Explanation and Elaboration of the Standards of Reporting of Neurological Disorders Checklist: A Guideline for the Reporting of Incidence and Prevalence Studies in Neuroepidemiology.

BACKGROUND: Incidence and prevalence studies of neurological disorders play an extremely important role in hypothesis-generation, assessing the burden of disease and planning of health services. However, the assessment of disease estimates is hindered by the poor quality of reporting for such studies. We developed the Standards of Reporting of Neurological Disorders (STROND) guideline in order to improve the quality of reporting of neurological disorders from which prevalence, incidence, and outcomes can be extracted for greater generalisability. METHODS: The guideline was developed using a 3-round Delphi technique in order to identify the 'basic minimum items' important for reporting, as well as some additional 'ideal reporting items.' An e-consultation process was then used in order to gauge opinion by external neuroepidemiological experts on the appropriateness of the items included in the checklist. FINDINGS: The resultant 15 items checklist and accompanying recommendations were developed using a similar process and structured in a similar manner to the Strengthening of the Reporting of Observational Studies in Epidemiology checklist for ease of use. This paper presents the STROND checklist with an explanation and elaboration for each item, as well as examples of good reporting from the neuroepidemiological literature. CONCLUSIONS: The introduction and use of the STROND checklist should lead to more consistent, transparent and contextualised reporting of descriptive neuroepidemiological studies that should facilitate international comparisons, and lead to more accessible information for multiple stakeholders, ultimately supporting better healthcare decisions for neurological disorders.

Development of the standards of reporting of neurological disorders (STROND) checklist: a guideline for the reporting of incidence and prevalence studies in neuroepidemiology.

Incidence and prevalence studies of neurological disorders play an important role in assessing the burden of disease and planning services. However, the assessment of disease estimates is hindered by problems in reporting for such studies. Despite a growth in published reports, existing guidelines relate to analytical rather than descriptive epidemiological studies. There are also no user-friendly tools (e.g., checklists) available for authors, editors and peer-reviewers to facilitate best practice in reporting of descriptive epidemiological studies for most neurological disorders. The Standards of Reporting of Neurological Disorders (STROND) is a guideline that consists of recommendations and a checklist to facilitate better reporting of published incidence and prevalence studies of neurological disorders. A review of previously developed guidance was used to produce a list of items required for incidence and prevalence studies in neurology. A three-round Delphi technique was used to identify the 'basic minimum items' important for reporting, as well as some additional 'ideal reporting items'. An e-consultation process was then used in order to gauge opinion by external neuroepidemiological experts on the appropriateness of the items included in the checklist. Of 38 candidate items, 15 items and accompanying recommendations were developed along with a user-friendly checklist. The introduction and use of the STROND checklist should lead to more consistent, transparent and contextualised reporting of descriptive neuroepidemiological studies resulting in more applicable and comparable findings and ultimately support better healthcare decisions.

Multiple sclerosis in gulf war era veterans. 2. Military deployment and risk of multiple sclerosis in the first gulf war.

BACKGROUND: Concern has been raised that US veterans of the 1990-1991 Gulf War (GW1) may be at increased risk to develop neurologic disease. METHODS: An incident cohort of multiple sclerosis (MS) and other demyelinating disease (ODD) was assembled from the US military comprising the Gulf War era (1990-2007). Cases of MS and ODD meeting standard diagnostic criteria were matched to a database of all active duty personnel from the Department of Defense. Relative risk (RR) estimates for MS and all demyelinating disease based on onset, deployment status, and exposures were calculated. RESULTS: For GW1, a total of 1,841 incident cases of definite MS and ODD were identified, with 387 among 696,118 deployed and 1,454 among 1,786,215 nondeployed personnel. The RR for MS alone among those deployed compared to those nondeployed was 0.69 (confidence interval, CI: 0.61-0.78), with 0.72 (CI: 0.62-0.83) in men and 0.96 (CI: 0.75-1.22) in women. Deployment was also nonsignificant or protective as an MS risk factor across racial groups, all age groups, and each military service. RRs for MS by service were: Air Force 0.71 (CI: 0.53-0.96), Army 0.80 (CI: 0.67-0.96), Marines 0.96 (CI: 0.63-1.47), and Navy 0.56 (CI: 0.43-0.74). CONCLUSION: Military deployment to GW1 was not a risk factor for developing MS.

Epidemiology in multiple sclerosis: a pilgrim's progress.

