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BackgroundNeurological 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 presentationAn 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.ConclusionThe 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.

What is known and objective Ifosfamide, an alkylating agent, is widely used in the treatment of malignant diseases. However, these treatments are often limited due to the incidence of neuropsychiatric symptoms such as delirium, seizures, hallucinations and agitation. In this study, we examined risk factors for neuropsychiatric symptoms in patients receiving ifosfamide-based chemotherapy. Methods The study cases were patients with cancer receiving ifosfamide-based chemotherapy between April 2007 and March 2018. Risk analysis for ifosfamide-related neuropsychiatric symptoms was determined by time-dependent Cox proportional hazard regression analysis. Results and discussion Of 183 eligible patients, 32 patients (17.5%) experienced ifosfamide-related neuropsychiatric symptoms. Time-dependent Cox proportional hazard model showed that the albumin-bilirubin (ALBI) score was significantly correlated with the incidence of ifosfamide-related neuropsychiatric symptoms (hazard ratio [HR] =1.45, 95% confidence interval [CI] = 1.05-2.01, p = 0.025). Additionally, there were correlations between the predicted risk of neuropsychiatric symptoms and ifosfamide-dose per cycle (HR =0.51, 95% CI = 0.27-0.94, p = 0.030) and creatinine clearance (Ccr) (HR = 0.53, 95% CI = 0.28-1.00, p = 0.050). In contrast, neither serum albumin nor total bilirubin was a significant risk factor for neuropsychiatric symptoms. What is new and conclusion These findings indicate that ALBI score may be a useful biomarker for predicting neuropsychiatric symptoms in patients receiving ifosfamide-based chemotherapy.

Swallowing function in long-term survivors of Creutzfeldt-Jakob disease (CJD) has not been elucidated. Herein, we report a patient with MM2-cortical-type sporadic CJD (MM2C-type sCJD) with long-term preservation of pharyngeal swallowing function using videofluoroscopic (VF) examination of swallowing. A 55-year-old woman was admitted to hospital because of dyscalculia and memory disturbance 3 years after the onset of these symptoms. Neurological examination revealed dementia, extrapyramidal signs, and delusion. Diffusion-weighted MRI revealed bilateral hyperintensity in the basal ganglia and frontal, temporal, and parietal cortices. No mutation with the methionine homozygote at codon 129 was found on PRNP gene analysis. VF was performed 68 months after the onset. Although bolus transport from the oral cavity to the pharynx worsened, the pharyngeal swallowing function was preserved even 68 months after onset. Serial MRI examinations revealed no apparent atrophy of the brainstem. Single photon emission computed tomography revealed that the regional cerebral blood flow in the brainstem was preserved. These findings suggest that pseudobulbar palsy is the pathophysiology underlying dysphagia in long-term survivors of MM2C-type sCJD, probably owing to preserved brainstem function even in a state of akinetic mutism.

In Kyudo (Japanese archery), there are four disorders that hinder an archer's performance: Hayake (releasing the bow too early), Motare (unable to release the bow when intended), Biku (jerking when aiming), and Yusuri (shaking when drawing the bow, or aiming). These disorders are similar to Yips, a psycho-neuromuscular movement disorder, recognized in various sports, but few studies have examined yips in Kyudo. This study examined the frequency, classification, and risk factors of yips in Kyudo among medical students. The results showed that 41 of 65 students (63.1%) experienced at least one disorder. The frequency of Hayake was the highest (35 patients; 85.3%). An experience of playing was associated with the increased risk of yips in Kyudo. Motare was the only disorder that appeared on its own, and without complications from other disorders. Based on its characteristics, it was suspected that task-specific focal dystonia involved in Motare.

A 70-year-old dextral woman was admitted to a hospital with agraphia for kanji (Japanese morphograms). She had a history of severe constipation, nightmares, and visual hallucinations. Neurological examinations revealed no obvious Parkinson's disease symptoms. She showed poor skills in writing the kanji for looking at picture objects, [e.g., writing the Japanese word “inu” (which means dog) when she saw a drawing of a dog] or dictated words. A reduced striatal uptake of [123I]-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) on single-photon-emission computed tomography and reduced meta-iodobenzylguanidine (MIBG) cardiac uptake on myocardial scintigraphy were detected. The accumulation of amyloid beta in the bilateral cerebral cortices was observed on amyloid-positron emission tomography. We herein report a case of Lewy body dementia with pure agraphia for kanji with underlying Alzheimer's disease pathology.

A 25-year-old woman had convulsions and disturbance of consciousness. Head magnetic resonance imaging (MRI) showed punctate areas in the occipital lobes with increased signals on T2-weighted imaging. The MRI abnormalities responded well to steroid pulse therapy, so we made a diagnosis of posterior reversible encephalopathy syndrome (PRES). Three months later, she developed a fever and dyspnea. Chest computed tomography revealed marked thickness of the tracheal and bronchial wall, and bronchoscopy showed a cobble-stone appearance of the tracheal mucosa, indicative of relapsing polychondritis (RPC). We consider that PRES had developed due to autoimmune vasculitis in the brain with RPC.

