The Modulation of Adipokines, Adipomyokines, and Sleep Disorders on Carcinogenesis.

Obesity and sarcopenia, i.e., decreased skeletal muscle mass and function, are global health challenges. Moreover, people with obesity and sedentary lifestyles often have sleep disorders. Despite the potential associations, metabolic disturbances linking obesity, sarcopenia, and sleep disorders with cancer are neither well-defined nor understood fully. Abnormal levels of adipokines and adipomyokines originating from both adipose tissue and skeletal muscles are observed in some patients with obesity, sarcopenia and sleep disorders, as well as in cancer patients. This warrants investigation with respect to carcinogenesis. Adipokines and adipomyokines may exert either pro-carcinogenic or anti-carcinogenic effects. These factors, acting independently or together, may significantly modulate the incidence and progression of cancer. This review indicates that one of the possible pathways influencing the development of cancer may be the mutual relationship between obesity and/or sarcopenia, sleep quantity and quality, and adipokines/adipomyokines excretion. Taking into account the high proportion of persons with obesity and sedentary lifestyles, as well as the associations of these conditions with sleep disturbances, more attention should be paid to the individual and combined effects on cancer pathophysiology.

Hashimoto Encephalopathy-Still More Questions than Answers.

The normal function of the nervous system is conditioned by the undisturbed function of the thyroid gland and its hormones. Comprehensive clinical manifestations, including neurological disorders in Hashimoto's thyroiditis, have long been understood and, in recent years, attention has been paid to neurological symptoms in euthyroid patients. Hashimoto encephalopathy is a controversial and poorly understood disease entity and the pathogenesis of the condition remains unclear. We still derive our understanding of this condition from case reports, but on the basis of these, a clear clinical picture of this entity can be proposed. Based on a review of the recent literature, the authors present the current view on the subject, discuss controversies and questions that still remain unanswered, as well as ongoing research in this area and the results of our own work in patients with Hashimoto's thyroiditis.

Ischemic stroke as a rare complication of wasp venom allergy: two clinical scenarios.

Neurological complications after a single Hymenoptera insect sting are very rare. The authors of this paper describe two instances of cerebral ischemic stroke that occurred immediately after a wasp sting. Two distinct pathomechanisms involved in the cases are put forward. When diagnosing such cases, it is vital to rule out the possibility of an immunoglobulin E (IgE)-dependent reaction of hypersensitivity. However, if sIgE antibodies against wasp venom extract and/or its allergenic components are detected, after hospitalization the patient should be qualified for venom immunotherapy, which is the only efficient method of protection from severe allergic reactions caused by an insect sting. Although the incidence of ischemic stroke in patients stung by insects is very low, it is important to be aware of this complication. This will allow rapid implementation of appropriate diagnostics and treatment. The optimal stroke treatment (thrombolysis or mechanical thrombectomy) in these rare cases has not yet been established.

The Role of Stem Cells in the Therapy of Stroke.

BACKGROUND: Stroke is a major challenge in neurology due to its multifactorial genesis and irreversible consequences. Processes of endogenous post-stroke neurogenesis, although insufficient, may indicate possible direction of future therapy. Multiple research considers stem-cell-based approaches in order to maximize neuroregeneration and minimize post-stroke deficits. OBJECTIVE: Aim of this study is to review current literature considering post-stroke stem-cell- based therapy and possibilities of inducing neuroregeneration after brain vascular damage. METHODS: Papers included in this article were obtained from PubMed and MEDLINE databases. The following medical subject headings (MeSH) were used: "stem cell therapy", "post-stroke neurogenesis", "stem-cells stroke", "stroke neurogenesis", "stroke stem cells", "stroke", "cell therapy", "neuroregeneration", "neurogenesis", "stem-cell human", "cell therapy in human". Ultimate inclusion was made after manual review of the obtained reference list. RESULTS: Attempts of stimulating neuroregeneration after stroke found in current literature include supporting endogenous neurogenesis, different routes of exogenous stem cells supplying and extracellular vesicles used as a method of particle transport. CONCLUSION: Although further research in this field is required, post stroke brain recovery supported by exogenous stem cells seems to be promising future therapy revolutionizing modern neurology.

Visual Evoked Potentials as Potential Biomarkers of Visual Function in Patients with Primary Sjögren's Syndrome.

