Neurological Symptoms Research Articles

Melatonin suppresses TLR4-mediated RSV infection in the central nervous cells by inhibiting NLRP3 inflammasome formation and autophagy.

Respiratory syncytial virus (RSV) infects neuronal cells in the central nervous system (CNS), resulting in neurological symptoms. In the present study, we intended to explore the mechanism of RSV infection-induced neuroinflammatory injury from the perspective of the immune response and sought to identify effective protective measures against the injury. The findings showed that toll-like receptor 4 (TLR4) was activated after RSV infection in human neuronal SY5Y cells. Furthermore, TLR4 activation induced autophagy and apoptosis in neuronal cells, promoted the formation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and increased the secretion of downstream inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumour necrosis factor-α (TNF-α). Interestingly, blockade of TLR4 or treatment with exogenous melatonin significantly suppressed TLR4 activation as well as TLR4-mediated apoptosis, autophagy and immune responses. Therefore, we infer that melatonin may act on the TLR4 to ameliorate RSV-induced neuronal injury, which provides a new therapeutic target for RSV infection.

Ptičja influenca u divljih kanida

The risk of cross-species transmission of infectious diseases and zoonoses has increased due to the adaptive evolution of pathogens and anthropogenic landscape changes. A current example is the avian influenza (AI) virus, which can infect not only avian species but also mammals. In these species, infections are often associated with severe neurological symptoms. AI viruses are primarily not well adapted to mammalian hosts and are not efficiently transmitted among them. To accomplish this, AI viruses must acquire adaptations or mutations that contribute to replication efficiency and virulence in mammals. The exact combination and interaction of mutations that result in optimal adaptation to mammals is still unknown and may vary between host species and virus subtypes. The globally increasing number of infected birds with highly pathogenic AI (HPAI) increases the likelihood of contact between birds and mammals, especially wildlife. One reason for the adaptation of HPAI to mammals is theexposure of wild mammals to infected birds or their carcasses. According to the current data, wild canids, such as red foxes, are among the most infected mammals. However, infections caused by neurotropic viruses, as well as HPAI, have been scarcely studied or not at all in jackals. Since jackals are scavengers that have spread rapidly in Europe and Croatia in recent years, surveillance of AI virus infection in these canids is of the utmost importance. Furthermore, interactions between wild carnivores and domestic animals are of concern, as infections with HPAI pose a public health threat due to the increased risk of mammalian adaptation.

The Blood-Brain Barrier Is Unaffected in the Ndufs4-/- Mouse Model of Leigh Syndrome.

Mitochondrial dysfunction plays a major role in physiological aging and in many pathological conditions. Yet, no study has explored the consequence of primary mitochondrial deficiency on the blood-brain barrier (BBB) structure and function. Addressing this question has major implications for pharmacological and genetic strategies aimed at ameliorating the neurological symptoms that are often predominant in patients suffering from these conditions. In this study, we examined the permeability of the BBB in the Ndufs4-/- mouse model of Leigh syndrome (LS). Our results indicated that the structural and functional integrity of the BBB was preserved in this severe model of mitochondrial disease. Our findings suggests that pharmacological or gene therapy strategies targeting the central nervous system in this mouse model and possibly other models of mitochondrial dysfunction require the use of specific tools to bypass the BBB. In addition, they raise the need for testing the integrity of the BBB in complementary in vivo models.

Surgical treatment options in chronic subdural hematoma: A literature review

Chronic subdural hematoma (cSDH) is one of the most common neurosurgery cases in daily practice. Chronic subdural hematoma is clot formation in the subdural space between the dura mater and the arachnoid layer. Due to its progression, clinical presentation of cSDH mostly appears 4 to 8 weeks after a traumatic brain injury. It is the duration needed for the hematoma to grow large enough to cause severe neurological symptoms such as decreased consciousness, hemiparesis, and other signs and symptoms of increased intracranial pressure. There are three main options to treat cSDH. Conservative treatment, surgical treatment, and embolization of the middle meningeal artery (MMA) are widely used to manage this condition. Predominantly, surgical treatments used by neurosurgeons around the world are craniotomy, burr hole (BH) craniostomy, and twist drill (TD) craniostomy. Each of these procedures has advantages and disadvantages. This literature review aimed to consider the characteristics of several treatment options for cSDH and their technique. This review recommends BH craniotomy due to its benefits based on its complication and recurrence rates. Burr Hole craniotomy has a lower complication rate than craniotomy and a lower recurrence rate than TD craniotomy. Twist drill craniotomy is selectively considered for certain patients since this procedure is commonly performed at the bedside without general anesthesia. Craniotomy is recommended as a treatment option for persistent recurrence of cSDH or patients with massive subdural hematoma.

