ABSTRACT
BACKGROUND: Although anaplastic lymphoma kinase (ALK) is overexpressed in several primary solid tumor types, its role in endometrial carcinoma (Em Ca) remains unclear. METHODS: We evaluated expression of ALK and its related molecules in clinical samples consisting of 168 Em Ca tissues. We also used Em Ca cell lines to evaluate the functional role of ALK. RESULTS: Cytoplasmic ALK immunoreactivity in the absence of chromosomal rearrangement was positively correlated with ALK mRNA expression, and was significantly higher in Grade (G) 3 Em Ca than in G1 or G2 tumors. ALK immunoreactivity was also significantly associated with expression of cancer stem cell (CSC)-related molecules (cytoplasmic CD133, ALDH1, Sox2) and neuroendocrine markers (CD56 and synaptophysin). Although the proliferative index was significantly higher in ALK-positive Em Ca when compared to ALK- negative malignancies, there was no association between ALK expression and other clinicopathological factors in this disease. In Em Ca cell lines, full-length ALK overexpression increased proliferation, decreased susceptibility to apoptosis, enhanced cancer stem cell features, and accelerated cell mobility, whereas these phenotypes were abrogated in ALK-knockdown cells. Finally, patients with tumors harboring either wild-type ALK or high ALK mRNA expression had a poorer prognosis than those with either mutant ALK or low ALK mRNA expression. CONCLUSION: Full-length ALK overexpression occurs in a subset of Em Ca, particularly in G3 tumors, and contributes to the establishment and maintenance of aggressive phenotypic characteristics through modulation of several biological processes.
Subject(s)
Anaplastic Lymphoma Kinase , Endometrial Neoplasms , Female , Humans , Anaplastic Lymphoma Kinase/genetics , Cytoplasm , Endometrial Neoplasms/genetics , Phenotype , RNA, MessengerABSTRACT
BACKGROUND: We intended to clarify the phenotypic and molecular diversities of spinocerebellar ataxia type 2 (SCA2) in Japan. METHODS: DNA was extracted from the peripheral blood of 436 patients, including 126 patients with chronic neuropathy, 108 with amyotrophic lateral sclerosis, and 202 with cerebellar ataxia. We then PCR-amplified and sequenced the ATXN2 gene. The biopsied sural nerves of mutation-positive patients were subjected to light-microscopic and electron-microscopic analyses. Transfection analyses were performed using a Schwann cell line, IMS32. RESULTS: We found PCR-amplified products potentially corresponding to expanded CAG repeats in four patients. Two patients in the chronic neuropathy group had a full repeat expansion or an intermediate expansion (39 or 32 repeats), without limb ataxia. The sural nerve biopsy findings of the two patients included axonal neuropathy and mixed neuropathy (axonal changes with demyelination). Schwann cells harbored either cytoplasmic or nuclear inclusions on electron microscopic examination. Both patients recently exhibited pyramidal signs. In the third patient in the cerebellar ataxia group, we identified a novel 21-base duplication mutation near 22 CAG repeats (c.432_452dup). The transfection study revealed that the 21-base-duplication mutant Ataxin-2 proteins aggregated in IMS32 and rendered cells susceptible to oxidative stress, similar to a CAG-expanded mutant. The fourth patient, with 41 repeats, had ataxia and spasticity. The two patients with cerebellar ataxia also had peripheral neuropathy. CONCLUSIONS: Patients with expanded CAG repeats can exhibit a neuropathy-dominant phenotype not described previously. The novel 21-base-duplication mutant seems to share the aggregation properties of polyglutamine-expanded mutants.
