Hippocampal neurometabolic and structural changes from pre-to post-COVID-19: A case-series study.

BACKGROUND: Neurological complications of the COVID-19 infection may be caused in part by local neurochemical and structural abnormalities that could not be detected during routine medical examinations. We examined within subject neurometabolic and structural brain alterations from pre-to post-COVID-19 in the hippocampal region of three elderly individuals (aged 63-68 years) who had a COVID-19 infection with mild symptoms. Patients were participating in an interventional study in which they were closely monitored at the time they were diagnosed with COVID-19. Patients 1 and 2 just completed 18-20 resistance training sessions prior to their diagnosis. Patient 3 was assigned to a non-training condition in the same study. METHODS: Whole brain magnetic resonance imaging (MRI) images and proton magnetic resonance spectroscopy (1H-MRS) of the left hippocampus were collected before and after infection. Structural and spectroscopic imaging measures post-COVID-19 were contrasted to the pre-COVID-19 measures and were compared with values for Minimal Detectable Change at 95% (MDC95) and 90% (MDC90) confidence from a group of six elderly (aged 60-79 years) without COVID-19 that participated in the same study. RESULTS: After SARS-COV-2 infection, we observed a reduction of glutamate-glutamine (Glx) in Patients 1 and 2 (≥ 42.0%) and elevation of myo-inositol (mIns) and N-acetyl-aspartate (NAA) in Patient 3 (≥ 36.4%); all > MDC90. MRI findings showed increased (Patients 1 and 2) or unchanged (Patient 3) hippocampal volume. CONCLUSIONS: Overall, findings from this exploratory study suggest that mild COVID-19 infection could be associated with development of local neuroinflammation and reduced glutamate levels in the hippocampus. Our 1H-MRS findings may have clinical value for explaining chronic neurological and psychological complaints in COVID-19 long-haulers.

Body fat and components of sarcopenia relate to inflammation, brain volume, and neurometabolism in older adults.

Obesity and sarcopenia are associated with cognitive impairments at older age. Current research suggests that blood biomarkers may mediate this body-brain crosstalk, altering neurometabolism and brain structure eventually resulting in cognitive performance changes. Seventy-four older adults (60-85 years old) underwent bio-impedance body composition analysis, handgrip strength measurements, 8-Foot Up-and-Go (8UG) test, Montreal Cognitive Assessment (MoCA), blood analysis of interleukin-6 (IL-6), kynurenine, and insulin-like growth factor-1 (IGF-1), as well as brain magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS), estimating neurodegeneration and neuroinflammation. Normal fat% or overweight was associated with larger total gray matter volume compared to underweight or obesity in older adults and obesity was associated with higher N-acetylaspartate/Creatine levels in the sensorimotor and dorsolateral prefrontal cortex. Muscle strength, not muscle mass/physical performance, corresponded to lower kynurenine and higher N-acetylaspartate/Creatine levels in the dorsal posterior cingulate and dorsolateral prefrontal cortex. The inflammatory and neurotrophic blood biomarkers did not significantly mediate these body-brain associations. This study used a multimodal approach to comprehensively assess the proposed mechanism of body-brain crosstalk.

N-acetyl-aspartate and Myo-inositol as Markers of White Matter Microstructural Organization in Mild Cognitive Impairment: Evidence from a DTI-1H-MRS Pilot Study.

We implemented a multimodal approach to examine associations between structural and neurochemical changes that could signify neurodegenerative processes related to mild cognitive impairment (MCI). Fifty-nine older adults (60-85 years; 22 MCI) underwent whole-brain structural 3T MRI (T1W, T2W, DTI) and proton magnetic resonance spectroscopy (1H-MRS). The regions of interest (ROIs) for 1H-MRS measurements were the dorsal posterior cingulate cortex, left hippocampal cortex, left medial temporal cortex, left primary sensorimotor cortex, and right dorsolateral prefrontal cortex. The findings revealed that subjects in the MCI group showed moderate to strong positive associations between the total N-acetylaspartate to total creatine and the total N-acetylaspartate to myo-inositol ratios in the hippocampus and dorsal posterior cingulate cortex and fractional anisotropy (FA) of WM tracts crossing these regions-specifically, the left temporal tapetum, right corona radiata, and right posterior cingulate gyri. In addition, negative associations between the myo-inositol to total creatine ratio and FA of the left temporal tapetum and right posterior cingulate gyri were observed. These observations suggest that the biochemical integrity of the hippocampus and cingulate cortex is associated with a microstructural organization of ipsilateral WM tracts originating in the hippocampus. Specifically, elevated myo-inositol might be an underlying mechanism for decreased connectivity between the hippocampus and the prefrontal/cingulate cortex in MCI.