Visual evoked potentials (VEP) are changes in potentials that arise in the central nervous system. In the interpretation of the VEP test results, it is assumed that the elongation of the latency time is caused by the demyelination of the nerve fibers, and the axon damage is responsible for the decrease in the amplitude. The observed VEP deviations are not specific for specific diseases, but indicate disturbances in visual conductivity. VEP may play a diagnostic role in the early detection of visual involvement. The aim of the study was the functioning of visual pathway assessment on the basis of visual evoked potentials (VEP) examination, in patients with primary Sjögren's Syndrome (pSS), without focal symptoms of central nervous system disorder. The effect of disease activity, as assessed by clinical parameters and antibody levels (anti-Ro52, SSA, and SSB), on the central nervous system was also evaluated. Thirty-two consecutive patient with pSS (31 females, 1 male) were included in the study. VEP was performed at baseline, and after 6 (T6) years. Their results were compared longitudinally between the baseline and T6, depending on the duration of the disease and treatment. The immunological activity of pSS was also analyzed. The group of patients showed a significant prolongation of the P100 implicit time (105.5 ± 5.1 vs. 100.6 ± 3.9; p = 0.000) and a significant higher the P100-N145 amplitude (12.3 ± 4.1 vs. 9.4 ± 3.0; p = 0.000). Abnormalities in electrophysiological parameters of VEP at baseline correlated with presentation of anti-Ro52 antibodies and aching joints. At baseline, the P100 implicit time was shorter for the patients with pSS than for those at T6 (105.50 ± 5.1 vs. 109.37 ± 5.67; p = 0.002). pSS patients without CNS involvement presented with dysfunction of visual pathway, as revealed by VEP abnormalities. Relationships were found between VEP parameters and with present of anti-Ro52 antibodies and aching joints. VEP may be a useful method for assessment and monitoring of subclinical visual deficit in the course of pSS.

Myasthenia Gravis-An Analysis of Multimodal Evoked Potentials.

INTRODUCTION: The aim of this study is a comprehensive analysis of the parameters of exogenous evoked potentials (visual, brainstem auditory, and somatosensory) in patients with myasthenia gravis (MG), a prototype of both neuromuscular junction disease and autoimmune disease. The study also seeks to isolate electrophysiological changes that may indicate disorders within the central and/or peripheral nervous system. METHODS: A total of forty-two consecutive patients with myasthenia gravis (24 women, 18 men) were included in the study. All of the patients underwent EP examination. MR images were also analyzed. RESULTS: In the group of MG patients, the latency of P100 (113.9 ± 13.9; p < 0.0001) VEP, wave III (3.92 ± 0.29; p = 0.015), wave V (5.93 ± 0.32; <0.0001), interlatency III-V (2.00 ± 0.12; p < 0.0001), interlatency I-V (4.20 ± 0.28; p < 0.001) BAEP, and all components of SEP (N9, P10, N13, P16, N20, P22) were significantly longer. Mean wave I and V amplitude BAEP were relatively lower. CONCLUSIONS: The results of the study suggest the presence of disturbances in the bioelectric activities of the central and peripheral nervous system in MG patients.

The Relationship between Occupationally Exposed Arsenic, Cadmium and Lead and Brain Bioelectrical Activity-A Visual and Brainstem Auditory Evoked Potentials Study.

The aim of this study was to evaluate the parameters of visual and brainstem auditory evoked potentials in patients occupationally exposed to arsenic, cadmium and lead. The study group comprised 41 copper smelter and refinery workers (average age: 51.27) with occupational exposure to arsenic, cadmium and lead. The control group consisted of 36 healthy volunteers (35 men and 1 woman, aged 27-66, average age: 51.08). Neurological examination, brain imaging, and visual and brainstem auditory evoked potentials were performed, and the relationship between blood Cd, Pb concentration (Cd-B, Pb-B), blood zinc protoporphyrin (ZnPP), and urine As concentration (As-U) were assessed. In the workers, exceedances of allowable biological concentrations were observed, with the urinary concentration of arsenic being 5.2%, the cadmium and lead in blood being 1.3%, while the case of ZnPP was 2.6%. The mean P100, relative P100, and N145 visual evoked potential (VEP) latencies were significantly longer in exposed workers than in the controls. The mean wave III and V brainstem auditory evoked potential (BAEP) latency and the mean wave III-V and I-V interpeak latencies were longer, and the I and V amplitude was lower in the workers than the controls. In summary, occupational exposure to As, Cd, and Pb is associated with prolonged latency and reduced evoked potential amplitude, but As-U, Pb-B, Cd-B, and ZnPP concentrations are not linearly related to potential components. The analysis of evoked potentials may be a useful method of assessment of the central nervous system in patients with occupational exposure to heavy metals.

