Dragan M. Pavlović

Cerebral Small Vessel Disease in Pseudoxanthoma Elasticum: Three Cases

BACKGROUND Cerebral small vessel disease is rarely described in association with pseudoxanthoma elasticum (PXE), a hereditary connective tissue disorder with skin, eye and vascular manifestations. This autosomally inherited elastic tissue disease has been attributed to mutations in the ABCC6 gene located on chromosome 16p13.1. Different stroke mechanisms are suggested in PXE patients, arterial hypertension and accelerated atherosclerosis being the leading ones. CASE DESCRIPTIONS Case 1: A 49-year-old man with history of mild hypertension presented with recurrent transient ischemic attacks. At the age of 42, evaluation for progressive visual loss and skin changes led to diagnosis of PXE. Brain magnetic resonance imaging (MRI) disclosed multiple lacunar infarctions and confluent periventricular white matter lesions (WML). Case 2: A 71-year-old woman with history of mild hypertension suffered right-sided stroke. Diagnosis of PXE was made at the age of 48 due to severe visual loss and skin changes. Brain MRI revealed multiple lacunar infarctions and subcortical ischemic leukoencephalopathy. Case 3: A 47-year-old woman with prominent skin changes and bilateral amblyopia developed right-sided weakness. Skin biopsy confirmed PXE. Several lacunar infarcts in deep white matter and pons were revealed on MRI. DISCUSSION We present three patients with clinical and histopathological features of PXE who presented with multiple lacunar strokes, two with extensive confluent WML. These cases illustrate that PXE is a rare but significant risk factor for small vessel disease and stroke in patients of all age groups. Occlusive small vessel disease and subsequent lacunar infarcts and WML represent important PXE manifestations.

Speech and language disorders secondary to diffuse subcortical vascular lesions: Neurolinguistic and acoustic analysis. A case report

BACKGROUND AND PURPOSE Subcortical white matter (WM) plays an important role in speech production and language processing. Most frequently, cerebral WM lesions are secondary to small vessel disease in patients with vascular risk factors. We report the case of a 53-year-old man with history of hypertension and ischemic subcortical lesions, who presented with speech difficulties and mild cognitive impairment. METHODS Language and cognitive assessment included Boston Diagnostic Aphasia Examination, Boston Naming Test, Rey Auditory-Verbal Learning Test, Rey-Osterrieth Complex Figure Test, Trail Making Test A and B, Wisconsin Card Sorting Test, Scale for Evaluation of Perceptive Characteristics of Voice and Speech, and Multidimensional Evaluation of Speech and Voice. RESULTS Brain MRI showed ischemic WM lesions and lacunar infarcts in the brainstem and right cerebellum. Cognitive testing revealed mild cognitive impairment, predominantly affecting attention and executive functions. Speech and language analysis demonstrated dysarthria, dysphonia with hypophonia, and imprecise articulation, as well as short rushes of speech, palilalia and mild subcortical dysphasia. CONCLUSIONS Neurolinguistic and acoustic analysis in patients with ischemic WM lesions can provide additional information in the understanding of language and speech disturbances, and can assist in patient management.

Mild cognitive impairment

Mild cognitive impairment (MCI) is a syndrome that spans the area between normal ageing and dementia. It is classified into amnestic and non-amnestic types, both with two subtypes: single domain and multiple domains. Prevalence of MCI depends on criteria and population and can vary from 0.1 to 42% persons of older age. In contrast to dementia, cognitive deterioration is less severe and activities of daily living are preserved. Most impaired higher cognitive functions in MCI are memory, executive functions, language, visuospatial functions, attention etc. Also there are depression, apathy or psychomotor agitation, and signs of psychosis. Aetiology of MCI is multiple, mostly neurodegenerative, vascular, psychiatric, internistic, neurological, traumatic and iatrogenic. Persons with amnestic MCI are at a higher risk of converting to Alzheimers disease, while those with a single non-memory domain are at risk of developing frontotemporal dementia. Some MCI patients also progress to other dementia types, vascular among others. In contrast, some patients have a stationary course, some improve, while others even normalize. Every suspicion of MCI warrants a detailed clinical exploration to discover underlying aetiology, laboratory analyses, neuroimaging methods and some cases require a detailed neuropsychological assessment. At the present time there is no efficacious therapy for cognitive decline in MCI or the one that could postpone conversion to dementia. The treatment of curable causes, application of preventive measures and risk factor control are reasonable measures in the absence of specific therapy.

