Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis.

Developmental defects affecting the heart and aortic arch arteries are a significant phenotype observed in individuals with 22q11 deletion syndrome and are caused by a microdeletion on chromosome 22q11. TBX1, one of the deleted genes, is expressed throughout the pharyngeal arches and is considered a key gene, when mutated, for the arch artery defects. Pax9 is expressed in the pharyngeal endoderm and is downregulated in Tbx1 mutant mice. We show here that Pax9-deficient mice are born with complex cardiovascular malformations that affect the outflow tract and aortic arch arteries with failure of the 3rd and 4th pharyngeal arch arteries to form correctly. Transcriptome analysis indicated that Pax9 and Tbx1 may function together, and mice double heterozygous for Tbx1/Pax9 presented with a significantly increased incidence of interrupted aortic arch when compared with Tbx1 heterozygous mice. Using a novel Pax9Cre allele, we demonstrated that the site of this Tbx1-Pax9 genetic interaction is the pharyngeal endoderm, therefore revealing that a Tbx1-Pax9-controlled signalling mechanism emanating from the pharyngeal endoderm is required for crucial tissue interactions during normal morphogenesis of the pharyngeal arch artery system.

Filamentous nestin and nonmuscle myosin IIB are associated with a migratory phenotype in neonatal rat cardiomyocytes.

Cardiomyocyte migration represents a requisite event of cardiogenesis and the regenerative response of the injured adult zebrafish and neonatal rodent heart. The present study tested the hypothesis that the appearance of the intermediate filament protein nestin in neonatal rat ventricular cardiomyocytes (NNVMs) was associated in part with the acquisition of a migratory phenotype. The cotreatment of NNVMs with phorbol 12,13-dibutyrate (PDBu) and the p38α/ß mitogen-activated protein kinase inhibitor SB203580 led to the de novo synthesis of nestin. The intermediate filament protein was subsequently reorganized into a filamentous pattern and redistributed to the leading edge of elongated membrane protrusions translating to significant lengthening of NNVMs. PDBu/SB203580 treatment concomitantly promoted the reorganization of nonmuscle myosin IIB (NMIIB) located predominantly at the periphery of the plasma membrane of NNVMs to a filamentous phenotype extending to the leading edge of elongated membrane protrusions. Coimmunoprecipitation assay revealed a physical interaction between NMIIB and nestin after PDBu/SB203580 treatment of NNVMs. In wild-type and heterozygous NMIIB embryonic hearts at E11.5-E14.5 days, nestin immunoreactivity was identified in a subpopulation of cardiomyocytes elongating perpendicular to the compact myocardium, at the leading edge of nascent trabeculae and during thickening of the compact myocardium. In mutant embryonic hearts lacking NMIIB protein expression, trabeculae formation was reduced, the compact myocardium significantly thinner and nestin immunoreactivity undetectable in cardiomyocytes at E14.5 days. These data suggest that NMIIB and nestin may act in a coordinated fashion to facilitate the acquisition of a migratory phenotype in neonatal and embryonic cardiomyocytes.

The World Federation of Neurology and the challenges in Environment Neurology.

Since its establishment the World Federation of Neurology (WFN) has manifested a keen interest in the environment and its relation to neurological diseases. Thus, in 2007 the WFN renamed the "Neurotoxicological Research Group" to "Environmental Neurology Research Group". In this short article, we review some recent events which illustrate the WFN involvement in Environmental Neurology as well its concerns about global health matters involving environmental issues.

Incidental MRI lesions suggestive of multiple sclerosis in asymptomatic patients in Karachi, Pakistan.

The objective of this study was to identify asymptomatic patients with brain MRI lesions suggestive of multiple sclerosis (MS) in a low-prevalence area of Pakistan. Brain MRIs for 864 patients were reviewed at the Aga Khan University (Karachi, Pakistan) during an 8-month period of 2006 and 2007 to identify patients with lesions suggestive of MS. The lesions were characterised based on modified Barkhof criteria. Six (two females) (0.7%) of 864 patients fulfilled brain MRI criteria suggestive of MS. The mean number of MRI lesions (total lesions on T2) were 9 (range 5-14). Although Pakistan is considered a low-prevalence area for MS, 0.7% of brain MRI scans in patients without clinical MS symptoms showed lesions fulfilling brain MRI criteria of MS.