Subject(s)
Ataxin-2/genetics , Spinocerebellar Ataxias , Ataxins , Humans , Japan , Phenotype , Spinocerebellar Ataxias/genetics , Trinucleotide RepeatsSubject(s)
Brain Edema/diagnostic imaging , Coronavirus Infections/diagnosis , Lung/diagnostic imaging , Pneumonia, Viral/diagnosis , Seizures/diagnosis , Adult , Anti-Bacterial Agents/therapeutic use , Anticoagulants/therapeutic use , Anticonvulsants/therapeutic use , Azithromycin/therapeutic use , Betacoronavirus , Brain Edema/etiology , Brain Infarction/surgery , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Decompression, Surgical , Enzyme Inhibitors/therapeutic use , Epilepsy/complications , Glucocorticoids/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Intracranial Hemorrhages/surgery , Magnetic Resonance Imaging , Male , Nephrosis/complications , Nephrosis/drug therapy , Olfaction Disorders/etiology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , Prednisone/therapeutic use , Pregnenediones/therapeutic use , SARS-CoV-2 , Seizures/drug therapy , Seizures/etiology , Severity of Illness Index , Sinus Thrombosis, Intracranial/etiology , Sinus Thrombosis, Intracranial/surgery , Tomography, X-Ray Computed , COVID-19 Drug TreatmentABSTRACT
We conducted a multicenter, randomized, patient- and assessor-blinded, sham-controlled trial to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) in patients with neuropathic pain (NP). Patients were randomly assigned to receive 5 daily sessions of active or sham rTMS of M1 corresponding to the part of the body experiencing the worst pain (500 pulses per session at 5 Hz). Responders were invited to enroll in an open-label continuous trial involving 4 weekly sessions of active rTMS. The primary outcome was a mean decrease in a visual analogue scale of pain intensity (scaled 0-100 mm) measured daily during the daily sessions in an intention-to-treat population. Secondary outcomes were other pain scores, quality-of-life measures, and depression score. One hundred forty-four patients were assigned to the active or sham stimulation groups. The primary outcome, mean visual analogue scale decreases, was not significantly different (P = 0.58) between the active stimulation group (mean, 8.0) and the sham group (9.2) during the daily sessions. The secondary outcomes were not significantly different between 2 groups. The patients enrolled in the continuous weekly rTMS achieved more pain relief in the active stimulation group compared with the sham (P < 0.01). No serious adverse events were observed. Five daily sessions of rTMS with stimulus conditions used in this trial were ineffective in short-term pain relief in the whole study population with various NP. Long-term administration to the responders should be investigated for the clinical use of rTMS on NP in the future trials.
Subject(s)
Duration of Therapy , Motor Cortex , Neuralgia/therapy , Transcranial Magnetic Stimulation/methods , Aged , Double-Blind Method , Female , Humans , Male , Middle Aged , Pain Measurement , Treatment OutcomeABSTRACT
OBJECTIVES: Abnormal swallowing or dysphagia is a potentially fatal symptom in Parkinson's disease (PD) and is characterized by frequent silent aspiration, which is an unrecognized risk for aspiration pneumonia. While the effects of oral levodopa on swallowing functions remain controversial, several small-scale studies have reported that rotigotine transdermal patch seems effective. The different effects between levodopa and rotigotine may be attributed to continuous dopaminergic stimulation (CDS), however, the absence of direct comparative evidence precludes conclusion. METHODS: In the present retrospective open-label study of 50 patients with PD, swallowing functions were assessed via videofluoroscopic (VF) examination before and after treatment. Treatment included 2â¯mg/day rotigotine transdermal patch (Nâ¯=â¯29) or 200â¯mg/day oral levodopa with carbidopa (Nâ¯=â¯21) in drug-naïve and add-on groups of patients. RESULTS: Rotigotine more consistently improved all measures assessed via VF examination. Such effects were similar to those in the drug-naïve and add-on groups. Improvement and responder rates of certain measures were significantly higher in the rotigotine group than in the levodopa group. CONCLUSIONS: Our finding that rotigotine (levodopa equivalent doseâ¯=â¯60â¯mg) was more consistently effective than 200â¯mg/day oral levodopa suggests that CDS is more important in improving swallowing functions.
