Characteristics and clinical course of patients referred to the NST.

Background and aims: The nutrition support team (NST) comprises doctors, nutritionists, pharmacists, and nurses who provide intensive nutritional treatment designed for each patient by evaluating their nutritional status of hospitalized patients. This study aimed to identify the clinical characteristics of patients referred to the NST among those admitted to a tertiary hospital and to understand the factors affecting their clinical course and changes in pressure sore grades. Methods: This study included 1,171 adult patients aged 18 years or older referred to the NST at a tertiary hospital in a metropolitan city between 1 January 2019 and 31 December 2020. Patients were divided into five age groups, neuro department and non-neuro department, those treated in the intensive care unit (ICU), and those not treated in the ICU. Patients were also compared based on the presence of pressure sores at the time of NST referral and changes in pressure sore grades at the first time of NST referral and discharge (improved pressure sores, no change in pressure sores, and aggravated pressure sores). In addition, this study examined the factors affecting changes in pressure sore grades. Results: As age increased, the proportion of both low albumin levels and pressure sores significantly increased (p < 0.001), and the neuro department showed a significantly lower proportion of low albumin levels and pressure sores (p < 0.001). The proportion of patients with pressure sores was higher (64.9%), and this patient group showed significantly higher rates of low albumin levels (p < 0.001) and treatment in the ICU (p < 0.001). The group with aggravated pressure sore grades had a significantly higher proportion of patients in the surgery department (p = 0.009) and those treated in the ICU (p < 0.001). Admission to the surgery department was a factor that aggravated the grade of pressure sores [adjusted odds ratio (aOR) = 1.985, 95% confidence interval (CI) = 1.168-3.371]. When patients were not treated in the ICU, the grade of the pressure sores was less likely to worsen (aOR = 0.364, 95% CI = 0.217-0.609). Conclusion: Pressure sores and low albumin levels are closely related, and the risk of developing and aggravating pressure sores is particularly high in patients in the surgery department and those receiving ICU treatment. Therefore, it is necessary to actively implement NST referral to ensure that overall nutrition, including albumin, is well supplied, especially for patients in the surgery department and treated in the ICU, as they are at high risk of pressure sore development and aggravation. Moreover, since low albumin levels frequently occur in elderly patients, it is necessary to consider including the elderly in the indications for referral to the NST.

Sex differences and risk factors in recurrent ischemic stroke.

Introduction: Recurrent ischemic stroke (RIS) is associated with increased mortality and poor outcomes. Therefore, secondary prevention is critical for reducing the risk of recurrent stroke. Previous studies have found sex differences in risk factors in patients with first-ever stroke; however, the results have been inconsistent for recurrent stroke. Therefore, this study aimed to investigate whether there are significant sex differences in the clinical characteristics and risk factors for recurrent ischemic stroke. Methods: We retrospectively studied 787 patients with recurrent ischemic stroke after first-ever stroke confirmation using magnetic resonance imaging (MRI) after visiting a regional tertiary hospital between 2014 and 2020. Demographic characteristics, laboratory findings, and risk factors were compared between the male and female patients. In addition, multivariate logistic regression was performed to identify the independent factors associated with stroke recurrence in male patients. Results: Among the 787 patients, 466 (59.2%) were males. Males were younger than females (67.6 vs. 71.9 years). Females had higher rates of hypertension, diabetes mellitus, dyslipidemia, and overweight than those of males. However, the alcohol drinking and smoking rate were significantly higher in males than that in females. There were no statistically significant sex-based differences in the laboratory findings. Among males, hypertension, alcohol drinking, smoking and dyslipidemia was a significant risk factor for ischemic stroke recurrence. Conclusion: Hypertension and dyslipidemia were significant risk factors of recurrent ischemic stroke in both genders. Smoking and alcohol drinking were significant risk factors associated with ischemic stroke recurrence in males. Therefore, smoking cessation and alcohol abstinence are recommended after the first stroke to prevent recurrent ischemic stroke especially for males. Diabetes was a significant risk factor of ischemic stroke recurrence in females. More extensive studies are needed to understand the causal relationship of each factors with ischemic stroke recurrence according to sex differences and specification of preventive management is needed.