Chronic basilar artery occlusion: a retrospective monocentric study.

Acute basilar artery occlusion is a life-threatening medical emergency with a highly elevated mortality rate when left untreated. Little is known about symptoms and clinical progression of chronic occlusions. The aim of this study was to systematically analyze the clinical presentation of patients with chronic basilar artery occlusion (CBAO). Monocentric retrospective analysis of adult patients with CBAO was treated between 2015 and 2023 in the Department of Neurology, Klinikum Kassel. Inclusion criteria were basilar artery occlusion without brainstem infarction as well as patients with a basilar artery occlusion in whom revascularization could not be achieved and a follow-up period of at least 3months. A total of 15 patients were found. In five patients basilar artery occlusion was diagnosed as an incidental finding, four patients had neurological symptoms but no proven brainstem infarction (3 × transient ischemic attack, 1 × isolated posterior artery infarct) and six patients presented with acute basilar artery occlusion and a follow-up > 3months. The most common site of occlusion was midbasilar (80%, n = 12), isolated (n = 7) or in combination with other locations (n = 5). In all cases collateralization could be demonstrated by the posterior communicatingarteries. The most common vascular risk factors (VRF) were hypertension (100%) and hypercholesterolemia (67%). Patients with CBAO may present with only mild symptoms or may even be asymptomatic. This condition may be survived for a long time. The high percentage of vascular risk factors and further cerebral vessel occlusions suggest arteriosclerosis as the major causing factor of CBAO.

Joubert syndrome presenting bilateral peroneal neuropathies: A case report.

Joubert syndrome (JS) is a rare genetic disorder that presents with various neurological symptoms, primarily involving central nervous system dysfunction. Considering the etiology of JS, peripheral nervous system abnormalities cannot be excluded; however, cases of JS accompanied by peripheral nervous system abnormalities have not yet been reported. Distinct radiological findings on brain magnetic resonance imaging were considered essential for the diagnosis of JS. However, recently, cases of JS with normal or nearly normal brain morphology have been reported. To date, there is no consensus on the most appropriate diagnostic method for JS when imaging-based diagnostic approach is challenging. This report describes the case of an adult patient who exhibited bilateral peroneal neuropathies and was finally diagnosed with JS through genetic testing. A 27-year-old man visited our outpatient clinic due to a gait disturbance that started at a very young age. The patient exhibited difficulty maintaining balance, especially when walking slowly. Oculomotor apraxia was observed on ophthalmic evaluation. During diagnostic workups, including brain imaging and direct DNA sequencing, no conclusive findings were detected. Only nerve conduction studies revealed profound bilateral peroneal neuropathies. We performed whole genome sequencing to obtain a proper diagnosis and identify the gene mutation responsible for JS. This case represents the first instance of peripheral nerve dysfunction in JS. Further research is needed to explore the association between JS and peripheral nervous system abnormalities. Detailed genetic testing may serve as a valuable tool for diagnosing JS when no prominent abnormalities are detected in brain imaging studies.

The pattern of neurological disorders requiring hospitalization during the COVID-19 era: an experience from Fayoum University Hospital, Egypt

BackgroundCoronavirus was primarily discovered in December 2019, causing pneumonia and severe acute respiratory syndrome. It was reported several neurological symptoms associated with COVID-19. Both the central and peripheral nervous systems could be affected which might result in a higher mortality rate in hospitalized patients. This study aimed to determine the spectrum of neurological clinical presentations among patients admitted to Fayoum University Hospital before, during, and after the COVID-19 era and to examine the influence of COVID-19 vaccines mandated by the Egyptian government on neurological disorders.MethodsThis is a historical cohort study that was conducted on patients admitted to the Neurology Department at Fayoum University Hospital before, during, and after COVID-19 outbreaks from January 1st, 2018, to July 31, 2022. All participants had undergone thorough history taking and neurological examination and the necessary investigations according to the suspected diagnosis. All hospitalized patients during the COVID-19 pandemic were positive for the virus, as determined by either a positive rapid antigen test or a positive real-time reverse transcription polymerase chain reaction (RT-PCR).ResultsIt was shown that the patients hospitalized during the COVID-19 era were notably older, smokers, and diabetic in comparison to other groups. Cerebrovascular disorders were more prevalent in the COVID-19 pandemic. Surprisingly, compared to prior times, individuals with autoimmune-mediated neurological diseases had higher hospitalization rates than those with other neurological disorders. Patients who were not vaccinated reported more vascular complications than those who got them. However, patients who received vaccination exhibited significantly higher neurological complications as regards, exacerbation of paroxysmal disorders.ConclusionIt was concluded that the frequency of hospitalizations with cerebrovascular disorders and autoimmune-mediated illnesses was significantly influenced during the pandemic era. Although COVID-19 vaccinations have potential adverse effects, they have played a crucial role in preventing serious neurological problems.

