Patient-reported outcomes in multiple sclerosis: a systematic comparison of available measures.

Multiple patient-reported outcomes (PROs) are currently being used in multiple sclerosis (MS) but their application is inconsistent and guidance on the appropriateness of each tool is lacking. The objective of our study was to identify MS-specific PROs and systematically to assess the development process and the reliability and validity of various instruments. A systematic literature search was conducted on multiple data sources, including MEDLINE, Embase (using the Ovid platform) and Google Scholar, from 1996 to March 2015. Search terms included combinations of MS, PROs and quality of life. Randomized controlled trials or observational studies conducted on patients with MS and published in English were included. In addition, the PROQOLID database was explored. The MS-specific PROs were systematically assessed using the Evaluating the Measurement of Patient-Reported Outcomes tool. In total, 8094 articles were screened and 405 PROs were identified from 1102 relevant articles. PROs were classified into MS-specific (n = 82) and non-MS-specific (n = 323). The results for the eight PROs that are most commonly used in MS clinical trials are presented here. For these eight PROs, the overall summary scores ranged between 50.1 and 68.7. The Multiple Sclerosis Impact Scale-29 had the best overall mean score (68.7), followed by the Leeds Multiple Sclerosis Quality of Life (67.0). This is the first study to provide a standardized assessment of all PROs for MS. There is a lack of data on content validity for PROs used in MS research, which indicates the need for a robust instrument in MS developed according to the US Food and Drug Administration guidelines.

Preoperative magnetic resonance spectroscopy improves diagnostic accuracy in a series of neurosurgical dilemmas.

OBJECT: The purpose of this study was to evaluate the usefulness of preoperative magnetic resonance spectroscopy (MRS) in neurosurgical patients with diagnostically challenging intracranial lesions. METHODS: Included in this study are twenty-three consecutive patients presenting to the neurosurgery service with diagnostically challenging intracranial lesions and who were investigated by conventional MR imaging and proton ((1)H) MRS, followed by surgery with subsequent histopathological diagnosis. An experienced neuroradiologist (RJ) blinded to the final histopathology evaluated the imaging studies retrospectively. Provisional diagnoses based on preoperative clinical and conventional MR data versus preoperative MRS data were compared with definitive histopathological diagnoses. RESULTS: Compared with preoperative clinical and conventional MR data, (1)H MRS improved the accuracy of MR imaging from 60.9% to 83%. We found (1)H MRS reliably distinguished between abscess and high-grade tumour, and between high-grade glioma and low-grade glioma, but was not able to reliably distinguish between recurrent glioma and radiation necrosis. In 12/23 cases (52%) the (1)H MRS findings positively altered our clinical management. Two representative cases are presented. CONCLUSIONS: Our study supports a beneficial role for (1)H MRS in certain diagnostic intracranial dilemmas presenting to neurosurgeons. The information gleaned from preoperative (1)H MRS can be a useful adjunct to clinical and conventional MR imaging data in guiding the management of patients with intracranial pathologies, particularly high-grade tumour versus abscess, and high-grade versus low-grade glioma. Further larger prospective studies are needed to clearly define the utility of (1)H MRS in diagnostically challenging intracranial lesions in neurosurgery.

A Study of Autologous Non-Cultured Epidermal Suspension (NCES) Transplant in Patients with Stable Vitiligo without the Use of NB-UVB.

Introduction:Vitiligo is a common form of localized depigmentation and an important public health problem which affects around one percent of the global population and about two percent of the population in India. The present study aimed to document the results and side effects of non-cultured melanocyte transplant in patients with stable vitiligo without post-procedure use of NB UVB. Methods:The present study was a prospective interventional study conducted among patients with stable vitiligo who were attending the outpatient department (OPD) of dermatology of a tertiary center of Delhi. Patients with stable vitiligo aged >10 years who gave their consent for non-cultured epidermal suspension (NCES) were included in the study. Autologous skin graft of size 0.2 mm was taken from the donor site and a melanocyte cell suspension was prepared using standardized procedure, which was later transplanted to the recipient area. All patients were asked to come for follow-up at the OPD after seven days, 15 days, one month, followed by every month till six months post-transplantation, and repigmentation was assessed visually by both graph paper and photography. Data was analyzed using SPSS vs. 21. Results:In our study, the majority of patients had vitiligo vulgaris (27 subjects with 47 patches). A total number of 59 patches were transplanted, of which 38 (64.4%) achieved excellent repigmentation, 28.8% good repigmentation, 3.4% fair repigmentation and 3.39% poor repigmentation. A total of 1302.5 cm² of the depigmented area was operated by NCES and the repigmentation of 874.5 cm2 (67.14%) was achieved by six months. Conclusion:The present study found that the majority of patients (93%) with vitiligo achieved excellent or good repigmentation after NCES and the rate of complication was very low.