What are the differences between younger and older patients with symptomatic small vessel disease

OBJECTIVE Although typically linked to aging, small vessel disease (SVD) is also observed in younger adult patients, with common vascular risk factors (RF). We aimed to investigate features of SVD occurrence at an early adult age. PATIENTS AND METHODS Vascular RF, functional and cognitive status and severity of lesions on MRI expressed as total score on Age-Related White Matter Changes (ARWMC) scale were analyzed in 200 consecutive patients with cerebral SVD admitted to a tertiary neurological hospital. Variables were compared between younger (35-55 years) and older (>56 years) patients. RESULTS In this study, 63 (31.5%) of patients were 55 years or younger. Both age groups had comparable RF profiles, but smoking emerged as an independent predictor for SVD at a younger age (OR 2.9; 95% CI 1.5-5.5; p=0.002). Younger patients had better functional (OR 1.8; 95% CI 1.3-2.5; p=0.0001) and cognitive (χ(2) 13.94; p=0.0009) status compared to older patients. However, two thirds of younger patients had some degree of cognitive deficit. Total score on ARWMC scale was lower in younger patients (mean 12.3 in younger versus 15.2 in older, OR 1.11; 95% CI 1.0-1.18; p=0.001). There was a strong correlation in both groups between functional score, cognitive status and ARWMC score (p<0.0001). CONCLUSION In our dataset, younger patients with SVD shared common vascular RF with older patients. In the group aged ≤55, better functional and cognitive status and less severe MRI changes were noted. However, a substantial number of younger SVD patients presenting with TIA or ischemic stroke had various deficits.

Diabetes mellitus and cognitive functioning in a Serbian sample

Introduction: Diabetes is associated with cognitive impairments, particularly in executive functioning and memory. Aim: The aim was to describe cognitive functioning in Type 1 (T1DM) and Type 2 (T2DM) diabetes compared to healthy controls in a Serbian sample. Method: We studied 15 patients with adult onset T1DM (age range 19–60 years), 37 patients with T2DM (age range 50–77 years), and 32 healthy controls (28–78 years). All participants underwent comprehensive neuropsychological assessment. Results: T2DM subjects exhibited poorer performance than healthy controls in global cognitive performance, as well as verbal learning and memory. After correcting for multiple comparisons, follow-up examination of individual tests showed significantly poorer performance only on Trail Making Test Part B (TMT-B). Effect sizes for T2DM versus healthy controls ranged from medium to large for several cognitive variables, while comparisons between T1DM and the other two groups tended to yield much smaller effects. Conclusion: T2DM is associated with poorer cognition, particularly in executive functions, learning/memory, and global cognition. Lack of group differences may be due to use of an adult onset T1DM sample, relatively young age of our T2DM sample, or characteristics of healthy control subjects in our Serbian sample.

The Impact of Homocysteine, Vitamin B12, and Vitamin D Levels on Functional Outcome after First-Ever Ischaemic Stroke

We explored the relationship between acute ischaemic stroke (IS) early functional outcome and serum levels of homocysteine, vitamin B12, and D in a noninterventional prospective clinical study. We enrolled 50 patients with first-ever IS and performed laboratory tests and functional assessment at three time points: on admission and three and six months after stroke. Modified Rankin Scale (mRS), NIHSS scale, and Barthel index (BI) scores were assessed in all participants by trained examiner blinded to laboratory data. Patients did not receive treatment that might alter laboratory data. Admission NIHSS correlated with homocysteine levels (r = 0.304, p < 0.05), B12 level (r = −0.410, p < 0.01), and vitamin D levels (r = −0.465, p < 0.01). Functional outcome measures (BI and mRS) did not significantly correlate with homocysteine and vitamin D3 levels at 3 and 6 months. However, a positive correlation with vitamin B12 levels was detected for BI both at 3 and 6 months and mRS at 6 months. Higher serum vitamin B12 levels were associated with better functional outcome at follow-up.