Identification of DAGLA as an autoantibody target in cerebellar ataxia

BackgroundWe aimed to investigate the clinical, imaging and fluid biomarker characteristics in patients with antidiacylglycerol lipase alpha (DAGLA)-autoantibody-associated cerebellitis.MethodsSerum and cerebrospinal fliud (CSF) samples from four index patients were subjected...

Unveiling the mystery: Infective endocarditis as an etiological cause of recurrent intracranial hemorrhage

Intracerebral hemorrhage (ICH) in the context of infective endocarditis (IE) is an uncommon and complex phenomenon involving diverse underlying mechanisms. We present a compelling case of a 48-year-old patient with recurrent ICH, ultimately leading to the diagnosis of IE with vegetation on the anterior leaflet of the mitral valve. The patient underwent a successful mitral valve replacement followed by a gradual improvement in neurological symptoms. This case report delves into the intricate diagnostic journey, highlighting the significance of suspecting IE in patients presenting with ICH. A multidisciplinary and comprehensive management approach played a pivotal role in achieving positive outcomes.

The tuberous sclerosis complex: a review of the literature

Tuberous sclerosis complex (TSC) is a neurocutaneous autosomal dominant genetic disorder characterized by mutations in the TSC1 and TSC2 genes, this leads to dysregulation of the mechanistic target of rapamycin (mTOR) pathway resulting in cellular hyperplasia and the formation of benign tumors in various organs, including the brain and skin. Clinical manifestations encompass a wide range of mainly neurological and dermatological symptoms, often presenting during early childhood and posing diagnostic challenges due to phenotypic variability. Recent advancements in diagnostic criteria, genetic testing, and imaging techniques have facilitated earlier diagnosis and increased disease incidence awareness. Neurologically, TSC commonly presents with cortical tubers, subependymal nodules (SENs), and epilepsy, with seizure control being paramount in preventing long-term neurodevelopmental sequelae. Dermatologically, hypomelanotic macules, facial angiofibromas, and ungual fibromas are hallmark features, often causing significant psychological distress due to disfigurement. Management of TSC requires a multidisciplinary approach, with emerging therapies such as mTOR inhibitors showing promise in addressing both neurological and dermatological manifestations. Early intervention, including epilepsy surgery and targeted treatments for skin lesions, is essential for optimizing outcomes and improving the quality of life for patients with TSC. Continued research into novel therapeutic modalities holds potential for further enhancing the management and prognosis of this complex disorder.

Peroneal Nerve Decompression in Patients with Multiple Hereditary Exostoses: Indications, Complications, and Recurrence.

To our knowledge, there have been no studies examining peroneal nerve decompression and proximal fibular osteochondroma excision exclusively in patients with multiple hereditary exostoses (MHE). The purpose of this study was to evaluate the indications, complications, and recurrence associated with nerve decompression and proximal fibular osteochondroma excision in patients with MHE. The records on patients with MHE undergoing peroneal nerve decompression from 2009 to 2023 were retrospectively reviewed. Indications, clinical status, surgical technique, recurrence, and complications were recorded and were analyzed using the Fisher exact test, logistic regression, and the Kaplan-Meier method. There were 126 limbs identified in patients with MHE who underwent peroneal nerve decompression. The most common indications were pain over the proximal fibula, tibialis anterior and/or extensor hallucis longus weakness, and dysesthesias and/or neuropathic pain. Seven cases experienced postoperative foot drop as a complication of the decompression and osteochondroma excision. Logistic regression found significant relationships between complications and excision of anterior osteochondromas (odds ratio [OR], 5.21; p = 0.0062), proximal fibular excision (OR, 14.73; p = 0.0051), and previous decompression (OR, 5.77; p = 0.0124). The recurrence rate was 13.8%, and all recurrences occurred in patients who were skeletally immature at the index procedure. The probability of skeletally immature patients not experiencing recurrence was 88% at 3 years postoperatively and 73% at 6 years postoperatively. Indications for peroneal nerve decompression included neurologic symptoms and pain. The odds of a complication increased with excision of anterior osteochondromas and previous decompression. Recurrence of symptoms following decompression and osteochondroma excision was found exclusively in skeletally immature patients. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Long COVID exhibits clinically distinct phenotypes at 3–6 months post-SARS-CoV-2 infection: results from the P4O2 consortium

