[Nicotine, pesticides, and tobacco, in Three Act Tragedy].

Since one of the main characters in Three Act Tragedy was an actor, the three murders described in the book have been likened to a curtain. The three seemingly unrelated murders were connected at the end of the story, a thrill unique to the author, Agatha Christie. Nicotine was used in all three murders in this book. Nicotine is highly toxic and was one of the main pesticides used until the mid-20th century. Although its use is currently prohibited, neonicotinoid pesticides, which have reduced toxicity, are still being used. Problems with nicotine intoxication include accidental ingestion by young children, green tobacco sickness, and suicide attempts. When nicotine enters the body, it binds to acetylcholine receptors and causes various symptoms.

[Adrenoleukodystrophy: Lorenzo's Oil].

Lorenzo's Oil, an American movie released in 1992, is based on a true story of a couple who spare no effort to search for a cure for their 5-year-old son who gradually develops eccentricities and signs of progressive motor and speech disturbances and is diagnosed with adrenoleukodystrophy. Despite lack of medical knowledge, Lorenzo's parents embark on a mission to study the disease on their own and eventually discover a therapeutic mixture referred to as Lorenzo's oil. Most characters in the movie retained real-life names. Even after its release in 1992, the movie has provided some subjects in many ways.

[The Myasthenia Gravis Activities of Daily Living score and associated factors to distinguish the refractory phase in generalized myasthenia gravis patients with 5 years or more disease duration].

Associated factors of the Myasthenia Gravis Activities of Daily Living (MG-ADL) score were investigated in 55 patients who had had generalized MG for more than 5 years. In multivariate analysis, correlates of the MG-ADL score at the last follow-up were the total number of fast-acting treatments (FTs) (standardized regression coefficient 0.617，P < 0.001) and Myasthenia Gravis Foundation of America (MGFA) classification (standardized regression coefficient 0.227，P = 0.032) (F = 32.7，P < 0.001). In patients with a score of 5 or more on MG-ADL at the last follow-up, tendency as follows were seen: 1) early-onset (P = 0.002), 2) longer duration (P = 0.014), 3) high frequency of MGFA classification V (P = 0.017), 4) high frequency of the total number of FTs (P < 0.001), and 5) higher dose of prednisolone at the last follow-up (P = 0.003). MGFA V, early-onset without depending on E-L-T classification, or difficulty of reduction for high doses of prednisolone can be the target of novel treatment for MG, and future prospective study will be expected.

[Essential Tremor That is Difficult to Improve with Standard Medical Treatment-Suppression: Excluding Surgical Treatment].

For essential tremors that are refractory to standard medical treatment, surgical treatment is considered when there is obstruction in activities of daily living. However, there are patients who do not wish to undergo or are contraindicated for surgical treatment. In this paper, we explored what is considered to be the standard medical treatment and when surgery cannot be performed. In Japan, medical treatment is based on the use of arotinolol and primidone, and combination therapy and second-line drugs are extensively discussed. Furthermore, an algorithm of the treatment for essential tremors in Japan has been provided.

Aseptic meningitis as an initial presentation of Sjögren syndrome: a report of two cases and literature review.

Sjögren syndrome (SS) is one of several collagen vascular diseases that occasionally involve the central nervous system. We report two cases of SS involving young patients who initially presented with aseptic meningitis. A male with recurrent AM was found to have anti-Ro/SSA and La/SSB antibodies in a screening test for autoimmune process. A minor salivary gland biopsy revealed lymphocytic infiltrations compatible with SS, although the patient did not exhibit sicca symptoms. A female presenting with AM and polyarthritis also reported xerophthalmia. Anti-Ro/SSA antibody testing and a positive result in a minor salivary gland biopsy led to the diagnosis of SS. In the literature review, we found that AM or aseptic meningoencephalitis (AME) preceded or had a concomitant onset with SS in approximately 70% of cases. Screening for anti-Ro/SSA antibody, as well as systemic assessment for rheumatic symptoms, may be useful for diagnosing AM/AME of unknown etiology.

Initial deterioration and intravenous methylprednisolone therapy in patients with myasthenia gravis.

