Somatosensory pathway dysfunction in patients with amyotrophic lateral sclerosis in a completely locked-in state.

OBJECTIVE: To investigate somatosensory pathway function in patients with amyotrophic lateral sclerosis (ALS) dependent on invasive ventilation and in a completely locked-in state (CLIS). METHODS: We examined median nerve somatosensory evoked potentials (SEPs) in 17 ALS patients in a CLIS, including 11 patients with sporadic ALS, one with familial ALS with genes not examined, four with a Cu/Zn superoxide-dismutase-1 (SOD1) gene variant (Val118Leu, Gly93Ser, Cys146Arg), and one with a fused-in-sarcoma gene variant (P525L). We evaluated N9, N13, N20 and P25, and central conduction time (CCT); the data were compared with those of 73 healthy controls. RESULTS: N20 and N13 were abolished in 12 and 10 patients, and their latencies was prolonged in four and three patients, respectively. The CCT was prolonged in five patients with measurable N13 and N20. Two patients with SOD1 gene mutations had absent or slightly visible N9. Compared to the CCT and latencies and amplitudes of N13 and N20 in the controls, those in the patient cohort were significantly abnormal. CONCLUSIONS: The central somatosensory pathway is severely involved in patients with ALS in a CLIS. SIGNIFICANCE: Our findings suggest that median nerve SEP cannot be utilized for communication in patients with ALS in a CLIS.

Benefits and Challenges of Pediatric-to-Adult Health Care Transition in Childhood-Onset Neurologic Conditions.

Background and Objectives: Although the importance of pediatric-to-adult health care transition (HCT) has been recognized, individuals with childhood-onset neurologic conditions often encounter challenges during pediatric-to-adult HCT, and HCT benefits for this population remain elusive. We assessed the current HCT situation in individuals with childhood-onset neurologic conditions to develop an improved transition system that incorporates patient perspectives. Methods: This cross-sectional study was conducted at the Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled from November 2020 to December 2020. We targeted adults with childhood-onset neurologic conditions who visited the Department of Internal Medicine and their families. Questionnaires provided to 127 patients asked them about their experiences with pediatric-to-adult HCT (i.e., educational opportunities regarding HCT during pediatric visits, difficulties in transition, and the merits/demerits of adult practice) and their families' perspectives regarding pediatric-to-adult HCT. We also reviewed the patients' medical records to examine the severity of their disabilities. Results: Responses were collected from 111 patients (response rate: 87%). Most patients had both severe physical and intellectual disabilities, and approximately half had a physical disability level of Gross Motor Function Classification System V and a profound intellectual disability. Half of the respondents were not transitioned through pediatric-to-adult HCT by their pediatricians, and they visited adult departments by themselves without a formal referral process. They experienced difficulties during HCT, such as a lack of knowledge regarding adult health care providers and consultants. However, those who underwent HCT benefited from it in terms of their health, experience, and service use, such as age- and condition-appropriate care, seeing adult specialists, and the introduction of adult services. They also addressed challenges in managing appointments and having adult doctors understand their medical history. Nonetheless, they were not informed about diseases and medical and welfare resources for adulthood during pediatric visits and desired to discuss future plans with pediatricians. Discussion: Systems that provide sufficient pediatric-to-adult HCT for individuals with childhood-onset neurologic conditions are required. Lifelong education for patients and families, training for pediatricians on HCT and neurologists on childhood-onset conditions and disabilities, and clinical practice and human resources that support patients and families are warranted.

[Current practices of transition from pediatric to adult health care for patients with neurological disease: promote the cooperation between child and adult neurologists].

The Special Committee for Measures Against Transition from Pediatric to Adult Health Care of the Japanese Society of Neurology, which consists of child and adult neurologists, started to tackle the issues of pediatric to adult health care transition for patients with neurological disease in July 2020. The Committee held a workshop with a theme of "cooperation between child and adult neurologists," which is a critical issue in the pediatric to adult health care transition. To solve the many problems in the pediatric to adult health care transition, it is crucial that child and adult neurologists and primary care physicians cooperate on the following issues: preparing child neurologists for the transition, encouraging adult neurologists to study child neurology, promoting the formation of multidisciplinary teams, improving the medical system and medical fees, appealing to governmental agencies for issues of community health care and welfare services.

Differential immunophenotypes of neuronal cytoplasmic inclusions in the dentate gyrus of multiple system atrophy and their association with clinicopathological features.

