Hussam Abou Al-Shaar

Parkinson's Disease in Saudi Patients: A Genetic Study

Parkinson’s disease (PD) is one of the major causes of parkinsonism syndrome. Its characteristic motor symptoms are attributable to dopaminergic neurons loss in the midbrain. Genetic advances have highlighted underlying molecular mechanisms and provided clues to potential therapies. However, most of the studies focusing on the genetic component of PD have been performed on American, European and Asian populations, whereas Arab populations (excluding North African Arabs), particularly Saudis remain to be explored. Here we investigated the genetic causes of PD in Saudis by recruiting 98 PD-cases (sporadic and familial) and screening them for potential pathogenic mutations in PD-established genes; SNCA, PARKIN, PINK1, PARK7/DJ1, LRRK2 and other PD-associated genes using direct sequencing. To our surprise, the screening revealed only three pathogenic point mutations; two in PINK1 and one in PARKIN. In addition to mutational analysis, CNV and cDNA analysis was performed on a subset of patients. Exon/intron dosage alterations in PARKIN were detected and confirmed in 2 cases. Our study suggests that mutations in the ORF of the screened genes are not a common cause of PD in Saudi population; however, these findings by no means exclude the possibility that other genetic events such as gene expression/dosage alteration may be more common nor does it eliminate the possibility of the involvement of novel genes.

Phenotypic comparison of individuals with homozygous or heterozygous mutation of NOTCH3 in a large CADASIL family

BACKGROUND Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy caused by mutations in NOTCH3, very rarely homoallelic. OBJECTIVE To describe the clinical, radiological, and neuropsychological features in an extended CADASIL family including members with either a homozygous or heterozygous NOTCH3 R1231C mutation. METHODS The pedigree included 3 generations of a family with 13 affected individuals. The patients were examined clinically and radiologically. Neuropsychological testing was performed on the proband. Sequencing of the entire coding DNA sequence (CDS) and flanking regions of NOTCH3 was undertaken using PCR amplification and direct Sanger sequencing. RESULTS Homozygous C3769T mutation, predicting R1231C in exon 22 of NOTCH3 was found in 7 family members. Six other family members harbored the same in the heterozygous state. Homozygous individuals showed a slightly more severe clinical and radiological phenotype of earlier onset compared to their heterozygous counterparts. CONCLUSION This study reports the largest number of patients with homozygous NOTCH3 mutation. The phenotype and imaging features of homozygous individuals is within the spectrum of CADASIL, although slightly at the severe end when compared to heterozygotes carrying the same mutation. Both genetic modifiers and environmental factors may play an essential role in modification and alteration of the clinical phenotype and white matter changes among CADASIL patients.

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.

Pancreatic Tail Schwannoma in a 44-Year-Old Male: A Case Report and Literature Review

Pancreatic schwannomas are exceedingly uncommon neoplasms. According to a recent study in 2012, less than 50 cases of pancreatic schwannoma have been described in the English literature over the past thirty years. The vast majority of pancreatic schwannomas take place in the head and body of pancreas, respectively. Herein, we report the case of pancreatic tail ancient schwannoma in a 44-year-old man who presented with a 4-month history of epigastric pain. On physical examination, epigastric region was moderately tender to palpation without evidence of a palpable mass. All laboratory tests were normal. Contrast-enhanced computed tomography (CT) scan showed a 9.2 × 9.5 × 11.5 cm, huge, and well-defined left suprarenal mass arising either from adrenal gland, pancreas, or retroperitoneum. The mass demonstrated mild heterogeneous enhancement with central cystic/necrotic area. No evidence of distant metastasis was identified. At laparoscopy, the mass was noticed to originate from pancreatic tail. Patient underwent surgical resection of pancreatic tail. Microscopic and immunohistochemical examination of the pancreatic tail specimen showed ancient schwannoma. Patient received no adjuvant therapy. At a postoperative 6-month followup, patient was completely asymptomatic and CT scan imaging showed no evidence of tumor recurrence. Moreover, a literature review on pancreatic schwannomas is presented.

Management of idiopathic intracranial hypertension with a programmable lumboperitoneal shunt: Early experience.

