Clinical utility of paced finger tapping assessment in idiopathic normal pressure hydrocephalus.

Background: The Finger Tapping (F-T) test is useful for assessing motor function of the upper limbs in patients with idiopathic normal pressure hydrocephalus (iNPH). However, quantitative evaluation of F-T for iNPH has not yet been established. The purpose of this study was to investigate the usefulness of the quantitative F-T test and optimal measurement conditions as a motor evaluation and screening test for iNPH. Methods: Sixteen age-matched healthy controls (mean age 73 ± 5 years; 7/16 male) and fifteen participants with a diagnosis of definitive iNPH (mean age 76 ± 5 years; 8/15 male) completed the study (mean ± standard deviation). F-T performance of the index finger and thumb was quantified using a magnetic sensing device. The performance of repetitive F-T by participants was recorded in both not timing-regulated and timing-regulated conditions. The mean value of the maximum amplitude of F-T was defined as M-Amplitude, and the mean value of the maximum velocity of closure of F-T was defined as cl-Velocity. Results: Finger Tapping in the iNPH group, with or without timing control, showed a decrease in M-Amplitude and cl-Velocity compared to the control group. We found the only paced F-T with 2.0 Hz auditory stimuli was found to improve both M-Amplitude and cl-Velocity after shunt surgery. Conclusion: The quantitative assessment of F-T with auditory stimuli at the rate of 2.0 Hz may be a useful and potentially supplemental screening method for motor assessment in patients with iNPH.

Memantine for the patients with mild cognitive impairment in Parkinson's disease: a pharmacological fMRI study.

BACKGROUND: Mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with an increased risk of cognitive decline. PD-MCI is characterized by impairments in executive function and visuospatial recognition. The visuospatial n-back test is useful for assessing both domains. The 0-back test reflects visuospatial recognition, while the 1-back and 2-back tests reflect working memory. Cholinesterase inhibitors are effective in the treatment of PD-MCI and dementia in PD (PDD). Although some studies have reported the efficacy of memantine for PDD, the therapeutic efficacy of memantine in patients with PD-MCI remains uncertain. METHODS: This study aimed to investigate the effects of memantine on brain function in patients with PD-MCI, using a randomized double-blinded crossover protocol and functional MRI (fMRI). Ten patients who completed 16 weeks of follow-up were included. They were randomly assigned to either the memantine or placebo. Patients in the memantine group received 5 mg/day of memantine in the first week. The memantine dose was increased by 5 mg/day per week, until a final dose of 20 mg/day. Patients in the placebo group received the placebo following the same regimen as memantine. After the intervention, they underwent a 4 weeks washout period. Following the crossover protocol, a second intervention was conducted after the washout period. In each intervention, fMRI and neuropsychological tests were performed at the maximum dose period. Comparing the memantine and placebo groups, we investigated difference in the brain regions using the visuospatial n-back test. RESULTS: There were no significant regions enhanced by memantine comparing with placebo at any load of n-back tests. In contrast, exploring regions reduced by memantine, we found significant reduction of activations within right lingual gyrus and left superior frontal gyrus in comparison between 2-back and 0-back test. A number of correct answers of the 2-back test and time to complete Trail Making Test-A were worse during memantine intervention. CONCLUSIONS: Memantine did not improve visuospatial working memory of the patients with PD-MCI. Treatment for PD should be planned carefully considering the impact on cognitive function. Further study is needed to establish new therapeutic strategy. TRIAL REGISTRATION: UMIN000046104. Retrospectively registered. First registration date: 28 Sept 2017.

Impairment of the visuospatial working memory in the patients with Parkinson's Disease: an fMRI study.

