ABSTRACT
Argyrophilic grain disease (AGD) is one of the major pathological backgrounds of senile dementia. Dementia with grains refers to cases of dementia for which AGD is the sole background pathology responsible for dementia. Recent studies have suggested an association between dementia with grains and parkinsonism. In this study, we aimed to present two autopsy cases of dementia with grains. Case 1 was an 85-year-old man who exhibited amnestic dementia and parkinsonism, including postural instability, upward gaze palsy, and neck and trunk rigidity. The patient was clinically diagnosed with progressive supranuclear palsy and Alzheimer's disease. Case 2 was a 90-year-old man with pure amnestic dementia, clinically diagnosed as Alzheimer's disease. Recently, we used cryo-electron microscopy to confirm that the tau accumulated in both cases had the same three-dimensional structure. In this study, we compared the detailed clinical picture and neuropathological findings using classical staining and immunostaining methods. Both cases exhibited argyrophilic grains and tau-immunoreactive structures in the brainstem and basal ganglia, especially in the nigrostriatal and limbic systems. However, Case 1 had more tau immunoreactive structures. Considering the absence of other disease-specific structures such as tufted astrocytes, astrocytic plaques and globular glial inclusions, lack of conspicuous cerebrovascular disease, and no history of medications that could cause parkinsonism, our findings suggest an association between AGD in the nigrostriatal system and parkinsonism.
ABSTRACT
We herein report a 45-year-old man with dentatorubropallidoluysian atrophy (DRPLA) who presented with mild dementia, ataxia, and involuntary movement and developed constipation, dysuria, and orthostatic hypotension. Thermography revealed an abnormal thermal response of the skin to cold stimulation. Skin temperature reflects the skin blood flow and is regulated by the sympathetic nervous system. Thermography is currently used to study diseases associated with vasomotor dysfunction of the skin. The thermography results suggested the possibility of autonomic dysfunction. Although little is known regarding autonomic dysfunction in DRPLA, this report demonstrates the importance of autonomic dysfunction in DRPLA.
Subject(s)
Autonomic Nervous System Diseases , Cerebellar Ataxia , Dementia , Male , Humans , Middle Aged , Autonomic Nervous System Diseases/complications , Autonomic Nervous System Diseases/diagnosis , Ataxia , AtrophyABSTRACT
Myasthenia gravis (MG) is the most common disorder of neuromuscular transmission and is a heterogeneous disorder generally caused by auto-antibody to the nicotinic acetylcholine receptor. The current study presented a rare case of MG that occurred a long time after surgical resection of lung cancer. A 58-year-old man with lung adenocarcinoma underwent upper lobectomy and mediastinal lymph node dissection. Severe myasthenic symptoms began 7 years after the operation, and emergent mechanical ventilation was needed because of myasthenic crises. Levels of serum anti-acetylcholine receptor antibody were high and typical decremental responses to repetitive stimulation on electromyography were observed. Appropriate therapies for a severe acute condition were performed, and MG has been controlled for 6 years since then. There is no recurrence of lung cancer or appearance of thymoma. In conclusion, although very rare, physicians should be aware of MG as a potential comorbidity developing in patients with a history of lung cancer.
ABSTRACT
Objectives: This retrospective study aimed to obtain information on the nutritional maintenance effects of Ninjin'yoeito (NYT) in elderly patients with chronic wasting diseases. Methods: Changes in body weight and serum levels of total protein and albumin were investigated in patients who received NYT for chronic wasting diseases for more than six months in Mito Medical Centre, University of Tsukuba-Mito Kyodo General Hospital, Mito, Japan, from April 2009 to October 2019. Results: During the study period, 11 patients (median age: 75 years) received NYT for six months or more. The median administration period of NYT was 14 months. The body weight and serum levels of total protein and albumin at the time of the last observation were not significantly different from those at the beginning of NYT administration (P = 0.176, P = 0.766 and P = 0.550, respectively). Conclusion: This study suggested the possibility of maintaining nutritional condition by administering NYT in elderly patients with chronic wasting disease of various aetiologies. More evidence will be required to confirm these results.
