Syed Ather Enam

Curcuminoids enhance memory in an amyloid-infused rat model of Alzheimer's disease

Alzheimers disease (AD) is a neurodegenerative disease. There are a limited number of therapeutic options available for the treatment of AD. Curcuminoids (a mixture of bisdemethoxycurcumin, demethoxycurcumin and curcumin) is the main chemical constituent found in turmeric, a well known curry spice, having potential in the treatment of AD. The objective of this study was to investigate the effects of curcuminoid mixture and individual constituents on spatial learning and memory in an amyloid-beta (Abeta) peptide-infused rat model of AD and on the expression of PSD-95, synaptophysin and camkIV. Curcuminoid mixture showed a memory-enhancing effect in rats displaying AD-like neuronal loss only at 30 mg/kg, whereas individual components were effective at 3-30 mg/kg. A shorter duration treatment with test compounds showed that the curcuminoid mixture and bisdemethoxycurcumin increased PSD-95 expression in the hippocampus at 3-30 mg/kg, with maximum effect at a lower dose (3 mg/kg) with respective values of 470.5 and 587.9%. However, after a longer duration treatment, two other compounds (demethoxycurcumin and curcumin) also increased PSD-95 to 331.7 and 226.2% respectively at 30 mg/kg. When studied for their effect on synaptophysin in the hippocampus after the longer duration treatment, the curcuminoid mixture and all three individual constituents increased synaptophysin expression. Of these, demethoxycurcumin was the most effective showing a 350.1% increase (P<0.01) at 30 mg/kg compared to the neurotoxin group. When studied for their effect on camkIV expression after longer treatment in the hippocampus, only demethoxycurcumin at 30 mg/kg increased levels to 421.2%. These compounds salvaged PSD-95, synaptophysin and camkIV expression levels in the hippocampus in the rat AD model, which suggests multiple target sites with the potential of curcuminoids in spatial memory enhancing and disease modifying in AD.

Curcuminoids rescue long-term potentiation impaired by amyloid peptide in rat hippocampal slices.

Curcuminoids are vital constituent of turmeric, with therapeutic potential in the treatment of Alzheimers disease. Electrically, stimulus train‐elicited plastic changes in hippocampal CA1 excitability were used as an experimental paradigm to study the effects of curcuminoid mixture and individual components on functional failure induced by Aβ peptide in vitro. Electrical stimulation was applied on Schaffer collaterals, and population spikes (PS) were recorded from stratum pyramidale. To induce long‐term potentiation (LTP) of PS, primed burst stimulation (PBs) was used. Aβ peptide inhibited PS LTP induction. Sinking PS LTP due to Aβ peptide was rescued when curcuminoid mixture was applied before PBs only at lower dose (0.1 μM) resulting in PS potentiation to 127.42% ± 1.83% at 5 min and 123.98% ± 1.06% at 60‐min post‐PBs. Similarly, when bisdemethoxycurcumin was applied, PS LTP was induced and lasted only at a single dose (0.1 μM). Demethoxycurcumin was effective at a middle dose (1 μM), so that the PS amplitude was changed to 140.15% ± 2.68% and 129.82% ± 0.44% at 5 and 60 min, respectively. PS LTP was effectively induced in the presence of curcumin at middle and high doses (1 and 30 μM) with resultant PS LTP to 155.68% ± 1.23% and 127.72% ± 1.23%, respectively, at 60‐min post‐PBs. These results showed that curcuminoids can restore susceptibility for plastic changes in CA1 excitability that is injured by exposure to Aβ peptide and rescue sinking PS LTP in Aβ‐peptide‐exposed hippocampal CA1 neurons. Synapse, 2011.

Craniocerebral aspergillosis in immunocompetent hosts: surgical perspective.