Although hippocampal pathologies of multiple system atrophy (MSA) and their association with dementia have been reported, no studies have reported clinicopathological differences among MSA patients with and without neuronal cytoplasmic inclusions (NCIs) in the dentate gyrus (dntNCIs). We investigated hippocampal NCI pathology in 18 MSA patient autopsies, focusing on phosphorylated α-synuclein (pAS)- and phosphorylated tau (pT)-positive dntNCIs. There were 8 MSA patients without and 10 with dntNCIs. The latter group was subclassified by immunophenotype: those with pAS-positive dntNCIs (pAS-dntNCI subtype), those with pT-positive dntNCIs (pT-dntNCI subtype), and those with both types of dntNCIs. MSA patients with dntNCIs survived longer with prolonged tracheostomy and had dementia more frequently than those without dntNCIs. The brain weights of patients with dntNCIs were lower than those without dntNCIs. The presence of dementia was similar among the dntNCI subtypes. The pAS-dntNCI subtype was associated with longer survival and smaller brain weights; the pT-dntNCI subtype exhibited more frequent tau pathologies than the pAS-dntNCI subtype. Thus, MSA with dntNCIs is a possible pathological subtype of longer survivors that correlates with longer disease duration, prolonged tracheostomy, and high frequency of dementia. Understanding clinicopathological differences in MSA patients with and without dntNCIs may lead to improved personalized management strategies.

Medical Needs of Adults with Down Syndrome Presenting at a Regional Medical and Rehabilitation Center in Japan.

BACKGROUND: Down syndrome (DS) is the most frequent chromosomal aberration; however, knowledge of associated health issues in adulthood is inadequate. We analyzed health data from Japanese adults with DS. METHODS: We conducted a retrospective chart review of 151 patients with DS who visited the Internal Medicine Outpatient Department of the Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled. RESULTS: Endocrine disorders such as obesity, hyperlipidemia, and hyperuricemia were most common in adulthood (≤40 years) and senescence (>40 years); neurological diseases were more prevalent in senescence. Multimorbidity was noted even patients with DS who were younger than 30 years, and the prevalence increased with age. Only 21 patients (13.9%) with DS visited our hospital with referral letters from pediatricians; 94 patients (62.3%) visited without such referrals from other medical institutions. Patients without a referral letter had a mean of 3.1 comorbidities per patient. Moreover, medical care for some people with DS was interrupted during childhood. CONCLUSIONS: Prevention and detection of comorbidities in patients with DS requires continuous medical care from childhood through adulthood. Recently, DS has been diagnosed by chromosome testing and genetic counseling. Clinical geneticists and genetic counselors can help patients with DS, and their caregivers, to obtain appropriate health care and achieve well-being on their own by seamlessly engaging them throughout childhood and adulthood.

Huxleyan utopia or Huxleyan dystopia? "Scientific humanism", Faure's legacy and the ascendancy of neuroliberalism in education.

In addition to the longstanding threat posed by narrow economism, faith in the possibility of peace and progress through democratic politics - central to the humanistic vision of the 1972 Faure report - today faces additional challenges. These challenges include the ascendancy of neurocentrism in the global policyscape. Whereas the effects of neoliberalism on education have been extensively critiqued, the implications of a newer, related ideological framework known as neuroliberalism remain under-theorised. Neuroliberalism combines neoliberal ideas concerning the role of markets in addressing social problems with beliefs about human nature ostensibly grounded in the behavioural, psychological and neurological sciences. This article critically examines a recent initiative of one of UNESCO's Category 1 Institutes - the Mahatma Gandhi Institute of Education for Peace and Sustainable Development (MGIEP) - that seeks to mainstream neuroscience and digital technology within global educational policy. Comparing the visions of the 1972 Faure, the 1996 Delors and the 2021 Futures of Education reports with MGIEP's International Science and Evidence Based Education Assessment (ISEEA), the authors analyse continuity and change in UNESCO's attempts to articulate a vision of "scientific humanism" which advocates the use of science for the betterment of humanity. They argue that ISEEA's overall recommendations - as represented in its Summary for Decision Makers (SDM) - reinforce a reductive, depoliticised vision of education which threatens to exacerbate educational inequality while enhancing the profits and power of Big Tech. These recommendations exemplify a neuroliberal turn in global education policy discourse, marking a stark departure from the central focus on ethics and democratic politics characteristic of UNESCO's landmark education reports. Reanimating, in cruder form, visions of a scientifically-organised utopia of the kind that attracted UNESCO's inaugural Director-General, Julian Huxley, ISEEA's recommendations actually point towards the sort of dystopian "brave new world" of which his brother, Aldous Huxley, warned.