The impact of chronic co-exposure to different heavy metals on small fibers of peripheral nerves. A study of metal industry workers.

BACKGROUND: Chronic exposure to heavy metals affects various organs, among them the brain and peripheral nerves. Polyneuropathy is mainly length-dependent with predominantly sensory symptoms. There have been few studies on small fiber neuropathy due to heavy metal intoxication. METHODS: We investigated 41 metal industry workers, mean age 51.3 ± 10.5 years, with at least 5 years' professional exposure to heavy metals, and 36 age- and sex-matched healthy controls. We performed neurological examinations, and assessed blood levels of cadmium, lead, and zinc protoporphyrin, urine levels of arsenic, standard, sensory and motor electrophysiological tests in the ulnar and peroneal nerves, sympathetic skin responses from the palm and foot, and quantitative sensation testing from dermatomes C8 and S1. DISCUSSION: The results of standard conduction tests of all nerves significantly differed between groups. The latency of sympathetic skin responses achieved from the foot was also statistically significantly prolonged in the study group. Significant differences were seen in both C8 and S1 regions for temperature and pain thresholds, and for vibratory threshold only in the S1 region, while the dispersions of low and high temperatures were important exclusively in the C8 region. CONCLUSIONS: We can conclude that co-exposure to many heavy metals results in explicit impairment of peripheral nerves. The lesion is more pronounced within small fibers and is predominantly connected with greater impairment of temperature-dependent pain thresholds. The evaluation of small fiber function should be considered in the early diagnosis of toxic polyneuropathy or in low-dose exposure to heavy metals.

Opsoclonus-myoclonus syndrome with severe clinical course and beneficial outcome: A case report.

RATIONALE: Opsoclonus-myoclonus syndrome (OMS) is a rare immune-mediated movement disorder, mostly of paraneoplastic or idiopathic origin. The disease usually has an acute onset, serious course and leads rapidly to disability in adult patients. To the best of our knowledge, this is the fourth presented case of OMS with a severe course and complete reversibility of neurological symptoms in a pregnant woman. This report includes videos and a literature review. PATIENT CONCERNS: A 30-year-old woman in the 12th week of pregnancy developed severe nausea and vomiting, after several days balance and gait disorders appeared. On admission to hospital, neurological examination revealed opsoclonus, dysarthria, myoclonic jerks with ataxia of the trunk and limbs with inability to sit, stand or walk. DIAGNOSIS: Well-known causes of OMS were excluded. Although in our patient the idiopathic origin of the disorder was taken under consideration, diagnosis of opsoclonus-myoclonus related to the pregnancy was highly likely. INTERVENTIONS: After administration of steroids and benzodiazepines the patient improved. OUTCOMES: In the 6th month of pregnancy, after termination of immunotherapy, she recovered completely and was able to sit, stand and walk independently. In the 39th week of pregnancy, she delivered a healthy child. LESSONS: We confirm that understanding of clinical symptoms and rare causes of OMS contributes to early diagnosis and therapy, which ensures an optimal outcome. One probable cause of OMS could be a physiological change to immune system regulation during pregnancy. The relationship between OMS and pregnancy remains uncertain and needs further investigation.

Assessment of Visual and Brainstem Auditory Evoked Potentials in Patients with Hashimoto's Thyroiditis.

