Making sense of the clinical spectrum of limb girdle muscular dystrophies.

The expansion of the spectrum of limb girdle muscular dystrophies (LGMDs) in recent years means that neurologists need to be familiar with the clinical clues that can help with their diagnosis. The LGMDs comprise a group of genetic myopathies that manifest as chronic progressive weakness of hip and shoulder girdles. Their inheritance is either autosomal dominant (LGMD1) or autosomal recessive (LGMD2). Their prevalence varies in different regions of the world; certain ethnic groups have documented founder mutations and this knowledge can facilitate the diagnosis. The clinical approach to LGMDs uses the age at onset, genetic transmission and clinical patterns of muscular weakness. Helpful clinical features that help to differentiate the various subtypes include: predominant upper girdle weakness, disproportionate respiratory muscle involvement, distal weakness, hip adductor weakness, 'biceps lump' and 'diamond on quadriceps' sign, calf hypertrophy, contractures and cardiac involvement. Almost half of patients with LGMD have such clinical clues. Investigations such as serum creatine kinase, electrophysiology, muscle biopsy and genetic studies can complement the clinical examination. In this review, we discuss diagnostic clinical pointers and comment on the differential diagnosis and relevant investigations, using illustrative case studies.

Efficacy and Safety of Rituximab in Central Nervous System Demyelinating Disorders.

BACKGROUND: Rituximab, an anti-CD20 monoclonal antibody, has been used worldwide as an off-label therapy in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). OBJECTIVE: The aim of the present study was to evaluate the efficacy and safety of rituximab in central nervous system demyelinating disorders in the Indian context. METHODS: We conducted a retrospective analysis of patients with MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) who were treated with rituximab at a single tertiary care centre in Mumbai. RESULTS: The study enrolled 102 patients (61 MS, 37 NMOSD and 4 MOGAD) from June 2008 to January 2020. Following rituximab therapy, 96.7% of MS, 67% of NMOSD, and 50% of MOGAD patients were free of relapses. The mean annualized relapse rate reduced from 2.17 to 0 for patients with relapsing remitting MS (RRMS), from 0.8 to 0 for secondary progressive MS (SPMS), from 2.5 to 0.14 for NMOSD, and from 3.43 to 1.04 for MOGAD. The median expanded disability status scale improved significantly in RRMS patients, worsened non-significantly in the SPMS group, and remained unchanged in NMOSD and MOGAD patients. On follow-up magnetic resonance imaging, there was a significant reduction in the number of MS patients developing new contrast enhancing lesions or new T2 lesions. Adverse events (infusion reactions or severe infections) occurred in 12 patients. CONCLUSION: Rituximab is effective and safe in Indian patients with MS and NMOSD.

Characterization of the possible mechanisms underlying the hypotensive and spasmogenic effects of Loranthus ferrugineus methanolic extract.

In the present study, L. ferrugineus methanol extract (LFME) was evaluated for its blood pressure lowering effect in anesthetized normotensive Sprague Dawley (SD) rats and its spasmogenic effect in isolated guinea pig ileum. The possible mechanism(s) of action were also investigated. LFME was obtained by Soxhlet extraction. The rats were fasted overnight and anesthetized with sodium pentobarbitone (60 mg/kg i.p.). LFME was administered in i.v. boluses in the concentrations of 25, 50, 100 and 200 mg/kg respectively, with concomitant monitoring of mean arterial pressure (MAP). It was found that LFME dose-dependently reduced MAP. An i.v. bolus injection of atropine significantly decreased the blood pressure lowering effect of LFME. Similarly, L-NAME (Nomega-nitro-L-arginine methyl ester) significantly lowered both the MAP and the action duration. Conversely, no significant change in MAP was seen following i.v. injections of neostigmine, hexamethonium, prazosin and propranolol. LFME also produced a dose-dependent contractile effect in guinea pig ileum. This contraction was significantly reduced in atropine pre-incubated tissue segments, yet it was significantly enhanced in the presence of neostigmine. No appreciable change in the ability of LFME to contract guinea pig ileum was seen in the presence of hexamethonium. Accordingly, it can be postulated that LFME possesses a marked hypotensive effect that can be attributed to stimulation of muscarinic receptors and/or stimulation of nitric oxide (NO) release. Moreover, LFME retains a considerable spasmogenic action due to its cholinergic properties. The hypotensive and spasmogenic effects of LFME justify its traditional uses.

Outcomes of definitive radiotherapy for early laryngeal cancer in terms of survival and patterns of failure.

