Том 44, № 8 (2018)

Various neurological diseases involving motor neurons damage lead to a decrease in the number of functioning motor units (MUs). Accurate estimation of the number of intact MUs plays significant role in evaluating motor neuron death. Quantitative analysis of MUs by methods of routine electromyography is usually not possible. Therefore, electrophysiological techniques for MU number estimation (so-called motor unit number estimation, MUNE), have been rapidly developing over the past decades. The first article on MUNE was published in 1971. Promising, accurate, and less time-consuming modifications have been developed since, and new methods for counting MU have been proposed. In recent years, one can see increasing interest in MUNE explained by the ongoing research on new possibilities of motor neuron disease treatment, and evaluation of their effectiveness, dynamic control of the disease. Today, MUNE is considered to be a potential biomarker in many clinical trials involving patients with motor neuron disease. This review provides in sights on available MUNE techniques, describes their comparative characteristics, advantages and disadvantages of each method and their application perspectives.

Amyotrophic lateral sclerosis (ALS) is a fatal progressive disorder of the central nervous system affecting the upper and lower motor neurons. It is important to study the specific nature of the disease course and the character of neurodegenerative process expansion in ALS, since no effective methods of treatment for this disease have been developed yet. Despite the clear evidence of multisystem brain damage in ALS, there are no objective biomarkers of the upper motor neuron lesion and extramotor brain areas involvement. In recent years, structural and functional neuroimaging, such as MR-morphometry, diffusion-tensor magnetic resonance imaging, MR spectroscopy, functional MRI, positron emission tomography (PET), etc., have been playing a significant role in research on ALS. This review analyzes the results of neuroimaging methods in the context of their application for diagnostics, prediction, and monitoring the ALS course. The most sensitive and specific techniques to diagnose the disease are diffusion-tensor MRI, MR spectroscopy, PET, a combination of several neuroimaging methods, and neuroimaging with transcranial magnetic stimulation. Diffusion-tensor MRI and MR spectroscopy can be used to monitor and predict the disease course. The main limitations and weak points of the published studies on this topic, as well as the prospective for neuroimaging in ALS, are discussed.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary CNS disease with autosomal dominant inheritance caused by NOTCH3 gene mutations. Typically, CADASIL manifests with headaches, recurrent strokes, and progressive cognitive decline. Neuroimaging plays an important diagnostic role as it reveals multiple lacunar infarcts in the basal ganglia, brainstem, and cerebellum, as well as focal white matter lesions and diffuse leukoaraiosis-type changes. CADASIL can sometimes have other symptoms and mimic different phenotypes atypical of the disease. We hereby present two genetically confirmed CADASIL cases that manifested with predominantly cerebellar or essential tremor combined with cognitive and affective disturbances. The main principles of diagnosis of this disease characterized by clinical polymorphism are discussed.

Introduction: Systemic thrombolytic therapy (STLT) with recombinant tissue plasminogen activator (rtPA) is the “gold standard” of reperfusion therapy in certain patients with ischemic stroke during the first 4.5 h after stroke onset. Objective: To assess the clinical (severity of neurological symptoms) and laboratory (complete blood cell count test) factors that affect the disease outcome after STLT. Materials and methods: Seventy patients (48 males and 22 females) aged 61 [54; 69] years with ischemic stroke who received rtPA therapy at a dose of 0.9 mg/kg were prospectively studied. Blood for the complete blood count test including neutrophil and lymphocyte counts was sampled before the thrombolytic therapy. The severity of neurological impairment was assessed using the NIH Stroke Scale (NIHSS). The functional outcome was assessed 3 months after stroke with the modified Rankin scale (mRS). ROC analysis was used to reveal factors of unfavorable outcome in acute phase of ischemic stroke (mRS score ≥ 3). Results: Severity of neurological deficit was assessed according to the NIHSS at admission was 15 [11; 17] points. Time between the manifestation of neurological symptoms and admission to the hospital was 138 [117; 170] min, and time between admission and initiation of STLT (the door-to-needle time), was 40 [30; 55] min. An unfavourable functional outcome of systemic thrombolytic therapy can be predicted according to the results of ROC analysis: the NIHSS score upon admission 12 or higher (sensitivity, 94%; specificity, 57%); neutrophil count, >7.8 × 10⁹/L (sensitivity, 45.5%; specificity, 90.6%); lymphocyte count < 1.8 × 10⁹/L (sensitivity, 81.8%; specificity, 59.4%). Conclusions: Personalized approach to systemic thrombolytic therapy may help to predict its effectiveness and contribute the development of more reliable strategies of patient management. Patients with potentially unfavorable outcome after intravenous thrombolysis can be the target group for mechanical reperfusion techniques such as thrombus extraction.

