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Objective: To characterize the clinical, radiological, and pathological manifestations of 18 cases showing neurogenic calf amyotrophy with creatine kinase (CK) elevation by entrapment radiculopathy (NCACKEER). Methods: We retrospectively reviewed and evaluated the medical records of patients who complained of weakness or atrophy of the calf muscles in our department between 2004 and 2019. We identified 18 cases fulfilling the proposed criteria of NCACKEER. We extracted neurological, laboratory, neurophysiological, and neuroradiological data from all cases. Moreover, we evaluated biopsy specimens from the gastrocnemius in four cases. Results: Eighteen NCACKEER cases exhibited the characteristic findings that can discriminate previously known myopathies or polyneuropathies affecting distal legs. We noticed male predominance (72%) with an average age at diagnosis of 65.6 years. Muscle weakness or atrophy was localized in the distal legs, with Achilles tendon reflexes absent in all cases. We observed elevated serum CK levels with a range from 237 to 2294 IU/L. All electromyography (EMG) studies showed neurogenic changes in the affected muscles. Lumbar spinal MRI exhibited either spinal canal stenosis at various vertebral levels or intervertebral foraminal stenosis at L4/5 and L5/S1 in all cases with significant straightening spinal and sacral alignments. All muscle biopsy specimens showed findings of neurogenic muscular degeneration with no inflammatory infiltrations. Cases with higher CK elevation had more necrotic muscle fibers. Conclusion: We established the clinical characteristics of NCACKEER. Evaluations of serum CK level and skeletal muscle CT imaging are useful for screening, and lumbar spinal MRI, EMG and/or muscle biopsy are necessary for diagnostic confirmation. [ABSTRACT FROM AUTHOR]

Neuroimages of cerebral amyloid-β (Aβ) accumulation and small vessel disease (SVD) were examined in patients with various types of cognitive disorders using 11C-labeled Pittsburgh Compound B-positron emission tomography (PiB-PET) and magnetic resonance imaging (MRI). The mean cortical standardized uptake value ratio (mcSUVR) was applied for a quantitative analysis of PiB-PET data. The severity of white matter lesions (WML) and enlarged perivascular spaces (EPVS) on MRI were assessed to evaluate complicating cerebral SVD using semiquantitative scales. In homozygous apolipoprotein E ɛ3/ɛ3 carriers, the incidence of more severe WML and EPVS was higher in PiB-positive than PiB-negative patients, indicating that WML and EPVS might be associated with enhanced Aβ accumulation. An association study between PiB-PET and MRI findings revealed that higher WML grades significantly correlate with lower mcSUVRs, especially in the frontal area, indicating that more severe ischemic MRI findings are associated with milder Aβ accumulation among patients with Alzheimer's disease. In these patients SVD may accelerate the occurrence of cognitive decline and facilitate early recognition of dementia. [ABSTRACT FROM AUTHOR]

The literature was reviewed with regard to the relationship between Alzheimer’s dementia (AD) and depression. Then comparison was made of the case for depression as a precursor symptom of AD versus the case for depression as the initial symptom of AD. We also discussed such points as the coexistence of depression and AD, pseudodementia, etc. Finally, we postulated that the relationship between AD and depression shows a spectrum, and on that basis we attempted to define six clinical patterns. [ABSTRACT FROM AUTHOR]

Phantom boarder symptom (PBS) is a hallucinatory and delusional syndrome that tends to occur in the elderly, in which the patient imagines that someone uninvited is living in their home. This article provides an overview of the historical background that has led to the current focus on PBS as a single symptom, from its classification as late paraphrenia to its being recognized as a type of misidentification, and discusses classification problems and PBS subclassifications. In addition, the results of our own investigation of PBS, which focused on PBS in senile dementia, support the findings of previous studies, such as the absence of a relationship between dementia severity and the occurrence of delusion. The discussion therefore focuses on the psychosocial factors that serve as the mechanism of PBS onset, and directions and possibilities for therapy are suggested. [ABSTRACT FROM AUTHOR]