Strength gains after 12 weeks of resistance training correlate with neurochemical markers of brain health in older adults: a randomized control 1H-MRS study.

Physical exercise is considered a potent countermeasure against various age-associated physiological deterioration processes. We therefore assessed the effect of 12 weeks of resistance training on brain metabolism in older adults (age range: 60-80 years). Participants either underwent two times weekly resistance training program which consisted of four lower body exercises performed for 3 sets of 6-10 repetitions at 70-85% of 1 repetition maximum (n = 20) or served as the passive control group (n = 21). The study used proton magnetic resonance spectroscopy to quantify the ratio of total N-acetyl aspartate, total choline, glutamate-glutamine complex, and myo-inositol relative to total creatine (tNAA/tCr, tCho/tCr, Glx/tCr, and mIns/tCr respectively) in the hippocampus (HPC), sensorimotor (SM1), and prefrontal (dlPFC) cortices. The peak torque (PT at 60°/s) of knee extension and flexion was assessed using an isokinetic dynamometer. We used repeated measures time × group ANOVA to assess time and group differences and correlation coefficient analyses to examine the pre-to-post change (∆) associations between PT and neurometabolite variables. The control group showed significant declines in tNAA/tCr and Glx/tCr of SM1, and tNAA/tCr of dlPFC after 12 weeks, which were not seen in the experimental group. A significant positive correlation was found between ∆PT knee extension and ∆SM1 Glx/tCr, ∆dlPFC Glx/tCr and between ∆PT knee flexion and ∆dlPFC mIns/tCr in the experimental group. Overall, findings suggest that resistance training seems to elicit alterations in various neurometabolites that correspond to exercise-induced "preservation" of brain health, while simultaneously having its beneficial effect on augmenting muscle functional characteristics in older adults.

Neurometabolic correlates of posturography in normal aging and older adults with mild cognitive impairment: Evidence from a 1H-MRS study.

Proton magnetic resonance spectroscopy (1H-MRS) holds promise for revealing and understanding neurodegenerative processes associated with cognitive and functional impairments in aging. In the present study, we examined the neurometabolic correlates of balance performance in 42 cognitively intact older adults (healthy controls - HC) and 26 older individuals that were diagnosed with mild cognitive impairment (MCI). Neurometabolite ratios of total N-acetyl aspartate (tNAA), glutamate-glutamine complex (Glx), total choline (tCho) and myo-inositol (mIns) relative to total creatine (tCr) were assessed using single voxel 1H-MRS in four different brain regions. Regions of interest were the left hippocampus (HPC), dorsal posterior cingulate cortex (dPCC), left sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (dlPFC). Center-of-pressure velocity (Vcop) and dual task effect (DTE) were used as measures of balance performance. Results indicated no significant group differences in neurometabolite ratios and balance performance measures. However, our observations revealed that higher tCho/tCr and mIns/tCr in hippocampus and dPCC were generic predictors of worse balance performance, suggesting that neuroinflammatory processes in these regions might be a driving factor for impaired balance performance in aging. Further, we found that higher tNAA/tCr and mIns/tCr and lower Glx/tCr in left SM1 were predictors of better balance performance in MCI but not in HC. The latter observation hints at the possibility that individuals with MCI may upregulate balance control through recruitment of sensorimotor pathways.

Inflammatory Blood Biomarker Kynurenine Is Linked With Elevated Neuroinflammation and Neurodegeneration in Older Adults: Evidence From Two 1H-MRS Post-Processing Analysis Methods.

