Indirect Fistula: A New Terminology for Cerebrospinal Fluid Fistula With Different 'Apparent Origin' and 'Real Origin'.

Fistulas are abnormal communications between body cavities. They can occur between the CNS and the extracranial space, presenting clinically as CSF leaks. Due to the variety of features, multiple classifications have been implemented to better study this pathology. A systematic review was conducted using the Scopus, Medline, and Web of Science databases. Observational studies such as cohort studies, case reports, case series, cross-sectional studies, systematic reviews, and publications that assess the classification of CSF leaks were included. The systematic review identified 29 publications that met the required criteria for inclusion. Although the primary focus of most of these publications was not on classification, they briefly mentioned it. The included publications describe classifications according to etiology, exiting flow pressure, anatomic site, and some new classification proposals. Of the 29 included studies, 11 referred to the appearance of CSF rhinorrhea or otorrhea with no relationship between the cause or site of origin and the site of the CSF leak. However, none of these publications names this situation. These results clearly indicate that a term for this circumstance needs to be established; none of the previously listed publications provide a name for this condition. This systematic review aims to demonstrate the necessity of implementing a new term to describe CSF leaks where the 'apparent origin' does not correspond to the 'real origin.' The results show no existing term that considers such cases; therefore, we propose the term 'Indirect Fistula' to designate these cases.

Accurate preoperative diagnosis of a Rathke cleft cyst with the aid of a novel classification for sellar cystic lesions and a diagnostic algorithm decision: Tools for differentiating cystic sellar lesions with a representative case.

Background: Rathke's cleft cyst (RCC) is a benign lesion in the sellar and suprasellar compartments. Similarly, pituitary adenomas can present with cystic morphology, making it a differential diagnosis when evaluating a patient with a cystic lesion in the sellar region. Surgical goals differ between RCCs and pituitary adenomas as the first can achieve remission of symptoms with cyst decompression in contrast to pituitary adenomas where complete resection would be the main goal. Imaging analysis alone may not be sufficient to define a preoperative surgical plan. The combination of imaging and conjoined use of validated tools may provide valuable insights to the clinician when defining a surgical approach. Case Description: We present a case of a 27-year-old male with a 3-month history of visual disturbances and headaches. Magnetic resonance imaging showed a cystic lesion in the sellar compartment with compression of nearby structures. The authors were able to accurately diagnose this sellar lesion as an RCC with the conjoined aid of two classifications proposed in the literature. Cyst evacuation was performed with relief of symptoms and improved visual outcomes at follow-up. Conclusion: While cystic adenomas can require total resection for cure, RCCs can show marked improvement with partial resection and evacuation of its contents. An accurate preoperative diagnosis can lead the surgeon to opt for the best surgical approach.

Simultaneous spine extradural and intradural teratomas in a pediatric patient: A rare presentation with insights in the flawed migration of germ cells theory.

Spinal teratomas are infrequent lesions in the pediatric population. These lesions can be extradural, intradural or intramedullary. We present a case of an 8-month-old boy that was assessed for underdevelopment of motor milestones. The neurologic examination revealed hyporeflexia, decreased sensation and flaccid paraplegia. MRI of the spine revealed two simultaneous and independent lesions in the extradural and intradural compartment. A laminectomy was performed for the T4-T7 vertebrae with total resection of both lesions. The histopathological analysis confirmed both lesions to be mature cystic teratomas. At the 1-year follow-up, the patient remained with no recovery of neurological function. A debate takes place regarding the etiology of formation of these lesions in the spine. The simultaneous presentation of two independent lesions in this patient could contribute to define the flawed migration of germ cells theory as the etiology for formation of teratomatous lesions in the spine.

A simple but effective solution for proximal mark absence on some microcatheters in intracranial aneurysm embolization: Technical note.