Utopie huxleyenne ou dystopie huxleyenne? « L'humanisme scientifique ¼, l'héritage de Faure et la montée du néolibéralisme dans l'éducation ­ Outre faire face à la menace que pose depuis longtemps l'économisme étroit, la foi dans la possibilité que la politique démocratique peut produire paix et progrès ­ un pilier de la vision humaniste du rapport Faure paru en 1972 ­ se heurte aujourd'hui à d'autres défis, entre autres à la montée du neurocentrisme dans le champ politique mondial. Tandis que les effets du néolibéralisme sur l'éducation ont été abondamment critiqués, peu d'hypothèses ont été formulées au sujet de ce qu'implique une notion plus récente, mais liée à lui sur le plan idéologique et connue sous le nom de neurolibéralisme. Le neurolibéralisme associe des idées néolibérales sur le rôle des marchés pour résoudre des problèmes sociaux avec la conviction que la nature humaine est prétendument ancrée dans les sciences comportementales, psychologiques et neurologiques. Cet article porte un regard critique sur une initiative récente d'un des instituts de catégorie 1 de l'UNESCO, l'Institut Mahatma Gandhi d'éducation pour la paix et le développement durable (MGIEP), qui cherche à intégrer les neurosciences et la technologie du numérique dans la politique mondiale de l'éducation. Les auteurs comparent les visions des rapports Faure en 1972 et Delors en 1996 et du rapport de 2021 sur les futurs de l'éducation avec l'évaluation internationale de l'éducation basée sur la science et des éléments concrets (ISEEA) réalisée par le MGIEP, pour analyser la continuité et les changements dans les tentatives de l'UNESCO d'articuler une vision de « l'humanisme scientifique ¼ prônant d'utiliser la science pour améliorer l'humanité. Ils avancent que les recommandations principales de l'ISEEA, telles que l'évaluation les présente dans son récapitulatif à l'intention des décideurs, renforce une vision réductrice et dépolitisée de l'éducation, qui menace d'exacerber les inégalités en matière d'éducation tout en accroissant les profits et la puissance des big tech. Ces recommandations illustrent un tournant neurolibéral dans le discours mondial sur la politique de l'éducation, qui se démarque absolument de l'intérêt central pour l'éthique et la politique démocratique, caractéristiques des rapports historiques de l'UNESCO sur l'éducation. Ravivant, sous une forme plus rudimentaire, des visions d'une utopie structurée scientifiquement du type de celles qui attiraient le premier directeur général de l'UNESCO, Julian Huxley, les recommandations de l'ISEEA laissent en réalité entrevoir la sorte de « meilleur des mondes ¼ dystopique contre laquelle son frère, Aldous Huxley, mettait en garde.

[Current Situation and Issues in the Transition from Pediatric to Adult Health Care: A Neurologist's Perspective].

Our hospital provides medical care and rehabilitation for individuals with disabilities. In our hospital, both neurologists and pediatricians have been working on the transition from pediatric to adult healthcare. We used a transition readiness checklist and pediatrician-neurologist transition consultation. We aimed to promote appropriate medical care, community-based healthcare coordination, and welfare services through interprofessional care with other health professionals. We assisted patients and their families in improving self-management and discussed patient issues with their best interests in mind through a shared decision-making process. Recently, the need for neurologists in transitioning patients from pediatric to adult healthcare has been increasing.

[Perspective on transition from pediatric to adult health care for patients with neurological disease: current situation and issues].

An improvement in efficacy treatment and development of the social support system has led to many patients with neurological disease being able to reach adulthood. Therefore health care for life from pediatrics to adulthood has become necessary. The Special Committee for Measures Against Transition from Pediatric to Adult Health Care of the Japanese Society of Neurology officially started to examine the current situation and issues of transition from pediatric to adult health care in July 2020. Pediatric neurologists and adult neurologists have an awareness of this issue of constructing a better transition from pediatric to adult health care. However, there are some tasks that need to be resolved in the medical system. We intend to improve the understanding of transition and assessment of medical service fees for transition in cooperation with the Japanese Society of Neurology and the Japanese Society of Child Neurology.