BackgroundFour months after SARS-CoV-2 infection, 22%–50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the...

Construction of an early differentiation diagnosis model for patients with severe fever with thrombocytopenia syndrome and hemorrhagic fever with renal syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high mortality rate. Differentiating between SFTS and hemorrhagic fever with renal syndrome (HFRS) is difficult and inefficient. Retrospective analysis of the medical records of individuals with SFTS and HFRS was performed. Clinical and laboratory data were compared, and a diagnostic model was developed based on multivariate logistic regression analyzes. Receiver operating characteristic curve analysis was used to evaluate the diagnostic model. Among the 189 patients, 113 with SFTS and 76 with HFRS were enrolled. Univariate analysis revealed that more than 20 variables were significantly associated with SFTS. Multivariate logistic regression analysis revealed that gender, especially female gender (odds ratio [OR]: 4.299; 95% confidence interval [CI]: 1.163-15.887; p = 0.029), age ≥65 years (OR: 16.386; 95% CI: 3.043-88.245; p = 0.001), neurological symptoms (OR: 12.312; 95% CI: 1.638-92.530; p = 0.015), leukopenia (<4.0 × 109/L) (OR: 17.355; 95% CI: 3.920-76.839; p < 0.001), and normal Cr (OR: 97.678; 95% CI: 15.483-616.226; p < 0.001) were significantly associated with SFTS but not with HFRS. The area under the curve of the differential diagnostic model was 0.960 (95% CI: 0.936-0.984), which was significantly better than that of each single factor. In addition, the model exhibited very excellent sensitivity and specificity (92.9% and 85.5%, respectively). In cases where HFRS and SFTS are endemic, a diagnostic model based on five parameters, such as gender, age ≥65 years, neurological symptoms, leukopenia and normal Cr, will facilitate the differential diagnosis of SFTS and HFRS in medical institutions, especially in primary care settings.

Face-off Droop: A Case Report of Pediatric Stroke

Introduction: Cerebrovascular accidents rarely occur in children; the incidence of ischemic stroke in patients &amp;lt;16 years of age is between 0.6&amp;ndash;7.9/100,000. However, they are the fourth most common cause of acute neurological deficits in the pediatric population, and possible cases should be evaluated with a high index of suspicion to ensure timely intervention. Case Report: We describe a previously healthy 17-year-old male who presented to the pediatric emergency department with a left facial droop and hemiparesis consistent with a stroke. The patient&amp;rsquo;s age and lack of comorbidities made this an extremely uncommon presentation. Our patient&amp;rsquo;s neurologic symptoms were believed to have been caused by a recent traumatic clavicular injury sustained two weeks prior, which subsequently led to vascular insult. Conclusion: Cerebrovascular accidents are an important cause of morbidity and mortality in pediatric patients. Cerebrovascular accidents in children are most often secondary to congenital causes; however, care should be taken to assess for acquired causes, such as trauma to major blood vessels. While rarely implicated in traumatic injuries, arterial structures posterior to the medial clavicle can result in severe complications.

