Okezie Obasi Kanu

Glioblastoma multiforme: a review of where we have been and where we are going

Malignant gliomas such as glioblastoma multiforme (GBM) present some of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements in oncology. Even with aggressive surgical resections using state-of-the-art preoperative and intraoperative neuroimaging, along with recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal: median survival after diagnosis is about 14 months. Established good prognostic factors are limited, but include young age, high Karnofsky Performance Status (KPS), high mini-mental status examination score, O6-methylguanine methyltransferase promoter methylation, and resection of > 98% of the tumor. Standard treatment includes resection, followed by concurrent chemotherapy and radiotherapy. GBM research is being conducted worldwide at a remarkable pace, with some of the more recent promising studies focused on identification of aberrant genetic events and signaling pathways, tumor stem cell identification and characterization, modulation of tumor immunological responses, combination therapies, and understanding of the rare long-term survivors. Past treatment strategies have failed for various reasons; however, newer strategies in trials today and on the horizon encourage optimism. To help illustrate ‘where we have been’ with this fatal disease and ‘where we are going’ with contemporary studies, we include in this review a detailed history of Phase III clinical trials for GBM, with a final emphasis on exciting new treatment strategies that offer hope for future GBM therapy.

Glioblastoma multiforme: a review of therapeutic targets

Glioblastoma is the commonest primary brain tumor, as well as the deadliest. Malignant gliomas such as glioblastoma multiforme (GBM) present some of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements in oncology. Even with aggressive surgical resections using state-of-the-art preoperative and intraoperative neuroimaging, along with recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal: survival after diagnosis is about 1 year. Established prognostic factors are limited, but include age, Karnofsky performance status, mini-mental status examination score, O6-methylguanine methyltransferase promoter methylation and extent of surgery. Standard treatment includes resection of > 95% of the tumor, followed by concurrent chemotherapy and radiotherapy. Nevertheless, GBM research is being conducted worldwide at a remarkable pace, in the laboratory and at the bedside, with some of the more recent promising studies focused on identification of aberrant genetic events and signaling pathways to develop molecular-based targeted therapies, tumor stem cell identification and characterization, modulation of tumor immunological responses and understanding of the rare long-term survivors. With this universally fatal disease, any small breakthrough will have a significant impact on survival and provide hope to the thousands of patients who receive this diagnosis annually. This review describes the epidemiology, clinical presentation, pathology and tumor immunology, with a focus on understanding the molecular biology that underlies the current targeted therapeutics being tested.

Glioblastoma Multiforme Oncogenomics and Signaling Pathways

In the adult population, glioblastoma multiforme is one of the most common primary brain tumors encountered. Unfortunately, this highly malignant tumor represents over 50% of all types of primary central nervous system gliomas. The vast majority of GBMs develops quite rapidly without clinical, radiological, or morphologic evidence of a less malignant precursor lesion (primary or de novo GBMs), as compared to secondary GBMs that develop slowly by progression from diffuse low-grade astrocytomas. These GBM subtypes must be kept in mind because they may constitute distinct disease entities. Even though they look histologically quite similar, they likely involve different genetic alterations and signaling pathways. Decades of surgical therapy, radiotherapy, and chemotherapy have failed to drastically change survival. Clearly, we do not fully understand this tumor; however, the exciting genetic revolution in glioma research over the past decade is providing a promising outlook for exploring this tumor at the genetic level. Science has begun to elucidate the numerous genetic alterations and critical signaling pathways, and it has opened new exciting areas of research such as glioma stem cell biology and neoangiogenesis. This work has already begun to improve our understanding of GBM cell proliferation, migration, and invasion. Indeed, exciting novel targeted therapies are making their way to clinical trials based on this increased knowledge. This review provides the current understanding of GBM oncogenomics, signaling pathways, and glioma stem cell biology and discusses the potential new therapeutic targets on the horizon.