Congenital miliaria crystallina - A diagnostic dilemma.

Miliaria crystallina is a transient, superficial obstruction of eccrine sweat ducts resulting in rapidly evolving noninflammatory vesicles. The disease is observed frequently in hot, humid, tropical climates and in the neonatal period, most likely due to lack of maturation of the sweat duct during the first few days following birth. It is rarely present at delivery and remains a diagnostic dilemma for the neonatologists. We report a rare case of "Congenital miliaria crystallina" that was present at birth.

Intra-operative transit time flowmetry reduces the risk of ischemic neurological deficits in neurosurgery.

Intra-operative transit time flowmetry (ITTF) can be used to quantify blood flow in local at risk vessels before and after surgical intervention. As inadvertent vessel compromise represents a major cause of neurological deficit following neurovascular surgery, the purpose of this study was to assess this technology in terms of its indications, ease of implementation and interpretation, safety and reliability. Patients were prospectively invited to participate. ITTF was recorded from at-risk vessels before and after surgical intervention, along with blood pressure and PaCO(2). Any episodes of flow compromise or change in surgical procedure were noted and correlated with post-operative neurological deficits and imaging. Twenty-eight patients undergoing 30 craniotomies were enrolled. Operations included n = 21 aneurysm clipping or exploration, 2 AVM excision, 2 dural AV fistula disconnections, 2 EC-IC bypass and 3 tumor resections. ITTF led to an alteration in surgery in 8 of the 30 cases (27%). In patients undergoing aneurysmal surgery, inadvertent vessel occlusion was identified in 3 cases, which led to immediate repositioning of the aneurysm clips. In 2 AV fistulae and 2 AVM surgeries, markedly reduced draining vein flow rates were confirmed quantitatively immediately before final surgical disconnection was carried out. In 1 EC-IC bypass patient, the measurement suggested graft vasospasm then treated with papaverine. One aneurysm person awoke with a stroke presumably from an embolic event undetected by ultrasonography. ITTF provides immediate feedback regarding vessel patency. Clip-related arterial compromise and local vasospasm are detected by this technology, but an embolic event may escape detection. This technology was found to have a broad utility in intra-cranial surgery, and was safe, rapidly performed, easy to interpret and generally reliable.

The clinical and cost impact of switching to fingolimod versus other first line injectable disease-modifying therapies in patients with relapsing multiple sclerosis.

BACKGROUND: There is limited evidence on the effectiveness and healthcare costs of switching to fingolimod versus another first line injectable therapy (FLIT) in patients with relapsing multiple sclerosis (RMS) who have already been treated with FLIT. OBJECTIVE: The objectives of the study were to assess the annualized relapse rate (ARR), socio-demographic and clinical characteristics, persistence and adherence rates, healthcare resource utilization and cost among patients with RMS who either switch to fingolimod or another FLIT in routine clinical practice. METHODS: A multicenter, observational, retrospective chart review was conducted across eight clinics in Canada between 1 May 2011 and 30 June 2013. The data was collected from two cohorts: patients who switched to fingolimod and patients who switched to FLIT from a previous FLIT. RESULTS AND CONCLUSIONS: A total of 124 patients were included in the study: 82 and 42 switched to fingolimod and FLIT, respectively. There were no significant differences in the patient characteristics at the date of switch except for number of previous disease-modifying therapies (DMTs) which was higher in the fingolimod cohort (fingolimod: 1.52; FLIT: 1.10, p < .001). The ARR during the first year of switching was numerically higher in the FLIT cohort compared to the fingolimod cohort (FLIT: 0.9 [95% CI 0.3-1.6]; fingolimod: 0.3 [95% CI 0.1-0.5]). The negative binomial model adjusted for the number of previous DMTs confirmed a statistically significant difference in ARR between the fingolimod and FLIT cohorts at 12 months of follow-up (p = .012). In the fingolimod cohort, 20.7% of patients experienced at least one relapse compared to 38.1% in the FLIT cohort. In both groups, a high proportion of patients (>90%) showed good treatment adherence (≥80% of prescribed doses).

Eruptive Vellus Hair Cyst: An Uncommon and Underdiagnosed Entity.