Subject(s)
Antiparkinson Agents/therapeutic use , Deglutition/drug effects , Dopamine Agonists/therapeutic use , Levodopa/therapeutic use , Parkinson Disease/drug therapy , Tetrahydronaphthalenes/therapeutic use , Thiophenes/therapeutic use , Administration, Oral , Aged , Aged, 80 and over , Antiparkinson Agents/administration & dosage , Dopamine Agonists/administration & dosage , Female , Humans , Levodopa/administration & dosage , Male , Parkinson Disease/physiopathology , Retrospective Studies , Tetrahydronaphthalenes/administration & dosage , Thiophenes/administration & dosage , Transdermal Patch , Treatment OutcomeABSTRACT
Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis. The disease predominantly affects women (1:5-1:10), with only 3 reports of autopsy findings in women being published to date. The present study reports findings from the first autopsy performed on a man with anti-NMDAR encephalitis. The patient had some scattered lesions in the limbic system with neuronal loss, gliosis, and microglial activation. The temporal and frontal cortices showed additional patchy demyelination. T-lymphocyte infiltration was detectable in the fusiform gyrus lesion. These findings were partly similar to those reported in female patients. Although clinical differences based on the sex of the patient are reported for this disease, the observed pathological similarities potentially help to establish common therapeutic strategies for all patients. Severe testicular damage was additionally observed in the male patient in this study. Biopsy-proven severe testicular damage was also confirmed in another, previously fertile man who became azoospermic. Moreover, serum follicle-stimulating hormone levels, which often increased in response to disturbed spermatogenesis, were elevated, and testosterone/luteinizing hormone ratio reflecting Leydig cell function was low in all 5 male patients in this study. Overall, these findings suggest similar brain pathology in patients of both sexes and severe testicular damage in male patients.
ABSTRACT
Spinocerebellar ataxia type 8 (SCA8) is a rare autosomal dominant neurodegenerative disease caused by expanded CTA/CTG repeats in the ATXN8OS gene. Many patients had pure cerebellar ataxia, while some had parkinsonism, both without causal explanation. We analyzed the ATXN8OS gene in 150 Japanese patients with ataxia and 76 patients with Parkinson's disease or related disorders. We systematically reassessed 123 patients with SCA8, both our patients and those reported in other studies. Two patients with progressive supranuclear palsy (PSP) had mutations in the ATXN8OS gene. Systematic analyses revealed that patients with parkinsonism had significantly shorter CTA/CTG repeat expansions and older age at onset than those with predominant ataxia. We show the imaging results of patients with and without parkinsonism. We also found a significant inverse relationship between repeat sizes and age at onset in all patients, which has not been detected previously. Our results may be useful to genetic counseling, improve understanding of the pathomechanism, and extend the clinical phenotype of SCA8.
Subject(s)
Spinocerebellar Degenerations/genetics , Spinocerebellar Degenerations/physiopathology , Aged , Brain/diagnostic imaging , Female , Humans , Male , Mutation , Phenotype , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Spinocerebellar Degenerations/diagnostic imaging , Trinucleotide Repeat ExpansionABSTRACT
OBJECTIVE: To assess the contribution of noncoding repeat expansions in Japanese patients with amyotrophic lateral sclerosis (ALS). METHODS: Sporadic ALS in Western countries is frequently associated with noncoding repeat expansions in the C9ORF72 gene. Spinocerebellar ataxia type 8 (SCA8) is another noncoding repeat disease caused by expanded CTA/CTG repeats in the ATXN8OS gene. Although the involvement of upper and lower motor neurons in SCA8 has been reported, a positive association between SCA8 and ALS remains unestablished. Spinocerebellar ataxia type 36 is a recently identified disease caused by noncoding repeat expansions in the NOP56 gene and is characterized by motor neuron involvement. We collected blood samples from 102 Japanese patients with sporadic ALS and analyzed the ATXN8OS gene by the PCR-Sanger sequencing method and the C9ORF72 and NOP56 genes by repeat-primed PCR assay. RESULTS: Three patients with ALS (3%) had mutations in the ATXN8OS gene, whereas no patient had a mutation in the C9ORF72 or NOP56 gene. The mutation-positive patients were clinically characterized by neck weakness or bulbar-predominant symptoms. None of our patients had apparent cerebellar atrophy on MRI, but 2 had nonsymptomatic abnormalities in the white matter or putamen. CONCLUSIONS: Our finding reveals the importance of noncoding repeat expansions in Japanese patients with ALS and extends the clinical phenotype of SCA8. Three percent seems small but is still relatively large for Japan, considering that the most commonly mutated genes, including the SOD1 and SQSTM1 genes, only account for 2%-3% of sporadic patients each.