An autopsied case report of spastic paraplegia with thin corpus callosum carrying a novel mutation in the SPG11 gene: widespread degeneration with eosinophilic inclusions.

BACKGROUND: The detailed neuropathological features of patients with autosomal recessive hereditary spastic paraplegia with a thin corpus callosum (TCC) and SPG11 mutations are poorly understood, as only a few autopsies have been reported. Herein, we describe the clinicopathological findings of a patient with this disease who received long-term care at our medical facility. CASE PRESENTATION: A Japanese man exhibited a mild developmental delay in early childhood and intellectual disability, followed by the appearance of a spastic gait by age 13. At the age of 25 years, he became bedridden and needed a ventilator. Genetic analysis revealed a homozygous splice site variant in the SPG11 gene (c. 4162-2A > G) after the provision of genetic counselling and acquisition of informed consent from his parents. He died of pneumonia at the age of 44. His brain weighed 967 g and was characterized by a TCC, and his spinal cord was flattened. Microscopically, degeneration was observed in the posterior spinocerebellar tract, the gracile fasciculus, and the posterior column in addition to the corticospinal tract. Marked neuronal loss and gliosis were observed in the anterior horn, Clarke's column, and hypoglossal and facial nuclei. Various types of neurons, in addition to motor neurons, showed coarse eosinophilic granules that were immunoreactive for p62. The loss of pigmented neurons with gliosis was apparent in both the substantia nigra and locus coeruleus. Lateral geniculate body degeneration was a characteristic feature of this patient. Furthermore, peripheral Lewy body-related α-synucleinopathy and scattered α-synuclein-immunoreactive neurites in the locus coeruleus and reticular formation of the brainstem were observed. CONCLUSIONS: In patients with hereditary spastic paraplegia with SPG11 mutations, a variety of clinical phenotypes develop due to widespread lesions containing p62-immunoreactive neuronal cytoplasmic inclusions. We herein report the lateral geniculate body as another degenerative site related to SPG11-related pathologies that should be studied in future investigations.

Tufted astrocyte-like glia in two autopsy cases of multiple system atrophy: Is it a concomitant neurodegenerative disorder with multiple system atrophy and progressive supranuclear palsy?

Tufted astrocytes are one of the core histopathological features of progressive supranuclear palsy (PSP). To our knowledge, only three cases of multiple system atrophy (MSA) with PSP pathology have been reported. Here, we report two autopsy cases of MSA associated with the appearance of tufted astrocyte-like glia (TuALG). Clinically, the patients' symptoms were atypical of MSA; one showed vertical gaze palsy, and the other was a long-term survivor who progressed to a bedridden state shortly after the onset of the disease. These neuropathological observations were characterized by the copresence of MSA-specific changes and TuALG in some of the cerebral cortices but few or none of the other PSP tau pathologies. These cases might emphasize the significance of TuALG in non-PSP neurodegenerative disorders.

Cerebral white matter tau-positive granular glial pathology as a characteristic pathological feature in long survivors of multiple system atrophy.

INTRODUCTION: It is unclear whether tau-positive granular glial pathology is a characteristic feature of MSA. We aimed to analyse the prevalence and significance of tau-positive granular glial pathology in MSA. METHODS: Fourteen MSA cases were clinicopathologically investigated, focusing on tau-positive granular glial pathology in the frontal and temporal white matter and putamen. RESULTS: In five MSA cases, the temporal white matter showed AT8-positive granular glial pathology; this pathology was detected in the frontal white matter in three cases. AT8-positive granular glia in the white matter were associated with long disease duration with long-term tube feeding and/or long-term tracheotomy. Alpha-synuclein-positive glial cytoplasmic inclusion intensity was not associated with AT8-positive granular glial pathology. The tau isoform of AT8-positive granular glia in the cerebral white matter exhibited three-repeat, not four-repeat, tau. Ten MSA patients showed tau-positive granular glial pathology in the putamen; the tau isoform was predominantly three-repeat tau and four-repeat tau in cases with disease duration ≥13 years and < 13 years, respectively. CONCLUSIONS: Tau-positive granular glia in the putamen is a characteristic pathological feature of MSA. Tau-positive granular glia appear in the cerebral white matter in MSA patients and are associated with long disease duration with long-term tube feeding and/or long-term tracheotomy.

[Effect of laryngeal closure on recurrent aspiration pneumonia in patients with neurodegenerative disease].

