Vol 15, No 2 (2021)

Original articles

The diagnostic value of NR2 antibodies level in patients with chronic cerebral ischemia

Voznyuk I.A., Ponomarev G.V., Kharitonova T.V., Gogoleva E.A., Ovdienko O.A., Sergeeva T.V., Lipatova L.V., Sivakova N.A., Dambinova S.A., Skoromets A.A.

Abstract

Introduction. Hypertension, diabetes mellitus, atherosclerosis, and other risk factors for cardiovascular disease (CVD) contribute to the development of cerebral hypoperfusion and neurotoxicity, leading to recurrent transient ischemic attacks and cerebral infarctions. These processes are accompanied by the release of the NR2 peptide into the bloodstream and the production of antibodies to it. The use of NR2 antibodies to identify and assess the severity of chronic cerebral ischemia (CCI) and the risk of stroke can improve the quality of care for patients with risk factors for CVD.

Aim of the study. To examine the NR2 antibody levels in patients with different CVD risk factors and CCI of varying severity.

Materials and methods. In 107 patients (mean age 60.1 ± 7.9 years, 62 women and 45 men), 1.5T magnetic resonance imaging in the T1, T2, and T2 FLAIR sequences was performed. White matter hyperintensity was assessed using the Fazekas scale, and the size of individual hyperintensity lesions was also estimated. Enzyme immunoassay was used to measure the serum level of NR2 antibodies.

Results. In patients with signs of CCI, serum NR2 antibody levels were significantly higher compared to the patients without cerebrovascular brain disease (p < 0.05). That trend was observed both in compensated cerebral ischemia (p = 0.005) and in decompensated cerebral ischemia (p = 0.001).

Conclusion. The study results indicate that elevated NR2 antibody levels (>2 ng/ml) can be considered a marker associated with the development and progression of cerebral ischemia in patients with risk factors for CVD. Further study of the NR2 peptide and NR2 antibodies in patients with CCI will help optimize the indications for magnetic resonance imaging and improve the interpretation of its results.

 

Annals of Clinical and Experimental Neurology. 2021;15(2):
views

Autosomal recessive spastic paraplegias types 7 and 76

Rudenskaya G.E., Kadnikova V.A., Ryzhkova O.P., Dyomina N.A., Sharkova I.V., Polyakov A.V.

Abstract

Introduction. Since 2017, the Research Centre for Medical Genetics has been conducting the first clinical and molecular study in Russia of a heterogeneous spastic paraplegia group based on the MPS high throughput sequencing method. Our group of molecularly diagnosed SPGs (types with known genes) includes 122 families with 22 SPG types. This article continues the publication series on the study results.

The study aimed to determine the proportion and analyze the clinical, molecular, and genetic characteristics of two autosomal recessive forms, SPG7 and SPG76, in a group of identified SPGs.

Materials and methods. We assessed three non-inbred Russian families: two with SPG7 (a non-familial and a familial case) and one with SPG76 (a non-familial cases). Molecular genetic methods included massive parallel sequencing (MPS) panel for spastic paraplegia, Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA)).

Results. SPG7 was detected in 2 families and accounted for 1.6% of the entire SPG group and 8.7% of the autosomal recessive subgroup (less than in several other studies). The compound heterozygous genotypes in both families included the most frequent mutation in the SPG7 gene, c.1529C>T (p.Ala510Val); the allelic mutation in one case was a 4-exon deletion not previously described, while the other was a known mutation, c.228T>C (p.Ile743Thr). Despite a similar age at onset (end of the 3rd–4th decade), the symptoms were different: ‘uncomplicated’ spastic paraplegia in the non-familial case, while in the affected brothers prevailed ataxia; in both families, brain MRI showed cerebellar atrophy. The SPG76 case is a rare one, especially in a non-inbred family, and the first in Eastern Europe. A total of 28 families, mostly inbred, have been described worldwide. Two new mutations were found in the CAPN1 gene in the compound heterozygous state: c.398_399insAGTGGTTCCGCCGGCC (p. Arg133Glnfs*39) and c.1535G>A (p.Arg512His). Clinical features of the 30-year-old patient were typical, with onset at 20 years of age, spastic paraplegia and ataxia, and without brain MRI abnormalities.

