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Biomedical subjects

I A Awad

Publications and source records attributed to I A Awad.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cerebral vascular malformations adjacent to sensorimotor and visual cortex. Functional magnetic resonance imaging studies before and after therapeutic intervention.

BACKGROUND AND PURPOSE: It is not known how cerebral vascular malformations affect the function of the surrounding brain. Functional magnetic resonance imaging (fMRI) can provide information about normal functional neuroanatomy and its alteration by vascular lesions and therapeutic intervention. METHODS: We performed fMRI studies in 24 patients harboring vascular malformations adjacent to primary somatosensory, motor, and visual cortex. The fMRI studies consisted of the acquisition of an image time series coupled with functional activation of motor, sensory, or visual cortex in both hemispheres. Activated voxels were identified using frequency domain analyses, and their number and anatomic location were compared between the affected and unaffected hemispheres. RESULTS: Every patient capable of performing the desired task showed functional activation. Eight patients without neurological deficits showed a symmetrical pattern of activation between the hemispheres. Each had a vascular malformation located one or more gyri from the functional region imaged. Three patients showed hemispheric symmetry in the location of activated cortex but with a marked asymmetry in the number of activated voxels. Each harbored vascular malformations located within one gyrus of the functional region and showed either subtle or no neurological deficit. Eleven patients showed hemispheric asymmetry in the location of activated cortex. In 6, the anatomic displacement appeared to be due to a mass effect of the lesion. In 5, the activation occurred at a different anatomic locale, and the patients exhibited gross neurological deficit in the respective function. Posttherapeutic changes in functional activation reflected elimination of the mass effect or recovery of clinical function. CONCLUSIONS: Systematic fMRI studies are possible in patients with vascular malformations in brain regions adjacent to primary somatosensory, motor, and visual cortex. Displacement of the activated region and hemispheric asymmetry in the number of activated voxels in the functional regions appear to reflect the anatomic and physiological impact of the vascular malformation. Changes in fMRI findings after intervention reflect the consequences of therapy and parallel clinical recovery.

Adolescent↗
PubMed1996

A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans.

BACKGROUND: Cerebral cavernous malformation is a vascular disease of the brain causing headaches, seizures, and cerebral hemorrhage. Familial and sporadic cases are recognized, and a gene causing familial disease has been mapped to chromosome 7. Hispanic Americans have a higher prevalence of cavernous malformation than do other ethnic groups, raising the possibility that affected persons in this population have inherited the same mutation from a common ancestor. METHODS: We compared the segregation of genetic markers and clinical cases of cavernous malformation in Hispanic-American kindreds with familial disease; we also compared the alleles for markers linked to cavernous malformation in patients with familial and sporadic cases. RESULTS: All kindreds with familial disease showed linkage of cavernous malformation to a short segment of chromosome 7 (odds supporting linkage, 4X10(10).1). Forty-seven affected members of 14 kindreds shared identical alleles for up to 15 markers linked to the cavernous-malformation gene, demonstrating that they had inherited the same mutation from a common ancestor. Ten patients with sporadic cases also shared these same alleles, indicating that they too had inherited the same mutation. Thirty-three asymptomatic carriers of the disease gene were identified, demonstrating the variability and age dependence of the development of symptoms and explaining the appearance of apparently sporadic cases. CONCLUSIONS: Virtually all cases of familial and sporadic cavernous malformation among Hispanic Americans of Mexican descent are due to the inheritance of the same mutation from a common ancestor.

Adolescent↗
PubMed1996

Giant aneurysms of the anterior circle of Willis: management outcome of open microsurgical treatment.