Background: Endovascular coil embolization is increasingly being used for the treatment of intracranial aneurysms and other pathologies such as arteriovenous (AV) malformations and AV fistulas. Appropriate embolization technique requires a microcatheter with two radiopaque marks, one proximal and one distal. We present an alternative coils deployment technique for intracranial aneurysms, using a microcatheter without a proximal radiopaque mark. Methods: We describe the technique for embolization that was used in a 36-year-old female patient, in which we used a microcatheter without a proximal radiopaque mark for coil embolization of an intracranial aneurysm. Results: We used a Headway Duo flow directed microcatheter for a coiling embolization of an intracranial aneurysm, solving the absence of the proximal radiopaque mark by cannulating the microcatheter with a Traxcess 0.014 microguidewire, and placing an external mark on the screen in the proximal portion of the microguidewire 30 mm radiopaque tip to indirectly mark the proximal mark of the microcatheter. Conclusion: There is scarce evidence supporting the use of microcatheters with no proximal radiopaque mark for coil embolization. This report attempts to disclose how an easy and simple technique can be used as a rescue method to solve the proximal radiopaque mark absence during endovascular coil release procedures. To the best of our knowledge, this technique has not been previously described; therefore, its use is not widespread among neurointerventionists.

Primary Neuroendocrine Carcinoma of the Cerebellopontine Angle: A Case Report and Literature Review.

Primary intracranial neuroendocrine tumors are extremely rare malignancies with very few cases reported in the world literature. We describe a primary neuroendocrine carcinoma arising from the right cerebellopontine angle, the second case that has been described in this location. The possible origin in this place and treatment are described. A 29-year-old male patient, diagnosed with schwannoma of the right cerebellopontine angle, and treated with radiosurgery at another institution, came to our hospital six months later, The patient presented with a history of rapid progression of numbness on the right side of the face, diplopia, dizziness, vomiting, and facial palsy. On examination, the right cranial nerves V, VI, VII, VIII, and IX were affected. The MRI showed tumor growth occupying the right cerebellopontine angle, with compression of the brain stem and cerebellum. A right retromastoid craniectomy removed the tumor partially and the histopathological examination revealed a high-grade neuroendocrine carcinoma. We describe a primary neuroendocrine tumor of the brain that, despite its rarity, must be considered in the differential diagnosis. There are currently no guidelines for the management of these tumors. According to previously reported cases, surgery is the first line of treatment, followed by radiotherapy or chemotherapy. We consider that such a rare case is needed to be reported for a better understanding of the disease and its neurobiology.

Aneurysms of the Lenticulostriate Artery: A Systematic Review.

BACKGROUND: Lenticulostriate artery aneurysms (LSAs) are rare vascular aberrations. Despite the potentially catastrophic sequelae of aneurysmal rupture, the optimal management strategy for LSA aneurysms has not been determined. The aim of the present review is to provide an overview of the clinical presentation and treatment strategies for LSA aneurysms. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a literature search was conducted in the PubMed, Cochrane, EBSCOhost, Scopus, Web of Science, and ProQuest search engines to identify reported studies of LSA aneurysms until July 1, 2020. A descriptive analysis was performed. RESULTS: A total of 71 studies with 112 cases of LSA aneurysms were included. Patient age ranged from 2 months to 83 years (median, 44.5 years). Male and female patients were affected similarly (49% and 51%, respectively). The most common presentation was aneurysmal rupture (78%), and headache was the most frequently reported symptom (36%). Overall, 48% of the patients had undergone underwent surgical treatment, 30% conservative management, 21% endovascular treatment, and 1% radiosurgery. Four patients died, all of whom had presented with aneurysmal rupture. CONCLUSION: We have summarized the reported cases of LSA aneurysms, with their clinical presentation, management, and outcomes, for physicians who may be confronted with this diagnosis. Future studies that use available classification systems and include as much detail as possible should be encouraged to fully elucidate the optimal management strategy for these patients.

Diagnostic and therapeutic challenge in intracerebral hemorrhage due to aneurysm of distal lenticulostriate artery.