Changes of Atherosclerotic Plaque in Cerebral Artery Stenosis According to High-Resolution MR Imaging.

Atherosclerosis can affect multiple arteries, and result in stroke and heart disease. Clinical and conventional imaging is insufficient to predict the progression of atherosclerosis. This study investigates risk factors that rely on high-resolution magnetic resonance imaging (HR-MRI). Patients with cerebral artery stenosis who had undergone HR-MRI at least twice were included. The demographics, risk factors, and proportion of patients with cerebral artery stenosis were investigated. The association between atherosclerotic plaque characteristics and the progression or regression of artery stenosis was also analyzed. A total of 42 patients were analyzed, with a median follow-up of 16.88 ± 12.53 months. The mean age of all subjects was 63.1 ± 9.15 years, and 83.3% of them were male. The incidences of stenosis of the basilar, proximal internal carotid, and middle cerebral arteries were 21.4%, 61.9%, and 16.7%, respectively. Intraplaque hemorrhage (IPH) was detected in 20 (47.6%) patients. Multivariate analysis showed that age (odds ratio (OR), 0.87; p = 0.014), smoking (OR, 0.11; p = 0.033), and IPH regression (OR, 10.13; p = 0.027) were associated with stenosis regression. The progression of IPH (OR, 115.80; p = 0.007) was associated with stenosis progression. Results suggest that IPH on HR-MRI is associated with changes in cerebral atherosclerotic stenosis.

Atypical Cognitive Impairment and Recovery in Two Colorectal Cancer Patients.

Cognitive impairment in cancer patients can be caused by various factors; in approximately 30% of cancer patients, the symptoms appear before starting treatment. Paraneoplastic limbic encephalitis (PLE) is a rare disease associated with an autoimmune response, and is characterized by memory loss, depression, and personality changes; it is one of the potential causes of cognitive dysfunction in cancer patients. Two patients were previously diagnosed with mild cognitive impairment and maintained clinical stability; after suffering a rapid change in personality and sudden cognitive decline, colorectal cancer was diagnosed within a few months. The patients did not meet the diagnostic criteria for PLE in several tests. The symptoms improved after the underlying cancer was treated, and the patients returned to their previous stable state. Sudden cognitive impairment may appear as an early cancer symptom, and PLE is considered an atypical cause for these symptoms. However, in patients with unexplained PLE-like symptoms who do not meet the diagnostic criteria for PLE, probable etiologies to be considered are the gut-brain connection, CD8+ T-cell-mediated limbic encephalitis, and somatic mutations in dementia-related genes. Currently, few studies have investigated these symptoms, and further research will offer significant therapeutic strategies for cognitive impairment in cancer patients.

Anti-NMDAR encephalitis with bilateral basal ganglia MRI lesions at a distance of time: a case report.

BACKGROUND: Approximately half (55%) of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is known to show abnormal brain images, including high signal intensity in T2 or fluid attenuated inversion recovery (FLAIR) images. In a minority of anti-NMDAR encephalitis cases, high signal intensity on diffusion-weighted imaging (DWI) has been reported, a finding that is highly suggestive of a stroke. CASE PRESENTATION: We present the case of a 66-year-old man who experienced two separate focal seizure events, which involved first the right and then the left upper extremity in a short period of time. The patient showed focal clonic seizures involving right arm and hand, which sometimes evolved to bilateral tonic-clonic seizures on his first admission. Brain magnetic resonance imaging (MRI) showed high signal intensity on DWI and low signal intensity on the apparent diffusion coefficient (ADC) map of the left caudate nucleus and putamen. The patient was discharged symptom-free with anti-epileptic drugs for 2 weeks. The second admission occurred 4 days after the discharge. He exhibited a new symptom of focal clonic seizures involving left arm and hand while showing a brain lesion on the opposite side which is hyperintense on DWI image and hypointense on ADC map. The patient was eventually diagnosed with anti-NMDAR encephalitis according to the cerebrospinal fluid (CSF) antibody test. CONCLUSIONS: This is the case of anti-NMDAR encephalitis patient whose DWI/ADC images revealed sequential involvement on the left and right basal ganglia with a short time interval. When stroke-like brain lesions on DWI are found in a patient with a focal seizure, a CSF study could help rule out autoimmune encephalitis. We also suggest that DWI/ADC map images may be useful for the early detection of anti-NMDAR encephalitis.