BACKGROUND: Early laryngeal cancer treated with definitive radiotherapy or surgery has a high cure rate. This study evaluated the patterns of treatment failure and long-term results of early laryngeal cancers treated with definitive radiotherapy. METHOD: From January 2002 to December 2014, a total of 242 patients with early-stage laryngeal cancers were treated with radical radiotherapy. RESULTS: All patients had squamous cell carcinoma of the larynx (92 per cent male and 8 per cent female). Median follow-up was 4.5 years. The majority of patients were smokers (57.4 per cent). Local failure was seen in 12.5 per cent of stage I patients and 22.8 per cent of stage II patients. The 5-year overall survival and disease specific survival were 84 per cent and 91 per cent, respectively. CONCLUSION: In summary, radiotherapy is a suitable treatment modality for patients with early-stage laryngeal cancer, with an overall locoregional control rate of 84 per cent. Patients who fail radiotherapy may still undergo salvage laryngectomy.

Clinical outcome of primary non-metastatic breast cancer: A single institution experience.

BACKGROUND: We report on prognostic factors and long-term survival of non-metastatic breast cancer patients treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC) in Pakistan. MATERIALS AND METHODS: This retrospective cohort study is based on a review of 2829 pathologically confirmed non-metastatic breast cancer patients managed from January 1995 to May 2009. Median age was 45 years. Stage at presentation: Stage I (9%), stage II (59%), and stage III (32%). Infiltrating ductal carcinoma (92%) constituted the most prevalent histological subtype. Estrogen (ER), progesterone (PR) and Her2-neu were positive in 49%, 50%, and 26%, respectively. A mastectomy was performed in 67% and conservative surgery in 33% of the patients. Post-operative radiotherapy was delivered in 85% of the cases. Ninety percent of the patients received chemotherapy and mainly consisted of anthracycline-based regimens + taxanes. Hormonal manipulation was done in ER/PR positive patients. RESULTS: The 5- and 10-year overall survival (OS) was 70% (95% confidence interval [CI]: 68.2-71.8%) and 54% (95%CI: 51.2-56.8%), while disease free survival (DFS) was 65% (95% CI: 63-67%) and 52% (95% CI: 49.2-54.8%), respectively. Recurrence following primary treatment was seen in 35% of the patients. On multivariate analysis T stage, number of axillary nodal involvement, tumor grade, ER status and family history, were found to be independent predictors for OS and DFS. CONCLUSIONS: Over 90% of non-metastatic breast cancer patients present with stagesII and III disease and a significant proportion develop distant metastasis accounting for overall long-term outcome inferior to developed countries. Efforts should be directed to raise the level of health awareness and screening programs to improve early detection in Pakistan.

Treatment results for 149 medulloblastoma patients from one institution.

PURPOSE: Retrospective analysis of patients with medulloblastoma to determine the effectiveness of previous treatments for medulloblastoma and plan for future management strategies. METHODS AND MATERIALS: During the period March 1976 to December 1991, 172 patients with cerebellar medulloblastoma were referred to King Faisal Specialist Hospital and Research Center. One hundred and forty-nine patients were treated with curative intent. There were six postoperative deaths, and 10 patients planned for radiotherapy treatment failed to complete the prescribed course. One hundred and thirty-three patients completed a course of radiotherapy after surgery. Adjuvant chemotherapy was not used routinely (six patients only). Tumors were staged retrospectively according to the Chang staging system. There were no T1 patients, 32 patients had T2 tumors, 76 had T3 tumors, and 29 had T4 tumors. The T stage could not be allocated in 12 patients. Ninety-nine patients required a shunting procedure either pre- or postoperatively. Forty-six patients had complete resection of tumor, 91 had incomplete resection, and 6 patients had biopsy only. The extent of resection could not he determined in six patients. The median radiation dose for the whole brain was 34 Gy, spine 32.5 Gy, and posterior fossa 52.8 Gy. Fraction sizes ranged from 1.7-1.8 Gy for craniospinal fields and 2 Gy for the posterior fossa boost. Seventy percent completed the prescribed course within 7 weeks. RESULTS: Actuarial survival for the whole group of 149 patients was 53% at 5 years and 38% at 10 years. On univariate analysis, patients with T2 tumors did significantly better as compared to patients with T3 and T4 tumors. Survival of patients who had clinical and radiological complete resection of tumor at surgery was significantly better than patients with incomplete tumor removal. The presence of a ventriculoperitoneal (VP) shunt had a significant negative impact on survival. Treatment failure by site was analyzed with respect to the radiation dose. Doses greater than 50 Gy for the posterior fossa, and greater than 30 Gy for craniospinal axis, resulted in significantly better survival. On multivariate analysis, the only significant prognostic factor was the presence of a VP shunt in patients with T2 tumors. CONCLUSION: T stage, VP shunt, radiation doses and extent of surgery were important prognostic factors. In this study, radiation doses of more than 50 Gy to the posterior fossa and 30 Gy to the craniospinal axis resulted in improved survival.