Background: The cerebrospinal fluid (CSF) levels of tau phosphorylated at threonine 217 (p217tau) or 181 (p181tau), and neurofilament light chain (NfL) are definite biomarkers of tauopathy and neurodegeneration in Alzheimer's disease (AD). Objective: To validate their utility in excluding other neurological diseases and age-related changes in clinical settings. Methods: We developed monoclonal antibodies against p217tau and NfL, established novel ELISAs, and analyzed 170 CSF samples from patients with AD or other neurological diseases. Results: In AD, p217tau is a more specific and abundant CSF component than p181tau. However, CSF NfL levels increase age-dependently and to a greater extent in central and peripheral nervous diseases than in AD. Conclusions: CSF p217tau correlates better with AD neurodegeneration than other tau-related biomarkers and the major phosphorylated tau species. The clinical usage of NfL as a neurodegeneration biomarker in AD requires exclusion of various central and peripheral neurological diseases. [ABSTRACT FROM AUTHOR]

Neuronal intranuclear inclusion disease (NIID) is a clinically complex neurological disorder that appears sporadically or autosomally. Expansions of intronic GGC trinucleotide repeats in the NOTCH2 N-terminal-like C (NOTCH2NLC) gene cause NIID. In this study, to clarify the clinical characteristics useful for the differential diagnosis of NIID, clinical data of neurological examination, neuroimaging, and nerve conduction studies of six NIID patients diagnosed by pathological or genetic investigations were analyzed. Clinically useful characteristics for diagnosing NIID include general hyporeflexia, episodic disturbance of consciousness, sensory disturbance, miosis, and dementia. Furthermore, neuroimaging findings, such as leukoencephalopathy in T2-weighted magnetic resonance imaging and a linear high intensity of subcortical U-fibers in diffusion-weighted imaging (DWI), as well as decreased motor nerve conduction velocity, are especially important biomarkers for NIID. However, it is necessary to remember that these features may not always be present, as shown in one of the cases who did not have a DWI abnormality in this study. This study also investigated whether expanded GGC repeats were translated into polyglycine. Immunohistochemical analysis using a custom antibody raised against putative C-terminal polypeptides followed by polyglycine of uN2CpolyG revealed that polyglycines were localized in the intranuclear inclusions in skin biopsy specimens from all six patients, suggesting its involvement in the pathogenesis of NIID. • Clinical, radiological, and molecular analyses of six cases of NIID were performed. • DWI linear high intensity of U-fibers was commonly, but not always, present. • Reduced motor nerve conduction velocity is an important feature of NIID. • Polyglycine-containing inclusions were identified in the skin biopsy specimens. • Polyglycines may be involved in the pathogenesis of NIID. [ABSTRACT FROM AUTHOR]

• Complement plays a major role in multiple system atrophy (MSA) • Complement deposition in the cerebral vessels and myelin sheaths is evident in MSA. • Blood brain barrier disruption is potentially a key factor in MSA pathogenesis. Multiple system atrophy (MSA) is a progressive and sporadic neurodegenerative disorder characterized by the histological appearance of glial cytoplasmic inclusions primarily composed of α-synuclein. Recently, complement-mediated neuroinflammation has been proposed as a key factor in the pathogenesis of numerous neurodegenerative disorders. We conducted immunohistochemical/immunofluorescent assays targeting a number of complements to explore the role of complements in MSA pathogenesis using brain samples from deceased patients and controls. Complement deposition was notably increased in the cerebral vasculature and myelin sheath in the MSA brains. Furthermore, fibrinogen leakage resulting from the disruption of the blood–brain barrier (BBB) was observed, along with the presence of C1q-positive microglia clusters surrounding the MSA brain vessels. These immunohistochemical/immunofluorescent findings suggest that complement activation and BBB disruption play critical roles in MSA progression. [ABSTRACT FROM AUTHOR]

BACKGROUND: There were no previous studies in Japan on the psychological distress of members of families with cancer patients which focussed on the disclosure of the diagnosis of cancer. This study was designed to investigate factors that may have an effect on the psychological distress of family members. METHODS: The subjects were 95 members of families of cancer patients in the surgical ward; one member was recruited from each patient's family. The psychiatrist investigated the demographic factors of both the patient and the family member: for the patient – gender, age, occupation, cancer site, disclosure (or not) of cancer diagnosis, cancer stage and performance status (PS); for the family member – gender, age, occupation, relationship to the patient, physical illness, frequency of visiting the ward, the period from when the family member was informed of the diagnosis, and any past experience of the loss of close relatives due to cancer. Furthermore, we conducted a survey on the family member's anxiety and depression by using the Spielberger State – Trait Anxiety Inventory (STAI) and the Center for Epidemiological Studies Depression Scale (CES-D). RESULTS: A multiple regression analysis indicated that the factors which were associated with the STAI scores independently were the lack of disclosure of the diagnosis to the patient (P=0.01), and advanced or recurrent cancer (P=0.01). The factors which were associated with the CES-D scores independently were the lack of disclosure of the diagnosis to the patient (P=0.03), advanced or recurrent cancer (P=0.01), and the family member's past history of psychiatric disorders (P=0.01). CONCLUSIONS: The results suggested that the psychological distress of a family member increases when the patient is not informed of the cancer diagnosis, when the cancer is advanced or recurrent, and when the family member has a past history of psychiatric disorders. (Int J Psych Clin Pract 2002; 6: 205–210). [ABSTRACT FROM AUTHOR]