Neurological complications in patients with Plasmodium vivax malaria from Karachi, Pakistan.

BACKGROUND: Malaria remains an endemic disease in Pakistan with an estimated healthcare burden of 1.6 million cases annually, with Plasmodium vivax accounting for 67% of reported cases. P. vivax is the most common species causing malaria outside of Africa, with approximately 13.8 million reported cases worldwide. METHOD: We report a series of P. vivax cases with cerebral involvement that presented at Aga Khan University Hospital, Karachi, Pakistan. RESULTS: The majority of the patients presented with high-grade fever accompanied by projectile vomiting and abnormal behaviour, seizures, shock and unconsciousness. Seven of 801 patients with P. vivax monoinfection presented or developed cerebral complications. P. vivax infections were diagnosed based on peripheral smears and rapid diagnostic testing. CONCLUSION: P. vivax infection can lead to severe complications, although not with the frequency of Plasmodium falciparum infection. Current cases highlight an increasing trend of cerebral complications caused by P. vivax.

Stroke-associated pneumonia: microbiological data and outcome.

INTRODUCTION: Pneumonia is a common complication after acute stroke. It affects the outcome adversely. However, data regarding microbiology of stroke-associated pneumonia and its effect on outcome is scarce. METHODS: Stroke-associated pneumonia was identified through chart review of all ICD-9 identified adult stroke patients admitted to our hospital over a period of four years (1998-2001). The demographical, laboratory, radiological, microbiological data and outcome of patients with stroke-associated pneumonia were recorded and analysed. RESULTS: 443 patients with stroke were admitted over the four-year period and 102 (23 percent) had stroke-associated pneumonia. Their ages range from 28 to 100 (mean 64+/-14) years. 69 (68 percent) were men. Median length of stay was nine days compared to four days for all stroke patients. 68 (67 percent) patients manifested pneumonia within 48 hours and 34 (33 percent) after 48 hours of admission. Yield of tracheal aspirate cultures was 38 percent and that of chest radiographs was 25 percent. Pseudomonas aeruginosa and Staphylococcus aureus were the most common organisms (12 percent each) followed by Streptococcus pneumoniae and Klebsiella pneumoniae (4 percent each). Patients with infiltrates on chest radiographs were more likely to have positive tracheal aspirate cultures (p-value is 0.003). 35 patients (34 percent) expired during hospital stay. Positive chest radiographs and tracheal aspirates were independent predictors of prolonged hospital stay (p-value is less than 0.005). CONCLUSION: Pneumonia is a common medical complication of stroke. It is associated with a high mortality and prolongs the hospital stay. The yield of chest radiographs and tracheal aspirates is low. However, these are independent predictors of prolonged hospital stay. Pseudomonas aeruginosa and Staphylococcus aureus are most common organisms in stroke-associated pneumonia.

Imaging Cleared Embryonic and Postnatal Hearts at Single-cell Resolution.

Single clonal tracing and analysis at the whole-heart level can determine cardiac progenitor cell behavior and differentiation during cardiac development, and allow for the study of the cellular and molecular basis of normal and abnormal cardiac morphogenesis. Recent emerging technologies of retrospective single clonal analyses make the study of cardiac morphogenesis at single cell resolution feasible. However, tissue opacity and light scattering of the heart as imaging depth is increased hinder whole-heart imaging at single cell resolution. To overcome these obstacles, a whole-embryo clearing system that can render the heart highly transparent for both illumination and detection must be developed. Fortunately, in the last several years, many methodologies for whole-organism clearing systems such as CLARITY, Scale, SeeDB, ClearT, 3DISCO, CUBIC, DBE, BABB and PACT have been reported. This lab is interested in the cellular and molecular mechanisms of cardiac morphogenesis. Recently, we established single cell lineage tracing via the ROSA26-CreERT2; ROSA26-Confetti system to sparsely label cells during cardiac development. We adapted several whole embryo-clearing methodologies including Scale and CUBIC (clear, unobstructed brain imaging cocktails and computational analysis) to clear the embryo in combination with whole mount staining to image single clones inside the heart. The heart was successfully imaged at single cell resolution. We found that Scale can clear the embryonic heart, but cannot effectively clear the postnatal heart, while CUBIC can clear the postnatal heart, but damages the embryonic heart by dissolving the tissue. The methods described here will permit the study of gene function at a single clone resolution during cardiac morphogenesis, which, in turn, can reveal the cellular and molecular basis of congenital heart defects.