Subject(s)
Wasting Disease, Chronic , Wasting Syndrome , Aged , Albumins , Animals , Body Weight , Drugs, Chinese Herbal , Humans , Nutritional Status , Retrospective StudiesABSTRACT
Lewy body-related α-synucleinopathy (Lewy pathology) has been reported in patients with myotonic dystrophy (DM) type 1 (DM1), but no detailed report has described the prevalence and extent of its occurrence. We studied consecutive full autopsy cases of DM1 at the National Center of Neurology and Psychiatry (NCNP) Brain Bank for intractable psychiatric and neurological disorders. Thirty-two cases, genetically determined to be DM1 (59.0 ± 8.7 years), obtained from the NCNP Brain Bank, were compared with control cases obtained from the Brain Bank for Aging Research (BBAR) in Japan. The investigated anatomical sites followed the Dementia with Lewy Bodies Consensus Guideline, expanding to the peripheral autonomic nervous system, temporal pole, and occipital cortex, in addition to the olfactory epithelium and spinal cord. Of the 32 patients, 11 (34.4%) had Lewy pathology, with a significantly higher prevalence than that in the control cases from the BBAR (20.1%). Lewy pathology detected in DM1 was widespread, but no macroscopic depigmentation of the substantia nigra was observed in any DM1 case; this was commensurate with the microscopic paucity of Lewy pathology in the substantia nigra and amygdala. Lewy pathology in DM1 does not appear to follow either Braak's ascending paradigm or the olfactory-amygdala extension. Lewy neurites and dots in DM1 were very sparse in the cerebral cortex and distinct from those observed in BBAR control cases. This study was the first demonstration of unique Lewy pathology in DM1 and may contribute to the understanding of the protein propagation hypothesis of Lewy pathology.
Subject(s)
Lewy Body Disease , Myotonic Dystrophy , Parkinson Disease , Brain/pathology , Humans , Lewy Bodies/pathology , Lewy Body Disease/pathology , Myotonic Dystrophy/pathology , Parkinson Disease/pathology , alpha-Synuclein/metabolismABSTRACT
A 24-year-old woman was admitted to our hospital after convulsive status epilepticus. A cerebral magnetic resonance venography revealed a persistent fetal falcine sinus. Additionally, the posterior third of the superior sagittal sinus was hypoplastic and the abnormal deep venous drainage was accompanied. These abnormalities had already been detected by magnetic resonance imaging several years ago. In the present scan, we discovered a sinus thrombosis in the hypoplastic superior sagittal sinus. In the cerebral angiography, we observed delayed venous return in the left parieto-occipital lobe and hypothesized that cerebral venous stasis due to the thrombus caused the convulsive status epilepticus. The patient was treated with intravenous administration of heparin along with an antiepileptic drug, and she recovered with no neurological defects. In the present case, the falcine sinus and the anomalous venous return were likely congenital while the status epilepticus was derived from thrombosis in the hypoplastic superior sagittal sinus. Although the falcine sinus functioned as an alternative pathway for the superior sagittal sinus, the hypoplastic superior sagittal sinus itself may also play an important role as a venous drainage channel.
Subject(s)
Central Nervous System Vascular Malformations/complications , Cranial Sinuses/abnormalities , Sagittal Sinus Thrombosis/etiology , Status Epilepticus/etiology , Anticoagulants/therapeutic use , Anticonvulsants/therapeutic use , Central Nervous System Vascular Malformations/diagnostic imaging , Central Nervous System Vascular Malformations/physiopathology , Cerebrovascular Circulation , Cranial Sinuses/diagnostic imaging , Female , Humans , Sagittal Sinus Thrombosis/diagnostic imaging , Sagittal Sinus Thrombosis/drug therapy , Sagittal Sinus Thrombosis/physiopathology , Status Epilepticus/diagnosis , Status Epilepticus/drug therapy , Status Epilepticus/physiopathology , Treatment Outcome , Young AdultABSTRACT
ErbB4 is the protein implicated in familial amyotrophic lateral sclerosis (ALS), designated as ALS19. ErbB4 is a receptor tyrosine kinase activated by its ligands, neuregulins (NRG), and plays an essential role in the function and viability of motor neurons. Mutations in the ALS19 gene lead to the reduced autophosphorylation capacity of the ErbB4 protein upon stimulation with NRG-1, suggesting that the disruption of the NRG-ErbB4 pathway causes motor neuron degeneration. We used immunohistochemistry to study ErbB4 in the spinal cord of patients with sporadic ALS (SALS) to test the hypothesis that ErbB4 may be involved in the pathogenesis of SALS. ErbB4 was specifically immunoreactive in the cytoplasm of motor neurons in the anterior horns of the spinal cord. In patients with SALS, some of the motor neurons lost immunoreactivity with ErbB4, with the proportion