Search

Purpose: The aim of this study was to investigate a structured approach for effective speech therapy (ST) for dysarthria and speech-related quality of life in patients with sporadic spinocerebellar degeneration (SCD), including cerebellar-type multiple-system atrophy and cerebellar cortical atrophy. Method: Twenty-two patients with SCD (cerebellar-type multiple system atrophy, 15 patients; cerebellar cortical atrophy, seven patients) who underwent intensive ST were examined. Dysarthria was evaluated using the Scale for Assessment and Rating of Ataxia Speech Dysfunction, Assessment of Motor Speech for Dysarthria Articulation, oral diadochokinesis (OD), and Voice Handicap Index-10 (VHI-10). Respiratory muscle strength (inspiratory and expiratory pressure) and respiratory-phonatory coordination (maximum phonation time) were measured. Cognitive function was evaluated using the Montréal Cognitive Assessment and the word fluency test. Mood was evaluated using the Hospital Anxiety and Depression Scale. The relationships between dysarthria scales (particularly, VHI-10) and clinical data were analyzed using stepwise regression. The differences in outcomes after intensive ST were analyzed using the Wilcoxon signed-rank test. The alpha level (p) for statistical significance was set at 0.0125 by Bonferroni correction. Results: For both pre- and post-ST, the patient's OD (p = 0.002) and maximum phonation time (p = 0.002) significantly improved, except for Speech Dysfunction scores of the Scale for Assessment and Rating of Ataxia (p = 0.705) and the VHI-10 (p = 0.018). The Assessment of Motor Speech for Dysarthria Articulation, OD, and inspiratory pressure were identified as independent variables of VHI-10 (adjusted R[subscript 2] = 0.820) for speech-related quality of life; no correlations among the Montréal Cognitive Assessment, word fluency test, and Hospital Anxiety and Depression Scale scores were observed. Conclusion: OD and VHI-10 showed improvements due to changes in speech function and respiratory-phonatory coordination, justifying intensive ST treatment for dysarthria in patients with SCD.

To examine whether hypermetabolism could predict the prognosis of early amyotrophic lateral sclerosis (ALS) patients with differing nutritional profiles. This single-center, retrospective study examined the prognosis of ALS patients with hypermetabolism in relation to their nutritional status at hospitalization. The metabolic state was estimated by the ratio of measured resting energy expenditure (mREE) to lean soft tissue mass (LSTM) (mREE/LSTM), wherein patients with ratios ≥ 38 were defined as hypermetabolic. Malnutrition was defined as %ideal body weight < 0.9. Forty-eight patients were enrolled in this study. The hypermetabolic group had shorter survival in the normal-weight group but more prolonged survival in the malnutrition group. Multiplication of nutritional and metabolic factors, such as [(body mass index (BMI) − 19.8) × (mREE/LSTM − 38)], designated as BMI-muscle metabolism index (BMM index), successfully predicted the prognosis in the group with a high BMM index (≥ 1), which showed shorter survival and a faster rate of weight loss and functional decline. Multivariate analysis using the Cox model showed high BMM index was an independent poor prognostic factor (hazard ratio: 4.05; p = 0.025). Prognostic prediction by hypermetabolism varies depending on the nutritional status in ALS, and the BMM index is a consistent prognostic factor. [ABSTRACT FROM AUTHOR]