INTRODUCTION: In myasthenia gravis (MG) patients on intravenous methylprednisolone (IVMP) therapy, initial deterioration should be carefully monitored because it may cause myasthenic crisis. The aim of this study was to investigate the onset, duration and related factors of initial deterioration from the first IVMP in MG patients. METHODS: A total dose of IVMP in the first cycle of 750 mg or less, over 750 to 1500 mg, and over 1500 to 3000 mg was used in the analysis. Initial deterioration was evaluated in qualitative and quantitative evaluation and was defined as an increase of 2 or more points on the The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale after the start of IVMP therapy in the quantitative evaluation. RESULTS: We enrolled 51 mainly mild MG patients. The mode of onset of initial deterioration from the first IVMP treatment was day 4 in the qualitative and quantitative evaluation. In addition, the mode of duration was 3 days. In multiple logistic regression analysis, factors related to initial deterioration were MGFA classification with overall disease duration up to just before IVMP and thymectomy before IVMP in both the qualitative and the quantitative evaluation (p < .001). One to four cycles of IVMP improved the MG-ADL score at hospital discharge from that at the start of IVMP (p < .001). CONCLUSION: Disease severity and thymectomy before IVMP are related to initial deterioration in MG patients. IVMP can be repeated after initial deterioration weekly in most patients.

Screening for Fabry Disease in Japanese Patients with Young-Onset Stroke by Measuring α-Galactosidase A and Globotriaosylsphingosine.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in GLA, which encodes the enzyme α-galactosidase A (α-Gal A). Although the prevalence of Fabry disease in patients with stroke has been reported to range from 0% to 4%, few cohort studies have examined Japanese stroke patients. We aimed to clarify the prevalence of Fabry disease and the frequency of GLA mutations among patients with young-onset stroke in Japan. METHODS: From April 2015 to December 2016, we enrolled patients with young-onset (≤60 years old) ischemic stroke or intracerebral hemorrhage. We measured α-Gal A activity and the concentration of globotriaosylsphingosine in plasma. Genetic evaluations were performed in patients with low α-Gal A activity or high concentrations of globotriaosylsphingosine. RESULTS: Overall, 516 patients (median age of onset, 52 years old; 120 women) were consecutively enrolled in this study. Five patients (4 men and 1 woman) had low α-Gal A activity, and no patients were detected with the screen for plasma globotriaosylsphingosine levels. The genetic analysis did not identify a causative mutation responsible for classic Fabry disease in any of the patients, but 2 patients (.4%) carried the p.E66Q in GLA. CONCLUSIONS: No patient with Fabry disease was detected in our young-onset stroke cohort.

A case of anti-MOG antibody-positive unilaterally dominant meningoencephalitis followed by longitudinally extensive transverse myelitis.

BACKGROUND: There are few reports of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive, unilaterally dominant cerebral cortical encephalitis onset with epilepsy. We present such a case in a young female patient with myelitis. CASE PRESENTATION: A 19-year-old female developed generalized tonic seizures lasting several minutes. She had a low-grade fever and headache without other clinical neurological abnormalities while at our hospital. Cerebrospinal fluid (CSF) showed mononuclear pleocytosis. Other laboratory tests indicated no apparent abnormalities. Unilateral meningeal hyperintensity was seen on T2 fluid-attenuated inversion recovery MRI with associated cortical swelling and gadolinium enhancement of the cortical layer. One thousand mg/day of levetiracetam and a 3-day course of intravenous methylprednisolone at 1000 mg/day were administered. Dysuria appeared on the twentieth day of illness, and spinal MRI revealed a longitudinally extensive cord lesion from C5 to L1 consistent with myelitis. Two cycles of a 3-day course of intravenous methylprednisolone at 1000 mg/day were administered, and all symptoms disappeared. We found the patient to be anti-MOG antibody-positive using serum and CSF (titer: serum 1:256; CSF 1:128). CONCLUSION: Our report illustrates a unique case of anti-MOG presenting as new onset epilepsy secondary to unilaterally dominant meningoencephalitis preceding the onset of longitudinally extensive transverse myelitis.

Acetylcholine receptor antibody-positive myasthenia gravis associated with small-cell lung cancer: A case report.

