Quality of life assessment when considering the introduction of device-assisted therapies in advanced Parkinson's disease: A retrospective observational cross-sectional study.

INTRODUCTION: Device-aided therapy (DAT) is an established treatment for improving the quality of life (QOL) in individuals with advanced Parkinson's disease (APD). Criteria for starting DAT, including motor and non-motor symptoms, have been proposed. However, it remains unclear whether QOL differences among patients with APD influence DAT introduction. Therefore, we aimed to investigate QOL differences between patients with and without DAT introduction. METHODS: This retrospective observational cross-sectional study included 245 patients with PD who were followed up between January 1, 2020, and June 30, 2022. We defined cases that underwent DAT introduction after evaluation as "planned-DAT" and those that did not as "not-planned-DAT." We performed between-group comparisons of the PD questionnaire-39 (PDQ-39) summary index (SI) in patients with APD who met the 5-2-1 criteria (≥5 times the oral levodopa dose/day, ≥2 h of "off" symptoms/day, and ≥ 1 h of troublesome dyskinesia/day). RESULTS: Seventy-nine patients met the inclusion criteria for APD (median age: 68 [61.0-73.0] years; 62.8% [N = 52] women). The PDQ-39 SI scores were higher in the planned-DAT group (N = 12) than in the not-planned-DAT group (N = 67) (29.2 [22.1-33.6] vs. 19.0 [10.3-49.6] points, P < 0.05). After propensity-score matching according to age and sex, the PDQ-39 SI scores remained higher in the planned-DAT (N = 9) than in the not-planned-DAT group (N = 18) (40.0 [25.4-60.0] vs. 18.5 [7.9-46.8] points, P < 0.05). CONCLUSIONS: Our results suggest that QOL assessment using PDQ-39 can be used to identify patients eligible for DAT.

Colocalization of TDP-43 and stress granules at the early stage of TDP-43 aggregation in amyotrophic lateral sclerosis.

TDP-43 aggregates (skeins and round inclusions [RIs]) are frequent histopathological features of amyotrophic lateral sclerosis (ALS). We have shown that diffuse punctate cytoplasmic staining (DPCS) is the earliest pathologic manifestation of TDP-43 in ALS, corresponding to nonfibrillar TDP-43 located in the rough endoplasmic reticulum. Previous in vitro studies have suggested that TDP-43 inclusions may be derived from stress granules (SGs). Therefore, we investigated the involvement of SGs in the formation of TDP-43 inclusions. Formalin-fixed spinal cords of six ALS patients with a disease duration of less than 1 year (short duration), eight patients with a disease duration of 2-5 years (standard duration), and five normal controls were subjected to histopathological examination using antibodies against an SG marker, HuR. In normal controls, the cytoplasm of anterior horn cells was diffusely HuR-positive. In short-duration and standard-duration ALS, the number of HuR-positive anterior horn cells was significantly decreased relative to the controls. DPCS and RIs were more frequent in short-duration ALS than in standard-duration ALS. The majority of DPCS areas and a small proportion of RIs, but not skeins, were positive for HuR. Immunoelectron microscopy showed that ribosome-like granular structures in DPCS areas and RIs were labeled with anti-HuR, whereas skeins were not. These findings suggest that colocalization of TDP-43 and SGs occurs at the early stage of TDP-43 aggregation.

First evidence of tick-borne encephalitis (TBE) outside of Hokkaido Island in Japan.

Tick-borne encephalitis (TBE) is an infection of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is endemic in parts of Europe and Asia. TBEV is transmitted to humans primarily by Ixodes ticks. There have been 5 TBE cases identified in Japan, all on the northern island of Hokkaido. Rodents with TBEV antibodies and Ixodes ticks have been identified throughout Japan, indicating that TBEV infection might be undiagnosed in Japan. Residual serum and cerebrospinal fluid (CSF) collected in 2010-2021 from 520 patients ≥1 year-of-age previously hospitalized with encephalitis or meningitis of unknown etiology at 15 hospitals (including 13 hospitals outside of Hokkaido) were screened by ELISA for TBEV IgG and IgM antibodies; TBEV infection was confirmed by the gold standard neutralization test. Residual serum was available from 331 (63.6%) patients and CSF from 430 (82.6%) patients; both serum and CSF were available from 189 (36.3%). Two patients were TBE cases: a female aged 61 years hospitalized for 104 days in Oita (2000 km south of Hokkaido) and a male aged 24 years hospitalized for 11 days in Tokyo (1200 km south of Hokkaido). Retrospective testing also identified a previous TBEV infection in a female aged 45 years hospitalized for 12 days in Okayama (1700 km south of Hokkaido). TBEV infection should be considered as a potential cause of encephalitis or meningitis in Japan. TBE cases are likely undiagnosed in Japan, including outside of Hokkaido, due to limited clinical awareness and lack of availability of TBE diagnostic tests.

