Cerebrospinal fluid analysis represents a key diagnostic instrument in confirming and differentiating various forms of CNS infections due to its ability to reveal specific cytologic, biochemical and microbiological changes. In cases where CNS infection is suspected, a basic cerebrospinal fluid examination includes the enumeration of nucleated cells and erythrocytes, the differentiation of nucleated cells into mononuclear and polymorphonuclear cells, and, if applicable, a detailed qualitative analysis from a permanent cytological slide. Furthermore, the determination of total protein, glucose and lactate concentrations and the coefficient of energy balance (KEB) is essential. In cases where the differential diagnosis is subarachnoid haemorrhage, an additional spectrophotometric examination is recommended. Multiplex PCR is a useful technique for identifying the causative agent in both serous and purulent inflammation. In cases of bacterial or mycotic infections, microscopic and culture examinations are also ne­cessary. Other examinations of the CSF include indirect diagnostics, such as the detection of an antibody response (e. g. in Central European tick-borne encephalitis) or, in selected diseases, the demonstration of intrathecal (IT) synthesis of specific antibodies. This test is particularly useful in the diagnosis of neuroborreliosis and neurosyphilis, and can also be used in suspected herpetic infections with EBV, HSV, VZV and CMV. However, it is important to note that confirmation of IT synthesis does not always indicate acute disease. Indeed, it may persist after a previous illness or be seen in a chronic inflammatory autoimmune process in the CNS. In the case of Lyme disease, the detection of the chemokine CXCL13 is also useful to support the diagnosis in cases where there is a negative IT synthesis at an early stage.

From a speech therapist's perspective, multiple sclerosis causes speech (dysarthria), voice (dysphonia), and language difficulties. Currently, automated analysis is increasingly used to assess voice, speech, and language deficits, as it is much more accurate than perceptual assessment or standard tests. Acoustic analysis can be used to detect features that might be potential biomarkers for the early detection of multiple sclerosis or indicators of the severity of the disease. The aim of this paper is to present speech and language deficits in people with multiple sclerosis, outline the possibilities for their assessment using available tools with automated speech analysis, and present digital biomarkers at the voice, speech, and language level.

A large proportion of neurological diseases have a genetic origin, and this genetic background cannot be simplified into a single category. Conversely, most genetically determined diseases have neurological manifestations. Furthermore, thanks to current molecular genetic methods and new treatment options for genetic diseases, we are on the threshold of a new era. Currently, exome sequencing is the gold standard for investigating heterogeneous diseases, which include most genetic neurological disorders. However, like other diagnostic molecular genetic methods, it has its limits and specific applications. Despite the rapid development of genetic diagnostic methods, we are only able to clarify the genetic background of neurological diseases in a fraction of patients. In addition, genetic testing brings specific challenges and risks, including ethical issues. Artificial intelligence tools are now also being introduced for processing genetic data. In any case, genetics will play an increasingly important role in neurology and medicine as a whole. Therefore, it is essential to realize what capabilities it currently has and what expectations we can have of it.

Epilepsy is a complex neurological disease that affects 40-60 million people worldwide. Multiple genetic factors play a significant role in the pathogenesis of epilepsy, leading to the growing importance of genetics in the field of epileptology. With the development of methodologies using massively parallel sequencing, many DNA variants causing epilepsy have been identified, improving our understanding of the molecular mechanisms involved in the clinical manifestations of genetically determined epilepsies. In this paper, we offer an overview of current but also future possibilities for genetic diagnostics of epilepsy, which, by identifying gene variants in patients with both monogenic and polygenic epilepsy, may open the way to targeted personalized diagnosis and treatment.

Cluster headache is a primary headache disorder classified under trigeminal autonomic cefalalgias. Its treatment is based on empirical recommendations and includes acute, preventative and bridging treatment strategies, and complemented by neuromodulatory methodes. Verapamil is considered first-line preventative medication, although its use in cluster headache is off-label. The treatment should be started at the very beginning of the cluster period with an initial dose of 240 mg/day, prior it is mandatory to rule out contraindications and confirm that patient´s echocardiographic finding is normal. During the first week of treatment, the typical effective therapeutic dose of 360 mg/day is achieved. Further increase of the dose is provided stepwise according the needs of the patient and with routine electrocardiogram monitoring. If high (≥ 480 mg/day) or very high doses (≥ 720 mg/day) of verapamil are necessary, treatment should be administered under the specialist´s supervision with close cardiological follow-up. The maximu recommended dose for preventative treatment of cluster headache is 960 mg/day. Preventative treatment usually continues for several weeks or months and must be withdrawn gradually.

