Neuromyelitis optica spectrum disorder presenting with repeated hypersomnia due to involvement of the hypothalamus and hypothalamus-amygdala linkage.

We report the case of a 46-year-old Japanese woman with neuromyelitis optica spectrum disorder presenting with repeated hypersomnia accompanied by decreased CSF orexin level. First episode associated with hypothalamic-pituitary dysfunction showed bilateral hypothalamic lesions that can cause secondary damage to the orexin neurons. The second episode associated with impaired memory showed a left temporal lesion involving the amygdala. The mechanism remains unknown, but the reduced blood flow in the hypothalamus ipsilateral to the amygdala lesion suggested trans-synaptic hypothalamic dysfunction secondary to the impaired amygdala. A temporal lesion involving the amygdala and hypothalamus could be responsible for hypersomnia due to neuromyelitis optica spectrum disorder.

18F-THK5351 Positron Emission Tomography Clearly Depicted Progressive Multifocal Leukoencephalopathy After Mantle Cell Lymphoma Treatment.

An 84-year-old Japanese woman presented with left hemiplegia 8 months after completing chemotherapy for mantle cell lymphoma. Brain magnetic resonance imaging (MRI) revealed a hyperintense lesion extending from the right parietal lobe to the left parietal lobe. Compared with these MRI results, 18F-THK5351 PET revealed more extensive accumulation. A brain biopsy showed progressive multifocal leukoencephalopathy (PML). Immunohistochemistry and John Cunningham virus (JCV) DNA-polymerase chain reaction indicated JCV infection. Therefore, a diagnosis of PML was made. 18F-THK5351 PET, indicative of activated astrocytes, clearly depicted PML lesions composed of reactive and atypical astrocytes. 18F-THK5351 PET may capture fresh progressive PML lesions better than MRI.

Temporal expression profiles of microRNAs associated with acute phase of brain ischemia in gerbil hippocampus.

Neuroprotective therapeutic potential for restoring dysregulated microRNA (miRNA) expression has previously been demonstrated in a gerbil cerebral infarction model. However, since temporal changes in miRNA expression profiles following stroke onset are unknown, miRNAs proving to be useful therapeutic targets have yet to be identified. We evaluated cognitive function, hippocampal neuronal cell death, and microarray-based miRNA expression profiles at 5, 9, 18, 36, and 72 h after 5-min whole brain ischemia in gerbils. A decline in cognitive function occurred in parallel with increased neuronal cell death 36-72 h after ischemia. The Jonckheere-Terpstra test was used to analyze miRNA expression trends 5-72 h after ischemia. The expression levels of 63 miRNAs were significantly upregulated, whereas 32 miRNAs were significantly downregulated, monotonically. Of the 32 monotonically downregulated miRNAs, 18 showed the largest decrease in expression 5-9 h after ischemia. A subset of these dysregulated miRNAs (miR-378a-5p, miR-204-5p, miR-34c-5p, miR-211-5p, miR-34b-3p, and miR-199b-3p) could be associated with brain ischemia and neuropsychiatric disorders.

Roles of Na⁺/H⁺ exchanger type 1 and intracellular pH in angiotensin II-induced reactive oxygen species generation and podocyte apoptosis.

A growing body of evidence suggests that podocyte apoptosis is a major cause of decreased podocyte number, which leads to albuminuria and glomerular injury. The aim of this study was to clarify the molecular mechanisms of angiotensin II (Ang II)-induced apoptosis in cultured mouse podocytes. We examined the effects of Ang II (100 nmol/L) on apoptosis, superoxide anions, and cytosol pH in podocytes. For intracellular pH measurements, image analysis was conducted using confocal laser microscopy after incubation with carboxy-seminaphthorhodafluor-1. Superoxide anions and intracellular pH were elevated with Ang II treatment. Apoptotic cell numbers, as measured by TUNEL staining and caspase 3 activity, were also augmented in the Ang II-treated group. Pre-treatment with olmesartan (100 nmol/L, an Ang II type 1-receptor blocker), apocynin (50 µmol/L, NADPH oxidase inhibitor), or 5-N,N hexamethylene amiloride [30 µmol/L, Na⁺/H⁺ exchanger type 1 (NHE-1) inhibitor] abolished Ang II-induced podocyte apoptosis, whereas NHE-1 mRNA and protein expression was not affected by Ang II treatment. Moreover, Ang II increased NHE-1 phosphorylation. These results suggest that superoxide production, NHE-1 activation, and intracellular alkalization were early features prior to apoptosis in Ang II-treated mouse podocytes, and may offer new insights into the mechanisms responsible for Ang II-induced podocyte injury.