Conclusion. The range of autosomal recessive SPGs in Russian patients includes both common and very rare forms occurring in non-inbred families. Of the 5 mutations found in the SPG7 and CAPN1 genes, 3 have not been previously described. Our observations demonstrate the close relationship between spastic paraplegia and ataxia and the significance of MPS and MLPA technologies in the diagnostics of SPG.

 

Annals of Clinical and Experimental Neurology. 2021;15(2):
views

Cervical spondylotic myelopathy: 10 years of treatment experience

Gushcha A.O., Dreval M.D., Yusupova A.R., Arestov S.O., Petrosyan D.V.

Abstract

Introduction. Cervical spondylotic myelopathy (CSM) results from prolonged cervical stenosis and is characterized by severe neurological disturbances. Given the high degree of disability and the ineffectiveness of conservative treatment for CSM, spinal decompression surgery is preferable. Two surgical treatment approaches are currently in competition — laminoplasty and corpectomy.

The study aimed to analyze the early (1 day after surgery) and long-term (12, 60, and 120 months after surgery) clinical, radiological, and neuroimaging results of CSM surgery.

Materials and methods. Two hundred and twenty-six patients (91 women and 135 men, average age 48.1 years) with degenerative cervical spinal stenosis accompanied by myelopathy underwent surgery. Pain severity (VAS score), proprioception (M. Doita’s scale), ability to perform self-care (Nurick scale), and recovery after surgery (JOA scale) were clinically evaluated. The stability of the cervical spine was evaluated radiologically. Stenosis severity and myelopathy lesions were assessed based on the neuroimaging data.

Results. Early and long-term clinical, radiological, and neuroimaging results were evaluated. Neck pain was 0–3 points on the VAS in the long-term (12, 60, and 120 months after surgery), decreasing from the initial 6–8 points. The JOA scale results showed that the efficacy of myelopathy treatment directly depended on disease history and the timing of surgical intervention. According to the Nurick scale, there was a tendency towards significant improvement in neurological status in patients with moderate disease. In contrast, the neurological status improved or remained stable in patients with the more pronounced disease, but this required more time. Improvement in proprioception as measured by the M. Doita scale was observed in patients at all stages of the disease.

Conclusion. Both surgical methods (laminoplasty and corpectomy) lead to good outcomes in CSM treatment. The effectiveness of surgical treatment for CSM directly depends on the disease duration and timing of the decompression surgery. Recovery is better when clinical symptoms of CSM are mild, moderate, and moderately severe and with a timely presentation to a surgeon.

 

Annals of Clinical and Experimental Neurology. 2021;15(2):
views

Mitochondrial arteriopathy, a suspected cause of spontaneous dissection of the internal carotid and vertebral arteries

Kalashnikova L.A., Sakharova A.V., Chaikovskaya R.P., Dobrynina L.A., Gulevskaya T.S., Gubanova M.V., Voronkova A.S., Sukhorukov V.S.

Abstract

Dissection of the internal carotid artery and vertebral artery (ICA/VA) is one of the leading causes of ischaemic stroke in young people. The reason for the arterial wall weakness leading to its dissection remains unclear. Morphological study of the ICA/VA, and clinical data, indicate the presence of connective tissue dysplasia in patients, which is not associated with any known hereditary diseases.

In this article, the authors summarize the results of their studies (histological and histochemical examination of muscle biopsies, electron microscopy of skin arteries) and observations (stroke-like episode, A3243G mutation in the mitochondrial genome in a patient with repeat ICA/VA dissections; increased peak lactate during MR spectroscopy in a patient who suffered an ICA dissection, then lobar hemorrhages a few years later). Based on these, the authors propose mitochondrial arteriopathy as the cause of arterial wall dysplasia leading to dissection. This article provides data on the presence of mitochondrial disorders in patients with ICA/VA dissection.

 

Annals of Clinical and Experimental Neurology. 2021;15(2):
views

The effect of education level on functional brain organization in patients with chronic cerebral ischemia

Fokin V.F., Ponomareva N.V., Konovalov R.N., Krotenkova M.V., Medvedev R.B., Lagoda O.V., Tanashyan M.M.

Abstract

The level of education is an important factor that prevents cognitive decline in normal and pathological aging, including in neurodegenerative and vascular diseases.

This study aimed to examine cerebral connectivity in patients with tertiary and secondary education suffering from chronic cerebral ischemia.

