eEF1A2 siRNA Suppresses MPP+-Induced Activation of Akt and mTOR and Potentiates Caspase-3 Activation in a Parkinson's Disease Model.

The tissue-specific protein eEF1A2 has been linked to the development of neurological disorders. The role of eEF1A2 in the pathogenesis of Parkinson's disease (PD) has yet to be investigated. The aim of this study was to determine the potential neuroprotective effects of eEF1A2 in an MPP+ model of PD. Differentiated SH-SY5Y cells were transfected with eEF1A2 siRNA, followed by MPP+ exposure. The expression of p-Akt1 and p-mTORC1 was determined using Western blotting. The expression of p53, Bax, Bcl-2, and caspase-3 was evaluated using qRT-PCR. Cleaved caspase-3 levels and Annexin V/propidium iodide flow cytometry were used to determine apoptosis. The effects of PI3K inhibition were examined. The results showed that eEF1A2 siRNA significantly reduced the eEF1A2 expression induced by MPP+. MPP+ treatment activated Akt1 and mTORC1; however, eEF1A2 knockdown suppressed this activation. In eEF1A2-knockdown cells, MPP+ treatment increased the expression of p53 and caspase-3 mRNA levels as well as increased apoptotic cell death when compared to MPP+ treatment alone. In cells exposed to MPP+, upstream inhibition of the Akt/mTOR pathway, by either LY294002 or wortmannin, inhibited the phosphorylation of Akt1 and mTORC1. Both PI3K inhibitors increased eEF1A2 expression in cells, whether or not they were also treated with MPP+. In conclusion, eEF1A2 may function as a neuroprotective factor against MPP+, in part by regulating the Akt/mTOR pathway upstream.

Caffeine Potentiates Ethanol-Induced Neurotoxicity Through mTOR/p70S6K/4E-BP1 Inhibition in SH-SY5Y Cells.

Caffeine is a popular psychostimulant, which is frequently consumed with ethanol. However, the effects of caffeine on neuronal cells constantly exposed to ethanol have not been investigated. Apoptosis and oxidative stress occurring in ethanol-induced neurotoxicity were previously associated with decreased phosphorylation of the mTOR/p70S6K/4E-BP1 signaling proteins. Evidence also suggested that caffeine inhibits the mTOR pathway. In this study, human SH-SY5Y neuroblastoma cells were exposed to caffeine after pretreatment for 24 hours with ethanol. Results indicated that both ethanol and caffeine caused neuronal cell death in a dose- and time-dependent manner. Exposure to 20-mM caffeine for 24 hours magnified reduced cell viability and enhanced apoptotic cell death induced by 200 mM of ethanol pretreatment. The phosphorylation of mTOR, p70S6K, and 4E-BP1 markedly decreased in cells exposed to caffeine after ethanol pretreatment, associated with a decrease of the mitochondrial membrane potential (ΔΨm). These findings suggested that caffeine treatment after neuronal cells were exposed to ethanol resulted in marked cell damages, mediated through enhanced inhibition of mTOR/p70S6K/4E-BP1 signaling leading to impaired ΔΨm and, eventually, apoptotic cell death.

Intravenous thrombolysis in Thai patients with acute ischemic stroke: role of aging.

BACKGROUND: Intravenous thrombolysis is a standard treatment in eligible acute ischemic stroke (AIS) patients. However, the advisability of treating patients >80 years of age is still debated. The aim of this study was to evaluate the role of aging on the outcomes in Thai patients treated with intravenous thrombolysis. METHODS: Patients with AIS treated with intravenous recombinant tissue-plasminogen activator (rtPA) between June 2007 and November 2010 were included. The demographics and measured outcome variables were compared between patients ≤70 and >70 years of age. Patients were also classified into 4 subgroups by the age ranges: ≤60 years, 61 to 70 years, 71 to 80 years, and ≥81 years of age. RESULTS: Two hundred sixty-one patients were included. Seventeen patients (6.5%) were >80 years old. Higher mortality (20.2% vs 5.1%; P < .001) and symptomatic intracerebral hemorrhage (7.7% vs 1.2%; P = .004) were found in the patients >70 years of age when compared with younger patients, and the rate of favorable outcome was lower (38.1% vs 55.4%; P = .010). Higher mortality rates were seen with increasing age: 3%, 8%, 20%, and 21% in patients aged ≤60, 61 to 70, 71 to 80, and ≥81 years of age, respectively. CONCLUSIONS: Thai stroke patients >70 years of age may carry a higher risk of mortality when treated with intravenous rtPA compared to patients ≤70 years of age.

