Saleh S. Baeesa

Synopsis on the linkage of Alzheimer's and Parkinson's disease with chronic diseases.

Neurodegeneration is the progressive loss of neuronal structure and function, which ultimately leads to neurological disorders such as Alzheimers disease (AD), Parkinsons disease (PD), multiple sclerosis, and Huntingtons disease. Even after the recent significant advances in neurobiology, the above‐mentioned disorders continue to haunt the global population. Several studies have suggested the role of specific environmental and genetic risk factors associated with these disorders. However, the exact mechanism associated with the progression of these disorders still needs to be elucidated. In the recent years, sophisticated research has revealed interesting association of prominent neurodegenerative disorders such as AD and PD with chronic diseases such as cancer, diabetes, and cardiovascular diseases. Several common molecular mechanisms such as generation of free radicals, oxidative DNA damage, aberrations in mitochondrial DNA, and dysregulation of apoptosis have been highlighted as possible points of connection. The present review summarizes the possible mechanism of coexistence of AD and PD with other chronic diseases.

Isolated Cerebral Aspergillosis in Immunocompetent Patients

BACKGROUND Isolated cerebral aspergillosis (ICA) traditionally has been associated with immunocompromised patients with dismal outcomes. Cases of ICA in immunocompetent patients are very rare and poorly described. We describe our experience of 5 immunocompetent patients with ICA and compare our experience with the literature. METHODS During the period 1996-2011, ICA was diagnosed in 5 otherwise healthy, immunocompetent patients at our institution. Medical records of the patients were reviewed with standardized data collection, including demographics, clinical presentation, radiologic features, histopathology results, treatment, and outcome. RESULTS All 5 patients had radiologic evidence of cerebral disease, purely parenchymal in 4 patients and dural-based in 1 patient. Radiology showed the paranasal sinuses and lungs to be clear in all patients. All patients underwent resection with antifungal therapy. All patients were female with a mean age of 23 years (range, 13-36 years). Headache (n = 5) and seizures (n = 4) were the primary presenting manifestations. Brain magnetic resonance imaging was performed in 5 patients preoperatively, and computed tomography was performed preoperatively in 4 patients. The diagnosis was made by histopathology (n = 5) and fungal cultures (n = 3) of the excised mass. Surgical resection was performed in all patients followed by treatment with amphotericin B for 2-4 weeks then oral voriconazole for 6 months. Overall mortality was 20% (n = 1). Average follow-up period was 32 months (range, 12-51 months) with interval brain magnetic resonance imaging to document eradication. CONCLUSIONS ICA in otherwise healthy immunocompetent hosts seems to have a more favorable prognosis than what is reported for immunocompromised hosts.

Alzheimer’s and Type 2 Diabetes Treatment via Common Enzyme Targeting

Alzheimers disease (AD) and type 2 diabetes mellitus (T2DM) are two devastating diseases that are currently incurable. Epidemiological, clinical and pathological evidence has confirmed the co-existence of these two disorders. Moreover, there has been promising progress made in the identification of the pathological linkage between T2DM and AD in the last decade. Hence, developing common treatment strategies for these diseases is important. Currently, enzyme targeting is a potential strategy to cure many diseases. In this communication, we tried to summarize the single enzymetargeted therapeutic approach for the treatment of AD and T2DM. This field of research continues to be active and progressive in identifying many promising enzymes that are involved in both diseases. Based on this review article, we also believe that enzyme inhibition is a promising and reliable strategy for the treatment of many incurable diseases. In the future, we expect that the scientific community will be able to develop common enzyme inhibitors for the treatment of both AD and T2DM.

Microarray Expression Data Identify DCC as a Candidate Gene for Early Meningioma Progression.

