Mechanical ventilation (MV) and cardiac protective therapy have improved the prognosis and quality of life of patients with Duchenne muscular dystrophy (DMD). To understand how these therapies have changed prognosis, we performed a cause-of-death analysis in DMD patients.
Mean age at death before initiation of MV (January 1977-July 1984) was 18.9±4.1 years. After the introduction of MV, from August 1984 to December 1993 (1^st term), it was 20.0±4.5 years, from January 1994 to December 2003 (2^nd term), it was 25.2±4.6 years, and from January 2004 to December 2010 (3^rd term), it was 31.1±5.4 years. Almost half of all deaths before MV were due to respiratory failure (RF). Because MV was performed by a tracheostomy in the initial stage, some patients were reluctant to use it, and as a result, RF accounted for 43% of deaths in the 1^st term. Over time, patients started to accept non-invasive ventilation and home mechanical ventilation, which became available in the 1990s. Consequently, no DMD patients have died from RF since 2000. Respiratory physiotherapy and risk management became important tools, because many patients undergo decades of respiratory managements at home.
Cardiac treatments for patients with DMD consisted mainly of diuretics and digitalis in the 1^st term, angiotensin-converting enzyme inhibitors (ACEI) in the 2^nd term, and a combination of ACEIs and beta blockers in the 3^rd term. Compared to the 2^nd term, the ratios of severe cardiac dysfunction (fractional shortening <10%, left ventricle diastolic dimension >75mm, plasma brain natriuretic peptide >1,000pg/ml) were reduced in the 3^rd term. In the 3^rd term, 14% of patients died from renal failure nevertheless their cardiac indices remained mildly abnormal or normal. We should pay enough attention for cardio-renal association.

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A 79-year-old woman was admitted to a nearby hospital for seven days due to low-grade fever, loss of appetite and general fatigue. She was diagnosed with normal condition and discharged. She was admitted to our hospital one week later with disturbed consciousness. Laboratory findings upon admission revealed anemia, elevated alanine amino transferase, elevated total birirubin and thrombocytopenia. Abdominal CT demonstrated multiple low intensity lesions in the liver. Enhanced brain CT revealed multiple lesions with increased signal intensity lesions in the white matter and cortex. The value of soluble IL-2 receptor antibody was 16,000U/ml. Intravascular lymphoma was suspected because of brain CT finding and IL-2 receptor antibody titer. Methylprednisolone pulse therapy was started considering her age and general condition, but she was died thirteen days after admission. Postmorten examination revealed widespread intravascular aggregation of malignant lymphoma cells in the liver, spleen, bone marrow, bladder, ovary and stomach indicating a diagnosis of an Asian variant of intravascular large B cell lymphoma (AIVL). Neurological abnormalities are not usually associated with AIVL, but this patient had rare AIVL presenting with initial progressive nonspecific neurological symptoms.

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A Japanese female patient presented with dysarthria and gait disturbance with ataxia at the age of 63. She was initially diagnosed with spinocerebellar degeneration because a head CT showed atrophy of the cerebellum and brainstem, and dilatation of the fourth ventricle. Symptoms including abnormal behavior, dementia, vertical gaze palsy, dysphagia, retrocollis, axial rigidity, grasp reflex and positive Babinski's sign were gradually observed. Tegmental atrophy of the brainstem and dilatation of the third ventricle were apparent on images. The diagnosis was modified to progressive supranuclear palsy (PSP), 6 years after the onset of symptoms. Gastrostomy and tracheotomy were performed 7 and 8 years after onset, respectively, and the patient died one year later.
At autopsy the brain weighed 1,030g and showed atrophy of the frontal lobe and cerebellum. The brainstem was also atrophic, particularly in the tegmentum and pontine base. Neurofibrillary tangles, mainly globose-type, were widespread in the subcortical structure, particularly in the globus pallidus, subthalamic nucleus, nucleus of the oculomotor nerve, substantia nigra, locus ceruleus, pontine nucleus, and the inferior olivary nucleus. Numerous glial fibrillary tangles and argyrophilic threads were also observed particularly in the frontal lobe, basal ganglia, brainstem and cerebellar white matter. The cerebellar dentate nucleus showed neuron loss with grumose degeneration and the Purkinje neuron layer showed neuron loss and Bergmann's gliosis with torpedoes. Tau positive inclusions in the Purkinje neurons, Bergmann glias and dentate nucleus neurons were observed. Pathological findings were consistent with the diagnosis of PSP but the olivopontocerebellar involvement and the quantity of Gallyas-positive/tau-positive structures were generally more severe than in typical PSP cases.
According to these clinicopathologic findings and a review of the literature, we speculate on the existence of a PSP subtype with severe olivopontocerebellar involvement that tends to be clinically misdiagnosed as spinocerebellar degeneration.