ABSTRACT
To our knowledge, this is the first study to report the time course of radiological imaging of 3 patients from 2 families with VCP-related amyotrophic lateral sclerosis (ALS) and dementia. Both families shared the same p.Arg487His mutation in the VCP gene encoding valosin-containing protein. The first patient started to have a typical form of ALS, followed by dementia 7 years later. The second patient, a brother of the first one, had frontotemporal dementia and parkinsonism. The third patient had simultaneous ALS and dementia. All patients seemed to have progressive brain atrophy as their clinical symptoms progressed. The common and characteristic finding was atrophy of the temporal lobes including the hippocampi. The relation between imaging findings and symptoms varied considerably among the 3 patients.
Subject(s)
Amyotrophic Lateral Sclerosis/pathology , Brain/pathology , Frontotemporal Dementia/pathology , Valosin Containing Protein/genetics , Aged , Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/genetics , Atrophy/diagnostic imaging , Atrophy/pathology , Brain/diagnostic imaging , Female , Frontotemporal Dementia/diagnostic imaging , Frontotemporal Dementia/genetics , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Mutation , Pedigree , PhenotypeABSTRACT
We have assessed the frequency of alpha-synuclein (SNCA) mutations in Japanese patients with familial or sporadic Parkinson's disease (PD) and surveyed their associated clinical manifestations. We screened SNCA exon 3 in 988 patients without SNCA multiplications (430 with autosomal dominant PD and 558 with sporadic PD). We detected 1 patient harboring a homozygous SNCA p.A53V substitution albeit with an autosomal dominant pattern of disease inheritance (frequency 2/860 = 0.2%). The proband manifested slow and progressive parkinsonism at 55 years. Later she complicated with cognitive decline and hallucinations. Several of her immediate family members also presented with parkinsonism, cognitive decline, and psychosis. Positron emission tomography imaging of 18F-6-fluoro-L-dopa (18F-DOPA) uptake, 11C(+)dihydrotetrabenzine (type 2 vesicular monoamine transporter), and 11C-d-threo-methylphenidate (a plasmalemmal dopamine transporter marker) binding in the striatum were significantly reduced. Hence, alpha-synuclein p.A53V homozygous mutation leads to a distinct phenotype of progressive parkinsonism and cognitive decline, commonly observed in patients with SNCA missense mutation or multiplications.
Subject(s)
Homozygote , Mutation, Missense/genetics , Parkinson Disease/genetics , alpha-Synuclein/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cognitive Dysfunction/etiology , Corpus Striatum/diagnostic imaging , Disease Progression , Exons/genetics , Female , Genes, Dominant/genetics , Hallucinations/etiology , Humans , Male , Middle Aged , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Phenotype , Positron-Emission Tomography , Young AdultABSTRACT
Dystonia is defined as a movement disorder characterized by sustained or intermittent muscles contraction causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. The precis diagnosis of dystonia is difficult for physicians because neurological brain imaging does not provide enough practical information. The diagnosis is depend on clinical experience of physicians. Botulinum toxin treatment is the accepted standard of care for patients with focal dystonia. Botulinum toxin treatment results in significant improvement of decreasing the symptom of dystonia. The success of treatment is dependent on muscle selection for treating involved muscles. Usually performance of botulinum toxin treatment is injected according to clinical experience of surface anatomy or clinical location method. However, the benefit of guidance of botulinum toxin treatment is improve outcome in dystonia. Injection techniques with ultra sound echogram or EMG guidance to identify dystonic muscles can be more benefit for patients.