Primary pancreatic non-Hodgkin's lymphoma in a renal transplant recipient.

Primary pancreatic non-Hodgkin's lymphoma (NHL) is rare and accounts for less than 1% of all lymphomas. The development of NHL following transplant is well recognized. However, there are no previous reports on localized lymphomatous pancreatic involvement in a transplant patient. We report on the first case of primary pancreatic NHL developing in a renal transplant recipient. The patient was treated without reducing immunosuppression and received combination chemotherapy and radiation. The patient is in complete remission at 10-month follow-up.

Impact of pregnancy on non-metastatic breast cancer: a case control study.

The diagnosis of breast cancer during pregnancy remains uncommon and therefore leads to non-standardized management. We reviewed retrospectively 28 such women treated at this centre and compared them with age and stage matched controls. Differences in management and outcome were analysed for statistical significance. There was no significant difference in overall survival (P = 0.86) and relapse-free survival (P = 0.48) between the two groups. Chemotherapy after the first trimester of pregnancy carried no significant morbidity. Pregnancy does not appear to be an adverse prognostic factor for breast cancer.

Primary Hodgkin's disease of the mandible: a case report and review of the literature.

Extranodal presentation in Hodgkin's disease is uncommon and bone involvement is rare at diagnosis. However, late in the course of this disease, bone involvement may occur in 9% to 35% of the cases. The mandible is very rarely involved even in advanced stages with only seven such cases reported in the literature. Of these only one had primary Hodgkin's disease of the mandible. A second case is described in this report.

Squamous cell carcinoma of the oral tongue: an analysis of prognostic factors.

AIM: To identify the prognostic significance of different factors in patients with squamous cell carcinoma of the tongue. PATIENTS AND METHODS: Seventy-seven patients with carcinoma of the tongue were treated radically at the King Faisal Specialist Hospital and Research Centre between 1980 and 1989. Twenty patients (26%) were treated by resection alone, 11 (14%) with radiotherapy alone, and 46 (60%) with combined resection and radiotherapy. RESULTS: Forty-seven patients (61%) had T(1-2), 28 (36%) T(3-4), and two T(x) tumours. The regional nodes were clear in 53 (69%) and contained metastases in 24 patients (31%). Thirty patients (39%) developed recurrences, which were local in 9, regional in 14, locoregional in 5, and locoregional with metastatic disease in 2. The five and 10-year overall actuarial survival for all patients were 65% and 53%, respectively, and the corresponding relapse-free survival 56% and 50%. Univariate and multivariate analyses were done of seven variables - age (<40 compared with >/=40 years), sex, chewing tobacco use, smoking, TNM stage, surgical margins (clear or invaded), and treatment (resection, radiotherapy, or the combination). On univariate analysis chewing tobacco (P=0.04), smoking (P=0.01), invaded resection margins (P=0.04), involved regional lymph nodes (P=0.009), T4 tumours, and patients treated with radiotherapy alone (P=0.001) were associated with poor overall survival. Factors associated with shorter relapse-free survival were age >40 (P=0.03), chewing tobacco (P=0.04), invaded resection margins (P=0.01), and smoking (P=0.01). On multivariate analysis, invaded resection margins and smoking (P=0.04)(P=0.02) were associated with shorter overall survival and relapse-free survival (P=0.03 and (P=0.01), while chewing tobacco independently influenced relapse-free survival only (P=0.03). CONCLUSION: Invaded resection margins and smoking were the only independent prognostic factors that affected both overall and relapse-free survival. Those who chewed tobacco were at high risk of locoregional failure.

Pseudotumor of urinary bladder.

The case of an old male is presented who had postoperative spindle cell nodule of urinary bladder. This benign condition mimics a sarcoma. However, the treatment modalities and the outcome are entirely different. Inflammatory pseudotumor/PSCN and leiomyosarcoma of the bladder overlap in clinical and immunohistochemical findings but are histologically as well as clinically distinct, correlating with different natural histories. Inflammatory Pseudotumor/PSCN are benign, not prone to metastasize, and is outside the spectrum of low-grade inflammatory sarcoma of urinary bladder.

Afro Middle East Asian symposium on cancer cooperation.

This manuscript captures the discussion and recommendations that came out of a special Afro Asian symposium involving 13 countries. Unmet needs and cost-effective solutions with special emphasis on training form the backbone of practical next steps.

Pulsed radiofrequency modulation for lingual neuralgia.