BACKGROUND: Mild cognitive impairment (MCI) is a common symptom in the patients with Parkinson's disease (PD). The characteristics of cognitive impairment in PD are executive function (including working memory) and visuo-perceptual processing. The visuospatial n-back test has the merit of minimizing the influence of educational biases involved in the verbal n-back test. Furthermore, it can assess both visuospatial recognition and working memory in a single test. METHODS: We aimed to clarify the advantage of the visuospatial n-back test as a tool for detecting impairments of working memory in PD. We enrolled 28 right-handed patients with PD (18 males, 10 females) and 12 age-matched healthy controls (HC; 7 males, 5 females). Thirteen patients were classified as MCI (PD-MCI), and 15 as cognitively normal PD (PD-CN). Using functional MRI (fMRI), we explored the specific brain regions associated with the performance of the n-back test in the PD-MCI, PD-CN, and HC groups. The 0-back test assesses visuospatial recognition, while the 1-back and 2-back tests assess visuospatial working memory. Group comparisons were performed for three loads of this test. RESULTS: Patients with PD performed significantly worse in terms of the correct answer rates of all n-back tests compared with HC. fMRI analyses performed during the 2-back test revealed reduced activation in the bilateral dorsolateral prefrontal cortex, middle frontal gyrus (MFG), and parietal lobule in the PD group compared with the HC group. In contrast, the fMRI result during the 0-back test showed only a marginal difference in the frontal lobe. On comparisons of task performance between the PD-MCI and PD-CN groups, we found that the correct answer rate in the 2-back test was lower in the PD-MCI group than in the PD-CN group. However, scores of the 0-back and 1-back tests were not significantly different between the two groups. The fMRI findings revealed that activations within the middle frontal gyrus (MFG) and inferior parietal lobule (IPL) during the 2-back test were reduced in the patients with PD-MCI when compared to those with PD-CN. CONCLUSIONS: This study reports reduced activation of the MFG and IPL in patients with PD-MCI. These regions may be associated with the pathophysiology of working memory impairment in patients with PD, which involves fronto-striatal network dysfunction.

Self-remitting Elevation of Adenosine Deaminase Levels in the Cerebrospinal Fluid with Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: A Case Report and Review of the Literature.

A 29-year-old man presented with a high-grade fever, headache, and urinary retention, in addition to meningeal irritation and myoclonus in his upper extremities. A cerebrospinal fluid (CSF) examination showed pleocytosis and high adenosine deaminase (ADA) levels with no evidence of bacterial infection, including Mycobacterium tuberculosis. T2-weighted brain magnetic resonance imaging showed transient hyper-intensity lesions at the splenium of the corpus callosum (SCC), bilateral putamen, and pons during the course of the disease. The CSF was positive for anti-glial fibrillary acidic protein (GFAP) antibodies. He was diagnosed with autoimmune GFAP astrocytopathy. The present case shows that the combination of an elevated ADA level in the CSF and reversible T2-weighted hyper-intensity on the SCC supports the diagnosis of autoimmune GFAP encephalopathy.

Voxel-based quantitative susceptibility mapping in Parkinson's disease with mild cognitive impairment.

OBJECTIVE: Brain iron accumulation has been proposed as one of the pathomechanisms in Parkinson's disease (PD). This study aimed to examine the whole-brain pattern of iron accumulation associated with cognitive impairment in patients with PD using voxel-based quantitative susceptibility mapping analysis. METHODS: We enrolled 24 patients with PD and mild cognitive impairment, 22 patients with PD and normal cognition, and 20 age-matched healthy controls in this cross-sectional study. All participants underwent global cognitive and physical assessments and brain MRI. Using a combined method of voxel-based morphometry and quantitative susceptibility mapping, we compared the voxel-wise magnetic susceptibility of the whole brain between the groups and analyzed its correlation with the cognitive and behavioral data. RESULTS: The PD and mild cognitive impairment group had lower Montreal Cognitive Assessment (MoCA) score than the PD and normal cognition and healthy control groups. There were no gray matter volumetric differences between the groups. In contrast, the voxel-based quantitative susceptibility mapping analysis showed that the PD and mild cognitive impairment group had significantly higher quantitative susceptibility mapping values in the cuneus, precuneus, caudate head, fusiform gyrus, and orbitofrontal cortex than did the PD and normal cognition group. These quantitative susceptibility mapping values were negatively correlated with the MoCA scores in the PD patients (cuneus: r = -0.510, P < .001; caudate head: r = -0.458, P = 0.002). CONCLUSIONS: This study suggests that cognitive impairment in PD is associated with cerebral iron burden and highlights the potential of quantitative susceptibility mapping as an auxiliary biomarker for early evaluation of cognitive decline in patients with PD. © 2019 International Parkinson and Movement Disorder Society.

