Invasive Tracheobronchial Aspergillosis: A Fatal Complication in a Patient With Treated Mediastinal Lung Adenocarcinoma.

Invasive tracheobronchial aspergillosis (ITBA) is a rare but severe form of invasive aspergillosis. This report presents a fatal case of ITBA in a 75-year-old man with a complex medical history including mediastinal lung adenocarcinoma, radiation pneumonitis, and pulmonary nocardiosis. The patient was admitted with worsening dyspnea and chest imaging revealed severe airway stenosis. Initially suspected to be cancer recurrence, post-mortem examination confirmed ITBA caused by Aspergillus penicillioides. Histopathological findings showed fungal invasion of the tracheobronchial tree with destruction, obstruction, and perforation of the airways. Multiple risk factors likely contributed to the development of ITBA in this patient, including diabetes, chronic obstructive pulmonary disease (COPD), long-term steroid use, prior COVID-19 infection, and a history of radiation therapy. This case highlights the diagnostic challenges of ITBA, particularly in patients with multiple comorbidities and a history of malignancy. It emphasizes the importance of considering fungal infections in the differential diagnosis of airway obstruction in high-risk patients.

Intermediate phenotype between CMT2Z and DIGFAN associated with a novel MORC2 variant: a case report.

Charcot-Marie-Tooth disease type 2Z is caused by MORC2 mutations and presents with axonal neuropathy. MORC2 mutations can also manifest as developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN). We report a patient exhibiting an intermediate phenotype between these diseases associated with a novel MORC2 variant. A literature review revealed that the genotype‒phenotype correlation in MORC2-related disorders is complex and that the same mutation can cause a variety of phenotypes.

Factors associated with a placebo effect in Parkinson's disease in clinical trials: a meta-analysis.

OBJECTIVES: Outcomes of clinical trials of treatment in patients with Parkinson's disease (PD) may be influenced by placebo effects. The aim of this study was to determine the factors associated with placebo effects in Parkinson's disease (PD) for guidance with design of future clinical trials. METHODS: Factors associated with placebo effects in PD were examined in a meta-analysis using a random effects model with pooling of placebo effects on the Unified Parkinson's Disease Rating Scale part III (UPDRS III) or Movement Disorder Society sponsored revision of UPDRS III (MDS-UPDRS III). The following prespecified variables were included in the analyses: with or without drug at baseline, with or without a placebo run-in phase, with or without motor fluctuation, published year, number of study sites, placebo administration period, age, sex, disease duration, and daily levodopa dose. Publication bias was assessed by visual inspection of funnel plots and adjusted using the trim-and-fill method. RESULTS: Thirty-eight articles with a total of 4828 subjects satisfied the inclusion criteria. There was a significant placebo effect using UPDRS III or MDS-UPDRS III (SMD = - 0.25; 95% CI - 0.35 to - 0.14; p < 0.001, I2 = 92%). Subgroup and/or multivariate meta-regression analyses revealed that placebo effects were associated with advanced PD (p = 0.04), drug exposure at baseline (p < 0.001), placebo administration period (p < 0.001), and disease duration (p < 0.01). CONCLUSIONS: The results of this study are important as guidance in design of future clinical trials in which the influence of placebo effects is minimized.

Clinical Association Between Immune-related Adverse Events and Treatment Efficacy in Patients With Non-small-cell Lung Cancer Treated With Nivolumab-Ipilimumab-based Therapy.

