Quantitative EEG in the Differential Diagnosis of Dementia Subtypes.

OBJECTIVE: Most neurodegenerative dementias present with substantial overlap in clinical features. Therefore, differential diagnosis is often a challenging task necessitating costly and sometimes invasive diagnostic procedures. A promising, non-invasive and cost-effective method is the widely available electroencephalography (EEG). METHODS: Twenty-three subjects with Alzheimer's disease (AD), 28 subjects with dementia with Lewy bodies (DLB), 15 subjects with frontotemporal dementias (FTDs), and 22 healthy controls (HC) were enrolled. Nineteen channel computerized EEG recordings were acquired. Mean relative powers were calculated using the standard frequency bands. Theta/alpha ratio (TAR), theta/beta ratio (TBR), a spectral index of (alpha + beta)/(theta + delta) and an alpha reactivity index (alpha in eyes-open condition/alpha in eyes-closed condition) were also calculated. Receiver operating characteristic (ROC) analyses were performed to assess diagnostic accuracy. RESULTS: For the comparison of EEG measures across groups, we performed a multivariate ANOVA followed by univariate ANOVAs controlling for the effects of age, with post hoc tests. Theta power and TBR were increased in DLB compared to other groups. Alpha power was decreased in DLB compared to HC and FTD; and in AD compared to FTD. Beta power was decreased in DLB compared to AD and HC. Furthermore, regional analyses demonstrated a unique pattern of theta power increase in DLB; affecting frontal, central, parietal, occipital, and temporal regions. In AD, theta power increased compared to HC in parietal, occipital, and right temporal regions. TAR was increased in DLB compared to other groups; and in AD compared to HC. Finally, alpha reactivity index was higher in DLB compared to HC and FTD. In AD, EEG slowing was associated with cognitive impairment, while in DLB, this was associated with higher DLB characteristics. In the ROC analyses to distinguish DLB from FTD and AD, measures of EEG slowing yielded high area under curve values, with good specificities. Also, decreased alpha reactivity could distinguish DLB from FTD with good specificity. EEG slowing in DLB showed a diffuse pattern compared to AD, where a posterior and temporal slowing predominated. CONCLUSION: We showed that EEG slowing was satisfactory in distinguishing DLB patients from AD and FTD patients. Notably, this slowing was a characteristic finding in DLB patients, even at early stages, while it paralleled disease progression in AD. Furthermore, EEG slowing in DLB showed a diffuse pattern compared to AD, where a posterior and temporal slowing predominated. These findings align with the previous evidence of the diencephalic dysfunction in DLB.

A comparative transcranial magnetic stimulation study: Assessing cortical excitability and plasticity in Alzheimer's disease, dementia with Lewy bodies and Frontotemporal dementia.

BACKGROUND: Here, we aimed to investigate the roles of long-term potentiation-like (LTP-like) plasticity using intermittent theta burst (iTBS) protocol and resting motor threshold (rMT) in the differential diagnosis of Alzheimer's disease (AD), diffuse dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). METHOD: We enrolled 21 subjects with AD, 28 subjects with DLB, 14 subjects with FTD, and 33 elderly subjects with normal cognitive functions into the study. We recorded rMT and percentage amplitude change of motor evoked potentials (MEPs) after the iTBS protocol in each group. RESULTS: In patients with AD and DLB, the percentage amplitude change of MEPs, and rMTs were significantly lower than in healthy subjects. However, no significant difference was observed in individuals with FTD. CONCLUSION: Our findings showed that transcranial magnetic stimulation measures, particularly rMTs and LTP-like plasticity, may be potential biomarkers to distinguish between different dementia subtypes. Impaired motor cortical excitability and synaptic plasticity were more prominent in AD and DLB than in FTD. This aligns with the evidence that cortical motor networks are usually spared in FTDs in early-to-middle stages.

Serum Sirtuin-1, HMGB1-TLR4, NF-KB and IL-6 levels in Alzheimer's: The Relation Between Neuroinflammatory Pathway and Severity of Dementia.

