Probable Multiple Sclerosis Research Articles

Neurochondrin Autoimmunity With Slow Saccades: A Case Report

Objective N/A. Background Neurochondrin is a cytoplasmic neuronal antigen that can be targeted by specific antibodies, resulting in an antigen-specific T-cell response and autoimmune cerebellar and brain stem degeneration.1 Previously reported cases of neurochondrin antibody positivity have been predominantly associated with rapidly-progressive rhombencephalitis, but various other neurological symptoms and signs may be present.1,2 Design/Methods N/A. Results 34-year-old woman presented with 2 years of constant numbness in her toes, gradually worsening to involve the entire lower and upper extremities. She also reported dysarthria, imbalance, and leg spasticity. Neurological examination showed a slow, wide-based gait, brisk reflexes bilaterally, and bilateral extensor plantar responses. MRI brain was normal and CSF analysis showed 7 oligoclonal bands. The patient was diagnosed with probable multiple sclerosis and steroids were initiated but resulted in no improvement of symptoms. Plasmapheresis was also ineffective. 3 months later, MRI showed subtly increased T2 signal of the central cord mainly involving the gray matter at the level of C5 and C6. CSF analysis showed 15 oligoclonal bands and an elevated IgG index of 1.39. VDRL was nonreactive. HTLV, ANCA, AQP4, CSF VZ PCR, HSV PCR, and HHV6 PCR were all negative. EMG showed mild length-dependent axonal sensory motor peripheral neuropathy. On neuro-ophthalmic examination, the patient showed slowed saccades with some preservation of optokinetic nystagmus (OKN) fast phases. Repeat MR showed abnormal T2 hyperintensity in the anterior horns of the gray matter from C1-2 to T1. Serum testing at that time showed a positive neurochondrin antibody. She was then started on cyclophosphamide and mycophenolate mofetil. 6 months after initiation of cyclophosphamide, dysarthria and upper limb mobility improved, and she had no further neurological deterioration at that time. Conclusions Neurochondrin IgG-related autoimmunity is rare and can result in a wide variety of neurological signs and symptoms. Ocular dysmotility, including slowed saccades, may be present.

Genetic and Molecular Biology of Multiple Sclerosis Among Iranian Patients: An Overview.

Multiple sclerosis (MS) is one if the common types of autoimmune disorders in developed countries. Various environmental and genetic factors are associated with initiation and progression of MS. It is believed that the life style changes can be one of the main environmental risk factors. The environmental factors are widely studied and reported, whereas minority of reports have considered the role of genetic factors in biology of MS. Although Iran is a low-risk country in the case of MS prevalence, it has been shown that there was a dramatically rising trend of MS prevalence among Iranian population during recent decades. Therefore, it is required to assess the probable MS risk factors in Iran. In the present study, we summarized all of the reported genes until now which have been associated with MS susceptibility among Iranian patients. To clarify the probable molecular biology of MS progression, we categorized these reported genes based on their cellular functions. This review paves the way of introducing a specific population-based diagnostic panel of genetic markers among the Iranian population for the first time in the world.

Multiple Sclerosis in Italy: A 40-Year Follow-Up of the Prevalence in Ferrara

Background: To assess a longitudinal follow-up of the prevalence of multiple sclerosis (MS) through 4 decades in the province of Ferrara, northern Italy, and reappraise the current rates on December 31, 2016. Methods: We conducted a community-based intensive prevalence study, by adopting a complete enumeration approach. MS cases were identified from administrative health data and medical records from the Units of Neurology and Motor Rehabilitation, Ferrara University Hospital, from other provincial neurological structures and from archives of the National Pension Institute and National Health Insurance scheme of the study area. Case ascertainment method and case definition are analogous to those adopted in previous surveys in the same area of study. Results: On December 31, 2016, 685 patients (478 women and 207 men) affected by definite or probable MS (Poser’s criteria) were living in the province of Ferrara (population 386,896), yielding a crude prevalence ratio of 194.91 (95% CI 180.4–209.6) per 100,000, 260.8 (95% CI 238.10–285.82) for women and 123.1 (95% CI 106.98–141.21) for men The prevalence ratio was 26.9 per 100,000 in 1978, increased to a value of 46.1 per 100,000 in 1981, 69.4 per 100,000 in 1993, 120.9 per 100,000 in 2004. Female to male ratio was 2.31 (1.2 on December 31, 1978). The mean duration of the disease at prevalence day was 17.5 ± 11.9 years (13.9 ± 10.8 years in 1978). The mean age at prevalence day was 52.04 ± 10.8 years (13.8 ± 10.8 years in 1978). Conclusion: Our study has confirmed the province of Ferrara is an area at high risk for MS, in line with epidemiological data from the regions of continental and insular Italy. The sharp increase in MS prevalence over time in this population can be imputed in part to a greater exposition to risk factors in genetically susceptible subjects but also to an increased survival and improved ascertainment. So, the results suggest that both methodologic and environmental factors are essential in determining the real distribution of MS. The need to get reliable estimates of MS prevalence must be highlighted as a public health and research priority, essential to support planning and prioritization of care services and to reduce the overall burden of chronic disease.

