Non-specific Neurological Symptoms Research Articles

Neurological and psychiatric effects of hepatitis C virus infection

Hepatitis C virus (HCV) infection is widespread and affects 71 million people worldwide. Although hepatic manifestations are the most frequent, ranging from chronic hepatitis to cirrhosis and hepatocellular carcinoma, it is also associated with several extrahepatic manifestations. Infected patients may present non-specific neurological symptoms, regardless of the presence of liver cirrhosis. Several pathogenetic mechanisms underlying neurological symptoms have been hypothesized: neuroinvasion, immune-mediated damage, neurotransmitter alterations and cryoglobulinemia. Alterations of the central nervous system include cerebral vasculopathy, acute or subacute encephalopathy and inflammatory disorders. HCV infection may be responsible for neuropathies, of which the most frequent form is symmetrical axonal sensory or sensory-motor polyneuropathy which causes loss of leg sensitivity and weakness. Up to 50% of patients with HCV infection may experience cognitive decline and psychological disorders, such as depression and fatigue. HCV associated neurocognitive disorder is independent of the presence of liver cirrhosis and affects different domains than in patients with hepatic encephalopathy. It can be studied using specific tests that mainly explore executive functions, verbal learning and verbal recall. These disorders significantly reduce the quality of life. The new antiviral therapies improve the extrahepatic symptoms of HCV infection and their success depends on the achievement of sustained virological response. However, the effect of therapy may differ depending on the type of organ involved; neurological symptoms can be irreversible if there is organic liver damage. The aim of this review is to provide a critical overview of physiopathological mechanisms, diagnostic and therapeutic strategies of the neurological and psychiatric effects of HCV infection.

Mural endocarditis - by default

We report on a case of a 33-year-old female patient with known adult congenital heart disease in the form of a coronary cameral fistula who, on prior presentation, had refused treatment and subsequently defaulted follow-up, but unfortunately developed a serious and rare complication. She presented with non-specific neurological symptoms of transient visual loss and headaches. Clinical examination revealed aortic regurgitation with peripheral features of infective endocarditis. This was confirmed with transthoracic echocardiogram, but additionally, we found mural endocarditis of the right atrial posterior wall. An initial CT brain scan and ophthalmology assessments were negative, blood cultures were positive and confirmed infective endocarditis, and she was referred for urgent cardiothoracic surgery. Unfortunately, she had further complications with a large intracranial haemorrhage which ultimately led to her death. This case illustrates a rare entity with disastrous complications.

Diagnosis of extracranial carotid stenosis by MRA of the brain

Severe extracranial carotid stenosis (SECS) patients may present with nonspecific neurological symptoms that require intracranial magnetic resonance imaging (MRI) and time-of-flight (TOF)-MR angiography (MRA) to exclude intracranial pathology. Recognition of SECS on intracranial TOF-MRA findings is beneficial to provide a prompt carotid imaging study and aggressive stroke prevention. Patients with SECS (January 2016 to May 2019) undergoing percutaneous transluminal angioplasty and stenting (PTAS) were included. Differences in normalized signal intensities (SRICA) and diameters (DICA) between bilateral petrous internal carotid arteries (ICAs) were calculated 1 cm from the orifice. A hypothesized criterion describing the opacification grades (GOPH) of bilateral ophthalmic arteries was proposed. We correlated SRICA (p = 0.041), DICA (p = 0.001) and GOPH (p = 0.012), with the severity of extracranial carotid stenosis on digital subtractive angiography (DSA) in the examined group (n = 113), and all showed statistical significance in predicting percentages of ICA stenosis. The results were further validated in another patient group with SECS after radiation therapy (n = 20; p = 0.704 between the actual and predicted stenosis grades). Our findings support the evaluation of the signal ratio and diameter of intracranial ICA on TOF-MRA to achieve early diagnosis and provide appropriate management of SECS.

Legionnaires\u2019 disease arising with hirsutism: case report of an extremely confusing event

BackgroundLegionella bacteria is a common cause of pneumonia, but the infection may affect several organs in the most serious cases. A systemic involvement ab initio could be non-specific, leading to a diagnostic misinterpretation.Case presentationA 33-year-old woman had been complaining of mental confusion, restlessness, aggressiveness, and, subsequently, hirsutism. After 3 weeks, the patient developed pneumonia and died during the hospitalization. The autopsy examination revealed a multi-organ necrotizing exudative disease involving the lung, the heart and the brain. The microbiological tests of tracheal aspirate were positive for Legionella pneumophila serotype 1.ConclusionThe Legionella infection may show a proteiform clinical course and an extra-pulmonary manifestation may be the first sign of the disease. Herein, we report a case of Legionella infection in a young female, presenting with non-specific neurological symptoms and hirsutism at onset, misdiagnosed as a metabolic disease.