Slow vital capacity as a useful indicator of the prognosis after percutaneous endoscopic gastrostomy in patients with amyotrophic lateral sclerosis.

OBJECTIVES: Forced vital capacity (FVC) is recommended as a respiratory function test in patients with amyotrophic lateral sclerosis (ALS). However, in ALS associated with orofacial palsy, FVC may be an unreliable test. Slow vital capacity (SVC) is an easier and more reliable test even in cases with bulbar symptoms. However, it remains unclear whether respiratory function tests using SVC and FVC are associated with prognosis after percutaneous endoscopic gastrostomy (PEG) placement. This study aimed to confirm whether both SVC and FVC are related to prognosis after PEG placement in patients with ALS. MATERIALS AND METHODS: We conducted this retrospective observational cohort study of 69 consecutive patients diagnosed with sporadic ALS who underwent PEG placement between July 2007 and February 2020. We analyzed the association with mortality 6 months after PEG placement and evaluated long-term prognosis. RESULTS: Forty-four patients met the inclusion criteria. In cases with decreased SVC (p < .01) and FVC (p < .01), a significant difference was observed in mortality 6 months after PEG placement, with an optimal cut-off of SVC ≤57.4% (sensitivity, 0.828; specificity, 0.867) and FVC ≤57.3% (sensitivity, 0.828; specificity, 0.867). Multivariate analysis showed that onset age ≥ 65 years (p < .05), SVC ≤57.4% (p < .01), and FVC ≤57.3% (p < .01) were associated with survival after PEG placement. CONCLUSIONS: SVC, like FVC, is an important prognostic factor after PEG placement in patients with ALS, and there is a possibility that evaluation using SVC can complement respiratory function testing even in cases where the evaluation of FVC is limited.

Case report: Adult-onset neuronal intranuclear inclusion disease with an amyotrophic lateral sclerosis phenotype.

Amyotrophic lateral sclerosis (ALS) is one of the differential diagnoses of diseases that occur in adulthood and lead to progressive generalized muscle weakness. Neuronal intranuclear inclusion disease (NIID) is a disease in which histopathologically eosinophilic nuclear inclusion bodies are found in various systems. Both familial and sporadic forms of the disease have been reported. Most cases of sporadic NIID are of the dementia type, in which the main symptom is dementia at the first onset. Familial NIID is more diverse, with the main dominant symptoms being muscle weakness (NIID-M), dementia (NIID-D), and parkinsonism (NIID-P). Furthermore, recently, a GGC-repeat expansion in the Notch 2 N-terminal like C (NOTCH2NLC) gene, which produces a toxic polyglycine-containing protein (uN2CpolyG) in patients with NIID, has been associated with the pathogenesis of ALS. These results suggest that sporadic NIIDs may have more diverse forms. To date, no autopsy cases of NIID patients with an ALS phenotype have been reported. Here, we describe the first autopsy case report of a patient with sporadic NIID who had been clinically diagnosed with ALS. A 65-year-old Japanese man with no family history of neuromuscular disease developed progressive muscle atrophy and weakness in all limbs. The patient was diagnosed with ALS (El Escoriral diagnostic criteria: probable ALS, laboratory-supported ALS). He had no cognitive dysfunction or neuropathies suggestive of NIID. He required respiratory assistance 48 months after onset. He died of pneumonia at the age of 79 years. Postmortem examinations revealed neuronal loss in the spinal anterior horns and motor cortex. In these affected regions, eosinophilic, round neuronal intranuclear inclusions were evident, which were immunopositive for ubiquitin, p62, and uN2CpolyG. No Bunina bodies or TDP-43-positive inclusions were observed in the brain or spinal cord. Our findings suggest that a small proportion of patients with NIID can manifest a clinical phenotype of ALS. Although skin biopsy is commonly used for the clinical diagnosis of NIID, it may also be useful to identify cases of NIID masquerading as ALS.