Nonrandomized comparison of local urokinase thrombolysis versus systemic heparin anticoagulation for superior sagittal sinus thrombosis.

BACKGROUND AND PURPOSE: We sought to compare the safety and efficacy of direct urokinase thrombolysis with systemic heparin anticoagulation for superior sagittal sinus thrombosis (SSST). METHODS: At University at Buffalo (NY) and University of Texas (Dallas, Houston), we reviewed 40 consecutive patients with SSST, treated with local urokinase (thrombolysis group) or systemic heparin anticoagulation (heparin group). The thrombolysis group (n=20) received local urokinase into the SSS followed by systemic heparin anticoagulation. The heparin group (n=20) received systemic heparin anticoagulation only. Neurological dysfunction was rated as follows: 0, normal; 1, mild (but able to ambulate and communicate); 2, moderate (unable to ambulate, normal mentation); and 3, severe (unable to ambulate, altered mentation). RESULTS: Age (P=0.49), sex (P=0.20), baseline venous infarction (P=0.73), and predisposing illnesses (P=0.52) were similar between the thrombolysis and heparin groups. Pretreatment neurological function was worse in the thrombolysis group (normal, n=5; mild, n=8; moderate, n=4; severe, n=3) than in the heparin group (normal, n=8; mild, n=8; moderate, n=3; severe, n=1) (P=NS). Discharge neurological function was better in the thrombolysis group (normal, n=16; mild, n=3; moderate, n=1; severe, n=0) than in the heparin group (normal, n=9; mild, n=6; moderate, n=5; severe, n=0) (P=0.019, Mann-Whitney U test). Hemorrhagic complications were 10% (n=2) in the thrombolysis group (subdural hematoma, retroperitoneal hemorrhage) and none in the heparin group (P=0.49). Three of the heparin group patients developed complications of the underlying disease (status epilepticus, hydrocephalus, refractory papilledema). No deaths occurred. Length of hospital stay was similar between the groups (P=0.79). CONCLUSIONS: Local thrombolysis with urokinase is fairly well tolerated and may be more effective than systemic heparin anticoagulation alone in treating SSST. A randomized, prospective study comparing these 2 treatments for SSST is warranted.

St Louis encephalitis: a review of 11 cases in a 1995 Dallas, Tex, epidemic.

OBJECTIVE: To update some of the clinical features of St Louis encephalitis (SLE), a common arboviral infection that occurs in epidemic patterns in the south-central and midwestern United States. METHODS: Eleven patients with SLE from a 1995 epidemic in Dallas, Tex, were studied clinically, radiologically, neurophysiologically, and neuropathologically (in 1 case). RESULTS: The electroencephalograms and magnetic resonance imaging (MRI) scans of our patients revealed features that have received little attention in previous studies. Of the 9 patients who were examined with electroencephalography, all 9 had seizures or other abnormalities, and 1 had nonconvulsive status epilepticus. Two of 6 patients who had MRIs showed substantia nigra edema. Finally, 2 (18%) of our patients had coinfection with the human immunodeficiency virus. CONCLUSIONS: The MRI findings of substantia nigra edema in patients with SLE have not been previously reported. Nonconvulsive status epilepticus can occur in patients with SLE and should be considered in patients with prolonged encephalopathy. Finally, human immunodeficiency virus coinfection may be a risk factor for symptomatic SLE infection.

Fatigue in multiple sclerosis: cross-sectional correlation with brain MRI findings in 71 patients.

Fatigue is an unexplained but common and disabling symptom in MS. We assessed fatigue in 71 patients with MS and identified MS-fatigue (MSF) and MS-nonfatigue (MSNF) groups. Fatigue severity did not correlate with regional or global MRI plaque load or atrophy assessed by conventional sequences. No significant differences were noted in any MRI measures between MSF and MSNF groups. We suggest that brain MRI disease topography or severity does not explain fatigue in MS and that fatigue is likely due to mechanisms poorly characterized by conventional MRI.