Introduction: Cervical artery dissection (CeAD) is the most frequent cause of ischemic stroke in young adults. Dysplasia of arterial wall underlies its weakness and predisposes to dissection. Objective: To assess clinical signs of connective tissue dysplasia (CTD) in patients with CeAD using special criteria of CTD, and to evaluate predisposing factors for the CeAD development. Materials and methods: We examined 80 patients (mean age 38.5 ± 13.5; 49 females) with CeAD verified by MRI/MRA and 20 healthy volunteers. We estimated 48 signs of CTD included into the Villefranche diagnostic criteria for the vascular type of Ehlers–Danlos syndrome, the Ghent criteria for Marfan syndrome, the Beighton criteria of joint hypermobility and some others, as well as history of headache. Each sign was counted as present or absent, yielding the individual and mean CTD group scores. Results: Clinical CTD signs were more frequently detected in patients with CeAD than in controls (mean score 7.9 ± 3.6 vs. 4.6 ± 2.5; p ≤ 0.05. Conclusions: The presence of the 4 main and 2 additional diagnostic criteria of CTD has a high predictive value of CeAD and can be used as its diagnostic and prognostic criterion. Dissection of the arterial wall with signs of dysplasia is provoked by various additional factors.

Introduction. Hemorheological abnormalities in patients with Ph-negative myeloproliferative disorders (MPD) may lead to the development and/or progression of cerebrovascular pathology. Adequate preventive therapy in such cases lowers the risk of cerebral thrombotic complications. Objective. Evaluation of the effect of dipyridamole and acetylsalicylic acid (ASA) on platelet and erythrocyte aggregation, as well as on morphofunctional properties of erythrocytes in patients with cerebrovascular disease (CVD) due to MPD. Materials and methods. The study comprised 40 patients with various forms of CVD and Рh-negative MPD: 20 patients received dipyridamole, and 20 received ASA for prevention of cerebral thrombotic complications. Mean patient’s age was 44.6 years [35; 58.5]. A thorough clinical and neurological examination was performed, as well as neuroimaging studies, coagulation tests, analysis of platelet aggregation and rheological properties of erythrocytes. Results. Within the observation period (median—6.3 months) no acute cerebrovascular events in both groups were registered. Platelet aggregation (induced by ADP or adrenaline) was similar in both groups. Dipyridamole and ASA were also similar in their effect on functional properties of erythrocytes. Conclusion. Our findings suggest that the therapeutic effect of dipyridamole concerning CVD is similar to that of ASA. Dipyridamole can be recommended for use in patients with Рh-negative MPD if other antiplatelet agents are contraindicated.

Introduction: Alzheimer’s disease is a chronic neurodegenerative disease leading to neuropsychiatric disorders and cognitive decline. A number of studies demonstrate an important role of the mitogen-activated protein kinase (MAPK) pathway and NLRP3 inflamasomes in β-amyloid metabolism impairment and insulin resistance in Alzheimer’s disease. Objective: To study the expression of NLRP3 in the cells of neuronal and glial nature, as well as the expression of MAPK in the amygdala neurons in animals with experimental Alzheimer’s disease. Materials and methods: Subjects of the study: (1) CD1 mice (males, 4 months old) divided in 2 groups, the experimental group (intra-hippocampal exposure to β-amyloid) and the control group (sham-operated animals); (2) mice with a genetic model of Alzheimer’s disease, the B6SLJ-line Tg (APPSwFlLon, PSEN1*M146L*L286V) 6799Vas (males, 12 months old) and the corresponding control group, C57BL/6xSJL mice (males, 12 months old). Immunohistochemistry on free-floating sections was applied for the study of NLRP3 and MAPK expression in the brain amygdala. Results: We revealed the statistically significant increase in the number of NeuN/NLRP3-positive cells (p = 0.043) of the amygdala in animals with a genetic model of Alzheimer’s disease (29.05 ± 2.67) compared with the control group of animals (17.10 ± 1.95). A same trend was obvious in β-amyloid-induced neurodegeneration (p = 0.021). Intra-hippocampal exposure to β-amyloid caused the decrease of MAPK expression in the amygdala neurons (5.97 ± 0.66) compared with the sham-operated animals (13.25 ± 2.65) (p = 0.018). This was also seen in animals with a genetic model of the Alzheimer’s disease (p = 0.031). Conclusions: The increase of NLRP3 inflammasomes expression in animals with experimental Alzheimer’s disease was found in neurons, but not in astrocytes, along with a decrease of the MAPK expression in neurons of the amygdala. These findings indicate coupling of the inflammatory process and the disorganization on the insulin-signaling mechanisms of the brain during neurodegeneration.