Eruptive vellus hair cyst (EVHC) is a rare follicular developmental abnormality of the vellus hair follicles. They are usually seen in children, adolescents, or young adults and manifest as reddish-brown smooth papules most commonly involving the chest, limbs, and abdomen. An 18-year-old male presented with asymptomatic papules on the trunk and flexor aspect of both forearms for the past 2 years. There was no family history of similar lesions. His medical history was also not contributory. A clinical diagnosis of steatocystoma multiplex and chronic folliculitis was given, and a punch biopsy from the papule was performed and sent for histopathological examination. On microscopic examination, a final diagnosis of EVHC was rendered. The patient was advised topical treatment of retinoic acid cream (0.05%) for 6 months, and he is currently under follow-up period. Due to its rarity and resemblance to many similar entities, histopathological examination plays a major role in establishing a definite diagnosis and further proper management of the patient. We report this unusual case to generate awareness about this rarely diagnosed condition.

mRNA expression in rabbit experimental aneurysms: a study using gene chip microarrays.

BACKGROUND AND PURPOSE: The molecular characteristics of intracranial aneurysms are still poorly documented. A rabbit elastase aneurysm model has been helpful in the evaluation of devices and strategies involved in endovascular treatment of aneurysms. The goal of this project was to document the molecular changes, assessed by gene chip microarrays, associated with the creation of aneurysms in this model compared with the contralateral carotid artery. MATERIALS AND METHODS: A microarray of rabbit genes of interest was constructed using rabbit nucleotide sequences from GenBank. Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery in 4 rabbits. Twelve weeks after aneurysm creation, RNA was isolated from the aneurysm as well as the contralateral common carotid artery and used for microarray experiments. Reverse transcription-polymerase chain reaction (RT-PCR) was performed on 1 animal as a confirmatory test. RESULTS: Ninety-six (46%) of 209 genes in the microarray were differentially expressed in the rabbit aneurysm compared with the contralateral common carotid artery. In general, differential gene expression followed specific molecular pathways. Similarities were found between rabbit aneurysms and human intracranial aneurysms, including increased metalloproteinase activity and decreased production of the extracellular matrix. RT-PCR results confirmed the differential expression found by the gene chip microarray. CONCLUSIONS: The molecular characteristics of the rabbit elastase-induced saccular aneurysm are described. The rabbit aneurysm model shares some molecular features with human intracranial aneurysms. Future studies can use the rabbit model and the new rabbit gene chip microarray to study the molecular aspects of saccular aneurysms.

Functional interdependence and colocalization of endothelial nitric oxide synthase and heat shock protein 90 in cerebral arteries.

Heat shock protein 90 (HSP90), an essential component of several signal transduction systems, participates in the activation of endothelial nitric oxide synthase (eNOS) in cells. The objective of the current study was to determine if HSP90 and eNOS were functionally interdependent and colocalized in the cerebral circulation. The authors used isometric force recording, cyclic 3'5'-guanosine monophosphate (cGMP) radioimmunoassay (RIA), and immunogold electron microscopy (EM) to study canine basilar artery. They found that geldanamycin (0.1 to 10 microg/mL), a selective HSP90 inhibitor, caused concentration-dependent contractions in arterial rings (n = 6 dogs). Contractions to geldanamycin were unaffected by a cyclooxygenase inhibitor, indomethacin (10 micromol/L; P < 0.05, n = 6). Functional evidence for interaction between HSP90 and nitric oxide (NO)-mediated signaling included observations that the contractile effect of geldanamycin was the following: (1) endothelium-dependent, (2) abolished by Ng-nitro-L-arginine methylester (L-NAME; 0.3 mmol/L), and (3) non-additive with the contractile effect of this NOS inhibitor (P < 0.01, n = 6 for each). Furthermore, RIA showed significant reduction in cGMP levels in arteries treated with geldanamycin (3 microg/mL; P < 0.02, n = 8), whereas immunogold EM demonstrated areas of colocalization of HSP90 and eNOS selectively in the cytoplasm of endothelial cells. The current findings suggest that in cerebral arteries, endothelial HSP90 plays an important role in modulation of basal NO-mediated signaling. This interaction may be particularly important in stress-induced up-regulation of HSP90 with subsequent alteration of vasomotor function.

Adenovirus-mediated gene transfer to human cerebral arteries.