Swallowing function in long-term survivors with Creutzfeldt-Jakob disease (CJD) remains unknown. Herein, we demonstrated serial evaluation of swallowing function in a case with V180I genetic CJD (gCJD) using videofluoroscopic examination of swallowing (VF). A 69-year-old woman was admitted to our hospital because of bradykinesia and memory disturbances 4 months after the onset of symptoms. Neurological examination revealed dementia, bradykinesia and frontal signs. Diffusion-weighted MRI revealed bilateral cortical hyperintensity in the frontal, temporal, and parietal cortices, and PRNP gene analysis indicated a V180I mutation. Her dysphagia gradually progressed, and she received percutaneous gastrostomy 42 months after the onset. VF was performed at 27, 31, 39, and 79 months after the onset. Although bolus transport from oral cavity to pharynx gradually worsened and initiation of the pharyngeal swallow was gradually delayed, the pharyngeal swallowing function was preserved even at 72 months after onset. MRI revealed no apparent atrophy of brainstem, and single photon emission computed tomography showed preserved regional cerebral blood flow in the brainstem. These findings suggest that the pathophysiology of dysphagia in a long-term survivor of V180I gCJD is that of pseudobulbar palsy, likely owing to preserved brainstem function even in the akinetic mutism state.

A 57-year-old woman with amyotrophic lateral sclerosis (ALS) receiving mechanical ventilation developed intractable right temporal headache. She was diagnosed with brain abscess secondary to chronic suppurative otitis media. In this case, the otitis media was caused by nasopharyngeal reflux associated with eustachian tube muscle weakness and a supine position. In addition, ALS patients under mechanical ventilation have a limited ability to convey their pain. Their complaints are often overlooked because many physicians do not know that pain is common in ALS. Physicians should recognize brain abscess as a severe complication of ALS and listen to the complaints of these patients.

Ifosfamide is extensively used to treat several malignant conditions. Administration of ifosfamide can cause encephalopathy and other neurotoxic effects. The aim of this study was to obtain novel information on the onset profiles of ifosfamide-induced encephalopathy (IIE) considering other associated clinical factors using the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) databases. We analyzed the reports of encephalopathy between 2004 and 2018 from the FAERS and JADER databases. To define IIE, we used the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms and standardized queries. The reporting odds ratios (ROR) at 95% confidence interval (CI) was used to detect the signal for IIE and adjusted for covariates using a multivariate logistic regression technique. We evaluated the time-to-onset profile of IIE and used the association rule mining technique to discover undetected associations, such as potential risk factors. In the FAERS database, the ROR (CI) for encephalopathy (preferred term, PT) and encephalopathy (standardized MedDRA queries, SMQ) was 56.58 (51.69–61.93) and 1.57 (1.48–1.67), respectively. In the JADER database, the ROR (95% CI) for encephalopathy (PT) and encephalopathy (SMQ) was 13.54 (9.91–18.50) and 1.24 (1.01–1.53), respectively. The multivariate logistic regression analysis showed a significant contribution in IIE signal in the ≥ 60 year group (p = 0.00094; vs.

Here, we report an autopsy-verified patient with MM2-coritical-type sporadic Creutzfeldt-Jakob disease (MM2C-type sCJD) presenting cortical blindness during a course of glaucoma and age-related macular degeneration, and focus on the difficulties involved in early clinical diagnosis. An 83-year-old man was admitted to our hospital 15 months after the onset of cortical blindness, and 9 months after the onset of progressive dementia. Neurological examination revealed dementia, frontal signs, visual disturbance, dysphagia, myoclonus and exaggerated tendon reflexes in the four extremities. Diffusion-weighted MRI (DW-MRI) showed cortical hyperintensities predominantly in the bilateral occipital lobes. PRNP gene analysis showed no mutations with methionine homozygosity at codon 129. Cerebrospinal fluid (CSF) examination revealed elevation of 14–3-3 and total tau protein. The symptoms progressed gradually, and the patient died of aspiration pneumonia, 30 months after the onset. Neuropathological examination revealed extensive large confluent vacuole-type spongiform changes in the cerebral cortices. Prion protein (PrP) immunostaining showed perivascular and plaque-type PrP deposits. We diagnosed our patient as MM2C-type sCJD. There are two difficulties in the early clinical diagnosis of MM2C-type sCJD with ocular disease in the elderly; delayed utilization of DW-MRI, and accompaniment of ocular disease. For early diagnosis of MM2C-type sCJD, we conclude that clinician should perform DW-MRI for patients with isolated dementia or cortical visual disturbance.

Background The treatment of chronic pancreatitis requires a surgical approach in patients who are refractory to medical therapy. During surgical treatment, ductal decompression is required, but a pancreatectomy is necessary for some patients, such as those with severe stenosis of the pancreatic duct. Indeed, suboptimal procedures lead to recurrent pancreatitis. We used a laparoscopic hybrid approach for patients with severe stenosis of the pancreatic duct. In this report, we present the feasibility and outcomes of our approach. Methods We selected a laparoscopic approach for the distal pancreatectomy, which is relatively safe and the effect of reducing the length of the wound is substantial. We selected an open approach for the Frey procedure because complete ductal compression has a high risk for injury to the vessels posterior to the pancreas. We recorded the operative outcomes, postoperative complications, and recurrence of pancreatitis. Results We performed the laparoscopic hybrid approach on 3patients between January and December 2018. There were no major intraoperative complications (Clavien-Dindo classification IIIa or more) and the postoperative course was uneventful in all patients. There were no recurrences of pancreatitis and no postoperative pain in all patients in > 2 years of follow-up. Conclusion Our hybrid method with a focus on complete ductal compression with safety and minimal invasiveness might be the optimal approach for the surgical treatment of chronic pancreatitis that requires a pancreatectomy with the Frey procedure.