Reduced striatal dopamine release during motor skill acquisition in Parkinson's disease.

BACKGROUND: Striatal dopamine is functionally important for the acquisition of motor skills. However, it remains controversial as to whether intrinsic processing of motor learning is impaired in patients with Parkinson's disease (PD), and if yes, whether the impairment is associated with altered striatal dopamine release. Additionally, most neuro-imaging studies of patients with PD have focused on motor sequence learning. In contrast, skill acquisition, specifically, the reconstruction of muscle control of isolated movements, has barely been studied. METHOD: In this study, we used a repetitive skill training task to measure the peak acceleration of left thumb movement during a process to achieve fine tuning of motor skill. Using 11C-raclopride (RAC) positron emission tomography, we investigated changes in striatal dopamine levels in two conditions of a skill acquisition task: initial skill training (Day 1) and acquired condition (Day 2) with eight patients with PD and age-matched healthy subjects (HS). RESULT: In HS, the mean acceleration of each session improved through repeated training sessions on Day 1. However, in patients with PD, the training-associated increase was less than that for HS, and this suggests that repetitive skill training does not result in the effective improvement of motor performance. The regions of interest (ROI) analysis revealed that the RAC-binding potential (BP) was significantly reduced in the right putamen on Day 1 compared with Day 2 in HS. In patients with PD, BP within the right putamen was unchanged. Further, we found that patients with PD had increased dopamine levels within the right ventral striatum (VST) and right caudate (CAU) on Day 2, which was greater than that in HS. These results suggest the impaired activation of the putamen during skill acquisition in patients with PD and compensated hyperactivation of the VST and CAU for the reduced dopamine release within the dorsal putamen (DPU). CONCLUSION: Our findings suggest that patients with PD had insufficiency in the process to improve motor skills. Different patterns of striatal dopamine release are relevant to the impairment of these motor functions in patients with PD, at the early stage of the disease.

Early treatment for IgG4-related disease may prevent cognitive impairment caused by cerebral vasculitis: A case report and review of the literature.

IgG4-related disease (IgG4-RD) is a recently recognized disease entity. A 74-year-old male presented with transient headache. He was diagnosed IgG4-RD by pancreatic biopsy at the age of 72. Magnetic Resonance Imaging (MRI) showed disseminated cerebral microbleeds and microinfarctions in time and space. It suggested cerebral vasculitis, however any causative factor were not confirmed. IgG4-RD rarely causes cerebral vasculitis. This might be a first case of an asymptomatic cerebral vasculitis due to IgG4-RD. Patient was started on oral prednisolone, and no neurological or neuropsychological symptom was clinically observed. The MRI findings improved after treatment, and revealed no indication of newly lesions at 6-months follow-up. Early treatment for IgG4-RD may be recommended to prevent irreversible cognitive dysfunction.

A longitudinal study of the effect of experimental osteoporosis on bone trabecular structure in the rat mandibular condyle.

