A validation study for wide-range remote assessment of cognitive functions in the healthy older Japanese population: a pilot randomised crossover trial.

BACKGROUND: The assessment of a wide range of cognitive functions using video teleconference (VTC) systems cannot be applied in practice yet. We aimed to determine the feasibility and reliability of previously unvalidated remote cognitive function tests in Japan using common information and communication technology (ICT) devices, software, and VTC systems compared with face-to-face (FTF) assessment. METHODS: The sample consisted of 26 participants from senior citizens clubs and an employment service centre in Sapporo Japan, including 11 females and 15 males (age averaged 78.6 ± 6.8 years). Tests included the RCPM, Story recall, 10/36 spatial recall, selective reminding test, SDMT, PASAT, FAB, TMT-A, TMT-B, visual cancellation task, digit span, tapping span. The experimental design was a counterbalanced crossover randomised controlled trial. Intraclass correlations (ICCs), paired-samples t-tests, Cohen's Kappa (κ) coefficients, and Wilcoxon signed-rank test were calculated to compare the scores between VTC and FTF assessments. RESULTS: All ICCs were significant and ranged from 0.47 (RCPM time) to 0.92 (RCPM score and PASAT), with a mean ICC of 0.75. Digit span using Cohen's Kappa (κ) coefficient was significant, but the tapping span was not. Paired samples t-test showed statistically significant differences in SDMT, RCPM time, and cancellation time. CONCLUSIONS: The results suggest that remote video conference-based neuropsychological tests even using familiar devices and software may be able to assess a wide range of cognitive functions in the Japanese older population. As for the processing speed tasks, we need to create our own standards for the remote condition. For the tapping span, we should consider increasing the number of trials.

Persistent intrathecal interleukin-8 production in a patient with SARS-CoV-2-related encephalopathy presenting aphasia: a case report.

BACKGROUND: Neurological manifestations of coronavirus disease 2019 (COVID-19) are increasingly recognized and include encephalopathy, although direct infection of the brain by SARS-CoV-2 remains controversial. We herein report the clinical course and cytokine profiles of a patient with severe SARS-CoV-2-related encephalopathy presenting aphasia. CASE PRESENTATION: An 81-year-old man developed acute consciousness disturbance and status epileptics several days after SARS-CoV-2 infection. Following treatment with remdesivir and dexamethasone, his consciousness and epileptic seizures improved; however, amnestic aphasia and agraphia remained. Two months after methylprednisolone pulse and intravenous immunoglobulin, his neurological deficits improved. We found increased levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1), but not IL-2 and IL-10 in the serum and cerebrospinal fluid (CSF), and the levels of serum IL-6 and MCP-1 were much higher than those in the CSF. The level of IL-8 in the CSF after immunotherapy was four times higher than that before immunotherapy. CONCLUSION: The cytokine profile of our patient was similar to that seen in severe SARS-CoV-2-related encephalopathy. We demonstrated (i) that the characteristic aphasia can occur as a focal neurological deficit associated with SARS-CoV-2-related encephalopathy, and (ii) that IL8-mediated central nervous system inflammation follows systemic inflammation in SARS-CoV-2-related encephalopathy and can persist and worsen even after immunotherapy. Monitoring IL-8 in CSF, and long-term corticosteroids may be required for treating SARS-CoV-2-related encephalopathy.

Correlation of active contact location with weight gain after subthalamic nucleus deep brain stimulation: a case series.

BACKGROUND: Weight gain (WG) is a frequently reported side effect of subthalamic deep brain stimulation; however, the underlying mechanisms remain unclear. The active contact locations influence the clinical outcomes of subthalamic deep brain stimulation, but it is unclear whether WG is directly associated with the active contact locations. We aimed to determine whether WG is associated with the subthalamic deep brain stimulation active contact locations. METHODS: We enrolled 14 patients with Parkinson's disease who underwent bilateral subthalamic deep brain stimulation between 2013 and 2019. Bodyweight and body mass index were measured before and one year following the surgery. The Lead-DBS Matlab toolbox was used to determine the active contact locations based on magnetic resonance imaging and computed tomography. We also created sweet spot maps for WG using voxel-wise statistics, based on volume of tissue activation and the WG of each patient. Fluorodeoxyglucose-positron emission tomography data were also acquired before and one year following surgery, and statistical parametric mapping was used to evaluate changes in brain metabolism. We examined which brain regions' metabolism fluctuation significantly correlated with increased body mass index scores and positron emission tomography data. RESULTS: One year after surgery, the body mass index increase was 2.03 kg/m2. The sweet spots for WG were bilateral, mainly located dorsally outside of the subthalamic nucleus (STN). Furthermore, WG was correlated with increased metabolism in the left limbic and associative regions, including the middle temporal gyrus, inferior frontal gyrus, and orbital gyrus. CONCLUSIONS: Although the mechanisms underlying WG following subthalamic deep brain stimulation are possibly multifactorial, our findings suggest that dorsal stimulation outside of STN may lead to WG. The metabolic changes in limbic and associative cortical regions after STN-DBS may also be one of the mechanisms underlying WG. Further studies are warranted to confirm whether dorsal stimulation outside of STN changes the activities of these cortical regions.

