Accelerating matchmaking of novel dysmorphology syndromes through clinical and genomic characterization of a large cohort.

PURPOSE: Dysmorphology syndromes are among the most common referrals to clinical genetics specialists. Inability to match the dysmorphology pattern to a known syndrome can pose a major diagnostic challenge. With an aim to accelerate the establishment of new syndromes and their genetic etiology, we describe our experience with multiplex consanguineous families that appeared to represent novel autosomal recessive dysmorphology syndromes at the time of evaluation. METHODS: Combined autozygome/exome analysis of multiplex consanguineous families with apparently novel dysmorphology syndromes. RESULTS: Consistent with the apparent novelty of the phenotypes, our analysis revealed a strong candidate variant in genes that were novel at the time of the analysis in the majority of cases, and 10 of these genes are published here for the first time as novel candidates (CDK9, NEK9, ZNF668, TTC28, MBL2, CADPS, CACNA1H, HYAL2, CTU2, and C3ORF17). A significant minority of the phenotypes (6/31, 19%), however, were caused by genes known to cause Mendelian phenotypes, thus expanding the phenotypic spectrum of the diseases linked to these genes. The conspicuous inheritance pattern and the highly specific phenotypes appear to have contributed to the high yield (90%) of plausible molecular diagnoses in our study cohort. CONCLUSION: Reporting detailed clinical and genomic analysis of a large series of apparently novel dysmorphology syndromes will likely lead to a trend to accelerate the establishment of novel syndromes and their underlying genes through open exchange of data for the benefit of patients, their families, health-care providers, and the research community.Genet Med 18 7, 686-695.

Evaluating the initial impact of the Riyadh Epilepsy Awareness Campaign.

OBJECTIVE: We determine the impact of an educational awareness campaign on the level of knowledge and the attitude of the Saudi population in Riyadh, Saudi Arabia in an attempt to improve the awareness and reduce the social stigma associated with epilepsy. METHODS: The Saudi Epilepsy Society organized a citywide awareness campaign in 2013. A survey consisting of 11 questions pertaining to epilepsy awareness was distributed to Saudi citizens living in Riyadh, aged 15 years and above, in malls, health clubs, mosques, universities, and schools during that campaign. The same questionnaire was administered before and after the awareness campaign to the same individuals on the same day to assess the impact of the campaign (n=2118). RESULTS: The epilepsy awareness campaign significantly raised the general knowledge about epilepsy: 1519 before vs. 1944 after (P<0.001) would allow their children to interact with an individual who had epilepsy; 1567 before vs. 688 after (P<0.001) would not want their children to marry an individual with epilepsy. Eight hundred twenty six before vs. 47 after (P<0.001) thought that epilepsy is untreatable. Regarding the causes of epilepsy, 1663 before vs. 896 after (P<0.001) believed that epilepsy is caused by supernatural powers, and 1224 before vs. 1874 after (P<0.001) chose brain disease as a cause of epilepsy. CONCLUSION: These findings suggest that epilepsy awareness campaigns can close knowledge gaps. A long-term reevaluation may be needed to assess awareness sustainability.

Role of community health outreach program "living for health" in improving access to federally qualified health centers in Miami-dade county, Florida: a cross-sectional study.

BACKGROUND: Care of the underserved remains one of the most compelling challenges to American healthcare. Federally Qualified Health Centers (FQHCs) address uninsurance and underinsurance by providing primary and preventive care to vulnerable populations with fees charged based on ability to pay. Our goal is to study the effectiveness of FQHCs system in engaging patients and the barriers to utilization, which have not been well defined. METHODS: Retrospective analysis was performed on data from "Living for Health" (L4H) program participants from 2008 to 2012. Univariate and multivariate logistic regression analysis were performed to determine factors associated with FQHC utilization. RESULTS: Among 9453 subjects screened, 1889 were referred to a FQHC, but only 201(11%) actually sought treatment. Public insurance, non-Hispanic ethnicity, and hypertension were associated with higher rates of FQHC utilization. Inability to afford costs, cultural factors and inflexible appointment times were the most common reasons for FQHC underutilization. CONCLUSION: The current status of FQHC utilization is sub-optimal. Community outreach programs like L4H can improve the access and utilization of FQHCs.