Cerebral white matter changes (leukoaraiosis), stroke, and gait disturbance.

OBJECTIVES: Leukoaraiosis, a radiological change of cerebral white matter thought to be caused by ischemia, is associated with gait disturbance. However, because of concomitant stroke and cerebral atrophy, the clinical relevance of leukoaraiosis is uncertain. We, therefore, sought to determine if leukoaraiosis is a predictor of gait disturbance after accounting for cerebral atrophy and stroke in patients with a high prevalence of cerebrovascular disease. DESIGN: Cross-sectional observational study. SETTING: Neurology service (inpatient and outpatient) of a Department of Veterans Affairs Hospital. PARTICIPANTS: Consecutive sample of 130 patients, 127 men and three women. MEASUREMENTS: The findings of a gait scale were correlated to vascular risk factors, neurological examination as quantified by the NIH stroke scale and supplemental motor scale, and to brain CT findings. Brain CT scans were rated for leukoaraiosis, cerebral infarction, and cerebral atrophy. RESULTS: Gait disturbance was more frequent and more severe in subjects with leukoaraiosis, of whom 31% had mild and 49% moderate/severe gait disturbance compared with 27% with mild and 12% with moderate/severe gait disturbance in subjects without leukoaraiosis (P < .001). Leukoaraiosis, cerebral atrophy, a history of multiple strokes, and weakness and ataxia of the legs were independent predictors of gait disturbance. The proportion and severity of leukoaraiosis increased with increasing gait disturbance in subgroups without leg deficit (P < .001) and without multiple strokes (P < .001), but no association with leukoaraiosis was shown in patients with leg deficit or a history of multiple strokes (P = .037 and P = .186, respectively). Gait disturbance was more severe when both leukoaraiosis and cerebral atrophy were present (P = .019). CONCLUSION: In our Veteran population, leukoaraiosis is an independent predictor of gait disturbance after accounting for stroke and cerebral atrophy. Although leukoaraiosis is a form of cerebrovascular disease, it appears to be most closely associated to gait disturbance in the absence of symptomatic stroke or leg deficit.

Intraventricular CSF pulsation artifact on fast fluid-attenuated inversion-recovery MR images: analysis of 100 consecutive normal studies.

BACKGROUND AND PURPOSE: CSF pulsation artifact is a pitfall of fast fluid-attenuated inversion-recovery (FLAIR) brain MR imaging. We studied ventricular CSF pulsation artifact (VCSFA) on axial FLAIR images and its relationship to age and ventricular size. METHODS: Fast FLAIR axial images were obtained on a 1.5-T unit (8000/150/2 [TR/TE/ excitations], inversion time = 2200, field of view = 24 cm, matrix = 189x256, and 5-mm interleaved sections). Two observers rated VCSFA (hyperintensity on FLAIR images) in the lateral, third, and fourth ventricles by using a three-point ordinal scale in 100 consecutive subjects (ages 20-86 years) with normal brain MR studies. Left-to-right third ventricular width was also measured. RESULTS: Seventy-two subjects had VCSFA in at least one ventricular cavity. The fourth ventricle was the most common site of VCSFA (n = 58), followed by the third ventricle (n = 47) and the lateral ventricles (n = 13). VCSFA was usually severe in the third and fourth ventricles and less severe in the lateral ventricles. Fourth ventricular VCSFA was significantly associated with third ventricular VCSFA. Increasing third ventricular size and, to a lesser extent, increasing age was significantly associated with VCSFA. Ghost pulsation of VCSFA occurred across the brain parenchyma in the phase-encoding direction. VCSFA seen in the fourth ventricle on axial FLAIR images disappeared on sagittal FLAIR images in one subject. CONCLUSION: VCSFA on axial FLAIR images represents inflow artifact caused by inversion delay and ghosting effects. VCSFA might obscure or mimic intraventricular lesions, especially in the third and fourth ventricles. Although common in adults of all ages, VCSFA is associated with advancing age and increasing ventricular size. Thus, altered CSF flow dynamics that occur with ventriculomegaly and aging contribute to VCSFA on axial FLAIR MR images.