Cerebral Vasoreactivity Evaluated by Transcranial Color Doppler and Breath-Holding Test in Patients after SARS-CoV-2 Infection.

From the beginning of the SARS-CoV-2 virus pandemic, it was clear that the virus is highly neurotrophic. Neurological manifestations can range from nonspecific symptoms such as dizziness, headaches and olfactory disturbances to severe forms of neurological dysfunction. Some neurological complication can occur even after mild forms of respiratory disease. This study’s aims were to assess cerebrovascular reactivity in patients with nonspecific neurological symptoms after SARS-CoV-2 infection. A total of 25 patients, aged 33–62 years, who had nonspecific neurological symptoms after SARS-CoV-2 infection, as well as 25 healthy participants in the control group, were assessed for cerebrovascular reactivity according to transcranial color Doppler (TCCD) which we combined with a breath-holding test (BHT). In subjects after SARS-CoV-2 infection, there were statistically significantly lower flow velocities through the middle cerebral artery at rest period, lower maximum velocities at the end of the breath-holding period and lower breath holding index (BHI) in relation to the control group. Changes in cerebral artery flow rate velocities indicate poor cerebral vasoreactivity in the group after SARS-CoV-2 infection in regard to the control group and suggest vascular endothelial damage by the SARS-CoV-2 virus.

COVID-19 and the Nervous System

Neurologic complications are a significant cause of morbidity and mortality in the COVID-19 pandemic. Besides respiratory disease, neurological manifestations such as headache, dizziness, hyposmia, hypogeusia, acute cerebrovascular disease, encephalopathy, encephalitis are common. These complications may result from various mechanisms; virus-induced hyperinflammation and hypercoagulable states, a direct viral effect on the central nervous system, and post-infectious autoimmunity. We must keep in mind diagnosing SARS-CoV-2 infection when patients present with specific or non-specific neurological symptoms during the pandemic.

Overcoming the Elusiveness of Neurosarcoidosis: Learning from Five Complex Cases.

The involvement of the central nervous system in sarcoidosis can manifest with a variety of neurological symptoms, and most of them can be nonspecific. The diagnosis of neurosarcoidosis (NS) can therefore be very challenging without a tissue biopsy. Both computed tomography (CT) and magnetic resonance imaging (MRI) are important imaging modalities in the diagnosis of NS, and MRI is the modality of choice due to its superior soft-tissue contrast resolution. We present a case series of NS with interesting neuroimaging features, complex neurological presentations, and clinical courses. We identify five cases presenting with clinically isolated neurosarcoidosis (CINS) without any other signs or symptoms of systemic disease which were diagnosed as NS on biopsy. In the first case, we describe a patient with an intramedullary cervical spinal cord lesion. In the second case we describe a patient presenting with inflammatory changes and enhancement in the orbit. The third case demonstrates a lesion with calcification around the region of the foramen of Monro. The fourth case shows multiple ring-enhancing lesions. Lastly, the fifth case exhibits unusual findings with both optic neuritis and a cerebellar nodule. We aim to describe the complicated clinical course with neurological workup, neuro-imaging, and eventual diagnosis and treatment of these challenging cases to highlight the variable presentations of NS. This case series will remind clinicians that NS should always be in the differential diagnosis when a patient presents with nonspecific neurological symptoms with unusual neuroimaging findings.

Cerebral venous sinus thrombosis with venous hemorrhagic infarct in a patient with high-grade glioma of the left thalamus

Cerebral venous sinus thrombosis (CVST) is an uncommon type of venous thromboembolism whose diagnosis is often difficult due to its vague and non-specific clinical findings. Sometimes, the diagnosis is delayed as the symptoms were considered to be attributable to the underlying etiology, especially in patients with brain tumors such as high-grade glioma (HGG). We described the case of a 60-year-old male patient who presented with headache, generalized seizures, and right hemiparesis soon after receiving brain radiation and temozolomide therapy for HGG of the left thalamus. Initially, his symptoms were considered to be due to his underlying tumor but the subsequent imaging revealed left transverse, left sigmoid, and superior sagittal sinus thrombosis with venous hemorrhagic infarct of the left occipitoparietal lobe. The patient was started on anticoagulant therapy and symptoms resolved completely within a month. Clinicians should always consider CVST in the differential diagnosis of non-specific neurological symptoms, especially in patients with underlying brain tumors.