Rationale and Objectives: Pro-inflammatory processes have been argued to play a role in conditions associated with cognitive decline and neurodegeneration, like aging and obesity. Only a limited number of studies have tried to measure both peripheral and central biomarkers of inflammation and examined their interrelationship. The primary aim of this study was to examine the hypothesis that chronic peripheral inflammation would be associated with neurometabolic changes that indicate neuroinflammation (the combined elevation of myoinositol and choline), brain gray matter volume decrease, and lower cognitive functioning in older adults. Materials and Methods: Seventy-four older adults underwent bio-impedance body composition analysis, cognitive testing with the Montreal Cognitive Assessment (MoCA), blood serum analysis of inflammatory markers interleukin-6 (IL-6) and kynurenine, magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS) of the brain. Neurometabolic findings from both Tarquin and LCModel 1H-MRS post-processing software packages were compared. The regions of interest for MRI and 1H-MRS measurements were dorsal posterior cingulate cortex (DPCC), left hippocampal cortex (HPC), left medial temporal cortex (MTC), left primary sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (DLPFC). Results: Elevated serum kynurenine levels were associated with signs of neuroinflammation, specifically in the DPCC, left SM1 and right DLPFC, and signs of neurodegeneration, specifically in the left HPC, left MTC and left SM1, after adjusting for age, sex and fat percentage (fat%). Elevated serum IL-6 levels were associated with increased Glx levels in left HPC, left MTC, and right DLPFC, after processing the 1H-MRS data with Tarquin. Overall, the agreement between Tarquin and LCModel results was moderate-to-strong for tNAA, tCho, mIns, and tCr, but weak to very weak for Glx. Peripheral inflammatory markers (IL-6 and kynurenine) were not associated with older age, higher fat%, decreased brain gray matter volume loss or decreased cognitive functioning within a cohort of older adults. Conclusion: Our results suggest that serum kynurenine may be used as a peripheral inflammatory marker that is associated with neuroinflammation and neurodegeneration, although not linked to cognition. Future studies should consider longitudinal analysis to assess the causal inferences between chronic peripheral and neuroinflammation, brain structural and neurometabolic changes, and cognitive decline in aging.

Diffuse Leptomeningeal Glioneuronal Tumour with 9-Year Follow-Up: Case Report and Review of the Literature.

In 2016, the World Health Organisation Classification (WHO) of Tumours was updated with diffuse leptomeningeal glioneuronal tumour (DLGNT) as a provisional unit of mixed neuronal and glial tumours. Here, we report a DLGNT that has been re-diagnosed with the updated WHO classification, with clinical features, imaging, and histopathological findings and a 9-year follow-up. A 16-year-old girl presented with headache, vomiting, and vertigo. Magnetic resonance imaging (MRI) demonstrated a hyperintense mass with heterogenous enhancement in the right cerebellopontine angle and internal auditory canal. No leptomeningeal involvement was seen. The histological examination revealed neoplastic tissue of moderate cellularity formed mostly by oligodendrocyte-like cells. Follow-up MRI scans demonstrated cystic lesions in the subarachnoid spaces in the brain with vivid leptomeningeal enhancement. Later spread of the tumour was found in the spinal canal. On demand biopsy samples were re-examined, and pathological diagnosis was identified as DLGNT. In contrast to most reported DLGNTs, the tumour described in this manuscript did not present with diffuse leptomeningeal spread, but later presented with leptomeningeal involvement in the brain and spinal cord. Our case expands the spectrum of radiological features, provides a long-term clinical and radiological follow-up, and highlights the major role of molecular genetic testing in unusual cases.

Odor Identification and Regional Gray Matter Atrophy in Patients with Alzheimer's Disease, Parkinson's Disease, and the Healthy Elderly: A Cross-Sectional Structural MRI Study.