Focal brainstem gliomas. Advances in intra-operative management.

Improved neuronavigation guidance as well as intraoperative imaging and neurophysiologic monitoring technologies have enhanced the ability of neurosurgeons to resect focal brainstem gliomas. In contrast, diffuse brainstem gliomas are considered to be inoperable lesions. This article is a continuation of an article that discussed brainstem glioma diagnostics, imaging, and classification. Here, we address open surgical treatment of and approaches to focal, dorsally exophytic, and cervicomedullary brainstem gliomas. Intraoperative neuronavigation, intraoperative neurophysiologic monitoring, as well as intraoperative imaging are discussed as adjunctive measures to help render these procedures safer, more acute, and closer to achieving surgical goals.

Ten self-inflicted intracranial penetrating nail gun injuries.

Penetrating craniocerebral injuries from nail gun use are rare. We describe a case of 10 self-inflicted nail gun injuries with intracranial penetrations. We also review the literature and discuss management strategies of such craniocerebral trauma. A 33-year-old male with a long-standing history of severe depression took a nail gun and sustained 10 penetrating intracranial injuries. Initial neuroimaging revealed 10 penetrating nails, all sparing the major cerebral vasculature. Immediate surgical removal was undertaken in the surgical suite using a combination of craniotomies, craniectomies, and blind removal. Intracranial injuries from self-inflicted nail gun misuse is becoming increasingly more frequent. Initial appropriate clinical decision-making are critical in preventing further cortical or vascular damage.

Length of MRI signal may predict outcome in advanced cervical spondylotic myelopathy.

OBJECTIVE: To study clinical and radiological factors that may correlate with independent walking (IW) following advanced cervical spondylotic myelopathy (CSM) surgery. METHODS: A retrospective case series including all advanced CSM patients (Nurick 4 and 5) who underwent surgery from 2003-2010 in the Division of Neurosurgery, Department of Surgery, College of Medicine, King Saud University and King Khalid University Hospital, Riyadh, Saudi Arabia. Only patients with 6 months or more follow-up were included. A neuroradiologist who was blinded to the clinical data reviewed all MRI studies. RESULTS: Forty-three patients were included (83% males, mean follow-up 29 months). A better preoperative neurological status was a positive predictor of IW after surgery (85.7% Nurick 4 versus 36.4% Nurick 5, p=0.001). Independent walking was less likely in patients with the following MRI features: longer T2-weighted image (T2WI) signal changes (p=0.001), well-circumscribed T2WI signal changes (p=0.028), T1WI hypointensity (p=0.001), and narrow spinal canal diameter (p=0.048). Multivariate regression revealed that both an increased T2WI signal change length and T1WI hypointensity were independent predictors. The risk of dependent walking increased by 1.35 times as the T2WI signal intensity length increased by one mm, and by 14-times with T1WI hypointensity. CONCLUSION: Regaining IW after surgery in patients with advanced CSM was less likely for cases showing MRI features of longer T2WI signal changes and T1WI hypointensity. Better baseline walking, less defined T2WI signal change, and a wider spinal canal were good prognostic factors.

Stroke awareness in the Saudi community living in Riyadh: prompt public health measures must be implemented.

BACKGROUND: Stroke is very prevalent in the Kingdom of Saudi Arabia, approaching 43.8 per 100,000 people. Stroke outcome is known to be affected by the level of stroke awareness in the community. We conducted this study to assess the level of stroke awareness in the Saudi population. METHODS: A validated survey of 11 questions was used to assess the level of stroke awareness among the Saudi population. The survey was distributed in a 1-month period to every adult Saudi citizen visiting 10 shopping centers, 10 large supermarkets, 4 hospitals, and 2 universities. RESULTS: Two thousand eight hundred sixty-two people completed the questionnaire (a 78% response rate). One thousand eight hundred forty-four people (64%) were able to define stroke correctly. One thousand four hundred twenty-eight people (49.9%) named mass media as the source of their knowledge. One thousand three hundred one (45.9%) believe stroke and brain death share the same pathologic mechanism and outcome, particularly those <40 years of age (P < .05). Six hundred twenty-two (21.7%) of the respondents correctly chose ≥5 risk factors and made ≤1 error. Five hundred twenty-seven (18.4%) of the participants in this study were able to correctly identify ≥3 symptoms of the list and make ≤1 error. CONCLUSIONS: There is an alarming deficit in the level of stroke awareness in the Saudi population. Urgent public health measures to correct this deficiency are promptly needed.

