Ayako Shioya

Lewy body pathology involves the olfactory cells in Parkinson's disease and related disorders

The “dual‐hit” and propagation hypotheses of α‐synuclein suggests that the olfactory cells of the olfactory epithelium are among the earliest sites of involvement in Parkinsons disease (PD). We investigated the olfactory epithelium in consecutive cases that had been registered with a brain bank.

Neurodegenerative changes in patients with clinical history of bipolar disorders

Neurodegeneration in bipolar disorder (BPD) is poorly understood. Therefore, the current study was designed to assess the immunohistochemical changes in neurodegenerative markers in patients with BPD. Eleven consecutive autopsy cases diagnosed with BPD were analyzed. Sections were obtained from archival paraffin blocks of representative areas and stained using conventional methods, as well as immunostained with several antibodies to screen for neurodegenerative diseases. Age‐ and non‐argyrophilic grains (AGs) degeneration matched controls were selected for each case. Clinical information was retrospectively collected from medical charts. All patients were men, and the average age of death was 70 years. Neuropathological diagnoses included dementia with grains (2), argyrophilic grain disease (2), corticobasal degeneration (CBD, 1), Lewy body disease (1), hypoxic encephalopathy (1) and cerebral infarction (1). All cases showed AGs to various degrees. Three patients died in their 50s; one demonstrated dementia with Lewy bodies, while the other two showed abundant AGs in the thalamus and amygdala. Of the three patients who died in their 60s, one showed AGs preferentially in the thalamus and amygdala, while the others demonstrated limbic predominance. The patients who died in/after their 70s demonstrated AGs similar to controls, except for the patient with CBD. Our data provides potentiality that neurodegenerative diseases may be an underlying pathology in certain cases of BPD.

Clinical, biochemical and molecular investigation of adult-onset glutaric acidemia type II: Characteristics in comparison with pediatric cases

INTRODUCTION An increasing number of adult patients have been diagnosed with fatty acid β-oxidation disorders with the rising use of diagnostic technologies. In this study, clinical, biochemical, and molecular characteristics of 2 Japanese patients with adult-onset glutaric acidemia type II (GA2) were investigated and compared with those of pediatric cases. METHODS The patients were a 58-year-old male and a 31-year-old male. In both cases, episodes of myopathic symptoms, including myalgia, muscle weakness, and liver dysfunction of unknown cause, had been noted for the past several years. Muscle biopsy, urinary organic acid analysis (OA), acylcarnitine (AC) analysis in dried blood spots (DBS) and serum, immunoblotting, genetic analysis, and an in vitro probe acylcarnitine (IVP) assay were used for diagnosis and investigation. RESULTS In both cases, there was no obvious abnormality of AC in DBS or urinary OA, although there was a increase in medium- and long-chain ACs in serum; also, fat deposits were observed in the muscle biopsy. Immunoblotting and gene analysis revealed that both patients had GA2 due to a defect in electron transfer flavoprotein dehydrogenase (ETFDH). The IVP assay indicated no special abnormalities in either case. CONCLUSION Late-onset GA2 is separated into the intermediate and myopathic forms. In the myopathic form, episodic muscular symptoms or liver dysfunction are primarily exhibited after later childhood. Muscle biopsy and serum (or plasma) AC analysis allow accurate diagnosis in contrast with other biochemical tests, such as analysis of AC in DBS, urinary OA, or the IVP assay, which show fewer abnormalities in the myopathic form compared to intermediate form.

A mild case of giant axonal neuropathy without central nervous system manifestation

An 11-year-old boy presented with progressive walking disturbances. He exhibited severe equinovarus feet that together presented with hyperreflexia of the patellar tendon and extensor plantar, resembling spastic paraplegia or upper neuron disease. He showed mild distal muscle atrophy, as well. We did not observe signs of cognitive impairment, cerebellar signs, or brain magnetic resonance imaging abnormalities. Nerve biopsy showed giant axon swellings filled with neurofilaments. Gene analysis revealed novel compound heterozygous missense mutations in the gigaxonin gene, c.808G>A (p.G270S) and c.1727C>A (p.A576E). He was diagnosed with mild giant axonal neuropathy (GAN) without apparent central nervous system involvement. Patients with classical GAN manifest their symptoms during early childhood. Mild GAN, particularly in early stages, can be misdiagnosed because of lack of typical hair features and incomplete or indistinct peripheral and central nervous system symptoms. This case is important since it can aid to identify atypical and milder clinical courses of GAN. This report widens the mild GAN clinical spectrum, alerting physicians for correct diagnosis.