Multiple associations between impaired olfactory performance and regional cortical and deep gray matter atrophy have been reported in separate studies of patients with Alzheimer's disease (AD), Parkinson's disease (PD), and of the healthy elderly. We aimed to evaluate such possible associations among these populations in a unified manner. Twenty AD, twenty PD patients' and twenty healthy age- and sex-matched controls' odor identification performance was assessed with the Lithuanian adaptation of the Sniffin' Sticks 12 odor identification test, followed by morphometric gray matter analysis by MRI using FreeSurfer. AD patients had significantly lower cognitive performance than both PD patients and the healthy elderly, as evaluated with the Mini-Mental State Examination (MMSE). Odor identification performance was significantly worse in AD and PD patients compared with the healthy elderly; AD patients performed slightly worse than PD patients, but the difference was not statistically significant. Among patients with AD, worse odor identification performance was initially correlated with atrophy of multiple cortical and deep gray matter regions known to be involved in olfactory processing, however, only two measures-decreased thicknesses of the right medial and left lateral orbitofrontal cortices-remained significant after adjustment for possible confounders (age, MMSE score, and global cortical thickness). Among patients with PD and the healthy elderly we found no similar statistically significant correlations. Our findings support the key role of the orbitofrontal cortex in odor identification among patients with AD, and suggest that correlations between impaired odor identification performance and regional gray matter atrophy may be relatively more pronounced in AD rather than in PD.

Volumetric MRI Analysis of Brain Structures in Patients with History of First and Repeated Suicide Attempts: A Cross Sectional Study.

Structural brain changes are found in suicide attempters and in patients with mental disorders. It remains unclear whether the suicidal behaviors are related to atrophy of brain regions and how the morphology of specific brain areas is changing with each suicide attempt. The sample consisted of 56 patients hospitalized after first suicide attempt (first SA) (n = 29), more than one suicide attempt (SA > 1) (n = 27) and 54 healthy controls (HC). Brain volume was measured using FreeSurfer 6.0 automatic segmentation technique. In comparison to HC, patients with first SA had significantly lower cortical thickness of the superior and rostral middle frontal areas, the inferior, middle and superior temporal areas of the left hemisphere and superior frontal area of the right hemisphere. In comparison to HC, patients after SA > 1 had a significantly lower cortical thickness in ten areas of frontal cortex of the left hemisphere and seven areas of the right hemisphere. The comparison of hippocampus volume showed a significantly lower mean volume of left and right parts in patients with SA > 1, but not in patients with first SA. The atrophy of frontal, temporal cortex and hippocampus parts was significantly higher in repeated suicide attempters than in patients with first suicide attempt.

Diagnostic Ability of Radiofrequency Ultrasound in Parkinson's Disease Compared to Conventional Transcranial Sonography and Magnetic Resonance Imaging.

We aimed to estimate tissue displacements' parameters in midbrain using ultrasound radiofrequency (RF) signals and to compare diagnostic ability of this RF transcranial sonography (TCS)-based dynamic features of disease affected tissues with conventional TCS (cTCS) and magnetic resonance imaging (MRI) while differentiating patients with Parkinson's disease (PD) from healthy controls (HC). US tissue displacement waveform parametrization by RF TCS for endogenous brain tissue motion, standard neurological examination, cTCS and MRI data collection were performed for 20 PD patients and for 20 age- and sex-matched HC in a prospective manner. Three logistic regression models were constructed, and receiver operating characteristic (ROC) curve analyses were applied. The model constructed of RF TCS-based brain tissue displacement parameters-frequency of high-end spectra peak and root mean square-revealed presumably increased anisotropy in the midbrain and demonstrated rather good diagnostic ability in the PD evaluation, although it was not superior to that of the cTCS or MRI. Future studies are needed in order to establish the true place of RF TCS detected tissue displacement parameters for the evaluation of pathologically affected brain tissue.

Diagnostic Ability of Structural Transcranial Sonography in Patients with Alzheimer's Disease.