There was more neurology taught under Harold G. Wolff at Cornell University Medical College in New York than perhaps anywhere else in the country when I attended from 1948 to 1952. I took my residency at the Veterans Administration Hospital in the Bronx, New York, a teaching hospital of Cornell, with Wolff as my Director of Training. While a resident, we thought we had found a treatment for multiple sclerosis. To test our conclusion, the first Class 1 treatment trial ever conducted for multiple sclerosis was performed. This showed no effect, but the participants began investigating multiple sclerosis among the 16 million persons at prime age for symptom onset who had served in the military in World War II. This led me to study its epidemiology worldwide, beginning with a detailed review of all published population-based estimates of frequency. Among these were nationwide surveys from Sweden, Denmark, Switzerland and later Norway and Finland, which showed in each country a concentration of the significantly high regions into contiguous areas forming a single 'focus' in each land, maximal in Denmark under the age of 15 years. The primary locus of high frequency multiple sclerosis seemed to be in the south-central inland lake region of Sweden, with spread to its contiguous neighbours. These concentrations in time and space indicated that multiple sclerosis was a disease probably acquired in early adolescence. Migration studies supported this: moves from high to low showed retention of birthplace risk only for those aged >15 years, whereas opposite moves indicated susceptibility limited to some 11-45 year olds. Epidemics of multiple sclerosis would suggest the disease is not only acquired but also infectious. If an infectious origin were true, transmission would have to occur before clinical onset, and would have to involve a much greater number of subjects than clinically involved. I believe there have been epidemics in Iceland, Shetland-Orkney and the Faroe Islands. On the Faroes there were no cases of multiple sclerosis among native-born resident Faroese from 1900 until 1943, when the first of 21 cases had clinical onset, heralding a type 1 epidemic with peak incidence rates >10 per 100,000 for 1945-46. British troops who occupied the islands from April 1940 to September 1945 we believe brought a widespread (because of the scatter of Faroese cases), asymptomatic (because they were healthy troops), persistent infection we called the primary multiple sclerosis affection that involved a large proportion of Faroese, with clinical multiple sclerosis ensuing in a very small proportion. Primary multiple sclerosis affection itself may have been manifest there as a newly introduced cause of acute infectious gastroenteritis and is possibly the underlying cause of multiple sclerosis in general.

The Gulf War era multiple sclerosis cohort: age and incidence rates by race, sex and service.

We characterize here a new nationwide incident cohort of multiple sclerosis from the US military-veteran population. This cohort provides an update to the only other US nationwide incidence study of multiple sclerosis performed during the 1970s. Medical records and data from the Department of Defense and Department of Veterans Affairs for cases of multiple sclerosis who served in the military between 1990, the start of the Gulf War era, and 2007 and who were service-connected for this disorder by the Department of Veterans Affairs from 1990 on, were reviewed. A total of 2691 patients were confirmed as having multiple sclerosis: 2288 definite, 190 possible, 207 clinically isolated syndrome and six neuromyelitis optica. Overall racial categories were White, Black and other, which included all Hispanics. There were 1278 White males and 556 females; 360 Black males and 296 females; and 200 others, 153 (77%) of whom were Hispanic. Mean age at onset of 30.7 years did not differ significantly by race or sex. Age at onset was 17-50 years in 99%, the same age range as 99% of the military. Average annual age specific (age 17-50 years) incidence rates per 100 000 for the entire series were 9.6 with 95% confidence interval of 9.3-10.0. Rates for Blacks were highest at 12.1 with confidence interval 11.2-13.1, Whites were 9.3 (interval 8.9-9.8) and others 6.9 (interval 6.0-7.9). For 83 Hispanics defined for 2000-07, the rate was 8.2 (interval 6.5-10.1). Much smaller numbers gave rates of 3.3 for Asian/Pacific Islanders and 3.1 for native Americans. Rates by sex for Whites were 7.3 and 25.8 male and female, respectively, for Blacks 8.4 and 26.3, and for Hispanics 6.6 and 17.0. Rates by service were high for Air Force (10.9) and Army (10.6), medium for Navy (9.1) and Coast Guard (7.9), and low for Marines (5.3). Relative risk of multiple sclerosis was 3.39 female:male and 1.27 Black:White. These new findings indicate that females of all races now have incidence rates for multiple sclerosis some three times those of their male counterparts and that among these groups, Blacks have the highest and others (probably including Hispanics) the lowest incidence rates regardless of sex or service. The low rate for Marines is unexplained. This Gulf War era multiple sclerosis cohort provides a unique resource for further study.