RATIONALE: Only few cases of myasthenia gravis (MG) associated with small-cell lung cancer (SCLC) have been reported, and cases positive for acetylcholine receptor antibody (AChR-ab) are even rarer. The efficacy of standard MG treatment, such as cholinesterase inhibitor therapy, immunosuppressive therapy using steroids and immunosuppressive drugs, plasma exchange, and intravenous immune globulin (IVIg), for these cases is unclear. PATIENT CONCERNS AND DIAGNOSES: A 71-year-old man complained of bilateral eyelid ptosis. He also presented with dysphagia and masticatory muscle fatigue after chewing. The edrophonium test was positive, and the serum AChR-ab level was increased; therefore, the patient was diagnosed with MG. Computed tomography scan showed a nodule on the left upper lobe of the lung and mediastinal lymphadenopathy. Further examination revealed the lesion as SCLC. Finally, he was diagnosed with AChR-ab-positive MG associated with SCLC. INTERVENTIONS AND OUTCOMES: Oral pyridostigmine and tacrolimus were administered to treat MG; however, his symptoms worsened. Therefore, methylprednisolone and IVIg were administrated, which temporarily improved his symptoms. However, they remained uncontrolled. Meanwhile, chemotherapy with carboplatin and etoposide was administered to treat his SCLC. The lesions shrunk, and the MG symptoms and serum AChR-ab level also improved. LESSONS: AChR-ab-positive MG may develop as a comorbidity of SCLC. In such cases, management might require treatment for SCLC in addition to the standard MG treatment to stabilize the MG symptoms.

Neurological Complications in Eosinophilic Granulomatosis with Polyangiitis (EGPA): The Roles of History and Physical Examinations in the Diagnosis of EGPA.

Objective To investigate the clinical symptoms, the physical and neurological findings, and the clinical course of neurological complications in eosinophilic granulomatosis with polyangiitis (EGPA). Methods A retrospective chart review of EGPA cases managed by two referral hospitals was performed, with a focus on the neurological findings. The study analyzed the symptoms at the onset of EGPA and investigated their chronological relationship. The patient delay (the delay between the onset of symptoms and the initial consultation), and the physician delay (the delay from consultation to the initiation of therapy) were determined and compared. The involved nerves were identified thorough a neurological examination. The cases with central nervous system (CNS) involvement were described. Results The average duration of symptoms prior to the initiating of therapy for sensory disturbances, motor deficits, rash, edema, and fever was 23, 5, 21, 18, and 24 days, respectively. Among the EGPA-specific symptoms, sensory disturbance was often the first symptom (63%), and was usually followed by the appearance of rash within four days (63%). The average physician delay (32.9±38.3 days) was significantly longer than the average patient delay (7.9±7.8 days; p=0.010). Reduced touch sensation in the superficial peroneal area, and weakness of dorsal flexion of the first toe secondary to deep peroneal nerve involvement, were highly sensitive for identifying the presence of peripheral nerve involvement in our series of patients with EGPA. Two cases, with CNS involvement, had multiple skin lesions over their hands and feet (Janeway lesions). Conclusion Japanese physicians are not always familiar with EGPA. It is important for us to consider this disease, when an asthmatic patient complains about the new onset of an abnormal sensation in the distal lower extremities, which is followed several days later by rash.

Carotid Artery Dissection and Ischemic Stroke Originating from Localized Aortic Arch Dissection.

Aortic dissection is an infrequent but important cause of acute ischemic stroke (AIS), and must not be overlooked because of a possible worse outcome, especially with the use of an intravenous recombinant tissue plasminogen activator. We report a case of left carotid artery dissection and AIS originating from localized aortic arch dissection, pathologically caused by cystic medial necrosis in the tunica media.

Familial amyloid polyneuropathy involving a homozygous Val30Met mutation in the amyloidogenic transthyretin gene presenting with superficial siderosis: a case report.