Manifestations neurologiques associées au COVID-19

Les manifestations neurologiques associées au COVID-19 sont fréquentes et variées. Alors que des symptômes non spécifiques tels que des céphalées, des vertiges, des douleurs et des myalgies sont décrits dans 2 à 30 % des cas, on retrouve des atteintes neurologiques plus sévères chez 8 à 13 % des patients hospitalisés. Il s’agit d’atteintes neurologiques centrales ou périphériques, avec au premier plan des encéphalopathies, des accidents vasculaires cérébraux mais également des encéphalites et des syndromes de Guillain–Barré. Les troubles du goût et de l’odorat, assez caractéristiques du COVID-19, touchent quant à eux 34 à 86 % des patients. À l’heure actuelle, les mécanismes en cause dans ces atteintes neurologiques sont imparfaitement compris. Les études autopsiques mettent en lumière le possible rôle du sepsis et de l’hypoxie, de l’infection/dysfonction endothéliale, de l’inflammation et d’atteintes immunomédiées. Le rôle pathogène direct du virus sur le parenchyme cérébral reste quant à lui incertain.

Posterior Reversible Encephalopathy Syndrome Induced by an Acute Postinfectious Glomerulonephritis.

Posterior reversible encephalopathy (PRES) is a rare but a serious disease that affects the central nervous system. PRES is responsible for various but nonspecific neurological symptoms, including confusion, coma, and seizures as well as visual disturbances. Diagnosis is made using cerebral MRI which typically shows at the early stage, bilateral symmetrical parietooccipital hyperintensities on T2 and fluid-attenuated inversion recovery (FLAIR) sequences. Case study. In this article, we base our research on a case study that includes, as a population sample, a 9-year-old boy who suffers from an acute postinfectious glomerulonephritis and arterial hypertension. Two days before diagnosis, he developed confusion with generalized tonic-clonic attacks. His blood pressure was 180/80 mmHg. A cerebral computed tomography made in emergency showed cerebral edema. It was supplemented by magnetic resonance imaging which revealed cortical and posterior cortical lesions which appear as hypointense on T1 and hyperintense on T2 and Flair. An MRI control was performed 40 days later which shows a clear improvement of the occipital lesions. PRES is a radioclinical syndrome characterized by the association of variable neurological signs which reversibility is conditioned by the early diagnosis and the correction of the contributing factors.

Neurological Disorders Associated With COVID-19 Hospital Admissions: Experience of a Single Tertiary Healthcare Center.

Background: Early reports have detailed a range of neurological symptoms in patients with the SARS-CoV-2 infection. However, there is a lack of detailed description and incidence of the neurological disorders amongst hospitalized COVID-19 patients. We describe a range of neurological disorders (other than non-specific neurological symptoms), including their clinical, radiological, and laboratory findings, encountered in our cohort of COVID-19 patients admitted to a large tertiary institution.Methods: We reviewed our prospectively collated database of all adult Neurology referrals, Neurology and Stroke admissions and Neurological multi-disciplinary team meetings for all hospitalized patients with suspected or proven COVID-19 from 17 March 2020 to 31 August 2020.Results: Twenty-nine of 1,243 COVID-19 inpatients (2.3%) presented with COVID-19-related neurological disorders. The mean age was 68.9 ± 13.5(SD) years, age range of 34–97 years, and there were 16 males. Twenty two patients had confirmed, five were probable and two had suspected COVID-19 infection according to the WHO case classification. Eight patients (27%) required critical care admission. Neurological symptoms at presentation included acute confusion and delirium, seizures, and new focal neurological deficits. Based on the pre-defined neurological phenotype, COVID-19 patients were grouped into four main categories. Sixteen patients had cerebrovascular events (13 with acute ischemic stroke and three had hemorrhagic features), seven patients were found to have inflammatory, non-inflammatory and autoimmune encephalopathy (including two with known Multiple Sclerosis), whilst disorders of movement and peripheral nervous system were diagnosed in three patients each.Conclusion: Although the exact prevalence and etiology remain unclear, new onset of neurological disorders, in addition to anosmia, is non-sporadic during the acute COVID-19-infection. Longitudinal follow-up of these patients is required to determine the clinical and functional outcome, treatment response and long-term effects of the SARS-CoV-2 infection.