BACKGROUND/AIM: Nivolumab and ipilimumab combination therapy has been extensively explored for the treatment of advanced non-small-cell lung cancer (NSCLC) through the pivotal phase III trials CheckMate 227 and CheckMate 9LA. However, the relationship between immune-related adverse events (irAEs) and the effectiveness of nivolumab plus ipilimumab-based therapy in a real-world clinical setting remains uncertain. PATIENTS AND METHODS: We performed a retrospective analysis of 28 patients with advanced or recurrent NSCLC who underwent treatment with nivolumab plus ipilimumab, with or without platinum-doublet chemotherapy, from February 2021 to January 2023. The primary objective was to elucidate the clinical association between irAEs and treatment efficacy associated with nivolumab plus ipilimumab-based therapy. RESULTS: Among the 28 patients, 22 (78.6%) experienced irAEs. The median progression-free survival (PFS) was significantly longer for patients with irAEs than for those without (p=0.0158), as was overall survival (OS) (p=0.000394). The severity of irAEs had no significant influence on PFS or OS. The objective response rate tended to be higher in patients with irAEs than in those without (50.0% versus 0.0%, respectively; p=0.0549). Multivariate analysis indicated that irAE occurrence was an independent factor for improved PFS (hazard ratio=0.2084, p=0.01383) and OS (hazard ratio=0.0857, p=0.001588). Interstitial lung disease was inferior to other irAE profiles for both PFS and OS. CONCLUSION: Patients with advanced NSCLC experiencing irAEs demonstrated superior clinical outcomes when treated with nivolumab plus ipilimumab-based therapy compared with those without irAEs. However, immune-related interstitial lung disease may be less linked with PFS and OS than other irAE profiles.

Complete nanopore repeat sequencing of SCA27B (GAA-FGF14 ataxia) in Japanese.

BACKGROUND: Although pure GAA expansion is considered pathogenic in SCA27B, non-GAA repeat motif is mostly mixed into longer repeat sequences. This study aimed to unravel the complete sequencing of FGF14 repeat expansion to elucidate its repeat motifs and pathogenicity. METHODS: We screened FGF14 repeat expansion in a Japanese cohort of 460 molecularly undiagnosed adult-onset cerebellar ataxia patients and 1022 controls, together with 92 non-Japanese controls, and performed nanopore sequencing of FGF14 repeat expansion. RESULTS: In the Japanese population, the GCA motif was predominantly observed as the non-GAA motif, whereas the GGA motif was frequently detected in non-Japanese controls. The 5'-common flanking variant was observed in all Japanese GAA repeat alleles within normal length, demonstrating its meiotic stability against repeat expansion. In both patients and controls, pure GAA repeat was up to 400 units in length, whereas non-pathogenic GAA-GCA repeat was larger, up to 900 units, but they evolved from different haplotypes, as rs534066520, located just upstream of the repeat sequence, completely discriminated them. Both (GAA)≥250 and (GAA)≥200 were enriched in patients, whereas (GAA-GCA)≥200 was similarly observed in patients and controls, suggesting the pathogenic threshold of (GAA)≥200 for cerebellar ataxia. We identified 14 patients with SCA27B (3.0%), but their single-nucleotide polymorphism genotype indicated different founder alleles between Japanese and Caucasians. The low prevalence of SCA27B in Japanese may be due to the lower allele frequency of (GAA)≥250 in the Japanese population than in Caucasians (0.15% vs 0.32%-1.26%). CONCLUSIONS: FGF14 repeat expansion has unique features of pathogenicity and allelic origin, as revealed by a single ethnic study.

Constipation in patients with motor neuron disease: A retrospective longitudinal study.

Background: Constipation has been recently recognized as a complication associated with motor and autonomic dysfunction in patients with motor neuron disease (MND), typified by amyotrophic lateral sclerosis (ALS). However, the long-term characteristics of constipation remain unclear in patients with MND. We longitudinally investigated the prevalence and risk factors of constipation in a consecutive cohort of patients with MND. Methods: Data from Japanese patients with MND enrolled in a single-center registry from June 2017 to December 2021 were retrospectively investigated. The diagnosis of ALS was based on the updated Awaji criteria, and other MND subtypes were also included. The presence or absence of constipation symptoms was determined by referring to the Rome III criteria. The clinical backgrounds and symptoms of patients with and without constipation were compared. Results: Among 155 consecutive patients (female, 63; age, 66.5 ± 12.4 years), 30.3% had constipation at diagnosis and 52.9% after a median follow-up of 18 months. Univariate analysis showed that female sex, use of tracheostomy and invasive ventilation, and delivery of enteral nutrition were more frequent in the constipation group. The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale score was significantly lower in the constipation group, especially for the sub-items related to physical motor function. Multivariate analysis showed that the use of enteral nutrition was an independent risk of constipation, with an odds ratio of 3.69 (95% CI, 1.49-9.17; p = 0.005). Conclusion: Constipation had a high prevalence in patients with MND with impaired motor function. Controlling defecation is important in patients with MND, especially during enteral nutrition.

