This study confirmed a positive survival effect with NIV, which was less effective in patients with bulbar dysfunction. Additional studies are required to determine the best timing for using NIV with ALS in patients with bulbar dysfunction.
Motor symptoms of Parkinson’s disease (PD) occur unilaterally and progress with asymmetry, while progressive supranuclear palsy (PSP) and multiple system atrophy of the parkinsonism subtype (MSA-P) lack this tendency. We assessed the laterality of specific binding ratios (SBRs) on dopamine transporter single-photon emission computed tomography (DAT-SPECT) for the differential diagnosis of these diseases in 311 PD, 33 PSP, 20 MSA-P, and 137 control patients. The average SBR in PD was higher than that in PSP (P = 0.035). Compared with Hoehn–Yahr (HY) stages, the average SBR in PD with HY stage I was only higher than that in PSP (P < 0.001). SBR laterality in PD with HY stage I was significantly higher than that in PSP (P = 0.001). This difference was not observed in PD with HY stage II. The average and laterality of SBRs in MSA-P were similar to those in PD and PSP. The asymmetry indices were similar among PD, PSP, and MSA-P. These data suggest that PSP shows a pattern of SBRs different from that in PD, attributed to HY stage I in PD. The limited usefulness of DAT-SPECT may be explained by the low discrimination between PD with bilateral motor symptoms and PSP.
Cell-to-cell transmission of a-synuclein (a-syn) pathology is considered to underlie the spread of neurodegeneration in Parkinson's disease (PD). Previous studies have demonstrated that a-syn is secreted under physiological conditions in neuronal cell lines and primary neurons. However, the molecular mechanisms that regulate extracellular a-syn secretion remain unclear. In this study, we found that inhibition of monoamine oxidase-B (MAO-B) enzymatic activity facilitated a-syn secretion in human neuroblastoma SH-SY5Y cells. Both inhibition of MAO-B by selegiline or rasagiline and siRNA-mediated knock-down of MAO-B facilitated a-syn secretion. However, TVP-1022, the S-isomer of rasagiline that is 1000 times less active, failed to facilitate a-syn secretion. Additionally, the MAO-B inhibition-induced increase in a-syn secretion was unaffected by brefeldin A, which inhibits endoplasmic reticulum (ER)/ Golgi transport, but was blocked by probenecid and glyburide, which inhibit ATP-binding cassette (ABC) transporter function. MAO-B inhibition preferentially facilitated the secretion of detergent-insoluble a-syn protein and decreased its intracellular accumulation under chloroquine-induced lysosomal dysfunction. Moreover, in a rat model (male Sprague Dawley rats) generated by injecting recombinant adeno-associated virus (rAAV)-A53T a-syn, subcutaneous administration of selegiline delayed the striatal formation of Ser129-phosphorylated a-syn aggregates, and mitigated loss of nigrostriatal dopaminergic neurons. Selegiline also delayed a-syn aggregation and dopaminergic neuronal loss in a cell-to-cell transmission rat model (male Sprague Dawley rats) generated by injecting rAAV-wild-type a-syn and externally inoculating a-syn fibrils into the striatum. These findings suggest that MAO-B inhibition modulates the intracellular clearance of detergent-insoluble a-syn via the ABC transporter-mediated non-classical secretion pathway, and temporarily suppresses the formation and transmission of a-syn aggregates.
A 68-year-old woman presented with a 2-year history of worsening unsteady gait. Her neurological examination revealed peripheral neuropathy with lower limb sensory dominance. T2-weighted imaging revealed a disorder of the posterior cervical cord. Blood test findings revealed vitamin B12 deficiency, and gastroscopy revealed typical findings of autoimmune gastritis. She received vitamin B12 supplementation, but some peripheral neuropathy symptoms persisted due to longstanding vitamin B12 deficiency. Asymptomatic patients should undergo gastroscopy to detect autoimmune gastritis, as chronic vitamin B12 deficiency causes irreversible peripheral neuropathy.
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