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Background/purpose: Orthostatic myoclonus (OM) is myoclonic jerks in both legs during standing. It may relate to gait unsteadiness and may be associated with various diagnoses, including neurodegenerative, systemic, and musculoskeletal diseases. Diagnosis is based on the surface electromyography (SEMG). Methods: From January 2016 to June 2020, we retrospectively reviewed 35 patients diagnosed with OM based on the SEMG criteria and analyzed the electrophysiological data. Results: The mean age was 75.3±8.9. Disease duration ranged from 2 days to several years. Genders were equally affected. The most common symptom was gait disturbance, and the next was leg tremulous sensation, followed by backward disequilibrium. 28.6% of our patients had falls. Electrophysiologically, bursting duration shorter than 100 ms supported the myoclonic origin from the cortex. The bursting activity occurred only on the upright and weight-bearing leg. The associated diagnoses included lumbosacral radiculopathy (28.6%), lumbosacral radiculopathy plus myasthenia gravis (2.9%), lumbosacral radiculopathy plus vascular parkinsonism (5.7%), diabetic polyneuropathy (5.7%), vascular parkinsonism (17.1%), Parkinson's disease (PD) (14.2%), normal pressure hydrocephalus (5.7%), medication-induced parkinsonism (2.9%), cervical myelopathy (2.9%), medication-related myoclonus (2.9%), and unknown (11.4%). In PD, OM was present before, along with, or after PD diagnosis. The myoclonic activity disrupted the parkinsonian tremor upon standing on SEMG. Conclusion: OM is a syndrome instead of a diagnosis. It is more prevalent in the elderly with gait disturbance and patients will not necessarily fall. It is associated with central and peripheral nerve system disorders, systemic diseases, and medication use. We hypothesize that OM is a pathological disintegration of motor circuit.

Background: Parkinson’s disease (PD) is characterized by intraneuronal α-synuclein aggregation called Lewy bodies and progressive dopaminergic neurodegeneration. Toll-like receptor (TLR) signaling is a major pathway mediating inflammation. The molecular link on how neuroinflammation upregulates neuronal TLRs and induces accumulation of α-synuclein aggregates to drive synucleinopathy remains to be determined.Objective: Despite conditioned medium from microglia and TLR agonists were utilized to study their effects on neuronal cells, a Transwell coculture system, comprising lipopolysaccharide-activated microglia on top and retinoic acid-differentiated SH-SY5Y cells at the bottom more mimicking in vivo neuroinflammation, was employed to elucidate the mechanism of activated microglia on neuronal cells.Methods: Genetic variants of TLRs in PD patients were genotyped and the multiplex cytokines, sRAGE, and HMGB1were assessed. A coculture system was employed to measure α-synuclein aggregates and neurite shortening by confocal microscope. The expression of TLR2/4 and autophagy flux was detected by western blot and immunofluorescence.Results: PD patients showed higher plasma levels of proinflammatory cytokines and genetic TLR4 variant, c.896 A > G (p. D299G). Elevated proinflammatory cytokines in coculture medium was also seen. Phosphorylation and aggregation of α-synuclein, shortening of neurite, upregulation of TLR2/4 expression, activation of downstream p38 and JNK, and dampening of autophagic flux were seen in SH-SY5Y cells cocultured with activated microglia. Those were prevented by inhibiting TLR2/4 and p38/JNK signaling.Conclusion: Activated microglia-derived neuroinflammation induced neuronal TLR2/4-p38/JNK activation to perturb autophagy, causing accumulation of α-synuclein aggregates and neurite shortening. Targeting neuronal TLR2/4 pathway might be a mechanistic-based therapy for neurodegenerative disease, such as PD.