Craniocerebral aspergillosis is a rare but dangerous variety of central nervous system infections. Surgery is being widely recognized as the cornerstone of management. Due to the rarity of the disease, difficulty and delay in diagnosis and poor outcome, there is very little in the literature regarding the various surgical strategies that may be adopted in these patients. Early aggressive surgery followed by chemotherapy offers the best chances. Surgical planning would depend upon the type and location of the disease process as well as the condition of the patient. Perioperative care holds immense importance and knowledge of possible complications is essential. Aspergillosis of the central nervous system is difficult to diagnose and equally difficult to treat. Surgery remains the cornerstone of management followed by systemic antifungal medications. Results are better in immunocompetent patients as compared to those who are immunocompromised.

Fuzzy logic: A “simple” solution for complexities in neurosciences?

Background: Fuzzy logic is a multi-valued logic which is similar to human thinking and interpretation. It has the potential of combining human heuristics into computer-assisted decision making, which is applicable to individual patients as it takes into account all the factors and complexities of individuals. Fuzzy logic has been applied in all disciplines of medicine in some form and recently its applicability in neurosciences has also gained momentum. Methods: This review focuses on the use of this concept in various branches of neurosciences including basic neuroscience, neurology, neurosurgery, psychiatry and psychology. Results: The applicability of fuzzy logic is not limited to research related to neuroanatomy, imaging nerve fibers and understanding neurophysiology, but it is also a sensitive and specific tool for interpretation of EEGs, EMGs and MRIs and an effective controller device in intensive care units. It has been used for risk stratification of stroke, diagnosis of different psychiatric illnesses and even planning neurosurgical procedures. Conclusions: In the future, fuzzy logic has the potential of becoming the basis of all clinical decision making and our understanding of neurosciences.

Pituitary Adenomas : Presentations and Outcomes in a South Asian Country

OBJECTIVE The purpose of this retrospective review of all operated cases of pituitary adenomas in the last decade, is to define the demographic patterns and characteristics of such tumors and to assess surgical outcomes with regards to safety and efficacy of trans-sphenoidal tumor removal in our institution. METHODS Surgically treated pituitary adenomas presenting from 1995 till 2005 were reviewed for different variables. Results were expressed as mean, standard deviation and median for continuous and number with percentage for categorical data. Chi square test was applied to measure differences and significance was taken atp value < 0.05. RESULTS One hundred and twenty-five patients were operated for pituitary adenoma. Sixty-three percent were male and mean age was 37 years. Sixty percent of the patients presented with headache and/or visual symptoms. Twelve percent presented with pituitary apoplexy and 28% presented with symptoms due to pituitary hyperfunction. Fifty-five percent of patients had functioning and 44% had nonfunctioning adenomas. Mean pre operative tumor diameter from 86 pre op MRI scans was 26.76 mm (3-78 mm). Eighty-four percent of patients underwent trans-sphenoidal tumor resection and three percent had craniotomy. Mean size of post op residual tumor as calculated from 76 available post operative scans was 5.3 mm (range 0-31 mm). 17.6% of the patients required hormone replacement beyond three months and 10% were re-operated. Overall mortality was 1.6%. CONCLUSION In Pakistan, patients are more likely to present either with apoplexy or with a giant pituitary adenoma than patients reported from developed countries. Overall, our results have been satisfactory and comparable with the literature.

Non-operative management is superior to surgical stabilization in spine injury patients with complete neurological deficits: A perspective study from a developing world country, Pakistan

Background: Surgical stabilization of injured spine in patients with complete spinal cord injury is a common practice despite the lack of strong evidence supporting it. The aim of this study is to compare clinical outcomes and cost-effectiveness of surgical stabilization versus conservative management of spinal injury in patients with complete deficits, essentially from a developing countrys point of view. Methods: A detailed analysis of patients with traumatic spine injury and complete deficits admitted at the Aga Khan University Hospital, Pakistan, from January 2004 till January 2010 was carried out. All patients presenting within 14 days of injury were divided in two groups, those who underwent stabilization procedures and those who were managed non-operatively. The two groups were compared with the endpoints being time to rehabilitation, length of hospital stay, 30 day morbidity/mortality, cost of treatment, and status at follow up. Results: Fifty-four patients fulfilled the inclusion criteria and half of these were operated. On comparing endpoints, patients in the operative group took longer time to rehabilitation (P-value = 0.002); had longer hospital stay (P-value = 0.006) which included longer length of stay in special care unit (P-value = 0.002) as well as intensive care unit (P-value = 0.004); and were associated with more complications, especially those related to infections (P-value = 0.002). The mean cost of treatment was also significantly higher in the operative group (USD 6,500) as compared to non-operative group (USD 1490) (P-value < 0.001). Conclusion: We recommend that patients with complete SCI should be managed non-operatively with a provision of surgery only if their rehabilitation is impeded due to pain or deformity.