OBJECTIVE: To present an atypical case of deep intracerebral hemorrhage caused by the rupture of an aneurysm of the distal lenticulostriate artery. A 42-year-old woman presenting with right-sided mild hemiparesis was diagnosed with an acute left-sided hemorrhage within the basal nuclei. Cerebral angiography revealed a microaneurysm of the distal portion of the left lenticulostriate artery. Conservative treatment under close neurological surveillance was recommended. After a few days of hospital stay, the patient's neurological symptoms improved, and she was discharged. The patient has remained asymptomatic for more than 6 months. Aneurysms of the distal lenticulostriate artery are extremely rare.

OBJETIVO: Presentar un caso atípico de hemorragia intracerebral profunda causada por la ruptura de un aneurisma de la arteria lenticuloestriada distal; se revisa la bibliografía y se analizan la fisiopatología y el tratamiento. Se presentó a la sala de emergencias una mujer de 42 años con hemiparesia leve del hemicuerpo derecho. Se la diagnosticó con una hemorragia aguda en los núcleos de la base izquierdos. La panangiografía cerebral reveló un microaneurisma de la porción distal de la arteria lenticuloestriada izquierda. Se recomendó tratamiento conservador bajo estrecha vigilancia neurológica. Después de unos cuantos días de hospitalización, los síntomas neurológicos de la paciente mejoraron y la paciente recibió el alta. La paciente ha permanecido asintomática durante más de seis meses. Los aneurismas de la arteria lenticuloestriada distal son extremadamente raros.

Cost analysis of materials used in the endovascular treatment of unruptured intracranial aneurysms in Mexico.

BACKGROUND: To prevent the potentially fatal consequences of intracranial aneurysmal rupture, exclusion from the circulation can be achieved through an endovascular approach. However, the elevated cost of such procedures can be prohibitive for patients in low resource settings. The objective of this study is to identify the factors that modify the cost of the materials used for endovascular treatment of unruptured intracranial aneurysms. METHODS: Medical records of patients who underwent an endovascular treatment for unruptured intracranial aneurysms between June 2013 and June 2019 in a hospital located in Northeast Mexico were reviewed. Descriptive statistics of the cost of consumable materials used during the procedure was performed, and a regression model was undertaken to examine potential associations between the studied variables and total cost of the intervention. RESULTS: A total of 128 patients were included in this analysis. The average intervention cost was $21,687.22 USD. The variables associated with increased material cost were aneurysm size (p = 0.03), aneurysm neck size (p < 0.001), and aneurysm localization in the cavernous segment of the internal carotid artery (p = 0.01). Other variables such as patient age and sex, other aneurysm localizations, laterality of the aneurysm, performing neurointerventionalist, and presence of intervention complications were not statistically significant. CONCLUSIONS: To our knowledge, this is the first study that examines the variables associated with the material cost of endovascular treatment of unruptured intracranial aneurysms. Awareness of which elements are important drivers of materials' costs provides a strategic advantage when making hospital administrative decisions and attempting to improve access to endovascular treatment in countries of low income.

Coiling as a Rescue Strategy for Flow Diverter Prolapse into a Giant Intracranial Aneurysm.

BACKGROUND: Up to 3.2% of the adult population has an unruptured intracranial aneurysm (IA). Flow diversion is a relatively new treatment technique that is especially useful for large and morphologically unfavorable IAs. METHODS: A previously healthy woman aged 32 years presented with a 6-month history of ptosis and ophthalmoplegia of the left eye. A magnetic resonance imaging scan revealed a giant left internal carotid artery aneurysm. She was admitted for treatment using flow diversion. After delivery of the flow diverter (FD), prolapse of the proximal end of the stent into the aneurysmal sac was observed. FD stabilization was achieved by deploying multiple coils through a previously placed microcatheter to push the prolapsed end away from the aneurysmal lumen. RESULTS: The patient had a favorable outcome, with reduction of preoperative mass effect symptoms and complete obliteration of the aneurysm persisting at the 3-month follow-up. CONCLUSIONS: Giant IAs remain one of the most daunting clinical problems to treat. FD displacement is a rare (0.5%-0.75%) and possibly fatal complication. Currently, no clinical guidelines exist for its management. Adjunctive coiling is a possible rescue strategy for stabilizing an FD that foreshortened and prolapsed into the aneurysmal sac. Further studies are needed to identify the best approach to this complication.

