Tsuyoshi Uchiyama

Anhedonia and its correlation with clinical aspects in Parkinson's disease

Anhedonia is one of the non-motor symptoms observed in the Parkinsons disease (PD). However, there is no clear relationship between anhedonia and its correlation with other symptoms of PD. The aim of this study is to evaluate the characteristics of anhedonia and its correlation with clinical aspects of PD in a relatively large cohort. We enrolled 318 patients with PD and 62 control subjects for this study. Patients and subjects were tested using the Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition for the assessment of anhedonia and depression. We also investigated the correlation among clinical aspects of PD, anhedonia, and depression in patients with PD. The Snaith-Hamilton Pleasure Scale Japanese version and the Beck Depression Inventory 2nd edition scores were significantly higher in patients with PD than in control subjects (p=0.03 and p=0.0006, respectively). All PD patients with anhedonia had a significantly higher score on the unified Parkinsons disease rating scale (UPDRS) parts I and II compared to PD patients without anhedonia. Additionally, all PD patients with depression scored significantly higher on UPDRS part I-IV than PD patients without depression. The patients with anhedonia and without depression had mild motor severity and their treatment was relatively low dosage. These results suggest that anhedonia and depression are slightly linked, but not the same. PD patients with only anhedonia may be closely linked apathy found in untreated early stages of PD.

Rhinorrhea in Parkinson's disease: A consecutive multicenter study in Japan

Recent reports suggest that rhinorrhea, defined as the presence of a runny nose unrelated to respiratory infections, allergies, or sinus problems, occurs more frequently among patients with Parkinsons disease (PD) than among healthy controls. We conducted a questionnaire survey in a multicenter study throughout Japan and compared the frequency of rhinorrhea between 231 PD and 187 normal control (NC) subjects. After excluding patients with rhinitis or paranasal sinusitis, a total of 159 PD and 59 NC subjects were included in our analysis. Rhinorrhea occurred more frequently in PD patients than NC subjects (33.3% vs. 11.9%; P=0.01). Among PD patients, rhinorrhea was more common in men than women (P=0.005). Rhinorrhea was not correlated with disease duration, modified Hoehn and Yahr score, disease type (akinesia rigidity vs. tremor dominant), or cardiac sympathetic function (evaluated by (123)I-metaiodobenzylguanidine uptake). To our knowledge, this is the first multicenter study on the frequency of PD-related rhinorrhea in Asian countries.

A Japanese multicenter survey characterizing pain in Parkinson's disease

BACKGROUND Pain is a frequent, troublesome symptom of PD but is under-recognized and poorly understood. AIM We characterized pain prevalence, severity, and location in PD, to better understand its pathophysiology and improve diagnosis and treatment. SUBJECTS AND METHODS A cross-sectional controlled study was conducted at 19 centers across Japan. A total of 632 subjects with Mini-Mental State Examination scores ≥24 were enrolled, including 324 PD patients and 308 controls. Sex and mean age did not differ between the two groups. Demographic and clinical data were collected. Pain was assessed using questionnaires, the SF-36v2 bodily pain scale, and a body illustration for patients to indicate the location of pain in 45 anatomical areas. RESULTS Pain prevalence in the PD group was 78.6%, significantly higher than in controls (49.0%), as was its severity. There was no correlation between SF-36v2 score and motor scores, such as Unified Parkinsons Disease Rating Scale III or Hoehn & Yahr scores. Pain distribution was similar between groups, predominantly in the lower back, followed by the gluteal region, lower legs, thighs, posterior neck, and shoulders. CONCLUSION Pain is a significant problem in the Japanese PD population and we discuss its pathophysiology.