The aim of this study was to assess the diagnostic ability of transcranial sonography (TCS) for the evaluation of the medial temporal lobe (MTL) in Alzheimer's disease (AD). Standard neuropsychological evaluation, TCS and 1.5 T MRI were performed for 20 patients with AD and for 20 age- and sex-matched healthy controls in a prospective manner. Measurements of the size of the third ventricle and heights of the MTL (A) and the choroidal fissure (B) were performed twice on each side by two independent neurosonologists for all participants. On MRI, both conventional and volumetric analyses of the third ventricle and hippocampus were performed. Receiver operating characteristic (ROC) curves analyses were applied. Height of the MTL on TCS had sensitivities of 73.7% (right)/63.2%(left) and specificities of 65% (right)/65-70% (left) Area under a curve (AUC) 75.4-77.2% (right), 60.4-67.8% (left)) for AD. A/B ratio on TCS had sensitivities of 73.7% (right)/57.9% (left) and specificities of 70.0% (right)/55.0% (left) (AUC 73.3% (right), 60.4% (left)) by the experienced neurosonologist, and sensitivities of 78.9% (right and left) and specificities of 60.0% (right)/65.0% (left) (AUC 77.8-80.0%) by the inexperienced neurosonologist for AD. On MRI, linear measurement of the hippocampus and parahippocampal gyrus height had sensitivities of 84.2% (right)/89.5% (left) and specificities of 80.0% (right)/85% (left) (AUC 86.1-92.9%) for AD. Hippocampal volume had sensitivities of 70% (right and left) and specificities of 75% (right)/80% (left) (AUC 77.5-78%) for AD. Atrophy of the right MTL in AD could be detected on TCS with a good diagnostic ability, however MRI performed better on the left.

Ultrasonic Assessment of the Medial Temporal Lobe Tissue Displacements in Alzheimer's Disease.

We aim to estimate brain tissue displacements in the medial temporal lobe (MTL) using backscattered ultrasound radiofrequency (US RF) signals, and to assess the diagnostic ability of brain tissue displacement parameters for the differentiation of patients with Alzheimer's disease (AD) from healthy controls (HC). Standard neuropsychological evaluation and transcranial sonography (TCS) for endogenous brain tissue motion data collection are performed for 20 patients with AD and for 20 age- and sex-matched HC in a prospective manner. Essential modifications of our previous method in US waveform parametrization, raising the confidence of micrometer-range displacement signals in the presence of noise, are done. Four logistic regression models are constructed, and receiver operating characteristic (ROC) curve analyses are applied. All models have cut-offs from 61.0 to 68.5% and separate AD patients from HC with a sensitivity of 89.5% and a specificity of 100%. The area under a ROC curve of predicted probability in all models is excellent (from 95.2 to 95.7%). According to our models, AD patients can be differentiated from HC by a sharper morphology of some individual MTL spatial point displacements (i.e., by spreading the spectrum of displacements to the high-end frequencies with higher variability across spatial points within a region), by lower displacement amplitude differences between adjacent spatial points (i.e., lower strain), and by a higher interaction of these attributes.

Neuropsychiatric complications and neuroimaging characteristics after deep brain stimulation surgery for Parkinson's disease.

Psychiatric complications after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease patients are common. The aim of this study was to evaluate a possible role of cortical thickness, cortical and subcortical volume for neuropsychiatric complications after STN-DBS implantation surgery. Twenty-two Parkinson's disease patients underwent STN-DBS. Control group consisted of 18 healthy volunteers who were matched by age and gender. All Parkinson's disease patients and control subjects underwent neuropsychological assessment and brain MRI. Control group subjects had normal MRI and neurocognitive testing results. Seven (31.8%) Parkinson's disease patients developed neuropsychiatric complications (psychosis and delirium) after STN-DBS implantation surgery with full recovery in short follow up. Two Parkinson's disease patients were excluded from further analysis, because they did not match image processing and analysis quality control. Volumetric analysis showed significant differences in cortical thickness between STN-DBS patients with and without postoperative neuropsychiatric complications in 13 gyruses on the right hemisphere (superior frontal, caudal middle frontal, pars triangularis and opercularis, temporal lobe, superior and inferior parietal, supramarginal) and in 7 gyruses on the left hemisphere (caudal middle frontal, inferior and middle temporal, pre and postcentral, superior parietal and supramarginal). White matter volume analysis showed also its reduction in the left caudal middle frontal area. Moreover, white matter volume and surface area reduction implicating that this area can be the most important for postoperative neuropsychiatric complication risk. Study results suggest that neuropsychiatric complications are common in Parkinson's disease patients after STN-DBS implantation and can be associated with excitation of frontal-striatum-thalamus and temporal-parietal circuits.

Retained Glass Fragment in the Cervical Spinal Canal in a Patient with Acute Transverse Myelitis: A Case Report and Literature Review.

