A plea for rational mitigation of poor outcomes in the 'off-label use' of medications for the management of pain.

Neuropathic pain is a common and difficult to manage public health problem characterized by frequent treatment failure and high management costs. The variable presentation and response to treatment among patients make it difficult for physicians to apply a single, standardized approach for management. The physician's role in treating neuropathic pain is complex. Clinical decisions must be drawn from personal and shared experience, case reports, and evidence-based, controlled trials performed on selected populations of patients with common, narrowly-defined conditions. Recent advances in our understanding of the mechanisms that underlie the processing of nociceptive stimuli and the perception of pain have led to the increased 'off-label use' of adjuvant medications in an attempt to provide relief for many patients who heretofore have suffered unnecessarily with intractable neuropathic pain. Unfortunately, as with any treatment, sound clinical decisions can occasionally result in an untoward adverse response. It is therefore imperative that potential adverse effects inherent to all medications be considered and weighed against the untoward consequences of withholding treatment prior to incorporating their use in any course of management. This commentary presents a case report that illustrates a particularly devastating consequence that was encountered when a medication was selected for 'off-label use' in the treatment of intractable pain and presents an opinion for consideration in developing guidelines for determining acceptable risk and standard of care based upon rational adherence or deviation from the approved indications offered for the use of a medication at the time of its introduction into practice is granted.

Acute renal failure is associated with higher death and disability in patients with acute ischemic stroke: analysis of nationwide inpatient sample.

BACKGROUND AND PURPOSE: Acute renal failure (ARF) in setting of acute ischemic stroke (AIS) is associated with worse outcome. We sought to determine the prevalence of ARF and effect on outcomes of patients with AIS. METHODS: Data from all patients admitted to US hospitals between 2002 and 2010 with a primary discharge diagnosis of ischemic stroke and secondary diagnosis of ARF were included. The effect of ARF on rates of intracerebral hemorrhage and discharge outcomes was analyzed after adjusting for potential confounders using logistic regression analysis. RESULTS: Of 7,068,334 patients with AIS, 372,223 (5.3%) had ARF during hospitalization. Dialysis was required in 2364 (0.6%) of 372,223 patients. Patients with AIS with ARF had higher rates of moderate to severe disability (41.3% versus 30%; P<0.0001), intracerebral hemorrhage (1.0% versus 0.5%; P<0.0001), and in-hospital mortality (8.4% versus 2.9%; P<0.0001) compared with those without ARF. After adjusting for confounding factors, patients with AIS with ARF had higher odds of moderate to severe disability (odds ratio, 1.3; 95% confidence interval, 1.3-1.4; P<0.0001), intracerebral hemorrhage (odds ratio, 1.4; 95% confidence interval, 1.3-1.6; P<0.0001), and death (odds ratio, 2.2; 95% confidence interval, 2.0-2.2; P<0.0001). CONCLUSIONS: ARF in patients with AIS is associated with significantly higher rates of moderate to severe disability at discharge and in-hospital mortality.

FMRI of working memory impairment after recovery from subarachnoid hemorrhage.

Recovery from aneurysmal subarachnoid hemorrhage (SAH) is often incomplete and accompanied by subtle but persistent cognitive deficits. Previous neuropsychological reports indicate these deficits include most prominently memory impairment, with working memory particularly affected. The neural basis of these memory deficits remains unknown and unexplored by functional magnetic resonance imaging (fMRI). In the present study, patients who experienced (SAH) underwent fMRI during the performance of a verbal working memory paradigm. Behavioral results indicated a subtle but statistically significant impairment relative to healthy subjects in working memory performance accuracy, which was accompanied by relatively increased blood-oxygen level dependent signal in widespread left and right hemisphere cortical areas during periods of encoding, maintenance, and retrieval. Activity increases remained after factoring out inter-individual differences in age and task performance, and included most notably left hemisphere regions associated with phonological loop processing, bilateral sensorimotor regions, and right hemisphere dorsolateral prefrontal cortex. We conclude that deficits in verbal working memory following recovery from (SAH) are accompanied by widespread differences in hemodynamic correlates of neural activity. These differences are discussed with respect to the immediate and delayed focal and global brain damage that can occur following (SAH), and the possibility that this damage induces subcortical disconnection and subsequent decreased efficiency in neural processing.

Artifact quantification and tractography from 3T MRI after placement of aneurysm clips in subarachnoid hemorrhage patients.

