Alexander disease with a novel GFAP insertion-deletion mutation mimicking progressive supranuclear palsy.

This report presents a case of Alexander disease showing clinical characteristics mimicking progressive supranuclear palsy (PSP). A 67-year-old woman complaining of motor disturbance exhibited severe atrophy of medulla, spinal cord, and midbrain tegmentum, as well as periventricular hyperintensity on cerebral MRI. Genetic analysis identified a novel in-frame deletion/insertion mutation in the exon 3 of the GFAP gene. Interestingly, neurological findings and decreased striatal uptake in dopamine transporter SPECT were suggestive of PSP. A novel GFAP gene mutation found in the present case may cause the unique clinical phenotype, which should be differentiated from PSP.

Role of complement activation and disruption of the blood-brain barrier in the pathogenesis of multiple system atrophy.

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.

High levels of plasma neurofilament light chain correlated with brainstem and peripheral nerve damage.

BACKGROUND AND OBJECTIVES: Blood neurofilament light chain (NfL) is a minimally invasive, but highly sensitive biomarker of neurological diseases. However, diseases and neurological damage associated with increased NfL remain unclear. Therefore, the present study investigated factors associated with increased plasma NfL levels in various neurological diseases, focal lesions and pathological processes. METHODS: This was a retrospective cohort study on 410 participants with various neurological diseases and 17 healthy and cognitively unimpaired controls (HCU). Plasma samples were analyzed to measure NfL using ECL immunoassay. The focal lesions were classified as the cerebrum, cerebellum, brainstem, meninges, spinal cord, peripheral nerves, neuromuscular junction, and muscles based on medical records. A multiple regression analysis and receiver operating characteristic curve (ROC) analysis were performed to investigate whether plasma NfL levels predict specific diseases and focal lesions. RESULTS: Plasma NfL levels discriminated between the HCU and all disease groups (area under the curve (AUC), 0.97), with a cut-off value of 63.4 pg/mL. A multiple regression analysis of focal lesions adjusted by pathogenic processes showed that brainstem and peripheral nerve involvement was associated with higher plasma NfL levels. A cut-off value of 53.8 pg/mL of NfL discriminated between the HCU and neurological disease group except for brainstem or peripheral disorders (AUC 0.962), while a cut-off value of 208.0 pg/mL distinguished this group from brainstem or peripheral nervous system disorders (AUC 0.716). DISCUSSION: These results demonstrate that plasma NfL has a potential to be a highly sensitive biomarker for neurological diseases and focal lesions.

Clinical, radiological, and molecular analyses of neuronal intranuclear inclusion disease with polyglycine inclusions.

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.

Striatal dopamine transporter binding differs between dementia with Lewy bodies and Parkinson's disease with dementia.

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.

Clinical Evaluation of Cerebrospinal Fluid p217tau and Neurofilament Light Chain Levels in Patients with Alzheimer's Disease or Other Neurological Diseases.

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.

Multimodal immunotherapy ameliorates myasthenia gravis preceded by thymoma-associated multiorgan autoimmunity.

Thymoma-associated multiorgan autoimmunity (TAMA) is a rare autoimmune disorder associated with thymoma that causes a pathology similar to graft-versus-host disease (GVHD) targeting the skin, digestive organs, and liver. Herein, we report the case of a 38-year-old male with myasthenia gravis (MG) preceded by TAMA. The patient developed intractable diarrhea 2 years before admission. Subsequently, dysphagia, dysarthria, and left blepharoptosis were observed. The patient was admitted to the hospital because of fever and dyspnea, was positive for anti-AChR antibody, and chest-computed tomography revealed thymoma, which led to the diagnosis of thymoma-related MG. Biopsied specimens from the sigmoid colon revealed apoptotic colonopathy with lymphocyte-rich lamina propria. Immunohistochemical staining revealed that the infiltrating cells were predominantly labeled with anti-CD3-antibody. The patient did not show skin lesions or liver dysfunction. Therefore, TAMA limited to the gastrointestinal tract was diagnosed. Although TAMA typically has a poor prognosis, immediate multimodal immunotherapy for MG was successful, resulting in a good outcome for TAMA of this case. TAMA is caused by the inability of the thymoma to suppress self-reactive T lymphocytes, which subsequently leads to a disease that is clinically indistinguishable from GVHD. Based on the characteristics of this case, limited gastrointestinal tract involvement in TAMA without lesions in other organs may lead to a favorable prognosis. TAMA cases lacking skin lesions may present with nonspecific gastrointestinal or liver disease. If a patient with thymoma-associated MG has gastrointestinal symptoms such as diarrhea, TAMA should be considered, and the diagnosis should be made early by pathological evaluation of gastrointestinal tissues.

