Emerging Concepts in Vascular Dementia: A Review.

OBJECTIVE: Vascular dementia (VaD) is the second most common cause of dementia and a major health concern worldwide. A comprehensive review on VaD is warranted for better understanding and guidance for the practitioner. We provide an updated overview of the epidemiology, pathophysiological mechanisms, neuroimaging patterns as well as current diagnostic and therapeutic approaches. MATERIALS AND METHODS: A narrative review of current literature in VaD was performed based on publications from the database of PubMed, Scopus and Google Scholar up to January, 2021. RESULTS: VaD can be the result of ischemic or hemorrhagic tissue injury in a particular region of the brain which translates into clinically significant cognitive impairment. For example, a cerebral infarct in the speech area of the dominant hemisphere would translate into clinically significant impairment as would involvement of projection pathways such as the arcuate fasciculus. Specific involvement of the angular gyrus of the dominant hemisphere, with resultant Gerstman's syndrome, could have a pronounced effect on functional ability despite being termed a "minor stroke". Small vessel cerebrovascular disease can have a cumulate effect on cognitive function over time. It is unfortunately well recognized that "good" functional recovery in acute ischemic or haemorrhagic stroke, including subarachnoid haemorrhage, does not necessarily translate into good cognitive recovery. The victim may often be left unable to have gainful employment, drive a car safely or handle their affairs independently. CONCLUSIONS: This review should serve as a compendium of updated information on VaD and provide guidance in terms of newer diagnostic and potential therapeutic approaches.

A comparison of the techniques of direct pars interarticularis repairs for spondylolysis and low-grade spondylolisthesis: a meta-analysis.

OBJECTIVE Spondylosis with or without spondylolisthesis that does not respond to conservative management has an excellent outcome with direct pars interarticularis repair. Direct repair preserves the segmental spinal motion. A number of operative techniques for direct repair are practiced; however, the procedure of choice is not clearly defined. The present study aims to clarify the advantages and disadvantages of the different operative techniques and their outcomes. METHODS A meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The following databases were searched: PubMed, Cochrane Library, Web of Science, and CINAHL ( Cumulative Index to Nursing and Allied Health Literature). Studies of patients with spondylolysis with or without low-grade spondylolisthesis who underwent direct repair were included. The patients were divided into 4 groups based on the operative technique used: the Buck repair group, Scott repair group, Morscher repair group, and pedicle screw-based repair group. The pooled data were analyzed using the DerSimonian and Laird random-effects model. Tests for bias and heterogeneity were performed. The I2 statistic was calculated, and the results were analyzed. Statistical analysis was performed using StatsDirect version 2. RESULTS Forty-six studies consisting of 900 patients were included in the study. The majority of the patients were in their 2nd decade of life. The Buck group included 19 studies with 305 patients; the Scott group had 8 studies with 162 patients. The Morscher method included 5 studies with 193 patients, and the pedicle group included 14 studies with 240 patients. The overall pooled fusion, complication, and outcome rates were calculated. The pooled rates for fusion for the Buck, Scott, Morscher, and pedicle screw groups were 83.53%, 81.57%, 77.72%, and 90.21%, respectively. The pooled complication rates for the Buck, Scott, Morscher, and pedicle screw groups were 13.41%, 22.35%, 27.42%, and 12.8%, respectively, and the pooled positive outcome rates for the Buck, Scott, Morscher, and pedicle screw groups were 84.33%, 82.49%, 80.30%, and 80.1%, respectively. The pedicle group had the best fusion rate and lowest complication rate. CONCLUSIONS The pedicle screw-based direct pars repair for spondylolysis and low-grade spondylolisthesis is the best choice of procedure, with the highest fusion and lowest complication rates, followed by the Buck repair. The Morscher and Scott repairs were associated with a high rate of complication and lower rates of fusion.

Do the clinicoradiological outcomes of endoscopic fenestration for intracranial cysts count on age? An institutional experience.

