Cerebrospinal fluid glial fibrillary acidic protein, in contrast to amyloid beta protein, is associated with disease symptoms in Huntington's disease.

INTRODUCTION: Huntington's disease (HD) is a hereditary neurodegenerative disease, currently lacking disease-modifying treatments. Biomarkers are needed for objective assessment of disease progression. Evidence supports both complex protein aggregation and astrocyte activation in HD. This study assesses the 42 amino acid long amyloid beta (Aß42) and glial fibrillary acidic protein (GFAP) as potential biomarkers in the cerebrospinal fluid (CSF) of HD mutation carriers. METHODS: CSF from participants was obtained from three sites in Sweden. Clinical symptoms were graded with the composite Unified Huntington's disease rating scale (cUHDRS). Protein concentrations were measured using ELISA. Pearson correlations were calculated to assess disease progression association. Results were adjusted for age and collection site. RESULTS: The study enrolled 28 manifest HD patients (ManHD), 13 premanifest HD gene-expansion carriers (PreHD) and 20 controls. Aß42 levels did not differ between groups and there was no correlation with measures of disease progression. GFAP concentration was higher in ManHD (424 ng/l, SD 253) compared with both PreHD (266 ng/l, SD 92.4) and controls (208 ng/l, SD 83.7). GFAP correlated with both cUHDRS (r = -0.77, p < 0.001), and 5-year risk of disease onset (r = 0.70, p = 0.008). CONCLUSION: We provide evidence that indicates CSF Aß42 has limited potential as a biomarker for HD. GFAP is a potential biomarker of progression in HD. Validation in larger cohorts measuring GFAP in blood and CSF would be of interest.

Symptom Analysis of Early Parkinson's Disease and its Correlation with High Sensitivity C-reactive Protein.

Parkinson's disease is a debilitating neurodegenerative disease for which there is no cure. It is characterized by bradykinesia, resting tremor, rigidity and postural instability, due to impairment of function of the basal ganglia which is involved in the coordination of body movement. Neuro-inflammation is pathogenesis of development in early Parkinson's disease. High-sensitivity C-reactive protein level is a useful non-specific biochemical marker of inflammation. Objective of this study was to analyze the symptoms of Parkinson disease and it's correlation with high sensitive CRP. Seventy-six Parkinson's disease patients were enrolled in this Cross-sectional observational study that was attended in the Department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from September 2014 to March 2016. Analysis of the symptoms of Parkinson disease and it's correlation with high sensitive CRP were done among these patients. This study was performed on 76 Parkinson disease patients with presented early with symptoms. a positive and highly significant correlation were seen in between duration of tremor and High sensitivity CRP (r=0.430, p<0.001) and between duration of bradykinesia and High sensitivity CRP (r=0.426, p<0.001) which indicate increase duration causes increase level of high-sensitivity C-reactive protein value. The neuro-inflammation plays a significant role in the pathogenesis of symptoms development in early Parkinson's disease.

Localizing apraxia in corticobasal syndrome: a morphometric MRI study.

Apraxia localization has relied on voxel-based, lesion-symptom mapping studies in left hemisphere stroke patients. Studies on the neural substrates of different manifestations of apraxia in neurodegenerative disorders are scarce. The primary aim of this study was to look into the neural substrates of different manifestations of apraxia in a cohort of corticobasal syndrome patients (CBS) by use of cortical thickness. Twenty-six CBS patients were included in this cross-sectional study. The Goldenberg apraxia test (GAT) was applied. 3D-T1-weighted images were analyzed via the automated recon-all Freesurfer version 6.0 pipeline. Vertex-based multivariate General Linear Model analysis was applied to correlate GAT scores with cortical thickness. Deficits in imitation of meaningless gestures correlated with bilateral superior parietal atrophy, extending to the angular and supramarginal gyri, particularly on the left. Finger imitation relied predominantly on superior parietal lobes, whereas the left angular and supramarginal gyri, in addition to superior parietal lobes, were critical for hand imitation. The widespread bilateral clusters of atrophy in CBS related to apraxia indicate different pathophysiological mechanisms mediating praxis in neurodegenerative disorders compared to vascular lesions, with implications both for our understanding of praxis and for the rehabilitation approaches of patients with apraxia.

Amyotrophic Lateral Sclerosis and Pain: A Narrative Review from Pain Assessment to Therapy.