Internal jugular phlebectasia: A systematic review.

BACKGROUND: Internal jugular phlebectasia (IJP), the abnormal dilatation of internal jugular vein, is generally considered a benign anomaly. However, because IJP is uncommon, little is known about its natural history, and currently, no consensus on the best treatment modality is available. METHODS: The purpose of this article is to conduct a systematic review of available literature on recently reported IJP cases to understand the main characteristics of IJP and its most frequent therapeutic approaches. Following the preferred reporting items for systematic reviews and meta-analyses guidelines, literature search for IJP cases was conducted in the COCHRANE, PUBMED, EBSCOHOST, SCOPUS, OVID, and SCIELO databases. RESULTS: A total of 97 original articles were found, with a total of 247 IJP cases reported including both pediatric and adult patients. CONCLUSIONS: To the best of our knowledge, this study is the largest systematic review analyzing all the reported cases of IJP. IJP is considered by most authors as a benign abnormality that predominantly affects the right jugular vein. It is most commonly diagnosed in children. At present, conservative treatment is preferred for pediatric but not for adult patients. Multicenter randomized prospective studies are required to further understand this rare anomaly.

Ectopic Germinoma in the Corpus Callosum with Severe Restrictive Anorexia: Case Report and Review of Literature.

BACKGROUND: Intracranial germ cell tumors are a rare group of neoplasms constituting 1% to 2% of primary intracranial tumors in North America and Europe. Germinomas of the corpus callosum are exceedingly rare, accounting for only 0.7% of all intracranial germ cell tumors. CASE DESCRIPTION: We report a case of germinoma in the corpus callosum of a 17-year-old woman with a 2-year history of personality change, anorexia, amnesia, hypersomnia, and depression. Magnetic resonance imaging showed a well-circumscribed, heterogeneous mass measuring 2.9 × 5 × 3.1 cm, with multiple cystic areas and heterogeneous enhancement with gadolinium. It arose in the corpus callosum and extended to the fornix and frontal lobes. There was mild perilesional edema but no evidence of hypothalamus or hippocampus involvement. No spinal drop metastases were visualized on magnetic resonance imaging. Cerebrospinal fluid and serum levels of alpha-fetoprotein, beta-human chorionic gonadotropin, carcinoembryonic antigen, and placental alkaline phosphatase were all normal. Immunohistologic staining of tumor cells was positive for OCT3/4, placental alkaline phosphatase, and CD117 and negative for CD30 and GPC3. Radiotherapy led to a substantial decrease in tumor size. CONCLUSION: This is a case of germinoma arising in the corpus callosum that presented clinically with an eating disorder manifested as restrictive anorexia.

Primary Spinal Cord Small-Cell Glioblastoma: Case Report and Literature Review.

BACKGROUND: Approximately 2%-10% of all central nervous system tumors are primary spinal cord tumors (SCTs). Spinal cord glioblastoma is a rare tumor type accounting for 1%-3% of all SCTs and 7.5% of all spinal cord gliomas. Notably, the small-cell variant of spinal cord glioblastoma is even rarer with only 2 previously reported cases. CASE DESCRIPTION: We present herein a case report of a rare primary spinal cord glioblastoma in a 48-year-old patient with a 2-month history of numbness in the left arm and mild cervical pain radiating to the occipital zone. Clinical examination revealed hypoalgesia and thermal dissociation of the left arm and the ipsilateral superior part of the trunk treated through subtotal surgical resection followed by adjuvant chemotherapy and radiotherapy. Histologic examination of the surgical tumor specimen revealed features of the small-cell spinal cord glioblastoma. CONCLUSIONS: To the best of our knowledge, this is only the third reported case of small-cell spinal cord glioblastoma. The aggressive nature of this tumor variant reduces overall survival rate regardless of the treatment.