Background: The treatment of chronic pancreatitis requires a surgical approach in patients refractory to medical therapy. During surgical treatment, ductal decompression is required, but a pancreatectomy is necessary for some patients, such as those with severe stenosis of the pancreatic duct. Importantly, inadequate procedures lead to recurrent pancreatitis. We used a novel minimally invasive approach for patients with severe stenosis of the pancreatic duct. In this report, we aim to present the feasibility and outcomes of our approach. Methods: We selected a laparoscopic approach for the distal pancreatectomy because these parts are relatively safe and the effect of reducing the length of the wound is substantial. We selected an open approach for parts of the Frey procedure because complete ductal compression has a high risk for injury to the vessels posterior to the pancreas. We examined operative outcomes, postoperative complications and recurrence of pancreatitis.Results: Our approach was performed in three patients from January 2018 to December 2018. No intraoperative complications occurred and the postoperative course was uneventful in all patients. There were no recurrence of pancreatitis and no postoperative pain in all patients in the over two years follow-up. Conclusion: Our hybrid method focusing on complete ductal compression with safety and minimal invasiveness is the optimal approach for the surgical treatment of chronic pancreatitis which requires a pancreatectomy with the Frey procedure.

Background An epithelial cyst in an intrapancreatic accessory spleen (ECIPAS) is rare. We report a case of ECIPAS that was treated with robot-assisted distal pancreatectomy with splenectomy. Case presentation The case was a 59-year-old woman who was referred to our hospital after a pancreatic tail tumor was found on computed tomography prior to surgery for small bowel obstruction at another hospital. A cystic lesion in the pancreatic tail was discovered and evaluated by magnetic resonance imaging and endoscopic ultrasonography. Based on clinical and radiological features, mucinous cystic neoplasm was included in the differential diagnosis. The patient underwent robot-assisted distal pancreatectomy with splenectomy. The postoperative course was uneventful. Pathological evaluation revealed a 20-mm ECIPAS in the pancreatic tail. Conclusions If a pancreatic tail tumor is present, ECIPAS should be included in the differential diagnosis. However, preoperative diagnosis is difficult, and a definitive diagnosis is often not obtained until after surgery. Surgery should be minimally invasive. Laparoscopic distal pancreatectomy has become a standard surgical procedure because it is minimally invasive. Robot-assisted surgery is not only minimally invasive, but also advantageous, because it has a stereoscopic magnifying effect and allows the forceps to move smoothly. Robot-assisted distal pancreatectomy may be a good option, when performing surgery for a pancreatic tail tumor.

Aim Intractable or persistent hiccups and nausea (IHN) are rarely associated with herpes zoster (HZ-IHN). We aimed to identify the clinical characteristics of HZ-IHN by comparing them with those of neuromyelitis optica spectrum disorder associated with IHN (NMOSD-IHN). Methods We collected 8 patients with HZ-IHN and 12 patients with NMOSD-IHN diagnosed between 2002 and 2020 from medical databases. Medical records including clinical information, laboratory data on serum anti-aquaporin 4 (AQP4) antibodies, serological or cerebrospinal fluid findings for the varicella zoster virus, medullary MRI findings, and efficacy of intravenous methylprednisolone pulse (IVMP) therapy were analyzed retrospectively. Results The age of onset (69 ± 13 years versus 46 ± 17 years, P = 0.003), percentage of men [7/8 patients (88%) versus 3/12 patients (25%), P = 0.020], serum CRP levels (1.41 ± 1.17 mg/dL versus 0.14 ± 0.33 mg/dL, P = 0.018), and frequency of hemi-cranial nerve involvement [6/8 patients (75%) versus 1/12 patients (8%), P = 0.004] were significantly higher in patients with HZ-IHN than in those with NMOSD-IHN. The hypoglossal and vagus nerves were involved in 5/8 patients (63%) with HZ-IHN. Other clinical parameters, excluding anti-AQP4 antibodies, were similar to those of NMOSD-IHN. MRI revealed ipsilateral hemi-dorsal medullar hyper-intense lesions in 5/8 patients (63%) with HZ-IHN. Acyclovir with IVMP therapy was effective for HZ-IHN. Conclusion Clinicians should include HZ-IHN in the differential diagnosis for IHN, and promptly administer acyclovir and IVMP therapy. HZ-IHN is frequently accompanied by lower hemi-cranial nerve palsies and ipsilateral hemi-dorsal medullary hyper-intensity on MRI. Data available statement The authors confirm that the data supporting the findings of this study are available within the article (Tables 1 and 2), or its supplementary materials (Table S1).