Episodic Headache, Periorbital Pain, and Multifocal Paresthesias as Presenting Symptoms of Central Neurocytoma: A Case Report.

Central neurocytoma (CN) is a rare intraventricular tumor. The common presenting symptoms of CN are headache, vomiting, and visual disturbance, which results from increased intracranial pressure. This report presents a case of CN with unusual clinical presentations. A 25-year-old female with CN presented with a one-day history of unilateral headache, ipsilateral periorbital pain, multifocal paresthesias, and vomiting. Magnetic resonance images showed an intraventricular mass with a soap-bubble appearance and numerous cystic areas typical for CN, causing obstructive hydrocephalus and a midline shift. After one night of rest, her headache, periorbital pain, and paresthesias disappeared. It is possible that the tumor could be mobile with regard to the patient's head position, causing occasional obstruction of the foramen of Monro. Due to the tumor size, which was larger than 4 centimeters, the surgical approach with either gross tumor resection or subtotal resection plus adjuvant radiotherapy should be carefully considered.

Evaluation of the Combination of Metformin and Rapamycin in an MPP+-Treated SH-SY5Y Model of Parkinson's Disease.

Metformin (MET) and rapamycin (RAPA) have been reported to protect against neurodegeneration in cellular and animal models of Parkinson's disease (PD). MET, which is a first-line drug for type 2 diabetes, and RAPA are known as mTORC1 inhibitors. MET also acts as an AMPK activator, which leads to the inhibition of mTORC1 activity. mTORC1 is a downstream target of Akt signaling. Inactivation of Akt/mTORC1 and its downstream S6K1 can promote autophagy, a process involved in PD pathogenesis. Based on their mechanisms and potential benefits, we evaluated the potential protective effect of pretreatment with combinations of MET and RAPA in a 1-methyl-4-phenylpyridinium ion (MPP+)-treated SH-SY5Y neuronal cell model of PD. The results showed that MET and RAPA combinations lowered cell viability after exposure to MPP+. Increased LC3-II levels by MPP+ were not altered by MET and RAPA pretreatment. In normal neuronal cells, MET and RAPA pretreatment inhibited the phosphorylation of both Akt and S6K1, and the phosphorylation remained suppressed after MPP+ exposure. These findings suggest that when cells were exposed to MPP+, suppressed phosphorylation of both Akt and S6K1 by the MET and RAPA combination may lead to an inappropriate autophagic response, resulting in increased cell death.

Early Flare-Ups of Myasthenia Gravis After Thoracoscopic Thymectomy in a Patient Recently Receiving BNT162b2 mRNA COVID-19 Vaccination.

Myasthenia gravis (MG) is an autoimmune disorder characterized by abnormal neuromuscular transmission. The thymus is believed to play a key role in the pathogenesis of MG, and thymectomy has been an optional treatment for the disease. Relapse of MG after thymectomy has been reported. Exacerbations and new onset of MG following COVID-19 vaccination have also been documented. This report presents a case of a stable MG patient with recent COVID-19 vaccination experiencing flare-ups of symptoms shortly after video-assisted thoracoscopic (VATS) thymectomy. A 31-year-old female received the second dose of the BNT162b2 mRNA COVID-19 vaccine eight days before thymectomy and developed flare-ups of symptoms four days after the surgery. Although the substantial link between MG exacerbations post-thymectomy and pre-thymectomy COVID-19 vaccination cannot be concluded, this observation warrants further research.

eEF1A2 knockdown impairs neuronal proliferation and inhibits neurite outgrowth of differentiating neurons.