Cytotoxic Lesions of the Corpus Callosum (CLOCC) Suggesting Exacerbation by Heterogeneous COVID-19 Booster Vaccination.

Cytotoxic lesions of the corpus callosum (CLOCC) is a disease entity associated with reversible lesions of the corpus callosum on magnetic resonance imaging (MRI). CLOCC is caused by a variety of etiologies, but CLOCC after vaccination is extremely rare. Four prior cases of CLOCC after the first dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine have been reported; these were localized to the splenium and showed early clinical and neuroradiological recovery. We experienced an unusual case in which a heterogeneous COVID-19 booster vaccination caused rather severe CLOCC damage. A 74-year-old Japanese woman presented with ataxia, high fever, and hearing loss several days after her third vaccination against COVID-19. This booster was an mRNA-1273 while her first and second vaccinations were both BNT162b2 type. SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis was negative, but serum SARS-CoV-2 S-IgG antibodies were elevated. Her cerebrospinal fluid (CSF) showed an elevated cell count and high levels of protein and interleukin-6 (IL-6). Brain MRI showed CLOCC spreading throughout the body of the corpus callosum. After the exclusion of other potential causes, the diagnosis of vaccination-related CLOCC was made. Six months later, recovery of clinical and MRI findings remained incomplete. It was suggested that the patient's CLOCC might have been caused by the increase in CSF IL-6 due to an enhanced immune response from the heterogeneous vaccination, resulting in more severe damage to the corpus callosum than usual.

Age­related brainstem degeneration through microRNA modulation in mice.

Histopathological changes occur in the brainstem during the early stages of Alzheimer's disease (AD), with the pathological changes of the brain lesions ascending progressively in accordance with the Braak staging system. The senescence­accelerated mouse prone 8 (SAMP8) mouse model has been previously used as a model of age­dependent neurodegenerative diseases, including AD. In the present study, microRNAs (miRNAs) that were upregulated or downregulated in SAMP8 brainstems were identified using miRNA profiling of samples obtained from miRNA arrays. The preliminary stage of cognitive dysfunction was examined using male 5­month­old SAMP8 mice, with age­matched senescence­accelerated mouse resistant 1 mice as controls. A Y­maze alternation test was performed to assess short­term working memory and miRNA profiling was performed in each region of the dissected brain (brainstem, hippocampus and cerebral cortex). SAMP8 mice tended to be hyperactive, but short­term working memory was preserved. Two miRNAs were upregulated (miR­491­5p and miR­764­5p) and two were downregulated (miR­30e­3p and miR­323­3p) in SAMP8 brainstems. In SAMP8 mice, the expression level of upregulated miRNAs were the highest in the brainstem, wherein age­related brain degeneration occurs early. It was demonstrated that the order of specific miRNA expression levels corresponded to the progression order of age­related brain degeneration. Differentially expressed miRNAs regulate multiple processes, including neuronal cell death and neuron formation. Changes in miRNA expression may result in the induction of target proteins during the early stages of neurodegeneration in the brainstem. These findings suggest that studying altered miRNA expression may provide molecular evidence for early age­related neuropathological changes.

Association of serum anti-periodontal pathogen antibody with ischemic stroke.