BACKGROUND: There is no uniform agreement to date regarding the optimal management of giant aneurysms (GAs) of the anterior circle of Willis. Endovascular therapeutic techniques have yielded unacceptable rates of aneurysm growth and recanalization (endosaccular) or high rates of complications (distal parent vessel occlusion). Despite size, frequent thrombosis and calcification (incollapsibility), and splaying of parent vessels, these aneurysms are readily amenable to direct surgical exposure and control of parent vessels intracranially. Published series have not considered these lesions separately and have often reflected a mixture of management strategies for these and other GAs. METHODS: Thirty-eight consecutive patients with symptomatic GAs of the anterior circle of Willis were managed by the senior author over a 7-year period. Twenty-six of these patients (68%) presented with subarachnoid hemorrhage (SAH). Temporary occlusion was performed under a protocol to enhance brain protection. Direct clip reconstruction or trapping was used in all instances, with intraoperative angiographic control. Revascularization procedures and suture vascular reconstructions were not used in any case. RESULTS: All patients were considered for direct microsurgical treatment. One patient refused surgery, and two patients were deemed a prohibitive medical risk. Thirty-five patients were treated surgically with complete obliteration of the aneurysm in 34 cases (97%), and patency of all parent arteries in 30 cases (86%). Overall mortality was 6% in the surgical cohort, with good or excellent clinical outcome in 71%. Mortality and poor outcome occurred exclusively in the setting of recent hemorrhage. CONCLUSIONS: The results are compared to the natural history of these lesions and to outcome (safety and effectiveness) of currently available endovascular techniques. This experience supports direct microsurgical intervention as the primary therapeutic modality for these lesions.

Adult↗
PubMed1996

Expression of angiogenic factors and structural proteins in central nervous system vascular malformations.

Little is known of the molecular mechanisms mediating the genesis and subsequent biological behavior of central nervous system vascular malformations. The role of angiogenic and permeability-inducing factors in the pathogenesis of these lesions has not bee previously explored. In this study, we subject specimens from 12 cases of excised vascular malformation to a battery of immunostaining for vascular endothelial growth factor, basic fibroblast growth factor, and selected structural and matrix proteins. The lesions consisted of seven arteriovenous malformations (AVMs), including one angiographically occult AVM, one arterialized vein from a dural AVM, and five cavernous malformations (CMs). Vascular endothelial growth factor was expressed by all lesions and was localized predominantly in the subendothelial layer and in perivascular spaces. Four of seven AVMs and four of five CMs demonstrated faint basic fibroblast growth factor expression that was localized to the media of AVM vessels and the subendothelial layer and intercavernous matrix of CMs. This pattern of angiogenic factor immunostaining was correlated with the expression of structural and matrix proteins in the same lesions. Laminin was not expressed in any of the CMs, confirming previous reports from our laboratory. By contrast, fibronectin expression was more prominent in CMs than in AVMs. Collagen Type IV and alpha smooth muscle actin expression occurred in every lesion. We conclude that angiogenic growth factors are expressed in all types of vascular malformations of the central nervous system. The pattern of expression suggests diffuse activation of angiogenesis without specific relation to individual vessel types or recent clinical behavior. Defining the role of angiogenesis in vascular malformations might provide insight into their pathogenesis and suggest novel strategies for modification of their behavior.

Actins↗
PubMed1996

Genetic heterogeneity of inherited cerebral cavernous malformation.

OBJECTIVE: Cerebral cavernous malformation (CCM) is frequently an inherited disorder showing autosomal dominant transmission. Genetic analysis has localized a gene causing CCM to a segment of the long arm of human chromosome 7 (7q). This evidence derives from investigation of a small number of families, mostly of Hispanic American descent. In this study, we have tested whether inherited CCM is always due to mutation in this 7q gene, or whether mutation in other genes can cause CCM. METHODS: We have studied subjects from two non-Hispanic families with inherited CCM. The clinical features of CCM in these families are indistinguishable from those in kindreds in which CCM is due to mutation in the 7q gene. To test whether CCM in these kindreds is caused by a mutation on 7q, we compared the inheritance of CCM to the inheritance of genetic markers on 7q. RESULTS: Genetic analysis demonstrates independent inheritance of CCM and markers on 7q in both families studied. This evidence excludes mutation in the 7q gene as the cause of CCM in these families, with odds against CCM being due to mutation in 7q in each family of more than 100,000:1 and 100:1, respectively. CONCLUSION: These findings demonstrate that inherited CCM is not always caused by a mutant gene on 7q, indicating the presence of at least a second gene in which mutation can cause CCM. These results have implications for genetic testing and the pathogenesis of this disorder.