Alzheimer's disease (AD), which affects the world's aging population, is a progressive neurodegenerative disease requiring markers or tools to accurately and easily diagnose and monitor the process accurately and easily. OBJECTIVE: In this study, serum Sirtuin-1(SIRT-1), High Mobility Group Box 1 (HMGB1), Toll-Like Receptor-4 (TLR4), Nuclear Factor Kappa B (NF-kB), Interleukine-6 (IL-6), Amyloid ßeta-42 (Aß-42), and p-tau181 levels in patients diagnosed with AD according to NINCS-ADRA criteria were studied. We investigated the inflammatory pathways that lead to progressive neuronal loss and highlight their possible relationship with dementia severity in the systemic circulation. METHODS: Patients over 60 years of age were grouped according to their Standard Mini Mental Test results, MRI, and/or Fludeoxyglucose positron emission tomography or according to their CT findings as Control n:20; AD n:32; Vascular Dementia (VD) n:17; AD + VD; n=21. Complete blood count, Glucose, Vitamin B12, Folic Acid, Enzymes, Urea, Creatinine, Electrolytes, Bilirubin, and Thyroid Function tests were evaluated. ELISA was used for the analysis of serum SIRT1, HMGB1, TLR4, NF-kB, IL-6, Aß-42, and p-tau181 levels. RESULTS: Levels of serum Aß-42, SIRT1, HMGB1, and IL-6 were significantly higher (p˂0.001, p<0.01, p<0.001, and p<0.001, respectively), and TLR4 levels were significantly lower (p˂0.001) in the dementia group than in the control group. No significant difference was observed between dementia and control groups for serum NF-kB and p-tau181 levels. CONCLUSION: Our results show that the levels of the Aß42, SIRT 1, HMGB1, and TLR4 pathways are altered in AD and VD. SIRT 1 activity plays an important role in the inflammatory pathway of dementia development, particularly in AD.

DNA repair gene OGG1 polymorphism and its relation with oxidative DNA damage in patients with Alzheimer's disease.

There is considerable evidence that oxidative DNA damage is increased, DNA repair capacity is decreased in patients with Alzheimer's disease. Base excision repair is the major pathway in removal of oxidative DNA damage. 8-oxo-deoxyguanosine DNA glycosylase 1 (OGG1) is the enzyme which is involved in the first step of this repair process. Alterations in DNA repair capacity may be related with polymorphisms in DNA repair genes. In order to investigate the effect of OGG1 Ser326Cys polymorphism on oxidative DNA damage level, OGG1 genotyping was performed, basal and oxidative DNA damage in lymphocytes and 8-OHdG level in plasma were examined in patients with Alzheimer's disease. Basal and oxidative DNA damage and 8-OHdG level were measured by OGG1-modified comet assay and enzyme-linked immunoassay, respectively. OGG1 genotyping was performed by polymerase chain reaction- restriction fragment length polymorphism assay. Basal and oxidative DNA damage and plasma 8-OHdG levels were found to be higher in the Alzheimer's disease group than those in the control group (P < 0.001). In the Alzheimer's disease group, the levels of oxidative DNA damage was higher in the patients having OGG1 (Ser326Cys + Cys326Cys) genotype than those in the patients having OGG1 Ser326Ser genotype. It was concluded that oxidative DNA damage is increased in patients with Alzheimer's disease and OGG1 Ser326Cys polymorphism may be responsible for this increase.

DNA damage, DNA susceptibility to oxidation and glutathione redox status in patients with Alzheimer's disease treated with and without memantine.

