent ischemic events may be important for preventing further recurrence.
We conducted a survey of 16 Japanese patients (9 males, 7 females) aged 48–70 years in the advanced-stage Okinawa-type neurogenic muscular atrophy (i.e. hereditary motor and sensory neuropathy with proximal dominant involvement: HMSN-P) by a questionnaire asking the patients’ disease name notification, acceptance, and expectations for treatment. In amyotrophic lateral sclerosis (ALS), since symptoms such as four-limb motor weakness and respiratory disorder are serious, patients are notified of the disease name at each progression stage. Individuals with HMSN-P exhibit ALS-like severe motor paralysis, but HMSN-P shows autosomal dominant inheritance, and progresses slowly (over >30 years). Many of the present patients who had one parent with the disease were able to predict what their diagnosis would be. However, several patients stated that they could not sleep for several months due to the shock of the diagnosis and their concern about how to explain to their children that the disease is hereditary. All patients in the advanced stage of HMSN-P progress to severe proximal dominant quadriplegia and ultimately need auxiliary tools such as a wheelchair. New developments toward a specific HMSN-P treatment are expected, with methods such as nucleic acid medicine.
A 70-year-old woman was admitted to our hospital due to bilateral optic neuritis and left facial sensory disturbance that became exacerbated over 10 days. Both serum and cerebrospinal fluid (CSF) were negative for aquaporin 4 antibody and myelin oligodendrocyte glycoprotein antibody. A high level of myelin basic protein (MBP) in her CSF was observed. Brain MRI showed a high T2 signal and contrast enhancement of the bilateral optic nerve, intramedullary tract and central myelin lesion in the trigeminal nerve. After intravenous methylprednisolone pulse therapy, her visual impairment and facial sensory disturbance gradually improved. She was diagnosed with clinically isolated syndrome, based on 2017 McDonald criteria. A diagnosis of multiple sclerosis (MS) was suspected due to the trigeminal myelin lesion confined to the central myelin portion and high level of MBP in the CSF. Treatment with dimethyl fumarate has been effective for preventing recurrence in 13 months in this patient. The central-peripheral myelin transitional zone at the trigeminal nerve is located 1–6 mm from the pons, where central myelin changes to the peripheral myelin. This patient showed a high T2 signal at the trigeminal nerve 3 mm from the pons on MRI, suggesting the involvement of a central trigeminal myelin lesion. Findings of a central trigeminal myelin lesion on MRI may aid in differentiating between MS and seronegative neuromyelitis optica spectrum disorder.