A Case of Anti-NXP2 Antibody-positive Juvenile Dermatomyositis with Characteristic Fascial Thickening on Muscle Ultrasound and Improvement with Immunotherapy.

We herein report a 12-year-old boy who presented with a fever, erythematous rash on the cheeks, back pain, and dysphagia. Blood tests revealed increased creatine kinase levels, and muscle ultrasonography (MUS) revealed characteristic fascial thickening in the lumbar paraspinal muscles, where myalgia was prominent. Sarcoplasmic expression of myxovirus-resistant protein A on a muscle biopsy and the presence of anti-nuclear matrix protein 2 (NXP2) antibodies confirmed the diagnosis of dermatomyositis. Prednisolone and intravenous immunoglobulin therapy improved the clinical and laboratory parameters as well as fascial thickening. MUS is useful for evaluating fasciitis associated with anti-NXP2 autoantibodies and monitoring therapeutic efficacy.

Segmental Zoster Paresis Accompanied by Horner's Syndrome.

We herein report a 90-year-old immunocompromised woman who developed right upper limb weakness and right ptosis with a miotic pupil 1 week after oral therapy for zoster on the right T2 dermatome. The right pupil was dilated with instillation of 1% apraclonidine, indicating Horner's syndrome. The patient was treated with intravenous acyclovir and methylprednisolone. Focal weakness related to zoster, generally known as segmental zoster paresis, improved over five months, but Horner's syndrome remained. We suggest that aggressive intravenous treatment should be considered for rare cases of zoster that occur with a combination of these two neurological conditions.

Autosomal Recessive Spinocerebellar Ataxia Type 9 With a Response to Phosphate Repletion: A Case Report.

Objective: Autosomal recessive spinocerebellar ataxia type 9 (SCAR9) has received attention due to its potential response to coenzyme Q10 (CoQ10) supplementation; however, the response has so far been limited and variable. Methods: We report a SCAR9 patient with severe hypophosphatemia who responded well to CoQ10 and phosphate repletion. Results: A 70-year-old man (the offspring of a consanguineous marriage) presented with cerebellar ataxia and intense fatigue after exercise. Whole-exome sequencing identified a novel homozygous deletion mutation (NM_020247.5:c.1218_1219del) in COQ8A. We thus diagnosed him with SCAR9. Supplementation of CoQ10 alleviated his symptoms, with the Scale for the Assessment and Rating of Ataxia (SARA) dropping from 16 to 14. During the course of the disease, he demonstrated continuous hypophosphatemia caused by renal phosphate wasting. Gait dysfunction due to weakness and eye movement was partially alleviated, and SARA dropped from 17 to 13 after phosphate repletion. Discussion: Phosphate repletion should be considered for patients with severe hypophosphatemia without any apparent subjective symptoms. In this case, phosphate repletion could have improved myopathy leading to partial improvement in the patient's symptoms. Further analyses regarding the association between COQ8A mutation and phosphate wasting are required to elucidate the detailed pathogenesis. Classification of Evidence: This provides Class IV evidence. This is a single observational study without controls.

Correlation of muscle ultrasound with clinical and pathological findings in idiopathic inflammatory myopathies.

INTRODUCTION/AIMS: In idiopathic inflammatory myopathies (IIMs), the change in muscle echogenicity and its histopathological basis are not well understood. We quantitatively measured muscle echogenicity in patients with IIMs and evaluated its correlation with disease activity and histopathological findings. METHODS: This study involved patients with IIMs who underwent both ultrasonography (US) and muscle biopsy, as well as age- and sex-matched rheumatoid arthritis patients as inflammatory disease controls. On US, axial images of the right biceps brachii and vastus medialis were obtained. Standardized histopathological scoring was used to quantitatively measure each pathological domain. RESULTS: Forty-two patients (17 with inclusion body myositis [IBM] and 25 with IIMs other than IBM) and 25 controls were included. The muscle echo intensity (EI) of patients with IIMs was significantly higher than that of controls. Muscle EI showed significant correlations with creatine kinase (r = 0.66, p < .001) and muscle strength (r = -0.73, p < .0001) in patients with non-IBM IIMs. In patients with IBM, moderate correlation was found between muscle EI and quadriceps muscle strength (r = -0.53, p = .028). Histopathologically, the number of infiltrating CD3+ inflammatory cells correlated with muscle EI in the non-IBM group (r = 0.56, p = .017), but not in the IBM group. DISCUSSION: Muscle EI may be useful as a surrogate marker of muscle inflammation in non-IBM IIM. Increased muscle EI may be difficult to interpret in patients with long-standing IBM, which has advanced and complex histopathology.