Three patients with neurodegenerative diseases who had developed repeated aspiration pneumonia underwent laryngeal closure, a surgical procedure at the larynx to prevent aspiration. None of these patients have developed aspiration pneumonia since the procedure. One patient needed endoscopic suction and cough assist machine to clear thick sputum, because tracheostomy bypassed the upper airway and so prevented moisturization of inhaled air. While two patients achieved freedom from tracheal cannulation, one needed continued cannulation because of narrowing of the stoma due to improvements in the nutritional condition. One patient was able to resume oral intake. Although the right timing to perform the procedure and optimal care along with long-term observation are important, laryngeal closure is an effective option for patients with neurodegenerative diseases to prevent recurrent aspiration pneumonia.

[Investigation of transition from pediatric to adult health care for patients with special health-care needs for neurological disease dating from childhood].

We investigated the patients followed in our hospital's adult neurology department to evaluate issues during the transition from pediatric to adult health care for patients with special health-care needs for neurological diseases. There has been an increase in the number of transition patients, and they were often recommended for the transition by pediatricians. Many patients had complications such as epilepsy, and there were also patients with an intractable disease. Therefore, patients undergoing this transition need neurologists. The transition requires a long time, and there is a difference in the medical administrative fees between pediatric and adult health care. The Japanese Society of Neurology and related societies need to take measures to improve these health-care transitions.

Non-motor manifestations in ALS patients with tracheostomy and invasive ventilation.

INTRODUCTION: This study aimed to investigate non-motor manifestations in amyotrophic lateral sclerosis (ALS) patients with tracheostomy and invasive ventilation (TIV) and their relevance to disease progression. METHODS: Sixty-seven ALS patients with TIV were enrolled, and followed-up prospectively. The patients were classified at the final evaluation into two subgroups according to the duration of TIV use or disease stage measured by communication impairment. We identified non-motor manifestations and investigated their frequencies and differences across the stages. RESULTS: The non-motor manifestations were macroglossia (22.4%), unstable blood pressure (38.8%), hypothermia (26.9%), dysuria (50.7%), and hyperglycemia (12.1%). These manifestations occurred significantly more frequently in patients with TIV ≥5 years than in patients with TIV <5 years, and more in patients with severe communication impairment than in those with preserved communication ability. DISCUSSION: Non-motor manifestations are observed at a high rate in ALS patients with TIV, and are possibly related to disease progression. Muscle Nerve 57: 735-741, 2018.

Clinicopathological characteristics of patients with amyotrophic lateral sclerosis resulting in a totally locked-in state (communication Stage V).

In the present study, we performed a comprehensive analysis to clarify the clinicopathological characteristics of patients with amyotrophic lateral sclerosis (ALS) that had progressed to result in a totally locked-in state (communication Stage V), in which all voluntary movements are lost and communication is impossible. In 11 patients, six had phosphorylated TAR DNA-binding protein 43 (pTDP-43)-immunoreactive (ir) neuronal cytoplasmic inclusions (NCI), two had fused in sarcoma (FUS)-ir NCI, and three had copper/zinc superoxide dismutase (SOD1)-ir NCI. The time from ALS onset to the need for tracheostomy invasive ventilation was less than 24 months in ten patients. Regardless of accumulated protein, all the patients showed common lesions in the pallido-nigro-luysian system, brainstem reticular formation, and cerebellar efferent system, in addition to motor neurons. In patients with pTDP-43-ir NCI, patients with NCI in the hippocampal dentate granule neurons (DG) showed a neuronal loss in the cerebral cortex, and patients without NCI in DG showed a preserved cerebral cortex. By contrast, in patients with FUS-ir NCI, patients with NCI in DG showed a preserved cerebral cortex and patients without NCI in DG showed marked cerebral degeneration. The cerebral cortex of patients with SOD1-ir NCI was preserved. Together, these findings suggest that lesions of the cerebrum are probably not necessary for progression to Stage V. In conclusion, patients with ALS that had progressed to result in communication Stage V showed rapidly-progressed symptoms, and their common lesions could cause the manifestations of communication Stage V.

Analysis of resting salivation rate in patients with amyotrophic lateral sclerosis using tracheostomy invasive ventilation.