Meningiomas are the most common primary brain tumors bearing in a minority of cases an aggressive phenotype. Although meningiomas are stratified according to their histology and clinical behavior, the underlying molecular genetics predicting aggressiveness are not thoroughly understood. We performed whole transcript expression profiling in 10 grade I and four grade II meningiomas, three of which invaded the brain. Microarray expression analysis identified deleted in colorectal cancer (DCC) as a differentially expressed gene (DEG) enabling us to cluster meningiomas into DCC low expression (3 grade I and 3 grade II tumors), DCC medium expression (2 grade I and 1 grade II tumors), and DCC high expression (5 grade I tumors) groups. Comparison between the DCC low expression and DCC high expression groups resulted in 416 DEGs (p-value < 0.05; fold change > 2). The most significantly downregulated genes in the DCC low expression group comprised DCC, phosphodiesterase 1C (PDE1C), calmodulin-dependent 70kDa olfactomedin 2 (OLFM2), glutathione S-transferase mu 5 (GSTM5), phosphotyrosine interaction domain containing 1 (PID1), sema domain, transmembrane domain (TM) and cytoplasmic domain, (semaphorin) 6D (SEMA6D), and indolethylamine N-methyltransferase (INMT). The most significantly upregulated genes comprised chromosome 5 open reading frame 63 (C5orf63), homeodomain interacting protein kinase 2 (HIPK2), and basic helix-loop-helix family, member e40 (BHLHE40). Biofunctional analysis identified as predicted top upstream regulators beta-estradiol, TGFB1, Tgf beta complex, LY294002, and dexamethasone and as predicted top regulator effectors NFkB, PIK3R1, and CREBBP. The microarray expression data served also for a comparison between meningiomas from female and male patients and for a comparison between brain invasive and non-invasive meningiomas resulting in a number of significant DEGs and related biofunctions. In conclusion, based on its expression levels, DCC may constitute a valid biomarker to identify those benign meningiomas at risk for progression.

Does the treatment of normal pressure hydrocephalus put the retinal ganglion cells at risk? A brief literature review and novel hypothesis.

Normal pressure hydrocephalus (NPH) is a poorly understood entity as well as a source of continuous controversy in the neuroscientific community. The surgical management of this disease requires that intracranial pressure (ICP), also referred to as the cerebrospinal fluid pressure (CSFP), be lowered using a cerebrospinal fluid (CSF) diversion procedure. Numerous complications are linked with this procedure; we believe that new evidence suggests that the induction or acceleration of glaucomatous optic neuropathy are possible sequelae that warrant further investigation. We also suggest potential solutions derived from the increased understanding of the diseases pathophysiology and new advances in imaging of the optic nerve head complex. The recent inclusion of the translaminar gradient (TLG) (the difference between the intraocular pressure (IOP) and the ICP/CSFP across the thickness of the lamina cribrosa in the optic nerve head complex) in the pathogenesis of normal tension glaucoma (NTG) suggests that the disease may be a complication encountered during the treatment of NPH with CSF diversion procedures. The significant decrease in CSFP required to treat NPH increases this gradient. In addition, there have been recent observations of an increased prevalence of NTG, as well as other forms of glaucoma, among patients with NPH, thought to be due to inherently fragile neurons in these patients. This new data suggest that patients who undergo ICP lowering therapy for their NPH may be at a higher risk of developing or accelerating already present NTG. We present the clinical and theoretical basis for our hypothesis after reviewing the relevant literature linking the two entities. We also propose a possible solution, as we believe that treatment guidelines for NPH should take the TLG into account. Indeed, recent advances in the imaging of the optic nerve head complex may provide an opportunity to detect the mechanical sequelae of an increased TLG in the preclinical stage, i.e., prior to optic nerve damage. If we are able to determine safe parameters for the TLG in this population, we may be able to recommend the initiation of prophylactic glaucoma therapy for selected patients.

Emergency Excision of Cardiac Myxoma and Endovascular Coiling of Intracranial Aneurysm after Cerebral Infarction

Cardiac myxoma is the most common primary tumor of the heart, located mainly in the left atrium. Cerebral embolization or intracranial aneurysm formation as a consequence of left atrial myxomas has been well documented, whereas myxoma embolization causing the combination of cerebral infarction and intracranial myxomatous aneurysm is rare. We report herein, a 67-year-old female with a cardiac myxoma who experienced a left hemispheric embolic ischemic stroke and in addition was found to have right internal carotid artery aneurysm. The patient underwent emergency surgical excision of left atrial myxoma 2 hours after the stroke onset and endovascular coiling of the aneurysm a week later. Although the timing of cardiac surgery is controversial in patients who have had recent ischemic stroke, we recommend immediate resection of cardiac myxoma, if feasible, and early endovascular treatment of associated intracranial myxomatous aneurysms.