Background/Aims: Nutritional status is a factor affecting prognosis in patients with amyotrophic lateral sclerosis (ALS). Here, we aimed to clarify the factors associated with hypermetabolism and the prognosticators of ALS. Methods: Forty-two inpatients (22 men, 20 women) diagnosed with ALS according to the revised El-Escorial criteria were investigated. The following data were retrospectively analyzed: anthropometric measurements, blood biochemistry, disease severity, basal energy expenditure (BEE), resting energy expenditure (REE) measured by indirect calorimetry, spirometry, and bioelectrical impedance analysis. Single and multiple regression analysis was performed to examine factors affecting REE and metabolic changes (defined as the ratio of REE to fat-free mass [FFM]). The Kaplan-Meier method was used to examine factors associated with the occurrence of cumulative events (death or tracheostomy). Results: Among the 42 inpatients, REE was significantly higher than BEE, indicating hypermetabolism in ALS. Multiple regression analysis revealed that REE/FFM is strongly associated with the skeletal muscle index (−3.746 to −1.532, p < 0.0001) and percent forced vital capacity (%FVC) (−0.172 to −0.021, p = 0.013). Moreover, both the skeletal muscle index and %FVC were significant prognosticators associated with the occurrence of cumulative events. Conclusions: Energy metabolism was elevated in ALS, and respiratory status and muscle mass were associated with the hypermetabolism and poor prognosis. Adequate nutritional support may improve outcomes in ALS by preventing deterioration of respiratory status and reduction in muscle mass. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) stimulates peripheral nerve regeneration. However, the origin of BNDF and its precise effect on nerve repair have not been clarified. In this study, we examined the role of BDNF from bone marrowderived cells (BMDCs) in post-injury nerve repair. Control and heterozygote BDNF knockout mice (BDNF+/-) received a left sciatic nerve crush using a cerebral blood clip. Especially, for the evaluation of BDNF from BMDCs, studies with bone marrow transplantation (BMT) were performed before the injury. We evaluated nerve function using a rotarod test, sciatic function index (SFI), and motor nerve conduction velocity (MNCV) simultaneously with histological nerve analyses by immunohistochemistry before and after the nerve injury until 8 weeks. BDNF production was examined by immunohistochemistry and mRNA analyses. After the nerve crush, the controls showed severe nerve dysfunction evaluated at 1 week. However, nerve function was gradually restored and reached normal levels by 8 weeks. By immunohistochemistry, BDNF expression was very faint before injury, but was dramatically increased after injury at 1 week in the distal segment from the crush site. BDNF expression was mainly co-localized with CD45 in BMDCs, which was further confirmed by the appearance of GFP-positive cells in the BMT study. Variant analysis of BDNF mRNA also confirmed this finding. BDNF+/- mice showed a loss of function with delayed histological recovery and BDNF+/+→BDNF+/- BMT mice showed complete recovery both functionally and histologically. These results suggested that the attenuated recovery of the BDNF+/- mice was rescued by the transplantation of BMCs and that BDNF from BMDCs has an essential role in nerve repair. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF)-α is a potent proinflammatory cytokine involved in the pathogenesis of diabetic neuropathy. We inactivated TNF-α to determine if it is a valid therapeutic target for the treatment of diabetic neuropathy. We effected the inactivation in diabetic neuropathy using two approaches: by genetic inactivation of TNF-α (TNF-α-/- mice) or by neutralization of TNF-α protein using the monoclonal antibody infliximab. We induced diabetes using streptozotocin in wild-type and TNF-α-/- mice. We measured serum TNF-α concentration and the level of TNF-α mRNA in the dorsal root ganglion (DRG) and evaluated nerve function by a combination of motor (MNCV) and sensory (SNCV) nerve conduction velocities and tail flick test, as well as cytological analysis of intraepidermal nerve fiber density (IENFD) and immunostaining of DRG for NF-κB p65 serine-276 phosphorylated and cleaved caspase-3. Compared with nondiabetic mice, TNF-α+/+ diabetic mice displayed significant impairments of MNCV, SNCV, tail flick test, and IENFD as well as increased expression of NF-κB p65 and cleaved caspase-3 in their DRG. In contrast, although nondiabetic TNF-α-/- mice showed mild abnormalities of IENFD under basal conditions, diabetic TNF-α-/- mice showed no evidence of abnormal nerve function tests compared with nondiabetic mice. A single injection of infliximab in diabetic TNF-α+/+ mice led to suppression of the increased serum TNF-α and amelioration of the electrophysiological and biochemical deficits for at least 4 wk. Moreover, the increased TNF-α mRNA expression in diabetic DRG was also attenuated by infliximab, suggesting infliximab's effects may involve the local suppression of TNF-α. Infliximab, an agent currently in clinical use, is effective in targeting TNF-α action and expression and amelioration of diabetic neuropathy in mice. [ABSTRACT FROM AUTHOR]