BACKGROUND: The present study was aimed to evaluate parameters of visual and brainstem auditory evoked potentials (VEP, BAEP) in euthyreotic Hashimoto's thyroiditis (HT) patients without central nervous system involvement. METHODS: 100 HT patients (92 women, 8 men), mean age 46.9 years, and 50 healthy controls. They underwent a neurological examination, thyroid hormone levels, thyroid autoantibody titers, and brain imaging. Latencies and amplitudes of the N75, P100, and N145 component of VEP and the I-V components of BAEP were analyzed. RESULTS: The neurological examination revealed in 31 patients signs of increased neurovegetative excitability. Brain resonance imaging showed no abnormalities in HT patients. The mean P100, relative P100, and N145 VEP latencies were significantly longer, and P100 amplitude significantly higher in HT patients than the controls. HT patients also had a longer mean wave BAEP V latency and mean wave III-V and I-V interpeak latencies, and significantly lower mean wave I and V amplitudes. Abnormal VEP and BAEP were recorded in 34% of the patients. There were no statistically significant correlations between the mean VEP parameters and thyroid profile and the applied dose of L-thyroxine. There was a relationship between the level of TSH and the wave BAEP III-V interpeak latency. CONCLUSIONS: There were changes in the brain's bioelectrical activity in one-third of the patients with HT without nervous system involvement. The increased amplitude of the VEP may indicate increased cerebral cortex activity. Disorders of the brain's bioelectrical activity in the course of HT may be associated with an autoimmune process.

The evaluation of Hashimoto's thyroiditis with event-related potentials and magnetic resonance spectroscopy and its relation to cognitive function.

Thyroid dysfunction is very often accompanied by cognitive and affective disorders. The frequency of these disorders in patients with compensated Hashimoto's thyroiditis (HT) is unknown. The aim of the present study was to evaluate brain dysfunction in euthyroid HT patients by means of event-related potentials (ERP) and magnetic resonance spectroscopy (MRS) and to correlate it with cognitive function. 68 patients with HT (59 female, 9 male) and 45 healthy controls were included in the study. All the patients underwent ERP including an analysis of N200 and P300 response parameters. MRS voxels were located in the posterior cingulate gyrus (PCG) and the left parietal white matter (PWM). The NAA/Cr, mI/Cr, and Cho/Cr ratios were analysed. The ERP parameters, MRS metabolite ratios and hormonal concentrations (TSH, fT3, fT4) as well as TGAb and TPOAb titer were also correlated. There was a significant prolongation of the latencies of N200 and P300 potentials and a significant decrease of P300 amplitude in HT patients than in the control group. There was a significant positive correlation between the mI/Cr ratio in the PCG area and P300 latencies. NAA/Cr ratio in the PCG region showed significant negative correlations with all N200 latencies. The results may suggest brain dysfunction in neurologically asymptomatic HT patients. ERPs undergo significant changes in patients with HT and may, in combination with MRS, constitute an important element in the recognition and monitoring of cognitive functions in this group of patients.

Sleep Disturbances and Cognitive Impairment in the Course of Type 2 Diabetes-A Possible Link.

There is an increasing number of patients worldwide with sleep disturbances and diabetes. Various sleep disorders, including long or short sleep duration and poor sleep quality of numerous causes, may increase the risk of diabetes. Some symptoms of diabetes, such as painful peripheral neuropathy and nocturia, or associated other sleep disorders, such as sleep breathing disorders or sleep movement disorders, may influence sleep quality and quantity. Both sleep disorders and diabetes may lead to cognitive impairment. The risk of development of cognitive impairment in diabetic patients may be related to vascular and non-vascular and other factors, such as hypoglycemia, hyperglycemia, central insulin resistance, amyloid and tau deposits and other causes. Numerous sleep disorders, e.g., sleep apnea, restless legs syndrome, insomnia, and poor sleep quality are most likely are also associated with cognitive impairment. Adequate functioning of the system of clearance of the brain from toxic substances, such as amyloid ß, i.e. glymphatic system, is related to undisturbed sleep and prevents cognitive impairment. In the case of coexistence, sleep disturbances and diabetes either independently lead to and/or mutually aggravate cognitive impairment.

Dysbiosis is one of the risk factor for stroke and cognitive impairment and potential target for treatment.