Association between executive dysfunction and hippocampal volume in Alzheimer's disease.

BACKGROUND: Some previous research has hypothesized that executive dysfunction in patients with early Alzheimer's disease (AD) occurs as a result of a disconnection between different cerebral areas. The aim of the present study was to evaluate how the hippocampal volume influences executive function as a non-memory cognitive function. METHODS: From 157 consecutive patients with AD or amnestic mild cognitive impairment (A-MCI), we recruited 107 subjects who had a global Clinical Dementia Rating (CDR) of 0.5 or 1.0 and whose degree of hippocampal atrophy had been measured using magnetic resonance imaging (MRI); the severity of atrophy was assessed using the voxel-based specific regional analysis for Alzheimer's disease (VSRAD) system. We divided the subjects into three groups: mild atrophy, 0 < Z-score < 1.0 (N = 21); moderate atrophy, 1.0 ≤ Z-score < 2.0 (N = 46); or severe atrophy, 2.0 ≤ Z-score < 4.0 (N = 40) according to the Z-score and compared the Frontal Assessment Battery (FAB) and its subtest scores between each atrophy group. RESULTS: The results demonstrated that age, sex ratio, duration of illness, education years, MMSE score, Behave-AD score, and proportion of atrophy area in total brain (%) were not significantly different among the three groups. Only the go/no-go score among the six subtests was significantly lower for increasing atrophy severity (P < 0.05). Furthermore, hippocampal atrophy significantly influenced the go/no-go score independently of interactions from whether the diagnosis was early AD or A-MCI (P < 0.05). CONCLUSION: These results support a significant association between hippocampal atrophy and executive dysfunction as a non-memory cognitive impairment in patients with early AD and A-MCI.

Differentiation between amnestic-mild cognitive impairment and early-stage Alzheimer's disease using the Frontal Assessment Battery test.

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.

Association between brain-derived neurotrophic factor (BDNF) gene polymorphisms and executive function in Japanese patients with Alzheimer's disease.

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.

Sibling Cases of Charcot-Marie-Tooth Disease Type 4H with a Homozygous FGD4 Mutation and Cauda Equina Thickening.

Charcot-Marie-Tooth disease type 4H (CMT4H) is an autosomal recessive inherited demyelinating neuropathy caused by an FYVE, RhoGEF, and a PH domain-containing protein 4 (FGD4) gene mutation. CMT4H is characterized by an early onset, slow progression, scoliosis, distal muscle atrophy, and foot deformities. We herein present sibling cases of CMT4H with a homozygous mutation in the FGD4 gene. Both patients exhibited cauda equina thickening on magnetic resonance imaging, which had not been reported among the previous CMT4H cases. This is the first report of CMT4H with a homozygous FGD4 c.1730G>A (p.Arg577Gln) mutation showing mild progression and cauda equina thickening.

Recurrent Lobar Hemorrhages and Multiple Cortical Superficial Siderosis in a Patient of Alzheimer's Disease With Homozygous APOE ε2 Allele Presenting Hypobetalipoproteinemia and Pathological Findings of 18F-THK5351 Positron Emission Tomography: A Case Report.

