Vol 11, No 4 (2017)

Original articles

Non-motor symptoms of Parkinson’s disease: the submerged part of the iceberg

Titova N.V., Chaudhuri К.R.

Abstract

James Parkinson, a physician from London, described the «shaking palsy» now known as Parkinson’s disease (PD) in his classic essay in 1817. Parkinson noted tremor, bradykinesia, rigidity and stooped posture as the key motor features of this condition but also drew attention to sleep dysfunction, delirium, dementia, and dysautonomia, now known to be non-motor symptoms (NMS) of PD. Inspite of their importance, NMS in PD still remain under-recognised and poorly studied. Description of neuropathological correlates of NMS, as well as the development of comprehensive tools for their assessment in the early 2000’s, such as the NMS questionnaire (NMSQuest) and scale (NMSS), helped to establish the importance of NMS in PD and their crucial link with quality of life. In many countries, NMS evaluation in PD is now a part of the good clinical practice standards. Studies of the integral role of NMS in PD clinical structure and natural history of PD led to the concept of PD as a complex combination of motor and non-motor manifestations with a long prodromal phase dominated by a number of NMS. The prodromal phase of PD is a major current research topic: NMS-associated biomarkers may help to identify subjects who are at risk of developing motor-phase PD and, potentially, are candidates for neuroprotective therapies. NMS burden grading with cut off values, which can be used as outcome measure in clinical trials in patients with PD, have been validated. The complex multi-neurotransmitter dysfunction of PD has been reported to manifest clinically as difeferent non-motor subtypes. Recognition of such subtypes may lead to the emergence of personalized and precision medicine approaches in PD.

Annals of Clinical and Experimental Neurology. 2017;11(4):
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Markers of connective tissue dysplasia in cervical artery dissection and its predisposing factors

Gubanova M.V., Kalashnikova L.А., Dobrynina L.А., Shamtieva К.V., Berdalin А.B.

Abstract

Introduction. Cervical artery dissection (CeAD) is the most frequent cause of ischemic stroke in young adults. Arterial wall dysplasia 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 and20 healthy volunteers. We estimated 48 signs of CTD included in the Villefranche diagnostic criteria for the vascular type of EhlersDanlos 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 < 0.0039). Significant signs (more than 8 points) were present in 53% of patients. Regression analysis was performed to determine diagnostic-prognostic value of CTD signs. The main diagnostic criteria included history of headache (p=0.022), arterial hypotension (р=0.012), extensive bruising (р=0.011), and widened atrophic scars (р=0.019). The additional diagnostic criteria included translucent skin (р=0.034), high palate (р=0.034), predisposition to constipation (р=0.050), nasal bleeding (р=0.043), and blue sclera (р=0.050). In the presence of the 4 main and 2 additional criteria, the predictive value of dissection according to regression model is 7577% (ROC analysis: AUC 0.90, 95% CI, 0.84–0.96). Most patients 97% had various predisposing factors of CeAD development, either isolated 47% or combined 50%.

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-prognostic criteria. Dissection of the arterial wall with signs of dysplasia is provoked by various additional factors.

Annals of Clinical and Experimental Neurology. 2017;11(4):
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Influence of the blood gas transport system on brain millivolt scale direct current potentials in patients with vascular encephalopathy

Fokin V.F., Ponomareva N.V., Medvedev R.B., Tanashyan М.М., Shabalina А.А.

Abstract

Introduction. Millivolt Scale direct current potentials (DCP) registered from human scalp differ from other types of estimated electrical activity by closer association with cerebral energetic processes. Intense energy metabolism in the brain increases the difference between acidic products concentrations on both sides of the blood brain barrier which is reflected by higher DCP. Oxygen consumption of is one of the most important components of cerebral energy metabolism. Delivery of oxygen to neuron depends on the characteristics of blood oxygen transport system and cerebral blood flow.

Objective. To test the hypothesis that brain DCP depends of the blood oxygen transport system characteristics and cerebral blood flow.

Materials and methods. Erythrocytes number, erythrocyte sedimentation rate, hemoglobin and fibrinogen levels in blood were examined in135 patients with vascular encephalopathy (VE) Blood flow velocity in major head arteries was estimated using Doppler ultrasound. Associations between blood characteristics and blood flow velocity and the brain DCP, recorded in frontal, central, occipital areas along the midline and in both temporal areas, were determined.

