Vol 13, No 2 (2019)

Introduction. Mitochondrial ataxias are an extremely heterogeneous group of diseases, which include the SANDO (an acronym stands for sensory ataxic neuropathy, dysarthria and ophthalmoparesis) syndrome. SANDO syndrome is one of the characteristic phenotypes associated with mutations in the POLG gene.

Study objective. To analyse the clinical picture and the results of clinical and laboratory tests in a Russian case series of genetically confirmed SANDO syndrome.

Materials and methods. Nine patients (4 men and 5 women aged 33.4±11.3 years) with SANDO syndrome and identified mutations in the POLG gene were examined. A clinical evaluation using the SARA and ICARS (for ataxia) and MoCA (cognitive function) scales, laboratory study of liver function, electrocardiography, stimulation electromyography and brain MRI were performed; 6 patients underwent electroencephalography. MLPA analysis and the original multigene NGS panel were used for genetic screening.

Results. The average age of disease onset was 27.7±8.2 years, with significant variability (from 14 to 49 years). The disease was characterized by a rather typical clinical picture, which included sensory ataxia, polyneuropathy, dysarthria and external ophthalmoparesis in all patients; the median score was 13.5/40 [11; 25] points on the SARA scale, 39.5/100 [33; 63] points on the ICARS scale, and 22 [20; 25] points on the MoCA scale. Two patients showed signs of frontal lobe dysfunction. In most patients, MRI revealed changes in the white matter of the cerebellar hemispheres, brainstem, thalamus and semioval centres, but no pathology was detected on MRI in 3 patients. The p.W748S mutation in the POLG gene made up 83% of the mutant alleles, while the p.L931R and p.L311P pathogenic mutations found in 2 patients are new variants and have not been described in international databases.

Conclusion. Our findings suggest that the true frequency of SANDO syndrome in the population may be higher than previously thought. Therefore, a suspicion of this disease should be maintained even in the absence of characteristic changes on neuroimaging. For the timely detection of SANDO syndrome, we propose an appropriate diagnostic algorithm, which should be followed when examining patients with ataxia.

Cerebral microangiopathy (CMA) is the main cause of vascular cognitive disorders, the leading cause of mixed dementia, and the main modifiable risk factor in Alzheimer’s disease.

Study objective. To investigate the role of arterial and venous blood flow and cerebrospinal fluid flow, as well as their interrelation in the development of cognitive disorders in patients with CMA.

Materials and methods. Ninety-six patients (32 men and 64 women, mean age 60.6±6.3 years) with cognitive complaints and CMA, diagnosed according to the STRIVE international MRI criteria, were examined. The severity of cognitive disturbance was assessed based on the overall cognitive level (MoCA scale and independence in daily life), the results of memory tests (10 words memory test) and executive brain function tests (TMT B-A). Phase contrast MRI was used to measure blood flow in the internal carotid and vertebral arteries (total arterial blood flow), the internal jugular veins and the straight and superior sagittal sinuses, as well as the aqueductal cerebrospinal fluid flow. Arterial pulsation and intracranial compliance indices were calculated.

Results. Dementia and severe memory impairment were statistically significantly associated with an increase in the arterial pulsation index, intracranial compliance index and the aqueductal CSF stroke volume. Significant disturbances in brain executive function were also associated with a decrease in the total arterial blood flow, as well as the venous blood flow in the straight and superior sagittal sinuses. The characteristics of blood flow and cerebrospinal fluid are closely related, and the arterial pulsation index affects all the studied parameters.

Conclusion. The severity of cognitive disturbance in CMA is determined by an increase in the arterial pulsation index, the intracranial compliance index and the aqueductal CSF stroke volume, while the severity of dysregulation disorders is determined by a concurrent decrease in the total arterial blood flow and venous blood flow in the straight and superior sagittal sinuses. The specific changes in blood flow and CSF flow and their interrelation in patients with cognitive impairment due to CMA suggest the pathogenetic importance of cerebral hydrodynamic disturbances in the aetiology of brain damage and the development of cognitive impairment in CMA.

The pathogenetic mechanisms of ischaemic stroke are complex and have not been fully studied, including the role of interhemispheric asymmetry in the brain’s biochemical organization.

Study objective. To study the levels of free amino acids (AA) and their derivatives in the cerebral cortex of rats with subtotal cerebral ischaemia.