Campylobacter coli infection causes spinal epidural abscess with Guillain-Barré syndrome: a case report.

BACKGROUND: Guillain-Barré syndrome (GBS) and spinal epidural abscess (SEA) are known as mimics of each other because they present with flaccid paralysis following an infection; however, they differ in the main causative bacteria. Nevertheless, the two diseases can occur simultaneously if there is a preceding Campylobacter infection. Here, we report the first case of SEA with GBS following Campylobacter coli infection. CASE PRESENTATION: A 71-year-old Japanese man presented with progressive back pain and paralysis of the lower limbs following enteritis. Magnetic resonance imaging showed a lumbar epidural abscess that required surgical decompression; therefore, surgical drainage was performed. Blood cultures revealed the presence of C. coli. Despite surgery, the paralysis progressed to the extremities. Nerve conduction studies led to the diagnosis of GBS. Anti-ganglioside antibodies in the patient suggested that GBS was preceded by Campylobacter infection. Intravascular immunoglobulin therapy attenuated the progression of the paralysis. CONCLUSIONS: We report a case of SEA and GBS following Campylobacter infection. A combination of the two diseases is rare; however, it could occur if the preceding infection is caused by Campylobacter spp. If a cause is known but the patient does not respond to the corresponding treatment, it is important to reconsider the diagnosis based on the medical history.

Phytobezoar Associated with Levodopa-carbidopa Intestinal Gel Infusion in Patients with Parkinson's Disease: A Case Report and Literature Review.

Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel (LCIG) is an established device-aided therapy for advanced Parkinson's disease (PD). Phytobezoar associated with LCIG is a rare device-related complication and presents with exacerbations of gastrointestinal and PD symptoms. We herein report the case of a phytobezoar that was formed at a knot on the pigtail-shaped J-tube and developed only in association with postprandial abdominal pain, similar to a feeling of a tube being pulled in without an exacerbation of PD symptoms. Such abdominal pain may be a warning sign of phytobezoar in LCIG-treated patients. Despite device-related complications, high-pressure alarms are not always present, and PD symptoms are not always exacerbated.

Sensory Nerve Conduction Study with Inching Test in Palmar Digital Neuropathy.

Mild palmar digital neuropathy may be underestimated because selective nerve conduction studies (NCS) of the palmar digital nerve are challenging. We herein report two cases of palmar digital neuropathy. We performed sensory NCS in each finger using the standard approach. Both cases showed a decrease in the amplitude of sensory nerve action potential (SNAP) in the localized finger. Furthermore, the sensory nerve inching test identified the lesion site. When performing NCS in patients with finger sensory impairment, we recommend recording the SNAP in each finger using standard NCS at the wrist, as well as sensory nerve inching testing.

Subarachnoid Hemorrhage Caused by Ruptured Aneurysm of the Artery of Adamkiewicz: a Case Report.

A 66-year-old man presented with a 6-day history of progressive posterior cervical pain that included lower back pain and fever. Neurological examinations revealed neck stiffness. Computed tomography demonstrated convexity subarachnoid hemorrhage. A spinal T2-weighted image revealed a hypointense signal lesion with contrast enhancement of the intradural extramedullary space at Th12-L1. Digital subtraction angiography showed a fusiform aneurysm with a 10 mm diameter in the artery of Adamkiewicz. We diagnosed the patient's condition as a ruptured aneurysm of the artery of Adamkiewicz. By day 41 the aneurysm had disappeared following conservative treatment. Aneurysms arising from the artery of Adamkiewicz are extremely rare and can cause both convexity and spinal subarachnoid hemorrhages. Clinicians should therefore look for spinal lesions if patients with convexity subarachnoid hemorrhage of an unknown origin have lower back pain as their initial symptom.

GABA storage and release in the medial globus pallidus in L-DOPA-induced dyskinesia priming.