Results. Associations between brain DCP and the blood oxygen transport system characteristics as well as the cerebral blood flow velocity were discovered in patients with VE. Averaged values of DCP in all examined areas were significantly different in groups with high and low hemoglobin levels (Fisher coefficient (F) = 5.5; p = 0.02) and corpuscular hemoglobin levels (F = 7.0; p <0.01). The blood flow velocity in the internal carotid artery correlated with DCP in central areas of the head (r = 0.37; p = 0.003). The values of averaged DCP (over all areas) negatively correlated with blood sedimentation rate (r = -0.31; p= 0.002) and fibrinogen levels (r = -0.37; p <0.001).

Conclusions. Evidences of the association between DCP and the brain oxygen transport system were obtained. Higher level of hemoglobin and a higher rate of cerebral blood flow promote more intensive rates of brain oxygen consumption. Discovered correlations between the blood oxygen transport system characteristics, cerebral blood flow and brain DCP confirm the potential benefit of using the millivolt range slow brain electrical activity measurement to characterize cerebral energy metabolism in clinical and experimental setting.

Annals of Clinical and Experimental Neurology. 2017;11(4):
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Laminoplasty and corporectomy in the treatment of cervical spondylotic myelopathy

Dreval' M.D., Arestov S.О., Petrosyan D.V., Kasheev А.А., Vershinin А.V., Poltorako Е.N., Guscha А.О.

Abstract

Introduction: Cervical Spondylotic myelopathy (CSM) is a disabling manifestation of extended cervical stenosis characterized by pronounced neurological dysfunction. Decompressive interventions contribute to significant regression of symptoms and, in some cases, complete recovery can be achieved.

Objective: To explore the potential of laminoplasty in patients with extended cervical spondylotic stenoses complicated by myelopathy, and to develop approaches for surgical intervention in these patients.

Material and methods: 56 patients were included in the study. Laminoplasty was performed in 34 patients (average age, 59.4 ± 12.8 years, women/men ratio, 9:25); 28 patients had compression on 3 levels of, 4 patients had compression on 4 levels and 2 patients had compression over 5 levels. Corporectomy was performed in 22 patients who made up the comparison group (average age, 43.8 ± 16.4 years, women/men ratio, 7:15). The frequency and initial severity of concomitant non-neurological disorders in both groups were comparable.

Results: Indications for laminoplasty were determined. They include: symptoms of spondylotic myelopathy, three or more levels of compression, preservation of lordosis, absence of segmental instability signs, inability to perform anterior decompression, and age over 55 years. The presence of segmental instability signs, kyphotic deformation and history of mental disorders may be considered as contraindications for this surgery. Early and late (> 3 years) clinical outcomes (evolution of pyramidal and sensory symptoms) and X-ray and neuroimaging postoperative parameters (spine canal width, preservation of lordosis, etc.) were evaluated.

Conclusions: Due to a number of advantages, lamynoplasty is the treatment of choice for extended cervical spondylotic stenosis. Adequate selection of patients based on the evaluation of clinical symptoms, extension of stenosis, neurological signs and neuroimaging features make possible to achieve excellent results. This type of surgery is preferable for elderly patients (>55–60 years).

Annals of Clinical and Experimental Neurology. 2017;11(4):
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Expression of MAPK and inflammasomes in cells of the brain in experimental Alzheimer's disease

Gorina Y.V., Lopatina O.L., Komleva Y.К., Chernykh A.I., Salmina A.B.