BACKGROUND: The clinicoradiological outcome of endoscopic fenestration of intracranial cysts and predictors of an unfavorable outcome, including age, are under reported in the neurosurgical literature. In this cohort, our experience in the endoscopic fenestration of intracranial cysts is reviewed. MATERIALS AND METHODS: Thirty consecutive patients treated with endoscopic fenestration for intracranial cysts were identified and analyzed. The study population in our series was followed clinically and radiographically. RESULTS: In this series, the overall resolution of clinical symptoms such as headache, seizures, and neurological deficits was 83%, P= 0.0001. The percentage of clinical resolution after endoscopic intervention was significantly higher (85% vs. 76%, P= 0.001) in arachnoid cysts compared to other cyst types. The reduction of arachnoid cyst size was significantly higher in adults with obstructive hydrocephalus compared to the children group (P = 0.037). In addition, requirement of a cystoperitoneal shunt placement (P = 0.0001) and its subsequent revision (P = 0.0001) was significantly lower in adults compared to children. Adults (P = 0.041), presence of an arachnoid cyst (P = 0.026), female gender (P = 0.016), and presence of communicative hydrocephalus (P = 0.015) were significant predictors for improvement in the symptoms of intracranial pressure. Lastly, adults (P = 0.028), presence of arachnoid cyst (P = 0.046), and presence of communicative hydrocephalus (P = 0.012) were significant positive predictors for shunt revision. CONCLUSIONS: This study revealed that endoscopic fenestration is an effective neurosurgical procedure for the management of intracranial cysts both in adults and children. Moreover, endoscopic fenestration is more beneficial in adults and patients with an arachnoid cyst compared to that in children and other cyst types, respectively.

Outcome of ventriculoperitoneal shunt and predictors of shunt revision in infants with posthemorrhagic hydrocephalus.

OBJECT: Ventriculoperitoneal (VP) shunts in infants with posthemorrhagic hydrocephalus (PHH) are prone to failures, with some patients at risk for multiple revisions. The objective of our study is to observe long-term outcomes and identify factors leading to proximal and distal multiple failures. METHODS: We performed a retrospective review of infants with PHH that required VP shunt placement between 1982 and 2014. These patients were monitored clinically and radiographically after VP shunt placement. RESULTS: A total of 502 surgical procedures (initial shunt insertion and revisions) were performed, with 380 shunt revisions in 102 (84 %) patients. Median shunt survival time was 54 months (0.03-220 months). Shunt survival was significantly affected by the following factors: intraventricular hemorrhage (IVH, grade II-III, 95 months vs. grade IV, 28 months, p = 0.022), birth weight (<1.5 kg, 59 months vs. >1.5 kg, 22 months, p = 0.005), gestational age (>27 weeks, 90 months vs. <27 weeks, 20 months, p < 0.0001), distal vs. proximal revision (133 months vs. 48 months, p = 0.013), obstruction (yes, 78 months vs. no, 28 months, p = 0.007), and infection (no, 75 months vs. yes, 39 months, p = 0.045). Regression analysis revealed that multiple gestation, head circumference (>27 cm), congenital anomalies, infection, and obstruction increased the proximal and distal shunt malfunction. CONCLUSION: Long-term outcome of VP shunt placement in infants revealed a relatively high rate of complications requiring shunt revision as late as 30 years after initial placement. Infants with VP shunts should be monitored lifelong of these patients by neurosurgeons.

Neuromodulation in intractable pain management: outcomes and predictors of revisions of spinal cord stimulators.

OBJECTIVE Spinal cord stimulators (SCSs) appear to be safe and efficacious for chronic intractable back pain. Although there are many reports on percutaneous SCSs, there are very few studies on outcomes of paddle lead SCSs. In addition, the predictors of requirement for SCS revision have not been well established. Here, the authors review the outcome of a case series and attempt to identify the predictors of SCS revisions. METHODS The clinical and radiological information of 141 patients with intractable chronic pain who underwent SCS implantation within the past 20 years was retrospectively reviewed. Paddle lead SCSs were used in this series. Statistical analysis was conducted using Kaplan-Meier curves and Cox proportional-hazards regression. RESULTS Among 141 cases, 90 (64%) did not require any revision after SCS implantations. Removal of the SCS was required in 14 patients. The average pain score was significantly reduced (preimplantation score of 8 vs postimplantation score of 1.38; p < 0.0001). Younger age, male sex, obesity, a preimplantation pain score ≥ 8, and the presence of neuromuscular pain were identified as predictors of the overall requirement for SCS revision. However, only a preimplantation pain score ≥ 8 was identified as a predictor of early failure of the SCS. CONCLUSIONS Implantation of a paddle lead SCS is a relatively less invasive, safe, and effective procedure for patients with intractable back pain. Revision of the procedure depends on many factors, including younger age, male sex, associated neuromuscular pain, and severity of the pain. Therefore, patients with these factors, for whom implantation of an SCS is planned, should be closely followed for the possible requirement for revision.