Clinical outcome and cost effectiveness of early tracheostomy in isolated severe head injury patients.

Background: Early tracheostomy (ET) has been shown to be effective in reducing complications associated with prolong mechanical ventilation. The study was carried out to evaluate the role of ET in reducing the duration of mechanical ventilation, duration of intensive care unit (ICU) stay, ICU-related morbidities, and its overall effect on outcome, in patients with isolated severe traumatic brain injury (TBI). Methods: This 7-year review included 100 ICU patients with isolated severe TBI requiring mechanical ventilation. ET was defined as tracheostomy within 7 days of TBI, and prolonged endotracheal intubation (EI) as EI exceeding 7 days of TBI. Of 100 patients, 49 underwent ET and 51 remained on prolong EI for ventilation. All patients were comparable in term of age and initial Glasgow Coma Scale (GCS). We evaluated groups regarding clinical outcome in terms of ventilator-associated pneumonia (VAP), ICU stay, and Glasgow Outcome Score (GOS). Results: The frequency of VAP was higher in EI group relative to ET group (63% vs. 45%, P value 0.09). ET group showed significantly less ventilator days (10 days vs. 13 days, P value 0.031), ICU stay (11 days vs. 13 days, P value 0.030), complication rate (14% vs. 18%), and mortality (8.2% vs. 17.6%). Clinical outcome assessed on the basis of GOS was also better in the ET group. Total inpatient cost was also considerably less (USD

Microsurgical excisions of vestibular schwannomas: A tumor-size-based analysis of neurological outcomes and surgical complications.

8027) in the ET group compared with the EI group (USD

Primary Central Nervous System Lymphoma Causing Multiple Spinal Cord Compression and Carcinomatous Meningitis in a 6-year-old A Case Report

9961). Conclusions: In patients with severe TBI, ET decreases total days of ventilation and ICU stay, and is associated with a decrease in the frequency of VAP. ET should be considered in severe head injury patients requiring prolong ventilatory support.

Clinical review of pediatric pilocytic astrocytomas treated at a tertiary care hospital in Pakistan.

Introduction: Vestibular schwannomas (VS) are benign tumors originating from Schwann cells in vestibulocochlear nerve. This study aimed at evaluating outcomes of microsurgical resections of VS based on tumor sizes in a South Asian country. Methods: The chart notes of 71 patients who underwent microsurgical resections of VS at a single academic center over a 20-year period (1990–2009) were reviewed, and relevant information was extracted. For analyzing outcomes, patients were divided into two groups based on tumor size at initial presentation: (1) Group A (tumor size ≤ 4 cm) and (2) Group B (tumor size > 4 cm). Pearsons chi-square and Fishers exact tests were used for comparison of proportions; the independent sample t-test was used for comparison of means. Results: The average tumor diameter was 4.1 ± 1.5 (range, 1–6.6) cm. Complete resection was achieved more frequently in patients in Group A (P < 0.001). Duration of hospital stay and cost of treatment were significantly higher in Group B patients (P < 0.003 and P < 0.04, respectively). The severity of postoperative facial nerve injury, assessed by House–Brackmann grading system, was significantly higher in Group B (P < 0.01). Cerebrospinal fluid (CSF) leak and lower cranial nerve deficits also occurred more frequently after resection in Group B (P = 0.031 and P = 0.003, respectively). Conclusion: We conclude that advanced stage tumors suggestive of delayed presentation are fairly common in Pakistan, and limit curative resection in the majority of patients. Postoperative morbidity is significantly higher in patients with tumor size > 4 cm.