Adult↗
PubMed1996

Expression of angiogenesis factors and selected vascular wall matrix proteins in intracranial saccular aneurysms.

OBJECTIVE: Little is known about the biological mechanisms associated with the genesis, growth, and rupture of intracranial saccular aneurysms. It is postulated that the vascular wall pathological response of aneurysmal disease is associated with abnormal angiogenesis factor expression. METHODS: We have examined the expression and distribution of immunoreactivity to angiogenesis growth factors (vascular endothelial growth factor and basic fibroblast growth factor) and selected vascular wall matrix proteins (fibronectin, Type IV collagen, and alpha smooth muscle actin) in the walls of human intracranial aneurysms from surgical biopsy or autopsy specimens. Double antibody immunohistochemical stains were performed in contiguous fixed sections from three control circle of Willis arteries, five berry aneurysms, four giant aneurysms, and one mycotic aneurysm (three unruptured and seven ruptured lesions). RESULTS: The aneurysmal wall exhibited diffuse disorganized expression of matrix proteins as compared to their organization in control vessels. There was strong patchy expression of vascular endothelial growth factor within the walls of all aneurysms, including marked staining of capillaries and small vessels within the thickened walls of giant lesions. The expression of basic fibroblast growth factor was more diffuse and occurred around the fibrocytes and myocytes within the disrupted media of 9 of 10 aneurysms. CONCLUSIONS: These results confirm the gross architectural molecular disruption in the walls of intracranial aneurysms and illustrate an apparent biological response involving angiogenesis factors. Further research should elucidate the time course and possible causal relationships of these changes to aneurysm growth and rupture with the aim of possible therapeutic manipulation.

Actins↗
PubMed1996

Misdiagnosis of symptomatic cerebral aneurysm. Prevalence and correlation with outcome at four institutions.

BACKGROUND AND PURPOSE: It is not known what fraction of patients with symptomatic cerebral aneurysms are misdiagnosed at initial medical presentation. It is also not clear whether misdiagnosed patients more frequently deteriorate before definitive aneurysm diagnosis and therapy or achieve a poorer outcome than correctly diagnosed patients. METHODS: We reviewed records of consecutive patients with symptomatic cerebral aneurysms managed by four tertiary-care neurosurgical services during a recent 19-month period. Clinical course and outcome were analyzed according to misdiagnosis or correct diagnosis at initial medical evaluation. RESULTS: Fifty-four of 217 patients (25%) were misdiagnosed at initial medical evaluation, including 46 of 121 patients (38%) initially in good clinical condition (clinical grade 1 or 2). Forty-six of 54 patients (85%) in the misdiagnosis group were initially grade 1 or 2 compared with 75 of 163 patients (46%) with correct initial diagnosis (P < .01). Twenty-six of 54 misdiagnosed patients (48%) deteriorated or rebled before definitive aneurysm treatment compared with 4 of 165 correctly diagnosed patients (2%) (P < .001). Among patients initially presenting as clinical grade 1 or 2, overall good or excellent outcome was achieved in 91% of those with correct initial diagnosis and 53% of patients with initial misdiagnosis (P < .001). Deterioration before correct diagnosis accounted for 16 of 67 patients (24%) with poor or worse final outcome in this series. CONCLUSIONS: Patients in good clinical condition with symptomatic cerebral aneurysms were commonly misdiagnosed. Misdiagnosed patients were more likely than correctly diagnosed patients to deteriorate clinically and had a worse overall outcome. Misdiagnosed cases accounted for a significant fraction of overall poor outcomes among consecutive cases of symptomatic aneurysms.