More than 50 million people have various forms of cognitive impairment basically caused by neurodegenerative diseases, such as Alzheimer's, Parkinson's, and cerebrovascular diseases as well as stroke. Often these conditions coexist and exacerbate one another. The damaged area in post-stroke dementia may lead to neurodegenerative lesions. Gut microbiome functions like an endocrine organ by generating bioactive metabolites that can directly or indirectly impact human physiology. An alteration in the composition and function of intestinal flora, i.e. gut dysbiosis, is implicated in neurodegenerative and cerebrovascular diseases. Additionally, gut dysbiosis may accelerate the progression of cognitive impairment. Dysbiosis may result from obesity; metabolic disorders, cardiovascular disease, and sleep disorders, Lack of physical activity is associated with dysbiosis as well. These may coexist in various patterns in older people, enhancing the risk, incidence, and progression of cerebrovascular lesions, neurodegenerative disorders, and cognitive impairment, creating a vicious circle. Recently, it has been reported that several metabolites produced by gut microbiota (e.g., trimethylamine/trimethylamine N-oxide, short-chain fatty acids, secondary bile acids) may be linked to neurodegenerative and cerebrovascular diseases. New treatment modalities, including prebiotic and probiotics, may normalize the gut microbiota composition, change the brain-gut barrier, and decrease the risk of the pathology development. Fecal microbiota transplantation, sometimes in combination with other methods, is used for remodeling and replenishing the symbiotic gut microbiome. This promising field of research is associated with basic findings of bidirectional communication between body organs and gut microbiota that creates new possibilities of pharmacological treatments of many clinical conditions. The authors present the role of gut microbiota in physiology, and the novel therapeutic targets in modulation of intestinal microbiota Personalized therapies based on their personal genome make up could offer benefits by modulating microbiota cross-talk with brain and cardiovascular system. A healthy lifestyle, including pre and probiotic nutrition is generally recommended. Prevention may also be enhanced by correcting gut dysbiosis resulting a reduced risk of post-stroke cognitive impairment including dementia.

Brainstem auditory evoked potentials in patients with primary Sjögren's syndrome without central nervous system involvement.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is an autoimmune, multisystem exocrinopathy characterized by dysfunction of the exocrine glands. Central nervous system (CNS) involvement is estimated to be present in 10-60% patients with pSS. The present study aimed to evaluate brainstem auditory evoked potentials (BAEP) in pSS patients without central nervous system involvement, and without otolaryngological abnormalities. METHOD: Thirty-six pSS patients (35 women, 1 man, mean age 48 years old) and 40 healthy volunteers were investigated. BAEP, brain imaging, laboratory parameters, and clinical neurological and otolaryngological examinations were performed. RESULTS: Abnormal BAEP were recorded in 16.7% patients. The mean wave BAEP I and V latency and mean wave III-V and I-V interpeak latencies were significantly longer in pSS patients than the controls. There were no statistically significant correlations between BAEP parameters and laboratory tests. None of the patients was found having the abnormalities on brain imaging. CONCLUSIONS: This study confirms that in pSS patients without clinical central nervous system impairment, auditory pathway disturbances could be found. Disorders of brain bioelectrical activity may be a consequence of ongoing autoimmune process. Key Points • BAEP abnormalities confirmed the clinically observed involvement of the central nervous system in patients with pSS. • Brain bioelectrical activity dysfunctions in pSS patients may be a consequence of ongoing inflammatory and/or immunological processes.

Ocular Paraneoplastic Syndromes.

Ocular-involving paraneoplastic syndromes present a wide variety of clinical symptoms. Understanding the background pathophysiological and immunopathological factors can help make a more refined differential diagnosis consistent with the signs and symptoms presented by patients. There are two main pathophysiology arms: (1) autoimmune pathomechanism, which is presented with cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), cancer-associated cone dysfunction (CACD), paraneoplastic vitelliform maculopathy (PVM), and paraneoplastic optic neuritis (PON), and (2) ectopic peptides, which is often caused by tumor-expressed growth factors (T-exGF) and presented with bilateral diffuse uveal melanocytic proliferation (BDUMP). Meticulous systematic analysis of patient symptoms is a critical diagnostic step, complemented by multimodal imaging, which includes fundus photography, optical coherent tomography, fundus autofluorescence, fundus fluorescein angiography, electrophysiological examination, and sometimes fundus indocyjanin green angiography if prescribed by the clinician. Assessment of the presence of circulating antibodies is required for diagnosis. Antiretinal autoantibodies are highly associated with visual paraneoplastic syndromes and may guide diagnosis by classifying clinical manifestations in addition to monitoring treatment.

The Links between Parkinson's Disease and Cancer.