The clinical characteristics of genetic Creutzfeldt-Jakob disease (gCJD) with a V180I mutation in the PRNP gene (V180I gCJD) are unique: elderly-onset, gradual progression, sporadic fashion, and cortical oedematous hyper-intensity on diffusion-weighted MRI (DW-MRI). This phenotype may become a potential target of future clinical therapeutic trials. The average disease duration of V180I gCJD patients is 23–27 months; however, considerably long-term survivors are also reported. The factors influencing survival and the clinicopathological characteristics of long-term survivors remain unknown. Herein, we report clinicopathological findings of a long-term survivor of V180I gCJD. A 78-year old woman was admitted to our hospital due to dementia and left hand tremor approximately 1.5 months after symptom onset. Neurological examination revealed dementia, frontal signs, and left hand tremor at admission. She had no family history of dementia or other neurological disease. DW-MRI revealed cortical oedematous hyper-intensities in the bilateral frontal lobes and the right temporal and parietal lobes. PRNP gene analysis indicated a V180I mutation with methionine homozygosity at codon 129. The symptoms gradually progressed, and she died of aspiration pneumonia 61 months after symptom onset. Neuropathological examination revealed severe cerebral atrophy with moderate to severe gliosis, but the brainstem was well preserved. Various-sized and non-confluent vacuole type spongiform changes were extensively observed in the cerebral cortices. Prion protein (PrP) immunostaining revealed weak and synaptic-type PrP deposits in the cerebral cortices. We consider that long-term tube feeding, and very mild brainstem involvement may be associated with the long-term survival of our V180I gCJD patient.

A 61-year-old dextral woman was admitted to the hospital with difficulty finding words. Neurological examinations confirmed that her speech was affected by frequent pauses and occasional phonological paraphasia without cognitive deficits. We detected atrophy, hypoperfusion, and hypometabolism in the right perisylvian and parietal regions, expanding to the right anterior temporal lobes and right inferior frontal gyrus (opercular region) by magnetic resonance imaging, single-photon emission computed tomography, and fluorodexyglucose-positron emission tomography (PET), respectively. Amyloid-PET did not identify the accumulation of amyloid beta (Aβ) in the bilateral cerebral cortices. We herein report a case of crossed aphasia with Aβ-negative logopenic primary progressive aphasia that was likely the result of frontotemporal lobar degeneration.

The clinical features of cerebellar ataxia associated with anti-metabotropic glutamate receptor 1 (mGluR1) autoantibodies, a rare autoimmune-mediated cerebellar ataxia, remain to be elucidated. Here, we describe a patient with non-paraneoplastic cerebellar ataxia associated with anti-mGluR1 autoantibodies, who was followed up over 5 years. She presented with relapses and remissions of subacute progressive cerebellar ataxia that were responsive to immunotherapy. Although serum anti-mGluR1 autoantibodies were continuously detected and cerebellar atrophy gradually progressed, repeated intravenous immunoglobulin therapy and oral immunosuppressants ensured cerebellar ataxia remained at almost the same level during the observation period.

AIM Older patients are considered to be at high risk for developing adverse drug reactions (ADR), because they commonly receive multidrug therapy despite changes in pharmacokinetic function with age. In the present study, we assessed the relationship between the number of prescribed drugs and the incidence of ADR or the time to discharge in older patients with neuromuscular disease. METHODS A retrospective study was carried out among 135 older patients (aged ≥65 years) who were admitted to the neurology ward from October 2007 through December 2011. Drugs that possess a high risk for initiation of grade ≥2 ADR were determined using logistic regression analysis. RESULTS A total of 38 patients (28.1%) experienced grade ≥2 ADR. Multivariate logistic regression analysis showed that corticosteroids, antibiotics, enteric nutrients and insulin were significant risks for grade ≥2 ADR. Notably, the time to discharge extended as the grade of ADR increased, with mean values of 24.4 days for grade 0, 38.3 days for grade 1, 47.5 days for grade 2 and 73.1 days for grade 3-4 events. Furthermore, the number of high-risk drugs for grade ≥2 ADR correlated well with the incidence of grade ≥2 events (R = 0.964, P = 0.008), as well as with the time to discharge (R = 0.473, P

Assessing central nervous system (CNS) involvement in patients with lymphoma or carcinoma is important in determining therapy and prognosis. Progranulin (PGRN) is a secreted glycosylated protein with roles in cancer growth and survival; it is highly expressed in aggressive cancer cell lines and specimens from many cancer types. We examined PRGN levels by Enzyme Immuno-Assay (EIA) in cerebrospinal fluid (CSF) samples from 230 patients, including 18 with lymphoma [12 with CNS metastasis (CNS+); 6 without CNS metastasis (CNS-)], 21 with carcinomas (10 CNS+; 11 CNS-), and 191 control patients with non-cancer neurological diseases, and compared PRGN levels among these disease groups. Median CSF PGRN levels in the CNS+ lymphoma group were significantly higher than in the CNS- lymphoma and control non-cancer groups; and were also significantly higher in the CNS+ carcinoma group than in the CNS- carcinoma and control groups, except for patients with infectious neurological disorders. Receiver operating characteristic curve analyses revealed that CSF PGRN levels distinguished CNS+ lymphoma from CNS- lymphoma and non-cancer neurological diseases [area under curve (AUC): 0.969]; and distinguished CNS+ carcinomas from CNS- carcinomas and non-cancer neurological diseases (AUC: 0.918). We report here, for the first time, that CSF PGRN levels are higher in patients with CNS+ lymphoma and carcinomas compared to corresponding CNS- diseases. This would imply that measuring CSF PGRN levels could be used to monitor CNS+ lymphoma and metastasis.