Amyotrophic lateral sclerosis (ALS) is the most frequent neurodegenerative disease of the motor system that affects upper and lower motor neurons, leading to progressive muscle weakness, spasticity, atrophy, and respiratory failure, with a life expectancy of 2-5 years after symptom onset. In addition to motor symptoms, patients with ALS have a multitude of nonmotor symptoms; in fact, it is currently considered a multisystem disease. The purpose of our narrative review is to evaluate the different types of pain, the correlation between pain and the disease's stages, the pain assessment tools in ALS patients, and the available therapies focusing above all on the benefits of cannabis use. Pain is an underestimated and undertreated symptom that, in the last few years, has received more attention from research because it has a strong impact on the quality of life of these patients. The prevalence of pain is between 15% and 85% of ALS patients, and the studies on the type and intensity of pain are controversial. The absence of pain assessment tools validated in the ALS population and the dissimilar study designs influence the knowledge of ALS pain and consequently the pharmacological therapy. Several studies suggest that ALS is associated with changes in the endocannabinoid system, and the use of cannabis could slow the disease progression due to its neuroprotective action and act on pain, spasticity, cramps, sialorrhea, and depression. Our research has shown high patients' satisfaction with the use of cannabis for the treatment of spasticity and related pain. However, especially due to the ethical problems and the lack of interest of pharmaceutical companies, further studies are needed to ensure the most appropriate care for ALS patients.

Safety Profile of Pimavanserin Therapy in Elderly Patients with Neurodegenerative Disease-Related Neuropsychiatric Symptoms: A Phase 3B Study.

Background: Pimavanserin, a 5-HT2A receptor inverse agonist/antagonist, is the only medication approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Further expanding knowledge of the safety profile of pimavanserin in PDP and neurodegenerative diseases (NDD) such as Alzheimer's disease is of great interest for informing its use in patients with PDP (with or without dementia), given this population is highly sensitive to adverse effects following antipsychotic use. Objective: This trial evaluated the effects of pimavanserin compared to placebo in frail older adults and elderly patients with neuropsychiatric symptoms related to NDD, such as hallucinations and delusions, to better understand the safety of pimavanserin in this population. Methods: This was a phase 3b, 8-week treatment (study duration of up to 16 weeks), multicenter, randomized, double-blind, placebo-controlled, two-arm parallel-group trial (NCT03575052). The primary endpoint was safety and tolerability, measured by treatment-emergent adverse events (TEAEs). Secondary safety endpoints were change from baseline in motor and cognitive function; exploratory endpoints included suicidality, sleep quality, and neuropsychiatric symptoms. Results: Incidences of TEAEs were similar between treatment groups; 29.8% reported ≥1 TEAE (pimavanserin: 30.4%; placebo: 29.3%), and 1.8% reported serious TEAEs (pimavanserin: 2.0%; placebo: 1.5%). Pimavanserin did not impact motor- or cognitive-related function. Conclusions: Pimavanserin was well tolerated and not associated with motor or cognitive impairment. Together, these findings highlight the manageable and generally favorable safety profile of pimavanserin in patients with NDD, contributing to our knowledge on the safety of pimavanserin as it generalizes to patients with PDP.

Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

High-Sensitivity Cardiac Troponin T and Cognitive Function Over 12 Months After Stroke-Results of the DEMDAS Study.

BACKGROUND: Subclinical myocardial injury in form of hs-cTn (high-sensitivity cardiac troponin)  levels has been associated with cognitive impairment and imaging markers of cerebral small vessel disease (SVD) in population-based and cardiovascular cohorts. Whether hs-cTn is associated with domain-specific cognitive decline and SVD burden in patients with stroke remains unknown. METHODS AND RESULTS: We analyzed patients with acute stroke without premorbid dementia from the prospective multicenter DEMDAS (DZNE [German Center for Neurodegenerative Disease]-Mechanisms of Dementia after Stroke) study. Patients underwent neuropsychological testing 6 and 12 months after the index event. Test results were classified into 5 cognitive domains (language, memory, executive function, attention, and visuospatial function). SVD markers (lacunes, cerebral microbleeds, white matter hyperintensities, and enlarged perivascular spaces) were assessed on cranial magnetic resonance imaging to constitute a global SVD score. We examined the association between hs-cTnT (hs-cTn T levels) and cognitive domains as well as the global SVD score and individual SVD markers, respectively. Measurement of cognitive and SVD-marker analyses were performed in 385 and 466 patients with available hs-cTnT levels, respectively. In analyses adjusted for demographic characteristics, cardiovascular risk factors, and cognitive status at baseline, higher hs-cTnT was negatively associated with the cognitive domains "attention" up to 12 months of follow-up (beta-coefficient, -0.273 [95% CI, -0.436 to -0.109]) and "executive function" after 12 months. Higher hs-cTnT was associated with the global SVD score (adjusted odds ratio, 1.95 [95% CI, 1.27-3.00]) and the white matter hyperintensities and lacune subscores. CONCLUSIONS: In patients with stroke, hs-cTnT is associated with a higher burden of SVD markers and cognitive function in domains linked to vascular cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01334749.