Adult↗
PubMed1996

Endovascular therapeutic approach to peripheral aneurysms of the superior cerebellar artery.

Peripheral aneurysms of the superior cerebellar artery may be difficult to treat surgically owing to their inaccessibility and to the frequent inability to preserve the involved parent artery. In fact, for most cases, surgical treatment consists of proximal parent artery occlusion and/or trapping with surgical clips. An equivalent endovascular therapeutic approach to these lesions may be an attractive alternative method of management. We describe two cases of peripheral superior cerebellar artery aneurysms that were treated successfully with endovascular embolization.

Adult↗
PubMed1996

Exceptional multiplicity of cerebral arteriovenous malformations associated with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome).

PURPOSE: To describe the clinical and imaging features of seven patients with hereditary hemorrhagic telangiectasia and an exceptional number of cerebral arteriovenous malformations (AVMs). METHODS: One hundred thirty-six patients from a dedicated hereditary hemorrhagic telangiectasia clinic were screened systematically for cerebral AVMs by means of MR imaging. Thirty-one were found to have abnormalities suggestive of a vascular malformation. Eighteen of these 31 patients subsequently underwent diagnostic cerebral angiography. RESULTS: Of the 18 patients who had cerebral angiography, all were found to have at least one AVM and seven were found to have three or more AVMs. The number of cerebral AVMs detected ranged from three to nine. At angiography, the AVMs varied in size from 3 to 25 mm in maximal dimension and consisted of a poorly defined plexiform nidus that typically had a single arterial feeding pedicle and a single draining vein. The two largest AVMs (20- and 25-mm nidus, respectively) contained intranidal aneurysms. Treatment included embolization, surgical excision, or follow-up management. CONCLUSIONS: Multiple cerebral AVMs are associated with hereditary hemorrhagic telangiectasia and further highlight the uniqueness of central nervous system involvement by this systemic angiodysplasia. MR imaging can underestimate the number and size of cerebral AVMs; therefore, catheter angiography is necessary to establish the extent of central nervous system involvement in this disorder.

Adult↗
PubMed1995

Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21.

Cerebral cavernous malformation is a common disease of the brain vasculature of unknown cause characterized by dilated thin-walled sinusoidal vessels (caverns); these lesions cause varying clinical presentations which include headache, seizure, and hemorrhagic stroke. This disorder is frequently familial, with autosomal dominant inheritance. Using a general linkage approach in two extended cavernous malformation kindreds, we have identified linkage of this trait to chromosome 7q11.2-q21. Multipoint linkage analysis yields a peak logarithm of odds (lod) score of 6.88 with zero recombination with locus D7S669 and localizes the gene to a 7-cM region in the interval between loci ELN and D7S802.

Brain↗
PubMed1995

Ischemic stroke and intracranial multifocal cerebral arteriopathy in Williams syndrome.

We describe an otherwise healthy 2-year-old patient with Williams syndrome who had a stroke as a result of intracranial multivessel focal and segmental stenotic disease. The diagnosis of Williams syndrome was confirmed by elastin gene deletion testing. Combined magnetic resonance imaging and magnetic resonance angiography, and transcranial Doppler flow studies, were used in diagnosing and monitoring the course of the disease.

Brain Ischemia↗
PubMed1995

Expression of basement membrane and endothelial cell adhesion molecules in vascular malformations of the brain: preliminary observations and working hypothesis.