Early outcome of combined endoscopic third ventriculostomy and choroid plexus cauterization in childhood hydrocephalus

OBJECT Although shunts have been the mainstay in treating hydrocephalus over the past 5 decades, the use of endoscopic techniques in addressing this disorder in children offers both the neurosurgeon and the patient a unique opportunity to avoid shunting and its attendant complications. The combination of endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) remains uncommon in most centers despite its potential promise. The authors sought to investigate the efficacy of combining ETV and CPC (ETV+CPC) in treating childhood hydrocephalus in Nigeria. Infection and spina bifida contribute a high percentage of the cases of hydrocephalus in Nigeria. METHODS Over a 2-year period, all children 0-18 years of age who had endoscopic treatment for hydrocephalus were prospectively evaluated to determine the need for subsequent treatment. Children who had the combination of ETV+CPC were identified as a subcategory and form the basis of this retrospective study. RESULTS Twenty-two of 38 endoscopically treated children had undergone the combination of ETV+CPC for hydrocephalus of varied etiology. There was a male preponderance (2.5:1), and 90% of the patients were infants. The overall success rate was 75%, with the best outcome in children with spina bifida. One child required a repeat ETV. CONCLUSIONS The combination of ETV+CPC is useful in treating children with hydrocephalus of varied etiology. The complication profile is acceptable, and the overall success rate is comparable to that associated with shunt insertion.

Intracranial epidural abscess of odontogenic origin.

Dental infection as a cause of epidural abscess is rare compared with other forms of intracranial suppurations. A 10-year-old boy was seen because of headaches and fever. There was no history of otitis media or sinusitis, but he had sought care for dental complaints. The patient was from an upper-middle-class family, was not immunocompromised, and had no other risk factor for a major infection. A CT brain scan confirmed a frontal epidural abscess. The patient underwent emergency surgery for evacuation of the epidural abscess, followed by antimicrobial therapy. His condition improved remarkably following surgery, with complete resolution of symptoms. He subsequently underwent extraction of 2 teeth following dental review. Dental infection as a cause of intracranial epidural abscess is rare, but should be considered when evaluating patients for intracranial infections. A review of the literature sheds light on the causal relationship and possible pathogenesis of this condition.

Efficacy of endoscopic third ventriculostomy in the management of hydrocephalus in children under 2 years of age: Experience from a tertiary institution in Nigeria

BACKGROUND The management of hydrocephalus in developing countries is challenging. Hydrocephalus is a common childhood disorder in developing countries in particular and its management is quite challenging. Ventriculoperitoneal (VP) shunt is associated with high failure rates and complications. Endoscopic third ventriculostomy (ETV) with potentially lower complication rate could improve care and reduce cost of management of hydrocephalus. OBJECTIVE The aim of this study was to evaluate the efficacy (success rate) of ETV in children ≤2 years and to find out factors that may be responsible for good outcome of ETV. METHODS This prospective observational study was conducted at Lagos University Teaching Hospital, Lagos. Nigeria. All consecutive children ≤2 years of age with hydrocephalus were recruited into the study. Relevant demographic and clinical data documented. All cases had ETV and were followed up to document 6 months outcome. RESULTS A total of 34 patients (M: F ratio 1.1:1) were recruited over a 2-year period. Age, sex, presumed aetiology and image findings were not statistically significant in influencing outcome of ETV. Good outcome (defined as uneventful postoperative period, not requiring repeat ETV or VP shunt) was documented in 26 (73.5%). A total of 8 (26.5%) experienced poor outcome. Complication occurred in 2 (5.9%) as follows: Wound infection 1 (2.9%) and ventriculitis 1 (2.9%). Aetiology was divided into non post-infective hydrocephalus-20 (58.8%), post-infective hydrocephalus-5 (14.7%) and post-myelomeningocoele repair-9 (26.5%). CONCLUSIONS This study shows that ETV success rate is high in the management of hydrocephalus in children ≤2 years in our clinical practice. Regardless of the clinical diagnosis, where the facilities are available, children with hydrocephalus will benefit from ETV irrespective of the age and aetiology in sub Saharan Africa.