OBJECTIVE To evaluate the clinical outcomes and complications rate among idiopathic intracranial hypertension (IIH) patients who underwent lumboperitoneal (LP) shunt insertion with a programmable Strata valve. METHODS We retrospectively evaluated patients who underwent LP shunt with a programmable Strata valve insertion at the University of Ottawa Civic Hospital from November 2012 to June 2013. The demographic data, clinical symptoms, opening pressure, pre-operative and post-operative visual fields, neuroimaging, visual acuity, disc status, and complications were recorded and analyzed. RESULTS Seven female patients with IIH underwent insertion of an LP shunt with a programmable Strata valve. The mean opening pressure was 35.8 cm H2O. The initial valve setting was 1.5, and four patients required post-operative valve pressure adjustment. All patients showed significant improvement in objective visual testing at follow-up as well as less frequent headaches. None of the patients developed intra- or post-operative complications. CONCLUSION LP shunts with programmable Strata valve systems are a potential alternative to conventional LP and programmable ventriculoperitoneal shunt systems as well as optic nerve sheath fenestration, due to their potential in avoiding brain injury, lower failure and complication rates, lower intracranial hypotension incidence, and flexibility in adjusting valve pressure settings post-operatively evading under- and overdrainage complications. They should be considered for the management of IIH instead of early design LP systems and VP shunts. A randomized multi-center trial should be conducted to compare the efficacy of these surgical techniques.

Clinical heterogeneity of PLA2G6-related Parkinsonism: analysis of two Saudi families

BackgroundRecessive mutations in PLA2G6 have been associated with different neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation and more recently, early-onset dystonia parkinsonism.MethodTargeted-next generation sequencing using a custom Neurology panel, containing 758 OMIM-listed genes implicated in neurological disorders, was carried out in two index cases from two different Saudi families displaying early-onset levodopa-responsive Parkinsonism with pyramidal signs and additional clinical features. The detected mutations were verified in the index cases and available family members by direct sequencing.Results and conclusionWe identified a previously described PLA2G6 homozygous p.R741Q mutation in three affected and two asymptomatic individuals from two Saudi families. Our finding reinforces the notion of the broadness of the clinical spectrum of PLA2G6-related neurodegeneration.

A novel missense mutation in the TBX5 gene in a Saudi infant with Holt-Oram syndrome

We report on a Saudi infant with Holt-Oram syndrome caused by a de novo missense mutation of the TBX5 gene. The mutation (Thr72Lys) is novel and has not been previously reported. The cardiac and limb defects in our patient were both severe, and the infant also had micrognathia and cleft palate. Previously reported cases of the Holt-Oram syndrome caused by missense mutations were reviewed and their phenotypes were compared with the phenotype of our patient.

Hypothalamic–Optochiasmatic Pilocytic Astrocytoma Associated with Occipital and Sacral Spinal Cavernomas: A Mere Coincidence or a True Association?

BACKGROUND The co-occurrence of cerebral gliomas and cavernous angiomas is rarely encountered in clinical practice. All reported cases with such association have occurred within the brain with none involving the spinal cord. CASE DESCRIPTION The authors report the case of a hypothalamic-optochiasmatic pilocytic astrocytoma coexisting with right occipital and sacral spinal cavernomas. This 30-year-old man had an 8-year history of chronic lower back pain. Spinal magnetic resonance imaging (MRI) demonstrated an 8.2-cm expansile multilobulated heterogeneously enhancing intradural mass within the sacral spinal canal, extending into the bilateral S1 and left S2 foramina. Brain MRI depicted a 2.9-cm lobulated heterogeneously enhancing sellar-suprasellar solid and cystic mass expanding the sella and displacing the infundibulum to the right, with a normal-appearing pituitary gland inside the sella, and an extensive supratentorial and infratentorial superficial hemosiderosis. L5-S4 laminectomy and pterional craniotomy were performed for the resection of these lesions. Histopathologic examination revealed a sacral spinal cavernoma and a suprasellar hypothalamic-optochiasmatic pilocytic astrocytoma. CONCLUSION The coexistence of hypothalamic-optochiasmatic pilocytic astrocytoma and occipital and sacral spinal cavernomas has not been reported previously. Especially for radiologically atypical suprasellar lesions, hypothalamic-optochiasmatic glioma should be included in the differential diagnosis of masses that can expand the sella. Besides previously postulated hypotheses of viral-induced or angiogenic factor-induced glial growth, we hypothesize that neoplastic origins of hypothalamic-optochiasmatic glioma might be due to the irritative mechanisms resulting from the frequent bleeds occurring from the spinal or cranial cavernoma.

Surgical implications of frontoethmoidal pneumosinus dilatans-associated proptosis caused by meningioma.

Pneumosinus dilatans (PSD) involves paranasal sinus enlargement without radiologic evidence of localized bone destruction, hyperostosis, or mucous membrane thickening. We discuss the surgical implications of PSD-associated proptosis in patients with anterior skull-base meningioma. A 20-year-old man with proptosis, hypoglobus, and lateral globe displacement had WHO grade I anterior skull-base and orbital meningiomas. Aggressive resection using anterior/medial orbitotomy and an anterior interhemispheric skull-base approach achieved Simpson grade I resection. Postoperatively, his symptoms improved, with no recurrence at 2-year follow-up. Although PSD-associated proptosis is relatively uncommon, it carries important clinical implications in surgical management of skull-base and orbital meningiomas.

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.