Predictors and short-term outcomes of post-stroke fatigue in initial phase of transition from hospital to home: A prospective observational study.

AIM: To analyse the interactions of associated factors with post stroke fatigue (PSF) after discharge home and determine the predictors of PSF and their impact on stroke survivors. DESIGN: A prospective observational study. METHODS: A total of 94 patients with acute stroke were recruited between May 2019 -July 2020. The main outcomes were fatigue, depression, insomnia, sarcopenia, and health-related quality of life (HRQOL) and were assessed at admission and 1 month after discharge. Fatigue was measured using the Fatigue Assessment Scale. Depression and Insomnia were assessed using the Hospital Anxiety and Depression Scale-Depression and Insomnia Severity Index, respectively. Sarcopenia was measured using the SARC-F questionnaire, and HRQOL was assessed using the Short Form-8. RESULTS: Acute phase PSF was an independent predictor of PSF after discharge home. Moreover the path analysis revealed that this effect is mediated through both the direct effect of acute-phase PSF on PSF after discharge home and through the indirect effect of interaction with pre-stroke SARC-F, acute phase depression, and acute phase insomnia, which remains a separate predictor of acute-phase PSF. In total, 17% of the survivors had persistent PSF. Persistent PSF was significantly associated with depression, insomnia, sarcopenia, and a lower quality of life scores. CONCLUSIONS: Post-stroke fatigue may occur in the acute phase and persists after discharge, it will not only affect later depression, insomnia, and quality of life, but also sarcopenia. IMPACT: Acute phase PSF was found to be an independent predictor of PSF after discharge home. In addition, the interaction with pre-stroke SARC-F, acute phase depression and insomnia had an indirect connection with PSF after discharge home, which remains a separate predictor of acute-phase PSF. Thus, early assessment and management of mental status, sleep problems, and sarcopenia during hospitalization might be an important step in post-stroke rehabilitation and home transition.

Development and Internal Validation of a Nomogram to Predict Post-Stroke Fatigue After Discharge.

OBJECTIVES: We aimed to develop and validate a nomogram for the individualized prediction of the risk of post-stroke fatigue (PSF) after discharge. MATERIALS AND METHODS: Fatigue was measured using the Fatigue Assessment Scale. Multivariable logistic regression analysis was applied to build a prediction model incorporating the feature selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the predictive model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was conducted using bootstrapping validation. Finally, a web application was developed to facilitate the use of the nomogram. RESULTS: We developed a nomogram based on 95 stroke patients. The predictors included in the nomogram were sex, pre-stroke sarcopenia, acute phase fatigue, dysphagia, and depression. The model displayed good discrimination, with a C-index of 0.801 (95% confidence interval: 0.700-0.902) and good calibration. A high C-index value of 0.762 could still be reached in the interval validation. Decision curve analysis showed that the risk of PSF after discharge was clinically useful when the intervention was decided at the PSF risk possibility threshold of 10% to 90%. CONCLUSION: This nomogram could be conveniently used to provide an individual, visual, and precise prediction of the risk probability of PSF after being discharged home. Thus, as an aid in decision-making, physicians and other healthcare professionals can use this predictive method to provide early intervention or a discharge plan for stroke patients during the hospitalization period.

Prevalence of stroke-related sarcopenia: A systematic review and meta-analysis.