A 76-year-old woman was admitted to our hospital because of transthyretin-related familial amyloid polyneuropathy (TTR-FAP). She had developed bilateral vitreous opacity at the age of 58 and paroxysmal atrial fibrillation at the age of 62. She suffered gait disturbance and dysesthesia of the limbs at the age of 68 and was diagnosed with FAP involving a homozygous Val30Met mutation in the amyloidogenic transthyretin (ATTR) gene after a genetic test. Her parents were cousins, and her aunt's medical history included pacemaker implantation and polyneuropathy. At the age of 74, the patient developed gait disturbance and dysesthesia of her extremities. A neurological examination revealed visual loss, hearing impairment, distal muscle weakness, dysesthesia, and decreased sensation in all modalities in her extremities. She could neither walk nor remain standing without support. Brain magnetic resonance imaging (MRI) revealed a low intensity lesion on the surface of the cerebellum on T2*-weighted images and susceptibility-weighted images. A low intensity pattern that was indicative of the classical type of superficial siderosis was detected. At the age of 76, when she was admitted to our hospital because of the deterioration of her gait disturbance and dysesthesia, brain MRI showed that the patient's cerebellar atrophy and hemosiderin deposition had worsened. Some reports suggest that FAP patients that are homozygous for the ATTR Val30Met mutation are more likely to develop central nervous involvement than those that are heterozygous for the mutation. Superficial siderosis may be responsible for the central nervous involvement.

[Diagnosis and treatment of superficial siderosis].

Superficial siderosis (SS) is a rare condition in which hemosiderin is deposited on the pial surface of the brain and/or spinal cord. Hemosiderin deposition is the consequence of recurrent or persistent hemorrhage in the subarachnoid space. There are two types of SS. In "classical"-type SS, hypointense MRI signals are observed in the brainstem and cerebellum with diffuse and symmetrical margins. Causes of hemorrhage in the "classical" type include tumor, vascular abnormality, injury, and dural defect. The source of hemorrhage is not apparent in approximately 50% of patients despite extensive examination. In "localized"-type SS, hypointense MRI signals are localized in the cerebral cortex. The most common causes of hemorrhage in the "localized" type are cerebral amyloid angiopathy and/or Alzheimer's disease. Patients with SS usually present with slowly progressive and irreversible cerebellar ataxia, sensorineural hearing loss, and/or myelopathy due to involvement of the acoustic nerve, cerebellum, and spinal cord. T2-weighted imaging (WI) or T2* WI demonstrates characteristic linear low-intensity signals along the surface of the brain and spinal cord. Treatment of SS involves identification and surgical correction of the bleeding source. Deferiprone, which is a lipid-soluble iron chelator that can penetrate the blood-brain barrier, is reportedly effective at improving the clinical symptoms and deposition of hemosiderin. It is thus a hopeful treatment option for SS.

[A case of MELAS with G13513A mutation presenting with chronic kidney disease long before stroke-like episodes].

The patient was a 35-year-old female with an 9-year history of chronic kidney disease awaiting renal transplantation. She was brought to hospital by ambulance due to a generalized convulsive seizure. Her consciousness remained disturbed after treatment for her seizure, and sensorineural deafness was noted. Lactic acid and pyruvic acid levels were extremely elevated in both the plasma and the cerebrospinal fluid, and brain atrophy was obvious on brain imaging. These findings suggested mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, which was confirmed by muscle biopsy. Previous renal biopsy specimen showed focal segmental glomerulosclerosis and granular swollen epithelial cells. She had no acute progression of the stroke-like episode with L-arginine treatment. However, the brain lesions expanded on MRI. Mitochondrial DNA analysis from a muscle biopsy specimen showed G13513A mutation. The G13513A mutation and the long history of preceding renal failure before the stroke-like episodes were distinctive features in this case.

[Clinical features of superficial siderosis].

Superficial siderosis (SS) of the central nervous system is a rare condition in which hemosiderin is deposited in the subpial layer of the brain and/or spinal cord. It is supposed that hemosiderin deposition is a result of recurrent or persistent hemorrhage in the subarachnoid space. The causes of hemorrhage are tumor, vascular abnormality, injury, dural defect, and others. The source of hemorrhage is not apparent despite of extensive examinations in about a half of the patients with SS. Patients with SS usually reveal slowly progressive and irreversible cerebellar ataxia and/or sensorineural hearing loss. MRI of T(2)WI or T(2)(*)WI demonstrates characteristic linear low intensity along surface of the brain and the spinal cord. There are two types of SS. One is a classical type, in which low intensity of MRI is diffuse and symmetrical. The other is a localized type. We attempted to make a clinical criteria of SS according to the world literature. Then, the criteria was applied to cases (53 cases of classical type and 7 cases of localized type) which are collected from Japanese nationwide questionnaires. The causes and symptoms of Japanese SS are similar with those of Western countries.