Real-world Efficacy and Safety of Atezolizumab Plus Bevacizumab, Paclitaxel and Carboplatin for First-line Treatment of Japanese Patients With Metastatic Non-squamous Non-small Cell Lung Cancer.

BACKGROUND/AIM: Platinum-doublet chemotherapy plus either programmed cell death 1 (PD-1) or programmed death ligand 1 (PD-L1) checkpoint inhibitors has been reported to improve the survival of patients with advanced non-small cell lung cancer (NSCLC). The IMpower150 study showed significant improvements in progression-free survival and overall survival with atezolizumab in combination with bevacizumab, a humanized anti-VEGF monoclonal antibody, paclitaxel, and carboplatin (ABCP therapy) in chemotherapy-naïve patients with non-squamous NSCLC. We herein report the efficacy and safety of ABCP therapy in Japanese patients with non-squamous NSCLC in clinical practice. PATIENTS AND METHODS: We retrospectively evaluated the efficacy and safety of ABCP therapy in 30 patients treated at our hospital from February 2019 to December 2021. RESULTS: The median age of patients was 69 years, 24 (80.0%) patients were male, 29 (96.7%) patients had a performance status of 0 or 1, 28 (93.3%) patients had adenocarcinoma histology, and 7 (23.3%) patients had epidermal growth factor receptor mutations. Evaluation of the PD-L1 tumor proportion score (TPS) showed that 12 (40.0%), 8 (26.7%), and 6 (20.0%) patients had a TPS of ≥50%, 1% to 49%, and <1%, respectively. The objective response rate of the intention-to-treat wild-type population was 73.9%, and the median progression-free survival was 8.3 months. Immune checkpoint inhibitor (ICI)-induced pneumonitis occurred in one (3.3%) patient. CONCLUSION: ABCP therapy for Japanese non-squamous NSCLC patients in a clinical setting achieved a high response rate with low incidence of ICI-induced pneumonitis equivalent to those observed in IMpower150 study.

M1/precuneus ratio as a surrogate marker of upper motor neuron sign in ALS.

OBJECTIVE: To investigate whether primary motor cortex (M1) volume measured with an automated approach in MRI reflects upper motor neuron dysfunction and whether it can serve as a potential diagnostic and/or disease-tracking biomarker for amyotrophic lateral sclerosis (ALS). METHODS: In this retrospective study, we enrolled 95 subjects, including 33 possible or laboratory supported probable ALS, 26 probable or definite ALS (Prob/Def), 2 primary lateral sclerosis patients, 8 progressive muscular atrophy patients, 19 normal controls (NC) and 7 ALS patients having a second structural MRI scan. Some subjects also underwent functional MRI. We calculated M1, primary sensory cortex, precuneus volumes, and total gray matter volume (TGMV) with FreeSurfer. The sensorimotor network (SMN) was identified using independent component analysis. RESULTS: The M1/precuneus ratio showed a significant difference between the NC and Prob/Def groups (p < 0.05). The diagnostic accuracy of the M1/precuneus ratio was moderate for distinguishing Prob/Def from NC (cutoff = 1.00, sensitivity = 0.42, specificity = 0.90). Two of eight cases without upper motor neuron dysfunction could be diagnosed with ALS using M1/precuneus ratio as a surrogate marker. A negative correlation between M1/precuneus ratio and functional activity was found in Brodmann area 6 in the SMN in all subjects. TGMV tended to decrease with disease progression (p = 0.04). INTERPRETATION: The M1/precuneus volume ratio, associated with the SMN, may have potential as a surrogate biomarker of upper motor neuron dysfunction in ALS. Furthermore, TGMV may serve as an ALS disease-tracking biomarker.