Induction of Paraquat-Mediated Parkinsonian Phenotype in Zebrafish.

Paraquat (PQ) is a well-known neurotoxin closely associated with neurodegenerative Parkinson's disease (PD). Zebrafish are utilized as a model for PD research because of their well-defined neuropathology and locomotor behavior. Here, we highlight protocols for inducing PD using PQ and analyzing locomotor activity in adult zebrafish. Basic Protocol 1 details the treatment of adult male zebrafish with 60 mg/kg PQ via intraperitoneal injection to induce a PD-like phenotype, followed by the steps to perform a locomotor assay. Basic Protocol 2 provides step-by-step guidance for processing the acquired videos in ToxTrac software to understand the locomotor parameters of 0.9% saline- and 60 mg/kg PQ-injected adult zebrafish. The simplicity of the treatment strategy, low-cost video acquisition setup, and free video processing make these protocols accessible without prior experience. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Development of Parkinson's disease features in adult zebrafish Basic Protocol 2: ToxTrac analysis for locomotor assay.

Vulnerability of Spatial Pattern Separation in 5xFAD Alzheimer's Disease Mouse Model.

Background: Alzheimer's disease (AD) is the most common cause of dementia and remains incurable. This age-related neurodegenerative disease is characterized by an early decline in episodic and spatial memory associated with progressive disruption of the hippocampal functioning. Recent clinical evidence suggests that impairment of the spatial pattern separation (SPS) function, which enables the encoding and storage of episodic spatial information, may be an indicator of the early stages of AD. Objective: The aim of our study was to characterize SPS performance at a prodromal stage in 5xFAD transgenic mouse model of AD. Methods: Behavioral performance of male wild-type (WT) and 5xFAD mice (n = 14 per group) was assessed from the age of 4 months in two validated paradigms of SPS function either based on spontaneous exploration of objects or on the use of a touchscreen system. Results: Compared with age-matched WT littermates, a mild deficit in SPS function was observed in the object recognition task in 5xFAD mice, whereas both groups showed similar performance in the touchscreen-based task. These results were observed in the absence of changes in locomotor activity or anxiety-like behavior that could have interfered with the tasks assessing SPS function. Conclusions: Our results indicate an early vulnerability of the SPS function in 5xFAD mice in the paradigm based on spontaneous exploration of objects. Our work opens up the possibility of examining the early neurobiological processes involved in the decline of episodic memory and may help to propose new therapeutic strategies in the context of AD.

Neurological Disorders in Takotsubo Syndrome: Clinical Phenotypes and Outcomes.

BACKGROUND: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS-associated neurological phenotypes and outcome. METHODS AND RESULTS: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short- and long-term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in-hospital stay (8 [interquartile range, 5-12] versus 6 [interquartile range, 5-9] days; P<0.01) and more often experienced in-hospital complications (27% versus 16%; P=0.01) mainly driven by cardiogenic shock and in-hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P<0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long-term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P<0.01). Neurological disorder was an independent predictor of both the 60-day and long-term mortality rate (odds ratio, 1.78 [95% CI, 1.07-2.97]; P=0.02; hazard ratio, 1.72 [95% CI, 1.33-2.22]; both P<0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long-term mortality rates, 29.2% and 9.7%, respectively). CONCLUSIONS: Neurological disorders identify a high-risk TTS subgroup for enhanced short- and long-term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed.

Senescence Targeting Methods Impact Alzheimer's Disease Features in 3xTg Mice.

Background: Cellular senescence has been associated with neurodegenerative disease and clearance of senescent cells using genetic or pharmaceutical strategies (senolytics) has demonstrated beneficial effects in mouse models investigating individual disease etiologies of Alzheimer's disease (AD). However, it has remained unclear if senescent cell clearance in a mouse model exhibiting both plaque and tau pathologies modifies the disease state (3xTg). Objective: To investigate the effects of senescent cell clearance in the 3xTg mouse model. Methods: 3xTg mice were treated with senolytics (ABT263 (navitoclax; NAVI), a combination of dasatinib and quercetin (D+Q)), or subjected to transgene-mediated removal of p16-expressing cells (via INK-ATTAC). Results: Senolytic treatments consistently reduced microgliosis and ameliorated both amyloid and tau pathology in 3xTg mice. Using RNA sequencing, we found evidence that synaptic dysfunction and neuroinflammation were attenuated with treatment. These beneficial effects were not observed with short-term senolytic treatment in mice with more advanced disease. Conclusions: Overall, our results further corroborate the beneficial effects senescent cell clearance could have on AD and highlight the importance of early intervention for the treatment of this debilitating disease.