Little is known about the pathogenesis and subsequent cellular biologic behaviour of human cerebral vascular malformations. Innovative therapeutic strategies will depend on more fundamental understanding of structural and functional lesion biology. We have freeze-processed four specimens of arteriovenous malformation (AVM), two cavernous malformations (CM), and resected cortex from one case of Sturge-Weber disease (SWD) for immunohistochemical studies. Probes of vascular maturity and cellular adhesion were examined, including Factor 8 related antigen (F8RAG), laminin, fibronectin, and adhesion molecules VCAM, ELAM and ICAM-1 (CD 54). Sections of the same lesions were permanently fixed and stained using Haematoxylin and Eosin, and MOVAT Pentachrome stain for identification of vascular wall structures. A double antibody staining battery was utilized with ultraviolet fluorescent microscopy, and was analysed by an observer blinded to the antibody and lesion type. All malformations showed strong expression on their luminal endothelial surface for F8RAG. There was no expression of ELAM in any lesion. Two AVMs expressed VCAM on the endothelial surface of some vessels. ICAM-1 was expressed faintly within two AVMs. The CMs expressed fibronectin within the endothelium and subendothelial matrix, and both lesions were devoid of laminin expression. The AVMs and the SWD vessels stained for laminin, while none of the AVMs expressed fibronectin. These preliminary observations are consistent with the hypothesis that AVMs and SWD represent more mature vessels, consistent with possible lesion genesis during early phases of embryonic vascular development (dysvasculogenesis). In contrast, CMs represent immature vessels devoid of laminin and other features of mature vessels, consistent with ongoing dysangiogenesis within a fibronectin rich matrix. Further studies should be aimed at better elucidation of these biologic probes, and correlation with specific lesion behaviour.

Basement Membrane↗
PubMed1995

Intracarotid amobarbital procedure as a predictor of material-specific memory change after anterior temporal lobectomy.

Memory testing during the intracarotid amobarbital procedure (IAP) is used extensively to identify temporal lobe surgery candidates "at risk" for developing severe postoperative anterograde amnesia. However, the utility of the IAP in predicting commonly observed material-specific memory deficits has not been thoroughly investigated. We examined the utility of contralateral IAP memory testing, as an index of the functional capacity of the surgical temporal lobe, to predict postoperative material-specific memory changes on the Wechsler Memory Scale-Revised (WMS-R) in patients with left hemisphere speech dominance undergoing left (n = 32) and right (n = 31) temporal lobectomy (TL). Left TL patients who "passed" contralateral IAP memory testing (> or = 68% recognition of memory items) had significantly greater verbal memory decrements than those who "failed" the IAP, presumably as a result of removal of functional tissue. A similar relationship between contralateral IAP performance and visual memory performance was not observed among right TL patients. Thus, the functional adequacy of the tissue to be resected appears to be inversely related to postoperative verbal memory decrement, at least among left TL patients. This relationship is consistent with results of recent studies demonstrating an inverse relationship between verbal memory decrements after left TL and preoperative neuropsychological verbal memory performance, magnetic resonance imaging (MRI) hippocampal volumes, and degree of mesiotemporal sclerosis (MTS).

Adolescent↗
PubMed1995

Sensitivity of magnetic resonance diffusion-weighted imaging and regional relationship between the apparent diffusion coefficient and cerebral blood flow in rat focal cerebral ischemia.