A 61-year-old woman was admitted to our hospital due to memory difficulties, visual hallucinations, and slowly progressing motor difficulties in the limbs. A clinical examination revealed bradykinesia, gait disturbance, left-side-dominant rigidity, ideomotor apraxia, dressing apraxia, left-sided spatial agnosia, impaired visuospatial ability, and executive dysfunction. Her symptoms were unresponsive to levodopa, and corticobasal syndrome (CBS) was diagnosed. One year later, amyloid positron emission tomography revealed amyloid beta accumulation in the bilateral cerebral cortices; at this point, CBS with underlying Alzheimer's disease pathology (CBS-AD) was diagnosed. Visual hallucinations may help differentiate CBS with corticobasal degeneration (CBS-CBD) from other pathologies, including CBS-AD.

Background Chronic neuroinflammation has been implicated in Alzheimer's disease (AD) pathology. Objective To investigate the association between cytokine and anti-amyloid-β (Aβ) autoantibody levels and the degree of brain atrophy and cognitive impairment in AD patients. Methods Cerebrospinal fluid (CSF) levels of C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 8, C-X-C motif chemokine ligand 10, interleukin 6, and anti-Aβ autoantibody were evaluated in 69 AD patients. Serum levels of CCL2 and anti-Aβ autoantibody were also examined. The degree of brain atrophy was assessed using the voxel-based specific regional analysis system for AD, which targets the volumes of interest (VOI) in medial temporal structures. Cognitive function was evaluated by neuropsychological testing, including the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB). Results CSF CCL2 levels correlated significantly with the severity (p = 0.023) and the extent (p = 0.022) of VOI atrophy, and with the extent of gray matter atrophy (p = 0.039) in AD patients. CSF anti-Aβ autoantibody levels were inversely correlated with the severity of VOI atrophy (p = 0.020), the extent of VOI atrophy (p = 0.015), and the ratio of VOI/GM atrophy (r = -0.358, p = 0.004). CSF CCL2 levels were also inversely correlated with MMSE (p = 0.0497) and FAB scores (p = 0.016). Conclusions CSF CCL2 levels are associated with the degree of medial temporal lobe and gray matter atrophy, and cognitive decline in AD.

We report the case of a 76-year-old woman presenting with 47-month history of progressive dementia and cortical blindness with no family history. Antibodies against thyroid glands and the N-terminus of α-enolase (NAE) were detected in her serum. Neurological examination revealed progressive dementia, frontal signs, visual disturbance, and exaggerated bilateral tendon reflexes in both legs. Diffusion MRI showed cortical hyper-intensities in the bilateral occipital and parietal, and the left frontal and temporal cortices. 99mTc-ethyl cysteinate dimer-single photon emission computed tomography indicated decreased regional cerebral blood flow throughout the bilateral parietal lobes and partially in the left frontal and temporal lobes. PRNP gene analysis showed no mutations with methionine homozygosity at codon 129 in peripheral blood. Cerebrospinal fluid examination, including 14-3-3 and total tau protein detection, revealed normal levels; however, prion proteins were amplified by the real-time quaking-induced conversion method. Hashimoto's encephalopathy was excluded on the basis of unresponsiveness to corticosteroids. The symptoms progressed slowly. Periodic sharp-wave complexes were observed on electroencephalogram 36 months after the onset of symptoms; the patient reached a state of akinetic mutism at 47 months. This was a probable case of MM2-cortical-type sCJD with anti-NAE antibodies based on the World Health Organization (WHO) diagnostic criteria for sCJD, genetic information, and the slowly progressive course. However, this case did not meet with the probable WHO diagnostic criteria until 3 years after symptom onset, highlighting the difficulty of diagnosing a living case of the MM2-type of sCJD. Therefore, establishment of clinical diagnostic criteria for MM2-type of sCJD is required.

We examined anti-complement C1q (C1q) autoantibody levels in serum and cerebrospinal fluid (CSF) samples of patients with neuromyelitis optica spectrum disorders (NMOSD). We analyzed the correlations between anti-C1q autoantibody levels and the clinical and other CSF characteristics of NMOSD. Serum and CSF anti-C1q autoantibody levels increased during the acute phase of NMOSD, reverting to the same levels as controls during remission. CSF anti-C1q autoantibody levels during the acute phase correlated with several markers reflecting disease severity, Expanded Disability Status Scale worsening, spinal cord lesion length in cases with myelitis, CSF protein and interleukin-6 levels, and CSF/serum albumin ratios.

Objective To address occipital neuralgia in patients with neuromyelitis optica spectrum disorder (NMOSD). Background NMOSD is an inflammatory demyelinating disease that commonly presents with pain; however, headache symptoms have received little attention. Methods We presented three cases of NMOSD in which the patients experienced acute-onset, severe, and steroid-responsive occipital neuralgia. All patients provided consent to use their demographic and imaging data retrospectively. Results In all three cases, MRI revealed a new high-intensity area in the cervical cord at the C1-C3 level of the spine, which was diminished in two of the three cases after corticosteroid pulse therapy. Conclusion Our cases support the recognition of NMOSD as a cause of secondary headache. As patients with NMOSD experience severe occipital neuralgia, a relapse should be considered and a cervical MRI should be performed.