The authors performed a longitudinal study of the microstructural changes occurring in the mandibular condyle during osteoporosis using the findings obtained from micro-CT. The subjects used in this study were eight Sprague-Dawley rats. Among them, five were administered the immunosuppressant drug FK506 by injection for five weeks, while the other three were administered saline solution in the same manner. Micro-CT images were taken of the bilateral mandibular condyle, hip, and knee joints in all animals on days 1, 8, 15, 22, 29, and 36 following injection. Six indices of morphometric analysis were compared between the two groups. Significant differences were observed in BV/TV, Tb.Th, Tb.N, and Tb.Sp in the mandibular condyle, while trabecular bone density appeared to decrease in the immunosuppressant group on three-dimensional (3D) imaging. And, in comparison with the mandibular condyle and femur, they were similar. These results suggested that osteoporosis affects not only the femur, but also the mandibular condyle.

Differences in dopaminergic modulation to motor cortical plasticity between Parkinson's disease and multiple system atrophy.

Dopamine modulates the synaptic plasticity in the primary motor cortex (M1). To evaluate whether the functioning of the cortico-striatal circuit is necessary for this modulation, we applied a paired associative stimulation (PAS) protocol that comprised an electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1, to 10 patients with Parkinson's disease (PD) and 10 with multiple system atrophy of the parkinsonian type (MSA-P) with and without dopamine replacement therapy (-on/off). To investigate the M1 function, motor-evoked potentials (MEPs) were measured before and after the PAS. In both patient groups without medication, the PAS protocol failed to increase the averaged amplitude of MEPs. The dopamine replacement therapy in PD, but not in MSA-P effectively restored the PAS-induced MEP increase. This suggests that not the existence of dopamine itself but the activation of cortico-striatal circuit might play an important role for cortical plasticity in the human M1.

Inclusion criteria provide heterogeneity in baseline profiles of patients with mild cognitive impairment: comparison of two prospective cohort studies.

BACKGROUND: Mild cognitive impairment (MCI) is considered to represent a transitional stage between ageing and Alzheimer's disease (AD). To aim at identifying neuroimaging measures associated with cognitive changes in healthy elderly and MCI patients, longitudinal multicentre studies are ongoing in several countries. The patient profiles of each study are based on unique inclusion criteria. OBJECTIVES: The purpose of the study is to clarify differences in baseline profiles of MCI patients between Studies on Diagnosis of Early Alzheimer's Disease-Japan (SEAD-J) and Alzheimer's Disease Neuroimaging Initiative (ADNI) and to examine the association between baseline profiles and risk of early conversion to AD. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: SEAD-J recruited 114 patients from nine facilities in Japan. A total of 200 patients in ADNI with fluorodeoxyglucose-positron emission tomography (FDG-PET) were enrolled from the USA. METHODS: Baseline profiles were statistically analysed. For FDG-PET at a time of inclusion, associations between each profile and cerebral metabolic rate for glucose (CMRgl) were examined using SPM5 software. In each study, the ratio of conversion to AD within the 1-year and 2-year period after inclusion was investigated and differences in baseline profiles between AD converters and non-converters were analysed. RESULTS: SEAD-J included MCI patients with more severe verbal memory deficits and extracted patients with higher depressive tendencies. These differences were likely to be associated with criteria. SEAD-J exhibited a higher rate of conversion within 1 year compared with ADNI (24.5% vs 13.5%). In FDG-PET analyses of SEAD-J, AD converters within 1 year showed more severe decrease of FDG uptake in bilateral inferior parietal regions compared with non-converters. CONCLUSIONS: Different inclusion criteria provided differences in baseline profiles. The severity of memory deficit might cause increase of the AD conversion within 1 year. Clinical outcomes of multicentre studies for early diagnosis of AD should be interpreted carefully considering profiles of patients.

Changes in striatal dopamine release associated with human motor-skill acquisition.