OBJECTIVES: Although the skeletal muscle is the main effector of disability in stroke, evidence on post-stroke skeletal muscle is scarce; especially, the prevalence of stroke-related sarcopenia remains unclear. Thus, we aimed to systematically search the prevalence of sarcopenia in stroke survivors and synthesize pooled estimates of overall prevalence of stroke-related sarcopenia and prevalence stratified by sex, country, time since stroke onset, and diagnostic criteria of sarcopenia. METHODS: We performed systematic searches in the MEDLINE, CINAHL, Embase, and Cochrane Library databases. English-language searches to identify included studies were completed August 25, 2019. Meta-analysis of data collected from cross-sectional or observational studies which were reported the prevalence of sarcopenia among stroke participants. All statistical analyses were performed using R version 3.5.2. RESULTS: A total of 855 articles were initially identified. Seven articles were included in this study. Total sample size across all included studies was 1695. Three studies were conducted in Japan, 2 in South Korea, 1 in Taiwan, and 1 in the U.S. Four included studies had a cross-sectional design, and 3 were retrospective cohort studies. Four and 3 studies included participants at <1 month and ≥6 months since stroke onset, respectively. The pooled prevalence estimate was 42% (95% confidence interval: 33%-52%), with a substantial heterogeneity (I2=91%). CONCLUSIONS AND IMPLICATIONS: Sarcopenia is frequently observed in stroke survivors, and a higher prevalence of sarcopenia is noted during the early phase after stroke. This study would be useful for researchers to design sarcopenia studies in this population. Further prospective longitudinal studies for sarcopenia and their prognostic outcomes in stroke survivors are urgently needed to propose appropriate physical and nutritional strategies in geriatric rehabilitation.

Sub-classification of apraxia of speech in patients with cerebrovascular and neurodegenerative diseases.

Some studies have hypothesized that primary progressive apraxia of speech (ppAOS) consists of heterogeneous symptoms that can be sub-classified; however, no study has classified stroke-induced AOS (sAOS) and ppAOS according to common criteria. The purpose of this study was to elucidate the symptoms and relevant brain regions associated with sAOS and ppAOS for sub-classification. Participants included 8 patients with sAOS following lesions in the left precentral gyrus and/or underlying white matter, and 3 patients with ppAOS. All patients with sAOS could be classified into three subtypes: type I, with prominent distorted articulation; type II, with prominent prosodic abnormalities or type III, with similarly distorted articulation and prosodic abnormalities. This sub-classification was consistent with the subtypes of ppAOS proposed in previous reports. All patients with ppAOS were classified as type III, and exhibited three characteristics distinguishable from those of sAOS. First, they showed prominent lengthened syllables compared with the segmentation of syllables. Second, they could not always complete the production of multi-syllabic single words in one breath. Finally, they showed dysfunctional lesions in the bilateral supplementary motor area. We conclude that sAOS and ppAOS can be sub-classified and are universal symptoms that are common between the English and Japanese populations.

[New entities and the criteria of FTLD].

This article provides an overview of the historical entity hitherto, the pivotal clinical symptoms of FTLD (frontotemporal lobar degeneration), and an introduction for the revised criteria for bvFTD (behavioral variant frontotemporal dementia): FTDC (International Behavioral Variant FTD Criteria Consortium) presented by Rascovsky et al(2011), and the classification criteria for PPA(primary progressive aphasia) heralded by Gorno-Tempini et al (2011). According to the former criteria, bvFTD can be diagnosed by the clinical symptoms as having possible bvFTD or probable bvFTD, and the pathological findings could lead definite bvFTD. In the latter classification criteria of PPA, two types are implicated in FTLD: one is the non-fluent/agrammatic variant PPA(PNFA/nfvPPA/naPPA), and the other is semantic variant PPA(SD/svPPA).

Cognitive impairment and cortical degeneration in neuromyelitis optica.

OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOsd) is an inflammatory and demyelinating syndrome characterized by optic neuritis and myelitis. Several magnetization transfer magnetic resonance imaging (MRI) studies have revealed abnormalities in normal-appearing gray matter in NMOsd. The aim of this study is to elucidate the characteristics and pathogenesis of cognitive impairment and neurodegeneration in NMOsd brains. METHODS: Fourteen Japanese patients with serologically verified NMOsd, 17 patients with multiple sclerosis (MS), and 37 healthy controls were assessed with the Rao's Brief Repeatable Battery of Neuropsychological Tests (BRBN). Using 128 tissue blocks from 6 other cases of NMOsd, 3 cases of MS, and 4 controls without central nervous system involvement, we performed quantitative analysis of cortical neuronal loss and layer-specific changes in NMOsd. RESULTS: In BRBN assessments, 57% of NMOsd patients and 47% of MS patients had impaired performance on at least 3 cognitive tests. Cognitive impairment in NMOsd was common even in the limited form of disease, indicating that NMOsd may progress insidiously from early stages of disease. Neuropathological assessments showed neuronal loss in cortical layers II, III, and IV, with nonlytic reaction of aquaporin-4 (AQP4)-negative astrocytes in layer I, massive activated microglia in layer II, and meningeal inflammation in NMOsd brains. All NMO cases showed no evidence of cortical demyelination. INTERPRETATION: We demonstrate cognitive impairment and substantial cortical neuronal loss with unique AQP4 dynamics in astrocytes in NMOsd. These data indicate pathological processes consisting not only of inflammatory demyelinating events characterized by pattern-specific loss of AQP4 immunoreactivity but also cortical neurodegeneration in NMOsd brains.

Cat Scratch Disease-associated Encephalitis Followed by Parkinsonism.

Cat scratch disease (CSD) is a zoonotic infection caused by Bartonella henselae typically resulting in self-limited regional lymphadenopathy. Encephalitis is a complication with a supposedly benign prognosis, but we encountered an exceptional case. A 19-year-old Japanese woman presented with status epilepticus. She was diagnosed with CSD-associated encephalitis based on her history of contact with a kitten and a high titre of serum IgG to B. henselae. Multimodal treatment ameliorated her encephalitis, but neurological sequelae including spastic paraparesis, persisted. After several months, she developed age-disproportionate parkinsonism inconsistent with a neurodegenerative disease. In conclusion, CSD-associated encephalitis can result in severe neurological sequelae and post-encephalitic parkinsonism.

Mirror writing and cortical hypometabolism in Parkinson's disease.

Mirror writing (MW) is the production of individual letters, words, or word strings in the reverse direction. Parkinson's disease (PD) is a progressive neurodegenerative disorder, and high MW rates have been reported in patients with PD. Thus, the present study sought to identify the factors that cause MW in patients with PD. We examined the frequency of MW in patients with PD and investigated the area of the brain where such frequency inversely correlates with reduced regional cerebral metabolic rates of glucose (rCMRglc). We also examined whether this area satisfied the motor and visual monitoring hypotheses of MW that have been presented in previous studies. Thirty-six subjects with idiopathic PD and 23 healthy controls were included in the study. We asked the participants to write down words, numerals, and sentences from left to right using their dominant and non-dominant hands. Patients with PD underwent an 18F-fluorodeoxyglucose positron emission tomography scan to measure the rCMRglc. Neither the patients with PD nor the healthy subjects exhibited MW in the use of the right hand. In the use of the left hand, MW occurred in 15 of the 36 patients with PD, but in none of the healthy controls. The right intraparietal sulcus was identified as the area where rCMRglc was inversely correlated with the number of left-right reversed characters. Previous functional imaging studies have suggested that the right superior parietal cortex and intraparietal sulcus play an important role in recognizing left-right reversed letters. Therefore, dysfunction in the intraparietal sulcus may hinder the recognition of left-right reversed characters, resulting in MW. Consequently, our findings in patients with PD are consistent with the visual-monitoring hypothesis of MW.

Clinical evaluation of childhood cerebral adrenoleukodystrophy with balint's symptoms.

BACKGROUND: Childhood cerebral adrenoleukodystrophy (CCALD) is the most common phenotype of adrenoleukodystrophy (ALD) and is characterized by the progression of intellectual, psychic, visual, and gait disturbances. Progression of this intractable disease can only be prevented by hematopoietic stem cell transplantation during the early stages of the disease. The aim of this study was to clinically evaluate children with CCALD who have visual symptoms to enable early diagnosis. METHODS: We enrolled 41 Japanese children with CCALD who had visual symptoms. We retrospectively analyzed age of onset, past medical history, initial symptoms, visual symptoms and findings on brain magnetic resonance imaging. RESULTS: The median age of disease onset was 7 years (range 5-10 years). The most common visual symptom was strabismus (n = 22). There was only one patient with the triad of symptoms of Balint's syndrome. Seventeen patients had incomplete Balint's syndrome and showed one or two of the triad of symptoms. Almost all patients with complete or incomplete Balint's syndrome showed bilateral parieto-occipital white matter lesions. CONCLUSIONS: CCALD could develop into Balint's syndrome, especially the incomplete form. Therefore, CCALD should be considered when boys show new symptoms, including lack of eye contact or bumping into objects.