OBJECTIVES: The translation elongation factor-1, alpha-2 (eEF1A2) plays an important role in protein synthesis. Mutations in this gene have been described in individuals with neurodevelopmental disorders. Here, we silenced the expression of eEFA2 in human SH-SY5Y neuroblastoma cells and observed its roles in neuronal proliferation and differentiation upon induction with retinoic acid. METHODS: eEF1A2 were silenced using siRNA transfection. Cell proliferation was qualitatively evaluated by Ki-67 immunocytochemistry. Neuronal differentiation was induced with retinoic acid for 3, 5, 7 and 10 days. Neurite length was measured. The expression of microtubule-associated protein 2 (MAP2) was analyzed by western blotting. Tyrosine hydroxylase expression was visualized by immunofluorescence. Cytotoxicity to a neurotoxin, 1-methyl-4-phenylpyridinium (MPP+), was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and western blotting of cleaved caspase-3. RESULTS: eEF1A2 knockdown suppressed the proliferative activity of undifferentiated SH-SY5Y cells as shown by decreased Ki-67 immunostaining. Upon retinoic acid-induction, differentiated neurons with eEF1A2 knockdown exhibited shorter neurite length than untransfected cells, which was associated with the reduction of tyrosine hydroxylase and suppression of MAP2 at 10 days of differentiation. eEF1A2 knockdown decreased the survival of neurons, which was clearly observed in undifferentiated and short-term differentiated cells. Upon treatment with MPP+, cells with eEF1A2 knockdown showed a further reduction in cell survival and an increase of cleaved caspase-3 protein. CONCLUSIONS: Our results suggest that eEF1A2 may be required for neuronal proliferation and differentiation of SH-SY5Y cells. Increased cell death susceptibility against MPP+ in eEF1A2-knockdown neurons may imply the neuroprotective role of eEF1A2.

Early outcome after intravenous thrombolysis in patients with acute ischemic stroke.

BACKGROUND: Patients with acute ischemic stroke who had early neurological improvement had better functional outcome. The purpose of this study was to determine factors associated with early clinical improvement and early worsening in patients with acute ischemic stroke treated with intravenous thrombolysis. PATIENTS AND METHODS: Patients treated with intravenous recombinant tissue plasminogen activator (rtPA) between August 2008 and November 2010 were the subjects of this study. Early improvement was defined by marked, clinical improvement or complete recovery at 24 h (National Institutes of Health Stroke Scale (NIHSS) 0-4 at 24 h). Early worsening was defined by an increase in NIHSS ≥1 from baseline. The baseline characteristics were compared between patients with and without outcome of interest. RESULTS: Of the 203 patients studied, 19 (9.4%) patients had complete recovery and 68 (33.5%) patients had marked clinical improvement (NIHSS 1-4) at 24 h. Most patients with early clinical improvement (86%) had favorable outcome at three months. Of the 22 (10.8%) patients who had early clinical worsening, only three (14%) patients achieved favorable outcome at three months and six (29%) patients died. Multivariate analysis revealed that older age (≥70 years old) (odd ratio (OR) 0.498, P = 0.049), severe stroke (NIHSS ≥15) (OR 0.154, P < 0.0001) and having intracerebral hemorrhage (ICH) (OR 0.364, P = 0.032) were inversely associated with early improvement. History of transient ischemic attack (TIA) (OR 7.724, P = 0.043) and ICH (OR 4.477, P = 0.008) were related to early worsening. CONCLUSIONS: The presence of early clinical improvement or worsening within 24 h after treatment with rtPA had major impact on the outcome at three months.

Effects of eEF1A2 knockdown on autophagy in an MPP+-induced cellular model of Parkinson's disease.

1-Methyl-4-phenylpyridinium ion (MPP+) is widely used to induce a cellular model of Parkinson's disease (PD) in dopaminergic cell lines. Downregulation of the protein translation elongation factor 1 alpha (eEF1A) has been reported in the brain tissue of PD patients. eEF1A2, an isoform of eEF1A, is associated with lysosome biogenesis that involves the autophagy process. However, the role of eEF1A2 on autophagic activity in PD has not been elucidated. In this work, we investigated the role of eEF1A2 on autophagy using eEF1A2 siRNA knockdown in differentiated SH-SY5Y neuronal cells treated with MPP+. We found that eEF1A2 was upregulated in differentiated cells, which could be silenced by eEF1A2 siRNA. Significantly, cells treated with MPP+ after eEF1A2 knockdown showed a decreased number of LC3 puncta, decreased LC3-II/LC3-I ratio, and decreased phospho-Beclin-1, compared to the MPP+ alone group. These cells showed extensive areas of mitochondria damage, with a reduction of mitochondrial membrane potential, but reduced mitophagy as indicated by the reduced colocalization of LC3 puncta with damaged mitochondria. Cells with eEF1A2 siRNA plus MPP+ treatment aggravated α-synuclein accumulation but reduced colocalization with LC3. As a result, eEF1A2 knockdown decreased viability, increased apoptotic nuclei, increased caspase-3/7 activation and increased cleaved caspase-3 when cells were treated with MPP+. These results suggest that eEF1A2 is essential for dopaminergic neuron survival against MPP+, in part through autophagy regulation.