Epidemiologic studies indicate a decreased incidence of most cancer types in Parkinson's disease (PD) patients. However, some neoplasms are associated with a higher risk of occurrence in PD patients. Both pathologies share some common biological pathways. Although the etiologies of PD and cancer are multifactorial, some factors associated with PD, such as α-synuclein aggregation; mutations of PINK1, PARKIN, and DJ-1; mitochondrial dysfunction; and oxidative stress can also be involved in cancer proliferation or cancer suppression. The main protein associated with PD, i.e., α-synuclein, can be involved in some types of neoplastic formations. On the other hand, however, its downregulation has been found in the other cancers. PINK1 can act as oncogenic or a tumor suppressor. PARKIN dysfunction may lead to some cancers' growth, and its expression may be associated with some tumors' suppression. DJ-1 mutation is involved in PD pathogenesis, but its increased expression was found in some neoplasms, such as melanoma or breast, lung, colorectal, uterine, hepatocellular, and nasopharyngeal cancers. Both mitochondrial dysfunction and oxidative stress are involved in PD and cancer development. The aim of this review is to summarize the possible associations between PD and carcinogenesis.

Pure word deafness in a patient with bilateral ischemic stroke in the superior temporal gyrus (STG).

INTRODUCTION: Pure word deafness is a rare neurological disorder linked with an inability to comprehend speech. The precise localization of damage is still unclear. CASE PRESENTATION: A 72-year-old woman presented with acute verbal contact disturbances, disorientation, and anxiety. In the neurological examination a slight right hemiparesis was found, together with a pure word deafness (PWD) in neuropsychological tests. Neuroimages confirmed bilateral ischemic lesions in the superior temporal gyrus (STG) acute in the left hemisphere. CONCLUSIONS: Our case suggested that bilateral, symmetric lesions in the region of STG could cause pure world deafness. The diversity and severity of symptoms confirm the necessity of pure world deafness classification for subtypes.

Abnormality of multimodal evoked potentials in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

INTRODUCTION: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, sometimes including the central nervous system. The aim of the study was the assessment of the prevalence of central sensory impairment and its reliance on peripheral nerve damage in patients with CIDP. MATERIAL AND METHODS: Multimodal (visual-VEP, brainstem auditory-BAEP, somatosensory-SEP) evoked potentials (EPs) were studied in 24 patients diagnosed with CIDP. The results were compared with neurographic parameters of sensory responses. The control group consisted of 35 healthy volunteers selected with respect to age and sex. RESULTS: Mean latency of most components of EP were considerably prolonged in patients compared with the control group. There were no correlations between the P100 VEP latency and the peripheral sensory parameters. Statistically significant negative correlations were obtained between BAEP and SEP responses and the amplitude and sensory conduction velocity of peripheral nerves. The inter-latencies were also longer. CONCLUSIONS: The authors indicated to the possibility of central sensory involvement in patients with CIDP, especially based on the prolonged inter-latency of BAEPs with simultaneously confirmed root affection. The severity of central damage correlates with the degree of peripheral nerve impairment.

Evaluation of brain volume alterations in HCV-infected patients after interferon-free therapy: A pilot study.

The study was performed to evaluate cerebral volume changes in HCV-infected subjects before and after interferon-free therapy with direct-acting antiviral agents (DAA). We aimed also to estimate the impact of successful DAA therapy on the neuropsychological state of patients. Eleven HCV genotype 1 (GT1) patients treated with ombitasvir/paritaprevir (boosted with ritonavir) and dasabuvir, with or without ribavirin underwent brain magnetic resonance (MR) before and 24 weeks after completion of therapy. All patients achieved sustained viral response. Precise automatic parcellation was made using the fully-available software FreeSurfer 6.0. Statistically significant volume deceleration six months after treatment was found in the subcallosal cingulate gyrus, transverse frontopolar gyri and sulci, anterior segment of the circular sulcus of the insula and horizontal ramus of the anterior segment of the lateral sulcus. After DAA therapy we found statistically significant improvement in the performance of all three tasks of the Rey Complex Figure Test that permits the evaluation of different functions (attention, planning, working,memory). Additionally, significant amelioration in Percentage Conceptual Level Responses in The Wisconsin Card Sorting Test (a neurocognitive test for assessing intellectual functioning) was also discovered. Successful interferon-free therapy may lead to transient cerebral atrophy, probably by reducing neuroinflammation and oedema. This is the first pilot study of the alterations in brain volume after successful interferon-free therapy in chronic HCV patients. Longitudinal follow-up study is needed to observe further effects of therapy on cerebral structures volume changes.