Reduced olfactory performance is associated with changed microbial diversity, oralization, and accumulation of dead biomaterial in the nasal olfactory area.

The partial or complete loss of the sense of smell, which affects about 20% of the population, impairs the quality of life in many ways. Dysosmia and anosmia are mainly caused by aging, trauma, infections, or even neurodegenerative disease. Recently, the olfactory area-a site containing the olfactory receptor cells responsible for odor perception-was shown to harbor a complex microbiome that reflects the state of olfactory function. This initially observed correlation between microbiome composition and olfactory performance needed to be confirmed using a larger study cohort and additional analyses. A total of 120 participants (middle-aged, no neurodegenerative disease) were enrolled in the study to further analyze the microbial role in human olfactory function. Olfactory performance was assessed using the Sniffin' Stick battery, and participants were grouped accordingly (normosmia: n = 93, dysosmia: n = 27). The olfactory microbiome was analyzed by 16S rRNA gene amplicon sequencing and supplemented by metatranscriptomics in a subset (Nose 2.0). Propidium monoazide (PMA) treatment was performed to distinguish between intact and non-intact microbiome components. The gastrointestinal microbiome of these participants was also characterized by amplicon sequencing and metabolomics and then correlated with food intake. Our results confirm that normosmics and dysosmics indeed possess a distinguishable olfactory microbiome. Alpha diversity (i.e., richness) was significantly increased in dysosmics, reflected by an increase in the number of specific taxa (e.g., Rickettsia, Spiroplasma, and Brachybacterium). Lower olfactory performance was associated with microbial signatures from the oral cavity and periodontitis (Fusobacterium, Porphyromonas, and Selenomonas). However, PMA treatment revealed a higher accumulation of dead microbial material in dysosmic subjects. The gastrointestinal microbiome partially overlapped with the nasal microbiome but did not show substantial variation with respect to olfactory performance, although the diet of dysosmic individuals was shifted toward a higher meat intake. Dysosmia is associated with a higher burden of dead microbial material in the olfactory area, indicating an impaired clearance mechanism. As the microbial community of dysosmics (hyposmics and anosmics) appears to be influenced by the oral microbiome, further studies should investigate the microbial oral-nasal interplay in individuals with partial or complete olfactory loss.IMPORTANCEThe loss of the sense of smell is an incisive event that is becoming increasingly common in today's world due to infections such as COVID-19. Although this loss usually recovers a few weeks after infection, in some cases, it becomes permanent-why is yet to be answered. Since this condition often represents a psychological burden in the long term, there is a need for therapeutic approaches. However, treatment options are limited or even not existing. Understanding the role of the microbiome in the impairment of olfaction may enable the prediction of olfactory disorders and/or could serve as a possible target for therapeutic interventions.

Behavioral Management of Respiratory/Phonatory Dysfunction for Dysarthria Associated With Neurodegenerative Disease: A Systematic Review.

PURPOSE: This systematic review represents an update to previous reviews of the literature addressing behavioral management of respiratory/phonatory dysfunction in individuals with dysarthria due to neurodegenerative disease. METHOD: Multiple electronic database searches and hand searches of prominent speech-language pathology journals were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. RESULTS: The search yielded 1,525 articles, from which 88 met inclusion criteria and were reviewed by two blinded co-investigators. A large range of therapeutic approaches have been added to the evidence base since the last review, including expiratory muscle strength training, singing, and computer- and device-driven programs, as well as a variety of treatment modalities, including teletherapy. Evidence for treatment in several different population groups-including cerebellar ataxia, myotonic dystrophy, autosomal recessive spastic ataxia of Charlevoix-Saguenay, Huntington's disease, multiple system atrophy, and Lewy body dementia-were added to the current review. Synthesis of evidence quality provided strong evidence in support of only one behavioral intervention: Lee Silverman Voice Treatment Program (LSVT LOUD) in people with Parkinson's disease. No other treatment approach or population included in this review demonstrated more than limited evidence, reflecting that these approaches/populations require urgent further examination. CONCLUSION: Suggestions about where future research efforts could be significantly strengthened and how clinicians can apply research findings to their practice are provided. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24964473.

Causal Association Between Sepsis and Neurodegenerative Diseases: A Bidirectional Two-Sample Mendelian Randomization Study.