Reversible cerebral vasoconstriction syndrome with basilar artery stenosis: A case report.

INTRODUCTION: Acute severe headaches in young patients may be associated with fatal neurological complications that necessitate imaging examinations. Among acute severe headaches, a thunderclap headache may indicate the rupture of a cerebral aneurysm or the onset of reversible cerebral vasoconstriction syndrome for which emergent evaluation is required. PATIENT CONCERNS: We report the case of a 36-year-old man who presented to our hospital with an acute severe headache after excessive exercise the previous day. He was prescribed a pain reliever and discharged under the suspicion of vestibular migraine but returned to the emergency room after 4 hours due to right hemiparesis, right facial palsy, severe dysarthria, and a mild drowsy mental status. DIAGNOSIS: After cerebral angiography, we diagnosed basilar artery stenosis with acute infarction in the posterior circulation due to reversible cerebral vasoconstriction syndrome. INTERVENTIONS: Brain computed tomography angiography revealed complete occlusion of the vertebrobasilar artery. Transfemoral cerebral angiography showed spontaneous improvement in the occlusion before thrombectomy. OUTCOMES: Ten months later, high-resolution vessel wall magnetic resonance angiography showed persisting severe stenosis of the basilar artery. CONCLUSIONS: A headache in young patients with risk factors of atherosclerosis, such as smoking history, uncontrolled hypertension, and dyslipidemia may be caused by reversible cerebral vasoconstriction syndrome or ischemic stroke, which has fatal neurological complications. Therefore, reversible cerebral vasoconstriction syndrome or ischemic stroke should be suspected and appropriately evaluated in such patients, even if the headache is not the thunderclap type.

Acute basilar artery occlusion with recurrent shivering: A case report.

RATIONALE: Shivering is an important physiological response of the body that causes muscle tremors to maintain temperature homeostasis. Traumatic brain injuries that affect the hypothalamus cause hypothermia, and physical removal of suprasellar tumors causes thermoregulation imbalance. However, no study has reported shivering due to ischemic stroke. PATIENT CONCERNS: A 58-year-old male patient was admitted to our emergency department to evaluate severe stenosis of the basilar artery. While waiting for further examination, he exhibited coarse shivering and severe dysarthria. DIAGNOSIS: Brain computed tomography angiography revealed occlusion of the entire basilar artery, and cerebral hypoperfusion was diagnosed in that area. INTERVENTIONS: Transfemoral cerebral angiography (TFCA) was immediately performed, followed by thrombectomy of the basilar artery. OUTCOMES: Neurological deficits, including shivering, were rapidly reversed. The same symptom reoccurred 5 hours later, and TFCA was performed for thrombectomy and stenting, and neurological symptoms immediately reversed. The patient's neurological symptoms did not worsen during hospitalization. LESSONS: Patients with acute basilar artery occlusion need prompt management because they have a higher mortality rate than those with other intracranial artery occlusions. When a patient exhibits neurological deficits accompanied by abrupt shivering for no specific reason, basilar artery occlusion must be considered.

Lithium induced reversible Splenial lesion in neuroleptic malignant syndrome like symptoms: two case reports.