Dysfonction endothéliale au cours du Purpura Thrombotique Thrombocytopénique : un nouvel axe de prise en charge ?

Immune Thrombotic Thrombocytopenic Purpura (iTTP) is a rare but severe disease with a mortality rate of almost 100 % in the absence of adequate treatment. iTTP is caused by a severe deficiency in ADAMTS13 activity due to the production of inhibitory antibodies. Age has been shown to be a major prognostic factor. iTTP patients in the elderly (60yo and over) have more frequent organ involvement, especially heart and kidney failures compared with younger patients. They also have non-specific neurologic symptoms leading to a delayed diagnosis. Factors influencing this impaired survival among older patients remain unknown so far. Alteration of the functional capacity of involved organs could be part of the explanation as could be the consequences of vascular aging. In fact, severe ADAMTS13 deficiency is necessary but likely not sufficient for iTTP physiopathology. A second hit leading to endothelial activation is thought to play a central role in iTTP. Interestingly, the mechanisms involved in endothelial activation may share common features with those involved in vascular aging, potentially leading to endothelial dysfunction. It could thus be interesting to better investigate the causes of mid- and long-term mortality among older iTTP patients to confirm whether inflammation and endothelial activation really impact vascular aging and long-term mortality in those patients, in addition to their presumed role at iTTP acute phase. If so, further insights into the mechanisms involved could lead to new therapeutic targets.

Cerebral venous sinus thrombosis associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

Introduction/Objective. Coagulopathy induced by severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2) can be an underlying cause of cerebral venous sinus thrombosis (CVST), a less common type of stroke with a variable clinical presentation and high mortality rate. The objective of the paper is to present a series of CVST cases associated with SARS-CoV-2 infection. Methods. This retrospective study evaluated clinical, laboratory and radiological presentations, risk factors, barriers to diagnosis, treatment and outcome of patients with SARS-CoV-2 infection-induced CVST. Results. The study comprised six patients diagnosed with COVID-19-induced CVST during an 18-month period. The majority (66.7%) had no significant risk factors for developing CVST. The median time from the initial COVID-19 diagnosis to the onset of neurologic deficit was seven days (interquartile range 0.5?7 days). Clinical presentation comprised non specific neurological symptoms: headache (83.3%) and decreased consciousness (33.3%), together with elevated levels of D-dimer and inflammatory biomarkers. The transverse (n = 4, or 66.7%), superior sagittal sinuses (n = 3, or 50%) and sigmoid sinus (n = 2, or 33.3%) were most commonly affected. Five patients (83.3%) had minimal to no symptoms at discharge (mRS ? 2). In-hospital mortality in our current series was relatively high (16.7%). Conclusion. The high mortality rate of SARS-CoV-2-associated CVST urges clinicians to suspect CVST in patients with a history of COVID-19 infection presenting with non-specific neurological symptoms in order to provide proper treatment and prevent complications.

Cerebral venous sinus thrombosis associated with oligosymptomatic COVID-19 infection: A case report

Introduction. Severe acute respiratory syndrome coronavirus 2 infection-induced coagulopathy may cause various thrombotic complications, such as cerebral venous sinus thrombosis, a less common type of stroke with a variable clinical presentation and high mortality rate. The objective of this paper was to identify clinical, laboratory and radiological characteristics, risk factors, therapeutic modalities, and outcome of a young patient with cerebral venous sinus thrombosis associated with oligosymptomatic coronavirus disease 2019 infection. Case Report. We present a case of a 32-year-old woman suffering from a stroke due to cerebral venous sinus thrombosis associated with a mild form of coronavirus disease 2019 infection. The patient was without a history of previous diseases and risk factors for cerebral venous sinus thrombosis. Two weeks before the cerebrovascular incident, the patient presented with oligosymptomatic coronavirus disease 2019 infection associated with headache. Laboratory findings were characterized by two conditions: hypercoagulability and systemic inflammation. Bilateral thalamic and right frontal hemorrhagic venous infarctions with superior sagittal and straight sinus thrombosis and thrombosis of the vein of Galen were established by magnetic resonance imaging of the head. The main therapeutic approaches included anticoagulant therapy, therapeutic protocol for coronavirus disease 2019 infection, seizure control therapy and intracranial hypertension management. The treatment outcome was good, with minimal residual symptoms. Conclusion. Physicians should always consider the high risk of cerebral venous sinus thrombosis with nonspecific neurological symptoms in patients with mild coronavirus disease 2019 infection in order to provide early diagnosis, the most effective individually tailored treatment, and to prevent complications.