Determining a person's death is generally unproblematic and requires no special education or skill. In a small proportion of cases, however, it is not at all easy to determine whether a person is dead or alive. The situation is further complicated by the need to define the time and cause of death. In the article, the authors discuss the history of defining and determining the death of a person from the 18th century (a period of accelerated anatomical-physiological knowledge) until the present day. Particular attention is paid to a concept used in the last half-century, namely brain death based on neurological criteria. Also, emphasis is placed on the fact that the issue of death is a combination of professional-medical, moral-ethical, philosophical-religious, and legislative-legal aspects along with the emotional background of those who are close to the deceased ones.

According to the definition of the European Medicines Agency, gene therapy is a treatment based on the insertion of a recombinant gene into a patient's body for therapeutic, prophylactic, or diagnostic purposes. In recent years, there has been a growing number of clinical studies as well as an increasing number of approved gene therapies, particularly for rare monogenic diseases. The first examples in the field of neurology include gene therapy for spinal muscular atrophy, gene therapy for primary disorders of biogenic amine synthesis (aromatic L-amino acid decarboxylase [AADC] deficiency), and gene therapy for metachromatic leukodystrophy. In the United States, gene therapy has also been approved for Duchenne muscular dystrophy and X-linked adrenoleukodystrophy. Clinical studies are already underway for gene therapy targeting Dravet syndrome, Leber's hereditary optic neuropathy, and certain types of mucopolysaccharidoses. Additionally, gene therapy is being investigated for some forms of limb-girdle muscular dystrophies and for amyotrophic lateral sclerosis (ALS) linked to the SOD1 gene. The effectiveness and side effect profile of gene therapy are always specific to the particular diagnosis and therapeutic product. The high financial cost and ethical considerations surrounding gene therapy remain subjects for broader societal discussion.

Chronic kidney disease significantly affects the pharmacokinetics of various neurological drugs, necessitating careful dosage adjustments. Due to reduced renal clearance, drugs eliminated via the kidneys experience prolonged biological half-lives and accumulation, increasing the risk of toxicity or delaying therapeutic effects. Hypoalbuminemia leads to an increased free fraction of drugs bound to plasma proteins, further complicating accurate interpretation of therapeutic drug levels, as demonstrated with valproic acid. The article addresses the impact of impaired renal function and extracorporeal elimination methods on neurologic renally eliminated drugs. Presented case studies illustrate clinical consequences of improperly adjusted drug dosages, including severe adverse effects.

Diagnosis of central nervous system (CNS) tumor involvement is a highly responsible and demanding discipline. Qualitative cytological examination of cerebrospinal fluid (CSF) plays a key role, particularly in meningeal tumor infiltrations, allowing the detection of morphological abnormalities of cells. Subsequent special staining immunocytochemical techniques and subsequent evaluation by a cytopathologist allow these atypical cells to be specified closer. If a tumor process originating from hematopoietic cells is suspected, immunophenotyping analysis is appropriate. In a limited sample, this allows the malignant leukocyte clone to be further characterized. For this purpose, we use flow cytometry. The presented case reports include the use of this method in cerebrospinal fluid diagnostics, highlight its limitation, and emphasize that the method should not be considered in isolation. It must be interpreted in the context of the basic cytological cerebrospinal fluid examination.

Laboratory biomarkers play a crucial role in the diagnosis, prediction, and monitoring of treatment efficacy in patients with multiple sclerosis (MS). Their use enables better individualization of therapy, increasing the chances of slowing disease progression and improving patients' quality of life. The most important diagnostic laboratory biomarkers in MS are oligoclonal IgG bands and free kappa light chains, while neurofilament light chains are essential for disease prediction and monitoring treatment efficacy. Research in this area is continuously evolving with the aim of discovering new indicators that further improve diagnostic accuracy and enable more detailed monitoring of disease progression.

Neurodegenerative diseases are broadly characterized by progressive damage of CNS with dementia being the most common clinical presentation. Several diseases fall into this category such as Alzheimer´s disease (AD), Parkinson´s disease (PD) and frontotemporal dementia (FTD). Coexisting brain pathology and clinical heterogeneity may hamper the diagnostic accuracy and delay effective treatment. Disease- specific biomarkers, alongside clinical features and imaging methods can substantially improve the diagnosis. Some of the most recent criteria rely on the involvement of CSF core biomarkers in the diagnostic work-up. Despite the distinct pathomechanism, fluid biomarkers are detectable before symptoms onset becoming helpful tools in the early diagnosis and possess the potential as screening tool, either. Recently, novel methods to measure core biomarkers in blood have been developed pointing toward the perspectives in the non-invasive diagnosis and screening of neurodegenerative disorders in the clinical settings.