BACKGROUND: Lithium is primarily used to treat bipolar disorder and is known to cause several acute neurological complications. Reversible splenial lesions (RSLs) may be evident in antiepileptic drug toxicity or withdrawal, infections, and other phenomena. We report two cases of RSL presenting as neuroleptic malignant syndrome-like symptoms (NMSLS) with lithium associated neurotoxicity. CASE PRESENTATION: A 28-year-old woman was admitted after taking increased dosages of lithium for schizophrenia. She experienced generalized tremor, rigidity, dysarthria, high fever, and tachycardia. Symptoms and brain lesion recovered 2 weeks after discontinuation of lithium. The second case involved a 59-year-old woman who was receiving treatment for bipolar disorder since 1988. When lithium was administered for impatience and aggressive behavior, her mental state deteriorated and fever developed, along with generalized tremor in the extremities. Brain magnetic resonance imaging (MRI) in both patients showed a reversible oval-shaped lesion localized to the splenium of the corpus callosum. Both patients were defined as neuroleptic malignant syndrome-like symptoms (NMSLS) based on the DSM-5 diagnostic criteria for neuroleptic malignant syndrome. The suspected etiology of our cases was lithium associated neurotoxicity according to their clinical course and medical information. Our patients fully recovered in 10-14 days after the discontinuation of lithium. CONCLUSIONS: The patients experienced similar clinical courses and had similar radiological findings of RSL. Manifestations in both cases were related to lithium associated neurotoxicity and this should be considered in patients with RSL and NMSLS.

Factors associated with temporal window failure in transcranial Doppler sonography.

BACKGROUND: Temporal window failure (TWF) is found in 8-20% of subjects. There are still insufficient studies about the factors affecting TWF. We aimed to elucidate the underlying causes of TWF. METHODS: We analyzed 376 patients who underwent both transcranial Doppler sonography and cerebral angiographic imaging. They were divided into two groups: with and without TWF. Demographics, cardiovascular factors, degree of stenosis from the proximal intracranial artery to the middle cerebral artery (MCA), MCA diameter, and skull features were examined. RESULTS: The subjects were 314 TWF-negative patients and 62 TWF-positive patients. The TWF-negative group was younger than that of the TWF-positive group (67.0 ± 12.1 vs. 75.2 ± 9.4, p < 0.001). The proportion of men in the TWF-negative group was higher than in the TWF-positive group (71% vs. 29%; p < 0.001). The TWF-negative group had a higher smoking rate than the TWF-positive group (34.4% vs. 12.9%; p = 0.001). In multivariate logistic regression analysis, age (odds ratio (OR), 1.05; p = 0.019), sex (OR, 4.64; p = 0.002), temporal bone thickness (OR, 6.03; p < 0.001), temporal bone density (OR, 0.996; p = 0.002), and soft tissue thickness (OR, 1.31; p = 0.004) significantly affected TWF. CONCLUSIONS: In addition to age, sex, temporal bone thickness, and temporal bone density which were previously reported as variables associated with TWF, we confirmed that soft tissue thickness of the temporal area is a new associated factor of TWF. Measuring soft tissue thickness of the temporal area for patients with suspected TWF could be useful in identifying measurement error due to technical problems.