The acquisition of new motor skills is essential throughout daily life and involves the processes of learning new motor sequence and encoding elementary aspects of new movement. Although previous animal studies have suggested a functional importance for striatal dopamine release in the learning of new motor sequence, its role in encoding elementary aspects of new movement has not yet been investigated. To elucidate this, we investigated changes in striatal dopamine levels during initial skill-training (Day 1) compared with acquired conditions (Day 2) using (11)C-raclopride positron-emission tomography. Ten volunteers learned to perform brisk contractions using their non-dominant left thumbs with the aid of visual feedback. On Day 1, the mean acceleration of each session was improved through repeated training sessions until performance neared asymptotic levels, while improved motor performance was retained from the beginning on Day 2. The (11)C-raclopride binding potential (BP) in the right putamen was reduced during initial skill-training compared with under acquired conditions. Moreover, voxel-wise analysis revealed that (11)C-raclopride BP was particularly reduced in the right antero-dorsal to the lateral part of the putamen. Based on findings from previous fMRI studies that show a gradual shift of activation within the striatum during the initial processing of motor learning, striatal dopamine may play a role in the dynamic cortico-striatal activation during encoding of new motor memory in skill acquisition.

Idiopathic trigeminal neuropathy with trigeminal mass lesion on MRI: Neoplasm or not?

The objective of the present study was to investigate clinical and magnetic resonance imaging (MRI) features of idiopathic trigeminal neuropathy with transient MR abnormalities mimicking a neoplasm (ITNmn). We retrospectively evaluated clinical and MRI features in two cases of ITNmn seen in our institution in comparison with those of previously reported five cases. The most common symptom was altered facial sensation and numbness limited to one or more trigeminal nerve divisions (100%). ITNmn commonly affected not only the second and third divisions (86% and 57%, respectively) but also the first division (71%). The most common findings on MRI were enlargement and gadolinium enhancement of the trigeminal nerve, which were similar to those seen in neoplasms (100%). The abnormalities spontaneously regressed in all five evaluable cases. ITNmn should be added in the differential diagnosis of non-specific mass-like lesions in trigeminal neuropathy and be observed carefully without surgical treatment.

Predicting the motor outcome of acute disseminated encephalomyelitis by apparent diffusion coefficient imaging: Two case reports.

We present two cases of young adults with acute disseminated encephalomyelitis (ADEM) who developed severe conscious and motor disturbances. Despite their similar initial clinical course and MRI findings, their motor function outcomes were quite different. In both cases, fluid attenuated inversion recovery (FLAIR) sequenced MRI showed multiple symmetric hyperintense lesions in the internal capsule and the brainstem at the subacute stage. However, in case 1 the apparent diffusion coefficient (ADC) was pathologically decreased in the internal capsule, whereas the ADC for case 2 was normal. At the end of the examination period, severe motor disability (bedridden state) with brain atrophy apparent on MRI remained in case 1, whereas case 2 made an almost full recovery without brain atrophy. These two cases suggest that altered ADC in the internal capsules at the subacute stage may reflect a different pathogenesis between cytotoxic and vasogenic edema, and may be a valuable indicator for the prognosis of motor disturbance.

[Case of paraneoplastic limbic encephalitis associated with malignant B cell lymphoma].

We report a case of a 62-year-old man with limbic encephalitis associated with diffuse large B cell lymphoma. He was hospitalized for the assessment of cognitive disturbance and changes in characteristics. Neurological examination revealed disturbance of recall and recent memory. Magnetic resonance (MR) imaging of the brain revealed bilateral atrophy of the medial temporal lobes. Cerebrospinal fluid (CSF) examination revealed mononuclear pleocytosis and elevated protein levels. Herpes simplex virus DNA was not detected in the CSF by the polymerase chain reaction. Immunological investigation of the patient's serum samples showed no evidence of acute infection with herpes simplex virus or cytomegalovirus. Chest computed tomography (CT) revealed a mass lesion on the right hilum of the lung. Therefore, tumor resection was performed. The pathological diagnosis was diffuse large B cell lymphoma. We diagnosed this patient with paraneoplastic limbic encephalitis. Chemotherapy was performed, but the patient's clinical symptoms failed to improve. We investigated 7 previously reported cases of paraneoplastic limbic encephalitis associated with malignant lymphoma in Japan. We suggest that an early diagnosis of paraneoplastic limbic encephalitis with progressive symptoms such as changes in characteristics is important. Early diagnosis and treatment of malignant tumors is desirable to facilitate clinical recovery and improve prognosis.