[A case of paraneoplastic limbic encephalitis associated with malignant lymphoma presenting with a late-onset bilateral thalamic lesion].

A 63-year-old man presented with cognitive impairment including disturbance of memory functions and character change. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) imaging revealed signal hyperintensities in the bilateral medial temporal lobes. Cerebrospinal fluid analysis revealed high protein concentrations, positive results for the oligoclonal band, and a slightly positive result for glutamate receptor ε2 (GluRε2) antibody. Voltage-gated potassium channel (VGKC) antibody was slightly positive in serum. Computed tomography showed enlargement of the left supraclavicular, left axillary, and renal hilar lymph nodes, and 18 F-fluoro-2-deoxy-D-glucose positron emission tomography revealed increased uptake at the same sites. Lymph node biopsy findings were consistent with diffuse large B-cell lymphoma. Based on these findings, the patient was diagnosed with paraneoplastic limbic encephalitis (PLE) associated with malignant lymphoma. The patient received intravenous injection of immunoglobulin and R-CHOP chemotherapy, but his neurological condition deteriorated. MR imaging showed atrophic changes in the medial temporal lobes during immunotherapy and chemotherapy. FLAIR/T2-weighted imaging revealed signal hyperintensities in the bilateral thalami after the first course of R-CHOP chemotherapy. This is the first report of PLE associated with diffuse large B-cell lymphoma presenting with late-onset bilateral thalamic lesions.

Cancer-associated ischemic stroke is associated with elevated D-dimer and fibrin degradation product levels in acute ischemic stroke with advanced cancer.

AIM: Although several studies have reported various causes of ischemic stroke in patients with cancer, only a few have evaluated the clinical relevance of ischemic stroke pathogenesis to cancer. The aim of the present study was to elucidate the clinical characteristics of cancer-associated ischemic stroke. METHODS: We evaluated 154 ischemic stroke patients without cancer and 57 ischemic stroke patients with cancer who had either received continuous treatment for cancer within 5 years before to the onset of ischemic stroke, or who had been diagnosed with cancer within 1 year after the onset of ischemic stroke. Cancer patients were grouped into "cancer-associated ischemic stroke," the "conventional ischemic stroke," or "other." RESULTS: A total of 15 patients (26%) were classified into the cancer-associated ischemic stroke in cancer patients. In univariate analysis of the cancer-associated ischemic stroke and the others, there were significant differences in the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of d-dimer, fibrin degradation product and hemoglobin. With multivariate regression analysis of those factors, the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of D-dimer and fibrin degradation product remained as statistically independent factors, which were associated with cancer-associated ischemic stroke (n = 111, χ(2) =67.21, P < 0.0001). CONCLUSION: In acute ischemic stroke, the cancer-associated ischemic stroke is associated with elevated D-dimer and fibrin degradation products, even after controlling hypertension, hyperlipidemia and advanced cancer (clinical stage IV).

Akinetic mutism caused by HIV-associated progressive multifocal leukoencephalopathy was successfully treated with mefloquine: a serial multimodal MRI Study.

We report a case of a patient with highly active anti-retroviral therapy-resistant human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML). The patient showed an improvement in imaging findings and clinical symptoms after mefloquine was introduced as an additional treatment. Serial assessment of white matter lesions was conducted by proton magnetic resonance spectroscopy ((1)H-MRS) and diffusion-weighted imaging (DWI). As the clinical symptoms improved, the N-acetylaspartate/creatine ratio increased, the choline/creatine ratio decreased, and the elevated ADC value decreased. These concomitant changes suggested that (1)H-MRS and DWI were useful for the assessment of the therapeutic effect on PML.