Different imaging patterns of PCNSL and IVL: a case report.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare, malignant, non-Hodgkin's lymphoma of the brain, leptomeninges, and rarely the spinal cord. PCNSL has characteristic magnetic resonance imaging (MRI) findings, and effective treatment strategies are available. It is characterized predominately by neurological symptoms, which are caused by tumor infiltration into the nervous system as well as ischemia. Chemotherapy is an effective treatment, if started prior to the ischemic damage. CASE PRESENTATION: A 62-year-old male patient with PCNSL presented with altered mental status. The initial brain MRI revealed high signal intensity on the T2-weighted images (T2WIs) of the putamen area of the right basal ganglia, and the clinical symptoms improved after steroid administration. However, the symptoms were later deteriorated, we considered the possibility of autoimmune encephalitis and, consequently, conducted an immunomodulatory therapy. In a follow-up brain MRI, enlargement lesions of T2WI in basal ganglia and pons were simultaneously enhanced. Subsequently, the patient's mental status deteriorated to a semi-coma and PCNSL was diagnosed after a surgical biopsy. Chemotherapy was started immediately; however, the patient died. CONCLUSIONS: Effective treatments are available for PCNSL and intravascular lymphoma; thus, their prognosis is generally good if they are diagnosed early. Herein, we report the case of a patient suspected with autoimmune encephalitis after brain MRI and treated with immunomodulation therapy. However, PCNSL was confirmed by a surgical biopsy. It is, therefore recommended to consider lymphoma in patients with neurological symptoms that are difficult to localize and rapidly progressive enhancing lesions showing a mass effect on brain MRI.

Myasthenia gravis following human papillomavirus vaccination: a case report.

BACKGROUND: Myasthenia gravis (MG), an autoimmune neuromuscular disorder, occurs owing to autoantibodies against acetylcholine receptors. MG symptoms can be triggered by various vaccines. Many studies have evaluated the safety and adverse events of the human papillomavirus (HPV) vaccine. Here, we present a life-threatening case of ocular and bulbar MG symptoms after HPV vaccination and a brief literature review. CASE PRESENTATION: A 23-year-old woman presented with binocular diplopia, ptosis, dysarthria, and dysphagia, which occurred on the 3rd day after the second HPV vaccine administration. She was diagnosed with MG based on history, clinical features, and test results. Her symptoms deteriorated on the 3rd day after admission, and she was transferred to the intensive care unit with mechanical ventilation. On the 7th day after admission, due to discomfort in the right chest, pulmonary embolism was suspected. A tracheostomy was performed on the 14th day of mechanical ventilation. In the 4th week, the tracheostomy tube was removed; all symptoms had completely resolved at discharge. She was followed up for 5 months without recurrence or further treatment. CONCLUSION: HPV vaccination may cause MG owing to unexpected abnormal autoimmune responses. Additional studies are needed to clarify the possible causal relationship between the HPV vaccine and neurological complications and to evaluate the safety of the vaccine.

Genetic Polymorphisms rs699947, rs1570360, and rs3025039 on the VEGF Gene Are Correlated with Extracranial Internal Carotid Artery Stenosis and Ischemic Stroke.

Extracranial internal carotid artery (ECICA) stenosis is a modifiable risk factor of ischemic stroke. VEGF plays a crucial role in the maintenance of endothelial integrity and physiological function. This study was designed to assess the correlations of VEGF polymorphisms with ECICA stenosis in ischemic stroke and to explore the relationships between these polymorphisms and different biochemical parameters. This study included a total of 650 ischemic stroke patients, 232 with ECICA stenosis while 418 had no ECICA stenosis as assessed by magnetic resonance angiography. Three SNPs in the VEGF gene, rs699947, rs1570360, and rs3025039, were assessed by real-time PCR coupled with melting curve analysis. Serum samples were analyzed for biochemical parameters in an automated clinical chemistry analyzer in the Laboratory Medicine Department. The CA and CA+AA (A allele bearing) genotype frequencies of the rs699947 polymorphism (AOR=1.46 and 1.47, respectively) and the GA genotype frequency of the rs1570360 polymorphism (AOR=7.33) showed a significant association with ECICA stenosis. However, the haplotype frequencies of C-A-A, T-A-C, and T-A-A (rs302503-rs1570360-rs699947) were significantly different between patients who experienced stroke with and stroke without ECICA stenosis. We found that the total homocysteine (tHcy) levels of stroke patients with ECICA stenosis with rs1570360 and rs699947 SNPs were significantly different compared to the wild-type reference genotype. In conclusion, VEGF rs699947 and rs3025039 polymorphisms were associated with increased risk of stroke, while rs1570360 and rs699947 were associated with stroke and ECICA stenosis.