Encefalopatia/Encefalite Ligeira com Lesão Reversível do Corpo Caloso: Entidade Benigna Rara com Diagnósticos Diferenciais Menos Benignos

A encefalopatia/encefalite ligeira com lesão reversível do corpo caloso é uma entidade clínico-radiológica benigna rara, caracterizada por sintomas neurológicos inespecíficos associados a achados imagiológicos, em ressonância magnética, e lesão do corpo caloso. De etiopatogénese desconhecida, têm sido sugeridos vários desencadeadores (infeções, alterações metabólicas, fármacos, entre outros). Apresenta-se o caso de um homem de 44 anos, previamente saudável, admitido na urgência com quadro súbito de cefaleias, ataxia, mioclonias da face e disartria, em contexto de síndrome gripal. Após diagnóstico presuntivo de encefalite vírica iniciou aciclovir empiricamente, suspenso após ressonância magnética revelando lesões no corpo caloso. O doente evoluiu favoravelmente sem terapêutica dirigida, com resolução clínica em menos de uma semana e controlo imagiológico, aos dois meses, normal. Esta entidade, que exige diagnóstico diferencial entre condições benignas e outras, de pior prognóstico, é habitualmente diagnosticada por exclusão, não exige terapêutica dirigida e apresenta, quase universalmente, um desfecho favorável.

The psychiatric and neuropsychiatric repercussions associated with severe infections of COVID-19 and other coronaviruses

IntroductionIt is known that viral infections are epidemiologically prevalent and some of them are harmful to the central nervous system (CNS) due to the development of neuropsychiatric syndromes which affect the cognitive, affective, behavioral and perceptual domains. ObjectiveTo carry out a comprehensive analysis of the psychiatric and neuropsychiatric repercussions of COVID-19 based on epidemiological, pathophysiological and clinical foundations observed in previous and recent pandemic events, and also to make a proposition about effective therapeutic interventions to help tackle this serious public health problem, more specifically in its neuropsychiatric developments. MethodThis current literature review has utilized literature reserves and scientific search engines MEDLINE, EMBASE and Web of Science. The search terms included, “SARS-CoV-2”, “etiology,” “psychiatric and neuropsychiatric repercussions”, “severe infections” “COVID-19”. Specific choices of unique papers from each of the searches were identified. The inclusion criteria were relevance and availability of full-text. Papers were excluded on the basis of relevance and non-availability of full-text. Papers were identified in the general literature reserve as pertinent to the search terms. ResultsThe main psychiatric and neuropsychiatric repercussions analyzed were depression, anxiety, post-traumatic stress disorder, psychosis, nonspecific neurological symptoms, delirium, cerebrovascular complications, encephalopathies, neuromuscular disorders, anosmia and ageusia. ConclusionThe psychiatric and neuropsychiatric symptoms of acute respiratory syndromes can appear during or after the infectious stage. Among the risk factors pointed out for such effects are the female gender, health professionals, presence of avascular necrosis and distressing pain.

A Noteworthy Case Report of Neuroborreliosis in an Unvaccinated Pediatric Patient.

IntroductionLyme disease typically presents with viral-like symptoms and a pathognomonic rash. With disease progression, symptoms of nervous system involvement usually include facial nerve palsy and meningitis, but other atypical neurologic manifestations have less commonly been documented.Case ReportA six-year-old male presented with prolonged fevers, rash, headache, and non-specific neurologic symptoms. The diagnosis of neuroborreliosis with meningitis and polyradiculitis was confirmed with laboratory evaluation and lumbar puncture.ConclusionNeuroborreliosis is a disseminated form of Lyme disease. While meningitis is a common sign, the presentation of polyradiculitis in children is rare and can lead to misdiagnosis and delay in treatment.