Prevalence of Multiple Sclerosis in Iceland

Background: In this study, we examined multiple sclerosis (MS) point prevalence in the well-defined island population of Iceland. Methods: This study included all registered residents of Iceland with MS on the prevalence day, December 31, 2007. All included patients met at least one of the following criteria: McDonald criteria; Poser criteria for clinically definite MS, laboratory-supported definite MS, clinically probable MS; or criteria for primary progressive MS. The patients’ medical records were reviewed, including all available MRI data acquired prior to the prevalence day. Results: We identified 526 patients, of whom 73% (382) were women. The crude point prevalence of MS was 167.1 per 100,000 population on the prevalence day. With age adjustment made to the 2000 U.S. population, the prevalence was 166.5 per 100,000 population. The mean patient age on the prevalence day was 47 years(range 13–89) for both men and women. The mean age at diagnosis was 36 years (range 13–77): 35 years for women and 36 years for men. Conclusion: MS prevalence was high in Iceland compared to the prevalence mentioned in reports from most of the world, and was similar to prevalence rates in other Nordic countries.

Multiple sclerosis in the Republic of San Marino, Italian peninsula: an incidence and prevalence study from a high-risk area.

Epidemiological studies on multiple sclerosis (MS) carried out in Southern Europe in the last years have shown a significant increase in the disease frequency. Previous surveys conducted in the Republic of San Marino, Northern Italian peninsula, identifiedthat the population is at high risk for MS, with a prevalence of 51.6 per 100,000 population in 1982 and of 166.7 in 2005 and with a mean annual incidence of 7.9 per 100,000 for the period 1990-2005. The present work is a community-based intensive prevalence and incidence survey, by a complete enumeration approach,to update the prevalence and incidence of MS in the Republic of San Marino. The mean annual incidence for the period 2005-14 was 7.7 (95% CI 4.9-11.4) per 100,000, 3.3 (95% CI 1.1-7.6) for men and 11.9 (95% CI 7.2-18.6) for women. On 31 December 2014, 67 patients (19 men and 48 women), suffering from definite or probable MS and living in the Republic of San Marino, yielded a crude prevalence of 204.3 (95% CI 158.4-259.5) per 100,000, 117.8 (95% CI 70.9-183.7) for men and 288.2 (95% CI 212.4-383.3) for women. Our study has confirmed San Marino is an area at high risk for MS, in line with epidemiological data from continental Italy. The marked increase in MS prevalence over time in this population can be ascribable to increased survival and improved ascertainment, in the presence of a substantially stable, yet high, incidence rate.

Excess mortality among patients with multiple sclerosis in Denmark has dropped significantly over the past six decades: a population based study

BackgroundLifetime expectancy in multiple sclerosis (MS) is reduced. Few studies have had sufficient follow-up or sufficient number of patients to assess if survival has improved with time. However, a recent...

Hormone therapy use and physical quality of life in postmenopausal women with multiple sclerosis.

To determine the association between hormone therapy (HT) and physical quality of life (QOL) in postmenopausal women with multiple sclerosis (MS). We included female participants from the prospective Nurses' Health Study, with a diagnosis of definite or probable MS, who had completed a physical functioning assessment (PF10; subscale of the 36-Item Short-Form Health Survey QOL survey) at a time point between 3 and 10 years after their final menstrual period (early postmenopause). We assessed the association between HT use at this time point (never vs at least 12 months of systemic estrogen with/without progestin) and both PF10 and the 36-Item Short-Form Health Survey Physical Component Scale. We used a linear regression model adjusting for age, MS duration, menopause type and duration, and further for additional covariates (only ancestry was significant). Among 95 participants meeting all inclusion criteria at their first postmenopausal assessment, 61 reported HT use and 34 reported none. HT users differed from non-HT users in MS duration (p = 0.02) and menopause type (p = 0.01) but no other clinical or demographic characteristics. HT users had average PF10 scores that were 23 points higher than non-HT users (adjusted p = 0.004) and average Physical Component Scale scores that were 9.1 points higher in the 59 women with these available (adjusted p = 0.02). Longer duration of HT use was also associated with higher PF10 scores (p = 0.02, adjusted p = 0.06). Systemic HT use was associated with better physical QOL in postmenopausal women with MS in this observational study. Further studies are necessary to investigate causality.