Gene therapy is being investigated as a putative treatment option for cardiovascular diseases, including cerebral vasospasm. Because there is presently no information regarding gene transfer to human cerebral arteries, the principal objective of this study was to characterize adenovirus-mediated expression and function of recombinant endothelial nitric oxide synthase (eNOS) gene in human pial arteries. Pial arteries (outer diameter 500 to 1,000 microm) were isolated from 30 patients undergoing temporal lobectomy for intractable seizures and were studied using histologic staining, histochemistry, electron microscopy, and isometric force recording. Gene transfer experiments were performed ex vivo using adenoviral vectors encoding genes for bovine eNOS (AdCMVeNOS) and Escherichia coli beta-galactosidase (AdCMVLacZ). In transduced arteries, studied 24 hours after exposure to vectors, expression of recombinant beta-galactosidase and eNOS was detected by histochemistry, localizing mainly to the adventitia (n = 4). Immunoelectron microscopy localized recombinant eNOS in adventitial fibroblasts. During contractions to U46619, bradykinin-induced relaxations were significantly augmented in AdCMVeNOS-transduced rings compared with control and AdCMVLacZ-transduced rings (P < 0.01; n = 6). The NOS inhibitor L-nitroarginine methylester (L-NAME) caused significantly greater contraction in AdCMVeNOS-transduced rings (P < 0.001; n = 4) and inhibited bradykinin-induced relaxations in control and transduced rings (P < 0.001; n = 6). The current findings suggest that in AdCMVeNOS-transduced human pial arteries, expression of recombinant eNOS occurs mainly in adventitial fibroblasts where it augments relaxations to NO-dependent agonists such as bradykinin. Findings from the current study might be beneficial in future clinical applications of gene therapy for the treatment or prevention of cerebral vasospasm.

Acute deterioration from thrombosis and rerupture of a giant intracranial aneurysm.

The authors describe a patient with an unusual clinicopathologic picture of giant aneurysmal hemorrhage followed by sudden deterioration due to acute intra-aneurysmal thrombosis and fatal rebleeding. This patient underscores the poor natural history associated with this devastating disease and serves to highlight the dangers inherent in the delayed treatment of these life-threatening lesions.

Cancer screening in the elderly population.

This article reviews the current state of knowledge regarding cancer screening in the geriatric population. Care of the elderly requires knowledge of underlying physiologic changes, comorbidities, quality-of-life factors, and life expectancies. There is always the danger that ageism may prevent elderly cancer patients from receiving the proper treatment. On the other hand, overzealous treatment can lead to adverse results if elderly patients are not properly targeted based on current evidence of the benefits and risks of specific screening practices.

Ruptured giant intracranial aneurysms. Part I. A study of rebleeding.

OBJECT: The present study was conducted to estimate the frequency and timing of rebleeding after initial subarachnoid hemorrhage (SAH) from ruptured giant aneurysms. METHODS: The authors reviewed records of 109 patients who suffered an initial SAH from a giant aneurysm and were treated at the Mayo Clinic between 1973 and 1996. They represented 25% of patients with giant intracranial aneurysms seen at this institution during that 23-year period. Seven of the patients were residents of Rochester, Minnesota, and the rest were referred from other institutions. The aneurysms ranged from 25 to 60 mm in diameter, and 74% were located on arteries of the anterior intracranial circulation. The cumulative frequency of rebleeding at 14 days after admission was 18.4%. Cerebrospinal fluid drainage, cerebral angiography, and delayed aneurysm recurrence were implicated in rebleeding in some of the patients. Rebleeding was not precluded by intraaneurysm thrombosis. Among those who suffered recurrent SAH at the Mayo Clinic, 33% died in the hospital. CONCLUSIONS: Rebleeding from giant aneurysms occurs at a rate comparable to that associated with smaller aneurysms, a finding that should be considered in management strategies.

Ruptured giant intracranial aneurysms. Part II. A retrospective analysis of timing and outcome of surgical treatment.

OBJECT: This retrospective study was made to determine the relationship between surgical timing and outcome in all patients with ruptured giant intracranial aneurysms undergoing surgical treatment at the Mayo Clinic between 1973 and 1996. METHODS: The authors studied 109 patients, 102 of whom were referred from other medical centers. The ruptured giant aneurysms were 25 to 60 mm in diameter. One hundred five of the patients survived the rupturing of the aneurysm to undergo operation, with direct surgery possible in 84% of cases. Excluding delayed referrals, the average time to surgery after admission to the Mayo Clinic was approximately 4 to 5 days. Patients admitted earlier tended to be in poorer condition, often undergoing earlier operation. On average, surgical treatment was administered later for patients with ruptured aneurysms of the posterior circulation than for those with aneurysms in the anterior circulation. Temporary occlusion of the parent vessel was necessary in 67% of direct procedures, with an average occlusion time of 15.5 minutes. Among surgically treated patients, a favorable outcome was achieved in 72% harboring ruptured anterior circulation aneurysms and in 78% with ruptured posterior circulation lesions. CONCLUSIONS: The overall management mortality rate was 21.1%, and the mortality rate for surgical management was 8.6%. The authors believe that because of the technical difficulties and risk of rebleeding associated with ruptured giant intracranial aneurysms, timely referral to and well-planned treatment at medical centers specializing in management of these lesions are essential to effect a more favorable outcome.

