Smoking affects global and regional brain entropy in depression patients regardless of depression: Preliminary findings.

OBJECTIVE: This study examines the effect of smoking on global and regional brain entropy in patients with Major Depressive Disorder (MDD), aiming to elucidate the relationship between smoking habits and brain network complexity in depression. METHODS: The study enrolled 24 MDD patients, divided into smokers and non-smokers, from Alanya Alaaddin Keykubat University and Istanbul Medipol University. Resting-state fMRI data were acquired and processed. The complexity of neuronal activity was assessed using dispersion entropy, with statistical significance determined by a suite of tests including Kolmogorov-Smirnov, Student's t-test, and Mann-Whitney U test. RESULTS: The smoking cohort exhibited higher global brain entropy compared to the non-smoking group (p = 0.033), with significant differences in various brain networks, indicating that smoking may alter global brain activity and network dynamics in individuals with MDD. CONCLUSION: The study provides evidence that smoking is associated with increased brain entropy in MDD patients, suggesting that chronic smoking may influence cognitive and emotional networks. This underscores the importance of considering smoking history in the treatment and prognosis of MDD. The findings call for further research to understand the mechanistic links between smoking, brain entropy, and depression.

Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial.

BACKGROUND: Alzheimer's disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress. METHODS: Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients. RESULTS: We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment. CONCLUSION: Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis. Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131.

The effect of Electromyography (EMG)-driven Robotic Treatment on the recovery of the hand Nine years after stroke.

OBJECTIVE: To investigate the effect of electromyography (EMG)-driven robotic therapy on the recovery of the hand in a stroke case lasting 9 years. CASE: An 18-year-old patient with hemiparesis due to the ischemic lesion was admitted to our clinic with hand impairment. Fifteen sessions (5 weeks x 3 times) of robotic rehabilitation were applied with the Hand of Hope. Average EMG (mV) of flexor digitorum superficialis (FDS) muscle, average force (N) and the rate of force development (RFD)(N/s) were also assessed before and after the treatment following the 5th and 10th sessions and at the end of treatment. Also, Fugl-Meyer Assessment of Upper Extremity Scale (FMU-UE), Motor Activity Log (MAL), Canadian Occupational Performance Score (COPM) and Visual Analog Scale (VAS) were used for assessment before and after the treatment. RESULTS: The average EMG measured from FDS increased from 0.093-0.133 mV. The average force and average RFD increased from 45.6-97.7 and from 135.6-172.6 respectively. While affected and/or unaffected side force ratio increased dramatically from 54%-82%, the FMA-UE score increased from 56-59. The MAL quality of use score increased from 3.93-4.13. Performance and satisfaction scores of COPM changed from 5.25-7.25 and 4.5-8.25 respectively. VAS score for fatigue changed from 6 to 4. DISCUSSION: The improvement achieved 9 years later with 15 sessions of rehabilitation suggests that improvement may be possible for chronic stroke patients.

The effects of cognitive, physical, and somatosensory rehabilitation after right temporo-parietal tumor resection on cognitive, motor, somatosensory, and electrophysiological parameters: A case report.

INTRODUCTION: This report examines the effects of a multimodal rehabilitation program which includes cognitive, physical, and somatosensory rehabilitation after right temporo-parietal tumor resection on cognitive, motor, somatosensory, and electrophysiological parameters. CASE DESCRIPTION: A 22-year-old patient presented with sensory loss in the dominant left hand and reduced writing ability after right temporo-parietal lobe resection. Cognitive, motor, and sensory evaluations were carried out pre and post-treatment. The patient's spontaneous electroencephalo-gram (EEG) and an EEG during application of transcutaneous electrical nerve stimulation (TENS) (TENS EEG) were recorded. As a reference for the patient's electrophysiological values, EEGs of 4 healthy individuals were also taken. Over a period of 1 year, the patient received multimodal rehabilitation which includes cognitive, physical, and somato-sensory rehabilitation on 2 days each week. OUTCOMES: An improvement of the patient's cognitive capacities, motor strength, superficial, deep and cortical sensations was achieved. After rehabilitation, an increase in parietal and occipital alpha activity as well as in frontal and parietal beta activity was seen both in spontaneous EEG and in TENS EEG. With increasing TENS intensity, alpha and beta power increased as well. CONCLUSION: Our findings suggest that a multimodal rehabilitation program may improve cognitive, sensory, and motor effects after resection due to tumor surgery.

Accelerated long-term forgetting after amygdalohippocampectomy in temporal lobe epilepsy.