To report the findings in a 72-year-old man with neuronal intranuclear hyaline inclusion disease (NIHID) with the negative-type electroretinogram (ERG) and without night blindness. Standard ophthalmological examinations including the medical history, measurements of the best-corrected visual acuity and intraocular pressures, slit-lamp biomicroscopy, ophthalmoscopy, spectral-domain optical coherence tomography, fundus autofluorescence, and perimetry were performed. In addition, neurological and electrophysiological examinations were performed. NIHID was confirmed by skin biopsy. The ophthalmologic examinations revealed sluggish pupillary reflexes without visual disturbances and retinal abnormalities. The amplitudes of the dark-adapted 0.01 ERG was absent, and light-adapted 3 ERG and light-adapted 30 Hz flicker ERG were reduced in amplitude and delayed in implicit time. The rod system was more severely affected than the cone system, indicating that NIHID is classified as one of rod-cone dysfunction syndrome. The dark-adapted 3 ERG consisted of a markedly reduced b-wave with larger a-wave (negative ERG), but the amplitude of a-wave was smaller than normal. Since the ophthalmoscopical findings and the subjective visual functions may be essentially normal, the characteristic ERG abnormalities can be an important findings in adult-onset NIHID without night blindness.

A 71-year-old woman with a 9-year history of Parkinson's disease was admitted to our hospital emergently because of consciousness disturbance. Her consciousness level was 200 on the Japan coma scale (JCS), and she presented with tenderness and distension of the lower abdomen. Brain computed tomography showed normal findings. Blood tests showed an increased ammonia level (209 μg/dl) with normal AST and ALT levels. We catheterized the bladder for urinary retention. Five hours after admission, the blood ammonia level decreased to 38 μg/dl, and her consciousness level improved dramatically. Corynebacterium urearyticum, a bacterial species that produces urease, was detected by urine culture. Therefore, she was diagnosed with hyperammonemic encephalopathy resulting from urinary tract infection caused by urease-producing bacteria. In this case, urologic active agents had been administered to treat neurogenic bladder. We suspect that these drugs caused urinary obstruction and urinary tract infection. It is important to recognize that obstructive urinary tract infection caused by urease-producing bacteria can cause hyperammonemia. Neurological disorders, such as Parkinson's disease, tend to complicate neurogenic bladder. This disease should be considered in elderly patients with Parkinson's disease who are receiving urologic active drugs.

A 32-year-old woman experienced several episodes of transient numbness on the left side of her face and body. MR angiography revealed severe stenosis in the right middle cerebral artery (MCA). Abnormal collateral vessel networks were not observed, and idiopathic MCA stenosis was diagnosed. She underwent superficial temporal artery (STA)-MCA anastomosis of the right hemisphere. The surgery eliminated the transient ischemic attacks; however, she developed hemiballism in the left side of her face and left upper limb 2 weeks after the surgery. The ballism disappeared 1.5 years after onset without any treatments. A few patients with development of chorea after STA-MCA anastomosis has been reported in moyamoya disease, but not in those with MCA stenoses. It has been previsouly reported that the development of an involuntary movement might be associated with hypermetabolism in the contra lateral striatum after STA-MCA anastomosis. We considered that a similar mechanism may have caused hemiallism in our patient. We need to recognize that STA-MCA anastomosis could cause hemichorea or hemiballism.

Causative genes in patients with idiopathic basal ganglia calcification (IBGC) (also called primary familial brain calcification (PFBC)) have been reported in the past several years. In this study, we surveyed the clinical and neuroimaging data of 70 sporadic patients and 16 families (86 unrelated probands in total) in Japan, and studied variants of PDGFB gene in the patients. Variant analyses of PDGFB showed four novel pathogenic variants, namely, two splice site variants (c.160 + 2T > A and c.457−1G > T), one deletion variant (c.33_34delCT), and one insertion variant (c.342_343insG). Moreover, we developed iPS cells (iPSCs) from three patients with PDGFB variants (c.160 + 2T > A, c.457−1G > T, and c.33_34 delCT) and induced endothelial cells. Enzyme-linked immunoassay analysis showed that the levels of PDGF-BB, a homodimer of PDGF-B, in the blood sera of patients with PDGFB variants were significantly decreased to 34.0% of that of the control levels. Those in the culture media of the endothelial cells derived from iPSCs of patients also significantly decreased to 58.6% of the control levels. As the endothelial cells developed from iPSCs of the patients showed a phenotype of the disease, further studies using IBGC-specific iPSCs will give us more information on the pathophysiology and the therapy of IBGC in the future.

The clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy remain to be elucidated. We describe here the clinical features of 14 patients with GFAP astrocytopathy confirmed by detection of GFAP-IgG in cerebrospinal fluid (CSF). The novel findings of this study are as follows. First, over half of the patients presented with movement disorders (tremor, myoclonus, and ataxia), autonomic dysfunction (mainly urinary dysfunction), and hyponatremia. Second, most patients showed transient elevation of adenosine deaminase activity levels in CSF. Finally, some patients showed bilateral hyperintensities in the posterior part of the thalamus on brain magnetic resonance imaging.