Occult rupture of a giant vertebral artery aneurysm following proximal occlusion and intrasaccular thrombosis. Case report.

The authors describe a unique clinicopathological phenomenon in a patient who presented with an unruptured giant vertebral artery aneurysm and who underwent endovascular proximal occlusion of the parent artery followed, several days later, by surgical trapping of the aneurysm after delayed subarachnoid hemorrhage (SAH). The intraoperative finding of a thrombus extruding from the wall of the aneurysm at a site remote from the origin of the SAH underscores the possibility that occult rupture of an aneurysmal sac can occur in patients with thrombosed giant aneurysms.

Parotid and neck metastases from cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: Approximately 5% of cutaneous squamous cell carcinomas (SCC) metastasize to regional nodes. Nodal involvement may be more common for cutaneous squamous cell carcinomas of the head and neck, but few large series have reported clinical outcome after treatment of parotid gland and neck metastases from these cancers. PATIENTS AND METHODS: A combined retrospective/prospective study of patients treated between 1983 and 1994 was performed. There were 69 men and 6 women, with a median age of 67 years. Twenty-nine patients had neck metastases, and 33 had parotid gland metastases, while 13 patients had involvement at both sites. Of the 75 patients, 68 were treated surgically and 50 received postoperative radiotherapy. RESULTS: The facial nerve was sacrificed totally in 6 patients and partially in 9. Histologic extranodal spread was present in 48 (71%) of all surgically treated patients. Among 61 patients followed up to recurrence, or for greater than 12 months, 26 (43%) developed recurrence--12 in the parotid gland, 7 in the neck, and 7 in both sites. Multiple recurrences were common and occurred at a median of 8 months after surgery. Positive surgical margins were associated with poorer local disease control (P < 0.05). Cumulative survival at 5 years was 61%, but only 15 of 70 evaluable patients (21%) were eligible for follow-up at this time. Neck involvement with or without parotid gland disease was associated with an increased risk of distant metastases, but this was not statistically significant. Postoperative radiotherapy was not associated with improved disease control. CONCLUSION: Cutaneous, metastatic SCC involving the parotid gland and neck is an aggressive disease with a tendency to an infiltrative growth pattern and multiple recurrences. More aggressive surgery may be justified to reduce the incidence of regional failure after parotidectomy and neck dissection.

Gastric mucosal fibrosis: a novel explanation for dyspepsia.

The etiology of functional dyspepsia has not been discerned yet which has led to inadequate treatment of this disease. It remains a common disorder with expensive and yet often ineffective therapy. We propose that the pathogenesis of this disease lies in the histological and ultrastructural changes inflicted on the gastric mucosa in chronic gastritis and fibrosis. This hypothesis, if substantiated will provide for therapy which will be based on the pathogenesis of the disease and which will be cheaper and easily available to most. It will also add impetus to the early eradication of Helicobacter pylori, which would prevent chronic gastritis and hence gastric fibrosis.

Management of giant intracranial aneurysms of the posterior circulation.

Between 1980 and 1995, 14 patients underwent treatment at Royal Prince Alfred Hospital for giant posterior circulation aneurysms. Two (14%) patients presented with subarachnoid haemorrhage (SAH). Eight (57%) of the 14 giant aneurysms were located at the basilar caput. A total of 7 (50%) contained significant intraluminal thrombus. Surgery was undertaken in 10 (72%) patients and endovascular embolization in the remaining 4 (28%). Of the patients treated surgically, 3 underwent clipping and a further 4 underwent Hunterian ligation. Of the 4 patients in whom embolization was carried out, 2 were coil treated and 2 balloon treated. Six (60%) patients undergoing surgery experienced significant complications, but in only 4 (40%) surgically treated patients was the complication directly attributable to the surgical procedure. All 4 (100%) patients treated interventionally suffered major complications, and in 3 (75%) of these the complication was directly attributable to the endovascular procedure. The clinical outcome at a median of 12 months follow-up was favourable in 8 (62%) of the 13 patients for whom follow-up information was available. We conclude that radiological techniques are not satisfactory for direct treatment of giant posterior circulation aneurysms and surgical exploration is advisable. In addition, timely referral to, and well planned management at, an experienced centre will undoubtedly contribute significantly towards securing a more favourable overall outcome.