Levo-dihydroxyphenylalanine (L-DOPA) is the most effective treatment for Parkinson's disease; however, most patients develop uncontrollable abnormal involuntary movements known as L-DOPA-induced dyskinesia. L-DOPA-induced dyskinesia can be reduced by pallidotomy of the medial globus pallidus or pallidal deep brain stimulation, suggesting that the medial globus pallidus plays a significant role in the development of L-DOPA-induced dyskinesia. In the present study, the pathological changes of the medial globus pallidus in L-DOPA-induced dyskinesia were studied in rat models of Parkinson's disease (unilateral 6-hydroxydopamine lesioning) and L-DOPA-induced dyskinesia (L-DOPA injection in Parkinson's disease-model rats twice daily for 2 weeks, confirmed by display of dyskinesia-like abnormal involuntary movements). L-DOPA-induced dyskinesia-model rats displayed medial globus pallidus hypertrophy, enlarged axon terminals surrounding the dendrites of medial globus pallidus neurons, and increased density of synaptic vesicles in enlarged axon terminals on the lesioned side. Synaptic terminal enlargement reversed after discontinuation of L-DOPA. Histological studies revealed the enlarged synaptic terminals were those of GABAergic striatal (direct pathway) neurons. A single injection of L-DOPA enhanced GABA release in the medial globus pallidus on the lesioned side in L-DOPA-induced dyskinesia-model rats compared to Parkinson's disease-model rats. In addition, microinjection of muscimol, a GABAA receptor agonist, into the medial globus pallidus on the lesioned side of Parkinson's disease-model rats induced dyskinesia-like abnormal involuntary movements. Microinjection of bicuculline, a GABAA receptor antagonist, into the medial globus pallidus on the lesioned side alleviated L-DOPA-induced dyskinesia in Parkinson's disease-model rats that had received L-DOPA prior to the microinjection. These results indicate that priming for L-DOPA-induced dyskinesia comprises excessive GABA storage in axon terminals of the direct pathway and that expression of L-DOPA-induced dyskinesia is associated with enhanced GABA release into the medial globus pallidus after L-DOPA dosing and the resultant excessive stimulation of GABAA receptors.

Assessing the relationship between non-motor symptoms and health-related quality of life in Parkinson's disease: a retrospective observational cohort study.

OBJECTIVES: Non-motor symptoms (NMSs) negatively impact the health-related quality of life (HrQOL) of patients with Parkinson's disease (PD). The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a comprehensive scale for evaluating PD. It remains unclear whether the NMSs evaluated with MDS-UPDRS are predictive of HrQOL. This study aimed to investigate whether NMSs, as evaluated with the MDS-UPDRS, could predict the HrQOL of patients with PD. MATERIALS AND METHODS: We conducted a 2-year retrospective observational cohort study assessing 108 patients with PD who were recruited from a single tertiary center between January 2015 and December 2017. MDS-UPDRS was used to assess NMSs and motor symptoms and Parkinson's Disease Questionnaire-39 (PDQ-39) to measure patients' HrQOL. RESULTS: The median age of patients was 69 years, and 65.7% were female. The median MDS-UPDRS part I, part II, part III, and PDQ-39-summary index scores were 8, 10, 22, and 25, respectively. The final stepwise multiple linear regression model showed that female sex (standard partial regression coefficient ß = 0.131, P < 0.05) and baseline MDS-UPDRS part I (ß = 0.272, P < 0.01) and part II (ß = 0.571, P < 0.01) scores significantly predicted the PDQ-39-SI scores at the 2-year follow-up. CONCLUSIONS: In addition to motor symptoms, NMSs at the 2-year follow-up may be useful for predicting the HrQOL of patients with PD. In clinical practice, MDS-UPDRS-guided assessment and treatment of motor symptoms and NMSs may contribute to improving HrQOL in patients with PD.

Hypoglossal Nerve Palsy due to Compression by a Persistent Primitive Hypoglossal Artery: Case Report.

A 51-year-old Japanese woman was admitted to our hospital because of speech difficulty following severe headache. Neurological examination showed dysarthria and tongue weakness on the right side, indicating right hypoglossal nerve palsy. Needle electromyography of the right side of the tongue showed fibrillation potentials. Magnetic resonance angiography and computed tomography angiography revealed a right, persistent, primitive hypoglossal artery (PPHA) that met Lie's diagnostic criteria. Digital subtraction angiography showed an extended PPHA with irregular caliber in the portion running through the right hypoglossal canal. We diagnosed compression neuropathy of the hypoglossal nerve due to PPHA enlargement based on the findings of ipsilateral hypoglossal nerve palsy, fibrillation that indicated peripheral nerve palsy, and the enlarged diameter of the portion of the PPHA running through the right hypoglossal canal. We prescribed antihypertensive therapy. At 1 year after onset, her tongue weakness was alleviated. Clinicians should consider compression neuropathy due to a PPHA as one of the possibilities in the differential diagnosis of hypoglossal nerve palsy.