Subject(s)
Botulinum Toxins/administration & dosage , Dystonic Disorders/diagnosis , Dystonic Disorders/drug therapy , Dystonic Disorders/classification , Dystonic Disorders/diagnostic imaging , Electromyography , Humans , Injections, Intramuscular , Muscle, Skeletal/diagnostic imaging , Treatment Outcome , UltrasonographyABSTRACT
INTRODUCTION: Early onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH)/ataxia with oculomotor apraxia 1 (AOA1) is an autosomal recessive disorder caused by mutations in the APTX gene. In contrast to the recent progress on the molecular mechanism of aprataxin in DNA repair, the genotype and phenotype correlation has not been fully established. A previous study demonstrated that patients with truncation mutations had earlier onset of disease than those with missense mutations METHODS: Genomic DNA analysis was performed in a consanguineous family with relatively late-onset EAOH/AOA1. In addition, mRNA and protein analyses were performed. RESULTS: The proband of the family had a homozygous two-base deletion in the middle of exon 3. Reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays of mRNA revealed an aberrantly spliced mRNA with a cryptic splice site located four bases upstream of the deletion site. The newly identified mRNA retained a frameshift mutation and encoded a truncated protein. Immunoblot analysis did not detect the truncated protein in the patient's fibroblasts, possibly because it was unstable. CONCLUSIONS: Although patients with truncation mutations had an earlier onset of disease, our findings suggest that patients with a truncation mutation resulting in an undetectable protein level can also have a later onset of disease.
Subject(s)
Ataxia/genetics , DNA-Binding Proteins/genetics , Frameshift Mutation , Nuclear Proteins/genetics , Sequence Deletion , Aged , Ataxia/physiopathology , Cells, Cultured , DNA-Binding Proteins/metabolism , Fatal Outcome , Female , Humans , Male , Middle Aged , Nuclear Proteins/metabolism , Phenotype , Protein Isoforms , RNA, Messenger/metabolismABSTRACT
Spinocerebellar ataxia type 6 (SCA6), an autosomal dominant triplet repeat disease, predominantly affects the cerebellum with a late onset and generally good prognosis. Dysphagia is commonly associated with the outcomes of neurodegenerative diseases such as SCA6. Although the characteristics of dysphagia have been rarely reported in SCA6, our previous study indicated that dysphagia is generally milder in SCA6 than in SCA3, another inherited ataxia with multisystem involvement. However, abnormalities in the pharyngeal phase in SCA6 were indistinguishable from those in SCA3, with no explainable reason. To determine the reason, we repeatedly performed videofluoroscopic examinations (VF) in 14 patients with SCA6. The results showed that the gross progression of dysphagia was apparently slow, but four patients had progressive dysphagia at an early disease stage; dysphagia began within 10 years from the onset of ataxia and rapidly progressed. A common clinical feature of the four patients was a significantly older age at the onset of ataxia (74.0 vs. 60.3 years), associated with significantly shorter triplet repeats. This finding surprisingly indicated that patients who had shorter repeats and thereby later onset and potentially better prognoses were at risk for dysphagia-associated problems. Ischemic changes, homozygous mutation, and diabetes mellitus as well as aging might have contributed to the observed progressive dysphagia. We found that conventionally monitored somatosensory evoked potentials at least partly reflected progressive dysphagia. Despite the small study group, our findings suggest that clinicians should carefully monitor dysphagia in patients with SCA6 who are older at disease onset (>60 years).