123I-ioflupane single-photon emission computed tomography (SPECT) is a highly sensitive and established neuroimaging technique for parkinsonian syndromes (PS). However, differentiating PS by visual inspection or analysis of regions of interest is challenging. To date, image analysis has not been able to differentiate dementia with Lewy bodies (DLB) from Parkinson's disease with dementia (PDD). This study aimed to differentiate PS based on the characteristics of striatal dopamine transporter (DAT) binding using voxel-based analysis. We acquired 123I-ioflupane SPECT data from patients with DLB (n = 30), Parkinson's disease (PD; n = 122), PDD (n = 19), multiple system atrophy with predominant parkinsonism (MSA-P; n = 18), and progressive supranuclear palsy (PSP; n = 45). DAT binding was reduced in the posterior striatum of patients with PD and PDD, whereas it was similar in MSA-P, PSP, and DLB. Hippocampal atrophy, visually evaluated by cerebral magnetic resonance imaging, did not affect striatal DAT binding in DLB. DAT binding in the anterior striatum was inversely correlated with the severity of parkinsonism in PD and PDD but not in DLB. Thus, the appearance of striatal DAT binding might indicate different pathological processes in DLB and PDD. • Striatal dopamine transporter (DAT) binding differentiated parkinsonian syndromes. • Mode of striatal DAT binding in PD and PDD is different from that in DLB. • Hippocampal atrophy did not affect striatal DAT binding in DLB. • DAT binding was reduced in the posterior striatum of patients with PD and PDD. • Process of disease progression may differ between PD/PDD and DLB. [ABSTRACT FROM AUTHOR]

A middle-aged male suffering from encephalopathy with cerebral amyloid angiopathy (CAA) with amyloid beta (Aβ) presented with initial symptoms of transient consciousness disturbance and left visual field photophobia. Lesions with aberrantly high signal on T2-weighted magnetic resonance imaging (MRI) of the brain appeared in the right temporal lobe posterior to the occipital lobe and spread to other areas. Brain biopsy revealed Aβ deposits in vascular walls and numerous diffuse plaques in parenchymal areas. Based on MRI findings, Initial corticosteroid therapy with beta methasone effectively improved the neurological symptoms of consciousness disturbance and motor deficits. After corticosteroid therapy was stopped at 4 weeks, recurrence occurred. Additional corticosteroids did not improve clinical symptoms and the patient progressed to a bed-ridden state with a severe consciousness disturbance. Notably, CSF Aβ1-42 and CSF Aβ1-40 decreased while the recurrent encephalopathy worsened. After intense deterioration, the patient became stable. CSF Aβ1-42 increased but remained at a very low level. This case of CAA encephalopathy with apolipoprotein E ε4/ε4 homozygosity showed Aβ deposits in vascular walls and numerous diffuse plaques in parenchymal areas. The clinical course suggests that reduction of CSF Aβ1-42 and Aβ1-40 might be related to clinical deterioration in cases of encephalopathy. [ABSTRACT FROM AUTHOR]