Knowledge and utilization of HIV counseling and testing services among students of a tertiary institution in Abia State, South East Nigeria

Introduction: As more and more people with human immunodeficiency virus (HIV) live longer and enjoy healthier lives because of antiretroviral therapy, there are an increasing number of sexual transmissions of HIV. It is exceedingly important to assess the proportion of unsafe sexual practices among people living with HIV/AIDS (PLWHAs) and their disclosure status so that behavioral intervention can be designed optimally for them in order to curb secondary HIV transmission and potential reinfection with different or drug resistant strain of HIV. Aim: To assess sexual behavior and serostatus disclosure of PLWHAs attending antiretroviral therapy (ART) center in Vadodara. Settings and Design: The current cross-sectional study was carried out at ART center of a tertiary care hospital - Shree Sayaji General (SSG) Hospital, Vadodara after taking necessary permissions and approval from institutional review board (IRB). Materials and Methods: A semistructured questionnaire was used for interview with PLWHA who are on ART after taking written and informed consent. Data was entered and analyzed using Epi Info software. Results: A total of 175 PLWHAs were enrolled in this study. Forty-three percent of the PLWHAs practiced premarital sex, while 15% of them practiced extramarital sex (EMS). Nearly 90% of these sexual practices were unsafe. Fifty-eight percent of the PLWHAs continued these unsafe sexual practices even after HIV diagnosis. Nearly 20% of the PLWHAs did not receive any counseling regarding sexual behavior. Ninety-five percent of respondents had disclosed their serostatus to their spouse. Conclusions: Still a remarkable proportion of PLWHAs indulge in unsafe sexual practices and the most common reason encountered among them was desire for child. Although majority of the participants had disclosed their serostatus to their spouse, many respondents did not mention their serostatus to other sexual partners. There is a need to stress on the importance of safe sex among PLWHAs not only to prevent transmission to their partners, but also to help them avoid receiving potentially resistant HIV strains in case of seroconcordant couples. A need-based sexual behavior-related motivational counseling needs to be focused on.Introduction: This study was carried out among people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) receiving antiretroviral therapy (ART) in a tertiary health facility in Nigeria and it is aimed at determining practice of adherence among these patients. Materials and Methods: A total of 282 HIV positive patients receiving ART in Nnamdi Azikiwe University Teaching Hospital, Nnewi were selected by systematic random sampling technique and using a semi-structured, interviewer administered questionnaire, responses were elicited from them on knowledge and perception of ART and adherence. Practice of adherence was determined by self-report. Findings were analyzed using Statistical Package for the Social Sciences version 17 (IBM Corp, Chicago Illinois, USA). Results: Most of the respondents were females (66.3%) and their mean age of the respondents was 36.63 ΁ 8.56 years. Most of the respondents have good knowledge of ART and adherence, even though most of them (64.2%) thought that ART cures HIV/AIDS. Most patients still considered HIV/AIDS as a serious illness (78.0%). Only about half of them (50.7%) were of the opinion that ART reduces the risk of HIV transmission. However, the general perception of adherence was good. The mean level of adherence was 97.8%, however, about 86% of them attained optimal adherence level. Conclusion: The study revealed fairly good knowledge and perception of ART and adherence among the patients. The level of ART adherence was also high; however there is a need to address some gaps in knowledge identified as part of measures aimed at improving adherence in the long run.Context: Disclosing ones human immunodeficiency virus (HIV) status helps in reducing the spread of the disease. Intimate partners are encouraged to reveal their status to each other. Such strategies aid in determining discordance and also target proven interventions to the correct demographic. Objective: The objective was to determine the rates of discordance among HIV positive pregnant women and their partners attending Nnamdi Azikiwe University Teaching