Utility of magnetic resonance cisternography with intrathecal gadolinium in detection of cerebrospinal fluid fistula associated with Mondini dysplasia in a patient with recurrent meningitis: Case report and literature review.

Background: The intrathecal contrast-enhanced magnetic resonance cisternography (MRC) is a diagnostic method that has been proven effective in selected patients with various disorders of the cerebrospinal system, including the detection of cerebrospinal fluid (CSF) leaks. The Mondini dysplasia is a malformation of the inner ear characterized by an incomplete cochlear development. The cerebrospinal fistula associated with Mondini dysplasia usually occurs in the first 5-10 years. Case Description: The case of a 34-year-old woman with CSF rhinorrhea and recurrent meningitis associated with CSF fistula into the right inner ear, which was detected by MRC with intrathecal gadolinium, is presented. The computed tomography (CT) cisternography failed to detect the exact location of the leak. The right Mondini dysplasia was identified on CT of the temporal bone. A subtotal right-sided petrosectomy and fistula closure into the bony labyrinth were performed. After the procedure the patient no longer presented meningitis or CSF leak. Conclusions: The radiological identification of the site of CSF leak through sensitive imaging studies such as MRC with intrathecal gadolinium is crucial for surgical approach.

Vertebroplasty and kyphoplasty for cervical spine metastases: a systematic review and meta-analysis.

BACKGROUND: Vertebroplasty (VP) and kyphoplasty (KP) are two minimally invasive techniques used to relieve pain and restore stability in metastatic spinal disease. However, most of these procedures are performed in the thoracolumbar spine, and there is limited data on outcomes after VP/KP for cervical metastases. The purpose of this article is to evaluate the safety and efficacy of VP and KP for treating pain in patients with cervical spine metastases. METHODS: A systematic review of the literature was conducted using the PubMed and Medline databases. Only studies that reported five or more patients treated with VP/KP in the cervical spine were included. Levels of evidence and grades of recommendation were established based on the Oxford Centre for Evidence-Based Medicine guidelines. Data was pooled to perform a meta-analysis for pain relief and complication rates. RESULTS: Six studies (all level 4 studies) met the inclusion criteria, representing 120 patients undergoing VP/KP at 135 vertebrae; the most common addressed level was C2 in 83 cases. The average volume of injected cement was 2.5 ± 0.5 milliliters at each vertebra. There were 22 asymptomatic cement leaks (16%; 95% CI, 9.8% - 22.2%) most commonly occurring in the paraspinal soft tissue. There were 5 complications (4%; 95% CI, 0.5% - 7.5%): 3 cases of mild odynophagia, 1 case of occipital neuralgia secondary to leak, and 1 case of stroke secondary to cement embolism. Pain relief was achieved in 89% of cases (range: 80 - 100%). The calculated average pain score decreased significantly from 7.6 ± 0.9 before surgery to 1.9 ± 0.8 at last evaluation (p=0.006). CONCLUSION: Although the calculated complication rate after VP/KP in the cervical spine is low (4%) and the reported pain relief rate is approximately 89%, there is lack of high-quality evidence supporting this. Future randomized controlled trials are needed.

The 100 most-cited articles in spinal oncology.