Subject(s)
Deglutition Disorders/etiology , Spinocerebellar Ataxias/complications , Aged , Aged, 80 and over , Deglutition Disorders/physiopathology , Disease Progression , Evoked Potentials, Auditory/physiology , Evoked Potentials, Somatosensory/physiology , Female , Humans , Male , Middle Aged , Retrospective Studies , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/physiopathologyABSTRACT
Charcot-Marie-Tooth (CMT) disease is a complex of peripheral nervous system disorders. CMT type 2U (CMT2U) is an autosomal dominant (AD) disease caused by mutations in the MARS gene encoding methionyl-tRNA synthetase; this disease has thus been newly called AD-CMTax-MARS. A few families with mutations in the MARS gene have been reported, without detailed histopathological findings. We describe a 70-year-old woman who had bilateral dysesthesia of the soles since the age of 66 years. Sural nerve biopsy showed a decrease in the density of large myelinated nerve fibers. Increased clusters of regenerating myelinated nerve fibers were noted. Electron microscopic analyses revealed degeneration of unmyelinated nerves. There was no vasculitis or inflammatory cell infiltration. Genetic analysis identified a heterozygous p.P800T mutation, a reported mutation in the MARS gene. We report the detailed histopathological findings in a patient with CMT2U/AD-CMTax-MARS. The findings are similar to those found in CMT2D caused by mutations in the GARS gene, encoding glycyl-tRNA synthetase.
Subject(s)
Charcot-Marie-Tooth Disease/genetics , Charcot-Marie-Tooth Disease/pathology , Mutation/genetics , Aged , Female , Genetic Testing , Humans , Methionine-tRNA Ligase/genetics , Microscopy, Electron , Neural Conduction/genetics , Sural Nerve/physiopathology , Sural Nerve/ultrastructureABSTRACT
Sporadic ataxia affecting multiple systems, such as cerebellar, extrapyramidal, and autonomic systems, is known as multiple system atrophy cerebellar type (MSA-C), while similar multisystem involvements are seen in certain types of hereditary ataxia, such as spinocerebellar ataxia type 3 (SCA3). Dysphagia is a common symptom that can predispose to aspiration pneumonia, a major cause of death in patients with these diseases. Although the progressions of dysphagia in patients with MSA-C have been reported sporadically, those in SCA3 have not been reported. We retrospectively compared the results of repetitive videofluoroscopic examinations in patients with SCA3 (n = 6) and in those with MSA-C (n = 7). The result showed that the gross progression of dysphagia was significantly slower in patients with SCA3 than in those with MSA-C, but the maximum progression speeds were not significantly different. The dysphagia severities were not associated with impaired activity of daily living evaluated by the Barthel index in MSA-C, but were associated in SCA3. Despite the small number of patients enrolled, these data suggest that physicians should monitor swallowing functions in patients with SCA3 after mild dysphagia develops because it may progress as rapidly as it does in MSA-C.
Subject(s)
Deglutition Disorders/diagnosis , Deglutition Disorders/genetics , Machado-Joseph Disease/diagnosis , Machado-Joseph Disease/genetics , Multiple System Atrophy/diagnosis , Multiple System Atrophy/genetics , Aged , Aged, 80 and over , Antigens, Neoplasm/genetics , Ataxin-3/genetics , Barium Sulfate/administration & dosage , Disease Progression , Female , Genotype , Humans , Male , Middle Aged , Neurologic Examination , Repressor Proteins/genetics , Retrospective Studies , Severity of Illness IndexABSTRACT
Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by central obesity, mental impairment, rod-cone dystrophy, polydactyly, hypogonadism in males, and renal abnormalities. The causative genes have been identified as BBS1-19. In Western countries, this disease is often reported, but remains undiagnosed in many patients until later in life, while only a few patients with no mutations identified have been reported in Japan. We thus conducted the first nationwide survey of BBS in Japan by sending questionnaires to 2,166 clinical departments with board-certified specialists and found 7 patients with clinically definite BBS. We performed exome analyses combined with analyses of mRNA and protein in these patients. We identified 2 novel mutations in the BBS5 gene (p.R89X and IVS7-27 T>G) in 2 sibling patients. The latter mutation that resided far from the authentic splicing site was associated with skipping of exon 8. We also found 3 previously reported mutations in the BBS2 (p.R413X and p.R480X) and BBS7 (p.C243Y) genes in 2 patients. To our knowledge, a nationwide survey of BBS has not been reported in any other country. In addition, this is the first study to identify genetic alterations in Japanese patients with BBS. Our results indicate that BBS in Japan is genetically heterogeneous and at least partly shares genetic features with BBS in other countries.
