Combined 18F-fluorodeoxyglucose positron emission tomography and event-related potentials study of the cognitive impairment mechanisms in Parkinson's disease.

This study aimed to analyze positron emission tomography with 18F-fluorodeoxyglucose data and event-related potentials in the Go/NoGo paradigm in patients with Parkinson's disease with and without cognitive impairment. In the group of cognitively impaired patients, glucose metabolism was decreased in the frontal, parietal, cingulate and posterior temporal cortex. Correlations were found between the cognitive scores and cerebral glucose metabolism in those areas. Event-related potentials analysis revealed a decrease in the amplitude of the late positive wave (P300 NoGo wave) in the group of cognitively impaired patients. The analysis revealed that decline in amplitude of P300 wave was accompanied by decreased glucose metabolism in several cortical areas associated with cognitive impairment in Parkinson's disease. Correlations of glucose metabolism in these areas with event-related potentials amplitude in the NoGo condition confirm the important role of executive functions disorders in the pathogenesis of cognitive impairment in Parkinson's disease.

[Cerebral metabolism in patients with cognitive disorders: a combined MRS and PET study]. / Tserebral'nyi metabolizm u bol'nykh s kognitivnymi rasstroistvami: kombinirovannoe issledovanie s primeneniem magnitno-rezonansnoi spektroskopii i pozitronno-émissionnoi tomografii.

AIM: Magnetic resonance spectroscopy (MRS) allows studying the content of many metabolites in neural tissue in vivo. There are numerous studies devoted to the MRS data analysis in Alzheimer's disease (AD), but their results are contradictory. Thus, it is rational to compare the data obtained with MRS and positron emission tomography (PET) with fluorodeoxyglucose (FDG), which allows evaluating the brain functional state. In this paper, the authors compared MRS data in AD and mild cognitive impairment (MCI) with the cerebral glucose metabolism changes according to FDG PET. MATERIAL AND METHODS: Multivoxel proton MRS of the supraventricular area was performed in patients with AD (n=16) and MCI (n=14). The following metabolites ratios were evaluated: NAA/Cr, Cho/Cr, NAA/Cho (NAA - N-acetylaspartate, Cr - creatine, Cho - choline). All patients underwent neurological examination, assessment of cognitive status and PET with FDG. RESULTS: A decrease in NAA/Cr and Cho/Cr ratios in the supraventricular white matter and medial cortex in both hemispheres was observed in AD patients. In the MCI group, NAA/Cr ratio were decreased only in left white matter adjusting to the parietal cortex. Positive correlations of NAA/Cr and Cho/Cr ratios with cognitive status, as well as the cerebral glucose metabolism rate according to the PET data in frontal, parietal, temporal and cingulate cortex were revealed. CONCLUSION: The decrease in the NAA/Cr ratio in the supraventricular white matter and the medial cortex in AD and the correlation of this index with the results of cognitive tests and cerebral glucose metabolism suggest that it can be of diagnostic significance, reflecting the severity of cognitive impairment. In this case, the NAA/Cr ratio should be evaluated taking into account the changes in concentrations of both metabolites (NAA and Cr) in dementia.

[Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease]. / Osobennosti tserebral'nogo metabolizma gliukozy u bol'nykh s kognitivnymi narusheniiami pri bolezni Parkinsona.

AIM: To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. MATERIAL AND METHODS: Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). RESULTS AND CONCLUSION: In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

[Capabilities of positron emission tomography to study mecha-nisms of multiple sclerosis: own data and literature]. / Vozmozhnosti pozitronno-emissionnoi tomografii dlya izucheniya mekhanizmov razvitiya rasseyannogo skleroza (literaturnye i sobstvennye dannye).

The article presents the literature data and results of our own researchon the use of positron emission tomography (PET) with different radiotracersin multiple sclerosis (MS). Informationon the operating principles of PET and PET studies with different radiotracers are considered. The results of PET studiesin different typesof MS, including determinationof the localization of neuronal damagein the corticalgray matter, assessmentof microglial activation, study of the relationship between glucose metabolismin the brain and the severity of cognitive impairmentin MS, can providenew information about the pathogenesis ofMS.

[Neuroprotection therapy of multiple sclerosis with high doses of ethylmethylhydroxypyridine succinate]. / Vozmozhnosti neiroprotektsii pri rasseyannom skleroze: opyt primeneniya vysokikh doz preparata etilmetilgidroksipiridina suktsinat.

AIM: To study the therapeutic action of ethylmethylhydroxypyridine succinate (mexidol) on the neurodegeneration in multiple sclerosis (MS). MATERIAL AND METHODS: Fifty-two MS patients and 24 healthy controls were examined using DTI MRI with tractography. RESULTS AND CONCLUSION: Ethylmethylhydroxypyridine succinate can prevent the progression of neurodegenerative processes in MS. However, further clinical trials are needed to confirm the results obtained in this study.