The efficacy of a percutaneous expandable titanium device in anatomical reduction of vertebral compression fractures of the thoracolumbar spine

Objectives: To evaluate the feasibility of a minimally invasive technique using a titanium expandable device to achieve anatomical restoration of vertebral compression fractures (VCF) of the thoracolumbar spine. Methods: This prospective study included 27 patients diagnosed with VCF (Magerl classification A.1.2, A.1.3, and A.3.1) of the thoracolumbar spine treated with percutaneous cement augmentation using the SpineJack® device. The study was conducted in Valladolid University Hospital, Valladolid, Spain from January to December 2012, with a minimum one-year follow up. Preoperative evaluation included visual analogue scale (VAS) for pain, and radiological assessment of the VCF using 3-dimensional computed tomography (3D-CT) scans for measurements of vertebral heights and angles. The patients were followed at 3, 6, and 12 months with clinical VAS and radiological assessments. Results: The procedure was performed in 27 patients with a mean age of 55.9 ± 17.3 years, 55.6% females. All patients underwent surgery within 6 weeks from time of injury. No procedure related complications occurred. Pain measured by VAS score decreased from 7.0 preoperatively to 3.2 within 24 hours, and remained 2.2 at 3 months, 2.1 at 6 months, and 1.5 at 12-months follow-up (p<0.05). Mean height restorations for the anterior was 3.56 mm, central was 2.49, and posterior vertebral was 1.28 mm, and maintained at 12-months follow-up (p=0.001). Conclusion: This new percutaneous technique for VCF has shown good clinical results in pain control and the possibility to reduce both vertebral kyphosis angles and fractured endplates seen in 3D-CT scans assessment method. Further studies are needed to confirm those results on larger cohorts with long-term follow up.

Primary Isolated Lymphoma of the Fourth Ventricle in an Immunocompetent Patient

Primary central nervous lymphoma (PCNSL) is a rare variant of extranodal non-Hodgkins lymphoma with a especially poor prognosis. The diagnosis is usually encountered in immunodeficient patients but is also encountered, albeit uncommonly, in the immunocompetent. We present a 50-year-old male who developed signs and symptoms of increased intracranial pressure. Imaging revealed the presence of a fourth ventricle mass with obstructive hydrocephalus. First, the patient underwent emergency endoscopic third ventriculostomy followed, few days later, by complete tumor resection via a posterior fossa craniotomy. Postoperative histopathology revealed the lesion to be a PCNSL. He received adjuvant chemotherapy and radiation and remained with no recurrence on regular imaging studies for 18-month followup. We report herein the fourth case of isolated PCNSL lesion to the fourth ventricle in the literature and provide the rationale for our belief that craniotomy and tumor resection, if feasible, should be the initial line of management in similar cases to relieve hydrocephalus and achieve the diagnosis.

Atlas Hypoplasia and Ossification of the Transverse Atlantal Ligament: A Rare Cause of Cervical Myelopathy

Myelopathy at the level of the atlas is rarely encountered by the practicing spine surgeon. Due to the regions unique anatomy, compression of the cord at this level is either caused by a large compressing lesion or an abnormally stenotic canal. We describe a rare instance of a congenitally stenotic canal due to a hypoplastic intact posterior arch of atlas, coexisting with an extremely rare ossified transverse ligament of the atlas. The coexistence of these two lesions has only been documented thrice before. We describe the clinical presentation, imaging findings, and favorable response to surgery.

Spinal cord compression secondary to idiopathic thoracic epidural lipomatosis in an adolescent: A case report and review of literature

Highlights • Idiopathic SEL is very rare, since no predisposing factors can be identified.• SEL should be included in the differential diagnosis when patients present with progressive spinal neurological compromise.• MRI is the imaging modality of choice.• Decompressive laminectomy and debulking of the fatty lesion is the main treatment modality.