Vol 13, No 4 (2019)

Introduction. Family planning for patients with multiple sclerosis (MS) raises many questions and requires an integrated approach from neurologists and obstetrician-gynaecologists.

The study aimed to define possible features of pregnancy and childbirth in patients with MS.

Materials and methods. 204 patients with definite moderate MS, who were planning a pregnancy and taking First-Line Disease-Modifying Therapies (DMTs) before pregnancy. First group included 94 patients with pregnancies; the second group consisted of 110 patients, who failed to conceive within a stated period of time; in the third group there were 50 healthy women with normal pregnancies. Probability of developing pregnancy complications, time and method of delivery, anaesthetic procedures, weight, and height of newborns were assessed, while in the groups of patients with MS the risk of exacerbations and severity of the complications were evaluated.

Results and discussion. In the first group, there were more frequent threats of miscarriage and preterm birth, which might have taken place due to a complex of factors (cancellation of DMTs, use of hormonal therapy for exacerbations during pregnancy). The high frequency of caesarean section in the first group was associated with the unreasonable alertness of obstetrician-gynaecologists and the fear of the patients that the course of MS would worsen. Frequent exacerbations during pregnancy were associated with the abolition of DMTs before pregnancy and the failure of physiological immunosuppression during pregnancy.

Conclusion. In Russia, there is no single protocol for managing patients with MS during the period of family planning, pregnancy, and the postpartum period, which causes certain difficulties. There is emerging evidence that certain DMTs can be prescribed during pregnancy and lactation, which will help minimize the risks of exacerbations and disability increase.

Introduction. The risk of Alzheimer’s disease (AD) is increased with cerebral insulin resistance, which may be caused by the impaired function of the cerebrovascular system, and may also have a direct effect on β-amyloid aggregation and Tau protein phosphorylation.

Aim. To study the molecular expression of insulin signal transduction components (IRS1, GSK3B and PKC) in the brain cells in an experimental model of AD.

Materials and methods. Experiments were conducted on 4-month-old C57BL/6 and B6.129S6-Nlrp3tm1Bhk/JJ male mice (NLRP3 knockout mice) with 5 animals in each group. AD was modelled in the experimental group of mice by administering β-amyloid; mice in the control group received sham surgery. IRS1, GSK3B and PKC expression in the amygdala was studied using immunohistochemistry methods.

Results. The C57BL/6 mice with AD had reduced IRS1 expression compared with the mice who received sham surgery (0.62±0.13 and 0.89±0.17; р=0.045), while the β-amyloid did not produce the same result in NLRP3 knockout mice. GSK3B expression was increased in C57BL/6 mice with AD (0.60±0.12) when compared with both the control group (0.20±0.02; p<0.0001) and the NLRP3 knockout mice with AD (0.27±0.08; p<0.0001). PKC expression in C57BL/6 mice with AD was reduced (0.52±0.14) when compared with the NLRP3 knockout mice with AD (0.89±0.18; p<0.05) and the control group (0.84±0.12; p<0.05).

Conclusion. The development of Alzheimer type-neurodegeneration is accompanied by disruptions in IRS1 and GSK3B expression, which is associated with impaired signal transmission along the PKC pathway. The suppression of neuroinflammation through NLRP3 inflammasome deletion has a protective effect in AD.

The article presents an overview of the most topical matters relating to functional neurosurgery in Parkinson’s disease: the historical aspects, an overview of the international recommendations, long-term effects of neurostimulation, and the selection criteria for the surgical intervention. Summary data are provided for deep brain stimulation surgery in Russia, as well as an analysis of the need for neurostimulation compared with the international data.

The risk of progressive multifocal leukoencephalopathy (PML) is one of the factors limiting the widespread use of natalizumab (NTZ). As a strategy for potentially reducing the frequency of the NTZ-associated PML, while maintaining the high therapy efficacy, in addition to the widely-used risk stratification strategy based on anti-JC virus antibody index and therapy duration, we propose the administration of NTZ with an extended dosing interval. Opinions vary on the effectiveness of plasmapharesis in confirmed cases of PML. The most challenging problem is how to manage patients, who develop PML, and what MS disease-modifying therapy should be considered for the subsequent use.