[Oxygen-dependent energy deficit as related to the problems of ontogenetic development disorders and human sociobiological adaptation (theoretical and applied aspects)].

The review states and argues theoretical propositions on the pathogenetic role of pre- and perinatal hypoxic-ischemic brain damage in the formation of sustained oxygen-dependent energy deficit underlying in further ontogenesis the following neurobiological abnormalities: a) a decline in the level of health and compensatory-adaptive capacities of the organism, b) disorders of the psycho-speech development and adaptive behavior in children, c) early development of neuropsychic diseases, g) addition of other types of brain energy metabolism (including glucose metabolism) disorders in chronic polyetiologic diseases young and middle-aged individuals. We highlight and theoretically substantiate the integrated physiological parameters of the oxygen-dependent energy deficit types. We address the features of abnormalities in neuroreflectory and neurohumora regulatory mechanisms of the wakefulness level and its vegetative and hemodynamic provision in different types of energy deficit in children with DSMD, ADHD and school maladjustment. The use of the state-of-the-art neuroimaging techniques significantly increased the possibility of the disintegration of regulatory processes and cognitive functions in children with psycho-speech delays and in a wide range of chronic polyetiologic diseases.

[The brain structures functional activity and aggression patients' multiple sclerosis].

The article is devoted to investigation of unconscious aggression in patients with multiple sclerosis. We carried out comparison of the relative assessments of metabolism speed of glucose (according to positron emission tomography) and indicators of unconscious aggression (in the Hand test). It is shown that an increased tendency to open aggression (unconscious aggression) in patients with multiple sclerosis, is mainly linked with a reduction in the functioning of different departments of the frontal lobes of the brain on the left and with changes of the metabolism speed of glucose in the structures of the limbic system of the left and right hemisphere. With increasing of unconscious aggression we observed decrease of glucose metabolism speed in certain areas of the lower and middle frontal gyrus.

[Regional metabolic changes of supraventricular tissue in patients with relapsing-remitting and secondary-progressive multiple sclerosis]. / Regionarnye osobennosti metabolizma strukturno neizmenennogo veshchestva supraventrikuliarnykh prostranstv golovnogo mozga pri remittiruiushchem i vtorichno-progressiruiushchem tipakh techeniia rasseiannogo skleroza.

AIM: To evaluate and compare the intensity of changes in a regional meta-analysis in relapsing-remitting and secondary-progressive multiple sclerosis (RRS and SPMS). MATERIAL AND METHODS: The results of longitudinal studies of multiple sclerosis (MS) using positron emission tomography, magnetic resonance spectroscopy and diffusion tensor imaging are presented. RESULTS: In MS, metabolic changes precede the structural ones. The markers of neuronal and axonal dysfunction (a decrease in NAA/Cr ratios in the white and grey matters, without the structural changes) are recorded in the early stages. The metabolic changes in the grey matter were recorded mostly in the middle frontal gyrus and posterior cingulate cortex. With the increase of duration and severity of MS, the metabolic changes spread to the other regions of supraventricular areas. The distribution of degeneration zones is related to MS course. CONCLUSION: There is substantial evidence on the irreversible damage of neurons in the medial prefrontal cortex in SPMS that confirms the vulnerability of the frontal cingulate gyrus in MS.

[Cortical atrophy in multiple sclerosis]. / Atrofiia kory golovnogo mozga pri rasseiannom skleroze.

Objective. To identify clear patterns of the cerebral cortex atrophy in multiple sclerosis that may provide valuable information for the development of additional paraclinical methods of stages and variants of MS objectification and verification and used for assessing treatment efficacy. Material and methods. The results of morphometric data analysis of 117 patients with different variants of MS and 25 healthy volunteers are presented. The original algorithm for postprocessing MRI images was used. Age, disease duration, type of disease, FS and EDSS scores, morphometric results were the source parameters for the statistical analysis. Results. The correlation analysis showed that the total cortex volume was in inverse correlation with EDSS score, pyramidal and cerebellar dysfunction, but not with disease duration. An analysis of regional changes in 43 bilateral regions of interest (ROI) demonstrated similar results in 7 ROIs in the left (dominant) hemisphere and in 4 ROIs in the right hemisphere. ANOVA revealed atrophic changes in 20 ROIs bilaterally. Deficit of certain functional systems was accompanied by the atrophy of various functional cortex regions. ANOVA of the regional cortical atrophy in groups with varying disease severity showed the presence of significant changes in patients with moderate to severe disability. Duration and type of MS were not predictive for development of atrophy, with the exception of the precuneus bilaterally, the right paracentral lobule and right posterior cingulate gyrus. Conclusion. Regional cortical atrophy is detected in the earliest stages of the disease and increases as the disease progresses. Inconsistency of data across studies can be explained by the lack of generally accepted morphometric standards and pathogenetic heterogeneity of MS. Regional cortical atrophy may be considered as a sensitive neuroradiological biomarker for MS.