Prevalence of multiple sclerosis: door-to-door survey in three rural areas of coastal Black Sea regions of Turkey.

BACKGROUND: Little information exists on multiple sclerosis (MS) in Turkey. With a door-to-door survey in an urban part of Istanbul, we recently reported a prevalence rate of 101/100,000 population. We therefore investigated three rural areas of Turkey at the same latitude. METHODS: The same survey methods were used for total populations of two rural areas (Kandira and Geyve) near Istanbul, and for half the population of Erbaa, all near 40° north latitude on the Black Sea coast. RESULTS: In Kandira, 5 of 8 suspects were diagnosed as having MS among 8,171 screened, resulting in a prevalence rate of 61/100,000. Geyve with 7 MS cases in 17,016 screened had a prevalence of 41/100,000, and Erbaa with 15 MS cases in 28,177 screened one of 53/100,000. Together they showed a prevalence of 51/100,000. Of the 27 patients, 20 were women; 25 had definite and 2 possible MS, the former all with abnormal laboratory findings. Average ages were 30.5 years at onset and 39.1 years at diagnosis. Clinical features and course were typical of European MS. CONCLUSION: These findings indicate that Turkey is a high-risk MS area, similar to most regions of Mediterranean Europe, where all recent increases are likely due to (undefined) environmental factors.

High prevalence of multiple sclerosis in the Swedish county of Värmland.

Previous epidemiological studies have indicated that the county of Värmland in western Sweden may be a high-risk zone for multiple sclerosis (MS). The objective of this study was to determine the prevalence in the area. Hospital and general practice medical files were scrutinized. The diagnostic criteria of Poser were used, with 31 December 2002 as prevalence day. The prevalence was 170.07 per 100,000 inhabitants. The average annual incidence was 6.39 to 6.46 per 100,000 (1991-1995, 1996-2000). Multiple sclerosis was 2.3 times more common among women than men. There was a variation in prevalence among the 16 municipalities, however it was not statistically significant. The rates seemed highest in the southwestern part of the county, roughly similar in location to findings some 70 years earlier. When the prevalence ratios by geographical units for the county in 1933 were applied to the current prevalence, the distribution from these estimated cases differed from homogeneity with very high significance (p < 0.00001 ). In conclusion, this study supports previous reports indicating that Värmland continues to be a high-risk zone for MS and shares in the diffusion of the disease at the county level which we had presented for the country as a whole.

Bridging the gap between experimental and non-experimental neuroepidemiology, and ultimately - between neuroepidemiological research and practice: round table discussion at the First International Congress on Clinical Neurology and Epidemiology.

A highlight of the congress was an interactive and inclusive discussion of the existing gaps between clinical neurology and epidemiology and the ways of bridging these gaps. Some perceptions, challenges and scientific issues between experimental and non-experimental neuroepidemiology were brought to light. Recognizing that all study designs have advantages and disadvantages, panelists stressed that studies should aim to complement each other while answering important research- or practice-related questions. Advocated strategies included introducing more epidemiology into the medical school or residency curriculum, developing consistency in the reporting of epidemiological data to improving the strength and utility of the evidence, as well as nurturing collaborations that recognize the usefulness of both experimental and non-experimental epidemiological studies. These strategies will in the end benefit clinical practice. Indeed, clinical knowledge improves with experience and critical scientific evidence that can change perceptions, yet, individualized disease management will probably always remain an art rather than an exact science. Nevertheless, strong epidemiological studies and collaborations can influence government and public health policies. Bridging the gap between neuroepidemiological research and practice - whether through improved communication, education or basic science- is clearly a pressing challenge that requires our concerted and sustained effort.

Historical and clinical perspectives of the expanded disability status scale.

BACKGROUND: The measurement of neurologic impairment in multiple sclerosis (MS) is of importance in treatment trials and course of illness. METHODS: This review describes the rationale underlying the formation and use of a bifid rating system, the (Expanded) Disability Status Scale (DSS) and the Functional Systems (FS). RESULTS: All signs found at neurologic examination in MS can be consolidated into 8 mutually exclusive FS: pyramidal, cerebellar, brain stem, sensory, bowel and bladder, visual, cerebral and other, each of which, save 'other', is given ordinal grades from 0 to 5 or 6. Each FS correlates with the DSS, a step scale from 0 (normal) to 10 (death due to MS), which is an overall measure of neurologic abnormality. Dividing steps 1-9 each into 2 gives the Expanded DSS. The FS and DSS were used in an Army series to describe neurologic status at first diagnosis and over the first 20 years of illness. DSS severity at 5 years after onset, but not earlier, was highly predictive of later severity. CONCLUSIONS: Combination of the (Expanded) DSS and FS has been used successfully to assess impairment for natural history and treatment studies in MS.