AIM OF THE STUDY: Temporal lobe epilepsy (TLE) has been associated with the phenomenon of accelerated long-term forgetting (ALF). In this study, we aimed to demonstrate the effect of surgery on the ALF phenomena thus contributing to potential explanation of the causal mechanism. MATERIALS AND METHODS: We evaluated 51 patients with TLE related to hippocampal sclerosis who had amygdalohippocampectomy and had remained seizure-free after surgery. A control group consisted of 24 healthy individuals. All were given a verbal learning test assessing recall after 30 min, 1 week and 6 weeks. RESULTS: In our study, the Left-TLE (L-TLE) group showed a statistically significant reduction in the performance at all assessment intervals from 30 min to 1 week compared to the Right-TLE and control groups regarding verbal learning memory test (VLMT) as well as for logical memory. The forgetting rates in the VLMT from 30 min to 1 week were not statistically significantly different between all 3 groups. The logical memory test results equally showed no statistically significant difference in the forgetting rates for the 3 groups between 30 min and 1 week. CONCLUSIONS AND CLINICAL IMPLICATIONS: These results may support ongoing debates assuming the initial low performance in the memory of L-TLE patients to be directly related with left hippocampal-temporal tissue loss irrespective of epileptic activity. The discovery of the ALF phenomenon explains that standard memory tests are unable to detect memory loss in some patients who are experiencing a significant level of problems with forgetfulness in their daily lives.

Minocycline Increases in-vitro Cortical Neuronal Cell Survival after Laser Induced Axotomy.

BACKGROUND: Antibiotic therapies targeting multiple regenerative mechanisms have the potential for neuroprotective effects, but the diversity of experimental strategies and analyses of non-standardised therapeutic trials are challenging. In this respect, there are no cases of successful clinical application of such candidate molecules when it comes to human patients. METHODS: After 24 hours of culturing, three different minocycline (Sigma-Aldrich, M9511, Germany) concentrations (1 µM, 10 µM and 100 µM) were added to the primary cortical neurons 15 minutes before laser axotomy procedure in order to observe protective effect of minocycline in these dosages. RESULTS: Here, we have shown that minocycline exerted a significant neuroprotective effect at 1 and 100µM doses. Beyond confirming the neuroprotective effect of minocycline in a more standardised and advanced in-vitro trauma model, our findings could have important implications for future studies that concentrate on the translational block between animal and human studies. CONCLUSION: Such sophisticated approaches might also help to conquer the influence of humanmade variabilities in critical experimental injury models. To the best of our knowledge, this is the first study showing that minocycline increases in-vitro neuronal cell survival after laser-axotomy.

Clinical, Electrophysiological, and Serological Evaluation of Patients with Cramp-Fasciculation Syndrome.

INTRODUCTION: Cramp-fasciculation syndrome (CFS) is a rare peripheral nerve hyperexcitability syndrome. There are only a few reports on clinical and serological profile of a CFS cohort that was followed up by a single outpatient clinic. METHODS: Clinical, electrophysiological, and serological features of 6 CFS patients (5 men, 1 woman; 27-65 years old) were investigated. RESULTS: All patients presented with cramps, fasciculations, muscle pain, and autonomic symptoms, and 2 also reported numbness and burning sensation in limbs, suggestive of neuropathic pain. Antibodies to uncharacterized voltage-gated potassium channel (VGKC)-complex proteins were found in 2 patients and to contactin-associated protein-like 2 (CASPR2) in 1 patient. None of the patients had a tumor. Most of the patients revealed prolonged after-discharges following tibial nerve stimulation. Nerve conduction studies and R-R interval variability tests were normal, whereas sympathetic skin responses were increased in amplitude in 3 seronegative patients. Five patients showed favorable response to carbamazepine or pregabalin treatment, whereas 1 VGKC-antibody-positive patient was resistant to carbamazepine and immunosuppressant treatment. CONCLUSION: Neuropathic pain and VGKC-complex antibodies may be encountered in CFS patients. Although autonomic symptoms are commonly found in CFS, routine autonomic system tests which are done in electrophysiology laboratories might yield normal results.

The neuroprotective effect of focused ultrasound: New perspectives on an old tool.

INTRODUCTION: Transcranial focused ultrasound (tFUS) is a novel technique that can noninvasively modulate the cortical function. Moreover, there are rapidly replicating evidence suggesting the role of tFUS for targeted neuroprotective drug delivery by increasing the permeability of the central nervous system barrier that results with increased neuroprotective activity. In contrast to the indirect neuroprotective effect, there is rare evidence suggesting the direct parenchymal neuroprotective effect of transcranial focused ultrasound (tFUS). In the light of these findings, we aimed to review the direct and indirect neuroprotective effect of FUS in various animal models of Stroke, Parkinson's Disease, Alzheimer's Disease and Major Depressive Disorder. METHODS: A literary search was conducted, utilizing search terms "animal", "focused ultrasound", "neuroprotection", "Alzheimer's Disease", "Parkinson's Disease ", "Stroke", "Neurodegenerative disease" and "Major Depressive Disorder". Items were excluded if they failed to: (1) include patients, (2) editorials, and letters. RESULTS: This mini-review article presents an up-to-date review of the neuroprotective effects of tFUS in animal studies and suggests the dual neurotherapeutic role of tFUS in various neurodegenerative diseases. CONCLUSION: Future well-conducted human studies are emergently needed to assess the neuroprotective effects of FUS.

Electroconvulsive therapy in drug-induced psychiatric states and neuroleptic malignant syndrome.

In the late-stage idiopathic Parkinson's disease (IDP), comorbid conditions such as depression and drug-induced psychosis may be observed. A patient with Parkinson disease, major depression, and paranoid psychosis who developed neuroleptic malignant syndrome (NMS) as the result of the sudden termination of high-dose (1200 mg/d) levodopa treatment is presented in this report. Because the patient did not respond to other treatment modalities, electroconvulsive therapy (ECT) was applied, and a rapid improvement was observed both in the patient's NMS and also in Parkinson's and psychiatric symptoms, with no additional side effects other than transient post-ictal confusions. The application of ECT allowed the patient to remain stable for a 5-year period with a quite low dose of levodopa (300 mg/d). Later, the patient had two episodes of depressive and psychotic symptoms, which were again successfully treated with the ECT. We suggest that ECT might be an effective and life-saving therapy in patients with severe, drug-resistant NMS.

Memory in patients with drug-responsive mesial temporal lobe epilepsy and hippocampal sclerosis.

PURPOSE: Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is the most common of the antiepileptic drug (AED)-resistant seizure syndromes that are remediable mostly with surgery, although a small group of patients have benign prognosis with fewer seizures. Material-specific memory impairment is an important feature in these patients and may be related to both the structural abnormality and the frequent seizures. In this study, we investigated the relation between memory deficit and HS by taking seizure frequency into account. METHODS: The patients were evaluated according to a standard protocol and divided into two groups, considering their response to AEDs: the good-responder group (GRg, n = 18) and the pharmacoresistant group (PRg, n = 95). They were administered a neuropsychological test battery that included verbal and nonverbal memory tests, compared with each other and with a normal control group (n = 29). The responder group was evaluated by the same battery once again (mean, 23 months; SD, 8.25; range, 14-38 months). RESULTS: Both GR and PR patient groups had poorer memory than the normal controls in all memory tests (p < 0.05). However, the comparison of GRg with PRg revealed that only the digit-span test was significantly worse in PRg (p = 0.0061), and no difference was found in any other memory scores. The reevaluation of the GRg showed no significant difference between the first and second evaluation. CONCLUSIONS: We concluded that the memory impairment in patients with MTLE-HS was permanent and might be related to the direct effect of HS itself. Therefore patients with good response to AEDs can be used as a model for investigating the memory problems in patients with MTLE-HS.

Correlation between 1H MRS and memory before and after surgery in mesial temporal lobe epilepsy with hippocampal sclerosis.

PURPOSE: Proton magnetic resonance spectroscopy (1H MRS), which can demonstrate neuronal loss and gliosis, may be used as a sensitive tool for lateralization of temporal lobe epilepsy (TLE). Although the correlation between the memory functions and 1H MRS has been investigated, its predictive value after surgery has not been studied previously. This study evaluated memory and 1H MRS values of medically intractable patients with mesial TLE and hippocampal sclerosis (MTLE-HS) before and after selective amygdalohippocampectomy (SAH). METHODS: Twenty-two patients underwent memory tests and 1H MRS investigation before and 6 months after SAH and were compared with nine control subjects. RESULTS: The 1H MRS scores were found to be significantly low on the pathological side of the patients. Both right-sided 1H MRS of right TLE and left-sided 1H MRS values of left TLE patients were correlated only with verbal memory scores. Statistical analysis did not reveal any significance for nonverbal memory scores for both TLE groups on either side, which showed no significant correlation between material specificity and 1H MRS findings. Conversely, regression analyses demonstrated that high right- and low left-sided 1H MRS values obtained before surgery may predict a decline in verbal learning scores after surgery. CONCLUSIONS: 1H MRS can be considered as a useful tool to determine the lateralization in patients with MTLE-HS before the surgery. Although only a weak relation exists between the MRS values and memory scores, presurgical MRS scores may be predictive for a possible deterioration in verbal memory after surgery. However, further studies with higher numbers of cases are needed for confirmation of the results.