of motor neurons with a loss of immunoreactivity correlated with the severity of motor neuron loss. The subcellular localization was altered, demonstrating nucleolar or nuclear localization, threads/dots and spheroids. The ectopic glial immunoreactivity was observed, mainly in the oligodendrocytes of the lateral columns and anterior horns. The reduction in the ErbB4 immunoreactivity was significantly correlated with the cytoplasmic mislocalization of transactivation response DNA-binding protein 43 kDa (TDP-43) in the motor neurons. No alteration in immunoreactivity was observed in the motor neurons of mice carrying atransgene for mutant form of the superoxide dismutase 1 gene (SOD1). This study provided compelling evidence that ErbB4 is also involved in the pathophysiology of SALS, and that the disruption of the NRG-ErbB4 pathway may underlie the TDP-43-dependent motor neuron degeneration in ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Receptor, ErbB-4/genetics , Spinal Cord/metabolism , Aged , Aged, 80 and over , Amyotrophic Lateral Sclerosis/metabolism , Animals , DNA-Binding Proteins/metabolism , Female , Humans , Immunohistochemistry , Male , Mice, Transgenic , Middle Aged , Motor Cortex/metabolism , Receptor, ErbB-4/metabolism , Superoxide Dismutase-1/geneticsABSTRACT
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-ß2-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.
Subject(s)
Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/drug therapy , Brain/diagnostic imaging , Intracranial Thrombosis/diagnosis , Intracranial Thrombosis/etiology , Tadalafil/adverse effects , Tadalafil/therapeutic use , Brain/physiopathology , Humans , Magnetic Resonance Imaging , Male , Middle AgedSubject(s)
Brain/diagnostic imaging , Demyelinating Diseases/diagnostic imaging , Diffusion Magnetic Resonance Imaging , Leukodystrophy, Globoid Cell/diagnostic imaging , Paresis/diagnostic imaging , Demyelinating Diseases/physiopathology , Diagnosis, Differential , Female , Humans , Leukodystrophy, Globoid Cell/physiopathology , Paresis/physiopathology , Young AdultABSTRACT
BACKGROUND: 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 Parkinson's disease (PD). We investigated the olfactory epithelium in consecutive cases that had been registered with a brain bank. OBJECTIVES: This study was undertaken to check the presence or absence of Lewy body pathology in olfactory cells. METHODS: Thirty-six male and 11 female patients were examined, including eight with PD, two with dementia with Lewy bodies, 11 with incidental Lewy body disease, and 26 with no Lewy-related alpha-synucleinopathy. The olfactory epithelium was sampled by craniotomy followed by resection of the cribriform plate, which was fixed in formalin and decalcified with ethylenediaminetetra-acetate. Coronal paraffin-embedded sections of the plate were stained with hematoxylin and eosin or immunohistochemically stained with antibodies against phosphorylated α-synuclein to detect Lewy body pathology and neuronal markers of protein gene product 9.5, phosphorylated neurofilament, and tyrosine hydroxylase. RESULTS: Lewy body pathology was detected in the olfactory cells of the olfactory epithelium in a single patient with incidental Lewy body disease and in six patients with PD, but it was not detected in patients who had dementia with Lewy bodies. CONCLUSIONS: We detected Lewy body pathology in the olfactory epithelium in six of the eight patients with Parkinson's disease and in one patient with incidental Lewy body pathology.
Subject(s)
Lewy Bodies/pathology , Olfactory Mucosa/pathology , Parkinson Disease/pathology , Sensory Receptor Cells/pathology , Aged , Aged, 80 and over , Female , Humans , Lewy Body Disease/pathology , Male , Middle Aged , Ubiquitin Thiolesterase/metabolism , alpha-Synuclein/metabolismABSTRACT
Here, we describe the case of a 47-year-old man with bilateral striatal lesions with diabetic uremia. Following 4 years of hemodialysis, the patient experienced sudden onset of rigidity, bradykinesia, gait disorder, and postural instability. Symptoms were remediated 2 months later, and were no longer responsive to levodopa approximately 1 year after the onset. Brain magnetic resonance imaging (MRI) during the acute phase showed T 2-weighted high signal edematous lesions in the bilateral striatum, subsequently developing into vacuolated lesions. A positron emission tomography (PET) scan using ((11)C)-labeled 2-carbomethoxy-3-(4-fluorophenyl) tropane [((11)C) CFT] and ((11)C)-labeled raclopride [((11)C) RAC] revealed significant decreases bilaterally in pre- and postsynaptic functions of the dopaminergic neurons. When we experience a case with bilateral putaminal destruction resulting in Parkinsonism, examination of the function of doperminergic neurons and dopamine receptors using molecular imaging is useful to predict levodopa response and prognosis.