E048 Spinal gout: an unusual cause of paraplegia

Abstract Background/Aims Gout is a common inflammatory arthritis caused by the deposition of monosodium urate crystals. Gout usually causes peripheral joint arthritis. Axial involvement is likely under-recognised, affecting an estimated 10-20% of gout patients. Spinal gout is an established phenomenon in patients with chronic tophaceous gout and sustained hyperuricaemia. Gout can affect any segment of the spine. Clinical presentation of spinal gout is variable including back pain, radiculopathy and cord compression. Due to its nonspecific presentation, it can be confused for other spinal pathologies such as epidural abscess, malignancy, spondylodiscitis and vertebral osteomyelitis. Methods We present a case report of a young male with tophaceous gout of the thoracic spine. Results A 37 year old man presented with 4 day history of acute thoracic back pain followed by flaccid lower limb paralysis. He was morbidly obese (BMI 60) and had a 13-year history of poorly controlled gout with most recent uric acid being 627. He had previously declined urate lowering therapy but commenced allopurinol treatment one month prior to admission. On examination power was 0/5 in both lower limbs with absent reflexes and a T12 sensory level. MRI showed multi-level facet joint arthropathy. An epidural collection was present at T8-10, causing complete occlusion of the vertebral artery. He underwent an urgent posterior thoracic decompression. ‘White cheese like epidural pus’ was removed and he was initially treated as facet joint infection. He had ongoing fevers [&amp;gt;38.5C], despite empirical antibiotics, and C-reactive-protein was persistently elevated [highest at 360mg/L]. Uric acid was 423. Enrichment culture of the epidural collection and serial blood cultures were negative. Repeat MRI of spine did not demonstrate any reoccurrence of collection. Subsequently the histology of the epidural collection was reported as characteristic of gout with ‘amorphous material and giant cells’. No urate crystals were identified as the sample was prepared with formalin, which would have dissolved any crystals present. He was referred to rheumatology who identified synovitis in his hands, wrist and elbows, consistent with active polyarticular gout. There were small tophi present on his heels and pinna. The patient was commenced on oral prednisolone and allopurinol was rapidly up-titrated. Unfortunately, the patient did not recover neurological function. Conclusion We present a unique case of acutely presenting tophaceous thoracic spinal gout causing irreversible paraplegia in a young patient, mimicking an epidural abscess. Our patient had hyperuricaemia for over 10 years without treatment, raising his risk of axial complications. A high index of suspicion for spinal gout is needed for patients presenting with acute back pain and neurological symptoms with a history of chronic gout. This case highlights diagnostic challenges in identifying spinal gout and the importance of treating tophaceous gout early to prevent devastating long-term complications. Disclosure C.A. Zollinger-Read: None. M. Cox: None. R. Kumari: None.

Eculizumab for Shiga‐toxin‐induced hemolytic uremic syndrome in adults with neurological involvement

AbstractThe role of eculizumab in treating Shiga‐toxin‐producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) patients with neurological involvement remains unclear. We describe two distinctly different STEC‐HUS patients with neurologic involvement successfully managed with eculizumab, and perform a literature review of all published cases. Both patients had complete resolution of neurological symptoms after initiation of eculizumab. Eighty patients with STEC‐HUS treated with eculizumab were identified in the literature, 68.7% had complete resolution of neurological symptoms. Based on our experience and literature review, three prevailing themes were noted: 1) Early eculizumab administration optimized neurological outcomes, 2) Symptom resolution may not be immediate, neurological symptoms may initially worsen before improvement, and 3) Plasma exchange yielded no benefit. Early administration of eculizumab may reverse neurotoxicity in patients with STEC‐HUS.

Phenotypic Variability Related to Mutations in Riboflavin Transporter in Brazilian Children: Pediatric Case Series

AbstractBrown–Vialetto–Van Laere syndrome or riboflavin transporter deficiency is a rare and genetically determined condition that results in a spectrum of neurological signs and symptoms from generalized muscle weakness to cranial nerve involvement with medullary symptoms and respiratory failure. Most patients have SLC52A3 gene biallelic variants, but some of them may have impairment of SLC52A2 gene, both related to the cell transport of riboflavin. We report the case of three unrelated Brazilian patients under 18 years of age with this diagnosis confirmed by molecular genetic sequencing. We observed that the clinical manifestations found were compatible with those already described in the literature by age group. Unusual findings of retinitis pigmentosa and immunodeficiency were identified related to pathogenic variants in the SLC52A2 gene. All patients received riboflavin replacement at a therapeutic dose without gastrointestinal intolerance and with clinical improvement after starting treatment.

Perinatal outcome in anti-NMDAr encephalitis during pregnancy-a systematic review with individual patients' data analysis.