Early computed tomography hypodensity predicts hemorrhage after intravenous tissue plasminogen activator in acute ischemic stroke.

Parenchymal hypodensity is a proposed risk factor for hemorrhage after recombinant tissue plasminogen activator (TPA) thrombolysis for ischemic stroke. In Buffalo, NY, and Houston, TX, the authors reviewed 70 patients who were treated with intravenous TPA for acute middle cerebral artery (MCA) stroke. Two observers blinded to clinical outcome analyzed initial noncontrast head computed tomography (CT) scans. Basal ganglia CT hypodensity was quantitated in Hounsfield units (HUs). Contralateral-ipsilateral difference in density was calculated using the asymptomatic side as a control. Ictus time to TPA averaged 2.5 hours. Six patients developed symptomatic intraparenchymal hematomas (2 fatal). The hemorrhage group had more severe basal ganglia hypodensity (mean 7.5 +/- 1.4, range 6-10 HU) than the nonhemorrhage group (2.2 +/- 1.4, range 0-9 HU) (P < .0001). The hemorrhage group had hypodensity of > 5 HU; the nonhemorrhage group had hypodensity of < or = 4 HU, except 1 patient with hypodensity of 9 HU. In predicting hemorrhage, the positive predictive value of hypodensity > 5 HU was 86%; the negative predictive value was 100%. Prethrombolysis NIH Stroke Scale (NIHSS) deficit (P = .0007) and blood glucose (P = .005) were also higher in the hemorrhage group. Age, gender, smoking, hypertension, and ictus time to TPA infusion did not differ between the 2 groups. Logistic regression indicated that basal ganglia hypodensity was the best single predictor of hemorrhage. Hypodensity and NIHSS score together predicted all cases of hemorrhage. The authors conclude that basal ganglia hypodensity quantified by CT may be a useful method of risk stratification to select acute MCA stroke patients for thrombolytic therapy.

Magnetic resonance imaging findings in bilateral Bell's palsy.

Bell's palsy (idiopathic facial paralysis) is the most common cause of unilateral peripheral facial neuropathy. Bilateral involvement occurs in less than 10% of cases. The authors describe a 20-year-old man with bilateral idiopathic facial weakness. Brain magnetic resonance imaging (MRI) showed abnormal bilateral enhancement of the proximal intracanalicular segments of VII/VIII nerve complexes. The enhancement was most prominent in the leptomeningeal regions. There was no facial nerve swelling. Three months later he had improving residual bifacial weakness. To the authors' knowledge, this is the first report of abnormal MRI findings in bilateral Bell's palsy.

Superior sagittal sinus thrombosis secondary to hyperthyroidism.

Superior sagittal sinus thrombosis (SSST) is associated with a variety of hypercoaguable states. Although coagulation disturbances are reported in hyperthyroidism, a direct link between hyperthyroidism and cerebral venous thrombosis is not established. We report a 39-year-old man who developed increased intracranial pressure, seizures, and rapid atrial fibrillation. Neuroimaging showed SSST, and laboratory studies were consistent with hyperthyroidism. No other causes of a hypercoaguable state were identified. Prompt treatment of his hyperthyroidism led to recanalization of the superior sagittal sinus and a full neurological recovery. Given the known effects of hyperthyroidism on factor VIII activity, we hypothesize that hyperthyroidism is an independent risk factor for SSST. A high index of suspicion for SSST is warranted in patients with hyperthyroidism and neurological symptoms. Furthermore, thyroid dysfunction should be excluded in patients with unexplained SSST.

Cost of acute stroke care at a tertiary care hospital in Karachi, Pakistan.