Subject(s)
Bardet-Biedl Syndrome/epidemiology , Adolescent , Bardet-Biedl Syndrome/genetics , Child , Child, Preschool , Cytoskeletal Proteins , Exome/genetics , Female , Humans , Japan/epidemiology , Male , Mutation/genetics , Oligonucleotide Array Sequence Analysis , Phosphate-Binding Proteins , Proteins/genetics , Surveys and Questionnaires , Young AdultABSTRACT
Abnormal swallowing, dysphagia, is a potentially fatal symptom in Parkinson's disease (PD) and is characterized by frequent silent aspiration, an unrecognized risk of suffocation and aspiration pneumonia. Several studies have reported that the injection of apomorphine, a dopamine agonist, alleviated dysphagia in some patients with PD. The effects of other antiparkinson medications against dysphagia remain controversial. Rotigotine is another dopamine agonist with non-oral administration, i.e., a transdermal patch. Its noninvasiveness seems to render this medicine even more suitable than apomorphine for dysphasic patients. However, no direct evidence has been reported. In the present retrospective open-label study, we for the first time objectively showed that rotigotine improved swallowing on videofluoroscopic examination in dysphagic patients with PD.
Subject(s)
Deglutition Disorders/etiology , Deglutition Disorders/physiopathology , Deglutition/drug effects , Dopamine Agonists/therapeutic use , Parkinson Disease/complications , Parkinson Disease/drug therapy , Tetrahydronaphthalenes/therapeutic use , Thiophenes/therapeutic use , Administration, Cutaneous , Aged , Aged, 80 and over , Dopamine Agonists/administration & dosage , Female , Humans , Male , Retrospective Studies , Tetrahydronaphthalenes/administration & dosage , Thiophenes/administration & dosageABSTRACT
Accumulating evidence has proven that mutations in the VCP gene encoding valosin-containing protein (VCP) cause inclusion body myopathy with Paget disease of the bone and frontotemporal dementia. This gene was later found to be causative for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, occurring typically in elderly persons. We thus sequenced the VCP gene in 75 Japanese patients with sporadic ALS negative for mutations in other genes causative for ALS and found a novel mutation, p.Arg487His, in 1 patient. The newly identified mutant as well as known mutants rendered neuronal cells susceptible to oxidative stress. The presence of the mutation in the Japanese population extends the geographic region for involvement of the VCP gene in sporadic ALS to East Asia.
Subject(s)
Adenosine Triphosphatases/genetics , Amyotrophic Lateral Sclerosis/genetics , Asian People/genetics , Cell Cycle Proteins/genetics , Genetic Association Studies , Genetic Predisposition to Disease/genetics , Mutation/genetics , Aged , Amyotrophic Lateral Sclerosis/pathology , Female , Humans , Male , Neuroblastoma/pathology , Oxidative Stress/genetics , Tumor Cells, Cultured , Valosin Containing ProteinABSTRACT
We describe the first case of a patient with eyelid tremor probably associated with anti-contactin-associated protein-like 2 (Caspr2) antibody. Encephalitis associated with anti-voltage-gated potassium channel antibody is now attributed to autoantibodies against leucine-rich glioma inactivated 1 (Lgi1) and less frequently against Caspr2. Eyelid tremor or blepharoclonus is a rare or underdiagnosed involuntary movement that has been found in patients with infarction in the thalamus or drug-induced or idiopathic parkinsonism. Since patients with anti-Caspr2 antibody-related encephalitis occasionally have extrapyramidal signs, we speculate that the eyelid tremor was also caused by anti-Caspr2 antibody in our patient. Partial resolution of his symptoms by plasmapheresis also supported the involvement in immunological processes.