Hospital, Nnewi. Materials and Methods: Partners of HIV positive pregnant women who had been notified of their spouses status were invited, counseled, and those who accepted, were tested for HIV using the national testing algorithm. Pre- and post-test counseling was offered to all tested partners. Results: A total of 10,070 new patients booked for antenatal care during the study period. Eight thousand nine hundred and seventy-nine (89.2%) of them were counseled, with 8317 (92.6%) of them accepted to do the HIV test. Seven hundred and ninety-seven women tested positive giving a sero-prevalence of 9.6%. Although 84.4% (673) of the positive mothers stated their intent to notify their partners, only 21% (141) of the partners presented for counseling and testing. On the whole, 98.6% (139) of the partners who presented accepted the test with 45.3% (63) of them testing positive, giving a sero-discordance rate of 54.7%. Conclusion: The discordance rate among tested partners is high in our center and suboptimal counseling, and testing rates were observed in the male partners. Interventions aimed at increasing partner involvement should be devised and adapted for our region. This will yield more data, give a truer picture of discordance rates as well as the aid in better management of scarce resources in program implementation.Opportunistic fungal infections account for a significant amount of morbidity associated with human immunodeficiency virus (HIV) disease. Oral candidiasis is one of the earliest premonitory signs of HIV infection and its diagnosis may have grave prognostic implications for the eventual development of full blown acquired immunodeficiency syndrome (AIDS). It is considered as an important marker of immune suppression and may be the initial manifestation of the disease in about 10% of HIV-infected adults. Careful history taking and detailed examination of the patients oral cavity are important parts of the physical examination, and diagnosis requires appropriate investigative techniques. Early recognition, diagnosis, and treatment of HIV-associated oral lesions may reduce morbidity. This review is intended to provide information on clinical variants of oral candidiasis and management as dental care providers are likely to be among the first to recognize such manifestations.Motor neuron diseases (MND) are extremely rare neurological manifestations of human immunodeficiency virus (HIV). We report a case of a 33-year-old known HIV seropositive male who presented with progressive asymmetrical onset of weakness and wasting of both distal limbs along with dysphagia and difficulty in speech. Examination revealed significant atrophy with visible fasciculations in thenar and hypothenar areas of both hands and dorsum of both feet associated with brisk deep tendon reflexes and jaw jerks, but diminished gag reflexes. Electromyography revealed evidence of denervation pattern. Investigations for underlying causes of MND other than HIV were noncontributory. Administration of riluzole along with continuation of antiretroviral therapy brought significant relief to his limb weakness, but bulbar features continued to progress. The case report highlights the rare, but definite association between HIV and amyotrophic lateral sclerosis (ALS) and partial reversibility of disabling clinical features on highly active antiretroviral therapy, which mandates ruling out HIV in all cases of ALS.through implementation of option B+ would have various other benefits. The total fertility rate in Malawi is high, around five to six births per woman, which is unlikely to be much lower in HIV‑infected women. Soon after the breastfeeding period (median duration 23 months) many women become pregnant again. Thus, a stop‑start approach to ART administration is almost redundant. Many women present for antenatal care late in pregnancy—an estimated 50% are thought to attend after 28 weeks of gestation—and continuing prophylaxis with antiretroviral drugs would mean that the next pregnancy could be protected from conception. The stopping of ART after cessation of breastfeeding might lead to viral rebound, with the risk of transmission to a sexual partner or fetus being notably raised. In women in Zimbabwe even those with CD4 cell counts higher than 350 cells per μL had a risk of death around six times higher than that in noninfected women within 24 months post‑partum [2,3] , and early ART could reduce mortality by 50‑90%. [4] Prevention