A 50-year-old male presented with a one-day history of right leg weakness, numbness, and urinary retention. Weakness was present for two weeks but worsened significantly during the last 24 hours. On the right there was sensory loss in the leg and below the Th8 dermatome. On the left there was sensory loss below the Th10 dermatome and distal loss of temperature sensation. Past medical history revealed a cervical trauma 30 years ago when a glass chip lodged into the left side of the neck. The patient did not seek medical attention after removing it himself. No neurological symptoms followed the incident. No cervical manipulation or other physical trauma occurred before current symptom onset. Magnetic resonance (MR) imaging showed features consistent with myelitis at the level of C4-Th3. At the level of C6-C7, a T1 and T2 hypointense lesion was noted. On computed tomography, this lesion was hyperdense and occupied the spinal canal and the left intervertebral foramen. It was deemed to be a glass fragment. Surgical removal was withheld because the fragment was clinically silent for 30 years, the risk of surgical removal would outweigh the benefits and the patient did not prefer surgical treatment. Acute demyelinating transverse myelitis was diagnosed and treated with methylprednisolone. 10 months later MR features of myelitis resolved and the patient's neurological condition improved. Our case shows that foreign bodies in the cervical spinal canal can remain asymptomatic for up to 30 years. In the case of a long asymptomatic retention period the need for surgical removal of a foreign body must be carefully evaluated, taking into account the probability that a foreign body is the cause of current symptoms, risk of a foreign body causing damage in the future, risk of damage to the spinal cord during removal, and probability of therapeutic success.

Brain MRI morphometric analysis in Parkinson's disease patients with sleep disturbances.

BACKGROUND: Sleep disturbances are common in patients with advanced Parkinson disease (PD). The aim of this study was to evaluate a possible association of cortical thickness, cortical and subcortical volume with sleep disturbances in PD patients. METHODS: Twenty-eight PD patients (14 men and 14 women, median age 58 years) were evaluated for sleep disturbances with PDSS and underwent brain MRI. Control group consisted of 28 healthy volunteers who were matched by age and gender. Automated voxel based image analysis was performed with the FreeSurfer software. RESULTS: PD patients when compared to controls had larger ventricles, smaller volumes of hippocampus and superior cerebellar peduncle, smaller grey matter thickness in the left fusiform, parahipocampal and precentral gyruses, and right caudal anterior cingulate, parahipocampal and precentral hemisphere gyruses, as well as smaller volume of left rostral middle frontal and frontal pole areas, and right entorhinal and transverse temporal areas. According to the Parkinson's disease Sleep Scale (PDSS), 15 (53.58%) patients had severely disturbed sleep. The most frequent complaints were difficulties staying asleep during the night and nocturia. The least frequent sleep disturbances were distressing hallucinations and urine incontinence due to off symptoms. Patients who fidgeted during the night had thicker white matter in the left caudal middle frontal area and lesser global left hemisphere cortical surface, especially in the lateral orbitofrontal and lateral occipital area, and right hemisphere medial orbitofrontal area. Patients with frequent distressful dreams had white matter reduction in cingulate area, and cortical surface reduction in left paracentral area, inferior frontal gyrus and right postcentral and superior frontal areas. Nocturnal hallucinations were associated with volume reduction in the basal ganglia, nucleus accumbens and putamen bilaterally. Patients with disturbing nocturia had reduction of cortical surface on the left pre- and postcentral areas, total white matter volume decrease bilaterally as well in the pons. CONCLUSIONS: PD patients with nocturnal hallucinations had prominent basal ganglia volume reduction. Distressful dreams were associated with limbic system and frontal white matter changes, meanwhile nocturia was mostly associated with global white matter reduction and surface reduction of cortical surface on the left hemisphere pre- and postcentral areas.