Dytrophinopathies are X-linked genetic dysorders caused by Dystrophine gene mutation. The phenotypes of patients include the well-known forms of Duchenne and Becker muscular dystrophy, DMD-related dilated cardiomyopathy in men, but also less well-known and highly variable forms of dystrophinopathies in female carriers. The disease in women is most often caused by inactivation of chromosome X. It may be manifested as an isolated elevation of muscle enzymes tests, other female patients may suffer from severe muscle weakness, dilated cardiomyopathy or other extramuscular complications. The diagnostic method of choice is a molecular genetic examination of the dystrophin gene. There is no causal therapy available, therapy is limited to symptomatic treatment, prevention of complications and genetic counselling.

The aim of this review article is to provide information on the clinical course of cluster headache (CH). Individual attacks, cluster periods, and the long-term course of the di­sease show significant variability, which contributes to diagnostic delay. Notably, some of the CH variants are not uncommon: in a retrospective analysis of own cohort of 70 patients with CH, eight (11,4 %) did not meet the strict wording of the criteria defined by the International Classification of Headache Disorders (ICHD-3). Five patients (7,1 %) due to a change in symptom lateralization, one (1,4 %) due to atypical localization outside the first trigeminal branch (orofacial cluster attacks), one due to the absence of cranial autonomic symptoms, and one due to persistent Horner's syndrome. Many other variant manifestations of CH beyond the ICHD-3 criteria have been described in the literature.

Cerebral venous thrombosis is a rarer cause of stroke. It can be a life-threatening condition. It mainly affects women, and pregnancy and the postpartum period are also significantly at risk. Lactational psychosis is a serious psychological condition in the postpartum period, in which the woman is dangerous to herself and the newborn baby. We present a case report in which the clinical picture of encephalopathy together with the symptoms of migraine attacks in the observed migraineur faithfully imitated lactational psychosis. Early diagnosis and treatment of multiple cerebral venous thrombosis reversed the unfavorable clinical development and prevented more extensive permanent consequences.

Encephalitis is a serious inflammatory disease of the brain that involves a complex differential diagnostic assessment due to the wide range of possible causes. This report presents a case of a 71-year-old patient who underwent neurosurgery and subsequently developed subacute cognitive deterioration and recurrent epileptic seizures. The diagnosis of autoimmune encephalitis was prolonged due to a premorbidly diagnosed and treated structural epilepsy and the detection of serous to purulent encephalitis, which presented an atypical cerebrospinal fluid profile. Due to the lack of evidence of an infectious cause and suspicion of autoimmune encephalitis, it was decided to administrate a total dose of 2.5 g of methylprednisolone followed by maintenance immunosuppressive therapy, after which the patient's condition improved rapidly, as evidenced by both clinical examination and extensive neuropsychological evaluation.

In this case report, we present a 51-year-old patient who sought medical help for approximately 3 years of complaints of impaired limb mobility and coordination, altered behavior, speech articulation disorders, and gait disorders. Magnetic resonance imaging of the brain in T2-weighted images showed pathological changes in the mesencephalon namely the "face of the giant panda" sign and also the rarer "double panda sign" in pons Varoli. These MRI findings were corresponding with a metabolic disease with copper accumulation. Laboratory tests confirmed decreased serum copper and ceruloplasmin levels. Following these results, increased urinary copper excretion was found, confirming a presumed systemic disorder of copper metabolism. Additional eye examination confirmed the presence of Keyser-Fleischer rings in both eyes. Additional molecular genetic testing confirmed the pathogenic variant p.His1069Gln, c.3207C>A in the ATP7B gene in a homozygous state, thus confirming the presumptive diagnosis of Wilson's disease.

The German guidelines are the first to have been developed following the introduction of novel therapeutic agents. Reimbursement of these therapies in the Czech Republic differs, as does the socioeconomic context. Nevertheless, the concept of extending clinicians' attention to all active forms of generalized myasthenia gravis, not only to refractory patients, clearly deserves consideration. Therefore, we present a very concise summary of the German guidelines in Czech for the professional community.

Rare diseases represent a broad and heterogeneous group of disorders that are predominantly genetically determined. Currently, more than six thousand clinical entities have been identified, which collectively affect approximately 68% of the global population and pose a significant healthcare and socioeconomic burden. Major advances in molecular genetics, particularly the introduction of whole-exome and whole-genome sequencing, have markedly shortened the time to diagnosis and enabled the discovery of new genetic causes of disease. Nevertheless, approximately half of all patients remain without a causal diagnosis. At present, targeted causal therapy is available for only a small proportion of these disorders, highlighting the need for continued research and innovation in the field of precision medicine. This article focuses on an overview of current diagnostic and therapeutic approaches and on the perspectives offered by emerging genomic technologies and targeted treatment strategies.