An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent. OBJECTIVE: This protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS). METHODS: EPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area. RESULTS: This trial began data collection in September 2021 and is expected to be completed in October 2023. CONCLUSIONS: This study can provide useful data to understand the characteristics of EPI-589. TRIAL REGISTRATION: Japan Primary Registries Network jRCT2061210031; tinyurl.com/2p84emu6. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42032.

[Peripheral Neuropathy in RFC1 CANVAS/Spectrum Disorders].

Recently, the biallelic expansion of an AAGGG repeat in RFC1 was reported as a cause of cerebellar ataxia with neuropathy and vestibular areflexia syndrome. This mutation has also been reported in more selected nervous disorders, including pure sensory axonal polyneuropathy. Thus, the multisystem disorders caused by this mutation are now considered RFC1-related spectrum disorders. Here, we review the previous reports about RFC1-related spectrum disorders from the aspect of neuropathy.

Regression of left ventricular hypertrophy after tafamidis therapy in a patient with transthyretin amyloidosis variant.

Transthyretin amyloidosis (ATTR) variant is a life-threatening hereditary disease predominantly affecting the peripheral nervous system and heart. Tafamidis, which prevents the deposition of amyloid by stabilizing transthyretin, is available for the treatment of neuropathy and cardiomyopathy of ATTR. However, whether tafamidis could eliminate established amyloid deposits and improve cardiac function remains unknown. We reported a case of regression of left ventricular hypertrophy after tafamidis therapy in a patient with an ATTR variant. J. Med. Invest. 69 : 320-322, August, 2022.

Application of ultrasound in a case of eosinophilic fasciitis mimicking stiff-person syndrome.

Eosinophilic fasciitis (EF) is a rare disorder characterized by muscle stiffness mimicking other neuromuscular diseases. The diagnosis of EF is made on the basis of typical skin lesions. We report a case of a 36-year-old male patient with suspected stiff-person syndrome (SPS), who presented with progressive limb muscle stiffness and limited mobility of both wrists without obvious skin changes. Ultrasound revealed fascial thickening of bilateral upper and lower limb muscles and enlargement of hypoechoic tissues around the flexor digitorum tendons of the wrist. Skin and fascia biopsy confirmed the diagnosis of EF. Prednisolone therapy resulted in the improvement of muscle stiffness and tightness. Our findings suggest the need to consider connective tissue diseases such as EF in a patient with atypical features of SPS. Ultrasound is helpful for visualizing the causes of muscle stiffness and joint contractures in EF patients.

Early diagnosis of amyotrophic lateral sclerosis based on fasciculations in muscle ultrasonography: A machine learning approach.

OBJECTIVE: Although fasciculation on muscle ultrasonography (MUS) is useful in diagnosing amyotrophic lateral sclerosis (ALS), its applicability to early diagnosis remains unclear. We aimed to develop and validate diagnostic models especially beneficial to early-stage ALS via machine learning. METHODS: We investigated 100 patients with ALS, including 50 with early-stage ALS within 9 months from onset, and 100 without ALS. Fifteen muscles were bilaterally observed for 10 s each and the presence of fasciculations was recorded. Hierarchical clustering and nominal logistic regression, neural network, or ensemble learning were applied to the training cohort comprising the early-stage ALS to develop MUS-based diagnostic models, and they were tested in the validation cohort comprising the later-stage ALS. RESULTS: Fasciculations on MUS in the brainstem or thoracic region had high specificity but limited sensitivities and predictive profiles for diagnosis of ALS. A machine learning-based model comprising eight muscles in the four body regions had a high sensitivity (recall), specificity, and positive predictive value (precision) for both early- and later-stage ALS patients. CONCLUSIONS: We developed and validated MUS-fasciculation-based diagnostic models for early- and later-stage ALS. SIGNIFICANCE: Fasciculation detected in relevant muscles on MUS can contribute to the diagnosis of ALS from the early stage.