Spinal meningiomas: clinicoradiological factors predicting recurrence and functional outcome.

OBJECTIVE Spinal meningiomas are benign tumors with a wide spectrum of clinical and radiological features at presentation. The authors analyzed multiple clinicoradiological factors to predict recurrence and functional outcome in a cohort with a mean follow-up of more than 4 years. The authors also discuss the results of clinical studies regarding spinal meningiomas in the last 15 years. METHODS The authors retrospectively reviewed the clinical and radiological details of patients who underwent surgery for spinal tumors between 2001 and 2015 that were histopathologically confirmed as meningiomas. Demographic parameters, such as age, sex, race, and association with neurofibromatosis Type 2, were considered. Radiological parameters, such as tumor size, signal changes of spinal cord, spinal level, number of levels, location of tumor attachment, shape of tumor, and presence of dural tail/calcification, were noted. These factors were analyzed to predict recurrence and functional outcome. Furthermore, a pooled analysis was performed from 13 reports of spinal meningiomas in the last 15 years. RESULTS A total of 38 patients were included in this study. Male sex and tumors with radiological evidence of a dural tail were associated with an increased risk of recurrence at a mean follow-up of 51.2 months. Ventral or ventrolateral location, large tumors, T2 cord signal changes, and poor preoperative functional status were associated with poor functional outcome at 1-year follow-up. CONCLUSIONS Spine surgeons must be aware of the natural history and risk factors of spinal meningiomas to establish a prognosis for their patients.

Epidemiology of adult-onset hydrocephalus: institutional experience with 2001 patients.

OBJECTIVE Adult-onset hydrocephalus is not commonly discussed in the literature, especially regarding its demographic distribution. In contrast to pediatric hydrocephalus, which is related to a primary CSF pathway defect, its development in adults is often secondary to other pathologies. In this study, the authors investigated the epidemiology of adult-onset hydrocephalus as it pertains to different etiologies and in reference to age, sex, and race distributions. METHODS The authors retrospectively reviewed the clinical notes of 2001 patients with adult-onset hydrocephalus who presented to Louisiana State University Health Sciences Center within a 25-year span. Significant differences between the groups were analyzed by a chi-square test; p < 0.05 was considered significant. RESULTS The overall mean (± SEM) incidence of adult hydrocephalus in this population was 77 ± 30 per year, with a significant increase in incidence in the past decade (55 ± 3 [1990-2003] vs 102 ± 6 [2004-2015]; p < 0.0001). Hydrocephalus in a majority of the patients had a vascular etiology (45.5%) or was a result of a tumor (30.2%). The incidence of hydrocephalus in different age groups varied according to various pathologies. The incidence was significantly higher in males with normal-pressure hydrocephalus (p = 0.03) or head injury (p = 0.01) and higher in females with pseudotumor cerebri (p < 0.0001). In addition, the overall incidence of hydrocephalus was significantly higher in Caucasian patients (p = 0.0002) than in those of any other race. CONCLUSIONS Knowledge of the demographic variations in adult-onset hydrocephalus is helpful in achieving better risk stratification and better managing the disease in patients. For general applicability, these results should be validated in a large-scale meta-analysis based on a national population database.

Role of radiological parameters in predicting overall shunt outcome after ventriculoperitoneal shunt insertion in pediatric patients with obstructive hydrocephalus.