The 3D measurement of dynamic knee kinematics under in vivo conditions is highly valuable for understanding the effects of joint diseases, dysfunction and for evaluating the outcome of surgical procedures. For artificial knee implants, to achieve 3D measurement of the dynamic kinematics, 2D/3D registration techniques which use X-ray fluoroscopic images and computer-aided design model of the implants have been applied to clinical cases. These fluoroscopic techniques have also been applied for motion measurement in joints without implants in recent years, where 3D bone models created from CT or MRI images are utilized. In previous studies, however, the pose estimation accuracy for patella was not sufficient for analyzing 3D knee kinematics, particularly out-of-plane rotation error was relatively large because of small shape and poor geometrical feature of patella. Therefore, this study presents a method to determine 3D kinematics of patella using single-plane fluoroscopic image. The 3D pose of patella is estimated using an intensity-based 2D/3D registration technique, which uses a digitally reconstructed radiography (DRR) image created from 3D bone volume model. The 3D bone volume model for patella was created using CT scan data from a single subject. The 3D pose of the patella model is estimating by maximizing similarity measures between the DRR and fluoroscopic images iteratively with an optimization technique. In order to validate the pose estimation accuracy of patella including femur and tibia/fibura using the intensity-based 2D/3D registration, computer simulation test was performed. A set of synthetic silhouette images was created for each knee model in known typical orientations, and the test was carried out using three similarity measure methods. The result of computer simulation test showed that the root mean square errors were around 1.0 mm, 1.0° except for out-of-plane translation, and the reliability and feasibility of present method was demonstrated.

Because clinical data to confirm the safety and effectiveness of fosphenytoin, a prodrug of phenytoin, are insufficient, the length of administration of fosphenytoin is restricted. Nevertheless, some cases require fosphenytoin administration for more than a few days. The aim of this study was to retrospectively investigate the serum concentration of phenytoin in adult Japanese patients who received intravenous fosphenytoin therapy for more than 3 days.Patients injected with intravenous fosphenytoin for more than 3 days at Gifu University Hospital between January 2012 and September 2014 were enrolled. Individual pharmacokinetic parameters were predicted by Bayesian estimation using NONMEM software, and the maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration (10-20 mcg/mL) was calculated from the parameters.Among a total of 8 patients, the serum trough concentration of phenytoin decreased with each day after repeated injection of fosphenytoin. The incidence rate of significant convulsive seizures was increased time dependently (0% on day 1, 12.5% on day 2, 25% on day 3, and 66.7% on day 4 and after). Phenytoin clearance showed a time-dependent increase. The maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration was simulated to be 779.8 ± 316.8 mg/d, a dose that was markedly higher than the actual maintenance dose (414.1 ± 55.7 mg/d).Prolonged use of fosphenytoin, for such patients as those with autoimmune-mediated encephalopathy accompanied with reflux disease and/or ileus, time dependently decreased the serum concentration of phenytoin and increased the risk of convulsion. Therefore, the maintenance dose should be increased to maintain the therapeutic serum concentration.

Drug-induced pressure ulcer (DIPU), which is a newly recognized adverse drug reaction, is associated with the administration of psychiatric drugs in geriatric patients with dementia. The notification of the causative drugs is crucial to the treatment of DIPU. We herein report the case of a 56-year-old woman with early-stage Parkinson's disease who developed DIPUs after starting olanzapine treatment for depressive symptoms. Our findings illustrate that if an akinetic patient with pressure ulcers is encountered, the patient's medication should be reviewed by a multidisciplinary team, to evaluate whether the development of the pressure ulcer is drug-related, regardless of the patient's age.

We report a case of autopsy-verified MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD) in a 46-year-old patient with a 16-month history of abnormal behavior, progressive dementia, insomnia, and speech disturbances without family history. Neurological examination revealed progressive dementia, frontal signs, insomnia, speech disturbance, gait disturbance and bilaterally exaggerated tendon reflexes. Both brain MRI and cerebrospinal fluid examinations, including 14-3-3 protein, yielded normal results. An easy Z-score (eZIS) analysis for (99m)Tc-ethyl cysteinate dimer-single photon emission computed tomography ((99m)Tc-ECD-SPECT) revealed decreased regional cerebral blood flow in the bilateral thalami and medulla oblongata. PRNP gene analysis revealed methionine homozygosity at codon 129 without mutation. Neuropathological examinations revealed severe neuronal loss, gliosis, and hypertrophic astrocytosis in the medial thalamus and inferior olivary nucleus. A slight depletion of Purkinje cells was observed. PrP immunostaining showed no obvious PrP deposits in the basal ganglia, thalamus, cerebellum, or brainstem; however, mild synaptic-type PrP deposits with some smaller plaque-like structures were only partially observed in the localized region of the frontal lobe with the spongiform change. Western blot analyses of protease-resistant PrP showed a type 2 pattern. In conclusion, eZIS analysis of (99m)Tc-ECD-SPECT images is useful for detecting both thalamic and medullary lesions. This is the first case of medullary lesions detected in a live patient with MM2-thalamic-type sCJD using SPECT.