OBJECTIVE: To evaluate cost of acute stroke care and its determinants at a tertiary care hospital in Karachi and to find out predictors of high cost care. Acute stroke is a leading cause of morbidity and mortality. Cost of care is the single most important determinant in availability of acute stroke care at a tertiary care hospital in Pakistan. It is also an important factor in development of public health policies and medical insurance plans. Average annual income in Pakistan is 4881 rupees (85 U dollars). METHODS: Medical and billing records of 443 patients with acute stroke were retrospectively reviewed from 1998-2001 at The Aga Khan University Hospital (AKUH), Karachi. Acute stroke care at AKUH usually includes routine laboratory investigation including Lipid profile, Magnetic resonance imaging/angiography (MRI/MRA), Echocardiogram, Carotid Doppler's ultrasound and medical management in the Stroke care unit. RESULTS: 443 patients were included in study. Age range was 25-98 years (Mean 58 years). 269 (61%) were male. Length of hospital stay was 1 day; 67 patients, 2 days; 83 patients, 3 days; 70 patients, 4-5 days; 87 patients, 6-10 days; 75 patients, 11-30 days; 49 patients and more than 30 days; 12 patients. Average length of stay was five days and median length was three days. Average total cost was 70,714 rupees (1179 U dollars) which included average radiology cost; 12,507 rupees (208 U dollars), average laboratory cost; 8365 rupees (139 U dollars), average pharmacy cost; 13,320 rupees (222 U dollars) and average bed/room charges; 27,552 rupees (459 U dollars). Length of hospital stay is the most important determinant of cost. Average total cost for patients who stayed for 1 day was 19,597 rupees (326 U dollars), 2-3 days; 25,568 rupees (426 U dollars), 4-7 days; 49,705 rupees (828 U dollars), 8-30 days; 153,586 rupees (2559 U dollars), more than 30 days; 588,239 rupees (9804 U dollars). Average cost for general ward was 60,574 rupees (1010 U dollars), private ward was 74,880 rupees (1248 U dollars) and intensive care unit was 155,010 rupees (2583 U dollars). CONCLUSION: Cost of acute stroke care is extremely high as compared to average national income at our hospital. Most important determinant of cost is length of hospital stay. Cost cutting measures and increased funding from state are necessary to increase the availability of acute stroke care.

Should carotid endarterectomy be performed for symptomatic carotid stenosis in Pakistan?

OBJECTIVE: The risk of stroke and death associated with carotid endarterctomy is operator dependant. Data regarding risks of this procedure are not available in Pakistan and therefore it is difficult to make accurate risk benefit analysis for individual patients. Our objective was to determine safety of carotid endarterectomy at an academic tertiary care center in Pakistan. METHODS: Patients who underwent carotid endarterectomy (CEA) at our hospital during a ten-year period were identified through ICD-9 coding system of the hospital medical records. Demographic features, associated medical problems and immediate postoperative complications were recorded and analyzed. RESULTS: Sixty-three carotid endarterectomies were performed on 59 patients. Ages range from 43 to 80 (mean 61 +/- 8) years; 53 were male and 10 were female. Common associated diseases among these patients were hypertension; 38 (64.4%), ischemic heart disease; 26 (44%), diabetes mellitus; 24 (40.7%), dyslipidemia; 19 (32.2%) and renal insufficiency; 13 (22%). Most common complication was neuropraxia (transient neuropathy); 5 (7.9%), followed by pneumonia and stroke; each in 3 (4.8%) patients. None of the strokes related to the surgical procedure were disabling. Two of the patients who had stroke, recovered fully within 17 weeks and one recovered partly but was independent in all daily activities of living (ADLs). One patient died following simultaneous coronary artery bypass graft (CABG) and CEA. The risk of stroke or death for patients undergoing CEA was high with simultaneous CABG (3/11, 27%) and low for patients undergoing CEA alone (1/52, 2%). CONCLUSION: Carotid endarterectomy is a safe procedure in patients with symptomatic carotid stenosis at our hospital and should be performed, when indicated.

Spectrum of complications and mortality of bacterial meningitis: an experience from a developing country.