OBJECTIVE Despite significant advances in the medical field and shunt technology, shunt malfunction remains a nightmare of pediatric neurosurgeons. In this setting, the ability to preoperatively predict the probability of shunt malfunction is quite compelling. The authors have compared the preoperative radiological findings in obstructive hydrocephalus and the subsequent clinical course of the patient to determine any association with overall shunt outcome. METHODS This retrospective study included all pediatric patients (age < 18 years) who had undergone ventriculoperitoneal shunt insertion for obstructive hydrocephalus. Linear measurements were taken from pre- and postoperative CT or MRI studies to calculate different indices and ratios including Evans' index, frontal horn index (FHI), occipital horn index (OHI), frontooccipital horn ratio (FOHR), and frontooccipital horn index ratio (FOIR). Other morphological features such as bi- or triventriculomegaly, right-left ventricular symmetry, and periventricular lucency (PVL) were also noted. The primary clinical outcomes that were reviewed included the need for shunt revision, time interval to first shunt revision, frequency of shunt revisions, and revision-free survival. RESULTS A total of 121 patients were eligible for the analysis. Nearly half of the patients (47.9%) required shunt revision. The presence of PVL was associated with lower revision rates than those in others (39.4% vs 58.2%, p = 0.03). None of the preoperative radiological indices or ratios showed any correlation with shunt revision. Nearly half of the patients with shunt revision required early revision (< 90 days of primary surgery). The reduction in the FOHR was high in patients who required early shunt revision (20.16% in patients with early shunt revision vs 6.4% in patients with late shunt revision, p = 0.009). Nearly half of the patients (48.3%) requiring shunt revision ultimately needed more than one revision procedure. Greater occipital horn dilation on preoperative images was associated with a lower frequency of shunt revision, as dictated by a high OHI and a low FOIR in patients with a single shunt revision as compared with those in patients who required multiple shunt revisions (p = 0.029 and 0.009, respectively). The mean follow-up was 49.9 months. Age was a significant factor affecting shunt revision-free survival. Patients younger than 6 months of age had significantly less revision-free survival than the patients older than 6 months (median survival of 10.1 vs 94.1 months, p = 0.004). CONCLUSIONS Preoperative radiological linear indices and ratios do not predict the likelihood of subsequent shunt malfunction. However, patients who required early shunt revision tended to have greater reductions in ventricular volumes on postoperative images. Therefore a greater reduction in ventricular volume is not actually desirable, and a ventricular volume high enough to reduce intracranial pressure is instead to be aimed at for long-term shunt compliance.

Outcomes and predictors of improved survival after gamma knife radiosurgery for metastatic brain tumors originated from breast carcinoma.

Gamma knife radiosurgery (GKRS) has emerged as a possible treatment option for metastasis brain tumor (MBTs) originated from breast cancer. However, the intermediate or long-term outcome of GKRS on MBTs originated from breast carcinoma is not well defined. The outcome of GKRS on MBTs derived from breast carcinoma was reviewed in our institution's case series. We performed a retrospective review (2000-2013) of 50 patients with MBTs originated from breast cancer who received GKRS. Out of 50 patients, 11 patients had recurrent tumors after microsurgical resection and the other 39 patients received GKRS alone. The study population was followed clinically and radiographically after GKRS treatment. GKRS on MBTs metastasized from breast cancer showed significant variations in tumor growth control (decreased in 14 (31.9 %) patients, arrested growth in 17 (38.6 %) patients, and progressed tumor in 13 (29.5 %) patients). The overall median survival in this case series was 33 months. In our case series, overall survival rate after 5 years was 20 %, whereas progression-free survival rate after 5 years was 30 %. The prognostic factors for improving survival in the patients with MBTs from breast cancer were recursive partitioning analysis (RPA) class I (p = 0.014), age ≤65 years (p = 0.025), controlled primary tumor (p = 0.04), and single number of MBTs (p = 0.022). Recent follow-up revealed that GKRS offers good overall survival period in both new and recurrent patients with MBTs originated from breast carcinoma. Thus, GKRS is a therapeutic option for new and recurrent patients with MBTs derived from breast cancer.

Factors predictive of improved overall survival following stereotactic radiosurgery for recurrent glioblastoma.