Anti-N-methyl-D-aspartate receptor (NMDAr) antibody encephalitis is an autoimmune disorder characterized by synaptic NMDAr current disruption and receptor hypofunction, often affecting women during pregnancy. Clinical manifestations associated with anti-NMDAr encephalitis can occur both in the mother and fetus. We generated a systematic search of the literature to identify epidemiological, clinical, and serological data related to pregnant women with anti-NMDAr encephalitis and their children, analyzing the fetal outcomes. We examined the age and neurologic symptoms of the mothers, the presence of an underlying tumor, immunotherapies used during pregnancy, duration of the pregnancy, and type of delivery. Data from 41 patients were extrapolated from the included studies. Spontaneous interruption of pregnancy, premature birth, and cesarean section were reported in pregnant women with NMDAr encephalitis. Several fetal and neonatal symptoms (e.g., movement disorders, spina bifida, poor sucking, respiratory distress, cardiac arrhythmias, infections, icterus, hypoglycemia, and low birth weight) depending on the mother's serum anti-NR1 concentration were also reported. We characterized the outcomes of children born from mothers with anti-NMDAr encephalitis, analyzing the pivotal risk factors related to pregnancy and maternal disorder. Neuropsychiatric involvement seems strictly related to pathogenic NMDAr antibodies detected in maternal and/or neonatal serum. These findings clarify a complex condition to manage, outlining the risks associated with pregnant women with anti-NMDAr encephalitis and also providing a concrete guide for therapeutic strategies to prevent potential harm to the fetus and the child's neurodevelopment.

Rituximab in non-systemic vasculitic neuropathy: a single-center experience.

This case series reports clinical features and outcome of four patients with non-systemic vasculitic neuropathy (NSVN) treated with the anti-CD20 agent rituximab. Clinical, electrophysiological and biopsy data were retrospectively obtained and evaluated. Only patients with pathological definite or probable NSVN were included. Extensive clinical and laboratory work-up excluded systemic vasculitis. Follow-up data for at least 12months and up to five years is provided. Outcome of the patients was assessed using the MRC-Sum Score, Prineas Score and Neurological Symptom Score. Two of four patients treated with rituximab achieved disease remission and one patient remained stable under anti-CD20 therapy after a required treatment switch due to toxic side effects of cyclophosphamide. One patient deteriorated under rituximab induction. Rituximab was well tolerated in all patients. Anti-CD20 therapy might be an alternative in NSVN patients requiring further treatment escalation or treatment switch due to side effects of corticosteroids or cyclophosphamide.

Dolutegravir and Folic Acid Interaction during Neural System Development in Zebrafish Embryos.

Dolutegravir (DTG) is one of the most prescribed antiretroviral drugs for treating people with HIV infection, including women of child-bearing potential or pregnant. Nonetheless, neuropsychiatric symptoms are frequently reported. Early reports suggested that, probably in relation to folic acid (FA) shortage, DTG may induce neural tube defects in infants born to women taking the drug during pregnancy. Subsequent reports did not definitively confirm these findings. Recent studies in animal models have highlighted the association between DTG exposure in utero and congenital anomalies, and an increased risk of neurologic abnormalities in children exposed during in utero life has been reported. Underlying mechanisms for DTG-related neurologic symptoms and congenital anomalies are not fully understood. We aimed to deepen our knowledge on the neurodevelopmental effects of DTG exposure and further explore the protective role of FA by the use of zebrafish embryos. We treated embryos at 4 and up to 144 h post fertilization (hpf) with a subtherapeutic DTG concentration (1 μM) and observed the disruption of the anterior-posterior axis and several morphological malformations in the developing brain that were both prevented by pre-exposure (2 hpf) and rescued by post-exposure (10 hpf) with FA. By whole-mount in situ hybridization with riboprobes for genes that are crucial during the early phases of neurodevelopment (ntl, pax2a, ngn1, neurod1) and by in vivo visualization of the transgenic Tg(ngn1:EGFP) zebrafish line, we found that DTG induced severe neurodevelopmental defects over time in most regions of the nervous system (notochord, midbrain-hindbrain boundary, eye, forebrain, midbrain, hindbrain, spinal cord) that were mostly but not completely rescued by FA supplementation. Of note, we observed the disruption of ngn1 expression in the dopaminergic regions of the developing forebrain, spinal cord neurons and spinal motor neuron projections, with the depletion of the tyrosine hydroxylase (TH)+ dopaminergic neurons of the dorsal diencephalon and the strong reduction in larvae locomotion. Our study further supports previous evidence that DTG can interfere with FA pathways in the developing brain but also provides new insights regarding the mechanisms involved in the increased risk of DTG-associated fetal neurodevelopmental defects and adverse neurologic outcomes in in utero exposed children, suggesting the impairment of dopaminergic pathways.