Materials and methods. We examined 54 patients (mean age 64.4 years) with chronic cerebrovascular disease who had completed either tertiary or secondary education. The Luria test was used to assess short-term memory, while the connectome organization was studied using resting-state functional magnetic resonance imaging.

Results. On average, patients with tertiary education recalled 35.0 ± 1.1 words out of a possible 50, while patients with secondary education only recalled 31.1 ± 1.2 words (p = 0.018). Patients with higher education had a higher number of interhemispheric connections in the connectome than the group without higher education. In patients without tertiary education, predominate the intrahemispheric connections in the right hemisphere. We hypothesize that this connectome organization provides a cognitive advantage in people with higher education, compared to patients without higher education.

 

Annals of Clinical and Experimental Neurology. 2021;15(2):
views

The relationship between the location of a lesion in the striatal dopaminergic innervation and its behavioral manifestation in a 6-hydroxydopamine-induced model of Parkinson's disease in rats

Stavrovskaya A.V., Voronkov D.N., Olshansky A.S., Gushchina A.S., Yamshikova N.G.

Abstract

Introduction. Animal modelling of Parkinson’s disease is an essential step in studying disease pathogenesis and searching for effective treatment methods. An accurate assessment of the resulting model is critical.

The aim of the study was to identify the correlation between the location of a lesion in the striatal dopaminergic innervation when the neurotoxin 6-hydroxydopamine (6-OHDA) was administered to rodents and the resulting behavior.

Materials and methods. The study was carried out on 75 male Wistar rats that received intranigral injection of 3 µl of 6-OHDA at a dose of 4 µg/µl. The animals were examined in the open field test and narrowing beam walking test 33 days after administration, after which some of the animals were decapitated (n = 25) for immunohistochemical analysis.

Results. The inactive animal group was statistically significantly different from the active animal group, with more pronounced damage to the dopamine endings in the dorsomedial (p = 0.0235) and ventral (p = 0.091) striatum. In contrast, in the active animals, the lesion was primarily in the dorsolateral striatum. In the inactive animal group, the mean distance travelled in the open field test was significantly shorter (p < 0.001), while freezing time (p < 0.0168) and the average score on the neuroticism scale (p < 0.001) were higher compared to the active animals. Spearman's correlation results showed a significant negative correlation (rS = –0.762; p < 0.0001) between tyrosine hydroxylase staining intensity in the dorsolateral striatum and freezing time in the open field test. No correlation was found between freezing time and damage to other striatal areas.

Conclusion. Damage to the dorsomedial and dorsolateral striatum causes less severe motor and emotional disturbances than damage to the ventral striatum. The narrowing beam walking test can be used to assess the presence and severity of striatal damage reliably. This evaluation is critical in studies of subsequent treatment efficacy to reduce Parkinsonian syndrome.

 

Annals of Clinical and Experimental Neurology. 2021;15(2):
views

Reviews

Certain aspects of brain tumor angiogenesis

Frantsiyants E.M., Rostorguev E.E., Sheiko E.A.

Abstract

Neuroepithelial tumors are one of the most common conditions with a high mortality rate. Despite the growing body of knowledge about the underlying biology of these tumors, their treatment has not changed significantly over the past decade.

Angiogenesis is a key component of the neoplastic process. Neoangiogenesis activity has a significant effect on tumor development and its metastatic potential. Studying how the growth and progression of gliomas are dependent on the degree of vascularisation has allowed the development of a new way of fighting tumors with antiangiogenesis therapy. Unfortunately, currently, antiangiogenesis therapy cannot cure a patient with glioma. The use of antiangiogenesis drugs to suppress tumor growth by inhibiting angiogenesis in gliomas is still limited despite being a promising direction. Information about molecular and genetic features of glial brain tumors, proangiogenic signalling pathways, mechanisms of angiogenesis, prognostic factors, etc., is essential to develop a new and effective therapy.

A recent literature review revealed quite contradictory data. On the one hand, neoangiogenesis of malignant brain tumors is considered to be an independent prognostic factor for glioma progression. However, some publications deny that angiogenesis in gliomas is a predictor of tumor development. All of the above underline the need for continued study into the relationship between angiogenesis and tumor growth.

 

Annals of Clinical and Experimental Neurology. 2021;15(2):
views

The pharmacogenomics of lamotrigine (a literature review)

Azhigova A.M., Broutian A.G., Vlasov P.N.