Early onset multiple sclerosis in Jordan: A retrospective analysis

A multicenter retrospective analysis of the clinical characteristics of early onset multiple sclerosis (EOMS) in Jordan was conducted using multiple sclerosis (MS) database of three major referral centers. The database was formulated by collecting information from consecutive MS patients fulfilling the McDonald’s criteria for clinically definite or clinically probable MS, attending neurology clinics in the participating hospitals in the period between August 2004 and September 2005. Patients with disease onset at or before the age of 18 years were included and their data were statistically analyzed. EOMS was seen in 30 patients (13.4%) out of 230, in the Jordan MS database. Estimated prevalence of pediatric MS in Jordan was 5.25/100,000. Female to male ratio was 4:1 (24 females: six males). Twenty-eight (93.3%) subjects had a relapsing-remitting course, while two were primary progressive. None of the patients had a secondary progressive pattern. The majority of our patients (77%) were monosymptomatic at onset. Weakness at onset was seen in 23.3% of patients, which was higher than most of previously reported percentages. Optic neuritis and sensory disturbances were equally observed as presenting symptoms (23.3% each). About 13% of our total patient population had a positive family history of MS in a first degree relative. Six patients were treated with interferon before the age of 18, and tolerated the treatment well. A tendency towards less current disability was noted with earlier age of onset, use of interferon, a relapsing-remitting course and a positive family history of MS. We conclude that EOMS in the Jordanian population is clinically similar to adult onset MS, but slightly different from EOMS in other countries, with a largely monosymptomatic presentation, a higher number of patients with weakness at onset, and the absence of a secondary progressive pattern. This emphasizes the importance of genetic and environmental factors in MS onset.

MOG cell-based assay detects non-MS patients with inflammatory neurologic disease.

Objective:To optimize sensitivity and disease specificity of a myelin oligodendrocyte glycoprotein (MOG) antibody assay.Methods:Consecutive sera (n = 1,109) sent for aquaporin-4 (AQP4) antibody testing were screened for MOG antibodies (Abs) by cell-based assays using either full-length human MOG (FL-MOG) or the short-length form (SL-MOG). The Abs were initially detected by Alexa Fluor goat anti-human IgG (H + L) and subsequently by Alexa Fluor mouse antibodies to human IgG1.Results:When tested at 1:20 dilution, 40/1,109 sera were positive for AQP4-Abs, 21 for SL-MOG, and 180 for FL-MOG. Only one of the 40 AQP4-Ab–positive sera was positive for SL-MOG-Abs, but 10 (25%) were positive for FL-MOG-Abs (p = 0.0069). Of equal concern, 48% (42/88) of sera from controls (patients with epilepsy) were positive by FL-MOG assay. However, using an IgG1-specific secondary antibody, only 65/1,109 (5.8%) sera were positive on FL-MOG, and AQP4-Ab– positive and control sera were negative. IgM reactivity accounted for the remaining anti-human IgG (H + L) positivity toward FL-MOG. The clinical diagnoses were obtained in 33 FL-MOG–positive patients, blinded to the antibody data. IgG1-Abs to FL-MOG were associated with optic neuritis (n = 11), AQP4-seronegative neuromyelitis optica spectrum disorder (n = 4), and acute disseminated encephalomyelitis (n = 1). All 7 patients with probable multiple sclerosis (MS) were MOG-IgG1 negative.Conclusions:The limited disease specificity of FL-MOG-Abs identified using Alexa Fluor goat anti-human IgG (H + L) is due in part to detection of IgM-Abs. Use of the FL-MOG and restricting to IgG1-Abs substantially improves specificity for non-MS demyelinating diseases.Classification of evidence:This study provides Class II evidence that the presence of serum IgG1- MOG-Abs in AQP4-Ab–negative patients distinguishes non-MS CNS demyelinating disorders from MS (sensitivity 24%, 95% confidence interval [CI] 9%–45%; specificity 100%, 95% CI 88%–100%).

Multiple sclerosis in the far north--incidence and prevalence in Nordland County, Norway, 1970-2010.