Neuroblastoma Cell Death Induced by eEF1A2 Knockdown Is Possibly Mediated by the Inhibition of Akt and mTOR Phosphorylation.

Background The protein kinase B/mammalian target of the rapamycin (Akt/mTOR) pathway is one of the most potent prosurvival signaling cascades that is constitutively active in neuroblastoma. The eukaryotic translation elongation factor-1, alpha-2 (eEF1A2) protein has been found to activate the Akt/mTOR pathway. However, there is a lack of data on the role of eEF1A2 in neuroblastoma. The present study investigated the effect of eEF1A2 silencing on the viability of neuroblastoma cells and its possible signaling. Materials and Methods: Human SH-SY5Y neuroblastoma cells were transfected with small interfering RNA (siRNA) against eEF1A2. After 48 h of transfection, cell viability was assessed using an MTT assay. The mRNA expression of p53, Bax, Bcl-2, caspase-3 and members of the phosphoinositide 3-kinases (PI3K)/Akt/mTOR pathway was determined using quantitative real-time RT-PCR (qRT-PCR). The protein expression of Akt and mTOR was measured using Western blot analysis. Results: eEF1A2 knockdown significantly decreased the viability of neuroblastoma cells. No significant changes were observed on the expression of p53, Bax/Bcl-2 ratio, and caspase-3 mRNAs; however, the upregulated trends were noted for the p53 and Bax/Bcl-2 ratio. eEF1A2 knockdown significantly inhibited the phosphorylation of both Akt and mTOR. Almost all of the class I (PIK3CA, PIK3CB, and PIK3CD) and all of the class II PI3K genes were slightly increased in tumor cells with eEF1A2 knockdown. In addition, a slightly decreased expression of the Akt2, mTORC1, and mTORC2 was observed. Conclusion: eEF1A2 knockdown induced neuroblastoma cell death, in part through the inhibition of Akt and mTOR, suggesting a potential role of eEF1A2 as a molecular target for neuroblastoma therapy.

Aberrant proteins expressed in skin fibroblasts of Parkinson's disease patients carrying heterozygous variants of glucocerebrosidase and parkin genes.

Parkinson's disease (PD) is a neurodegenerative disorder that affects movement, and its development is associated with environmental and genetic factors. Genetic variants in GBA and PARK2 are important risk factors implicated in the development of PD; however, their precise roles have yet to be elucidated. The present study aimed to identify and analyse proteins from the skin fibroblasts of patients with PD carrying heterozygous GBA and PARK2 variants, and from healthy controls. Liquid chromatography coupled with tandem mass spectrometry and label-free quantitative proteomics were performed to identify and compare differential protein expression levels. Moreover, protein-protein interaction networks were assessed using Search Tool for Retrieval of Interacting Genes analysis. Using these proteomic approaches, 122 and 119 differentially expressed proteins from skin fibroblasts of patients with PD carrying heterozygous GBA and PARK2 variants, respectively, were identified and compared. According to the results of protein-protein interaction and Gene Ontology analyses, 14 proteins involved in the negative regulation of macromolecules and mRNA metabolic processes, and protein targeting to the membrane exhibited the largest degree of differential expression in the fibroblasts of patients with PD with a GBA variant, whereas 20 proteins involved in the regulation of biological quality, NAD metabolic process and cytoskeletal organization exhibited the largest degree of differential expression in the fibroblasts of patients with PD with a PARK2 variant. Among these, the expression levels of annexin A2 and tubulin ß chain, were most strongly upregulated in the fibroblasts of patients with GBA-PD and PARK2-PD, respectively. Other predominantly expressed proteins were confirmed by western blotting, and the results were consistent with those of the quantitative proteomic analysis. Collectively, the results of the present study demonstrated that the proteomic patterns of fibroblasts of patients with PD carrying heterozygous GBA and PARK2 variants are different and unique. Aberrant expression of the proteins affected by these variants may reflect physiological changes that also occur in neurons, resulting in PD development and progression.