Subject(s)
Diabetes Complications/complications , Dopamine Plasma Membrane Transport Proteins/metabolism , Molecular Imaging , Parkinsonian Disorders/complications , Parkinsonian Disorders/metabolism , Receptors, Dopamine/metabolism , Uremia/complications , Adult , Diabetes Complications/metabolism , Humans , Ligands , Male , Parkinsonian Disorders/diagnostic imaging , Protein Binding , Uremia/metabolismABSTRACT
INTRODUCTION: An increasing number of adult patients have been diagnosed with fatty acid ß-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.
Subject(s)
Multiple Acyl Coenzyme A Dehydrogenase Deficiency/metabolism , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/pathology , Adult , Age Factors , Carnitine/analogs & derivatives , Carnitine/blood , Humans , Male , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/blood , Muscle Weakness/blood , Muscle Weakness/pathology , Muscular Diseases/blood , Muscular Diseases/pathologyABSTRACT
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.
Subject(s)
Giant Axonal Neuropathy/pathology , Axons/pathology , Child , Cytoskeletal Proteins/genetics , Genetic Association Studies , Giant Axonal Neuropathy/genetics , Humans , Magnetic Resonance Imaging , Male , Pedigree , Pyramidal Cells/pathologyABSTRACT
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.
Subject(s)
Bipolar Disorder/pathology , Brain/pathology , Neurodegenerative Diseases/pathology , Aged , Aged, 80 and over , Bipolar Disorder/complications , Humans , Male , Middle Aged , Neurodegenerative Diseases/complicationsSubject(s)
Bezafibrate/therapeutic use , Carnitine/analogs & derivatives , Carnitine/therapeutic use , Electron-Transferring Flavoproteins/genetics , Hypolipidemic Agents/therapeutic use , Iron-Sulfur Proteins/genetics , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/drug therapy , Oxidoreductases Acting on CH-NH Group Donors/genetics , Riboflavin/therapeutic use , Adult , Carnitine/blood , Drug Therapy, Combination , Humans , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/blood , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/genetics , Mutation , Treatment OutcomeABSTRACT
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 Dorello's 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 Dorello's 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 Dorello's 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 Dorello's canal obstruction by sarcoidosis. Complete remission can be achieved with proper treatment.
Subject(s)
Abducens Nerve Diseases/complications , Muscular Diseases/complications , Sarcoidosis/complications , Abducens Nerve/physiopathology , Brain/pathology , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Muscle, Skeletal/pathologySubject(s)
Brain Damage, Chronic/pathology , Cerebellum/pathology , Hepatolenticular Degeneration/pathology , Aged , Balloon Occlusion , Brain Damage, Chronic/complications , Brain Damage, Chronic/therapy , Diagnostic Imaging/methods , Hepatolenticular Degeneration/complications , Hepatolenticular Degeneration/diagnosis , Hepatolenticular Degeneration/therapy , Humans , Magnetic Resonance Imaging/methods , Male , Treatment OutcomeABSTRACT
A 38-year-old Japanese man with Nasu-Hakola disease (NHD) had repeated pathological fractures and frontal lobe symptoms which developed when he was 18 and 26 years old, respectively. Neuropsychological testing showed memory impairment, and in particular, visuo-spatial memory at the age of 35. Furthermore, single-photon emission computed tomography revealed precuneus hypoperfusion. The patient later suffered prolonged convulsive seizures, which left him in a persistent vegetative state. Genetic testing confirmed a heterozygous mutation in the DAP12 gene (a single-base deletion of 141 G in exon 3) specific to NHD. Precuneus dysfunction might contribute to characteristic memory impairment of NHD.