Pediatric brainstem tumors. Classifications, investigations, and growth patterns.

Brainstem gliomas occur in 10-20% of brain tumors in pediatrics. Over the past 3 decades, the treatment of brainstem gliomas has significantly progressed as a result of the gradual advancements in microsurgical techniques, sophisticated imaging technology and, most importantly, the availability of MRI. In this article, we review the current literature on brainstem gliomas and cover diagnosis, imaging, classification, and management. Surgical approaches and intraoperative modalities to tackle operable cases of brainstem gliomas will be discussed in a follow up article.

Epilepsy: What do health-care professionals in Riyadh know?

PURPOSE: The objective of this study was to report on the knowledge of epilepsy, as well as attitudes and practices toward individuals with epilepsy, among health-care professionals in Riyadh, the capital city of Saudi Arabia. METHODS: A survey consisting of 23 questions pertaining to epilepsy awareness was distributed to health education workers (n=51), nutritionists (n=56), physicians (n=265), dentists (n=58), pharmacists (n=41), nurses (n=224), physiotherapists (n=65), and fifth-year medical students (n=62) in three tertiary hospitals in Riyadh. RESULTS: Of the 822 respondents who completed the questionnaire, 100% had heard about epilepsy, and 92.6% would allow their children to interact with an individual who has epilepsy. However, 67% of respondents would not want their children to marry an individual with epilepsy, 97.9% of respondents believed that individuals with epilepsy should have the same employment opportunities as the general population, 10.5% believe that supernatural power is the cause of epilepsy, 67.2% did not know how to deal with an individual experiencing an epileptic episode, and 56% did not know that surgery was a treatment option for individuals with epilepsy in Saudi Arabia. Of the 822 respondents, 39% would not abide by a physician's advice not to operate a motor vehicle because of their illness, 91% of whom cited problems with the public transportation system as a reason for disregarding the doctor's advice. When asked if the participants had access to any information on how to deal with epilepsy during their professional training, 60.3% had access to such information during their graduate studies. Ninety-eight percent of those with access to this information were physicians and health-care educators (p<0.001). Physicians and health-care educators were significantly more aware of epilepsy than any of the other groups. CONCLUSION: The level of epilepsy awareness among health-care professionals in Riyadh needs improvement.

C2/3 instability: unusual cause of cervical myelopathy in a child with Down syndrome.

We report a rare cause of cervical myelopathy (CM) in a 10-year-old Down syndrome (DS) girl. She presented with progressive CM over 1 year affecting her ability to ambulate or feed herself. The myelopathy was secondary to C2/3 instability. Surgical reduction and instrumented fusion have significantly improved her neurological status. This case emphasizes the importance of close follow-up of DS patients for early diagnosis and treatment of cervical spine abnormalities.

Prevalence of symptoms and risk of sleep apnea in patients with ruptured cerebral aneurysm.

OBJECTIVE: To determine the prevalence of symptoms and risk of obstructive sleep apnea (OSA) among patients with ruptured cerebral aneurysms. METHODS: In this case-control study, a validated Arabic version of the Berlin Questionnaire (BQ) was administered to patients admitted to King Fahd Medical City, Riyadh, Saudi Arabia with cerebral aneurysms between January 2006 and July 2011 (n=53). The same questionnaire was administered to a control group comprised of patients attending primary health care clinics who were matched for age, body mass index (BMI), and gender (n=212). RESULTS: The mean age of patients with ruptured cerebral aneurysms was 50.7 +/- 15.2 years, and the mean BMI was 27.9 +/- 4.8 kg/m2. In this group, 75.5% complained of snoring compared with 46.7% of the controls (p=0.000). Hypertension was present in 67.9% of cases compared with 30.2% of the controls (p=0.000). Based on the BQ scores, 60.4% of the cases were considered to be at high risk for OSA compared with 31.6% of the controls (p=0.000). CONCLUSION: The prevalence of OSA symptoms among patients with ruptured cerebral aneurysms is very high. Almost 60% of patients with ruptured cerebral aneurysms are at risk for OSA.