BACKGROUND: Previous observational studies suggested an association between sepsis and neurodegenerative diseases, but causality remains unclear. OBJECTIVE: Determining the causal association between sepsis and four neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Lewy body dementia) through bidirectional two-sample Mendelian randomization (MR) analysis. METHODS: Genome-wide association study summary statistics for all traits were obtained from publicly available databases. Inverse variance weighted (IVW) was the primary method for evaluating causal associations. In addition, three additional MR methods (MR-Egger, weighted median, and maximum likelihood method) were employed to supplement IVW. Furthermore, various sensitivity tests were conducted to assess the reliability: 1) Cochrane's Q test for assessing heterogeneity; 2) MR-Egger intercept test and MR-PRESSO global test for evaluating horizontal pleiotropy; 3) leave-one-out sensitivity test for determining the stability. RESULTS: The results of IVW indicated that sepsis significantly increased the risk of Alzheimer's disease (OR = 1.11, 95% CI: 1.01-1.21, p = 0.025). In addition, three additional MR methods suggested parallel results. However, no causal effect of sepsis on the three other neurodegenerative diseases was identified. Subsequently, reverse MR analysis indicated that the four neurodegenerative diseases do not causally affect sepsis. Furthermore, sensitivity tests demonstrated the reliability of the MR analyses, suggesting no heterogeneity or horizontal pleiotropy. CONCLUSIONS: The present study contributes to a deeper comprehension of the intricate interplay between sepsis and neurodegenerative disorders, thereby offering potential avenues for the development of therapeutic agents that can effectively mitigate the multifarious complications associated with sepsis.

APOE4 is a Risk Factor and Potential Therapeutic Target for Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, the main pathological hallmark of which is the loss of neurons, resulting in cognitive and memory impairments. Sporadic late-onset AD is a prevalent form of the disease and the apolipoprotein E4 (APOE4) genotype is the strongest predictor of the disease development. The structural variations of APOE isoforms affect their roles in synaptic maintenance, lipid trafficking, energy metabolism, inflammatory response, and BBB integrity. In the context of AD, APOE isoforms variously control the key pathological elements of the disease, including Aß plaque formation, tau aggregation, and neuroinflammation. Taking into consideration the limited number of therapy choices that can alleviate symptoms and have little impact on the AD etiology and progression to date, the precise research strategies guided by apolipoprotein E (APOE) polymorphisms are required to assess the potential risk of age-related cognitive decline in people carrying APOE4 genotype. In this review, we summarize the evidence implicating the significance of APOE isoforms on brain functions in health and pathology with the aim to identify the possible targets that should be addressed to prevent AD manifestation in individuals with the APOE4 genotype and to explore proper treatment strategies.

Neuronal intranuclear inclusion disease with cortical involvement in left hemisphere: a case report.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare highly heterogeneous disease. In this paper, we present a case of NIID featured in cortical involvement in left hemisphere of brain and the imaging changes in the process of the disease. CASE PRESENTATION: A 57-year-old female was hospitalized due to recurrent attacks of headache with cognitive impairment and tremor for 2 years. The symptoms of headache episodes were reversible. The characteristic radiologic change was high intensity signal involving the grey matter-white matter junction on the brain diffusion-weighted imaging (DWI), which existed in the frontal lobe and then extended backwards. Atypical features on fluid-attenuated inversion recovery (FLAIR) sequences showing small patchy high signals in the cerebellar vermis. High signals and edema were detected on FLAIR images along the cortex of the left occipito-parieto-temporal lobes, expanding and gradually shrinking in the follow-up visit. Besides, cerebral atrophy and bilateral symmetrical leukoencephalopathy were also detected. Skin biopsy and genetic testing confirmed the diagnosis of NIID. CONCLUSION: Except for typical radiological change strongly suggesting NIID, it is also necessary to notice the insidious symptoms of NIID combining with some atypical imaging features to make an early diagnosis. Skin biopsies or genetic testing should be carried out early in patients with highly suspected NIID.

Recovery after Prolonged Disturbance of Consciousness and Repeated Cerebral Perfusion Changes in Neuronal Intranuclear Inclusion Disease.

Encephalitic episodes are a clinical manifestation of neuronal intranuclear inclusion disease (NIID) and often show transient disturbance of consciousness. We herein report a genetically confirmed patient with NIID who initially presented progressive dementia and showed prolonged disturbance of consciousness preceded by an acute-onset headache. During that time, we performed N-isopropyl-p-[123I] iodoamphetamine single-photon-emission computed tomography twice and found that the blood flow increased in different regions. Prolonged disturbance of consciousness following an encephalitic episode may be associated with repeated hyperperfusion in various regions resulting from mitochondrial dysfunction. NIID patients presenting with encephalitic episodes can recover gradually and spontaneously even after prolonged disturbances of consciousness.