[Polyfunctionality of neurons: blocking of the extreme pathological afferentation leads to an improvement of the higher functions of the brain (on the example of patients in a vegetative state)].

In this paper possible mechanism of improvement of the functional state of the brain areas, maintaining movement, visual, auditory, and higher functions of the brain during correction of generalized spastic syndrome (botulinotherapy with Xeomin) in patients in a vegetative state (VS) is discussed. If to consider the vegetative state as stable pathological condition (SPC) of the brain, then from the perspective of the theory of structural and functional organization of the brain with systems with rigid and flexible elements (N.P. Behtereva), the therapy led to an unbalance of SPC, "functional release" of neurons and redistribution of their functions to provide other activities, the formation of new interneuronal connections. Taking into account the functional variability of neurons (S.V. Medvedev), blocking neuromuscular transmission in spastic muscles leads to a reduction of abnormal afferent and efferent hyperactivity of motor and sensory neuronal circuits, which releases the brain for other activities. This allows to consider botulinotherapy of pharmacoresistant muscle spasticity in patients in VS and minimal consciousness, not only as a symptomatic treatment, but also as a "indirect neuroprotection".

[PET-patterns of cognitive impairment in patients with multiple sclerosis].

Neuropsychological and PET-FDG examination and assessment with the EDSS scale in patients with different types (relapsing-remitting or progressive) of multiple sclerosis (MS) were performed in order to determine the relationship between cognitive impairment and changes in the regional cerebral metabolic rate of glucose (rCMRglu) in the brain gray matter. A study included 61 patients with relapsing-remitting (n=38) and progressive (n=23) types of MS. A statistical analysis revealed significant correlations between cognitive impairment and rCMRglu dependent on the type of MS. The changes in the functional activity of the brain gray matter during the progression of the disease and increasing disability were identified.

[The role of brain glucose metabolism in the development of cognitive dysfunctions in patients with remitting and secondary-progressive multiple sclerosis].

To study mechanisms of development of cognitive dysfunctions in multiple sclerosis (MS), brain glucose metabolism has been investigated using PET method. We have studied 61 patients with different types of MS course. Correlations between cognitive dysfunctions and regional glucose metabolic rate were revealed. The authors suggest that metabolic dysfunctions of the grey matter play the important role in the pathogenesis of cognitive disturbances in MS.

[Low-manifest infections with CNS damage in patients in prolonged unconscious state of non-inflammatory etiology].

AIM: Study of specter of low-manifest infections (LMI) with central nervous system (CNS) damage and their role in patients in prolonged unconscious state (PUS) of noninflammatory etiology. MATERIALS AND METHODS: 32 patients (23 male, 9 female; age 14-58) in PUS of various etiology were examined. The main group (18 patients) received therapy against all infectious diseases including LMI; control group (14 patients)--only against common and nosocomial microflora. Patients were immunologically, infectologically and neurologically examined in dynamic. The data obtained were treated by using STATISTICA for Windows (version 5.5). RESULTS: Significant differences in immune and infectologic status depending on the nature of primary CNS damage were not detected. Immunodeficiency was detected in all patients; 94% of patients had increased non-specific IgM and IgE. Among LMI agents Chlamydia spp. were predominant. Cultural and/or PCR methods detected this microorganism during the primary examination in cerebrospinal fluid samples in 56% patients and in blood samples in 56%; during the second diagnostics or autopsy--only in 13 and 25%, respectively. Detection of Bacteroides fragilis, Human Herpes Virus (HHV-6), Virus Epstein Barr (VEB), Cytomegalovirus (CMV) in cerebrospinal fluid, blood and on mucous membranes of nasopharynx and conjunctiva was grouped more frequently with the presence of Chlamydia spp. in the CNS (p < 0.05) than with other LMI agents. Sanation of CNS from LMI was significantly accompanied by regeneration of communicative activity in comparison with the control group. CONCLUSION: In patients with PUS high frequency of CNS infection by various LMI agents and primarily Chlamydia spp. should be considered. Sanation from LMI can become a "window" for effective neuro-regenerative treatment.

[Factor analysis of brain structure reorganization in patient with multiple sclerosis (based on pet data)].