The currently accepted standard of care for primary glioblastoma (GBM) consists of maximal surgical resection followed by fractionated external beam radiotherapy (EBRT) with concomitant temozolomide chemotherapy. The role of stereotactic radiosurgery (SRS) in the treatment of GBM is not well defined, but SRS has typically been applied as a salvage therapy for GBM recurrence. This paper reviews our single institution experience using gamma knife radiosurgery (GKRS) for the treatment of GBM. Thirty-six patients treated with GKRS for pathologically proven GBM at LSU Health in Shreveport from February 2000 to December 2013 were identified and analyzed. Patient characteristics, treatment variables, and survival were correlated. Seven patients received GKRS in the immediate postoperative period for an average tumor volume of 10.9 cm(3), and 29 patients were treated for a recurrent average tumor volume of 11.4 cm(3) with a prescribed dose ranging from 10 to 20 Gy at the 50 % isodose line. The median overall survival was significantly higher in recurrence group compared to up-front group [7.9 months (0.77-32.1 months) vs. 3.5 months (range 0.23-11.7 months) respectively, (p = 0.018)]. The predictive factors for improved survival in the patients with GBM were as follows: Karnofsky performance scale (KPS) > 70 (p = 0.026), age ≤ 50 years (p = 0.006), absence of neurodeficits (p = 0.01), and initial postoperative treatment with EBRT (p = 0.042). Adjuvant therapy with GKRS following GBM recurrence demonstrates statistical superiority over immediate postoperative boost therapy.

Role of apolipoprotein E polymorphism as a prognostic marker in traumatic brain injury and neurodegenerative disease: a critical review.

OBJECT The difference in course and outcome of several neurodegenerative conditions and traumatic injuries of the nervous system points toward a possible role of genetic and environmental factors as prognostic markers. Apolipoprotein E (Apo-E), a key player in lipid metabolism, is recognized as one of the most powerful genetic risk factors for dementia and other neurodegenerative diseases. In this article, the current understanding of APOE polymorphism in various neurological disorders is discussed. METHODS The English literature was searched for various studies describing the role of APOE polymorphism as a prognostic marker in neurodegenerative diseases and traumatic brain injury. The wide ethnic distribution of APOE polymorphism was discussed, and the recent meta-analyses of role of APOE polymorphism in multiple diseases were analyzed and summarized in tabular form. RESULTS Results from the review of literature revealed that the distribution of APOE is varied in different ethnic populations. APOE polymorphism plays a significant role in pathogenesis of neurodegeneration, particularly in Alzheimer's disease. APOE ε4 is considered a marker for poor prognosis in various diseases, but APOE ε2 rather than APOE ε4 has been associated with cerebral amyloid angiopathy-related bleeding and sporadic Parkinson's disease. The role of APOE polymorphism in various neurological diseases has not been conclusively elucidated. CONCLUSIONS Apo-E is a biomarker for various neurological and systemic diseases. Therefore, while analyzing the role of APOE polymorphism in neurological diseases, the interpretation should be done after adjusting all the confounding factors. A continuous quest to look for associations with various neurological diseases and wide knowledge of available literature are required to improve the understanding of the role of APOE polymorphism in these conditions and identify potential therapeutic targets.

Microsurgical clipping following failed coiling of a giant ophthalmic aneurysm.

With the advent of endovascular modalities, endovascular coiling has become a progressively more common method of addressing intracranial aneurysms. When despite coiling, an aneurysm continues to enlarge, open microsurgical clipping is a viable, though technically demanding option. We present a unique case of failed coiling of a giant ophthalmic region aneurysm, in which the aneurysm was successfully managed via open microsurgical approach. We highlight the unique challenges faced and demonstrate the surgical process in an operative video presentation. The video can be found here: http://youtu.be/k2P4c4Lvq7g .

Technical nuances of clipping a middle cerebral artery bifurcation aneurysm.

Broad-necked middle cerebral artery aneurysms present unique challenges for the vascular neurosurgeon, who must contend with smaller vessels and often a complex clipping strategy. Due to their superficial location, these lesions are still commonly selected for microsurgical clipping. We present a case of a 42-year-old woman with significant vascular disease with a right middle cerebral artery aneurysm. We discuss the key surgical steps, demonstrate the microsurgical dissection and intraoperative rupture encountered and the final clipping strategy, as well as the postoperative course in this operative video presentation. The video can be found here: http://youtu.be/qZ2gvqz7XdQ .

Elucidating the role of incidental use of beta-blockers in patients with metastatic brain tumors in controlling tumor progression and survivability.

