Prabal Deb

Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis

Stroke is a serious neurological disease, and constitutes a major cause of death and disability throughout the world. The pathophysiology of stroke is complex, and involves excitotoxicity mechanisms, inflammatory pathways, oxidative damage, ionic imbalances, apoptosis, angiogenesis and neuroprotection. The ultimate result of ischemic cascade initiated by acute stroke is neuronal death along with an irreversible loss of neuronal function. Therapeutic strategies in stroke have been developed with two main aims: restoration of cerebral flow and the minimization of the deleterious effects of ischemia on neurons. Intense research spanning over the last two decades has witnessed significant therapeutic advances in the form of carotid endarterectomy, thrombolytics, anticoagulant therapy, antiplatelet agents, neuroprotective agents, and treating associated risk factors such as hypertension and hyperlipidemia. However, the search for an effective neuroprotectant remains frustrating, and the current therapeutic protocols remain suboptimal. Till date only one FDA-approved drug is available for ischemic stroke; i.e., the serine protease tissue-type plasminogen activator (tPA), utility of which is limited by short therapeutic window. The objective of this review is to critically evaluate the major mechanisms underlying stroke pathophysiology, with emphasis on potential novel targets for designing newer therapeutic modalities.

Dorsal approach in transfer of the distal spinal accessory nerve into the suprascapular nerve: histomorphometric analysis and clinical results in 14 cases of upper brachial plexus injuries.

PURPOSE The spinal accessory nerve (SAN) is conventionally transferred to the suprascapular nerve (SSN) through an incision in the supraclavicular region (the anterior approach) to improve shoulder function in brachial plexus injuries. This approach carries a risk of partial denervation of upper trapezius muscle. Here we describe how dorsal nerve transfer through an incision placed directly over the scapular spine preserves the proximal branches to the upper trapezius muscle and allows nerve transfer close to target muscles. METHODS We report our experience with the dorsal approach in 14 cases managed between February 2007 and January 2008. Results were compared with 21 control cases treated by the anterior approach. In addition, we submitted proximal cut ends of the SAN in 10 cases from the experimental group for histomorphometry. RESULTS A total of 11 patients had C5 and C6 injuries, whereas 3 had associated C7 injuries. The denervation period ranged between 3 and 10 months. In all cases, the distal SAN could be transferred to the SSN without a graft. Histomorphometry revealed an average of 1,671 myelinated axons. Shoulder abduction and external rotation were restored in 13 and 9 cases, respectively, compared with 16 and 12, respectively, in the control group. Electromyography revealed the first sign of reinnervation of infraspinatus muscle at 23 ± 4 weeks, compared with 30 ± 4 weeks in the control group. Initial evidence of shoulder abduction appeared earlier in the study population (28 ± 4 vs 34 ± 4 weeks). Shoulder abduction and external rotation in the study group ranged between 70° and 170° and 30° and 80°, compared with 65° and 160° and 22° and 55° in the control group. Using the Medical Research Council (MRC) grading system, at 6 months postreconstruction, 13 patients had M4 power in the trapezius muscle, whereas 1 had M3, compared with 5 in the control group who displayed grade 3 weakness. CONCLUSIONS A dorsal approach for transfer of the distal SAN into the SSN is an alternative and effective technique in restoring shoulder function in upper brachial plexus injuries. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic III.

Sister Mary Joseph nodule as the presenting sign of disseminated prostate carcinoma.

Sister Mary Josephs nodule is referred to as metastasis of visceral malignancy to the umbilicus. Most common primaries are in the gastrointestinal or genital tract, while other locations are rare. We recently encountered a 76-year-old male who was referred to the surgery clinic with an erythematous nodule in the umbilicus measuring 6 cm in diameter with complaints of painless profuse hematuria. History revealed severe obstructive voiding symptoms of 2-year duration, along with significant loss of weight and difficulty in walking. A detailed examination showed hard nodular hepatomegaly, along with grade IV prostatomegaly. Serum prostate-specific antigen was 3069 ng/ml. A pelvic radiograph displayed multiple osteolytic lesions, while ultrasonography showed multiple iso- and hypoechoic lesions in both lobes of the liver, suggestive of metastasis. Histopathology of a Tru-cut biopsy of the prostate confirmed an adenocarcinoma (Gleason score 9) with umbilical metastasis. The patient was on regular follow-up and died 3 months later.

Intraoperative neurocytology of primary central nervous system neoplasia: A simplified and practical diagnostic approach

Intraoperative consultations may pose considerable diagnostic challenge to the neuropathologist in diagnosing primary and metastatic neoplasms of the central nervous system (CNS). Cytological preparations in the form of squash, touch, imprint or smears are few of the available modalities in addition to the frozen section (FS). Although the latter is superior in providing both histologic patterns and cytomorphologic details yet smears are of vital importance when tissue available is limited (stereotactic biopsy), scrutinisation of intercellular matrix (astrocytoma versus oligodendroglioma) and evaluation of discohesive cells (lymphoma, pituitary adenoma) and in inflammatory lesions. This review is intended to emphasize the value, applicability and limitations of neurocytology aiming to expedite the intraoperative smear-based diagnoses of CNS neoplasia as per the World Health Organization (WHO) classification. We recommend that whenever possible, both smears and FS should be examined concomitantly and in a correlative manner. In the unlikely event of a mismatch between the findings on smear and FS, intraoperative diagnosis is primarily based on FS, if adequate tissue is available. However, each case must be evaluated on its own merit and in difficult cases relevant differential diagnoses should be offered to facilitate surgical decisions and optimally triage patient management.