The goal of present study was to investigate the functional reorganization of brain structures in patients with multiple sclerosis (MS). The patterns of distribution of relative estimations of local cerebral metabolic rate of glucose (ICMRglu) in regions of interest (ROIs), corresponding to anatomo-functional brain areas are obtained in groups of healthy volunteers (n=31 subjects) and patients with relapsing-remitting and progressive types of MS (n=59 and 39 accordingly). The analysis of factor structure of the obtained patterns allowed to make a conclusion about the existence of a common features with the factor structure of the distribution of another functional parameter--a regional cerebral blood flow (rCBF). This indicates that both factor solutions mainly reflect the functional organization of a brain. The differences revealed in factor structures of ICMRglu distribution in groups of patients with various types of MS and healthy volunteers allowed to assume that even at early stages of the disease despite the close anatomic and functional connectivity that normally exists between basal ganglia, MS patients have a functional dissociation of these structures. The bipolarity of revealed factors probably reflects the different directionality of the processes: relative decrease of functional activity in the areas which are directly responsible for performance of broken functions, caused by the deafferentation of the specified areas and its compensatory relative increase in functionally connected zones.

[Vegetative state (prolonged coma) as manifestation of stable pathological state].

Complex examination of 25 patients in vegetative state was performed before and after correction of secondary brain damage. Catamnesis over a period of at least 6 months was traced. Preliminary results showed that better recovery of consciousness and cognitive functions was observed if before treatment diffuse glucose hypometabolism was significantly more widespread than morphological changes. Minimal positive dynamics was detected in cases in which the reduction of glucose metabolism was minimal. This and other paradoxical results become explainable if to consider vegetative state as stable pathological state of the brain. This open new approaches to treatment of this group of patients.

[Brain atrophy and neurological impairment in patients with multiple sclerosis].

An aim of the study was to investigate a relationship between global and local brain atrophy with neurological impairment (motor dysfunction) in multiple sclerosis (MS) patients with different levels of disease severity. Fifty five patients with definite MS (Mc Donald's criteria), aged 18-60 years, disease duration 1-30 years, and 25 healthy age-matched controls have been studied. Neurological assessment (Kurtzke and EDSS scales) was performed in the all patients. The patients were divided into 3 groups: EDSS<3.5 mild disability, EDSS 3.5-6.0 moderate disability, EDSS>6.0 severe disability. In MS patients, the global brain atrophy was accompanied by the local atrophy of subcortical structures (thalamus, basal ganglia) and cerebellum. The processes of cerebral grey matter total and local atrophy were not similar. The progression of MS, neurological impairment is accompanied by the cerebellum and lentiform nuclei atrophy. There was the decrease of brain parenchyma volume, nucleus caudate and cerebellar local atrophy in patients with moderate disability. The severe disability was correlated with the thalamic atrophy and marked basal ganglia and cerebellar atrophy. Thus, we can suppose that the thalamic atrophy is important for the development of severe motor dysfunctions in MS patients.

[Neuromyelitis optica: problems of heterogeneity and systematization].

Prospective-retrospective data on 10 cases of neuromyelitis optica (NO) have been analyzed. Demographic and clinical features of patients with primary NO as well as NO comorbid with other organospecific disorders are discussed. Magnetic-resonance imaging data of the brain and spinal cord are summarized and discussed in the context of its heterogeneity. Positron emission tomography with the functional imaging of the brain performed in 3 patients revealed changes in glucose metabolism in the brain regions corresponding to deficits in motor and sensory functional systems. The issues of additional laboratory analyses, including those of cerebrospinal fluid, are reviewed.

Characteristics of neurological and cognitive status in patients with multiple sclerosis in relation to the location and volumes of demyelination foci and the severity of brain atrophy.

A total of 65 patients with clinically significant diagnoses of remitting multiple sclerosis in the stage of remission were studied. Neurological status was investigated with assessment on the FS and EDSS scales, with neuropsychological testing, and MRI scans (1.5 T). The severity of brain atrophy (in terms of the parenchyma volume) and the total volume of foci on T2 images were assessed as proportions of intracerebral volume. The severity of neurological deficit depended on the volume of intratentorial focal lesions and the level of brain atrophy. Cognitive disorders were identified in 89% of patients, and the severity of these was associated with the level of atrophy and the volume of foci on T2 images in the dominant hemisphere.

[Positron-emission tomography in the diagnosis of middle cerebral artery lesions].

The regional brain glucose metabolism after the intravenous drop-by-drop infusion of saline and 50 mg of cavinton was measured with positron-emission tomography (PET) in the right middle brain artery in 5 patients with ischemic stroke. The increase of glucose metabolism was found in the region of post stroke cystic-focal and perifocal changes as well as in contralateral regions. The dose of cavinton (50 mg) was safe and well-tolerated by patients. The use of PET in evaluating of glucose metabolism changes in the brain helps in prognosis of the disease.