BACKGROUND: Beta-adrenergic antagonists have demonstrated beneficial effects in tumor progression and survivability in patients with various cancers by inhibiting norepinephrine-induced tumor cell migration. However, little is known about their effects on the outcomes of metastatic brain tumors (MBTs). This study was undertaken to evaluate the effects of beta-blockers, if any, on the outcome of MBTs, and their possible role in controlling tumor progression and survivability. MATERIALS AND METHODS: A retrospective cohort analysis of 225 patients identified as having MBTs presenting to our institution from 2001 through 2013 was conducted by reviewing electronic patient records. Patients were categorized into three groups: Group A comprised hypertensives on beta-blockers only (40, 18%), Group B comprised hypertensive patients on antihypertensive medications other than beta-agonists (65, 29%), and Group C comprised normotensives (120, 53%). All outcomes were compared using the data on pre - and post-gamma knife radiosurgery (GKRS) for these groups. One-way analysis of variance (ANOVA) was used to compare the radiological and clinical outcomes in the patient population following beta-blockers usage in Group A versus groups B and C. Cox regression model was used to demonstrate prognostic factors for the outcome in patients having different primaries. Overall survival period was plotted on Kaplan-Meier curves. The log-rank (Mantel-Cox) test was used to analyze the survival difference in the cases. P < 0.05 was considered significant. RESULTS: The mean age of patients was 57.34 ± 10.98 years (range: 30-87 years) and 44% were males. More than half (130/225, 58%) of patients with MBT had their primary tumor source in the lung, 16% in the breast, and 7% each in the kidneys and the rectum. Frontal lobe was the most commonly affected (80, 35.5%). Statistically significant control of tumor growth (P = 0.001), tumor progression (P = 0.0001), and higher survival outcomes (P = 0.015) were observed in Group A as compared to other groups. In comparing the different groups, breast primaries showed the strongest correlation to survival benefit (P = 0.049) from beta-blocker usage as a primary antihypertensive medication. CONCLUSION: Concomitant use of beta-blockers with conventional therapy may offer potential benefit to hypertensive patients developing MBTs by ameliorating tumor progression and conferring a survival advantage. This effect was most notable in patients with primary tumors originating in the breast. Prospective studies, molecular research, and randomized controlled trials are warranted to further explore this promising effect.

First 1,000 Cases of Gamma Knife Surgery for Various Intracranial Disorders in LSU Health-Shreveport: Radiological and Clinical Outcome.

OBJECTIVE: Gamma knife radiosurgery (GKRS) has emerged as an important therapeutic alternative for different intracranial lesions. We have reviewed our institution's first 1,000 cases of radiosurgeries. MATERIALS AND METHODS: We performed a retrospective review (2000-2013) of 1,017 radiosurgeries in 911 patients with various intracranial lesions including vestibular schwannoma (82), meningioma (136), metastatic brain tumors (298), astrocytoma (49), pituitary adenoma (92), arteriovenous malformation (85) and trigeminal neuralgia (169). RESULTS: GKRS in different intracranial lesions showed significant variations in outcome and complications. Overall, the local tumor growth control for benign and malignant tumors was 89 percent and 70 percent respectively. The rate of obliteration of arteriovenous malformation nidus was 79 percent. The complete and partial relief of pain in the patients with trigeminal neuralgia was 55.6 percent and 22.4 percent respectively. CONCLUSION: At recent follow-up, GKRS showed good control of different tumor growth, obliteration of AVM nidus and remission of trigeminal neuralgia pain, good overall and progression free survival rate, possible preservation of neurological functions, lesser number of complications, and improvement of quality of life. Therefore, GKRS is an important treatment option for patients with different benign intracranial tumors, AVM and trigeminal neuralgia. However, GKRS is not effective for recurrent malignant tumors in the brain.

Redox balance dynamically regulates vascular growth and remodeling.

Vascular growth and remodeling responses entail several complex biochemical, molecular, and cellular responses centered primarily on endothelial cell activation and function. Recent studies reveal that changes in endothelial cell redox status critically influence numerous cellular events that are important for vascular growth under different conditions. It has been known for some time that oxidative stress actively participates in many aspects of angiogenesis and vascular remodeling. Initial studies in this field were largely exploratory with minimal insight into specific molecular mechanisms and how these responses could be regulated. However, it is now clear that intracellular redox mechanisms involving hypoxia, NADPH oxidases (NOX), xanthine oxidase (XO), nitric oxide and its synthases, and intracellular antioxidant defense pathways collectively orchestrate a redox balance system whereby reactive oxygen and nitrogen species integrate cues controlling vascular growth and remodeling. In this review, we discuss key redox regulation pathways that are centrally important for vascular growth in tissue health and disease. Important unresolved questions and issues are also addressed that requires future investigation.