The aim of the current study was to compare oxidative DNA damage, DNA susceptibility to oxidation, and ratio of GSH/GSSG in patients with Alzheimer's disease (AD) treated with acetylcholinesterase inhibitor (AChEI) and combined AChEI+memantine. The study included 67 patients with AD and 42 volunteers as control. DNA damage parameters (strand breaks, oxidized purines, H2O2-induced DNA damage) in lymphocyte DNA and GSH/GSSG ratio in erythrocytes were determined by the comet assay and spectrophotometric assay, respectively. DNA damage was found to be higher, GSH/GSSG ratio was found to be lower in the AD group than those in the control group. DNA strand breaks and H2O2-induced DNA damage were lower in the patients taking AChEI+memantine than those in the patients taking AChEI but no significant difference was determined between the groups for oxidized purines and GSH/GSSG ratio. In conclusion, increased systemic oxidative DNA damage and DNA susceptibility to oxidation may be resulted from diminished GSH/GSSG ratio in AD patients. Although DNA strand breaks and H2O2-induced DNA damage are lower in the AD patients treated with combined AChEI and memantine, this may not indicate protective effect of memantine against DNA oxidation due to similar levels of oxidized purines in the patients treated with AChEI and AChEI+memantine.

Startle responses after different stimulus modalities differ in stroke.

OBJECTIVES: The auditory startle reaction (ASR) and startle reflex to somatosensory inputs (SSS) are stereotypical responses to sudden and unexpected stimuli, which are generated in the caudal brainstem reticular formation. Changes of ASR are relatively well known in stroke. Here, we aimed to investigate central pathways of SSS and plasticity changes of SSS circuits in different stages and localizations of stroke, by comparing with ASR. METHODS: We prospectively included 39 patients with stroke between June 2009 and June 2013, and 23 age and gender-matched healthy subjects. ASR and SSS were recorded over orbicularis oculi, sternocleidomastoid, biceps brachii (BB), and abductor policis brevis muscles (APB) using surface electrodes. RESULTS: There were supratentorial and infratentorial lesions in both acute and chronic stages. Overall, ASR probability was similar between groups (P=0.981). However, ASR probability was increased for BB and APB recordings on symptomatic sides of stroke patients with high amplitudes and long durations, most prominently on symptomatic sides of pontine strokes. Latencies and presence rates of SSS did not differ between any subgroups of stroke and healthy subjects. CONCLUSION: ASR is facilitated in arm and hand muscles on symptomatic sides of stroke patients, whereas SSS did not show any significant changes according to stroke.

Inflammatory hypothesis as a link between Alzheimer's disease and diabetes mellitus.

AIMS: The aim of the present study was to evaluate whether there was an inflammation-mediated link between Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) status. METHODS: An age-matched control group and patient groups designated as AD without treatment (AD); AD under cholinesterase inhibitors (AD-CEI); DM without treatment (DM); DM under oral antidiabetic agents (DM-OAD); AD under treatment, who had newly diagnosed DM (AD-CEI+DM); and DM under treatment, who had newly diagnosed probable AD (DM-OAD+AD) were studied. Serum inflammation status was evaluated by the determination of serum C-reactive protein (CRP), tumor necrosis factor-alpha, interleukin (IL)-1ß and IL-6 levels. CRP levels were determined by an immunonephelometric method. The others were assayed by enzyme-linked immunosorbent assay methods. RESULTS: IL-1ß levels were found to be significantly lower in the DM group than in the control group (P < 0.01). The AD group had significantly higher serum IL-1ß levels than the DM group (P < 0.01). IL-6 levels were significantly higher in the AD and DM groups than in controls (P < 0.01 and P < 0.01). Serum tumor necrosis factor-alpha and CRP levels in the AD (P < 0.05 and P < 0.001, respectively) and DM groups (P < 0.05 and P < 0.001, respectively) were significantly higher when compared with the controls. The presence of AD or DM or therapies of the diseases did not significantly change in serum tumor necrosis factor-alpha levels. The AD-CEI + DM and DM-OAD+AD groups had significantly higher CRP levels than the AD-CEI group (P < 0.05) and DM-OAD groups (P < 0.001), respectively. Serum CRP levels showed a positive correlation with Mini-Mental State Examination scores (r = 0.339, P < 0.01). CONCLUSION: Our findings support the presence of a low-grade systemic inflammation link between AD and DM. Geriatr Gerontol Int 2016; 16: 1161-1166.