Targeting the enhanced ER stress response in Marinesco-Sjögren syndrome

BACKGROUND AND OBJECTIVE Marinesco-Sjögren syndrome (MSS) is an autosomal recessive infantile-onset disorder characterized by cataracts, cerebellar ataxia, and progressive myopathy caused by mutation of SIL1. In mice, a defect in SIL1 causes endoplasmic reticulum (ER) chaperone dysfunction, leading to unfolded protein accumulation and increased ER stress. However, ER stress and the unfolded protein response (UPR) have not been investigated in MSS patient-derived cells. METHODS Lymphoblastoid cell lines (LCLs) were established from four MSS patients. Spontaneous and tunicamycin-induced ER stress and the UPR were investigated in MSS-LCLs. Expression of UPR markers was analyzed by western blotting. ER stress-induced apoptosis was analyzed by flow cytometry. The cytoprotective effects of ER stress modulators were also examined. RESULTS MSS-LCLs exhibited increased spontaneous ER stress and were highly susceptible to ER stress-induced apoptosis. The inositol-requiring protein 1α (IRE1α)-X-box-binding protein 1 (XBP1) pathway was mainly upregulated in MSS-LCLs. Tauroursodeoxycholic acid (TUDCA) attenuated ER stress-induced apoptosis. CONCLUSION MSS patient-derived cells exhibit increased ER stress, an activated UPR, and susceptibility to ER stress-induced death. TUDCA reduces ER stress-induced death of MSS patient-derived cells. The potential of TUDCA as a therapeutic agent for MSS could be explored further in preclinical studies.

Cortical subarachnoid haemorrhage with reversible cerebral vasoconstriction syndrome in an elderly woman

A woman aged 65 years had a sudden onset of severe headache after swimming. She had prolonged headache; therefore, she presented at the emergency department. During the examination in the emergency department, her physical and neurological examinations were unremarkable. Haematological findings were normal. The CT scan of the head revealed a cortical subarachnoid haemorrhage (cSAH) in the right frontal and left temporal lesion (figure 1A, B). The cerebrospinal fluid analysis revealed normal protein and cell counts. A brain MRI showed only high-intensity changes for cSAH with no findings of microbleeds (figure 1C, D). The magnetic resonance angiography (MRA) showed mild stenotic changes on the right posterior cerebral artery (PCA) …

Proteinase 3-antineutrophil cytoplasmic antibody-positive ulcerative colitis presenting with abducens neuropathy

A 72-year-old man with ulcerative colitis (UC) presented with complete left abducens nerve palsy. Although MRI showed no significant changes, cerebrospinal fluid analysis revealed pleocytosis and elevated protein and interleukin (IL)-6 levels. His serum proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) level was also elevated to 31.1 U/mL, but granulomatosis with polyangiitis was not observed. On the basis of the diagnosis of autoimmune cranial neuropathy, he was treated with steroid therapy. While tapering steroid therapy, his serum PR3-ANCA levels; cerebrospinal fluid findings, including IL-6 levels; and symptoms improved. Serum PR3-ANCA could be a useful parameter of neurological disorders associated with ANCA-positive UC.

Arterial spin-labelled perfusion MRI demonstrates early spontaneous recanalisation of clot after cardiogenic embolism

A 71-year-old man with atrial fibrillation was presented to the emergency department 30 min after the sudden onset of disturbance of consciousness. On examination, he showed a disturbance of consciousness (Glasgow Coma Score: E4V2M5) and severe right hemiplegia, which subsequently improved, and he finally presented with moderate sensory aphasia alone. CT of the head showed no haemorrhage. Diffusion-weighted MRI (DW-MRI) of the brain showed a high-intensity spot lesion in the left insular cortex (figure 1A). Arterial spin-labelled (ASL) perfusion MRI showed hyperperfusion in the same …

Orbital myositis presenting with only unilateral orbital pain

A 24-year-old woman developed sudden severe periorbital pain characterised by severe, unilateral, pounding, short-lived, repetitive pain. Consequently, she was diagnosed with paroxysmal haemicrania at the first visit. There was no history of diplopia or other ophthalmic symptoms. Her physical and other neurological findings were normal. Anti-thyroid and antinuclear antibodies were negative. IgG4, soluble interleukin-2 receptor, C-reactive protein and creatine kinase levels; cerebrospinal fluid analysis; and CT scan were normal. MRI revealed enlargement and increased signal in the left medial …