BACKGROUND: The application of advanced 3T MRI imaging techniques to study recovery after subarachnoid hemorrhage (SAH) is complicated by the presence of image artifacts produced by implanted aneurysm clips. To characterize the effect of these artifacts on image quality, we sought to: 1) quantify extent of image artifact in SAH patients with implanted aneurysm clips across a range of MR sequences typically used in studies of volumetry, blood oxygen level dependent signal change (BOLD-fMRI), and diffusion-weighted imaging (DW-MRI) and 2) to explore the ability to reconstruct white matter pathways in these patients. METHODS: T1- and T2-weighted structural, BOLD-fMRI, and DW-MRI scans were acquired at 3T in two patients with titanium alloy clips in ACOM and left ACA respectively. Intensity-based planimetric contouring was performed on aligned image volumes to define each artifact. Artifact volumes were quantified by artifact/clip length and artifact/brain volume ratios and analyzed by two-way (scan-by-rater) ANOVAs. Tractography pathways were reconstructed from DW-MRI at varying distances from the artifacts using deterministic methods. RESULTS: Artifact volume varied by MR sequence for length (p = 0.007) and volume (p < 0.001) ratios: it was smallest for structural images, larger for DW-MRI acquisitions, and largest on fMRI images. Inter-rater reliability was high (r = 0.9626, p < 0.0001), and reconstruction of white matter connectivity characteristics increased with distance from the artifact border. In both patients, reconstructed white matter pathways of the uncinate fasciculus and inferior fronto-occipital fasciculus were clearly visible within 2 mm of the artifact border. CONCLUSIONS: Advanced 3T MR can successfully image brain tissue around implanted titanium aneurysm clips at different spatial ranges depending on sequence type. White matter pathways near clip artifacts can be reconstructed and visualized. These findings provide a reference for designing functional and structural neuroimaging studies of recovery in aSAH patients after clip placement.

Frequency-specific electrocorticographic correlates of working memory delay period fMRI activity.

Electrocorticography (ECoG) and functional MRI (BOLD-fMRI) have been used previously to measure brain activity during working memory delay periods. These studies have separately reported oscillation changes in the theta (4-8 Hz) band and BOLD-fMRI increases during delay periods when information is maintained in memory. However, it is not known how intracranial cortical field potential (CFP) changes relate to BOLD-fMRI responses during delay periods. To answer this question, fMRI was obtained from six epilepsy patients during a visual working memory task. Then, following subdural macroelectrode implant, continuous ECoG was used to record CFPs during the same task. Time-frequency analyses showed delay period gamma band oscillation amplitude increases on electrodes located near fMRI activity, while in the theta band changes were higher for electrodes located away from fMRI activation. The amplitude of the ECoG gamma band response was significantly positively correlated with the fMRI response, while a negative correlation was found for the theta band. The findings are consistent with previous reports of local field potential (LFP) coupling in the gamma band with BOLD-fMRI responses during visual stimulation in monkeys, but are novel in that the relationship reported here persists after the disappearance of visual stimuli while information is being maintained in memory. We conclude that there is a relationship between BOLD-fMRI increases and human working memory delay period gamma oscillation increases and theta decreases. The spectral profile change provides a basis for comparison of working memory delay period BOLD-fMRI with field potential recordings in animals and other human intracranial EEG studies.

Microdiscectomy for lumbosacral disc herniation and frequency of failed disc surgery.

BACKGROUND: Microdiscectomy for lumbosacral disc herniations is one of the most commonly performed neurosurgical procedures. The patient demographics, symptomatology, and recovery are highly variable, and surgical outcomes depend on several factors, including patient demographics. Failed disc surgery refers to failure of improvement in patient's symptoms following microdiscectomy, and has been observed to occur in up to 12% of patients. To date, no study form Pakistan has looked into patient demographics and failed disc surgery rates within the local context. OBJECTIVE: The aim of this study was to review the demographics of the patient population presenting for surgical treatment of lumbosacral disc herniations and to review our results of lumbosacral microdiscectomy at a university hospital in Pakistan. METHODS: This is a retrospective analysis of all adult patients admitted from January 2003 to January 2008 for symptomatic lumbosacral disc herniation requiring microdiscectomy, at the Aga Khan University Hospital, Karachi. Data were collected through our medical records, on a standardized form. Basic information about the patient population, disease process, modes of nonsurgical treatment, and details on surgery and postoperative course were recorded and analyzed using SPSS. RESULTS: Five hundred one patients were studied, based on inclusion criteria. The mean age was 41.2 years; 347 (69%) patients were male and 154 (31%) female. Mean body mass index of the population was 26 and was higher in females. All patients primarily presented with radiculopathy, and the mean duration of these symptoms was 438 days. Mean duration of nonoperative management was 53 weeks. Fifty-one patients (10.2%) had previously undergone spine surgery. A total of 442 (88%) patients were operated at single disc level, and the rest at two levels. Sixty-six (13%) patients were operated for upper lumbar disc herniations. Mean operative time was 94 minutes, and the most common complication was dural tear. Mean length of hospital stay was 5 days (2-12 days). Mean follow-up was 48.3 weeks (4 weeks to 14 years). Complete resolution of symptoms was seen in 360 (71.9%) patients and failed disc surgery was diagnosed in 42 (8.4%) patients. Twenty-six patients (5.2%) were reoperated upon, with gradual improvement. The authors report an overall failed back surgery rate of 8.38%. CONCLUSIONS: Overall our results were comparable to published international literature. However, the authors observed significant differences in demographics, especially in terms of age, gender distribution, and mean BMI of patient population as well as frequency of involvement of upper lumbar discs.

Follicular thyroid carcinoma presenting as solitary skull metastasis: report of two cases.

We report two otherwise healthy patients with no prior history of thyroid cancer, who presented to us with a solitary scalp lump. Neuroimaging of both patients showed osteolytic lesions involving the cranium which were subjected to complete excision biopsy and cranioplasty. Histopathological examination revealed metastases from well differentiated follicular thyroid carcinoma (FTC). Subsequent workup confirmed occult primary carcinoma of the thyroid gland in both patients.

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.