Creutzfeldt-Jakob disease (CJD) is characterized by rapidly progressing dementia with death usually occurring within 6 months. There is no verified disease-specific pre-mortem diagnostic test besides brain biopsy. We describe a 66 y old previously high functioning male who presented with a 5 month history of rapidly progressive dementia. Neurological examination revealed a score of 19/30 on MOCA testing. An extensive workup into various causes of dementia including electroencephalography and imaging studies was unremarkable. The cerebrospinal fluid was sent to National Prion Disease Center and it revealed elevated RT-QuIC levels with negative 14-3-3 and T tau proteins. Based on literature review, our case is one of few living subjects with elevated RT-QuIC levels and negative 14-3-3 and tau proteins.

Introduction Idiopathic basal ganglia calcification (IBGC), also called Fahr's disease or recently primary familial brain calcification (PFBC), is characterized by abnormal deposits of minerals including calcium mainly and phosphate in the brain. Mutations in SLC20A2 (IBGC1 (merged with former IBGC2 and IBGC3)), which encodes PiT-2, a phosphate transporter, is the major cause of IBGC. Recently, Slc20a2-KO mice have been showed to have elevated levels of inorganic phosphorus (Pi) in cerebrospinal fluid (CSF); however, CSF Pi levels in patients with IBGC have not been fully examined. Methods We investigated the cases of 29 patients with IBGC including six patients with SLC20A2 mutation and three patients with PDGFB mutation, and 13 controls. The levels of sodium (Na), potassium (K), chloride (Cl), calcium (Ca), and Pi in sera and CSF were determined by potentiometry and colorimetry. Moreover, clinical manifestations were investigated in the IBGC patients with high Pi levels in CSF. Results The study revealed that the average level of Pi in the CSF of the total group of patients with IBGC is significantly higher than that of the control group, and the levels of Pi in CSF of the IBGC patients with SLC20A2 mutations are significantly higher than those of the IBGC patients with PDGFB mutations, the other IBGC patients and controls. Conclusion Results of this study suggest that the levels of CSF Pi will be a good biomarker for IBGC1.

Here we report an autopsy-verified case of frontotemporal lobar degeneration (FTLD)-transactivation responsive region (TAR) DNA binding protein (TDP) type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD). A 69-year-old woman presented with an 11-month history of progressive dementia, irritability, insomnia, and gait disturbance without a family history of dementia or prion disease. Neurological examination revealed severe dementia, frontal signs, and exaggerated bilateral tendon reflexes. Periodic sharp-wave complexes were not observed on the electroencephalogram. Brain diffusion MRI did not reveal abnormal changes. An easy Z score (eZIS) analysis for 99mTc-ECD-single photon emission computed tomography (99mTc-ECD-SPECT) revealed a bilateral decrease in thalamic regional cerebral blood flow (rCBF). PRNP gene analysis demonstrated methionine homozygosity at codon 129 without mutation. Cerebrospinal fluid (CSF) analysis showed normal levels of both 14-3-3 and total tau proteins. Conversely, prion protein was slowly amplified in the CSF by a real-time quaking-induced conversion assay. Her symptoms deteriorated to a state of akinetic mutism, and she died of sudden cardiac arrest, one year after symptom onset.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is a corticosteroid-responsive meningoencephalomyelitis with a poorly understood pathogenesis. We examined and compared the levels of cytokines and biological markers in the cerebrospinal fluid (CSF) of patients with GFAP-A and other neurological disorders. We identified four cytokines (tumor necrosis factor alpha [TNFα], Interleukin [IL]-27, IL-6, and chemokine [C-C motif] ligand 20) and three biological markers (GFAP, S100 calcium-binding protein B, and neurofilament light chain) present at elevated levels in CSF samples during the acute phase of GFAP-A. Additionally, we identified significant correlations between CSF TNFα, IL-27, IL-6, and CSF biological markers.

A 61-year-old woman was admitted to our hospital due to memory difficulties, visual hallucinations, and slowly progressing motor difficulties in the limbs. A clinical examination revealed bradykinesia, gait disturbance, left-side-dominant rigidity, ideomotor apraxia, dressing apraxia, left-sided spatial agnosia, impaired visuospatial ability, and executive dysfunction. Her symptoms were unresponsive to levodopa, and corticobasal syndrome (CBS) was diagnosed. One year later, amyloid positron emission tomography revealed amyloid beta accumulation in the bilateral cerebral cortices; at this point, CBS with underlying Alzheimer's disease pathology (CBS-AD) was diagnosed. Visual hallucinations may help differentiate CBS with corticobasal degeneration (CBS-CBD) from other pathologies, including CBS-AD.

We report an 84-year-old woman with left lower limb muscle weakness and numbness who also had weakness in her right lower limb, which showed spontaneous partial improvement. Neurological examination revealed lower extremity weakness and sensory disturbance in all modalities, predominantly distally on the left side. Laboratory studies yielded normal results, except for a slightly high erythrocyte sedimentation rate. Nerve conduction studies showed axonal neuropathy in the right tibial nerve, and loss of action potentials in other lower limb nerves. Histological study of the left sural nerve revealed mainly loss of axons and differences in the density of fascicules in the axons. In addition, inflammatory cells infiltrated around small blood vessels. Therefore, we diagnosed nonsystemic vasculitic neuropathy. Magnetic resonance imaging revealed that she also had spondylosis deformans and radiculopathy, which was more difficult to differentiate. Neural biopsy was important for diagnosis.