Serum NfL and CHI3L1 for ALS and parkinsonian disorders in the process of diagnosis.

Serum neurofilament light chain (NfL) and chitinase 3-like 1 (CHI3L1, also called YKL-40) concentrations are attractive candidate biomarkers for neurodegenerative disorders, which include amyotrophic lateral sclerosis (ALS) and parkinsonian disorders. We aimed to assess the diagnostic power of serum NfL and CHI3L1 concentrations with regard to the early diagnosis of ALS and Parkinson's disease (PD). We studied 157 individuals, which included 41 healthy controls, 8 patients with ALS mimics, 18 patients initially diagnosed with ALS (ID-ALS), 32 patients late-diagnosed with ALS (LD-ALS), 29 patients with PD, 12 patients with PD mimics, and 17 patients initially diagnosed with atypical parkinsonian disorders (ID-APDs) at the initial stage of diagnosis. Electrochemiluminescence was used to measure the concentrations of serum NfL and CHI3L1, the diagnostic performance of which was assessed using the area under the receiver operating curves (AUCs). The AUCs of serum NfL were 0.90 for discriminating ALS mimics from LD-ALS at the initial stage of diagnosis and 0.89 for discriminating ALS mimics from ALS (LD/ID-ALS). The AUCs of serum NfL were 0.76 for discriminating PD from PD mimics at the initial stage of diagnosis, and 0.80 for discriminating PD from APD. No significant difference existed in serum CHI3L1 concentrations between individuals with suspected ALS or parkinsonism (p = 0.14, and p = 0.44, respectively). Serum NfL had excellent and almost good diagnostic performances for patients with ALS and PD, respectively, at the initial stage of diagnosis, whereas no significant difference existed in serum CHI3L1 between any groups.

The Cerebellum Is a Common Key for Visuospatial Execution and Attention in Parkinson's Disease.

Cognitive decline affects the clinical course in patients with Parkinson's disease (PD) and contributes to a poor prognosis. However, little is known about the underlying network-level abnormalities associated with each cognitive domain. We aimed to identify the networks related to each cognitive domain in PD using resting-state functional magnetic resonance imaging (MRI). Forty patients with PD and 15 normal controls were enrolled. All subjects underwent MRI and the Mini-Mental State Examination. Furthermore, the cognitive function of patients with PD was assessed using the Montreal Cognitive Assessment (MoCA). We used independent component analysis of the resting-state functional MRI for functional segmentation, followed by reconstruction to identify each domain-related network, to predict scores in PD using multiple regression models. Six networks were identified, as follows: the visuospatial-executive-domain-related network (R2 = 0.54, p < 0.001), naming-domain-related network (R2 = 0.39, p < 0.001), attention-domain-related network (R2 = 0.86, p < 0.001), language-domain-related network (R2 = 0.64, p < 0.001), abstraction-related network (R2 = 0.10, p < 0.05), and orientation-domain-related network (R2 = 0.64, p < 0.001). Cerebellar lobule VII was involved in the visuospatial-executive-domain-related and attention-domain-related networks. These two domains are involved in the first three listed nonamnestic cognitive impairment in the diagnostic criteria for PD with dementia (PDD). Furthermore, Brodmann area 10 contributed most frequently to each domain-related network. Collectively, these findings suggest that cerebellar lobule VII may play a key role in cognitive impairment in nonamnestic types of PDD.

Lung squamous cell carcinoma with severe hypomagnesemia due to cisplatin plus gemcitabine in combination with necitumumab therapy: A case report.

A 72-year-old man, diagnosed with advanced lung squamous cell carcinoma, was administered of cisplatin plus gemcitabine with necitumumab, a human monoclonal antibody that binds to the epidermal growth factor receptor (EGFR), as a sixth-line treatment. Tumor shrinkage was observed, but asymptomatic grade 4 hypomagnesemia occurred on day 8 of the second cycle. He received magnesium replenishment and hypomagnesemia recovered on day 40, but tumor progression was observed during the period of magnesium correction. Hypomagnesemia is known as a major adverse event of treatment with anti-EGFR antibodies, but there have been no case reports of severe hypomagnesemia or its clinical course.