OBJECTIVE: The aim of this study was to obtain data on predisposing factors, causative organisms and their associated mortality and complications related to acute bacterial meningitis. METHODS: The chart review of all patients in whom acute bacterial meningitis was diagnosed at The Aga Khan University Hospital from January 1995 through December 2001. RESULTS: One hundred ninety-four patients were included in study. There were 146 males and 48 females. The mean age of our study population was 41 +/- 12.3 years. One hundred and ninety (97.9%) patients had community-acquired meningitis; only 4 (2.0%) patients developed meningitis nosocomially. The two most common predisposing factors were diabetes mellitus (13.9%) and otitis media (7.7%) among all 194 patients. A significant proportion of patients with complications had diabetes mellitus (24.6%, p < 0.001). CSF and blood cultures were positive in 53 (27.3%) and 42 (21.6%) patients respectively; there was no statistical difference found. The most common organisms isolated were Streptococcus pneumoniae in 35 (36.8%) patients followed by Neisseria meningitides in 30 (31.5%) patients. Approximately 68% of positive cultures yielded S. pneumoniae and N. meningitides (p < 0.0001). The overall mortality rate was 22.1%. The mortality rate for Streptococcus pneumoniae was 17.1%. The highest mortality was observed in patients with Pseudomonal meningitis where all four patients expired followed by mortality rate of 85.7% in Escherichia coli afflicted patients (p < 0.001). Complications occurred in 73 (37.6%) patients with persistent complications in 31 (42.4%) patients. Complications resolved in 34 (46.5%) patients. The most common complications were seizures (12.8%) and cranial nerve palsies (11.3%). Seizures were more likely to occur in older patients (p < 0.05) whereas hydrocephalus was more common in younger patients (p < 0.05). CONCLUSION: Bacterial Meningitis remains a serious disease associated with substantial morbidity and mortality. Most cases are community acquired with S. Pneumoniae being the most common pathogen. Old age, diabetes mellitus, a positive culture, seizures as a complication and late stage in the disease are the important predictors of a poor outcome.

Ischemic stroke subtypes in Pakistan: the Aga Khan University Stroke Data Bank.

OBJECTIVE: Frequency of ischemic stroke subtypes is influenced by ethnic and geographic variables. Our objective was to identify various stroke subtypes and its determinants at a tertiary care hospital. METHODS: We prospectively collected data on ischemic stroke subtypes admitted to The Aga Khan University Hospital in Karachi. RESULTS: A total of 596 patients were enrolled in 22 months in the Aga Khan Universtiy Stroke Registry. These included 393 patients with Ischemic stroke, 126 patients with intracerebral hemorrhage, 50 patients with subarachnoid hemorrhage and others. The ischemic stroke group was classified according to the TOAST criteria and comprised of lacunar 168/393 (42.7%); large artery atherosclerosis 106/393 (26.9%); cardioembolic 24/393 (6.1%); undetermined 80/393 (20.3%); and other determined types 15/393 (3.8%). The high proportion of lacunar strokes in our population may be due to high burden of inadequately treated hypertension and diabetes. Clear cut cardioembolic stroke was relatively infrequent in our population. CONCLUSION: Lacunar stroke is the most common subtype of stroke in our patient population. This is most likely secondary to uncontrolled hypertension.

Prognostic indicators in patients with intracranial tuberculoma: a review of 102 cases.

OBJECTIVE: To see the characteristics, course and outcome of patients suffering from intracranial tuberculoma. METHODS: Retrospective review of 102 patients diagnosed as intracranial tuberculoma at a tertiary care center over 10 years. RESULTS: A total of 102 cases were seen with an age range of 1 to 75 years (mean, 30 years). Predisposing factors included Diabetes mellitus (8 patients) and pregnancy or puerperium (7 patients). Five pediatric patients had tuberculoma despite documented BCG vaccination. Fever (59%), headache (57%), meningeal irritation (36%) were the commonest presenting features; one-third of patients were drowsy or comatosed at presentation. Cerebrospinal fluid analysis was performed in 63 patients, of whom 88% had elevated protein, 83% had low glucose, and 84% had pleocytosis (one-third with neutrophilia). Forty-nine (50%) patients had clinical or laboratory evidence of concomitant tuberculous meningitis. Chest radiographs showed active or old tuberculous infection (25%), with a miliary pattern in 20%. Two-thirds of subjects had multiple tuberculomas (mean, 4.5 lesions per patient) on contrast CT or MRI scan. Hydrocephalus was present in 37 (37%) patients of which 21 required shunt surgery. Thirty-nine patients had > 9 months of follow up; 17 patients showed complete recovery, 20 patients had partial recovery, and 2 patients had no response. Coma at presentation and miliary pattern on chest X-ray were predictors of poor prognosis. CONCLUSION: The study demonstrate that fever, headache, signs of meningeal irritation and cranial nerve palsies are common presenting features. Complete recovery was seen in 40% patients. Coma and military TB are predictors of poor prognosis.