BACKGROUND AND PURPOSE: Magnetic resonance (MR) diffusion-weighted imaging (DWI), a noninvasive procedure, may play an important role in detecting and accurately localizing the extent of evolving infarction within the period immediately following stroke. We evaluated the sensitivity and specificity of DWI in detecting ischemia and compared a quantitative measure derived from the DWI, the apparent diffusion coefficient (ADC), with autoradiographic cerebral blood flow (CBF) in an experimental model of focal cerebral ischemia in rats. METHODS: MR imaging data were obtained with a General Electric 4.7-T horizontal bore magnet CSI II system with self-shielded gradients. DWI was acquired within 41 +/- 6 minutes (mean +/- SD) after onset of ischemia and repeated at 169 +/- 14 minutes, followed by CBF determination at 237 +/- 21 minutes. DWI, ADC, and CBF images from each animal were then compared. RESULTS: The sensitivities for detecting an abnormality at 1 and 3 hours for DWI were significantly different, and the sensitivity of 3-hour DWI did not differ from the CBF sensitivity of 99%. A mean +/- SD ADC threshold of 460 +/- 95 microns 2/s was defined as 45% higher than the low ADC in the ischemic core compared with the contralateral ADC. Subthreshold ADC area and ischemic area were significantly correlated (r2 = .69, P < .05). In 19 of 48 regions of interest classified as ischemic (< 35 mL.100 g-1.min-1) from both the 3-hour ADC and CBF images, 3-hour ADC correlated significantly with CBF (r2 = .27, n = 19, P < .05), whereas in the nonischemic regions ADC was inversely correlated with CBF. Several ischemic regions showed a sharp drop in ADC to 37% (P < .001, n = 5) compared with all other regions (n = 43) from 1 to 3 hours. CONCLUSIONS: Because of the change in the sensitivity of detecting ischemia with DWI, the difference in correlation of CBF with ADC between ischemic and nonischemic cortex, and the presence of several regions in which ADC dropped to 37% from 1 to 3 hours, our data suggest that ADC values potentially can be used to monitor evolving infarction.

Animals↗
PubMed1995

Intracranial cavernous malformations: lesion behavior and management strategies.

Intracranial cavernous malformations are vascular anomalies consisting of endothelium-lined caverns filled with blood at various stages of thrombosis and organization and separated by a collagenous stroma devoid of mature vessel wall elements. They occur in an estimated 0.45 to 0.9% of the population, with male and female patients equally affected and all ages represented. They commonly manifest as seizures, gross intracranial hemorrhage, and focal neurological deficits. Lesions are frequently multiple in the same patient, and 10 to 30% are associated with familial clustering. Several reports have documented a dynamic clinical-radiological lesion behavior with de novo lesion genesis, intralesional and perilesional hemorrhage, and corresponding fluctuations in lesion size. Hemorrhagic risk and neurological disability seem to be related to multiple factors, including lesion location, age, gender, state of reproductive cycle, and previous hemorrhage. Lesions may behave aggressively with repetitive hemorrhages and cumulative disability or may remain quiescent for many years. Management strategies include expectant follow-up in patients with asymptomatic or inaccessible lesions, excision of symptomatic and accessible lesions, and radiosurgery of progressively symptomatic lesions in inoperable locations. Relevant disease-specific outcome parameters are proposed to guide clinical decisions and future research. Prospective, stratified, hypothesis-driven studies using rigorous epidemiological methods must be undertaken to delineate patient and lesion factors influencing clinical aggressiveness. Biological studies are essential to uncover strategies to predict and modify lesion behavior.

Adolescent↗
PubMed1995

Galen's anecdote of the fallen sophist: on the certainty of science through anatomy.

In this paper the author recounts an anecdote presented by Galen of Pergamum (circa 130-200 A.D.) about a sophist named Pausanias, who fell from his mount and struck his back against a rock. The patient developed a subsequent loss of sensation in the fingers of his left hand with complete sparing of motor function. Numerous medications were applied to his hand but to no avail. Galen stated that he applied the same medications to the original point of dorsal tenderness, resulting in the patient's dramatic and full recovery. Galen attributed the healing to local drug action at the site of a presumed spinal root injury, at the level of C-7. Galen repeated this anecdote elsewhere to illustrate the remote effects of spinal cord and nerve injury and the importance of treating the site of pathology, rather than its somatic manifestations. Galen's observation is interpreted in light of his earlier experiments on spinal cord and nerve transections in live animals and his evolving concepts of functional and correlative neuroanatomy. This anecdote is also discussed as a striking example of the dangers of conjecture and the temptation to confuse association with causation when interpreting the effects of therapy in light of widely accepted paradigms.

Greece, Ancient↗