Neonatal seizures in full-term and preterm infants represent a common neurological syndrome. Levetiracetam (LEV) is one of the new and widely prescribed second- or third-line antiepileptic drug for the treatment of seizures. Routine therapeutic drug monitoring of LEV was not recommended due to its almost ideal pharmacokinetic profile: linear pharmacokinetics, predictable dose-concentration relationship, wide therapeutic index, favourable safety profile, and unlikely clinically significant drug-drug pharmacokinetic interactions.

In newborns, drug pharmacokinetics may be under the influence of maturation process. LEV pharmacokinetics in newborns appears to be age (gestational, postnatal) dependent and highly variable within the age ranges. These aspects make therapeutic drug monitoring a useful procedure for therapy optimization in this specific patient population.

In population modeling based on therapeutic drug monitoring and nonlinear mixed effects models, covariates were found that should significantly affect the LEV clearance and volume of distribution in newborns — creatinine clearance and total body weight. Using of these regression equations can help to adjust the LEV doses without the patient's measured concentration data. But the significant magnitudes of the interindividual variability remaining in these final regression models justify the need for therapeutic drug monitoring and Bayesian adaptive control for personalization of LEV dosage regimens in neonates.

Research Center of Neurology, Moscow, Russia

Parkinson's disease (PD) is a progressive neurodegenerative disorder with a characteristic pathological hallmark of loss of the dopaminergic neurons in the compact part of the substantia nigra in the midbrain. Despite the significant progress made in learning about this disease, early diagnosis continues to be a complex clinical issue. Currently, many studies are focused on finding and implementing meaningful markers which are valid for the early PD diagnosis. One of the most promising areas in that field is investigation of specific changes in the substantia nigra, found when examining the nigrosomes (specific clusters of the dopaminergic neurons) and neuromelanin, using high-field magnetic resonance imaging (MRI).

This article presents the current understanding of the structural and functional organization of the substantia nigra, and examines in detail the new informative MRI-markers of neurodegeneration in PD: the loss of dorsolateral nigral hyperintensity (disappearance of the nigrosome-1) and a reduction in the intensity/area of the magnetic resonance signal from the substantia nigra when imaging the neuromelanin. We present our own experience of using the abovementioned technologies to diagnose PD, by analysing susceptibility-weighted images and images taken in neuromelanin-sensitive MRI mode.

GNE myopathy (Nonaka myopathy) is a rare recessive muscular dystrophy associated with the GNE gene, which is involved in sialic acid synthesis. Typical onset is in the third decade of life with distal weakness of the arms and legs, gradually progressing to the proximal muscles, along with severe generalized myopathy and loss of ambulation usually occurring 10–20 years after disease onset. Exomе sequencing methods have greatly increased the possibility of diagnosis of this and other rare hereditary diseases. A case of GNE myopathy with onset at 26 years of age and a prolonged search for a diagnosis, which was finally made after 12 years, is presented. Whole exome sequencing with subsequent Sanger sequencing verification found compound heterozygosity of the GNE mutations not previously described: с.787delA (p.Met263CysfsTer4) and c.2005G>T (p.Ala669Ser). Differential diagnosis and a literature review are presented.

The study of dystonic hyperkinesias has a thousand-year-old history. Beginning with drawings and sculptures from antiquity and up to the present day, modern ideas gradually developed about the phenomenology, origin, and treatment methods of dystonia. Mentions of spastic torticollis, blepharospasm and Meige syndrome can even be found in the writings of Hippocrates and Celsus. Images and monuments from antiquity and ancient civilizations indicate the existence of focal dystonias in those times.

The Middle Ages left science with records of cervical dystonia and numerous illustrations in religious images. The first well-known mention of the term ‘torticollis’ belongs to François Rabelais. The term started to appear in medical texts later on. One of the earliest medical records on cervical dystonia was made by the Swiss physician Felix Platerus. During the Age of Enlightenment, dystonias became a separate class in disease classification.

Modern tendencies in studying dystonia are characterized by identifying the genes responsible for different forms of primary dystonia along with description of their phenotypes. There is an ongoing research on the role of mental disorders in the clinical presentation of dystonia.