BACKGROUND: Periodontitis increases the risk of atherosclerotic cardiovascular disease and ischemic stroke. In this study, we evaluated whether serum antibody levels against individual periodontal pathogens are significantly associated with ischemic stroke subtypes and their risk factors. METHODS: Patients with acute ischemic stroke (n = 132; 74 male and 58 female, 71.3 ± 10.7 years) and patients with no previous stroke (n = 77; 38 male and 39 female, 70.7 ± 9.5 years) were consecutively enrolled in this study. Stroke subtype was evaluated based on the Trial of Org 10172 in Acute Stroke Treatment classification. Serum was obtained from each patient after obtaining their consent to participate in the study. The levels of serum antibodies against Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg) and Prevotella intermedia (Pi) were evaluated by ELISA. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured by nephelometry. RESULTS: Serum hs-CRP levels were significantly associated with acute ischemic stroke even after controlling for acute ischemic stroke, hypertension, diabetes mellitus and bulb/ internal carotid artery (ICA) atherosclerosis which were statistically selected (coefficient 0.245, 95% CI 0.142-0.347, p < 0.0001). The serum-antibody level of Pi was significantly higher in atherothrombotic-stroke patients than in patients with no previous stroke (p = 0.0035). Detectable serum anti-Pg antibody was significantly associated with atrial fibrillation (overall χ(2) = 35.5, R(2) = 0.18, n = 209, p < 0.0001; anti-Pg antibody: OR 4.36, 95% CI 1.71-12.10, p = 0.0017), and detectable serum anti-Pi antibody was significantly associated with bulb/ICA atherosclerosis after controlling for the statistically selected associated factors (overall χ(2) = 46.1, R(2) = 0.18, n = 209, p < 0.0001; anti-Pg antibody: OR 16.58, 95% CI 3.96-78.93, p < 0.0001). The levels of serum anti-Pi antibody were significantly associated with atherothrombotic stroke with the statistically selected associated factors excluding bulb/ICA atherosclerosis (overall χ(2) = 77.0, R(2) = 0.44, n = 129, p < 0.0001; anti-Pi antibody: OR 23.6, 95% CI 2.65-298.2, p = 0.008). However, when we included bulb/ICA atherosclerosis in this model, the levels of serum anti-Pi antibody were no longer significantly associated with atherothrombotic stroke (overall χ(2) = 98.0, R(2) = 0.56, n = 129, p < 0.0001; anti-Pi antibody: p = 0.107). CONCLUSIONS: Our results suggest that anti-Pg antibody is associated with atrial fibrillation and that anti-Pi antibody is associated with carotid artery atherosclerosis. In addition, anti-Pi antibody may be associated with atherothrombotic stroke through its association with carotid artery atherosclerosis. Thus, periodontitis may lead to serious systemic diseases.

Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor.

Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia.

Aldosterone induces p21-regulated apoptosis via increased synthesis and secretion of tumour necrosis factor-α in human proximal tubular cells.

1. Aldosterone has been shown to mediate p21-dependent cellular senescence in rat kidney proximal tubules in vivo and in cultured human proximal tubular cells. The p21-induced senescent cells express higher levels of apoptotic cytokines, such as tumour necrosis factor (TNF)-α compared with non-senescent cells. The aim of the present study was to investigate the hypothesis that aldosterone increases proximal tubular apoptosis by increasing the secretion of apoptosis-inducing factors through a p21-dependent mechanism. 2. Human proximal tubular cells were incubated with aldosterone (10 nmol/L) and cell senescence was detected by senescence-associated ß-galactosidase staining and expression of p21. Apoptosis was analysed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling and annexin/propidium iodide staining, whereas p21 localization was determined by immunofluorescence. 3. Exposure of cells to aldosterone for 3 or 5 days increased senescence-associated ß-galactosidase staining, p21 and TNF-α mRNA expression and secretion of TNF-α into the culture medium. These changes were abolished by gene silencing of p21. Aldosterone failed to increase the number of apoptotic cells on day 3, but did increase them on day 5. A neutralizing antibody against TNF-α prevented the aldosterone-induced apoptotic changes. Aldosterone did not affect localization of p21. 4. These findings indicate that aldosterone increases TNF-α synthesis and secretion in proximal tubular cells via p21/senescence-dependent cell phenotypic changes and that the TNF-α secreted plays an important role as a paracrine factor in mediating cell apoptosis, indicating a possible involvement in aldosterone-induced renal damage.