Objective: Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts.Methods: The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994–2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality.Results: Low cholesterol (LDL-C

Pain is a common non-motor symptom of Parkinson's disease (PD) and the prevalence of pain among PD patients varies because of the disease stage, co-morbidities, and evaluating tools. Risk factors for pain in PD include an early age of onset, long disease duration, motor complications, concomitant depressive symptoms, female gender, and associated medical conditions. In patients with PD, pain can be classified as musculoskeletal pain, chronic body pain (central or visceral), fluctuation-related pain, nocturnal pain, orofacial pain, pain with discolouration/oedema/swelling, and radicular/neuropathic pain; musculoskeletal pain as the most common type. Potential underlying mechanisms include a disruption of peripheral nociception and alterations in central pain threshold/processing. Genetic polymorphisms in genes that confer pain susceptibility might also play a role in the occurrence of pain in PD. In advanced stage of patients with PD, polyneuropathy could occur in patients using high dosage of levodopa. Pain often correlates to other non-motor symptoms of PD, including depression, sleep, and autonomic symptoms. Dopaminergic drugs, non-dopaminergic medications, botulinum toxin, deep brain stimulation, and physiotherapy have shown some benefits for certain types of PD-related pain. An increased awareness of pain as a common non-motor symptom of PD provides further insights into sensory system dysregulation in this disease. In this review, we aim to summarizes the clinical features of pain in patients with PD and emphasize the latest evidence of pain related to levodopa treatment.

Abstract Objective Emerging evidence suggests that gut microbiome composition alterations affect neurodegeneration through neuroinflammation in the pathogenesis of Parkinson’s disease (PD). Here, we evaluate gut microbiota alterations and host cytokine responses in a population of Taiwanese patients with PD. Methods Fecal microbiota communities from 80 patients with PD and 77 age and gender-matched controls were assessed by sequencing the V3–V4 region of the 16S ribosomal RNA gene. Diet and comorbidities were controlled in the analyses. Plasma concentrations of IL-1β, IL-2, IL-4, IL-6, IL-13, IL-18, GM-CSF, IFNγ, and TNFα were measured by a multiplex immunoassay and relationships between microbiota, clinical characteristics, and cytokine levels were analyzed in the PD group. We further examined the cytokine changes associated with the altered gut microbiota seen in patients with PD in another independent cohort of 120 PD patients and 120 controls. Results Microbiota from patients with PD was altered relative to controls and dominated by Verrucomicrobia, Mucispirillum, Porphyromonas, Lactobacillus, and Parabacteroides. In contrast, Prevotella was more abundant in controls. The abundances of Bacteroides were more increased in patients with non-tremor PD subtype than patients with tremor subtype. Bacteroides abundance was correlated with motor symptom severity defined by UPDRS part III motor scores (rho = 0.637 [95% confidence interval 0.474 to 0.758], P

Cerebrospinal fluid (CSF) leak can be spontaneous or nonspontaneous. The management options include conservative treatments, blood patch, and surgical repairs. We compared clinical symptoms, image findings, management options, hospitalization, and relapse rates among different causes of CSF leaks. Eighty-one patients were recruited: 20 with spontaneous and 61 with nonspontaneous CSF leaks. Nonspontaneous causes included lumbar puncture, surgery, and trauma. Surgery sites comprised sphenoid, spine, skull base, and calvaria. Spontaneous CSF leak came from the sphenoid or spine. Age, gender, body mass index, initial symptoms, hospitalization, treatment courses, and recurrence rates showed no difference between the groups. The spontaneous group had higher CSF accumulations on their MRIs. MRI pachymeninge enhancement showed the highest sensitivity (78.6%) for intracranial hypotension. Meningitis occurred in 1/3 of sphenoid, skull base, and calvarian surgeries. Earlier reoperation was correlated with shorter hospitalization (r = 0.651), but the recurrence rates were similar. Longer intervals between surgery and CSF leak encouraged reoperation. Among the spontaneous spine and lumbar puncture-related CSF leaks, 57.1% of them responded to 4 days of conservative treatment. Among the trauma-related CSF leaks, 90.9% of them required surgical repair. The demographic data and symptoms were similar in various groups of CSF leak. The symptom onset durations and treatment strategies were different. However, the recurrence rates were similar.

Abstract Background To determine the association of prior traumatic brain injury (TBI) with subsequent diagnosis of neurodegeneration disease. Methods All studies from 1980 to 2016 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, Embase, study references, and review articles. The data and study design were assessed by 2 investigators independently. A meta-analysis was performed by RevMan 5.3. Results There were 18 studies comprising 3,263,207 patients. Meta-analysis revealed a significant association of prior TBI with subsequent dementia. The pooled odds ratio (OR) for TBI on development of dementia, FTD and TDP-43 associated disease were 1.93 (95% CI 1.47–2.55, p