What Does One Sleep-Onset REM Period­During Either Nocturnal Polysomnography or Multiple Sleep Latency Test­Mean in Differential Diagnosis of Central Hypersomnias?

PURPOSE: The differentiation of narcolepsy without cataplexy from idiopathic hypersomnia is based on the number of sleep-onset rapid eye movement periods (SOREMPs) observed by multiple sleep latency test (MSLT) and nocturnal polysomnography. The main aim of this study was to investigate the utility of SOREMP in differential diagnosis of central hypersomnias. METHODS: The authors retrospectively evaluated consecutive 101 patients with a normal polysomnography other than the presence of SOREMP and/or REM without atonia and a latency of ≤8 minutes in MSLT. RESULTS: The authors classified patients as follows: 52 patients had at least 2 SOREMPs (narcolepsy group), 23 had no SOREMPs (idiopathic hypersomnia group), and 26 patients had only 1 SOREMP (intermediate group). In polysomnographic recordings, both mean sleep latency and REM latency were significantly shorter in the narcolepsy (P = 0.012, P < 0.001, respectively) and intermediate groups (P = 0.005 and P = 0.035, respectively) compared with the idiopathic hypersomnia group. In MSLT recordings, sleep latency was 2.7 ± 2.2 minutes in the narcolepsy group, 3.6 ± 1.4 minutes in the intermediate group, and 5.2 ± 2.7 minutes in the idiopathic hypersomnia group (P < 0.001). The mean REM latency and sleep stages SOREMPs arised from were similar between the narcolepsy and intermediate groups. CONCLUSIONS: To date, SOREMPs in MSLT and polysomnography remain the sole electrodiagnostic feature that discriminates narcolepsy without cataplexy from idiopathic hypersomnia. Different parameters or combined criteria are being increasingly investigated to increase the sensitivity and specificity of MSLT. The findings showed an altered instability of REM sleep not only in patients with 2 or more SOREMPs in MSLT but also in patients with one SOREMP.

Magnetic resonance imaging findings in probable Creutzfeld-Jacob disease: comparison with electroencephalography and cerebrospinal fluid characteristics.

BACKGROUND: Creutzfeld-Jacob disease (CJD) is a rare, progressive disease that has a vast clinical manifestation range. Cranial magnetic resonance imaging (MRI), electroencephalography (EEG), and measurement of 14-3-3 in cerebrospinal fluid (CSF) may offer a pragmatic approach in the diagnosis of CJD as an alternative to histopathological confirmation. PURPOSE: To present the symptoms and signs of the CJD patients in regard to radiological and neurophysiological findings. MATERIAL AND METHODS: We collected all cases with the diagnosis of probable CJD admitted to our neurology department between June 2010 and June 2014. The medical records and laboratory data, clinical features, results of MRI (including diffusion weighted images), EEG and CSF evaluations, and other laboratory data to exclude other possible diagnoses were recorded. None of the patients underwent biopsy or autopsy for histological diagnosis. RESULTS: Of 20 patients, 11 (55%) were men and nine (45%) were women. The mean age at disease onset was 60.0 ± 9.5 years (age range, 47-80 years). All patients without exception had characteristic abnormalities in DWI and/or FLAIR on admission, about 4 months after the initial symptom. Periodic complexes on EEGs characteristic for CJD were detected only in 10 patients (50%) on admission and in 13 patients (65%) during disease course. Out of 14 patients who underwent CSF examination, 11 (78.5%) were positive for 14-3-3 protein. CONCLUSION: Although the definite diagnosis of CJD is made histopathologically, we aimed to discuss the value of magnetic resonance imaging in the diagnosis of CJD in respect to EEG findings and protein 14-3-3 levels in CSF.

Hypercholesterolemia as one of the risk factors of intracerebral hemorrhage.