Materials and methods. Subtotal cerebral ischaemia was modelled in 6 rats in the experimental group by ligation of both carotid arteries for 2 hours. Six rats with sham surgeries served as the control. The levels of AA and their derivatives was analysed in perchlorate tissue extract using reversed-phase chromatography.

Results. Subtotal cerebral ischaemia was accompanied by changes in the AA pool, with differences found between the cortex of the left and right hemispheres. Glutamate, threonine, taurine, tyrosine, tryptophan and α-aminoadipic acid levels decreased in the left frontal lobe cortex, and ornithine levels increased. Asparagine, serine and phenylalanine levels decreased in the right frontal lobe cortex.

Conclusion. The nature of changes in the AA levels in the left and right halves of the cerebral cortex indicates interhemispheric asymmetry of amino acid imbalance, which develops in cerebral ischaemia.

Using specific keywords; we searched for articles from the last 10 years on haemorrhagic transformation (HT) of cerebral infarction (CI); which were available on the PubMed database. This article provides an analysis and a summary of the information on the classification; pathogenesis and predictors (clinical; laboratory; neuroimaging; including the use of integrative assessment scales) of HT; as well as its impact on the functional outcome of the condition. It is emphasized that HT is a multifactorial pathological process in its phenomenology; including brain ischaemia; the development of coagulopathy; disturbances in the integrity of the blood–brain barrier and reperfusion injury. The emphasis is placed on careful monitoring of patients with acute ischaemic infarct after intravenous thrombolytic therapy and/or endovascular intervention; as well as those patients with a high predicted risk of HT. Timely and regular neuroimaging should be carried out to detect HT as soon as possible. Type 2 parenchymal haematomas; the most severe type of HT; are most often associated with high mortality and an unfavourable functional outcome.

In clinical neurology, biomarkers of central neurotransmitter imbalance have been of particular interest in the study of motor disorders and examination of patients with Parkinson’s disease (PD) and other extrapyramidal diseases, primarily to assess the exchange of dopamine and other monoamines in the brain. Radioisotope visualization methods, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) with the corresponding radiopharmaceuticals, are the most informative for these purposes. This article presents a comparative analysis of the wide range of existing ligands and molecular targets for functional neuroimaging using radioisotopes of the nigrostriatal system and the other monoaminergic systems of the brain, with emphasis on the study of the dopamine transporter, dopamine receptors and dopamine-metabolysing enzymes. The modern possibilities of PET and SPECT for the early diagnosis of PD, and the differential diagnosis of this disease with clinically similar syndromes (dystonia, atypical and drug-induced parkinsonism, essential tremor), as well as for monitoring the pathological process and assessing the results of various therapeutic interventions are evaluated. The role of functional neuroimaging in the objective assessment in vivo of the non-motor symptoms of PD, such as depression, impulse control disorders, pathological fatigue and orthostatic hypotension, is emphasized.

This review analyses the current understanding and diagnostic approaches to the management of patients with autoimmune encephalitis. Cellular and synaptic targets, involved in the pathological process in autoimmune encephalitis, are described. The presence of clinical and immunological differences in the pathology is emphasized: on the one hand, non-structural damage to the nervous system is combined with the subacute development of cognitive impairment, epileptic and psychopathological syndromes, which, on the other hand, are associated with polymorphic immunological heterogeneity. The algorithm for clinical and laboratory diagnosis is described, based on our own clinical observations of three patients. The first patient was diagnosed with a cross-autoimmune syndrome with a combination of Hodgkin’s lymphoma and anti-NMDA encephalitis, probably triggered by the reactivation of the Epstein–Barr virus with a fatal outcome. The second patient was diagnosed with autoimmune anti-LGI1 limbic encephalitis, and the third patient was seronegative to the available immunological antigens. The authors note the need to rethink the concept of ‘encephalitis of unknown aetiology’ and its transformation into ‘autoimmune encephalitis’ with the immunological diagnosis of three antigens (NMDA, LGI1, CASPR2). Considering the rarity of the disease, the high probability of initial admission to an infectious diseases or psychiatric hospital, it is worthwhile to explore this problem more widely at various research forums and to create a comprehensive, interdisciplinary approach to the diagnosis of this disease in the Russian Federation.