Different MRI-defined tuber types in tuberous sclerosis complex: Quantitative evaluation and association with disease manifestations.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare genetic disorder with multisystem involvement. A magnetic-resonance (MRI) based classification of tubers into types A, B and C has been proposed. However, the relationship between different tuber types and their quantitative characteristics, also the non-neurological manifestations of TSC remains unknown. AIMS: To quantitatively evaluate different MRI-defined tuber types and to explore their relationships with major disease manifestations in patients with tuberous sclerosis complex. METHODS: We performed quantitative manual assessment of tubers visible on T1W, T2W/FLAIR images and DW/ADC maps of 20 patients with TSC. Tubers were classified into types A, B and C based on their signal intensity on MRI. General clinical information and quantitative tuber characteristics were evaluated. Between-group comparisons were made using the nonparametric Mann-Whitney U test with Bonferroni correction. RESULTS: In total, 20 patients with 770 tubers were evaluated. Type A tubers were most numerous followed closely by Type B tubers, whereas Type C tubers were relatively rare. Tuber size was markedly different among the three tuber types: it increased from Type A to Type B to Type C. Infantile spasms, generalized-tonic clonic seizures, poor seizure control, cardiac rhabdomyomas, SEGA and developmental delay were not associated with quantitative tuber characteristics. Increased total Type B tuber load was associated with early onset epilepsy, while individually larger Type A and Type B tubers were associated with the presence angiomyolipoma (AML) and renal cysts. CONCLUSIONS: MRI-defined tuber types differ significantly in their size and number. Larger total Type B tuber load and larger individual Type A and Type B tubers were found to be most associated with early seizure onset and renal angiomyolipomas, respectively. One possible explanation for the observed differences in the clinical phenotype based on MRI-defined tuber types is not the intrinsic qualitative distinctions between different tuber types, but rather their individual size and total tuber load.

Characteristics of headache in relation to the manifestation of Susac syndrome.

Susac syndrome is characterized by a clinical triad of encephalopathy, branch retinal artery occlusion, and hearing loss. Due to the absence of the whole complex of the triad in the majority of cases at disease presentation, the syndrome often remains underdiagnosed and untreated. Headache is estimated to affect up to 80% of Susac syndrome patients, but the relevance of headache characteristics and profile is not yet clear. The proposed diagnostic criteria of the European Susac Consortium acknowledge headache as a possible brain manifestation if it is new, described as migrainous or oppressive, and precedes the other symptoms by not more than 6 months. Herein, a case series of different migraine-like headache associations attributed to Susac syndrome is presented and discussed in relevance with previously published literature. Our patients experienced different presentations of migraine-like headache related with Susac syndrome: exacerbation and chronification of headache just before the manifestation of the first symptoms of Susac syndrome, the manifestation of headache during the first episode of the syndrome, and an increasing frequency of headache during the course of the disease. The diagnosis of Susac syndrome in all three cases was confirmed by typical clinical symptoms and findings in retinal fluorescein angiography, audiometry, and brain magnetic resonance imaging, based on the diagnostic criteria of the European Susac Consortium. Based on the analysis of our presented cases, we conclude that headache attributed to Susac's syndrome is of migraine-like type but could be of different presentations in relation to the onset of the syndrome.

Peripheral Blood Leukocytes Interleukin-1 Beta (IL-1ß) Cytokine Hyper-Reactivity in Chronic Periodontitis.

BACKGROUND Levels of pro-inflammatory cytokine (IL-1ß) released by peripheral blood leukocyte medium (PBLM), isolated from chronic periodontitis patients (P) before therapy and matched to controls, were determined in the presence or absence of non-opsonized Escherichia coli and Staphylococcus aureus. MATERIAL AND METHODS In this investigation, 26 patients with untreated, severe, generalized, chronic periodontitis and 26 healthy subjects (H) were enrolled. Periodontal status was assessed by measuring bleeding on probing (BOP), clinical attachment loss (CAL), probing pocket depth (PPD), and Ramfjord index (PDI). The levels of IL-1ß (µg/ml) were assayed by a standard Immunoenzymetric Assay Diasource IL-1ß ELISA kit in PBLM. RESULTS Our study showed that the values of IL-1ß levels in PBLM of the P group (stimulated with non-opsonized E. coli and S. aureus) were significantly higher than in the analogous medium of H group subjects (P<0.001). All correlations between the cytokine levels of IL-1ß in the samples of PBLM (stimulated with non-opsonized E. coli and S. aureus) and clinical parameters such as BOP, PPD, CAL, and PDI were significantly higher in the group of patients with periodontitis. CONCLUSIONS Levels of IL-1ß secreted by leukocytes may help measure severe, generalized, chronic periodontitis, and can be predictive of future detrimental clinical sequelae associated with chronic periodontitis.