A refined experimental model of fusiform aneurysms in a rabbit carotid artery.

OBJECTIVE: Reliable animal models are an important aspect of translational research, especially for relatively uncommon clinical entities such as fusiform aneurysms. While several animal models exist, very few are tailored to cerebral fusiform aneurysms, which have unique attributes compared to abdominal fusiform aneurysms. The authors aimed to build from previous models to create a cerebral fusiform aneurysm model that is simple to use and reliable. METHODS: Twelve female New Zealand White rabbits were assigned to 3 groups: group E, elastase only; group C, CaCl2 only; group EC, elastase + CaCl2. All rabbits underwent surgical exposure of the right common carotid artery (CCA) and 20 minutes of peri-carotid incubation with their respective chemicals. Angiography was performed 6 weeks later for arterial dilation measurements, with 50% increase in diameter being defined as fusiform aneurysm formation. The arterial segments, along with the contralateral CCAs, were harvested and assessed histologically for wall component measurements and elastin semiquantification. A separate rabbit underwent aneurysm creation per the group EC protocol and was treated with an endovascular flow-diversion device. RESULTS: All of the group EC rabbits developed fusiform aneurysms (mean dilation of 88%), while none of the group E or group C rabbits developed aneurysms (p = 0.001). Histological analysis revealed increased internal elastic lamina fragmentation in the group EC aneurysms, which also had less tunica intima hyperplasia. All aneurysms exhibited thinning of the tunica media and reduction in elastin content. The use of an endovascular flow-diverting stent was successful, with complete parent vessel remodeling, as expected, 4 weeks after deployment. CONCLUSIONS: The peri-arterial application of combined elastase and CaCl2 to the CCA appears sufficient to reliably produce fusiform aneurysms after 6 weeks. Exposure to elastase or CaCl2 individually appears insufficient, despite the observed histological changes to the arterial wall. The proposed fusiform aneurysm model is able to accommodate endovascular devices, simulating the tortuous pathway experienced in using such devices in human cerebral aneurysms and thus is a satisfactory model to use in translational research.

The utility of ultrasound for surgical spinal decompression.

Surgery is routinely performed to decompress the spinal cord. While a number of imaging modalities are currently used in the perioperative setting of surgical spinal cord decompression including computed tomography scan and magnetic resonance imaging, ultrasound (US) usage is relatively new. Therefore, only a few studies in the literature describe its value in the perioperative setting. US is a simple, safe, rapid, non-invasive, and inexpensive modality that constitutes a potential alternative when other modalities are not suitable or unavailable. It enables surgeons to generate high-resolution real-time images that can aid in diagnosing pathologies, guiding surgeries, and evaluating surgical outcomes. This review discusses the present literature and utility of pre-, intra-, and post-operative US in patients undergoing surgical spinal decompression. We also delineate three cases in which US was utilized at King Saud University hospital, which is considered one of the first centers in our region to report the use of US to guide treatment in spine surgery.

High resolution ultrasound in the evaluation and management of traumatic peripheral nerve injuries: review of the literature.

High-resolution ultrasound has been used as an important tool in the diagnosis, management and monitoring of both acute and chronic peripheral nerve injuries. According to literature, it demonstrated high sensitivity and specificity for the detection of specific pathologies and its ability to differentiate between them. Literature has been reviewed, summarizing the specific finding of such modality in various peripheral neuropathies and with a specific focus over its role in evaluation and management of traumatic peripheral neuropathies.

Causes and patterns of spine trauma in children and adolescents in Saudi Arabia: implications for injury prevention.