[Classification and Diagnosis of Primary Progressive Aphasia].

I have introduced primary progressive aphasia (PPA) with regard to frontotemporal lobar degeneration (FTLD) and evaluated the following elementary language symptoms for its diagnosis: agrammatism in speech production, apraxia of speech, phonemic paraphasia, naming impairment, impairment of single-word comprehension, and repetition. Furthermore, I have described the clinical symptoms, causative lesions, and pathological findings of three PPA variants -nonfluent/agrammatic, semantic, and logopenic PPA- according to the criteria proposed by Gorno-Tempni et al. (2011).

Non-Pharmacological Interventions for Post-Stroke Fatigue: Systematic Review and Network Meta-Analysis.

Post-stroke fatigue (PSF) is one of the most serious sequelae, which often interferes with the rehabilitation process and impairs the functional recovery of patients. Due to insufficient evidence, it is unclear which specific pharmacological interventions should be recommended. Therefore, in this paper, we compare the effectiveness of non-pharmacological interventions in PSF. A systematic review and network meta-analysis of randomized controlled trials were performed using EMBASE, MEDLINE, CINAHL, Cochrane library, ClinicalTrials.gov, CNKI, and CQVIP, from inception to January 2018, in the English and Chinese languages. RCTs involving different non-pharmacological interventions for PSF with an outcome of fatigue measured using the Fatigue Severity Scale were included. Multiple intervention comparisons based on a Bayesian network are used to compare the relative effects of all included interventions. Ten RCTs with eight PSF non-pharmacological interventions were identified, comprising 777 participants. For effectiveness, most interventions did not significantly differ from one another. The cumulative probabilities of the best non-pharmacological intervention for fatigue reduction included Community Health Management (CHM), followed by Traditional Chinese Medicine (TCM) and Cognitive Behavioral Therapy (CBT). Network meta-analysis based on data from the selected RCTs indicated that the eight PSF non-pharmacological interventions shared equivalent efficacy, but CHM, TCM, and CBT showed potentially better efficacy. In the future, fatigue needs to be recognized and more accurate assessment methods for PSF are required for diagnosis and to develop more effective clinical interventions.

Clinical factors affecting evoked magnetic fields in patients with Parkinson's disease.

Studies on evoked responses in Parkinson's disease (PD) may be useful for elucidating the etiology and quantitative evaluation of PD. However, in previous studies, the association between evoked responses and detailed motor symptoms or cognitive functions has not been clear. This study investigated the characteristics of the visual (VEF), auditory (AEF), and somatosensory (SEF) evoked magnetic fields in patients with Parkinson's disease (PD), and the correlations between evoked fields and the patient's clinical characteristics, motor symptoms, and cognitive functions. Twenty patients with PD and 10 healthy controls (HCs) were recruited as participants. We recorded VEF, AEF, and SEF, collected clinical characteristics, performed physical examinations, and administered 10 cognitive tests. We investigated differences in the latencies of the evoked fields between patients with PD and HCs. We also evaluated the correlation of the latencies with motor symptoms and cognitive functioning. There were significant differences between the two groups in 6 of the cognitive tests, all of which suggested mild cognitive impairment in patients with PD. The latencies of the VEF N75m, P100m, N145m, AEF P50m, P100m, and SEF P60m components were greater in the patients with PD than in the HCs. The latencies mainly correlated with medication and motor symptoms, less so with cognitive tests, with some elements of the correlations remaining significant after Bonferroni correction. In conclusion, the latencies of the VEF, AEF, and SEF were greater in PD patients than in HCs and were mainly correlated with medication and motor symptoms rather than cognitive functioning. Findings from this study suggest that evoked fields may reflect basal ganglia functioning and are candidates for assessing motor symptoms or the therapeutic effects of medication in patients with PD.

Video-tutorial for the Movement Disorder Society criteria for progressive supranuclear palsy.