Morphometric study of microvessels in primary CNS tumors and its correlation with tumor types and grade

INTRODUCTION Alterations of microvasculature are integral to CNS neoplasia, and a diagnostic feature of high-grade gliomas. The objectives of this study were two fold: First, to correlate morphometrically measured microvessel density (MVD), microvessel caliber (VC), and percentage of total microvessel area (%TVA) with WHO histologic grade in various types of primary CNS tumors. Second, to evaluate if such a correlation could be further refined by using mathematical derivatives of measured parameters namely coefficient of variation of VC (COofVC), microvessel cross-sectional area (VCSA), and percentage of total VCSA (%TVCSA). MATERIALS AND METHODS Various microvessel parameters were assessed in a variety of 30 primary CNS tumors as consecutively encountered in routine surgical pathology practice including gliomas, meningiomas and others by image morphometry using CD34-immunostained sections. We introduced a novel method of effectively determining VC. Results were correlated with tumor type and grade. Appropriate statistical analysis was performed. RESULTS Microvessel characteristics, especially VC (p<0.0022), VCSA (p<0.0164), CVofVC (p<0.0001), %TVCSA (p<0.0002) and %TVA (p<0.0003) of tumors were significantly greater than normal tissue. MVD increased in all tumors, excepting meningiomas, and was significantly higher in gliomas (p<0.0062). MVD showed negative correlation with VC (r=-0.808) and VCSA (r=-0.848) in the normal brain but was less significant in tumors. Unlike tumors, caliber distribution of microvessels in normal brain was noted to follow a Gaussian pattern. Histological grades of tumors showed positive correlation with MVD (r=0.547), VC (r=0.606), CVofVC (r=0.623), VCSA (r=0.485), %TVCSA (r=0.783) and %TVA (r=0.603). Calculated scores, estimated from multiple regressions of vessel parameters, correlated well with histological grade, with S2 (calculated using all measured as well as mathematically derived microvessel parameters) being better than S1 (calculated using measured parameters: MVD and VC). CONCLUSION Tumor grades positively correlated with all microvessel parameters, with %TVCSA displaying the best. The correlation of %TVA with tumor grade was weaker than %TVCSA mainly due to the impact of MVD. These findings emphasize the value of VC as effectively measured using our novel method and best illustrated by its derivative %TVCSA (an indicator of blood flow), in addition to the well-recognized value of MVD in tumor prognostication. Multiple regressions of microvessel parameters provided the best correlation with grade. Morphometric analysis of microvessels in CNS tumor facilitates a better understanding of the tumor grade, tumor progression and overall prognosis.

Correlation of expression pattern of aquaporin-1 in primary central nervous system tumors with tumor type, grade, proliferation, microvessel density, contrast-enhancement and perilesional edema.

OBJECTIVES Brain edema, a hallmark of malignant brain tumors, continues to be a major cause of mortality. The underlying molecular mechanisms are poorly understood and thought to be mediated through membrane water-channels: aquaporins (AQP1,4,9). The abnormal upregulation of AQP1 in certain glial neoplasms has suggested a potential role in tumor pathogenesis, apart from being a novel target for newer therapeutic regimen. This study was undertaken to evaluate the expression of AQP1 in primary CNS tumors of various histologic types and grades, and its correlation with contrast-enhancement, perilesional edema, histomorphology, proliferation index and microvessel density. MATERIALS AND METHODS Biopsy tissues from 30 patients (10 each from gliomas, meningiomas and other primary CNS tumors) were studied. Autopsy brain sections served as control. AQP1-immunoreactivity was correlated with histomorphology, radiology, proliferation index and microvessel density (MVD). RESULTS AQP1 expression was increased in gliomas and ependymal tumors as compared to meningiomas. Intratumoral expression was homogenous in high-grade and membranous in low-grade neoplasms, while peritumoral areas showed expression around vessels and reactive astrocytes. High-grade tumors showed peritumoral upregulation, while low-grade had intense intratumoral expression. A trend of positive correlation was observed between AQP1-immunopositivity and increasing grade, higher MIB-1LI, increasing contrast-enhancement and more perilesional edema, and elevated MVD with raised AQP1:MVD ratio. CONCLUSIONS AQP1-immunoexpression had a good correlation with high-grade tumors. AQP-upregulation in perilesional areas of high-grade tumors suggests its role in vasogenic edema. Further studies involving other AQP molecules, vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 α (HIF-1α) should be undertaken to evaluate its possible role as a potential surrogate marker of high-grade tumors heralding poor outcome, inhibition of which may serve as the basis for future targeted therapy.