Vascular dementia: Facts and controversies

Vascular dementia (VaD) is the second most frequent dementia after Alzheimers disease, and is diagnosed during lifetime in 20% of demented patients. Five-year survival rate in VaD is 39%, while it is estimated to be 75% in healthy persons of the same age. It is therefore important to make correct diagnosis of VaD early in the course of the disease. Risk factors forVaD are identical to stroke risk factors, and there are significant possibilities for the prevention of vascular cognitive decline. Cognitive decline develops acutely or step-by-step within three months after stroke, but more gradual progression of intellectual decline is also possible. Neurological examination can reveal pyramidal and extrapyramidal signs, pseudobulbar palsy, gait disturbance and urinary incontinence. Neuropsychological profile comprises the loss of cognitive set shifting, decline in word fluency, verbal learning difficulties, perseverations, difficulties in complex figure copying, and in patients with cortically located lesions also problems with speech and praxia. The basis of the diagnosis is, besides history, neurological examination and neuropsychological assessment, computed tomography and/ or magnetic resonance brain imaging. Vascular risk factors control is the most important measure in VaD prevention. Modern guidelines for the treatment of cognitive decline in VaD emphasize that donepezil can be useful in the improvement of cognitive status at the level of Class Ila recommendation at the level of evidence A, while memantine may be useful in patients with mixed VaD and Alzheimers disease dementia.

The Impact Of Sports Activities On Quality Of Life Of Persons With A Spinal Cord Injury: VPLIV ŠPORTNIH AKTIVNOSTI NA KAKOVOST ŽIVLJENJA OSEB S POŠKODBO HRBTENJAČE.

Abstract Objectives Studying the quality of life of people with a spinal cord injury is of great importance as it allows the monitoring of both functioning and adaptation to disability. The aim of this study was to determine the difference between persons with a spinal cord injury involved in sports activities and those not involved in sports activities in relation to their quality of life and the presence of secondary health conditions (pressure ulcers, urinary infections, muscle spasms, osteoporosis, pain, kidney problems-infections, calculosis and poor circulation). Methods The study included a total of 44 participants with spinal cord injury-paraplegia of both genders; 26 of them were athletes and 18 were not athletes. The athletes were training actively for the last two years, minimally 2-3 times per week. A specially designed questionnaire, medical documentation and the Spinal Cord Injury Quality of Life Questionnaire (SCI QL-23) were used for research purposes. Chi-square test was used to analyze the differences between the groups, while multiple analysis of variance (MANOVA) was used to determine the differences between the sets of variables. Results Among the participants, the athletes perceived higher quality of life than the non-athletes (male gender p<0.001 and female gender p<0.05). Regarding secondary health conditions, the athletes reported the presence of less pain (p=0.034) and a subjective feeling of better circulation (p=0.023). Conclusion The implementation of sports activities significantly improves quality of life in the population of people with spinal cord injury-paraplegia. However, sports activities only partially affect secondary health conditions.

Generalized traveling current source return stroke model with current reflections and attenuation along the channel

The generalized traveling current source return stroke model (GTCS), Cvetic and Stanic [1995] is extended to take into account current reflections occurring at ground and at the upper end of the lightning channel, as well as current attenuation along the channel. The ground reflection factor and the top reflection factor of the current pulses are taken from the extended TCS model, Heidler [2007]. Current sources are placed along the activated length of the lightning channel, represented by the channel discharge function introduced in the GTCS model. Multiple reflections give rise to current waves moving up and down along the lightning channel. The total current is composed of the source current according to the original GTCS model and the reflected currents. The current along the channel can be represented as a sum of integrals of current sources along the channel. The traveling-current-source-type of “engineering” return stroke models can be regarded as special cases of the extended GTCS model. Moreover, for a convenient set of input parameters, the transmission-line-type of return stroke models can be also derived from the extended GTCS model. Simultaneously, the existence of the current source at the channel base, inherently built in all transmission-line-type of models is explained. This result is purely theoretical, since these two classes of “engineering” models are based on different physical pictures that describe processes in the lightning channel during the return stroke.

Lightning corona sheath dynamics based on a generalized space charge distribution

A model of corona sheath that surrounds the thin core of the lightning channel has been investigated by using a new space charge function. The lightning channel is modeled by a charged corona sheath that stretches around a highly conductive central core through which the main current flows. The channel core with the negatively charged outer channel sheath forms a strong electric field, with an overall radial orientation. The return stroke process is modeled as the negative leader charge in the corona sheath being discharged by the positive charge coming from the channel core. The corona sheath model [1-5] divides the sheath into two zones with charges: zone 1 (surrounding the channel core with net positive charge) and zone 2 (surrounding zone 1 with negative charge). We introduced a new expression for space charge distribution inside both zones that represents a generalization of previously used space charges. Using appropriate parameter values, previously examined corona charge densities are obtained as special cases of this generalized distribution. Furthermore, the influence of the new distribution of space charge on the corona sheath dynamics is examined. Expressions that describe how the corona sheath radius evolves during the return stroke are obtained from the adopted corona sheath model and the new sheath space charge density. The new distribution can also be readily applied to transmission-line type models.