Patients with amyotrophic lateral sclerosis (ALS) often suffer from salivation problems such as drooling and dry mouth. We examined resting salivation rate cross-sectionally in 66 advanced ALS patients with tracheostomy invasive ventilation using a cotton roll method, and investigated clinical factors associated with salivation rate. Resting salivation rate in the patients was well preserved (median value 0.6 g/min), and was significantly more increased in patients with impairment of jaw movement (P = 0.007) or mouth opening (P = 0.003) than in patients with less impairment, and in patients with the mouth being constantly open ≥ 10 mm in rostrocaudal length than in patients with < 10 mm. These data indicate that salivation rate was increased with progression of dysfunction of voluntary jaw movement. Appropriate oral care is required in advanced ALS patients to maintain their oral hygiene and to avoid penetration of saliva into the airway.

A Japanese familial ALS patient with autonomic failure and a p.Cys146Arg mutation in the gene for SOD1 (SOD1).

We describe a Japanese man with familial amyotrophic lateral sclerosis (ALS) associated with a p.Cys146Arg mutation in the copper/zinc superoxide dismutase gene (SOD1). The patient developed bulbar signs followed by rapidly progressive limb muscle weakness. The prominent clinical feature was orthostatic hypotension due to autonomic failure, which occurred after he underwent tracheostomy 1 year and 3 months after the onset. Thereafter, he required mechanical ventilation and progressed to communication stage V (totally locked-in state) 7 years after the onset. Neuropathology showed ALS with posterior column degeneration and multiple system degeneration. Severe neuronal loss in the intermediolateral nucleus was also observed. Two previously reported cases of ALS patients with autonomic failure showed severe neuronal loss in the intermediolateral nucleus in addition to degeneration of the motor neurons. Thus, autonomic failure due to neuronal loss in the intermediolateral nucleus could present in patients with ALS associated with certain mutations in SOD1.

ALS patients with ability to communicate after long-term mechanical ventilation have confined degeneration to the motor neuron system.

OBJECTIVE: To clarify the position in the amyotrophic lateral sclerosis (ALS) spectrum, of a subgroup of patients who maintained the ability to communicate after long-term mechanical ventilation (LTMV) by tracheostomy. METHODS: We undertook a clinicopathological investigation of sporadic ALS in three patients who maintained the ability to communicate after approximately 30-year survival on LTMV by tracheostomy. RESULTS: The age of onset and duration of disease was 48 years and 31 years in patient 1, 55 years and 29 years in patient 2, and 31 years and 33 years in patient 3, respectively. Each patient displayed slow disease progression. In all patients, both upper and lower motor neurons were markedly degenerated, while other neuronal systems and the brainstem tegmentum were spared. A few normal-looking motor neurons remained in the anterior horn of the spinal cord. There were no TAR DNA-binding protein 43-immunoreactive inclusions in the lower motor neurons in any patient and only occasional inclusions in the cerebral cortex of one patient. CONCLUSION: The clinicopathological findings of these three patients suggest that there is a distinct subgroup of ALS patients characterized by the above-mentioned features.

Frequent globular neuronal cytoplasmic inclusions in the medial temporal region as a possible characteristic feature in multiple system atrophy with dementia.

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease, which is characterized clinically by parkinsonism, cerebellar ataxia and/or autonomic dysfunction, and pathologically by alpha-synuclein-related multisystem neurodegeneration, so-called alpha-synucleinopathy, which particularly involves the striatonigral and olivopontocerebellar systems, with glial cytoplasmic inclusions and neuronal cytoplasmic/nuclear inclusions (NCIs/NNIs). In the recent consensus criteria for the diagnosis of MSA, dementia is described as one of the features not supporting a diagnosis of MSA. However, MSA with dementia has been reported, although the location of the lesion responsible for the dementia remains unclear. In the present study, we aimed to investigate where this lesion may be found, by analyzing 12 autopsy-proven MSA cases, with a particular focus on the medial temporal region. Three of 12 cases with MSA had dementia (MSA-D). Compared with MSA cases without dementia, MSA-D cases had frequent globular NCIs (G-NCIs) in the medial temporal region, especially in their subiculum. In addition, MSA-D cases could be divided into two types; MSA-D with distinct fronto-temporal lobar degeneration (FTLD type) and without distinct fronto-temporal lobar degeneration (non-FTLD type). There was no association between dementia and Alzheimer pathologies, such as neurofibrillary tangles and senile plaques. We suggest that frequent G-NCIs in the medial temporal region, and particularly the subiculum, is one of the important pathological findings of MSA-D, even when a case with MSA-D reveals no significant cerebral atrophy.