BACKGROUND AND OBJECTIVES: Knowledge regarding traumatic spine injuries (TSIs) is essential for effective prevention strategies, particularly in the developing world, where majority of the population is younger and organized prevention programs are scarce. Therefore, our objective was to describe TSI mechanisms, demographics, patterns, and outcomes in children and adolescents. DESIGN AND SETTINGS: Retrospective chart review in a major trauma center from May 2001 to May 2009 in Riyadh, Saudi Arabia. PATIENTS AND METHODS: Detailed chart reviews were done for all consecutive TSI patients ≤18 years old.Cases were identified through the trauma database registry that included admitted patients. RESULTS: Of the 3796 cases identified, 120 cases (3.2%) sustained 141 TSIs (mean age: 13.5 years; males:83.8%). TSI was most common among children from 16 to 18 years old. Overall, motor vehicle collision (MVC)was the most common injury mechanism (60.8%). However, younger patients (<12 years) sustained more pedestrian injuries (40.6%). Among MVC cases with known seat belt statuses (43.8%), 90.6% were not wearing seat belts. The cervical spine level was the most commonly affected (55.8%) region, especially in children <12 years old (88%). More than 1 affected spinal level was found in 23.3% cases. Spinal cord injuries were found in 19.2% cases. Overall, mortality was 8.3%, and half of these mortalities were secondary to pedestrian injuries. A total of 22.7% of cases were discharged with neurological deficits. CONCLUSION: The high frequency and severity of MVC and pedestrian injuries observed in the present study raise significant concerns regarding the safety of children on the roads. Spine involvement was age specific;younger patients tended to have more cervical injuries, and older patients exhibited more thoracic spine involvement.

Epilepsy; what do Saudi's living in Riyadh know?

PURPOSE: Epilepsy is very common in the Kingdom of Saudi Arabia, with a prevalence of 6.54 per 1000. The present study was conducted to investigate the level of public awareness, and the attitudes and knowledge regarding epilepsy in the Saudi population in Riyadh - capital city of Saudi Arabia. METHODS: A survey consisting of 19 questions pertaining to epilepsy awareness was distributed to Saudi citizens living in Riyadh older than 15 years of age in malls, supermarkets, health clubs, mosques, universities and schools. RESULTS: Of the 7078 respondents who completed the questionnaire, 6756 (95.5%) had heard about epilepsy, 3024 (42.7%) had witnessed what they believed to be a seizure and 5164 (73%) would allow their children to interact with an individual who had epilepsy. However, 5382 (76%) respondents would not want their children to marry an individual with epilepsy, 1004 (14.2%) believed that epilepsy was infectious and 574 (8.1%) believed that epilepsy was a type of mental illness. A total of 1509 (21.3%) respondents were not aware of a single potential cause of epilepsy, 3493 (50.6%) would not seek medical advice if one of their relatives had epilepsy, 2221 (31.4%) did not know how to deal with an individual experiencing an epileptic episode and 6554 (92.6%) did not know that surgery was a treatment option for individuals with epilepsy in Saudi Arabia. Of the 7078 respondents, 3237 (45.7%) would not abide by a physician's advice not to operate a motor vehicle because of their illness, of whom 1631 (50.4%) cited problems with the public transportation system as a reason for disregarding the doctor's advice. The effect of age and level of education were statistically significant on most of the study variables. CONCLUSION: The level of epilepsy awareness in the Saudi population needs improvement.

Causes and patterns of adult traumatic head injuries in Saudi Arabia: implications for injury prevention.

BACKGROUND AND OBJECTIVES: Data on the epidemiology of traumatic head injuries (THI) is essential for any organized prevention program. Such data are few in the developing world. Our primary goal was to study the causes, descriptive features, and outcomes of THI in adults in Saudi Arabia. DESIGN AND SETTINGS: The present study is a retrospective review. METHODS: This retrospective review included all consecutive cases of adults with THI ( > 18 years) who were admitted to a major trauma centre in Riyadh, Saudi Arabia, from May 2001 to July 2010. Patients were identified through a trauma database, which includes cases that required hospital admission or died in the emergency department. RESULTS: A total of 1870 patients met the inclusion criteria with a mean age of 32.6 years and a male predominance (91.2%). Most injuries were secondary to motor vehicle collisions (MVC; 69.4%). Pedestrian injuries were second (16.8%) and had 40% risk of mortality (odds ratio 0.62, 95% CI 0.48-0.8). Most patients (56.7%) had a severe THI (Glasgow coma score, GCS < 8). The overall mortality rate was 30%. Mortality was significantly associated with older age (P=.0001), lower GCS (P=.0001), and a higher injury severity score (ISS; P=.0001). CONCLUSION: The most common causes of hospital admission following injury were MVC and pedestrian injuries. Both were also the most common causes for injury-related deaths. Safety on the roads should be the primary target for any organized injury prevention programs to be successful.