Relationship between bone disorders and stroke.

Bone disorders are among the most uncommon causes of stroke, but they should be considered as stroke cause in particular clinical scenarios. On the other hand, osteoporosis/osteopenia and increased fracture risk are well documented post stroke complications. The relationship between stroke and bone health is complex. The current facts suggest that these two conditions share same risk factors, but also are risk factors for each other. However, the evidence shows more clear effect of stroke on the bone health, than in the opposite direction. This extensive review is aiming to fill the huge gap of evidence about this topic, and since bone pathology is extremely rare cause of cerebrovascular accident, although a complex connection between these two conditions definitely exists.

Hyperbaric oxygen therapy in acute stroke: is it time for Justitia to open her eyes?

Hypoxia is a critical component of neuronal death in patients with stroke. Therefore increasing oxygenation of brain tissue seems to be a logical therapy against cerebral ischemia. Oxygen therapy exists in two modalities: normobaric hyperoxia therapy and hyperbaric oxygen therapy (HBO). HBO is a therapeutic procedure in which pure (100%) oxygen is administered at greater than atmospheric pressure in HBO therapy chambers. In this review article, we aimed to summarize the current knowledge regarding the therapeutic use of HBO in acute stroke patients. Literature review and electronic search were performed using PubMed, Medscape, and UpToDate with the keywords stroke, acute stroke, hyperbaric oxygen therapy, and hyperoxia. According to the reviewed literature, the use of HBO as routine stroke therapy cannot be justified in acute stage of stroke. More randomized, controlled studies are needed regarding safety and especially effectives of HBO in stroke patients. Also, standardized definitionof HBO should be proposed and used in all future studies.

Role of prediabetes in stroke.

Stroke is one of the leading causes of death and probably the greatest cause of adult disability worldwide. Diabetes mellitus (DM) is a state of accelerated aging of blood vessels. Patients with diabetes have increased risk of stroke. Hyperglycemia represents a risk factor for poor outcome following stroke, and probably is just a marker of poor outcome rather than a cause. Lowering of blood glucose levels has not been shown to improve prognosis. Also, prevention of stroke risk among patients with DM is not improved with therapy for reduction of glucose levels. On the other hand, prediabetes, a metabolic state between normal glucose metabolism and diabetes, is a risk factor for the development of DM type 2 and subsequently for stroke. Several methods are known to identify prediabetes patients, including fasting plasma glucose levels, 2-hour post load glucose levels, and glycosylated hemoglobin levels. In this text, we tried to summarize known data about diagnosis, epidemiology, risk factors, pathophysiology, and prevention of prediabetes in relation to DM and stroke.

Post-stroke dementia - a comprehensive review.

Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients ('at risk brains') from those with better prognosis or to discriminate Alzheimer's disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing.

Vascular depression consensus report - a critical update.

BACKGROUND: Vascular depression is regarded as a subtype of late-life depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. Although the term is commonly used in research settings, widely accepted diagnostic criteria are lacking and vascular depression is absent from formal psychiatric manuals such as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition - a fact that limits its use in clinical settings. Magnetic resonance imaging (MRI) techniques, showing a variety of cerebrovascular lesions, including extensive white matter hyperintensities, subcortical microvascular lesions, lacunes, and microinfarcts, in patients with late life depression, led to the introduction of the term "MRI-defined vascular depression". DISCUSSION: This diagnosis, based on clinical and MRI findings, suggests that vascular lesions lead to depression by disruption of frontal-subcortical-limbic networks involved in mood regulation. However, despite multiple MRI approaches to shed light on the spatiotemporal structural changes associated with late life depression, the causal relationship between brain changes, related lesions, and late life depression remains controversial. While postmortem studies of elderly persons who died from suicide revealed lacunes, small vessel, and Alzheimer-related pathologies, recent autopsy data challenged the role of these lesions in the pathogenesis of vascular depression. Current data propose that the vascular depression connotation should be reserved for depressed older patients with vascular pathology and evident cerebral involvement. Based on current knowledge, the correlations between intra vitam neuroimaging findings and their postmortem validity as well as the role of peripheral markers of vascular disease in late life depression are discussed. CONCLUSION: The multifold pathogenesis of vascular depression as a possible subtype of late life depression needs further elucidation. There is a need for correlative clinical, intra vitam structural and functional MRI as well as postmortem MRI and neuropathological studies in order to confirm the relationship between clinical symptomatology and changes in specific brain regions related to depression. To elucidate the causal relationship between regional vascular brain changes and vascular depression, animal models could be helpful. Current treatment options include a combination of vasoactive drugs and antidepressants, but the outcomes are still unsatisfying.