OBJECTIVE The authors' objective was to identify the 100 most-cited research articles in the field of spinal oncology. METHODS The Thomson Reuters Web of Science service was queried for the years 1864-2015 without language restrictions. Articles were sorted in descending order of the number of times they were cited by other studies, and all titles and abstracts were screened to identify the research areas of the top 100 articles. Levels of evidence were assigned on the basis of the North American Spine Society criteria. RESULTS The authors identified the 100 most-cited articles in spinal oncology, which collectively had been cited 20,771 times at the time of this writing. The oldest article on this top 100 list had been published in 1931, and the most recent in 2008; the most prolific decade was the 1990s, with 34 articles on this list having been published during that period. There were 4 studies with Level I evidence, 3 with Level II evidence, 9 with Level III evidence, 70 with Level IV evidence, and 2 with Level V evidence; levels of evidence were not assigned to 12 studies because they were not on therapeutic, prognostic, or diagnostic topics. Thirty-one unique journals contributed to the 100 articles, with the Journal of Neurosurgery contributing most of the articles (n = 25). The specialties covered included neurosurgery, orthopedic surgery, neurology, radiation oncology, and pathology. Sixty-seven articles reported clinical outcomes. The most common country of article origin was the United States (n = 62), followed by Canada (n = 8) and France (n = 7). The most common topics were spinal metastases (n = 35), intramedullary tumors (n = 18), chordoma (n = 17), intradural tumors (n = 7), vertebroplasty/kyphoplasty (n = 7), primary bone tumors (n = 6), and others (n = 10). One researcher had authored 6 studies on the top 100 list, and 7 authors had 3 studies each on this list. CONCLUSIONS This study identified the 100 most-cited research articles in the area of spinal oncology. The studies highlighted the multidisciplinary and multimodal nature of spinal tumor management. Recognition of historical articles may guide future spinal oncology research.

Thoracic epidural spinal angiolipoma with coexisting lumbar spinal stenosis: Case report and review of the literature.

BACKGROUND: Spinal angiolipomas (SALs) are uncommon benign lesions that may present insidiously with back pain or acutely with weakness due to tumor bleeding/thrombosis. Given their rarity, these lesions are often overlooked in the differential diagnosis of epidural masses. The purpose of this article is to report the case of an epidural SAL and to conduct a literature review on the topic. METHODS: A case report and review of the literature using the PubMed/Medline databases. All case reports and case series were reviewed up to June 2015. RESULTS: A 65-year old female presented with neurogenic claudication and magnetic resonance imaging (MRI) revealed lumbar spinal stenosis. Following decompressive surgery, she experienced symptom resolution, but three months postoperatively she presented to the emergency department with acute paraparesis. A thoracic MRI revealed a lesion located between T8 and T10 causing severe spinal cord compression. Following emergent laminectomy and en bloc resection, the patient regained function and the lesion was diagnosed as SAL. Our literature review revealed 178 reported cases, with a female and thoracic predominance. The majority of patients underwent surgical treatment, achieving a gross total resection in most cases. Similarly, complete symptom resolution was the most common outcome. CONCLUSION: Spinal angiolipomas are uncommon spinal tumors. However, they may be treated as any other space-occupying lesion, and surgical resection allows for complete symptom recovery in most patients.

Current standing and frontiers of gene therapy for meningiomas.

Meningiomas are among the most common intracranial tumors. The treatment of choice for these lesions is complete resection, but in 50% of cases it is not achieved due to tumor location and/or surgical morbidities. Moreover, benign meningiomas have high recurrence rates of up to 32% in long-term follow-up. Molecular analyses have begun to uncover the genetics behind meningiomas, giving rise to potential genetics-based treatments, including gene therapy. The authors performed a literature review on the most relevant genes associated with meningiomas and both current and potential gene therapy strategies to treat these tumors. Wild-type NF2 gene insertion, oncolytic viruses, and transfer of silencing RNA have all shown promising results both in vitro and in mice. These strategies have decreased meningioma cell growth, proliferation, and angiogenesis. However, no clinical trial has been done to date. Future research and trials in gene insertion, selective inhibition of oncogenes, and the use of oncolytic viruses, among other potential treatment approaches, may shape the future of meningioma management.

Cranioplasty with polymethylmethacrylate prostheses fabricated by hand using original bone flaps: Technical note and surgical outcomes.