Amelioration of acylcarnitine profile using bezafibrate and riboflavin in a case of adult-onset glutaric acidemia type 2 with novel mutations of the electron transfer flavoprotein dehydrogenase (ETFDH) gene

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD), also known as glutaric acidemia type 2 (GA2), was first described in 1976 [1]. GA2 is a rare autosomal recessive disorder whose biochemical abnormalities result from a deficiency of one of the two electron transfer flavoproteins (ETF and ETFDH) that transfer electrons from acyl-CoA dehydrogenases to the respiratory chain [2]. The disorder affects multiple metabolic pathways involving branched amino acids, fatty acids, and tryptophan, and results in a variety of distinctive organic acids being discharged. The heterogeneous clinical features of patients with GA2 fall into three subclasses: two neonatal-onset forms (types I/ II) and a late-onset form (type III) [3]. The late-onset form is typically characterized by intermittent vomiting, hypoglycemia, hepatomegaly, metabolic acidosis, and/or hyperammonemia, symptoms that are often triggered by general infections or catabolic conditions [4]. Here, we describe the case of a man with lipid-storage myopathy, low muscle carnitine, and an adult-onset form of GA2 with two novel mutations in the ETFDH gene. In this case, a combination of a hypolipidemic drug (bezafibrate), riboflavin, and L-carnitine was effective in treating the disease.

The Development of Cerebral Venous Thrombosis after Tadalafil Ingestion in a Patient with Antiphospholipid Syndrome

We report a case of cerebral venous thrombosis related to the ingestion of tadalafil. A 45-year-old man presented with posterior headache and was diagnosed with tension headache. Five days later, he was transported to our hospital via ambulance due to a tonic-clonic seizure. Head MRI showed cerebral venous thrombosis (CVT). He confessed to having recently taken a large doses of tadalafil. His anti-cardiolipin antibody and anti-caldiolipin-β2-glycoprotein-I complex antibody levels were elevated. Our case suggests the possibility that tadalafil is related to both cardiovascular complications and CVT in patients with hypercoagulability. Patients with conditions associated with hypercoagulability, including antiphospholipid syndrome may be better advised to avoid the use of tadalafil.

Sixth nerve palsy associated with obstruction in Dorello's canal, accompanied by nodular type muscular sarcoidosis

A 52-year-old Japanese woman complaining of horizontal double vision for 10 days was admitted to our hospital. Neurological examination revealed left abducent nerve palsy and muscle swelling in her thighs. Brain MRI showed obstruction in the spinal fluid space of the left Dorellos canal, which transmits a portion of the abducent nerve. In Ga-67-enhanced citrate scintigraphy, wide accumulation was seen in her bilateral thighs, lower legs, and gluteus muscles. Muscular MRI showed a star-shaped central structure on short tau inversion recovery (STIR) images, and the three stripes sign on T2-weighted images. These MRI findings indicated nodular-type muscular sarcoidosis. A muscle biopsy from the quadriceps femoris showed granulomatous epithelioid giant cells and non-necrotizing chronic lymphadenitis, which also indicate sarcoidosis. Her condition was considered to be caused by sarcoid granulomas obstructing Dorellos canal. She was treated with oral prednisolone (1 mg·kg(-1)·day(-1)) and her symptoms and MRI findings improved. This is the first known report of abducent nerve impairment in Dorellos canal, other than fetal hypoplasia. Brain MRI, muscular MRI, and muscle biopsy are useful for the diagnosis of abducent nerve palsy, and it is important to consider Dorellos canal obstruction by sarcoidosis. Complete remission can be achieved with proper treatment.

A case of vitiligo vulgaris showing a pronounced improvement after treatment for myasthenia gravis.

This is a report of a 64 year-old male patient whose myasthenia gravis (MG) was accompanied by vitiligo vulgaris. Depigmentation of the face, trunk, and hands was noted. He was diagnosed with vitiligo vulgaris according to macroscopic findings and a skin biopsy. He was also found to have blepharoptosis, and proximal dominant muscle weakness of the extremities. He was anti-acetylcholine receptor antibody-positive, with repetitive nerve stimulation showing a waning phenomenon and chest computed tomography showing invasive thymoma, which led to the diagnosis of generalised MG. His myasthenic symptoms were relieved by the use of steroids and the removal of the thymoma. His vitiligo vulgaris began to improve a month after the relief of myasthenic symptoms. Such improvement was pronounced during the next several months. The clinical or immunological relationship between MG and vitiligo vulgaris is still not known, but these findings might indicate clinical correlation between MG and vitiligo vulgaris.