Migraine with aura and TCD bubble-test: The significance of positive result.

BACKGROUND/AIM: The association between the right-to-left shunt (RLS) and migraine with aura (MA) has been proven so far. The aim of this study was to determine if the presence of RLS detected as a result of transcranial doppler (TCD) bubble-test, makes any difference in clinical presentation, aura and headache in patients with MA. METHODS: A single-group descriptive study was conducted on 153 patients diagnosed with MA. TCD bubble-test was performed on 135 of them. The recorded demographic and clinical features of patients were analyzed and compared with the results of the TCD bubble test. RESULTS: In the group of 135 patients, 88 (65.2%) had positive TCD bubble-test. The difference in the investigated clinical features of patients of the patients and aura between the patients with and without RLS, was not found. CONCLUSION: The results of our study confirm a high prevalence of right-to-left shunt in patients with MA, but the clinical relevance of this association was not shown.

Cluster headache as a first manifestation of multiple sclerosis: case report and literature review.

Cluster headache (CH) is estimated to be the most common primary trigeminal autonomic headache, although it is a rare disabling medical condition. Dominant symptoms of CH include severe unilateral orbital, supraorbital, and/or temporal pain, lasting from 15 to 180 minutes if untreated, associated with at least one of various autonomic symptoms during the headache, such as conjunctival injection, lacrimation, nasal congestion and rhinorrhea, facial sweating, miosis, ptosis, and eyelid edema. Headache is not frequently a symptom of multiple sclerosis (MS). The most commonly reported primary headaches are migraine without aura and a tension-type headache. Several described cases involved complicated migraine, ophthalmoplegic migraine-like headache, and finally cluster-like headache. We present a case of a 45-year-old male patient who had typical CH attacks as the initial and only clinical manifestation of MS, which was diagnosed after cerebrospinal fluid (CSF) isoelectric focusing and brain magnetic resonance imaging (MRI) investigation. He presented as a typical cluster-like headache patient since in the background of the CH symptoms and signs, were MS demyelinating lesions. In a patient with CH symptoms one should always think about the possibility of cluster-like-headache, which presents the CH patient with different underlying diseases, so we proposed a protocol to evaluate such patients and exclude diseases that could be in the background of CH symptoms.

Transcranial brain parenchymal sonography in neurodegenerative and psychiatric diseases.

Transcranial sonography is a highly sensitive noninvasive sonographic method for detection of early and specific echogenic changes in basal ganglia of patients with some neurodegenerative diseases. Transcranial sonography showed substantia nigra hyperechogenicity as a typical echo feature in idiopathic Parkinson disease and lenticular nucleus hyperechogenicity as a characteristic finding in atypical parkinsonian syndromes. Brain stem raphe hypoechogenicity or interruption has been shown to be highly prevalent in patients with unipolar depression as well as depression associated with certain neurodegenerative diseases. Transcranial sonography also revealed basal ganglia hyperechoic changes in movement disorders with trace metal accumulation such as Wilson disease, some entities of neurodegeneration with brain iron accumulation, as well as several forms of spinocerebellar ataxia. Transcranial sonography is a valuable neuro imaging method for early and differential diagnosis and follow-up of patients with neurodegenerative and psychiatric diseases.

Is sonothrombolysis an effective stroke treatment?

New therapeutic strategies under development aim to improve recanalization rates and clinical outcomes after ischemic stroke. One such approach is ultrasound (US)-enhanced thrombolysis, or sonothrombolysis, which can improve thrombolytic drug actions and even intrinsic fibrinolysis. Although the mechanisms are not fully understood, it is postulated that thrombolysis enhancement is related to nonthermal mechanical effects of US. Recent results indicate that US with or without microbubbles may be effective in clot lysis of ischemic stroke even without additional thrombolytic drugs. Sonothrombolysis is a promising tool for treating acute ischemic stroke, but its efficacy, safety, and technical details have not been elucidated and proved yet in stroke treatment.