Neonatal burns in Lagos, South-Western Nigeria: Epidemiology and outcome of management.

BACKGROUND Burns in the neonate are rare and result mostly from iatrogenic sources in developed countries. The socioeconomic settings of developing countries are different from those in the developed countries. A review of the epidemiology and management of burns in the neonates in Lagos, Nigeria is presented. METHODS The case notes of burns in patients less than 29 days-old from 2004 to 2008 in 4 tertiary health institutions in Lagos were retrieved from the Medical Records Department; necessary data were extracted and analyzed. RESULTS There were 21 neonates with burns within the study period. The incidence of neonatal burns ranged between 0.5 and 2.5%/year. The mean age was 16.38 ± 1.84 days and the mean BSA of 26.00 ± 5.53%. The etiology of burns was thermal in 19(90.5%) and chemical in 2(9.5%). Hypokalemia was common at early stages of their treatment. Burns were sustained at home in 90.5% of the cases. The mortality rate was 43.5%. Inhalation and thermal injuries were associated with most of the deaths. CONCLUSION Domestic incidents from flames are the commonest causes of neonatal burns in the study environment. These are associated with prolonged morbidity and high mortality rate. Health education, highlighting methods of prevention should be undertaken in the community. Well equipped burn centers should be established to treat burns in all age groups.

Infantile subdural empyema: The role of brain sonography and percutaneous subdural tapping in a resource-challenged region

Background: This study explored the outcome of children with patent anterior fontanelles who were treated with trans-fontanelle ultrasound scan (TFUSS), which is more affordable and available than CT scan and MRI in the diagnosis of childhood intracranial pathologies and treatment of subdural empyema, in developing countries. Patients and Methods: Seventeen infants with post-meningitic subdural empyema, diagnosed using trans-fontanelle ultrasound alone and treated with subdural tapping over a 31-months period, were studied. Results: Eleven patients presented with grades II and III Bannister and William grading for level of consciousness in intracranial subdural empyema. Aspirate from 7 (41.2%) patients were sterile. The most common organisms isolated were Streptococcus faecalis 3 (17.6%), Haemophilus Influenza 2 (11.8) and Staphylococcus aureus 2 (11.8), multiple organisms were isolated in three of the patients. Ninety-four percent (94%) of the patients had good outcome. Five subjects developed hydrocephalus, one patient had a recurrence of subdural empyema, four patients had residual hemiparesis, two of the four patients had speech difficulties, while one patient (~6%) died. Conclusion: While CT and MRI remain the gold standard for investigating intracranial lesions, transfontanelle ultrasonography is adequate for diagnosis of infantile subdural empyema in resource-challenged areas. Percutaneous subdural tap is an affordable and effective therapy in such patients with financial challenges.

Surgical decompression for traumatic spinal cord injury in a tertiary center

Background: There are controversies regarding the importance and timing of spinal cord decompression following trauma. Documented evidence shows that early decompression in the setting of acute spinal cord injury (SCI) improves neurologic outcomes. Our objective was to evaluate the outcome of posttraumatic spinal cord decompression with or without spinal stabilization in our region. Methodology: We performed a cross-sectional study on adult patients who presented with acute spinal cord compression of traumatic etiology within a 2-year period. The primary outcome was change in Frankels grading 6 months after surgery. Secondary outcomes were complication rates and mortality. Results: A total of 35 patients made up of 24 (68.6%) males and 11 (31.4%) females were recruited into the study. The spectrum of injuries included cervical 27 (77.1%), thoracic 7 (20.0%), and lumbar vertebrae 1 (2.9%). The outcome as measured by Frankels grade at 6 months after surgery showed improvement in 9 (25.7%) patients following intervention. All patients who presented with Frankels Grade C and D improved to Grade E while none of those who presented with Frankels Grade E deteriorated. The common complications of spine decompression and fixation in this series were surgical site infections (11.4%) and chest infections (11.4%), especially in high cervical injury. Conclusion: Spinal cord decompression with spinal stabilization enhances the rehabilitation of patients with unstable spine and completes spinal cord injuries. Our experience shows improvement in neurological function in patients with spinal cord decompression despite the challenges of instrumentation in Sub-Saharan Africa.