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare disease associated with the presence of anti-glycine receptor (GlyR) antibodies. We herein report an autopsy case of an 80-year-old man diagnosed with anti-GlyR antibody-positive PERM who presented with symptoms of oculomotor dysfunction and autonomic failure. Despite intensive immunotherapy, the neurological symptoms showed almost no improvement, and the patient succumbed to aspiration pneumonia and bacterial translocation. Postmortem pathology revealed mild inflammatory changes and neuronal loss that were disproportionate to a severe clinical presentation. These results suggest that the clinical symptoms of PERM may result from antibody-mediated GlyR internalization, leading to neuronal disinhibition, rather than a neuroinflammatory signature.

Introduction: This study sought to identify the optimal caloric intake to improve function and survival in ALS patients by comparing oral intake per ideal body weight (IBW) and its discrepancy with total energy expenditure (TEE) using the Shimizu formula., Methods: A retrospective analysis of 104 ALS patients was conducted, categorizing them based on their average intake during the first week after admission using two primary intake cutoffs: 25 kcal/kgIBW and 30 kcal/kgIBW. The variance between oral intake and TEE was also evaluated using -300 kcal and 0 kcal as reference points., Results: Oral caloric intake per IBW and functional decline rate (rs = -0.35, p  < 0.001), but the variance from TEE was not significantly correlated (-0.11, p  = 0.27). Survival data showed that patients consuming less than 25 kcal/kgIBW had a median survival of 24 months, increasing to 38 months for those consuming between 25-30 kcal/kgIBW and 63 months for those consuming 30 kcal/kgIBW or more. Deviations from the TEE did not significantly affect survival ( p  = 0.36). Among patients consuming less than their TEE, those consuming less than 25 kcal/kgIBW had a shorter median survival (24 months) compared to their counterparts (46 months) ( p  = 0.022). Consumption of less than 25 kcal/kgBW emerged as a significant negative predictor of patient outcome, independent of factors such as age, gender or disease progression., Discussion: Intakes of 25 kcal/kgIBW or more are correlated with improved ALS outcomes, and larger, multi-regional studies are recommended for deeper insights., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nakamura, Kurihara, Kobashi, Tamaki, Ogawa, Kitamura, Yamakawa, Bamba, Terashima and Urushitani.)

Competing Interests: Competing interests: None declared.

A 23-year-old woman was admitted for slowly progressive proximal limb muscle weakness from childhood with elevated muscle enzyme levels. Although muscular diseases were suspected, an electromyogram showed remarkable neurogenic changes, and a muscle echogram indicated selective muscle involvement, including dissociation between the soleus and gastrocnemius, which was consistent with previous reports using magnetic resonance imaging (MRI). She was diagnosed with SMA type 3 following genetic testing, and nusinersen was soon initiated. An early diagnosis is mandatory to maximize the benefit of treatment. A muscle echogram may facilitate an early diagnosis in a non-invasive and time-saving manner compared to MRI.

We herein report a 65-year-old man with progressive multifocal leukoencephalopathy (PML) after 2-year remission from acute myeloid leukemia who developed recurrent episodes of left hemiparesis with gadolinium enhancement on magnetic resonance imaging. Steroid pulse therapy for each exacerbation induced clinical and radiological improvement, suggesting that exacerbations are an excessive immune response to the JC virus and distinct from immune reconstitution inflammatory syndrome (IRIS). Although glucocorticoids are recommended only for IRIS, steroid pulse therapy should be considered as a therapeutic option in cases of exacerbation of hematologic malignancy-associated PML. Importantly, neuroimaging is not sufficient to differentiate excessive inflammation from a controlled inflammatory response, for which steroids are not recommended.