Abstract

Introduction. Alzheimer's disease is a chronic neurodegenerative disease that leads to neuropsychiatric disorders and decrease in cognitive activity. A number of studies demonstrate the important role of the mitogen-activated protein kinase (MAPK) pathway and inflamasome NLRP3 in disturbing the metabolism of β-amyloid and insulin resistance in Alzheimer's disease.
Objective. To study the expression of NLRP3 on cells of neuronal and glial nature, as well as MAPK on neurons in the amygdala of animals with experimental Alzheimer's disease.
Material and methods. Subjects of the study were: 1) CD1 mice (males, 4 months old) divided in 2 groups, the experimental group (intra-hippocampal
intjection of β-amyloid) and the control group (sham-operated animals); 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 used to study the expression of NLRP3 and MAPK in the brain amygdala.
Results. It was found that NeuN/NLRP3-positive cells were increased in animals with a genetic model of Alzheimer's disease in the amygdala (29.05±2.67) compared with the control animals (17.10±1.95) (p=0.043). A similar picture was observed in β-amyloid-induced neurodegeneration (p=0.021). Intra-hippocampal injection of β-amyloid caused the decrease of MAPK expression in the amygdala neurons (5.97±0.66) compared with sham-operated animals (13.25±2.65) (p=0.018). A similar situation was observed in animals with a genetic model of Alzheimer's disease (p=0.031).
Conclusion. Increase of expression of inflammasomes NLRP3 was observed on neurons, but not astrocytes, in animals with experimental Alzheimer's disease. Wefound a decrease of the expression of MAPK on neurons in the amygdala. This indicates coupling of the inflammatory process and the disturbances of insulin-signaling mechanisms in the brain in neurodegeneration.

Annals of Clinical and Experimental Neurology. 2017;11(4):
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Videonystagmography in the diagnosis of oculomotor disorders

Belyakova-Bodina A.I., Bril' Е.V., Zimnyakova О.S., Anikina М.А., Brutyan A.G.

Abstract

Videostagmography is a dynamically developing method of objective quantitative eye movement recording in various neurological diseases which has a few advantages over those used previously. The review describes the basics of the method and the most commonly used tests for a number of eye movements. The principles of research into various types of saccades, including pro-saccades, antisaccades, memory-guided saccades and voluntary saccades, as well as other types of eye movements such as smooth pursuit and optokinetic nystagmus, are also covered. Reviewed are parameters which need to be assessed in each case, with possible deviations in these parameters to be recorded during videonystagmography in patients with neurological diseases. Data from previously published studies allowing to anticipate the development of a technique that would enable the presymptomatic and early differential diagnosis of a number of diseases are presented. The review also considers the potential influence of the disease progression, as well as of therapeutic interventions, on the parameters assessed during videonystagmography.

Annals of Clinical and Experimental Neurology. 2017;11(4):
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PET-CT in early detection of Alzheimer’s disease: а case report

Prokopenko S.V., Barankin B.V., Mar'ina N.М., Mozheyko Е.Y., Bezdenezhnykh А.F., Koryagina T.D., Chanchikova N.G., Tokarev N.А., karlova Е.А., Ozerskaya А.V., Badrin Е.А., Belugin К.V., Savel'eva А.А., Shepelevich N.V.

Abstract

The article describes a clinical case of a female Alzheimer disease patient at an early stage of the neurodegenerative process. The patient did not have any complaints. She was taken to the neuropsychologist’s by her husband that was concerned because of the patient's family history (his mother-in-law suffered of Alzheimer's disease) and the emergence of some memory problems in his wife. The diagnosis was suspected based on the results of neuropsychological evaluation of cognitive functions which corresponded to mild cognitive impairment. To confirm the presence of a neurodegenerative disease brain positron-emission tomography with F-18 fluorodesoxyglucose (FDG) was performed. Hypometabolism of the imaging agent was detected in the temporal and parietal lobes cortex, in the association cortex of the left temporal and the right occipital lobes, and in the posterior part of the left cyngulate gyrus. This findings correlated with the data of the patient’s cognitive evaluation and thus provided the nosological diagnosis at an early stage of the disease. 

 

Annals of Clinical and Experimental Neurology. 2017;11(4):
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Ischemic stroke and inherited thrombophilias

Pizova N.V.

Abstract

In this review the impact of the most common thrombophilias on the risk of ischemic stroke and atherothrombosis is thoroughly analyzed. The functional role of different β-fibrinogen genotypes was reviewed and their correlations with ischemic cerebrovascular diseases, brachiocephalic artery atherosclerosis and arterial hypertension are evaluated. In addition, associations of stroke with key genetic factors such as the Leyden mutation (factor V), mutations in the genes of prothrombin, PAI-1 (plasminogen activator inhibitor), glycoprotein IIIa, etc. are assessed. Results of the authors’ own works on the occurrence of various inherited thrombophilias in a group of 43 patients with ischemic stroke of undefined origin are presented.

Annals of Clinical and Experimental Neurology. 2017;11(4):
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