Characteristics of Devic's disease (neuromyelitis optica) in Mexico.

OBJECTIVE: To report clinical and epidemiological data of Devic's disease in Mexico. DESIGN: Retrospective study of hospital case records. SETTING: The medical records were those of the National Institute for Neurology and Neurosurgery (INNN), a tertiary care referral center in Mexico City. PATIENTS: There were 424 medical histories available for review among 561 discharges with diagnoses of multiple sclerosis (MS), neuromyelitis optica (NMO), or equivalents. 390 met the diagnostic criteria of MS and 34 the NMO criteria. MAIN OUTCOME MEASURES: We recorded clinical signs, visual acuities, and the Expanded Disability Status Scale (EDSS) at the initial diagnostic admission and during follow-up. All patients had examination of cerebrospinal fluid (CSF) at diagnosis; head and spine magnetic resonance imaging (MRI) were performed at diagnosis and at follow-up. RESULTS: All 34 patients were Mexican Mestizos, who comprise 79 % of the residents of Mexico City. There were 23 monophasic and 11 relapsing cases. Intervals between initial and defining events for the 8 ON and 12 myelitis onsets were 17 and 24 months (means) and 15 and 17 months (medians), respectively. Mean follow- up from onset was 70.2 months and 42.9 months from diagnostic examination. No patient showed improvement in EDSS scores. Visual loss was severe. CONCLUSION: A provisional prevalence rate of about 1 per 100,000 population for NMO in Mexican Mestizos might be offered. The disease seems more severe in our population than in other recent series.

Migration and multiple sclerosis in immigrants from United Kingdom and Ireland to Australia: a reassessment. III: risk of multiple sclerosis in UKI immigrants and Australian-born in Hobart, Tasmania.

Our previous work suggested that migrants from the United Kingdom and Ireland (UKI) to Australia who left their home country at a young age had a longer interval between immigration and onset and likely acquired MS in Australia. In the present study, we reassessed Australian-born cases of MS identified in Hobart, Tasmania, a relatively high-risk zone, in our 1981 survey and compared these with cases of MS in UKI immigrants incident in Australia. The incidence of MS in Australian-born residents rose from 1.63 per 100,000 in 1941-1965 to 3.48 per 100,000 in 1966-1981. The bulk of UKI immigrants who developed MS in Australia migrated after the age of 15 years, and likely acquired their disease in the UKI. The mean interval from immigration to onset differed significantly (p < 0.01) between those migrating before (22 years) versus after (6 years) the age of 15, suggesting acquisition of MS in Australia in the former group. Identified environmental risk factors such as smoking, sunlight and exposure to Epstein-Barr virus do not fully account for the epidemiology of multiple sclerosis. The apparent introduction of MS into Hobart from the mid-1940s on could provide circumstantial support for the theory that MS is a transmissible disease.

Epidemiology and etiology of multiple sclerosis.

The author believes that the Faroese saga provides major insight into what seems to him to be the essential nature of MS: There is a specific, widespread, but unidentified, infection that we call the primary multiple sclerosis affection (PMSA). PMSA is a persistent infection that is transmitted from person to person. A small proportion of persons who has PMSA will develop clinical neurologic multiple sclerosis (CNMS) years later. Prolonged exposure is needed to acquire PMSA. Acquisition follows first adequate exposure. Susceptibility to PMSA is limited to approximately age 11 to age 45 at start of exposure. CNMS is not transmissible.PMSA transmissibility is limited to a period that is less than the usual age of onset of CNMS. On the Faroe Islands, this period is approximately from age 13 to age 26. The existence of PMSA now must be inferred from the presence of CNMS.

On the origin of EDSS.