Background: Previous research has described the executive dysfunction that occurs in patients with amnestic-mild cognitive impairments (A-MCI) and early-stage Alzheimer's disease (EAD), which are comparatively similar stages of dementia. The aim of the present cross-sectional study is to evaluate executive dysfunction using the Frontal Assessment Battery (FAB) screening test in two groups and to investigate the interaction with other cognitive impairments. Methods: Among 170 consecutive patients with Alzheimer's disease or A-MCI, we recruited 48 subjects who were under 75 years of age and had been diagnosed as having either A-MCI or EAD. We then compared the total and the subtest scores of the mini-mental state examination (MMSE) and the FAB between the two groups. Moreover, we investigated the statistical interactive associations of the FAB subtest scores with the influential MMSE subtest scores or the diagnosis (A-MCI or EAD). Results: No significant differences in the age, sex ratio, duration of illness, and education years were observed between the two groups. However, significant differences in the FAB total and subtest scores (conflicting instructions and go/no-go) were found between the two groups. Furthermore, significant differences in the MMSE total and subtest scores (orientation, memory delayed recall, and attention and calculation) were also noted between the two groups. In a generalized linear model analysis, only two FAB subtest scores (conflicting instructions and go/no-go) were significantly influenced by the diagnosis (A-MCI or EAD) in a manner that was independent of the interaction with the orientation or memory delayed recall. Conclusion: The present findings suggest that the FAB total score and subtest scores reflecting interference performances (conflicting instructions and go/no-go) significantly declined in patients with EAD, independent of the disorientation and memory disorder. Such characteristics of neuropsychological screening test scores may be useful to clinicians for differentiating EAD and A-MCI at bedside. [ABSTRACT FROM AUTHOR]

Background: To address the functional roles of genetic polymorphisms of brain-derived neurotrophic factor ( BDNF) in Alzheimer's disease (AD) from a neuropsychological aspect, we used a cross-sectional study design to investigate the association between novel single nucleotide polymorphisms (SNPs) of the BDNF gene (Val66Met (G196A) and C270T) and the Frontal Assessment Battery (FAB) score, which reflects executive function as a non-memory cognitive impairment. Methods: One hundred and sixty-nine outpatients with AD or amnestic mild cognitive impairment (A-MCI) were recruited to the study and divided into three genotypic groups for each representative BDNF functional polymorphism as follows: (i) Val66Met (G196A): G/G ( n= 45), G/A ( n= 104), and A/A ( n= 20); and (ii) C270T: C/C ( n= 160), C/T ( n= 9), and T/T ( n= 0). Then, age, sex ratio, duration of illness (months), education years, Mini-Mental State Examination (MMSE) score, behavioral pathology in Alzheimer disease (Behave-AD) score, Clinical Dementia Rating (CDR) ratio, and total and subtest FAB scores were compared between the genotypic groups for each SNP. Results: Significant differences were found in the total ( P < 0.01) and subtest (conflicting instructions and prehension behavior; P < 0.01) FAB scores between the C270T polymorphism groups (C/C and C/T), but not among the G196A polymorphism groups. However, no significant differences in age, sex ratio, duration of illness (months), education years, Behave-AD score, CDR ratio, or MMSE score (reflecting attention and memory function) were found between the individual polymorphism genotypes (G196A and C270T). Conclusion: Of the known BDNF polymorphisms, the C270T SNP may influence executive dysfunction as a non-memory cognitive impairment in Japanese patients with AD. [ABSTRACT FROM AUTHOR]

Aims: The purpose of the present study was to investigate the relationship between delusional thoughts (delusional ideation or misidentification) and frontal lobe function using the Japanese version of the Frontal Assessment Battery (FAB) bedside screening neuropsychological test in early stage Alzheimer's disease (AD) patients. Methods: Forty-eight probable AD patients with Mini-Mental State Examination score ≧18 points and a clinical dementia rating score of either 0.5 or 1.0 were divided into two groups based on data obtained from interviews with their caregivers: a delusional thought group ( n = 19) and a non-delusional thought group ( n = 29). The FAB total and subtest scores were then compared for the two groups. Results: Significant differences were found between the FAB total ( P < 0.01) and subtest scores (similarities, motor series, conflicting instructions; P < 0.05) for the two groups. Multiple regression analysis showed that delusional thought was significantly associated with the FAB total score. Conclusions: In addition to episodic memory disorders, a reduction in the FAB score may reflect frontal lobe dysfunctions, including executive function, in patients with AD, leading to delusional ideation. [ABSTRACT FROM AUTHOR]

Anticonvulsants have been used for the treatment of impulsive aggression since the 1980s. A 50-year-old man suffered from irritability and agitation after developing a right ipsilateral frontal lobe infarction as a result of Moyamoya disease; these symptoms caused difficulties with his working and interpersonal relationships. The patient had been treated using multiple benzodiazepine agents for 2 years but his symptoms had not improved. However, after treatment with carbamazepine (CBZ; 200 mg) was begun, the patient's irritability and agitation gradually decreased. The efficacy of CBZ treatment in this patient suggests a method for controlling benzodiazepine-resistant impulsive aggression. [ABSTRACT FROM AUTHOR]