Pulsed radiofrequency modulation (PRM) is a minimally invasive procedure that has been used successfully to treat neuropathic pain. Its use to treat lingual neuralgia has not to our knowledge been described previously, and we report a case.

Pharmacological mechanisms underlying the vascular activities of Loranthus ferrugineus Roxb. in rat thoracic aorta.

AIM OF THE STUDY: The present study was aimed to investigate the pharmacological basis for the use of Loranthus ferrugineus in hypertension. MATERIALS AND METHODS: Loranthus ferrugineus methanol extract (LFME) was obtained using Soxhelt extractor and then successively fractionated using chloroform, ethyl acetate and n-butanol. The n-butanol fraction of LFME (NBF-LFME) was studied using isolated rat thoracic aorta. RESULTS: NBF-LFME (1.0 x 10(-5) to 3.0mg/ml) was found to be the most potent to concentration-dependently relax the endothelium-intact phenyephrine (PE, 1 microM)- and high K(+) (80 mM)-precontracted rat aortic rings. Removal of the endothelium completely abolished the vascular relaxing properties of NBF-LFME. Pretreatment with atropine (1 microM), L-NAME (10 microM), indomethacin (10 microM) and methylene blue (10 microM) significantly blocked NBF-LFME-mediated relaxation. Endothelium-dependent and -independent relaxations induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were significantly enhanced in aortic rings pretreated with NBF-LFME when compared to those observed in control aortic rings. On the contrary, glibenclamide (10 microM), propranolol (1 microM) and prazosin (0.01 microM) did not alter NBF-LFME-induced relaxation. CONCLUSIONS: The results suggest that NBF-LFME induced vascular relaxation by stimulating muscarinic receptors, activating the endothelium-derived nitric oxide-cGMP-relaxant pathway, promoting prostacyclin release and/or possibly through its ability to lengthen the released nitric oxide half-life. The present data further supports previous in vivo findings and explain the traditional use of Loranthus ferrugineus as an anti-hypertensive agent.

Primary pancreatic non-Hodgkin's lymphomas.

Primary pancreatic lymphomas are rare. We reviewed our experience at King Faisal Specialist Hospital and Research Center; the hospital tumor registry identified five patients with primary pancreatic lymphoma among the 1,212 adult non-Hodgkin's (NHL) cases referred to this institute during 1987-1994. The histology was diffuse large cell in all cases. According to the Ann Arbor classification, four patients had stage IE and one patient stage IIE disease. The diagnosis was established by laparotomy in three and ultrasound or CT-guided biopsy in two patients. All patients received chemotherapy. Radiotherapy was used in two cases; in one patient the pancreatic bed was irradiated, whereas in the other radiation was given for obstructive jaundice. Four patients are alive with no evidence of disease at 84, 26, 24, and 21 months follow-up. One patient relapsed at 12 months following chemotherapy and is alive with disease at 23 months follow-up. The clinical and radiological findings in primary pancreatic NHL are not pathognomonic, and the diagnosis is only established on histopathological examination. The management should be nonsurgical as the response to chemotherapy and radiation appears to be no different from NHL at other sites.

Pericardial metastasis in carcinoma of the uterine cervix.

Cardiac metastasis from gynecological malignancies is rare. Only six cases of carcinoma of the uterine cervix have been reported where the diagnosis of malignant pericardial effusion was made antemortem. The treatment of neoplastic pericardial effusion is controversial; both surgical and nonsurgical treatments are advocated. We present a patient with pericardial effusion secondary to carcinoma of the cervix and recommend subxiphoid pericardial fenestration for reliable long-term control of malignant effusion.

Low-grade astrocytoma--a retrospective analysis of 102 patients.

One hundred and two patients (57 males, 45 females, median age 17 years) with histologically proven low-grade astrocytoma (grades I, II) treated between 1978 and 1994 were retrospectively analyzed at the King Faisal Specialist Hospital & Research Center. Microscopic investigation showed 50 patients (48%) with grade I tumors as opposed to 52 patients (52%) with grade II tumors. Fifteen patients (15%) had complete surgical excision, 55 (52%) had partial excision and 32 (31%) had biopsy only; 68 patients (66%) received external radiotherapy with a median dose of 54 Gy (range 45-68.5 Gy). With a median follow-up of 3.3 years, the 5 and 10 years, overall actuarial survival rates were 78% and 62%, respectively while the progression-free survival rates at 5 and 10 years were 69%, and 35%, respectively. Age and performance status were significant prognostic factors in terms of overall survival on univariate (p = 0.05 and 0.05, respectively) and multivariate analysis (p = 0.005 and 0.006, respectively).