Hereditary neuromuscular disorders (NMD) are a broad group of diseases affecting peripheral nerves, muscles, or neuromuscular transmission. They are considered rare diseases with variable clinical presentation. A common feature of NMD is muscle weakness, which is progressive and can lead to respiratory failure in some patients. In the past, therapy for genetically conditioned NMD consisted only of symptomatic care without the possibility of influencing the natural course of the disease. A breakthrough occurred with the advent of gene therapy for spinal muscular atrophy (SMA). Progress has also been made in the treatment of muscular dystrophies. The effectiveness of gene therapy goes hand in hand with the availability of modern diagnostic methods such as next-generation sequencing or the use of newborn screening to detect asymptomatic patients.

Aromatic L-amino acid decarboxylase deficiency (AADC-D) is a rare and underdiagnosed neurotransmitter disorder caused by autosomal recessive mutations in the DDC gene. The resulting enzyme deficiency leads to reduced synthesis of monoamine neuromodulators, causing severe impairment of motor, behavioral, and autonomic functions. Until recently, therapy was purely symptomatic, relying on dopamine agonists, monoamine oxidase inhibitors, and pyridoxine. The introduction of eladocagene exuparvovec gene therapy represents a major breakthrough. This stereotactically guided intraputaminal administration of an AAV vector carrying the functional DDC gene enables causal treatment with excellent clinical outcomes. The authors present an overview of this therapeutic approach for AADC-D.

Metachromatic leukodystrophy (MLD), caused by arylsulfatase A deficiency, is characterized by three clinical subtypes: late infantile, juvenile (early and late) and adult form. Regression of motor and mental functions with finding of leukodystrophy on brain MRI is the reason for further laboratory examination. The diagnosis of MLD is established by confirmation of arylsulfatase enzyme deficiency, finding of sulfatides in urine and subsequent genetic examination of pathogenic variants of the ARSA gene. Targeted therapy is allogenic hematopoietic stem cell transplantation (HSCT), which is used in patients with pre- and very early symptomatic forms of MLD. Autologous HSCT using gene-modified hematopoietic stem cells (also known as ex vivo gene therapy) is approved for presymptomatic patients with late infantile and juvenile MLD or in the early phase of juvenile MLD in mildly symptomatic patients with preserved walking ability, before onset of cognitive decline.

The field of genetic epilepsies, and especially developmental and/or epileptic encephalopathies, has undergone literally revolutionary changes over the past 15 years. With the rapidly growing number of identified "epilepsy-associated" genes and the increasing understanding of the enormous genotypephenotype variability, modern molecular-genetic methods based on the principle of massive parallel sequencing have been developed and implemented in clinical practice. These methods make it possible to diagnose, etiologically classify, and clinically characterize a wide range of new monogenic entities, to better understand their pathogenetic basis, and, last but not least, to develop innovative therapeutic strategies. The possibilities of so-called individualized therapy have thus already become a reality, and in the case of Dravet syndrome, the first gene therapy has already entered clinical testing.

Transthyretin amyloidosis (ATTR) is a severe, progressive multisystem disorder caused by the deposition of amyloid fibrils derived from pathologically unstable transthyretin in various tissues. Clinically, it most commonly manifests as rapidly progressive axonal sensory‑motor polyneuropathy with early autonomic nervous system involvement and/or cardiomyopathy. The development of disease‑modifying therapies, particularly gene "silencers" (molecules that suppress the expression of a specific gene at the mRNA level) based on small interfering RNAs (patisiran, vutrisiran) and antisense oligonucleotides (inotersen, eplontersen), has fundamentally changed the prognosis of affected patients. These agents reduce hepatic transthyretin synthesis, slow the progression of neuropathy or cardiomyopathy, and improve quality of life. This article summarizes the current options for genetic therapy of ATTR in the Czech Republic and discusses the perspectives of emerging therapeutic approaches.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with limited therapeutic options. Tofersen, an antisense oligonucleotide targeting SOD1 mutations, represents the first approved gene therapy for ALS. Clinical studies demonstrated a significant biological effect through reduction of SOD1 protein and neurofilament levels, although short-term clinical benefit was not consistently confirmed. Long-term and real-world data suggest slowed disease progression, particularly when treatment is initiated early. Despite the occurrence of adverse events, the overall benefitrisk balance is considered favorable, as reflected by conditional approval in the USA and EU. We also have roughly one year of experience with the treatment in the Czech Republic as part of the compassionate use program.

In today's digital age, patients with multiple sclerosis (MS) are increasingly going online in search of information to help them manage this chronic disease. This article focuses on the different ways patients use digital media, including social networking sites, professional websites, mobile apps, and virtual communities, and their impact on quality of life, disease knowledge, and treatment decisions.

This review summarizes current options for both disease-modifying and symptomatic treatment of degenerative cerebellar ataxias, with a particular focus on two conditions that are significantly reshaping everyday neurological practice: Friedreich's ataxia (FA), with the recent availability of the targeted therapy omaveloxolone, and spinocerebellar ataxia type 27B (SCA27B), for which accumulating evidence supports the efficacy of 4-aminopyridine (4-AP).