Posterior Approach for Both Spinal Accessory Nerve to Suprascapular Nerve and Triceps Branch to Axillary Nerve for Upper Plexus Injuries

Restoration of stability and movements at the shoulder joint are the 2 most important goals in the management of brachial plexus injuries. The 2 nerves that are preferentially targeted for this purpose are the suprascapular (SSN) and the axillary (AXN) nerves. These nerve transfers have conventionally been performed by the anterior approach, but recently transfers performed by posterior incisions have been gaining popularity, by virtue of being selective and located close to the target muscles. Herein, we describe the technical details of spinal accessory nerve (SAN) to SSN and triceps branch to AXN for upper plexus injuries, both performed by the posterior approach.

Fascicular Selection for Nerve Transfers: The Role of the Nerve Stimulator When Restoring Elbow Flexion in Brachial Plexus Injuries

PURPOSE Restoration of elbow flexion is an important goal in brachial plexus injuries. Double nerve transfers using fascicles from ulnar and median nerves have consistently produced good results without causing functional compromise to the donor nerve. According to conventional practice, these double nerve transfers are dependent on the careful isolation of ulnar and median nerve fascicles, which are responsible for wrist flexion, using a handheld nerve stimulator. Here we suggest that fascicular selection by nerve stimulation might not be a necessity when executing double nerve transfers for restoration of elbow flexion in brachial plexus injuries. METHODS This is a retrospective case control study in 26 patients with C5, C6 brachial plexus injuries that were managed with double nerve transfers between March 2005 and January 2008. Our technique consisted of transferring 2 fascicles, one each from the ulnar and the median nerve, directly onto the biceps and brachialis motor branches. Contrary to the standard practice, the ulnar or median nerve fascicles were selected without using a handheld nerve stimulator. Results were compared to 21 cases (control group) in which a nerve stimulator was used for fascicular selection. The denervation period ranged from 3 to 9 months. RESULTS Twenty-four patients of the study group experienced full restoration of elbow flexion, and 2 had an antigravity flexion of 120° and 110°. The EMG revealed the first sign of reinnervation of biceps and brachialis muscle at 9 ± 2 weeks and 11 ± 2 weeks, as compared to 9 ± 2 weeks and 12 ± 4 weeks in the control group. After surgery, the appearance of initial evidence of elbow flexion, the range and mean of elbow flexion strength, and the difference between preoperative and postoperative grip and pinch strengths were comparable in both groups. At 24 to 28 months follow-up, 19 patients of the study group had M4 power and 7 had M3, compared to 18 and 3 cases, respectively, in the control group. The P values for Medical Research Council grade, strength of elbow flexion, and range of elbow flexion between the 2 groups did not reveal any significant statistical difference. CONCLUSIONS Double nerve transfer is a reliable technique for restoring elbow flexion in brachial plexus injuries. There is no advantage of using a nerve stimulator in selecting fascicles before performing the nerve transfer.

Intraventricular cystic meningioma

We report a case of a 45-year-old male patient with intraventricular cystic meningioma located in the left lateral ventricle. He presented with complaints of global headache, progressively increasing loss of memory, and frequent episodes of abnormal behavior, of 1 month duration. At the time of hospital admission, his general and neurological examination was normal. Neuroimaging studies showed a left lateral ventricular enhancing mass, composed of mixed solid and cystic areas. The tumor was completely excised via the anterior transcallosal approach. A histological examination revealed a meningothelial meningioma without any atypia. The aim of this report is to present the occurrence of an intraventricular cystic meningioma.

Idiopathic hypertrophic cranial pachymeningitis: Three biopsy-proven cases including one case with abdominal pseudotumor and review of the literature

Hypertrophic pachymeningitis (HP) is a rare disorder of diverse etiology. It presents with headaches, cranial neuropathies and ataxia occurring alone or in combination. Dural biopsy is essential to exclude secondary causes of pachymeningitis. There is paucity of data on biopsied cases of HP. We report three biopsy-proven cases of idiopathic hypertrophic cranial pachymeningitis. All our patients had headaches and multiple cranial neuropathies; ataxia was seen in one patient. One patient had recurrent anterior and posterior cranial neuropathies, while one each had recurrent anterior and posterior cranial neuropathies. Two patients had profound irreversible mono-ocular visual loss. All of them showed prominent pachymeningeal thickening on imaging. Infarcts were seen in one patient, which have rarely been documented. All patients showed biopsy evidence of meningeal thickening and nonspecific chronic inflammation of the dura. The disease may have a remitting and relapsing course, and usually responds to steroids. Clinical improvement was excellent in two patients and modest in one on steroid therapy. All our patients required azathioprine during the course of therapy. Early institution and long-term maintenance of steroid therapy prevents neurologic sequelae. Occurrence of abdominal inflammatory pseudotumor in a patient of HP possibly as part of multifocal fibrosclerosis has not been described earlier.