Patterns of symptom development in patients with motor neuron disease

<p><i>Objective</i>: To investigate whether symptom development in motor neuron disease (MND) is a random or organized process. <i>Methods</i>: Six hundred patients with amyotrophic lateral sclerosis (ALS), upper motor neuron (UMN) or lower motor neuron (LMN) phenotypes were invited for a questionnaire concerning symptom development. A binomial test was used to examine distribution of symptoms from site of onset. Development of symptoms over time was evaluated by Kaplan-Meier analysis. <i>Results</i>: There were 470 respondents (ALS = 254; LMN = 100; UMN = 116). Subsequent symptoms were more often in the contralateral limb following unilateral limb onset (ALS: arms <i>p</i> = 1.05 × 10⁻⁸, legs <i>p</i> < 2.86 × 10⁻¹⁵; LMN phenotype: arms <i>p</i> = 6.74 × 10⁻⁹, legs <i>p</i> = 6.26 × 10⁻⁶; UMN phenotype: legs <i>p</i> = 4.07 × 10⁻¹⁴). In patients with limb onset, symptoms occurred significantly faster in the contralateral limb, followed by the other limbs and lastly by the bulbar region. Patterns of non-contiguous symptom development were also reported: leg symptoms followed bulbar onset in 30%, and bulbar symptoms followed leg onset in 11% of ALS patients. <i>Conclusions</i>: Preferred spread of symptoms from one limb to the contralateral limb, and to adjacent sites appears to be a characteristic of MND phenotypes, suggesting that symptom spread is organized, possibly involving axonal connectivity. Non-contiguous symptom development, however, is not uncommon, and may involve other factors.</p

Circulating microRNAs in patients with intracranial aneurysms

<div><p>Introduction</p><p>We compared circulating microRNA (miRNA) levels in plasma of patients with intracranial aneurysms (IA) to those of controls as a first step towards finding potential biomarkers for individuals at high risk of IA development and its subsequent rupture.</p><p>Patients and methods</p><p>Using a PCR array we measured 370 miRNAs in plasma of 15 patients with prior aneurysmal subarachnoid hemorrhage (aSAH), of whom 11 had an additional unruptured IA (UIA), and of 15 controls. MiRNAs with a difference in levels with an absolute fold change (FC) > 1.2 and p<0.01 were further tested using real-time (RT) PCR in an additional independent set of 15 aSAH patients, 15 untreated UIA patients and 15 controls for replication (absolute FC >1.2 and p<0.05). We used receiver operating characteristic (ROC) curves to illustrate the diagnostic potential of these miRNAs.</p><p>Results</p><p>Three of five miRNAs with a difference in levels in the PCR array study were replicated with miRNA-183-5p decreased in all patients (FC = -2.2, p = 1.7x10^-3), miRNA-200a-3p increased in aSAH patients (FC = 1.8, p = 2.8x10^-2) and miRNA-let7b-5p decreased in UIA patients (FC = -1.7, p = 1.27x10^-3) as compared to controls. In distinguishing aSAH patients from controls, the area under the ROC curve (AUC) was 0.80 (95% confidence interval (95% CI) 0.63–0.97) for miRNA-183-5p, and 0.74 (95% CI 0.55–0.94) for miRNA-200a-3p. In distinguishing untreated UIA patients from controls, AUC was 0.83 (95% CI 0.69–0.98) for miRNA-183-5p and 0.92 (95% CI 0.81–1) for miRNA-let-7b.</p><p>Discussion/Conclusions</p><p>We identified three specific circulating miRNAs that are able to discriminate between IA patients and controls. Follow-up studies should assess if these miRNAs may be used biomarkers for identifying individuals at high risk of IA development and its subsequent rupture.</p></div

Baseline characteristics of the study population.

<p>FIA indicates familial intracranial aneurysm, N: number, SAH: subarachnoid hemorrhage, NA: not applicable.</p><p>Baseline characteristics of the study population.</p