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Polyneuropathy associated with antibodies directed against myelin-associated glycoprotein (MAG) is a chronic symmetric sensorimotor demyelinating neuropathy caused by monoclonal IgM against MAG (anti-MAG neuropathy). Intravenous immunoglobulin therapy (IVIg) has been partially successful in patients with anti-MAG neuropathy. A placebo-controlled trial of rituximab in patients with anti-MAG neuropathy has been reported. We report rapid improvement in a patient with anti-MAG neuropathy using rituximab.
A 58-year-old man presented with abnormal sensation, weakness of the limbs, and unsteadiness. He was previously diagnosed with chronic inflammatory demyelinating neuropathy and was treated with steroid pulse therapy and IVIg. However, these treatments were not effective. On examination at our hospital, he showed areflexia in all limbs, mild weakness in distal portions of upper and lower extremities, sensory ataxia, and hypesthesia/hypalgesia except for his face. He showed high serum IgM levels (323mg/dl). He did not show M protein on immunoelectrophoresis; however, anti-MAG and anti-sulfoglucuronyl paragloboside (SGPG) antibodies were detected by immunoblot and enzyme-linked immunosorbent assay, respectively. He was diagnosed with anti MAG neuropathy and was administered four cycles of intravenous rituximab at a dose of 375mg/m²/week. After the first cycle of rituximab administration, he showed improvement in two-point discrimination of middle fingers (10/13 before therapy to 7/7mm after administration). Two-point discrimination and vibration markedly improved after four cycles of rituximab administration. Romberg sign became negative after 7 months. Anti-SGPG antibody titers reduced from 0.554 before rituximab administration to 0.307 (OD) at 1,600 dilution, 4 months after administration.
We concluded that rituximab was effective for the treatment of anti-MAG neuropathy. We suggested that rapid and long-term improvement in our patient might be caused not only by preventing the formation of new antibody-secreting cells and antibody-titer reduction but also affecting the balance of proinflammatory cytokines and regulatory cytokines production.

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Vocal cord movement disorders are increasingly recognized in patients with amyotrophic lateral sclerosis (ALS). We describe a patient with limb-onset ALS who developed vocal cord paralysis.
A 74-year-old Japanese male consulted our clinic with a 6-month history of weakness in both arms. His family history was unremarkable. There were fasciculations and mild atrophy of the tongue and both arms. In the legs, muscle strength was almost normal but widespread fasciculations were present. All tendon reflexes were hypoactive and pathological reflexes were absent. Thereafter, he developed weakness of the legs and showed increased eating time. Babinski sign was positive bilaterally at this stage. The forced vital capacity dropped from 90% at the initial evaluation to 62% of the predicted value 14 months later. Two years after disease onset, the patient developed aspiration pneumonia with hoarseness and had difficulty clearing his throat of phlegm. Laryngoscopy demonstrated severe vocal cord paresis on both sides, particularly in the abductor muscles possibly leading to obstruction. Tracheotomy was performed because of the risk that the patient could choke to death.
A review of the literature suggests that severe impairment of vocal cord abduction could be a prelude to sudden death in ALS. Follow up by laryngoscopic examination is necessary.

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A 40 year-old man with migraine presented cerebral ischemic attacks several times in one year. He had no risk factors for cerebrovascular disease including hypertension, but had strong family history suggesting autosomal dominant inheritance. A brain MRI on T₂ weighted and FLAIR images revealed patchy and confluent hyper intensity areas in the subcortical white matters and bilateral external capsules, while no anterior temporal pole lesions characteristic of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) were detected. His skin biopsy demonstrated granular osmiophilic materials (GOM) on the basement membrane of the vascular smooth muscle cells in dermis as shown by an electron microscope. The following mutational analysis of the Notch3 gene disclosed a missense mutation of p.Arg133Cys in exon 3. Molecular diagnosis of CADASIL may be time consuming because Notch3 is a huge gene and mutations may occur at multiple sites. GOM on skin biopsy is diagnostic especially in cases where anterior temporal pole involvement on MRI is negative.

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We report a 55-year-old woman with limbic encephalitis associated with leucine-rich glioma-inactivated 1 (LGI1) antibody. She first developed a generalized seizure, following by consciousness loss. Although anticonvulant was initially effective, she began to present frequently with seizure and memory impairment. After eleven months from onset, she was admitted due to generalized seizure. Neurological examination after recovering from the treatment with anesthetic agent demonstrated disorientation and memory impairment. Cerebrospinal fluid analysis was unremarkable. MR brain FLAIR imaging demonstrated high intensity lesions in the medial parts of the both temporal lobes, suggesting limbic encephalitis. There were no signs of malignant tumor detected on systemic examination. LGI1 antibody was positive in the cerebrospinal fluid and we finally diagnosed this patient as having limbic encephalitis associated with LGI1 antibody. She demonstrated a good response to steroid therapy and was discharged after one month.

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We report a 62-year-old man who have taken major tranquilizer for schizophrenia for the past 24 years. He had sudden generalized tonic-clonic seizure and consciousness loss on April 2010. He was administered diazepam, phenytoin, phenobarbital intravenously and drip-infused with midazolam continuously, but the seizure persisted. For a possible comorbidity of neuroleptic malignant syndrome, we administered dantrolene sodium intravenously and bromocriptine through a nasal gastric tube. The refractory status epilepticus disappeared immediately after the administration. Status epilepticus remitted 2 days later but again disappeared with repeated injection of dantrolene. These results suggested that intravenous administration of dantrolene may have alleviated the refractory symptoms of status epilepticus.

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A previously healthy 34-year-old man sustained multiple skull fractures in a traffic accident. Radiological findings and visual field examination did not detect any abnormality. Shortly after the accident, he noticed blurred vision in both eyes. Six months after the accident, he gradually developed disturbance of visual acuity in the right eye. His best corrected visual acuity (BCVA) was 0.8 OD and 1.2 OS and brain MRI did not show any abnormality, while Humphrey visual field analysis demonstrated right homonymous hemianopsia. Two months after the initial presentation, his BCVA showed 0.1 OD and 0.08 OS. Visual field examination suggested that both right homonymous hemianopsia and left blind spot had become enlarged. Mitochondrial DNA analysis demonstrated G11,778A mutation and a diagnosis of Leber's hereditary optic neuropathy (LHON) was made. A few reports have documented mild acute insult to the head or blunt optic trauma as triggers of optic neuropathy in subjects with LHON. Although, the precise mechanism of LHON following trauma remains unknown, it appears that an acute insult may be sufficient to precipitate neuropathy in the optic nerve already compromised by mitochondrial dysfunction. Asymptomatic carriers should be advised to avoid possible precipitating factors such as head trauma.

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