Significance of Cortical Ribboning as a Biomarker in the Prodromal Phase of Sporadic Creutzfeldt-Jakob Disease.

A 63-year-old woman who presented for orofacial dystonia showed cortical ribboning, a typical MRI finding in sporadic Creutzfeldt-Jakob disease (sCJD). However, real-time quaking-induced conversion (RT-QuIC), the most sensitive method for an early diagnosis of sCJD, was negative. She developed sCJD six months later, at which time RT-QuIC became positive. The cerebral blood flow showed a decrease in the cerebral cortex (especially in the supramarginal gyrus) consistent with cortical ribboning, but an increase in the basal ganglia, probably involved in orofacial dystonia. Cortical ribboning on MRI might be a better biomarker than RT-QuIC in the prodromal phase of sCJD.

A cerebrospinal fluid microRNA analysis: Progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy described as a syndrome of postural instability, supranuclear vertical gaze palsy, dysarthria, dystonic rigidity of the neck and trunk, dementia, and pseudobulbar palsy. The clinical diagnosis of PSP is often difficult because there are no established biomarkers, and diagnosis is currently based on clinical and imaging findings. Furthermore, the etiology and pathogenesis of PSP remain unknown. Dysregulation of microRNAs (miRNAs/miRs) has been reported to serve an important role in neurodegenerative diseases. However, the miRNA profiles of patients with PSP are rarely reported. The present study aimed to examine cerebrospinal fluid miRNAs, which are considered to be more sensitive indicators of changes in the brain, to elucidate the pathophysiology of PSP and to establish specific biomarkers for diagnosis. The present study used a microarray chip containing 2,632 miRNAs to examine cerebrospinal fluid miRNA expression levels in 11 patients with PSP aged 68­82 years. A total of 8 age­ and sex­matched controls were also included. A total of 38 miRNAs were significantly upregulated and one miRNA was significantly downregulated in the cerebrospinal fluid of patients with PSP. The patients were divided into two groups based on disease stage (early onset and advanced), and changes in miRNA expression were examined. The miRNAs that were most significantly upregulated or downregulated in the early onset group were miR­204­3p, miR­873­3p and miR­6840­5p. The target genes of these miRNAs were associated with molecules related to the ubiquitin­proteasome system and autophagy pathway. Furthermore, these miRNAs were found to target genes that have been reported to have epigenetic changes following an epigenome­wide association study of brain tissues of patients with PSP. This suggested that these miRNAs and genes may have some involvement in the pathogenesis of PSP. However, the sample size of the present study was small; therefore, a greater number of patients with PSP should be examined in future studies.

Effect of efonidipine on TGF-ß1-induced cardiac fibrosis through Smad2-dependent pathway in rat cardiac fibroblasts.

Transforming growth factor beta-1 (TGF-ß1) plays a critical role in progression of cardiac fibrosis, which may involve intracellular calcium change. We examined effects of efonidipine, a dual T-type and L-type calcium channel blocker (CCB), on TGF-ß1-induced fibrotic changes in neonatal rat cardiac fibroblast. T-type and L-type calcium channel mRNAs were highly expressed in cultured cardiac fibroblasts. TGF-ß1 (5 ng/mL) significantly increased Smad2 phosphorylation and [(3)H]-leucine incorporation, which were attenuated by pretreatment with efonidipine (10 µM). Neither R(-)efonidipine (10 µM), selective T-type CCB, nor nifedipine (10 µM), selective L-type CCB, efficaciously inhibited both TGF-ß1-induced Smad2 phosphorylation and [(3)H]-leucine incorporation. However, both were markedly attenuated by combination of R(-)efonidipine and nifedipine, EDTA, or calcium-free medium. Pretreatment with Smad2 siRNA significantly attenuated [(3)H]-leucine incorporation induced by TGF-ß1. These data suggest that efonidipine elicits inhibitory effects on TGF-ß1- and Smad2-dependent protein synthesis through both T-type and L-type calcium channel-blocking actions in cardiac fibroblasts.