Abstract

Pharmacogenomics aims to optimize drug therapy with respect to genetic variations in various human genes, whose products affect drug pharmacokinetics and pharmacodynamics. Among neurological diseases, selecting effective drug therapy is especially important in epilepsy since recurrent epileptic seizures can lead to persistent epileptic brain activity and patient traumatization.

Lamotrigine is a new generation broad-spectrum antiepileptic drug and is recommended as the drug of choice in focal and generalized epilepsy. By genotyping single-nucleotide polymorphisms (SNPs) associated with decreased or increased lamotrigine blood concentration, predicting the drug dose that will achieve the therapeutic serum concentration is possible. Selecting an appropriate individual drug dose avoids the development of dose-dependent side effects, which occur when the serum drug concentration is exceeded and drug discontinuation due to a lack of the expected effect because of insufficient blood levels.

This review presents the results of studies of the polymorphism in genes that directly or indirectly alter lamotrigine serum levels. These include genes that encode the UGT enzymes, responsible for the conjugation and elimination of lamotrigine from the body; genes that encode transport proteins (P-glycoprotein, organic cation transporter, multidrug resistance protein, and breast cancer resistance protein); genes that encode the transcription factors HNF4α and pregnane X receptor, which regulate the expression of several liver transport proteins and enzymes. The reviewed data demonstrate the relationship between polymorphisms in these genes and changes in lamotrigine concentration.

 

Annals of Clinical and Experimental Neurology. 2021;15(2):
views

Clinical analysis

Sphenopalatine ganglion stimulation in refractory cluster headache: clinical case and literature review

Dzhafarov V.M., Dmitriev A.B., Moysak G.I., Rzaev J.A.

Abstract

Cluster headache is characterized by specifically intense pain when compared to other types of headache. About 10–20% of patients report no effect from conservative therapy. Research in this area has led to the use of sphenopalatine ganglion stimulation. The authors provide an up-to-date review of this method, how to select suitable patients, indications for surgery, determining its efficacy, and the risk of complications. The article presents a clinical case of a patient with cluster headache who was implanted with a stimulation system and followed up for 17 months.

 

Annals of Clinical and Experimental Neurology. 2021;15(2):
views

Phenotypic features of a Russian family with spinocerebellar ataxia type 6 from Khabarovsk Krai

Proskokova T.N., I. D.V., Serdyuk N.B., Abramycheva N.Y.

Abstract

The article presents a familial case of spinocerebellar ataxia type 6, consisting of 7 people across 4 generations from a mixed marriage of Yakut, Even, and Russian ethnicities, living in Khabarovsk Krai. The mutant allele of the CACNA1A gene had 27 stable CAG repeats in all patients (normal is <18 CAG repeats), while the normal allele had 13 CAG repeats. Clinical features included rapidly progressing cerebellar ataxia in males (0.96–9.00 points per year on the SARA scale); presence of psychological disorders in the form of alcoholism, early-onset binge drinking, completed suicidal behaviors; life expectancy reduced in 2 patients to 27 and 36 years.

 

Annals of Clinical and Experimental Neurology. 2021;15(2):
views

Technologies

Principles of personalized medicine and modern pharmaceutical technologies to optimize levodopa therapy of Parkinson's disease

Abaimov D.А., Fedotova E.Y., Poleshchuk V.V., Andreev M.N., Trifonova O.P., Lokhov P.G., Illarioshkin S.N.

Abstract

Levodopa (3-hydroxy-L-tyrosine, the levorotatory isomer of 3,4-dihydroxyphenylalanine) is a biological precursor of the neurotransmitter dopamine and has been the "gold standard" in the treatment of Parkinson’s disease for over 50 years. The widespread use of levodopa in clinical practice has not only provided neurologists with unique data from many years of symptomatic replacement therapy for a severe neurodegenerative disease but has also clearly identified several serious problems associated with levodopa absorption and metabolism. This article discusses the modern approaches to personalized medicine, which aim to overcome the numerous difficulties in managing patients with Parkinson’s disease and long-term levodopa use. A major focus is the review of strategies for selecting the optimal levodopa dosage regimen in specific patients and the main innovative dosage forms of this drug that improve its pharmacokinetics.

 

Annals of Clinical and Experimental Neurology. 2021;15(2):
views

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies