A high-throughput liquid chromatography-tandem mass spectrometry method for simultaneous determination of direct oral anticoagulants in human plasma.

Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. In addition, laboratory monitoring might help improve patient and drug non-compliance and thus individualize therapy. In the present study, we developed a sensitive and high throughput ultra-high-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification of apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma. A one-step extraction procedure in 96-well formate for phospholipid and protein removal was used for sample pre-treatment, and analytes were separated using gradient elution over 4.2 min. Analytes were detected on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode. The method was validated according to the European Medicine Agency guideline for the selectivity, linearity, and lower limit of detection, precision and accuracy, matrix effects, extraction recovery, carryover, dilution integrity, and stability over a concentration range of 3.0-1000 ng/ml for all analytes. The validated method was applied to real clinical samples of patients treated with one of the drugs. Therefore, we can conclude that our method is suitable for therapeutic drug monitoring of direct oral anticoagulants.

Biomedical research brings mTBI biomarkers a step closer to the bedside - implementation in clinical practice.

Research in the field of TBI (traumatic brain injury) has long been focused on severe brain injury, while the number of mild injuries far overweigh severe injuries. Mild head injuries constitute up to 95% of all traumatic head injuries. The purpose of this work is to identify mTBI (mild traumatic brain injury) patients who are unlikely to benefit from CT (computed tomography) scanning. Biomarkers capable of clearly discriminating between CT-positive and CT-negative subjects are needed. Biomarkers hold the potential to document whether a concussion occurred, especially when the history is unclear and neurocognitive sequelae persist. Recently, following advances in proteomics analysis, investigators have introduced ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) as two promising brain injury biomarkers. The authors provide an update on the current knowledge of TBI biomarkers, especially protein biomarkers for neuronal cell body injury (UCH-L1) and astroglial injury (GFAP, S100B), and a focused literature review dealing with implementation of mTBI biomarkers in clinical practice.

Oxidative stress parameters and their relation to motor subtype of Parkinson's disease and levodopa treatment status.

Parkinson's disease (PD) is an oxidative stress-linked neurodegenerative disorder, with the highest prevalence among seniors. The objective of this study were: (1) to analyse levels of following oxidative stress parameters: total antioxidant capacity (TAC), uric acid (UA), total glutathione (tGSH), bilirubin (Bil) and albumin (Alb), in blood of PD patients and healthy controls; (2) to find possible associations of examined oxidative stress parameters with PD subtypes and levodopa treatment status; and (3) to evaluate power and relevance of the aforementioned oxidative stress parameter for the prediction of onset and progression of PD by utilizing Random Forest machine learning (RFML). Oxidative stress parameters were determined in 125 PD patients and 55 healthy controls. Evaluated with frequentist statistics, our data revealed that UA is the only oxidative stress parameter associated with PD. However, when the PD cohort was divided in gender-dependent manner, tGSH and Bil were also significantly associated with PD in subgroup of female patients. RFML rendered no predictive power of any of the tested oxidative stress parameters in respect to PD, its subtypes, and/or status of levodopa treatment. In conclusion, despite the positive association of UA with PD (in complete cohort of PD patients) and of tGSH and Bil with PD but only in female patients, these oxidative stress parameters are of no use in clinical practice due to the lack of the predictive/diagnostic power.

Plasma levels of direct oral anticoagulants in atrial fibrillation patients at the time of embolic stroke: a pilot prospective multicenter study.

BACKGROUND: Patients with atrial fibrillation (AF) who are on long-term direct oral anticoagulants (DOAC) with low anti-Xa or anti-IIa levels may be at higher risk of recurrent stroke. However, no prospective post-marketing study has investigated these DOAC plasma levels at the time of embolic stroke. The aim of this study was to assess the anti-Xa (rivaroxaban, apixaban) and anti-IIa (dabigatran) plasma levels in DOAC-treated AF patients at the time of acute embolic stroke. PATIENTS AND METHODS: We prospectively identified 43 patients with AF on long-term DOAC who experienced embolic strokes. We compared the DOAC plasma levels of these patients with a control sample of 57 patients who tolerated long-term therapeutic dose DOAC therapy without any adverse event. DOAC levels were assessed with drug-specific anti-Xa chromogenic analysis (rivaroxaban, apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). RESULTS: Dabigatran-treated patients with stroke had significantly lower anti-IIa levels when compared with the trough (40.7 ± 36.9 vs. 85.4 ± 57.2 ng/mL, p < 0.05) and peak samples of the controls (40.7 ± 36.9 vs. 138.8 ± 78.7 ng/mL, p < 0.001). Similarly, there were significantly lower anti-Xa levels in apixaban-treated patients with stroke compared to the trough control samples (72.4 ± 46.7 vs. 119.9 ± 81.7 ng/mL, p < 0.05), and in rivaroxaban- and apixaban-treated patients when compared to peak control samples (rivaroxaban: 42.7 ± 31.9 vs. 177.6 ± 38.6 ng/mL, p < 0.001; apixaban: 72.4 ± 46.7 vs. 210.9 ± 88.7 ng/mL, p < 0.001). CONCLUSION: This observational study showed significantly lower anti-IIa and anti-Xa plasma levels in AF patients with embolic stroke compared to those who tolerated long-term therapeutic dose DOAC therapy.

Atypical presentation of Charcot-Marie-Tooth disease type 1C with a new mutation: a case report.

BACKGROUND: Charcot-Marie-Tooth 1C (CMT1C) is a rare form of dominantly inherited CMT1 neuropathy caused by a mutated gene encoding lipopolysaccharide-induced tumour necrosis alpha factor (LITAF). CASE PRESENTATION: We report a 56-year-old patient with an atypical clinical phenotype of CMT1C, which started as progressive weakness of a single upper limb resembling acquired inflammatory neuropathy. Nerve conduction studies (NCS) and temporarily limited and partial effects of immunotherapy supported the diagnosis of inflammatory neuropathy. Significant progression of polyneuropathy, despite intensive long-lasting immunotherapy, together with repeatedly negative auxiliary investigations (CSF, MRI and antibodies) and genetic testing results finally led to the diagnosis of CMT1C neuropathy. CONCLUSIONS: CMT1C should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy.

Current Methods of Magnetic Resonance for Noninvasive Assessment of Molecular Aspects of Pathoetiology in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune disease with expanding axonal and neuronal degeneration in the central nervous system leading to motoric dysfunctions, psychical disability, and cognitive impairment during MS progression. The exact cascade of pathological processes (inflammation, demyelination, excitotoxicity, diffuse neuro-axonal degeneration, oxidative and metabolic stress, etc.) causing MS onset is still not fully understood, although several accompanying biomarkers are particularly suitable for the detection of early subclinical changes. Magnetic resonance (MR) methods are generally considered to be the most sensitive diagnostic tools. Their advantages include their noninvasive nature and their ability to image tissue in vivo. In particular, MR spectroscopy (proton 1H and phosphorus 31P MRS) is a powerful analytical tool for the detection and analysis of biomedically relevant metabolites, amino acids, and bioelements, and thus for providing information about neuro-axonal degradation, demyelination, reactive gliosis, mitochondrial and neurotransmitter failure, cellular energetic and membrane alternation, and the imbalance of magnesium homeostasis in specific tissues. Furthermore, the MR relaxometry-based detection of accumulated biogenic iron in the brain tissue is useful in disease evaluation. The early description and understanding of the developing pathological process might be critical for establishing clinically effective MS-modifying therapies.

Anaplastic astrocytoma mimicking progressive multifocal leucoencephalopathy: a case report and review of the overlapping syndromes.

BACKGROUND: Co-occurrence of multiple sclerosis (MS) and glial tumours (GT) is uncommon although occasionally reported in medical literature. Interpreting the overlapping radiologic and clinical characteristics of glial tumours, MS lesions, and progressive multifocal leukoencephalopathy (PML) can be a significant diagnostic challenge. CASE PRESENTATION: We report a case of anaplastic astrocytoma mimicking PML in a 27-year-old patient with a 15-year history of MS. She was treated with interferon, natalizumab and finally fingolimod due to active MS. Follow-up MRI, blood and cerebrospinal fluid examinations, and biopsy were conducted, but only the latter was able to reveal the cause of progressive worsening of patient's disease. CONCLUSIONS: Anaplastic astrocytoma misdiagnosed as PML has not yet been described. We suppose that the astrocytoma could have evolved from a low grade glioma to anaplastic astrocytoma over time, as the tumour developed adjacent to typical MS plaques. The role of the immunomodulatory treatment as well as other immunological factors in the malignant transformation can only be hypothesised. We discuss clinical, laboratory and diagnostic aspects of a malignant GT, MS lesions and PML. The diagnosis of malignant GT must be kept in mind when an atypical lesion develops in a patient with MS.

Primary diffuse leptomeningeal gliomatosis as a rare cause of pain in cervical spine.

BACKGROUND: Primary diffuse leptomeningeal gliomatosis (PDLG) is a very rare neuro-oncological disease, with only 90 cases of PDLG described in medical literature so far. CASE PRESENTATION: We present a case report of a 56-years-old female patient, who was originally hospitalized due to cervical spine pain lasting several months. Despite complex diagnostics and treatment, the neurological state of the patient progressively deteriorated. Patient died 10 months after the first reported symptom. Postmortem pathological findings resulted in the diagnosis of PDLG. CONCLUSIONS: Affection of the cervical spine in early stages of PDLG is rare and has been described in only six patients so far. PDLG is a fatal neuro-oncological disease and it must be kept in mind in the differential diagnosis of persistent back pain syndromes.

Detection of occult paroxysmal atrial fibrilation by implantable long-term electrocardiographic monitoring in cryptogenic stroke and transient ischemic attack population: a study protocol for prospective matched cohort study.

BACKGROUND: Cardio-embolic etiology is the most frequently predicted cause of cryptogenic stroke/TIA. Detection of occult paroxysmal atrial fibrillation is crucial for selection of appropriate medication. METHODS: Enrolment of eligible cryptogenic stroke and TIA patients began in 2014 and will continue until 2018. The patients undergo long-term (12 months) ECG monitoring (implantable loop recorder) and testing for PITX2 (chromosome 4q25) and ZFHX3 (chromosome 16q22) gene mutations. There will be an appropriate control group of age- and sex-matched healthy volunteers. To analyse the results descriptive statistics, statistical tests for group differences, and correlation analyses will be used. DISCUSSION: In our study we are focusing on a possible correlation between detection of atrial fibrillation by an implantable ECG recorder, and PITX2 and/or ZFHX3 gene mutations in cryptogenic stroke/TIA patients. A correlation could lead to implementation of this genomic approach to cryptogenic stroke/TIA diagnostics and management. The results will be published in 2018. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02216370 .

Exploring CJD incidence trends: insights from Slovakia.

Authors are commenting on the evolving geographical incidence trends observed with the genetic form of Creutzfeldt-Jakob disease and discussing the diverse array of factors contributing to the heightened incidence rates observed in specific geographical regions.

Gastrointestinal Complications of Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome Managed By Parenteral Nutrition.

MELAS - an acronym for mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes - is a multiorgan disease caused by a mutation in mitochondrial DNA (mtDNA). Its clinical manifestations are highly variable; mainly stroke-like episodes, seizures, recurrent headaches, or muscle weakness. However, gastrointestinal complications such as chronic intestinal pseudo-obstruction (IPO), pancreatitis, gastroparesis and hepatopathy are also common. In this report we describe a young patient with gastrointestinal complication of MELAS which led to superior mesenteric artery syndrome (SMAS). It is rare but not surprising combination and should be considered in cases with significant weight loss and resistance to symptomatic treatment. The optimal energy support is the main pillar of the treatment. LEARNING POINTS: Gastrointestinal complications of MELAS such as chronic intestinal pseudo-obstruction, pancreatitis and gastroparesis can lead to undernutrition.Superior mesenteric artery syndrome is a rare condition but should be considered in cases with significant weight loss and resistance to symptomatic treatment.Optimal caloric intake and energy support can improve the condition of patients with MELAS.

Predictors of Outcome after Direct Aspiration of Basilar Artery Occlusion.

Background: Basilar artery occlusion (BAO) is a serious disease with a poor prognosis if left untreated. Endovascular therapy (EVT) is the most effective treatment that is able to reduce mortality and disability. Treatment results are influenced by a wide range of factors that have not been clearly identified. In the present study, direct aspiration was chosen as a first-line treatment. The safety and effectiveness of direct aspiration in BAO were determined, and factors affecting patient outcomes were identified. Methodology: Data for patients with BAO treated between November 2013 and December 2021 were evaluated using a database. The association between clinical and procedural parameters and functional outcome was assessed. Results: A total of 89 patients with BAO were identified. Full recanalization was achieved in 69.7% of cases and partial recanalization in 19.1%. Intracranial hemorrhage was detected in 11 (12.4%) patients, of which, eight (9.0%) patients experienced symptomatic intracranial hemorrhage. Patients with good outcomes presented with milder strokes (mean NIHSS score of 12.58 vs. 24.00, p < 0.001), had higher collateral scores (6.79 vs. 5.88, p = 0.016), more often achieved complete recanalization (87.9% vs. 58.9%, p = 0.009), and more often experienced early neurological improvement (66.7% vs. 26.8%, p < 0.001). On the contrary, patients with worse outcomes had higher serum glucose levels (p = 0.05), occlusion of the middle portion of the basilar artery (MAB) (30.3% vs. 53.6%, p = 0.033), longer thrombus lengths (10.51 vs. 16.48 mm, p = 0.046), and intracranial hemorrhage (p = 0.035). Conclusions: The present study results suggest that direct aspiration is a safe and effective treatment for patients with BAO. We identified several factors affecting the patients' outcome.

Forecasting extremely high ischemic stroke incidence using meteorological time serie.

MOTIVATION: The association between weather conditions and stroke incidence has been a subject of interest for several years, yet the findings from various studies remain inconsistent. Additionally, predictive modelling in this context has been infrequent. This study explores the relationship of extremely high ischaemic stroke incidence and meteorological factors within the Slovak population. Furthermore, it aims to construct forecasting models of extremely high number of strokes. METHODS: Over a five-year period, a total of 52,036 cases of ischemic stroke were documented. Days exhibiting a notable surge in ischemic stroke occurrences (surpassing the 90th percentile of historical records) were identified as extreme cases. These cases were then scrutinized alongside daily meteorological parameters spanning from 2015 to 2019. To create forecasts for the occurrence of these extreme cases one day in advance, three distinct methods were employed: Logistic regression, Random Forest for Time Series, and Croston's method. RESULTS: For each of the analyzed stroke centers, the cross-correlations between instances of extremely high stroke numbers and meteorological factors yielded negligible results. Predictive performance achieved by forecasts generated through multivariate logistic regression and Random Forest for time series analysis, which incorporated meteorological data, was on par with that of Croston's method. Notably, Croston's method relies solely on the stroke time series data. All three forecasting methods exhibited limited predictive accuracy. CONCLUSIONS: The task of predicting days characterized by an exceptionally high number of strokes proved to be challenging across all three explored methods. The inclusion of meteorological parameters did not yield substantive improvements in forecasting accuracy.

Safety and efficacy of simple training protocol in patients after mild traumatic brain injury.

AIMS: Mild Traumatic Brain Injury (mTBI) is the most common type of craniocerebral injury. Proper management appears to be a key factor in preventing post-concussion syndrome. The aim of this prospective study was to evaluate the effect and safety of selected training protocol in patients after mTBI. METHODS: This was a prospective study that included 25 patients with mTBI and 25 matched healthy controls. Assessments were performed in two sessions and included a post-concussion symptoms questionnaire, battery of neurocognitive tests, and magnetic resonance with tractography. Participants were divided into two groups: a passive subgroup with no specific recommendations and an active subgroup with simple physical and cognitive training. RESULTS: The training program with slightly higher initial physical and cognitive loads was well tolerated and was harmless according to the noninferiority test. The tractography showed overall temporal posttraumatic changes in the brain. The predictive model was able to distinguish between patients and controls in the first (AUC=0.807) and second (AUC=0.652) sessions. In general, tractography had an overall predictive dominance of measures. CONCLUSION: The results from our study objectively point to the safety of our chosen training protocol, simultaneously with the signs of slight benefits in specific cognitive domains. The study also showed the capability of machine learning and predictive models in mTBI patient recognition.

Deep brain stimulation electrode position impact on parkinsonian non-motor symptoms.

BACKGROUND: In this study we evaluated the impact of location of deep brain stimulation electrode active contact in different parts of the subthalamic nucleus on improvement of non-motor symptoms in patients with Parkinson's disease. METHODS: The subthalamic nucleus was divided into two (dorsolateral/ventromedial) and three (dorsolateral, medial, ventromedial) parts. 37 deep brain stimulation electrodes were divided according to their active contact location. Correlation between change in non-motor symptoms before and one and four months after deep brain stimulation electrode implantation and the location of active contact was made. RESULTS: In dividing the subthalamic nucleus into three parts, no electrode active contact was placed ventromedially, 28 active contacts were located in the medial part and 9 contacts were placed dorsolaterally. After one and four months, no significant difference was found between medial and dorsolateral positions. In the division of the subthalamic nucleus into two parts, 13 contacts were located in the ventromedial part and 24 contacts were placed in the dorsolateral part. After one month, significantly greater improvement in the Non-motor Symptoms Scale for Parkinson's disease (P=0.045) was found on dorsolateral left-sided stimulation, but no significant differences between the ventromedial and dorsolateral positions were found on the right side. CONCLUSION: This study demonstrated the relationship between improvement of non-motor symptoms and the side (hemisphere, left/right) of the deep brain stimulation electrode active contact, rather than its precise location within specific parts of the subthalamic nucleus in patients treated for advanced Parkinson's disease.

Proton magnetic resonance spectroscopy changes in the brainstem in patients after mild traumatic brain injury with loss of consciousness.

INTRODUCTION: Loss of consciousness (LOC) is used as a diagnostic feature of mild traumatic brain injury (MTBI). However, only 10% of concussions result in LOC. There are only a limited number of in-vivo studies dealing with unconsciousness and structural and functional integrity of the brainstem in patients with MTBI. The aim of our pilot study was to assess the sensitivity of proton magnetic resonance spectroscopy (1H-MRS) to detect metabolic changes in the brainstem in patients after MTBI with unconscioussness. METHODS: Twenty-four patients (12 with LOC, and 12 without LOC) within 3 days of MTBI and 19 healthy controls were examined. All subjects underwent single-voxel 1H-MRS examination of the upper brainstem. Spectra were evaluated using LCModel software. Ratios of total N-acetylaspartate (tNAA), total choline-containing compounds (tCho) and glutamate plus glutamine (Glx) to total creatine (tCre) were used for calculations. RESULTS: We found a significant decrease in tNAA/tCre and tCho/tCre ratios in the patient group with LOC when compared with the control group of healthy volunteers (P=0.002 and P=0.041, respectively), and a significant decrease in the tNAA/tCre ratio in the LOC group when compared with patients without LOC (P=0.04). Other metabolite ratios in the brainstem did not show any significant group differences. CONCLUSION: Our findings indicate that decrease of tNAA/tCre ratio in the upper brainstem using single-voxel 1H-MRS may provide a potential biomarker for MTBI associated with LOC.

Leptin, adiponectin and ghrelin, new potential mediators of ischemic stroke.

OBJECTIVES: Fat tissue is an important endocrine organ that produces a number of hormones and cytokines (leptin, adiponectin, resistin, plasminogen activator inhibitor-1, Tumour necrosis factor TNF α) with essential roles in regulation of many physiological functions. METHODS: We targeted implications of adipokines in ischemic stroke patients. Patients with acute stroke were examined (n=145) and the results were compared with the control group (n=68). We have examined potential associations between leptin, adiponectin and ghrelin, and different types of stroke and traditional risk factors. RESULTS: Significantly higher levels of leptin and lower levels of adiponectin and ghrelin were confirmed in the stroke group. The level of leptin in women with stroke was three-times higher than in men, and the leptin levels positively correlated with obesity in both sexes. Ghrelin levels correlated mildly with triglyceride levels, and were dominant in men with cardioembolic stroke. Adiponectin levels were not different between men and women with acute stroke, and correlated with atherothrombotic and lacunar stroke types in men. CONCLUSIONS: Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced. More research is required to confirm our results.

Virtual Reality Visual Training in an Adult Patient with Anisometropic Amblyopia: Visual and Functional Magnetic Resonance Outcomes.

A case of an adult with anisometropic amblyopia who underwent a successful vision therapy program playing videogames in a virtual reality environment is described, reporting changes in conventional visual clinical data, as well as in brain activity. The patient was a 22 year old man on baseline examination that never previously wore correction for his anisometropia. After prescribing contact lens correction for the anisometropia and after 44 h of virtual reality-based vision therapy over a period of 1.5 years, the best corrected distance visual acuity (BCDVA) in the amblyopic eye improved from 0.05 to 0.5 (Sloan chart). One year after finishing the visual training, the BCDVA experienced a slight decrease to 0.4 (Sloan chart). Through the visual training, the patient gradually developed stereopsis. Likewise, changes were also detected after visual therapy on functional magnetic resonance imaging while the patient was viewing 2D and 3D stimuli. The preliminary results of this case show the potential of using virtual reality-based visual training as a treatment for adult amblyopia.

Fatigue as the limiting factor for vaginal birth in patients with multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune and neurodegenerative disease. This study evaluated pregnancy-related issues in patients with MS in one perinatological centre. MATERIAL AND METHODS: A single-centre, retrospective study of the perinatal period in patients with MS admitted at the Dpt. of Gynaecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University and the University Hospital in Martin, Slovak Republic, European Union from January 1, 2015 to December 1, 2020 was performed. Selected parameters from personal, obstetric, and neurological histories were analysed. RESULTS: A cohort of 15 patients (32.5±5.3 years) with a relapsing-remitting form of MS gave birth to 16 children. The mean length of MS at the time of delivery was 9±3.6 years. The severity of the Expanded Disability Status Scale score was 2.0±1.5. Caesarean section (CS) was indicated in 14 deliveries (87.5%). It was elective CS in 10 patients. The most common indication for elective CS was a combination of significant chronic fatigue syndrome and neurological deficit (paresis). CONCLUSIONS: The basis for the management of pregnancy, childbirth, and the postpartum period in women with MS is a planned pregnancy based on close cooperation among patients, gynaecologists, and neurologists. Vaginal delivery is not primarily contraindicated. Indications for CS should be considered individually. One way to minimise the indications for CS is a more accurate diagnosis and personalised treatment of fatigue in pregnant women with MS. Presumably, both obstetricians and neurologists prefer vaginal delivery as the first choice in patients with fatigue syndrome.

Proton magnetic resonance spectroscopy in patients with early stages of amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting upper and lower motor neurons. Due to relative fast progression of the disease, early diagnosis is essential. Proton magnetic resonance spectroscopy ((1)H-MRS) is used for objectivization of upper motor neuron (UMN) lesions. The aim of this study was to assess the use of (1)H-MRS in the early stages of ALS. METHODS: Eleven patients with clinically definite (n=2), probable (n=7), and probable laboratory-supported (n=2) diagnosis of ALS with disease duration of less than 14 months were studied. Control group consists of 11 sex- and age-matched healthy subjects. All subjects underwent assessment of functional disability using revised ALS Functional Rating Scale (ALSFRS-R) and single-voxel (1)H-MRS examination of both precentral gyri, pons, medulla oblongata, and occipital lobe. Spectra were evaluated with LCModel software. RESULTS: The mean disease duration was 6.5 ± 3.5 months. The median ALSFRS-R was 42. Significant decrease between patient and control groups was found in the NAA/Cre ratio in the left and right precentral gyri (p=0.008, p=0.040). Other metabolite ratios in other areas did not show significant differences. Total ALSFRS-R score weakly positively correlated with NAA/Cre ratio in the left precentral gyrus (p=0.047). CONCLUSIONS: (1)H-MRS is sensitive to detect metabolic changes caused by neurodegeneration processes during ALS and can be used for detection of UMN dysfunction. These MRS changes in the early stages of ALS are most prominent in motor cortex.