Rapid Eye Movement Sleep Behavior Disorder-like Symptoms Due to Arousal Responses Associated with Severe Obstructive Sleep Apnea-hypopnea.

A 78-year-old man suspected of having α-synucleinopathies received a high score on a validated questionnaire for rapid eye movement (REM) sleep behavior disorder (RBD). Although he did in fact have unpleasant dreams and vigorous behaviors, polysomnography (PSG) found only obstructive sleep apnea-hypopnea (OSAH). The RBD-like symptoms corresponded with arousal responses, namely augmented inspiratory effort and leg movements, to his frequent apnea-hypopnea events during REM sleep. Thus, severe OSAH might cause RBD-like symptoms. PSG can discriminate real RBD from RBD-like symptoms associated with severe OSAH and therefore may be essential for determining an appropriate course of treatment in certain patients.

Ascending spinal tract formation in chick embryo originating from different spinal regions.

The present study aimed to assess spinal tract formation in neurons originating from cervical (C7), brachial (C14), and thoracic (T4) regions, with the lumbar (LS2) region as a reference, in a chick embryo. For the assessment of the spinal tracts, we introduced a vector expressing human placental alkaline phosphatase into progenitor cells generated after neural tube closure and belonging to the above segments, using in ovo electroporation. The ascending axons took primarily similar paths: dorsal commissural, ventral commissural, and dorsal non-commissural paths, with some variance depending on their originating segments. Some populations of non-commissural neurons later extended their axons following a ventral path. The elongation rates of these axons are primarily constant and tended to increase over time; however, some variations depending on the originating segments were also observed. Some of the dorsally ascending axons entered into the developing cerebellum, and spinocerebellar neurons originating from T4 projected their axons into the cortex of the cerebellum differently from those from LS2. These results unveil an overall picture of early ascending spinal tract formation.

Premedication of hemin for eradication therapy of Helicobacter pylori in patients with porphyria.

Eradication therapy of Helicobacter pylori may be safe if hemin has been intravenously administered in advance, even in patients with a history of recurrent acute porphyria attack.

Gastrointestinal Residue Removal Using a Balloon Overtube under Ultrathin Endoscopic Navigation: Ex Vivo and In Vivo Experimental Studies.

Pooled gastric residues involving blood clots and food interrupt appropriate endoscopic intervention, leading to poor outcomes in endoscopic hemostasis and lifesaving. However, procedures and devices that enable the effective removal of gastrointestinal residues remain unsatisfactory. This study aimed to evaluate the efficacy and safety of our developed suction method in ex vivo and in vivo studies. We created a hand-made device with a large suction diameter, consisting of a balloon overtube and an ultrathin endoscope for navigation. In the ex vivo study, we compared the success rate and the suctioning time for four types of simulated residue between a standard endoscope and our device. Our device had s significantly higher suction ability and a shorter procedure time than the standard endoscope. The subsequent in vivo animal study involved five beagle dogs that were administered with food jelly to mimic gastric residue. Suction was performed twice for five dogs (ten attempts). The outcome measure was the successful procedure rate; secondary outcomes were procedure-associated complications and procedure time. The procedure was successful in all attempts, without any complications. The mean procedure time was 5 min. This novel method enabled the efficient and safe removal of gastric residue, and our findings will likely lead to the development of the instrument.

An autopsy case of Creutzfeldt-Jakob disease with a V180I mutation of the PrP gene and Alzheimer-type pathology.