Cerebral Venous Sinus Thromboses in Patients with SARS-CoV-2 Infection: Three Cases and a Review of the Literature

IntroductionEarly studies suggest that acute cerebrovascular events may be common in patients with coronavirus disease 2019 (COVID-19) and may be associated with a high mortality rate. Most cerebrovascular events described have been ischemic strokes, but both intracerebral hemorrhage and rarely cerebral venous sinus thrombosis (CVST) have also been reported. The diagnosis of CVST can be elusive, with wide-ranging and nonspecific presenting symptoms that can include headache or altered sensorium alone. ObjectiveTo describe the presentation, barriers to diagnosis, treatment, and outcome of CVST in patients with COVID-19. MethodsWe abstracted data on all patients diagnosed with CVST and COVID-19 from March 1 to August 9, 2020 at Boston Medical Center. Subsequently, we reviewed the literature and extracted all published cases of CVST in patients with COVID-19 from January 1, 2020 through August 9, 2020 and included all studies with case descriptions. ResultsWe describe the clinical features and management of CVST in 3 women with COVID-19 who developed CVST days to months after initial COVID-19 symptoms. Two patients presented with encephalopathy and without focal neurologic deficits, while one presented with visual symptoms. All patients were treated with intravenous hydration and anticoagulation. None suffered hemorrhagic complications, and all were discharged home. We identified 12 other patients with CVST in the setting of COVID-19 via literature search. There was a female predominance (54.5%), most patients presented with altered sensorium (54.5%), and there was a high mortality rate (36.4%). ConclusionsDuring this pandemic, clinicians should maintain a high index of suspicion for CVST in patients with a recent history of COVID-19 presenting with non-specific neurological symptoms such as headache to provide expedient management and prevent complications. The limited data suggests that CVST in COVID-19 is more prevalent in females and may be associated with high mortality.

Head Computed tomography during emergency department treat-and-release visit for headache is associated with increased risk of subsequent cerebrovascular disease hospitalization.

The occurrence of head computed tomography (HCT) at emergency department (ED) visit for non-specific neurological symptoms has been associated with increased subsequent stroke risk and may be a marker of diagnostic error. We evaluate whether HCT occurrence among ED headache patients is associated with increased subsequent cerebrovascular disease risk. We conducted a retrospective cohort study of consecutive adult patients with headache who were discharged home from the ED (ED treat-and-release visit) at one multicenter institution. Patients with headache were defined as those with primary ICD-9/10-CM discharge diagnoses codes for benign headache from 9/1/2013-9/1/2018. The primary outcome of cerebrovascular disease hospitalization was identified using ICD-9/10-CM codes and confirmed via chart review. We matched headache patients who had a HCT (exposed) to those who did not have a HCT (unexposed) in the ED in a one-to-one fashion using propensity score methods. Among the 28,121 adult patients with ED treat-and-release headache visit, 45.6% (n=12,811) underwent HCT. A total of 0.4% (n=111) had a cerebrovascular hospitalization within 365days of index visit. Using propensity score matching, 80.4% (n=10,296) of exposed patients were matched to unexposed. Exposed patients had increased risk of cerebrovascular hospitalization at 365days (RR: 1.65: 95% CI: 1.18-2.31) and 180days (RR: 1.62; 95% CI: 1.06-2.49); risk of cerebrovascular hospitalization was not increased at 90 or 30days. Having a HCT performed at ED treat-and-release headache visit is associated with increased risk of subsequent cerebrovascular disease. Future work to improve cerebrovascular disease prevention strategies in this subset of headache patients is warranted.

Genetics Of Gluten Intolerance

Celiac disease, or extreme gluten intolerance, is an autoimmune disease that primarily causes damage to the small intestine. It is caused by dietary intake of gluten in genetically predisposed individuals. The presentation of celiac disease consists of digestive tract symptoms, mainly diarrhea and subsequent weight loss. Other related symptoms and findings are iron deficiency anemia, decreased bone density, and some nonspecific neurological symptoms. In the recent past, the diagnosis of celiac disease was made based on specific serological tests, small intestinal mucosa biopsy results, and fading away of symptoms after gluten-free diet is applied. After the identification of the disease-specific genes HLA-DQ2 and DQ8 , genetic testing was considered the gold standard for the diagnosis of celiac disease, because the presence of a specific genotype is a prerequisite for the development of this disease. Risk variants of HLA-DQ2 and DQ8 are found in about 30% of the general European population. Determining the genetic status allows adequate subsequent clinical decisions. The lack of genetic variants predisposing to celiac disease leads to the exclusion of the diagnosis, while the detection of high-risk variant(s) in an individual prompts additional diagnostic steps through a number of serological and invasive tests. The introduction of genetic analysis has led to a significant reduction in the number of invasive intestinal tests (biopsies). The purpose of this article is to present the current practical approach in the diagnosis of celiac disease, which includes mandatory genetic analysis, and to explain the nature of this autoimmune disease from a genetic point of view.