Sporadic Creutzfeldt-Jakob disease with unusual initial presentation as posterior reversible encephalopathy syndrome: a case report.

BACKGROUND: Creutzfeldt - Jakob disease (CJD) is a rapidly progressive and fatal neurodegenerative prion disease. MRI findings are included in diagnostic criteria for probable CJD, giving a sensitivity and specificity more than 90%, but the atypical radiological presentations in the early stage of the disease could cause the diagnostic difficulties. CJD can be definitively diagnosed by histopathological confirmation, brain biopsy or at autopsy. CASE PRESENTATION: We present a case of 53-year-old woman with a history of a rapidly progressive dementia with symptoms of visual impairment, increased extrapyramidal type muscle tonus, stereotypical movements and ataxic gait resulting in the patient's death after13 months. The clinical symptoms deteriorated progressively to myoclonus and akinetic mutism already on the 14th week. The series of diagnostic examinations were done to exclude the possible causes of dementia. Initial MRI evaluation as posterior reversible encephalopathy syndrome (PRES) on the 9th week after the onset of symptoms created us a diagnostic conundrum. Subsequent MRI findings of symmetrical lesions in the basal ganglia (nucleus caudatus, putamen) on the 13th week and EEG with periodic sharp wave complexes (PSWC) in frontal regions on the 18th week allowed us to diagnose the probable sCJD. The histopathological findings after brain biopsy on the 14th week demonstrated the presence of the abnormal prion protein deposits in the grey matter by immunohistochemistry with ICSM35, KG9 and 12 F10 antibodies and confirmed the diagnosis of sCJD. CONCLUSIONS: In this article we focus our attention on a rare association between radiological PRES syndrome and early clinical stage of sCJD. Although concurrent manifestation of these conditions can be accidental, but the immunogenic or neuropeptide mechanisms could explain such radiological MRI findings. A thorough knowledge of differential diagnostic of PRES may be especially useful in earlier diagnosis of sCJD.

Ultrasonographic (TCS) and clinical findings in overlapping phenotype of essential tremor and Parkinson's disease (ET-PD).

BACKGROUND: Essential tremor (ET) and Parkinson's disease (PD) are considered distinct disorders. The aim of the study was to look for a link or any distinguishing features by transcranial sonography (TCS), together with the clinical examination findings in a group of patients with overlapping phenotype of ET and PD (ET-PD). METHODS: A prospective observational case-control study was carried out from the 3rd January 2011 until 30th January 2013 at the Hospital of Lithuanian University of Health Sciences. The final study group consisted of 15 patients with ET-PD, 116 patients with ET-only and 141 patients with PD-only. The control group included 101 subjects. Clinical diagnosis was of a diagnostic standard. RESULTS: The main ultrasonographic findings in the ET-PD group were similar to those of the PD-only: hyperechogenicity of the substantia nigra (66.7%, p < 0.001) and nuclei raphe interruptions/absence (38.5%, p < 0.001). The single distinguishing TCS finding in ET-PD group was a lentiform nucleus hyperechogenicity (26.7%), however this was only significant when compared to controls (p = 0.006). An asymmetrical onset of symptoms (73.3%) in ET-PD group was characteristic to PD-only. The ET-PD patients had the longest disease duration (median 6 years, p < 0.001), the most frequent rate of positive family history (53.3%, p = 0.005), rather low prevalence of cogwheel rigidity (26.7%, p < 0.001), and higher mean Hoehn & Yahr scores compared to PD-only (2.6 ± 0.8 vs. 1.8 ± 0.8, p = 0.012). CONCLUSIONS: The main TCS findings of the present study in patients with overlapping ET-PD phenotype were similar to the PD-only group. The highest positive family history rate among ET-PD patients indicates a strong hereditary predisposition and needs genetic underpinnings. Some ET patients, who look like they may be developing co-morbid PD clinically, may have an alternative diagnosis for Parkinsonism, which could be delineated by TCS examination.