BACKGROUND: Decompressive craniectomies (DC) mandate future cranioplasties, accounting for the large array of biomaterials for this purpose. Polymethylmethacrylate (PMMA) is a very reliable thermoplastic that can be prefabricated or even molded intraoperatively to create an adequate prosthesis. Preformed PMMA implants made by hand have been superseded by newer 3-D printed implants, but this is accompanied by higher costs and timing issues, apart from having limited availability in developing and third-world countries. METHODS: A total of 26 patients were operated over a span of 11 years. A total of 26 custom hand-made PMMA prostheses were fabricated using original bone flaps with the aid of a prosthodontist, in a process that took approximately 70 minutes for each implant. The result was an exact duplication of the patient's bone flap. RESULTS: Of the 26 patients who underwent cranioplasty, the majority of patients were males, with a mean age of 39.2 years and traumatic brain injury as main indication for DC. After a mean interval of 2.4 months, all 26 patients underwent a cranioplasty and prosthesis placement. Only two patients (7.6%) suffered from direct cranioplasty-related complications after a median follow-up of 10.4 months. Median Glasgow Outcome Scale scores improved significantly from 3 to 4 after cranioplasty (P = 0.008). CONCLUSION: Prefabrication of custom PMMA prostheses by hand when original bone flaps are available is an excellent alternative to newer 3-D printing techniques, because it is relatively cheaper, less time consuming, and offers excellent results in terms of anatomical reconstruction and improvement of neurological function in long-term follow-ups.

Differentiation of CD133+ stem cells from amyotrophic lateral sclerosis patients into preneuron cells.

Improvements in quality of life and life expectancy have been observed in amyotrophic lateral sclerosis (ALS) patients transplanted with CD133(+) stem cells into their frontal motor cortices. However, questions have emerged about the capacity of cells from these patients to engraft and differentiate into neurons. The objective of this work was to evaluate the in vitro capacity of CD133(+) stem cells from 13 ALS patients to differentiate into neuron lineage. Stem cells were obtained through leukapheresis and cultured in a control medium or a neuroinduction medium for 2-48 hours. Expression of neuronal genes was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical techniques. Fluorescence microscopy demonstrated that CD133(+) stem cells from ALS patients incubated for 48 hours in a neuroinduction medium increased the detection of neuronal proteins such as nestin, ß-tubulin III, neuronal-specific enolase, and glial fibrillary acidic protein. RT-PCR assays demonstrated an increase in the expression of ß-tubulin III, nestin, Olig2, Islet-1, Hb9, and Nkx6.1. No correlation was found between age, sex, or ALS functional scale and the CD133(+) stem cell response to the neuroinduction medium. We conclude that CD133(+) stem cells from ALS patients, like the stem cells of healthy subjects, are capable of differentiating into preneuron cells.

Stem cell transplantation in amyotrophic lateral sclerosis patients: methodological approach, safety, and feasibility.

Amyotrophic lateral sclerosis is characterized by the selective death of motor neurons. Stem cells have been proposed as a potential therapeutic strategy. The safety of stem cell transplantation into the frontal motor cortex to improve upper motor neuron function is described. Sixty-seven patients with definite amyotrophic lateral sclerosis were included. After giving their informed consent, the patients underwent magnetic resonance imaging, functional rating, pulmonary function test, and laboratory tests. Their bone marrow was stimulated with daily filgrastim (300 µg) given subcutaneously for 3 days. Peripheral blood mononuclear cells were obtained by leukapheresis. Isolated CD133(+) stem cells were suspended in 300 µl of the patient's cerebrospinal fluid and implanted into the motor cortex. Adverse events were recorded at each step of the procedure and were classified according to the Common Terminology Criteria for Adverse Events v3.0. The survival at 1 year was 90% after transplantation. with a mean long-term survival rate of 40.17 months from diagnosis. The most common adverse events were in grades I-II and involved transient skin pain (19.5% of patients) attributed to the insertion of the Mahurkar catheter into the subclavian vein, minor scalp pain (15.9%), and headache (12.2%) from the surgical procedure. Several patients (1.5 - 4.5%) reported diverse grade I adverse events. There were two deaths, one considered to be associated with the procedure (1.5%) and the other associated with the disease. Autologous stem cell transplantation into the frontal motor cortex is safe and tolerated well by patients. Further controlled studies are required to define the efficacy of this procedure.