Comparison of image performance between cone-beam computed tomography for dental use and four-row multidetector helical CT.

The authors evaluated the imaging performance of cone-beam computed tomography (CBCT) for dental use using 3DX multi-image micro-CT (Morita Co., Kyoto, Japan) and four-row multi-detector helical computed tomography (MDCT) using an Asteion (Toshiba, Tokyo, Japan). A dried right maxillary bone was cut into eight slices 2 mm thick toward the zygomatico-palate and used as a phantom. Images of the phantom were then taken using 3DX and MDCT. The images of two bone slices were evaluated by five dentists for image quality and reproducibility of cancellous bone, as well as enamel, dentin, pulp cavity, periodontal ligament space, lamina dura and the overall image. Using the MDCT images as the standard, the 3DX images were evaluated with a subjective 5-level scale: 3 for an image equal to the MDCT image, 4 or greater for better, and 2 or lower for worse. The scores for all parameters exceeded 4 points. Maximum mean score was 4.8 for the lamina dura. Statistically significant differences were found for all items (P < 0.01). Our subjective evaluation of imaging performance clarified that 3DX was superior to MDCT. The results of this study suggest that 3DX is useful for imaging in the dental field.

Relationship between sex, age, and the minimum thickness of the roof of the glenoid fossa in normal temporomandibular joints.

This autopsy study investigates the minimum thickness of the roof of the glenoid fossa of grossly normal temporomandibular joints (TMJ) and correlates this to gender and age. This study was based on 49 TMJ specimens collected from 26 male and 23 female cadavers whose mean age at death was 73.8 years (range=50-96). No information was available about TMJ symptoms before death. A digital micrometer was used to measure the minimum thickness of the glenoid fossae. Comparisons were made based on gender and age. The mean value for the minimum roof thickness of all joint specimens examined was 0.8 mm. Mean values for male and female specimens were 0.8 and 0.7 mm, respectively, which were not significantly different. In addition, no age-related differences were observed. The average thickness was 0.7 mm for individuals in their fifties, 0.8 mm for those in their sixties and seventies, 0.6 mm for those in their eighties, and 0.8 mm for individuals in their nineties. Although these data indicate that the minimum thickness of the glenoid fossa of the TMJ is not significantly correlated with sex or age in patients 50 years of age and older, they nonetheless provide additional information about normal TMJ anatomy, particularly with regard to our knowledge of joint remodeling and function in the disease and non-disease states. Thickness of the glenoid fossa has also been implicated as a factor in facial trauma involving superior displacement of the mandibular condyle into the middle cranial fossa. The thickness of the glenoid fossa is also of potential interest during surgeries involving the glenoid fossa, such as TMJ arthroplasty or joint reconstruction.

A comparison of a new limited cone beam computed tomography machine for dental use with a multidetector row helical CT machine.

OBJECTIVE: We sought to compare a new limited cone beam computed tomography (CT) machine for dental use (3DX) with the multidetector CT machine for image quality and skin doses. STUDY DESIGN: Images of the right maxillary central incisor and the left mandibular first molar of an anthropomorphic phantom were taken by both the 3DX and the multidetector CT. A 5-point method was used to evaluate the depiction of cortical and cancellous bone, enamel, dentin, pulp cavity, periodontal ligament space, lamina dura, and overall impressions. Furthermore, the skin doses for both modalities were compared. RESULTS: The image quality of the 3DX was better than the multidetector CT for all items (P < .01). Moreover, the mean skin doses with the multidetector CT were 458 mSv per examination, whereas the doses with the 3DX were 1.19 mSv per examination. CONCLUSIONS: These results clearly indicate the superiority of the 3DX in the display of hard tissues in the dental area while substantially decreasing the dose to the patient.