Stroke is still a major cause of morbidity and mortality throughout the world, although better stratification and treatment modalities are being developed. As compared to ischemic stroke, intracerebral hemorrhage (ICH) possesses many unknown data and lacks guidelines for better prophylaxis. In this study, we aimed to investigate patients with ICH hospitalized in our neurology department within 5 years in terms of risk stratification. A total of 4,449 patients were hospitalized; 1,378 of patients (31%) were diagnosed as having cerebrovascular disease and of these 165 patients (3.7%) had ICH. The risk factors of patients with ICH were investigated and compared with age- and gender matched 75 healthy subjects. We observed that hypercholesterolemia (p = 0.002) was one of the most common risk factors in patients with ICH as compared to controls, together with hypertension (p = 0.010). On the other hand, hypolipidemia (LDL-cholesterol level < 50 mg/dl) was not present in any of the patients. As our purpose as neurologists is to reduce the occurrence and fatal outcome of cerebrovascular events, we aimed to emphasize the importance of risk factors to be well defined, for which every effort should be exhibited for both primary and secondary prevention.

Plasma oxidative and inflammatory markers in patients with idiopathic Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative disorder after alzheimer's disease. Neuroinflammation and oxidative damage are implicated to be responsible for the pathogenesis of neurodegenerative diseases. However, there are a few studies showing the changes in the biomarkers for neuroinflammation and oxidative damage in neurodegenerative diseases. In our study we aimed to examine the role of the molecules that are involved in oxidative stress and inflammation in PD patients taking L: -dopa treatment. Oxidized-LDL (ox-LDL), high-sensitivity C-reactive protein (hs-CRP) and the soluble intracellular adhesion molecule (ICAM) were chosen as biomarkers for systemic inflammation and oxidative damage. The patients were classified according to the Hoehn-Yahr staging system. Forty-five idiopathic L: -dopa-given PD patients and 25 age-matched healthy controls were examined. Plasma ox-LDL and ICAM levels were significantly higher in PD patients when compared with controls (p < 0.001 and p < 0.05, respectively). PD patients at all stages had significantly higher plasma ox-LDL levels than controls (p < 0.001). Plasma ICAM levels at stage 1 and 2 and CRP levels at stage 2 patients were significantly higher than controls (p < 0.05, p < 0.05, and p < 0.01, respectively). We insist that further studies have to be conducted to establish neuroinflammation and oxidative damage in PD. Establishing the roles of these pathological processes in PD might be the key to effective therapy at an early stage by antioxidants and/or anti-inflammatory drugs.

Atherothrombotic ischemic stroke in patients with atrial fibrillation.

OBJECTIVES: About one in five patients with atrial fibrillation have significant carotid artery disease, but not all strokes are cardioembolic in origin in these patients. PURPOSE: We investigated stroke sub-types based mainly on clinical, carotid ultrasonographic, and neuroimaging findings in ischemic stroke patients with non-valvular atrial fibrillation (NVAF). PATIENTS AND METHODS: The etiology of stroke was classified as definite or probable cardioembolic, possible lacunar, or possible atherothrombotic, as proposed by Hart et al. and the TOAST criteria. Clinical features and risk factors (gender, age, diabetes mellitus, hypertension, hyperlipidemia, cigarette smoking, and alcohol consumption) were designated as clinical variables. RESULTS: One hundred and six of 1938 patients (5.5%) had NVAF. In patients with and without NVAF, hyperlipidemia was more common in patients without NVAF (p<0.001), while the prevalence of other risk factors was not statistically different. On the basis of the TOAST criteria, none of the patients with NVAF could be classified as having had an atherothrombotic stroke. According to the classification by Hart et al., of the patients with NVAF, 49 patients (46.3%) had a definite embolic stroke, 17 (16.0%) had a probable embolic stroke, 12 (11.3%) had a possible atherothrombotic stroke, 17 (16.0%) had a possible lacunar infarction, and 11 (10.4%) had a stroke of undetermined etiology. Besides the presence of significant carotid stenosis (p<0.001), none of the variables related to stroke were different among the sub-groups. CONCLUSION: Patients with significant carotid stenosis were more likely to develop atherothrombotic stroke, while other risk factors associated with stroke failed to point to an etiologic cause. It should also be emphasized that the conventional classification system failed to aid in the correct diagnosis and risk stratification in patients with multiple confounding risk factors.