In Alzheimer's disease, the apolipoprotein E gene (APOE) ε2 allele is a protective genetic factor, whereas the APOE ε4 allele is a genetic risk factor. However, both the APOE ε2 and the APOE ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the APOE ε2 allele remains unknown. Here, we describe the case of a 79-year-old Japanese female with Alzheimer's disease, homozygous for the APOE ε2 allele. This patient presented with recurrent lobar hemorrhages and multiple cortical superficial siderosis. The findings on the 11C-labeled Pittsburgh Compound B-positron emission tomography (PET) were characteristic of Alzheimer's disease. 18F-THK5351 PET revealed that the accumulation of 18F-THK 5351 in the right pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule, reflecting the lesions of the previous lobar intracerebral hemorrhage in the right frontal lobe. Moreover, 18F-THK5351 accumulated in the bilateral globus pallidum, amygdala, caudate nuclei, and the substantia nigra of the midbrain, which were probably off-target reaction, by binding to monoamine oxidase B (MAO-B). 18F-THK5351 were also detected in the periphery of prior lobar hemorrhages and a cortical subarachnoid hemorrhage, as well as in some, but not all, areas affected by cortical siderosis. Besides, 18F-THK5351 retentions were observed in the bilateral medial temporal cortices and several cortical areas without cerebral amyloid angiopathy or prior hemorrhages, possibly where tau might accumulate. This is the first report of a patient with Alzheimer's disease, carrying homozygous APOE ε2 allele and presenting with recurrent lobar hemorrhages, multiple cortical superficial siderosis, and immunohistochemically vascular amyloid ß. The 18F-THK5351 PET findings suggested MAO-B concentrated regions, astroglial activation, Waller degeneration of the pyramidal tract, neuroinflammation due to CAA related hemorrhages, and possible tau accumulation.

Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease.

Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aß) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aß1-42, Aß1-40, Aß1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by 99mTc-ethyl cysteinate dimer single photon emission computerized tomography (99mTc ECD-SPECT), as well as the mean cortical standard uptake value ratio by 11C-labeled Pittsburgh Compound B-positron emission tomography (11C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aß1-38, Aß1-40, Aß1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant.

Relationship of frontal lobe dysfunction and aberrant motor behaviors in patients with Alzheimer's disease.

BACKGROUND: In order to address the neuropsychological pathogenesis of aberrant motor behaviors in Alzheimer's disease (AD), we used a cross-sectional study design to investigate the association between frontal lobe function, including executive function, and activity disturbances (wandering, purposeless activities and inappropriate activities). METHODS: Among 75 consecutive outpatients with AD, 50 subjects with a Clinical Dementia Rating (CDR) score of 1 or 2 were selected and divided into two groups based on data obtained from interviews with their caregivers: an aberrant motor behaviors (AMB) group (n = 22), and a non-aberrant motor behaviors (NAMB) group (n = 28). Aberrant motor behavior was defined according to whether the "activity disturbance" score (ranging from 0 to 9) of the Behavioral Pathology in Alzheimer Disease (Behave-AD) scale was 0 or >or=1. The total and subtest scores of the Frontal Assessment Battery (FAB) were then compared between the two groups. RESULTS: Significant differences were found between the FAB total (P < 0.05) and the subtest scores (lexical fluency, conflicting instructions; P < 0.05) in the two groups. The FAB score was significantly associated with the activity disturbance score (r = -0.49; P<0.001). A stepwise multiple regression analysis showed that only the FAB score significantly influenced the activity disturbance score (P < 0.001). CONCLUSIONS: This finding suggested that in addition to episodic memory disturbance, frontal lobe dysfunctions might lead patients with AD to develop aberrant motor behavior.

Neurogenic calf amyotrophy with CK elevation by entrapment radiculopathy; clinical, radiological, and pathological analyses of 18 cases.

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.

Increased Neurofilament Light Chain and YKL-40 CSF Levels in One Japanese IBMPFD Patient With VCP R155C Mutation: A Clinical Case Report With CSF Biomarker Analyses.