The origin of EDSS, the Expanded Disability Status Scale for multiple sclerosis, was some 30 years before its only publication in 1983 when we were trying to assess a potential treatment and found no published methods. Findings from the complete neurologic examinations in over 200 patients were consolidated into mutually exclusive but all-inclusive neurophysiologic entities called Functional Systems (FS), and these provided the basis for an 11 step 0-10 rank order scale, the Disability Status Scale (DSS). This was used successfully, as well as in the first two Class I treatment trials performed, with the second one also incorporating the 8 FS. Both measures were part of an assessment of a natural history series derived from men hospitalized for MS in the US Army in World War II and followed for some 20 years. Describing each of the 8 FS as affected (1) or normal (0) defined 256 possible patterns of involvement for all patients. Half the patients at diagnosis had one of the 14 most common patterns. Each FS worsened in frequency and severity of involvement in correlation with the DSS, which overall showed a unimodal distribution, until in another series of patients 16 years post onset bimodality first appeared. Observations that the 11 step DSS might have too few steps for treatment trials led to the EDSS of 20 steps with each grade between 1 and 9 divided into two. The system of EDSS+FS to summarize all the CNS involvement as defined by objective findings on neurologic examination thereafter remained unchanged to the present. I just learned that the unpublished system copyrighted in Switzerland as "neurostatus" has been called and referenced as my EDSS. It is not.

Development of the Standards of Reporting of Neurological Disorders (STROND) checklist: A guideline for the reporting of incidence and prevalence studies in neuroepidemiology.

BACKGROUND: Incidence and prevalence studies of neurologic disorders play an important role in assessing the burden of disease and planning services. However, the assessment of disease estimates is hindered by problems in reporting for such studies. Despite a growth in published reports, existing guidelines relate to analytical rather than descriptive epidemiologic studies. There are also no user-friendly tools (e.g., checklists) available for authors, editors, and peer reviewers to facilitate best practice in reporting of descriptive epidemiologic studies for most neurologic disorders. OBJECTIVE: The Standards of Reporting of Neurological Disorders (STROND) is a guideline that consists of recommendations and a checklist to facilitate better reporting of published incidence and prevalence studies of neurologic disorders. METHODS: A review of previously developed guidance was used to produce a list of items required for incidence and prevalence studies in neurology. A 3-round Delphi technique was used to identify the "basic minimum items" important for reporting, as well as some additional "ideal reporting items." An e-consultation process was then used in order to gauge opinion by external neuroepidemiologic experts on the appropriateness of the items included in the checklist. FINDINGS: Of 38 candidate items, 15 items and accompanying recommendations were developed along with a user-friendly checklist. CONCLUSIONS: The introduction and use of the STROND checklist should lead to more consistent, transparent, and contextualized reporting of descriptive neuroepidemiologic studies resulting in more applicable and comparable findings and ultimately support better health care decisions.

No creative medical science without humor.

In his time with the Journal of Clinical Epidemiology and before, Dr. Alvan Feinstein espoused a philosophy of the study of epidemiology as a beneficial, valid science. Not only was Feinstein somewhat of a nonconformist in the field of epidemiology, he had a self-denigrating sense of humor as well. This sense of humor can be showcased by taking a look at one of the articles he approved for publication, which could be retitled as "The Finster Saga."

Migration and multiple sclerosis in Alaskan military veterans.

The objective is to provide the first estimates of the prevalence of multiple sclerosis (MS) in Alaskan white males including those migrant to and from the state. A case-control cohort design was utilized with a nationwide series of United States (US) veterans service-connected for MS and matched to pre-illness controls who had entered military service between 1960 and 1994. Among 3,758 white male MS cases and their 7,426 controls were 7 MS and 28 controls resident in Alaska at service entry, who provided an adjusted case/control (C/C) risk ratio for developing MS of 0.47 and an estimated prevalence rate of 22/100,000 population, but only 1 of the 7 had also been born in Alaska, for an estimated prevalence rate of 3.2 per 100,000 (95% confidence interval (CI): 0.08-17.80). The other 6 MS patients and their 26 controls, who migrated from another state to Alaska before onset, had an adjusted C/C ratio of 0.44 for a prevalence rate of 20.6 (95% CI: 7.56-44.90), significantly lower than the reported rate of 45.23 per 100,000 for all US white males in 1976. Another 9 MS patients and 7 controls born in Alaska, who had migrated to another state before entering service, provided an adjusted C/C risk ratio for developing MS of 2.44, with a highly significant elevated prevalence rate of 115 per 100,000 (95% CI: 52.6-218.1). In conclusion, these data suggest that Alaska is not a high-risk area for MS and indicate that migration before onset to Alaska from the high-risk coterminous US decreases the risk of MS and the opposite migration increases it. A formal prevalence survey of MS in Alaska is needed to support or refute these findings.