Meralgia paresthetica-like syndrome may be caused by transient lumbar nerve root injury without definite compression: a case report.

Meralgia paresthetica is a well-known sensory syndrome describing paresthesia and/or anesthesia in the anterolateral aspect of the thigh that is supplied by the lateral femoral cutaneous nerve. Compression of the nerve usually occurs at the point where it passes between the anterior superior iliac spine and the inguinal ligament. Proximal lesions such as lumbar radiculopathy, lumbar disc herniation, and spinal stenosis have been reported to cause meralgia paresthetica-like syndrome. These proximal lesions directly injure L2 and L3 spinal nerve roots and cause a constant compression of the nerve roots. The presented paper introduces a hypothesis that this syndrome can be caused by transient injury to the L2 and L3 nerve roots by the upper adjacent disc bulge without definite compression. This hypothesis is supported by lumbar spine magnetic resonance imaging of a patient presenting with a meralgia paresthetica-like symptom during bending forward and twisting of the body, showing no L2/L3 herniated disc but mildly posterior bulging of T12/L1 disc. This hypothesis emphasizes an importance of appropriate postures in patients with meralgia paresthetica-like symptoms in order to prevent long-term morbidity.

Inhibition of the antioxidant enzyme PRDX1 activity promotes MPP+-induced death in differentiated SH-SY5Y cells and may impair its colocalization with eEF1A2.

AIM: eEF1A2 is highly expressed in postmitotic cells and has been reported to interact with the antioxidant enzyme peroxiredoxin 1 (PRDX1). PRDX1 is involved in motor neuron differentiation. Here, we studied the relationship between eEF1A2 and PRDX1 during dopaminergic neuron differentiation, and examined their possible association in an oxidative stress model of Parkinson's disease (PD). MAIN METHODS: Expression of eEF1A2 and PRDX1 in SH-SY5Y cells at various durations of retinoic acid (RA) induction was detected using qRT-PCR, Western blotting and immunofluorescence. Neurons of 10-day differentiation were treated with the PRDX1 inhibitor H7, MPP+ and H7 plus MPP+. The cell viability, the amounts of apoptotic nuclei, DHE signals, and the expression of p53, p-Akt and p-mTOR were determined. The colocalization of eEF1A2 and PRDX1 was visualized using confocal microscopy. KEY FINDINGS: eEF1A2 gradually increased after RA-induced differentiation of SH-SY5Y cells, while PRDX1 protein gradually decreased. MPP+ treatment increased eEF1A2 in both undifferentiated and differentiated neurons; however, PRDX1 appeared to elevate only in mature neurons. The inhibition of the PRDX1 activity with H7 promoted MPP+-induced cell death, as evidenced by decreased cell viability, increased apoptotic nuclei, increased the DHE signal, and increased p53. However, H7 induced the activation of the prosurvival Akt and mTOR in MPP+-treated cells. Besides, a colocalization of eEF1A2 and PRDX1 was evidenced in MPP+-treated neurons. This colocalization was possibly prevented by inhibiting the PRDX1 activity, resulting in aggravated neuronal death. SIGNIFICANCE: Our results suggest that the possible association between eEF1A2 and PRDX1 may be a promising target for modifying neuronal death in PD.

Downregulation of eEF1A/EFT3-4 Enhances Dopaminergic Neurodegeneration After 6-OHDA Exposure in C. elegans Model.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the aggregation of α-synuclein protein and selective death of dopaminergic (DA) neurons in the substantia nigra of the midbrain. Although the molecular pathogenesis of PD is not completely understood, a recent study has reported that eukaryotic translation elongation factor 1 alpha (eEF1A) declined in the PD-affected brain. Therefore, the roles of eEF1A1 and eEF1A2 in the prevention of DA neuronal cell death in PD are aimed to be investigated. Herein, by using Caenorhabditis elegans as a PD model, we investigated the role of eft-3/eft-4, the worm homolog of eEF1A1/eEF1A2, on 6-hydroxydopamine (6-OHDA)-induced DA neuron degeneration. Our results demonstrated that the expressions of eft-3 and eft-4 were decreased in the 6-OHDA-induced worms. RNA interference (RNAi) of eft-3 and eft-4 resulted in dramatic exacerbation of DA neurodegeneration induced by 6-OHDA, as well as aggravated the food-sensing behavior, ethanol avoidance, and decreased lifespan when compared with only 6-OHDA-induced worms. Moreover, downregulation of eft-3/4 in 6-OHDA-induced worms suppressed the expression of the anti-apoptotic genes, including PI3K/age-1, PDK-1/pdk-1, mTOR/let-363, and AKT-1,2/akt-1,2, promoting the expression of apoptotic genes such as BH3/egl-1 and Caspase-9/ced-3. Collectively, these findings indicate that eEF1A plays an important role in the 6-OHDA-induced neurodegeneration through the phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (Akt)/mammalian target of rapamycin (mTOR) pathway and that eEF1A isoforms may be a novel and effective pro-survival factor in protective DA neurons against toxin-induced neuronal death.