BACKGROUND: The International Parkinson and Movement Disorder Society-endorsed Progressive Supranuclear Palsy Study Group published clinical diagnostic criteria for progressive supranuclear palsy in 2017, aiming to optimize early, sensitive and specific diagnosis. OBJECTIVE: To assist physicians in the application of these criteria, we developed a video-based tutorial in which all core clinical features and clinical clues are depicted and explained. METHODS: Patients provided written informed consent to the publication of their videos. High-quality videos along with essential descriptions were collected by the study group members. Most educational videos were selected in a structured consensus process. RESULTS: We provide 68 videos of all core clinical features and clinical clues defined by the diagnostic criteria, along with instructive descriptions of the depicted patients, examination techniques and clinical findings. CONCLUSIONS: This comprehensive video-based tutorial will support physicians in the application of the diagnostic criteria of progressive supranuclear palsy.

[A case of subarachnoid hemorrhage presenting with supplementary motor aphasia as an initial symptom].

Supplementary motor aphasia results from impairment of the supplementary motor area in the left mesial frontal cortex. We report a rare case of subarachnoid hemorrhage presenting with supplementary motor aphasia as an initial symptom. A 52-year-old woman was brought to our hospital by ambulance due to sudden severe headache and supplementary motor aphasia. CT demonstrated subarachnoid hemorrhage that appeared to be particularly thick in the pericallosal cistern. She had undergone neck clipping of a left vertebral artery aneurysm for subarachnoid hemorrhage 14 years earlier. At that time, she underwent neck clipping of a de novo anterior communicating artery aneurysm. The postoperative course was uneventful and supplementary motor aphasia had disappeared in 4 weeks. To our knowledge, this is the first reported case of subarachnoid hemorrhage presenting with supplementary motor aphasia as an initial symptom. In this case, adhesion of the arachnoid membrane resulting from old subarachnoid hemorrhage might have prevented new subarachnoid hemorrhage from spreading diffusely. Hematomas spread mainly into the pericallosal cistern from ruptured aneurysm of the anterior communicating artery. Therefore, thick hematoma in this cistern might have compressed the supplementary motor area, resulting in supplementary motor aphasia. Aphasia disappeared as pressure from the hematoma dissipated. Neurosurgeons may be likely to encounter a patient showing a transient consciousness disturbance after the use of the anterior interhemispheric approach or within a period of vascular spasm. Supplementary motor aphasia might also be included in such consciousness disturbance. Supplementary motor aphasia might be a reversible symptom if there is no irreversible damage to the supplementary motor area by infarction or intraparenchymal hemorrhage.

[A Patient with Progressive Multifocal Leukoencephalopathy Who Developed Bálint Syndrome Improved by Combination Therapy Using Mefloquine and Mirtazapine].

We describe a 62-year-old man who developed subacute visual loss after cord blood stem cell transplantation for malignant lymphoma. Brain magnetic resonance imaging (MRI) showed bilateral hyperintense lesions in the occipital and parietal lobes. A diagnosis of progressive multifocal encephalopathy (PML) was established following brain biopsy and detection of JC virus (JCV) deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF). He developed optic ataxia and visual inattention, and was then diagnosed as having Bálint syndrome. After he was treated with mefloquine and mirtazapine, his Bálint syndrome and, MRI findings improved and the copy number of JCV DNA in the CSF decreased. In summary, we demonstrate that patient with PML may develop Bálint syndrome and that combination therapy using mefloquine and mirtazapine may be an effective treatment. (Received August 23, 2018; Accepted November 29, 2018; Published March 1, 2019).

[Aphasia in practice--recent progress].

In terms of practical view, the type of aphasia can be classified by four elementary symptoms: anarthria (apraxia of speech), phonemic paraphasia, word comprehension impairment, word finding difficulty. Each elementary symptom has been established by causative lesion: anarthria for lowed posterior part of the left precentral gyrus, phonemic paraphasia for the left marginal gyrus and underlying white matter, word comprehension impairment for the left middle frontal gyrus or the posterior part of superior and middle temporal gyrus (the area called Wernickle's area), word finding difficulty for the left inferior frontal gyrus or the left angular gyrus or the left posterior part of the inferior temporal gyrus. In addition to ordinary estimation of language some devised examination enables distinction of the symptoms due to frontal lesion and the symptom due to the posterior lesion. This methods taking advantage of the symptoms related apahasia is also useful for making diagnosis and knowing prognosis of progressive aphasia.