We report an autopsy case of Creutzfeldt-Jakob disease with a codon 180 point mutation of the prion protein gene (PRNP). A 77-year-old woman developed gait instability, followed by dementia and limb/truncal ataxia. She became akinetic and mute 18 months and died of pneumonia 26 months after the disease onset. Analysis of the PRNP gene revealed a codon 180 point mutation. Post-mortem examination revealed marked spongiosis, neuronal loss, and astrocytic gliosis in the cerebral cortex. Mild to moderate spongiosis and neuronal loss were observed in the limbic cortex and basal ganglia. There was no spongiform change in the hippocampus, brain stem or cerebellum. Many senile plaques and neurofibrillary tangles were found, and the Braak stages were stage C and stage IV, respectively. Immunostaining for prion protein (PrP) revealed granular (synaptic-type) and patchy PrP deposition in the cerebral cortex and especially in the hippocampus. Most patchy PrP deposits were colocalized with amyloid beta plaques, but some of them were isolated. The relatively strong PrP deposition and coexistence of Alzheimer-type pathology of this case are remarkable. We suppose that amyloid beta plaques might act as a facilitating factor for PrP deposition.

Light exercise without lactate elevation induces ischemic tolerance through the modulation of microRNA in the gerbil hippocampus.

Previously we studied the possible neuroprotective effects of ischemia-resistant exercise in a gerbil model of transient whole-brain ischemia and evaluated the histology, expression of specific proteins, and brain function under different conditions. The present study investigated the neuroprotective effects of light exercise, without lactate elevation, in a gerbil model of ischemia/reperfusion injury. Transient whole-brain ischemia was induced by occlusion of the bilateral common carotid arteries for 5 min. A group of animals was subjected to treadmill exercise before ischemia induction. Hippocampal neuronal damage and miRNA expression, as well as behavioral deficits and plasma lactate levels, were evaluated. Light exercise suppressed hippocampal neuron loss and preserved short-term memory. Moreover, 14 miRNAs (mmu-miR-211-3p, -327, -451b, -711, -3070-3p, -3070-2-3p, -3097-5p, -3620-5p, -6240, -6916-5p, -6944-5p, 7083-5p, -7085-5p, and -7674-5p) were upregulated and 6 miRNAs (mmu-miR-148b-3p, -152-3p, -181c-5p, -299b-5p, -455-3p, and -664-3p) were downregulated due to ischemia. However, the expression of these miRNAs remained unchanged when animals performed light exercise before the ischemic event. Differentially expressed miRNAs regulate multiple biological processes such as inflammation, metabolism, and cell death. These findings suggest that light exercise reduces neuronal death and behavioral deficits after transient ischemia by regulating hippocampal miRNAs.

Repeated anti-N-methyl-D-aspartate receptor encephalitis coexisting with anti-myelin oligodendrocyte glycoprotein antibody-associated diseases: A case report.

The coexistence of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated diseases has been reported. We report the case of a 36-year-old woman who presented with repeated typical anti-NMDAR encephalitis coexisting with unusual symptoms not consistent with anti-NMDAR encephalitis. Apart from the anti-NMDAR encephalitis, her first episode was characterized by balance disability with bilateral medial frontal cortical lesions, suggesting the involvement of the cortico-reticular projections and the basal ganglia-brainstem projections. The second episode presented with Broca's aphasia caused by involvement of the Broca's area and lower part of the precentral gyrus. The detection of MOG-Ab in both episodes suggested the coexistence of MOG-Ab-associated diseases. Thus, an evaluation of MOG-Ab should be considered when anti-NMDAR encephalitis presenting with atypical symptoms is encountered.

Orexin secretion abnormality involved in excessive somnolence in CNS lymphoma without hypothalamic lesions.

A 72-year-old woman developed excessive somnolence as one of the symptoms of diffuse large B-cell lymphoma in the central nervous system (CNS). Although somnolence might be caused by reduced orexin secretion associated with hypothalamic lesions, neither brain MRI nor 18F-fluorodeoxyglucose positron emission tomography identified hypothalamic lesions. However, the decreased cerebrospinal fluid (CSF) orexin levels recovered to near normal values with improvement of somnolence after chemotherapy. The alteration of CSF orexin levels suggested the involvement of potential hypothalamic lesions. Therefore, measurements of CSF orexin levels may be useful for understanding the pathological background of somnolence in CNS lymphoma without hypothalamic lesions.