[Continuous hyperCKemia without calf muscle hypertrophy associated with S1 radiculopathy].

A 72-year-old man presented with continuous hyperCKemia and intermittent claudication. He exhibited no calf muscle hypertrophy at that time or afterward. Other than an increased creatine kinase (CK) level (1,525 U/l), none of the laboratory tests was abnormal, including that for myositis-related autoantibodies. Electromyography showed neurogenic changes in the left gastrocnemius. Lumbar magnetic resonance imaging revealed spinal canal stenosis (L3/4, L4/5), left L4 radiculopathy, and bilateral S1 radiculopathy. T2-weighted and short tau inversion recovery images showed high signal intensity in the bilateral biceps femoris and gastrocnemius. Histopathological evaluation of a specimen obtained from the right gastrocnemius muscle revealed neurogenic changes. The patient was diagnosed with S1 radiculopathy caused by lumbar spinal canal stenosis with hyperCKemia. Although S1 radiculopathy with hyperCKemia is usually associated with calf muscle hypertrophy, we should consider S1 radiculopathy in patients with intermittent claudication and hyperCKemia even in the absence of calf muscle hypertrophy.

Helicopter Transport for Patients with Cerebral Infarction in Rural Japan.

OBJECTIVES: Physician-staffed helicopter transport is faster than ground transport and allows for prompt medical care of patients in rural areas. In this study, we evaluated the relationship between helicopter transport and the prognosis of patients with acute cerebral infarction in rural Japan. METHODS: This retrospective, observational study included 546 patients with acute cerebral infarction attending Aomori Prefectural Central Hospital, which serves a rural region of Japan. Patients were separated into 2 transport groups: physician-staffed helicopter emergency medical services and ground emergency medical services. Patients were assessed for stroke severity, treatment, and prognosis. RESULTS: Of the 546 patients, 11.2% were transported by physician-staffed helicopter emergency medical services and 88.8% by ground emergency medical services. Although the distance transported was significantly longer in the physician-staffed helicopter emergency medical services group, the time from onset to reaching our hospital was similar between the groups. National Institutes of Health Stroke Scale on admission and final prognosis were significantly worse with physician-staffed helicopter emergency medical services than with ground emergency medical services. Multivariate analysis showed no association between transport system and prognosis. CONCLUSIONS: In this study, patients transported by physician-staffed helicopter emergency medical services had more severe stroke symptoms and poorer functional outcomes than those transported by ground emergency medical services. However, the transport time was shorter for physician-staffed helicopter emergency medical services; thus, physician-staffed helicopter emergency medical services may be useful for reducing transport time for patients in rural Japan.

Subacute Sensory Ataxic Neuronopathy With Thymoma Presenting Marked Improvement After Steroid Therapy.

Subacute sensory ataxic neuronopathy is a well-known form of paraneoplastic syndrome. Most sensory neuronopathies are associated with small cell lung cancer and anti-Hu antibodies, and usually show only slight improvement with immunotherapy. To date, there have been few reports of neuropathy associated with thymoma and no treatment strategy has been established for thymoma-related neuropathy. Here, we provide the first report of a case of sensory ataxic neuronopathy with thymoma that showed marked improvement after steroid therapy, even though preceding intravenous immunoglobulin treatments and tumor resection were less effective. A 57-year-old Japanese man was referred to our hospital with a 6-week history of distal paresthesia in his four limbs and an unsteady gait. He presented with left-dominant ataxia in his four limbs due to reduced sensation in his extremities. He also complained of constipation, difficulty urinating, and erectile dysfunction. Upon investigation, including electrodiagnostic studies, the patient was diagnosed as having sensory ataxic neuronopathy with invasive thymoma. A first round of intravenous immunoglobulin therapy, a following thymectomy, and a second round of intravenous immunoglobulin therapy after the surgery were not effective in treating his neurological symptoms. Subsequently, oral steroid therapy was started, which brought about a remarkable improvement; 6 weeks after the beginning of the steroid therapy, his neurological symptoms were resolved, except for slight distal paresthesia in his feet. Although rarely reported, thymoma can underlie sensory neuronopathy, and the response of thymoma-associated sensory neuronopathy to immunotherapy might be better than that of anti-Hu antibody-related neuropathies. Even if the first immunotherapy is not effective in treating neuropathy with thymoma, further immunomodulatory treatment should be tried after treating the tumor.