Inclusion body myopathy (IBM) with Paget's disease of bone (PDB) and frontotemporal dementia (IBMPFD) presents with multiple symptoms and an unknown etiology. Valosin-containing protein (VCP) has been identified as the main causative gene of IBMPFD. However, no studies on neurofilament light chain (NFL) as a cerebrospinal fluid (CSF) marker of axonal neurodegeneration or on YKL-40 as a CSF marker of glial neuroinflammation have been conducted in IBMPFD patients with VCP mutations. A 65-year-old man presented with progressive muscle atrophy and weakness of all limbs, non-fluent aphasia, and changes in personality and behavior. Cerebral MRI revealed bilateral frontal and temporal atrophy. 99mTc-HMDP bone scintigraphy and pelvic CT revealed remodeling changes and active osteoblastic accumulations in the right medial iliac bone. Muscle biopsy demonstrated multiple rimmed vacuoles in muscle cells with myogenic and neurogenic pathological alterations. After the patient was clinically diagnosed with IBMPFD, DNA analysis of the VCP gene revealed a cytosine (C) to thymine (T) (C→ T) mutation, resulting in an amino acid exchange of arginine to cysteine (p.R155C mutation). The CSF levels of NFL at two time points (12 years apart) were higher than those in non-dementia controls (CTR) and Alzheimer's disease (AD); lower than those in frontotemporal dementia with motor neuron disease (FTD-MND); and comparable to those in patients with behavioral variant frontotemporal dementia (bvFTD), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). The CSF levels of YKL-40 were comparable at both time points and higher than those in CTR; lower than those in FTD-MND; and comparable to those in bvFTD, PSP, CBS, and AD. The CSF levels of phosphorylated tau 181 (P-Tau) and total tau (T-Tau) were not significantly different from those in CTR and other neurodegenerative diseases, except those in AD, which were significantly elevated. This is the first report that demonstrates increased NFL and YKL-40 CSF levels in an IBMPFD patient with a VCP mutation (p.R155C); NFL and YKL-40 levels were comparable to those in bvFTD, PSP, CBS, and AD and higher than those in CTR. Our results suggest that IBMPFD neuropathology may involve both axonal neurodegeneration and glial neuroinflammation.

Correlation between a reduction in Frontal Assessment Battery scores and delusional thoughts in patients with Alzheimer's disease.

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 >or=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.

Temporal Changes on 123I-Iomazenil and Cerebral Blood Flow Single-photon Emission Computed Tomography in a Patient with Anti-N-methyl-D-aspartate Receptor Encephalitis.

A 45-year-old man was admitted due to tonic seizures, aphasia, disturbance of consciousness, and abnormal behavior. Because cerebral magnetic resonance imaging findings were normal and mild cerebrospinal fluid (CSF) pleocytosis was observed, autoimmune encephalitis was suspected. The presence of anti-N-methyl-D-aspartate (NMDA) receptor antibodies in the CSF was subsequently confirmed. 123I-Iomazenil and cerebral blood flow single photon emission computed tomography (SPECT) revealed an abnormal uptake in the left frontotemporal region. Multimodal immunotherapy was administered, which remarkably improved the level of consciousness. Progressive reversibility of SPECT findings with clinical improvement suggested that the disorder-related functional deficits had been caused by anti-NMDA receptor antibodies.

Deep White Matter Lesions Are Associated with Early Recognition of Dementia in Alzheimer's Disease.

Neuroimages of cerebral amyloid-ß (Aß) 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 Aß 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 Aß accumulation among patients with Alzheimer's disease. In these patients SVD may accelerate the occurrence of cognitive decline and facilitate early recognition of dementia.

[Charcot-Marie-Tooth disease showing transient central nervous system lesions after a large amount of alcohol intake: A case report].

A 23-year-old man experienced numbness in the perioral region and right arm, and right leg weakness on the second day after drinking a large amount of alcohol during foreign travel. His symptoms disappeared but then reappeared repetitively. Cerebral MRI performed on the third day after onset showed multiple white matter lesions; however, these lesions disappeared 26 days after onset. Neurological examination and nerve conduction studies revealed demyelinating polyneuropathy. Genetic testing for Charcot-Marie-Tooth disease, X-linked dominant 1 (CMTX1) due to GJB1 mutation was conducted based on the symptoms of transient central nervous system lesions and polyneuropathy exhibited by the patient and his mother. As a result, a c.530T>C (p.V177A) substitution in exon 2 of GJB1 was identified. CMTX1 patients should be advised to avoid excessive drinking because this could induce central nervous system lesions.