Correlation of VEGF genetic polymorphisms and lipid profile to aortic calcification.

BACKGROUND: Aortic calcification is developed due to accumulation of a large amount of calcium in the aorta of the heart and it is the leading cause of aortic valve replacement and third leading cause of cardiovascular disease. The purpose of this study was to investigate the relation between aortic calcification and VEGF SNPs (-2578C>A, -1154G>A and +936C>T) and to evaluate the association of these SNPs with biochemical parameter in relation to aortic calcification. METHODS: Aortic calcification was diagnosed by examining the posteroanterior chest X-rays by a radiologist and graded into four groups. The real-time polymerase chain reaction with melting curve analysis in LightCycler was used to genotype the VEGF SNPs. RESULTS: Among the VEGF SNPs, a significant genetic difference was found only between the aortic calcification and control group with VEGF SNP -2578C>A but haplotypes T-A-A of (+936/-1154/-2578) were significantly different in control and aortic calcification and could enhance the aortic calcification development. By regression analysis, it was found that age, hypertension, diabetes, dyslipidemia, and hyperhomocysteinemia were found significantly different with the different genotypes of VEGF SNPs which may induce aortic calcification development. CONCLUSION: Age, hypertension, diabetes, dyslipidemia, and hyperhomocysteinemia were established as aggravating factors for the aortic calcification in association with different VEGF genotypes.

Ocular vestibular evoked myogenic potentials induced by air-conducted sound in patients with acute brainstem lesions.

OBJECTIVE: The ocular vestibular-evoked myogenic potential (oVEMP), a recently documented otolith-ocular reflex, is considered to reflect the central projections of the primary otolithic afferent fibers to the oculomotor nuclei. The aim of our study is to define air-conducted sound oVEMP abnormality in patients with acute brainstem lesions and to determine the brainstem structures involved in the generation of oVEMPs. METHODS: In response to air-conducted tone burst sounds (ACS), oVEMP was measured in 52 patients with acute brainstem lesions. Individualized brainstem lesions were analyzed by means of MRI-based voxel-wise lesion-behavior mapping, and the probabilistic lesion maps were constructed. RESULTS: More than half (n=28, 53.8%) of the patients with acute brainstem lesions showed abnormal oVEMP in response to ACS. The majority of patients with abnormal oVEMPs had lesions in the dorsomedial brainstem that contains the medial longitudinal fasciculus (MLF), the crossed ventral tegmental tract (CVTT), and the oculomotor nuclei and nerves. CONCLUSION: MLF, CVTT, and the oculomotor nuclei and nerves appear to be responsible for otolith-ocular responses in the brainstem. SIGNIFICANCE: Complemented to cervical VEMP for the uncrossed otolith-spinal function, oVEMP to ACS may be applied to evaluate the crossed otolith-ocular function in central vestibulopathies.

Routine Shunting is Safe and Reliable for Cerebral Perfusion during Carotid Endarterectomy in Symptomatic Carotid Stenosis.

BACKGROUND: The purpose of this report is to describe the perioperative outcomes of standard carotid endarterectomy (CEA) with general anesthesia, routine shunting, and tissue patching in symptomatic carotid stenoses. MATERIALS AND METHODS: Between October 2007 and July 2011, 22 patients with symptomatic carotid stenosis (male/female, 19/3; mean age, 67.2±9.4 years) underwent a combined total of 23 CEAs using a standardized technique. The strict surgical protocol included general anesthesia and standard carotid bifurcation endarterectomy with routine shunting. The 8-French Pruitt-Inahara shunt was used in all the patients. RESULTS: During the ischemic time, the shunts were inserted within 2.5 minutes, and 5 patients (22.7%) revealed ischemic cerebral signals (flat wave) in electroencephalographic monitoring but recovered soon after insertion of the shunt. The mean shunting time for CEA was 59.1±10.3 minutes. There was no perioperative mortality or even minor stroke. All patients woke up in the operating room or the operative care room before being moved to the ward. One patient had difficulty swallowing due to hypoglossal nerve palsy, but had completely recovered by 1 month postsurgery. CONCLUSION: Routine shunting is suggested to be a safe and reliable method of brain perfusion and protection during CEA in symptomatic carotid stenoses.