Odilon Marc Lannelongue (1840-1911) and strip craniectomy for craniosynostosis.

In the 19th century, Dr. Odilon Marc Lannelongue was a pioneering French surgeon who introduced a surgical technique for the treatment of craniosynostosis. In 1890, Dr. Lannelongue performed correction of sagittal synostosis by strip craniectomy. From his procedure, multiple techniques have been developed and endorsed for this condition, ranging from simple suturectomies to extensive calvarial vault remodeling. In addition, even today, endoscopically aided strip craniectomy is performed as a surgical treatment of craniosynostosis. This article describes the life and works of the surgeon who revolutionized the management of craniosynostosis.

Hydrogen sulfide chemical biology: pathophysiological roles and detection.

Hydrogen sulfide (H2S) is the most recent endogenous gasotransmitter that has been reported to serve many physiological and pathological functions in different tissues. Studies over the past decade have revealed that H2S can be synthesized through numerous pathways and its bioavailability regulated through its conversion into different biochemical forms. H2S exerts its biological effects in various manners including redox regulation of protein and small molecular weight thiols, polysulfides, thiosulfate/sulfite, iron-sulfur cluster proteins, and anti-oxidant properties that affect multiple cellular and molecular responses. However, precise measurement of H2S bioavailability and its associated biochemical and pathophysiological roles remains less well understood. In this review, we discuss recent understanding of H2S chemical biology, its relationship to tissue pathophysiological responses and possible therapeutic uses.

Nitrite anion stimulates ischemic arteriogenesis involving NO metabolism.

Nitric oxide (NO) is a potential regulator of ischemic vascular remodeling, and as such therapies augmenting its bioavailability may be useful for the treatment of ischemic tissue diseases. Here we examine the effect of administering the NO prodrug sodium nitrite on arteriogenesis activity during established tissue ischemia. Chronic hindlimb ischemia was induced by permanent unilateral femoral artery and vein ligation. Five days postligation; animals were randomized to control PBS or sodium nitrite (165 µg/kg) therapy twice daily. In situ vascular remodeling was measured longitudinally using SPY angiography and Microfil vascular casting. Delayed sodium nitrite therapy rapidly increased ischemic limb arterial vessel diameter and branching in a NO-dependent manner. SPY imaging angiography over time showed that nitrite therapy enhanced ischemic gracillis collateral vessel formation from the profunda femoris to the saphenous artery. Immunofluorescent staining of smooth muscle cell actin also confirmed that sodium nitrite therapy increased arteriogenesis in a NO-dependent manner. The NO prodrug sodium nitrite significantly increases arteriogenesis and reperfusion of established severe chronic tissue ischemia.

Carotid atherosclerotic disease: A systematic review of pathogenesis and management.

Carotid stenosis is an important contributor to ischemic stroke risk with resultant significant impact on neurological disability and death in adults and with worldwide implications. Management of carotid stenosis is impacted by whether there are associated symptoms along with the degree of stenosis. Understanding of the pathogenesis of carotid atherosclerosis or stenosis is important in management of carotid stenosis. Atherosclerotic plaque formation is a chronic insidious process with a number of potential contributors to the formation of such a plaque. The definition of atherosclerosis is not simply limited to abnormal deposition of lipid but also includes a chronic, complex, inflammatory process. Molecularly, in atherosclerosis, there is decreasing nitric oxide (NO) bioavailability, activity and/or expression of endothelial NO synthase, or increasing degradation of NO secondary to enhanced superoxide production. These above changes cause endothelial dysfunction leading to formation of foam cell followed by formation on lipid plaque. After lipid plaque formation, stable or unstable atherosclerotic plaque is formed depending on the calcium deposition over the lipid plaque. It continues to be clearly established that carotid intervention for symptomatic high-grade carotid stenosis is best managed with intervention either by carotid endarterectomy or carotid stenting. However, asymptomatic carotid stenosis is the subject of considerable controversy in terms of optimal management. This review of carotid atherosclerosis is an attempt to incorporate the information provided by more recent studies on pathogenesis and management which may help in the decision-making process for optimal management for protection against stroke.