Simultaneous multiple cranial nerve neuropathies and intravenous immunoglobulin treatment in diabetes mellitus.

Asymmetrical, simultaneous multiple cranial nerve palsies and mild signs of peripheral neuropathy in diabetic patients may cause difficulties in diagnosis as they are relatively rare. A case of a 55-year-old diabetic woman who developed simultaneous right VII and left III, IV, VI cranial nerve palsies with spared pupils is presented here. We also discuss the role of intravenous immunoglobulin (IVIG) in the management of this condition and suggest that simultaneous multiple cranial palsies may have a good response to IVIG treatment.

Is the level of C-reactive protein correlated with the extent of carotid atherosclerosis?

BACKGROUND: Increased intima-media thickness (IMT) of the common carotid arteries (CCA) and elevated levels of highly sensitive C-reactive protein (hsCRP) are both shown to be associated with the occurrence of stroke. We investigated whether elevated hsCRP level is a risk factor for the increased IMT of the CCA independent of other proven risk factors for the ischemic stroke and studied the interaction between hsCRP level and the extent of carotid atherosclerosis. METHODS AND RESULTS: We studied 104 patients aged between 30 to 92 years who were admitted to our neurology department with acute ischemic stroke. All patients underwent a clinical evaluation, laboratory investigations, and neuroultrasonographic examination. In 24 patients with normal ultrasonographic examination, mean hsCRP levels was 8.6 + 6.7 mg/L. Mean hsCRP level was 18.0 + 25.6 mg/L in patients having increased intima to media thickness (> 1.2 mm); 32.7 + 49.1 mg/L in patients who had atheromatous plaques without significant narrowing; and 23.9 + 27.3 mg/L in patients with internal carotid artery stenosis more than 50%. hsCRP levels and the extent of the atherosclerosis showed a significant relationship (p = 0.040). In multiple regression analyses, this relationship was found to be independent of other proven risk factors. The only variable that showed a significant relation with the level of hsCRP was the HDL level. A negative correlation was found between hsCRP and HDL levels. CONCLUSIONS: We conclude that elevated hsCRP level is an indirect risk factor for the ischemic stroke through its relation with the extent of the carotid atherosclerosis, and this relation is independent of other known risk factors.

Cluster headache with obstructive sleep apnea and periodic limb movements during sleep: a case report.

We report the case of a man with episodic cluster headache who suffered from severe obstructive sleep apnea (OSA) as well as periodic limb movements during sleep (PLMS). His attacks of headache occurred primarily during sleep being timely to REM sleep as 90 to 120 minutes interval. OSAs were more frequent and prolonged during REM sleep and oxygen saturation decreased to 81% during this sleep period. Periodic limb movements were also observed in our patient that were more frequent during the first half of the polysomnographic recordings. This case is one of the few reporting cases with CH who had both OSA and PLMS.

Childhood onset of narcolepsy-cataplexy syndrome in Turkey: clinical and genetic study.

Narcolepsy is a disabling sleep disorder characterized by excessive daytime sleepiness and abnormal manifestations of rapid eye movement (REM) sleep including cataplexy, sleep paralysis and hypnagogic hallucinations. It is known to be complex disorder in which both genetic predisposition and environmental factors play a role. In humans, susceptibility to narcolepsy is tightly associated with a specific HLA allele, DQB1*0602. In this report, we took advantage of the ongoing genetic study in Turkish narcoleptic patients to document clinical and genetic data of eight patients whose onset of symptoms were in the childhood period.