Bone marrow-derived mesenchymal stem cells for the treatment of ischemic stroke.

Bone marrow-derived mesenchymal stem cells (MSCs) have great potential as therapeutic agents in stroke management, since they are easily accessible and can be rapidly expanded ex vivo for autologous transplantation. Increasing evidence suggests that bone marrow cells migrate throughout the brain and differentiate into neurons and glial cells. Both non-human and human MSCs have been used to treat stroke in murine models with satisfactory results. Several factors, such as transdifferentiation, induction of neurogenesis and angiogenesis, neuroprotection, and activation of endogenous neurorestorative processes, contribute to the benefits of MSCs in the ischemic brain. Many variables, including types of MSCs, cell dose, timing of treatment, route of cell delivery, and characteristics of stroke patients, influence the efficacy of MSC treatment of stroke. Although the first trials of autologous MSC therapy in stroke patients showed promising results, the optimal approach for different clinical settings has yet to be determined. The fundamental properties of MSCs and their potential short-term and long-term toxicities also need to be determined before moving forward to use of these cells in clinical practice.

Metformin restores the mitochondrial membrane potentials in association with a reduction in TIMM23 and NDUFS3 in MPP+-induced neurotoxicity in SH-SY5Y cells.

SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP+) develop mitochondrial dysfunction and other cellular responses similar to those that occur in the dopaminergic neurons of patients with Parkinson's disease (PD). It has been shown in animal models of PD that neuronal death can be prevented by metformin, an anti-diabetic drug. Both MPP+ and metformin inhibit complex I of the mitochondrial respiratory chain. It has been reported that decreased levels of the mitochondrial inner membrane proteins TIMM23 and NDUFS3 are associated with the increased generation of reactive oxygen species and mitochondrial depolarization. In the present study, we investigated the effects of metformin on MPP+-induced neurotoxicity using differentiated human SH-SY5Y neuroblastoma cells. The results showed that pretreatment with metformin increased the viability of MPP+-treated SH-SY5Y cells. Pretreatment with metformin decreased the expression of TIMM23 and NDUFS3 in MPP+-treated SH-SY5Y cells. This was correlated with reduced mitochondrial fragmentation and an improvement in the mitochondrial membrane potential. These results suggest that metformin pretreatment protects against MPP+-induced neurotoxicity, and offer insights into the potential role of metformin in protecting against toxin-induced parkinsonism.

Sports-related internal carotid artery dissection: pathogenesis and therapeutic point of view.

BACKGROUND: Extracranial and intracranial internal carotid artery (ICA) dissections following sports-related activities have been reported as a result of blunt traumatic injuries. The incidence of carotid artery dissection in sports is not known. Failure of physicians to suspect a dissection in the context of a minor injury or to obtain a history from the patient can lead to permanent neurologic deficits. REVIEW SUMMARY: The presentation of this entity is variable. We present 2 cases of ICA dissection with differences in causative mechanism and management in order to emphasize the importance of a physician's awareness, and we review the literature on this subject. CONCLUSIONS: Pathogenesis of sports-related ICA dissections may be multifactorial. Structural aberrations in the arterial walls and defective connective tissue components are assumed in some patients. Several genes have been shown to be candidates for the connective tissue aberrations. Since sports-related ICA dissection can occur extracranially or intracranially, the combined use of proper diagnostic techniques that provides information on the extracranial and intracranial vessels is recommended. Although the mechanisms and treatment modalities for intracranial and extracranial dissections might be different, the initial steps of evaluation and stabilization should be standardized for both. There is no randomized controlled study for the best treatment or management of ICA dissection.