New novel mutation of the ATP7B gene in a family with Wilson disease.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The WD gene codes for a copper transporting P-type ATPase (ATP7B) are located on chromosome 13q14.3. Mutation of this gene disrupts copper homeostasis, resulting in the accumulation of copper in the liver, brain, kidneys and corneas and copper toxication at these sites. Since the detection of the WD gene in 1993, approximately 300 disease-specific muations have been identified. We recently evaluated a Korean family with WD. The proband, a 17-year-old boy, visited our hospital due to abnormal behaviors including generalized slow movement, dysphagia, drooling and ataxia. Laboratory results revealed decreases in serum copper and ceruloplasmin and an increase in urinary excretion of copper. He had liver cirrhosis, brain lesions and Kayser-Fleischer corenal rings. Molecular genetic analysis of the ATP7B gene demonstrated that he was heterozygous for deletion mutation c.2697_2723del27 in exon 11. Further study of family members revealed that his father and younger brother had the same mutation. The c.2697_2723del27 deletion mutation in exon 11 has not yet been reported as a causative muation of WD and is an in-frame deletion not expected to lead to a frame shift. Therefore, we report a novel mutation of the ATP7B gene in a family with WD.

Selective saccadic palsy after cardiac surgery.

We report a patient who showed a selective deficit of voluntary saccades and quick phases of nystagmus after cardiac surgery. Voluntary saccades in the horizontal plane were very slow, while vertical saccades, vestibular and optokinetic nystagmus, were absent. However, smooth pursuit, the vestibulo-ocular reflex, and the ability to hold steady eccentric gaze were preserved.

Neural precursors derived from embryonic stem cells, but not those from fetal ventral mesencephalon, maintain the potential to differentiate into dopaminergic neurons after expansion in vitro.

Neural precursors (NPs) derived from ventral mesencephalon (VM) normally generate dopaminergic (DA) neurons in vivo but lose their potential to differentiate into DA neurons during mitogenic expansion in vitro, hampering their efficient use as a transplantable and experimental cell source. Because embryonic stem (ES) cell-derived NPs (ES NP) do not go through the same maturation process during in vitro expansion, we hypothesized that expanded ES NPs may maintain their potential to differentiate into DA neurons. To address this, we expanded NPs derived from mouse embryonic day-12.5 (E12.5) VM or ES cells and compared their developmental properties. Interestingly, expanded ES NPs fully sustain their ability to differentiate to the neuronal as well as to the DA fate. In sharp contrast, VM NPs almost completely lost their ability to become neurons and tyrosine hydroxylase-positive (TH(+)) neurons after expansion. Expanded ES NP-derived TH(+) neurons coexpressed additional DA markers such as dopa decarboxylase and DAT (dopamine transporter). Furthermore, they also expressed other midbrain DA markers, including Nurr1 and Pitx3, and released significant amounts of DA. We also found that these ES NPs can be cryopreserved without losing their proliferative and developmental potential. Finally, we tested the in vivo characteristics of the expanded NPs derived from J1 ES cells with low passage number. When transplanted into the mouse striatum, the expanded NPs as well as control NPs efficiently generated DA neurons expressing mature DA markers, with approximately 10% tumor formation in both cases. We conclude that ES NPs maintain their developmental potential during in vitro expansion, whereas mouse E12.5 VM NPs do not.