[Incompetence of internal jugular vein valve in patients with transient global amnesia].

BACKGROUND/AIM: Transient global amnesia (TGA) could be related to acute ischemic disturbances in mesial parts of temporal lobes, which are important for memory. Incompetence of internal jugular vein (IJV) valve with venous congestion causes venous microthrombosis of hippocampus. The aim of this study was to investigate the frequency of IJV valve incompetence, as well as other hemodynamic and structural properties of cerebral circulation in TGA patients. METHODS: IJV valve competence was investigated in 40 TGA patients and 30 persons of the control group (matched by age and sex), as well as detection of microembolic signals and detection of right to left cardiopulmonal shunt, cerebral vasomotor reactivity and echocardiography by color triplex ultrasonography and transcranial doppler. RESULTS: A significant difference in frequency of IJV valve incompetence was found between the TGA patients and the control persons (55% TGA vs. 30% controls; p < 0.001). We did not find a significant structural (plaques frequency) or hemodynamic (flow velocity, pulsatility index) differences on arteries of the neck and cerebral arteries between the TGA patients and the controls, except for the increased pulsatility index on the basilar artery (40% TGA vs. 16.6% controls; p < 0.01) and decreased vasomotor reactivity in TGA patients (50% TGA vs 26.6% controls;p < 0.001). Microembolic signals were detected very rarely (17.5% TGA patients vs. 13.3% controls; p > 0.05), as well as right to left cardiopulmonal shunt (15% TGA vs. 16.6% controls; p > 0.05), indicating that embolism was not important for pathogenesis of TGA. Transesophageal echocardiography confirmed it, because only one TGA patient had a potent foramen ovale. CONCLUSION: We found a significantly increased frequency of IJV incompetence in the TGA patients, which confirmed the role of vein drainage disturbances in pathogenesis of TGA.

Transcranial sonography in depression.

Transcranial sonography, which displays tissue echogenicity of the brain through the intact skull, reveals reduced echogenicity of the brainstem raphe (BR) as a characteristic finding in unipolar depression and in depression associated with Parkinson's or Wilson's disease, but in general not in healthy adults, bipolar affective disorders, schizophrenia, multiple sclerosis with depression, or Parkinson's disease without concomitant depression. The reason for the reduced echogenicity of the BR is not entirely clear. Magnetic resonance imaging investigations, however, provide evidence that the signal alteration may be caused by a modification of tissue cell density, the interstitial matrix composition, or an alteration of fiber tracts integrity. An involvement of the basal limbic system in the pathogenesis of unipolar depression and depression associated with certain neurodegenerative diseases is assumed.

[Transcranial Doppler test for evaluation of cerebral artery embolism--microemboli detection].

About one third of ischaemic cerebrovascular diseases have embolic properties. Because of that, transcranial Doppler (TCD) test for detection of microembolic signals (MES), as the only one method for detection of microemboli, is a very important test for the evaluation of cerebral artery embolism. Cerebral emboli are particles of thrombus or atheromatous plaque, platelet aggregates, lipid or air particles in cerebral circulation, which can occlude arterioles and cause ischaemic transient attack (TIA) or stroke. Most frequently, they derive from exulcerated plaques of the carotid bifurcation or the aortic arch, from the atrial thrombus, prosthetic heart valves, as well as during carotid endarterectomy, arterial stent, aortocoronary by-pass. For MES detection, bilateral monitoring of a. cerebri mediae (ACM) is performed with each probe held in place over a temporal bone. MES are represented as brightly coloured embolic tracks as they pass through the insonated arteries. A computer hard disk provides continuous recording that is replayed for counting embolic signals. Colour intensity or acoustic range indicate the size and structure of MES. MES in the range of one ACM indicate the source of embolism on the ipsilateral carotid artery, while the bilateral detection of MES suggests a cardiogenic source. Indications for TCD detection of MES are the evaluation of pathogenesis and risk for embolic stroke or TIA and assessing the source of embolism. We started applying this method at the Institute of Neurology in Belgrade 2 years ago. We have investigated 78 patients till today and detected MES in 23 patients (28.7%). The Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology, 2004, considers that TCD is probably useful for detection of cerebral MES in various cardiovascular and cerebrovascular disorders and procedures.