BackgroundThe risk of multiple sclerosis (MS) increases with increasing latitude. Taking into consideration that Norway has a large latitude range, a south-to-north gradient would be expected. However, previous studies have reported an uneven distribution of the disease in Norway, with a relatively low prevalence in the most northern parts of the country.We describe the incidence and prevalence of MS in a county in the north of Norway over a period of 40 years.MethodsAll patients with MS living in Nordland County in the period 1970–2010 were identified by reviewing hospital charts. The patients were included if they met the criteria of definitive or probable MS according to Poser [Ann Neurol 13:227-231, 1983] or MS according to McDonalds [Ann Neurol 50:121-127, 2001]. Point prevalence at the beginning of the decades was calculated. The average annual incidence was calculated for 5-year periods.ResultsThe total crude prevalence on January 1, 2010 was 182.4 per 100 000. The annual incidence continuously increased from 0.7 per 100 000 in 1970 – 1974 to 10.1 per 100,000 in 2005 – 2009. The time delay from the first symptom to diagnosis was stable from 1975 to 2010. The proportion of primary progressive MS in the prevalence numbers was 38.2% in 1980, and decreases continuously, to 18.6% in 2010. The female to male prevalence ratio has been stable since 1990 at 2.2 to 1.ConclusionThe prevalence and the incidence of MS have steadily increased over a 40 year period. Nordland County is a high-risk area for MS.

IMPROVEMENT METHODS OF DIAGNOSIS THE VISUAL ANALYSER OF PATIENTS WITH MULTIPLE SCLEROSIS

137 (274 eyes) relapsing-remitting multiple sclerosis patients have been given detailed neuroophthalmologic examination. 58 of these patients (74 eyes) had a previous history of optic neuritis. As a result, the most informative methods of examination have been identified. These include the estimation of the frequency characteristics of the vision (vizokontrastoperimetriya, low-contrast tests Sloan), standard static automated perimetry, pattern visual evoked potentials, and optical coherence tomography which is used to measure macular volumes and retinal nerve fiber layer thickness. The above – mentioned methods make it possible to reveal the involvement of the optic analyzer in the inflammatory and neurodegenerative process at the pre-clinical stage. The obtained results allow us to recommend inclusion of the methods in the standard algorithm for the examination of patients with probable multiple sclerosis.

Incidence of Multiple Sclerosis in the General Population in the Netherlands, 1996–2008

Background: We estimated the multiple sclerosis (MS) incidence in the Netherlands for better active monitoring of potential vaccine safety signals. Methods: A retrospective cohort study (1996–2008) was conducted using a population-based general practice research database containing electronic medical records. Additional information was collected to validate incident probable cases. Results: In the source population (648,656 persons), 146 incident probable MS cases were identified. Overall incidence rate was 6.3/100,000 person years (py; 95% CI, 5.2–7.2). In the subgroup in which MS could be fully validated, the incidence increased from 4/100,000 py (95% CI, 3–5) in 1996–2004 to 9/100,000 py in 2007/8 (95% CI, 6–16). This increase was highest among women, but not statistically significantly different by gender. The median lag time between first recorded symptoms and MS diagnosis decreased from 32 months (<1998) to 2 months (>2005). Conclusions: MS is rare in the Netherlands. In recent years, there was a slight increase in the incidence especially among women during the fertile age. This increase coincided with a decrease in lag time between symptoms and diagnosis, both for men and women. This trend should be taken into account in the interpretation of MS cases occurring in a population where new vaccinations will be introduced shortly.

Relapsing Inflammatory Optic Neuropathy: A Multicenter Study of 62 Patients (P07.251)

Objective: The aim is to evaluate a multicenter cohort of RON in order to define their characteristics. Background Optic neuritis (ON) may be the first symptom of a central nervous system demyelinating, systemic or infectious diseases. Although ON is frequently limited to a single episode, few patients experience recurrent episodes with a negative workup for multiple sclerosis (MS), neuromyelitis optica (NMO) or other causes. That disorder named relapsing ON (RON), is poorly describe in view of the lack of a large cohort. Medical literature shows 2 forms of RON: chronic relapsing inflammatory ON (CRION) which is a progressive ON relapsing after steroids withdrawal and relapsing inflammatory ON (RION) which is a non-progressive ON without steroids dependence. Design/Methods: 62 patients, retrospectively included, were diagnosed with RON when they have been presented ON relapsing as the only sign, without criteria for MS or NMO, during a follow up of 8 years. Results: The age of onset was 33 years and sex ratio F/M was 3/1. Mean final visual acuity (VA) was 0,71 and mean final retinal nervous fiber layer thickness was 77 μm. Seventy percent of patient with RON presented a RION pattern while 30% presented as CRION. Cohort of RON is composed of aproximately 10% of probable NMO (IgG-AQP4 positive, severity of ON more important), 20% of probable MS (CSF oligoclonal bands positive and MRI abnormalities frequently observed) and 10% of ON related to a systemic disease. 60% of RON are of unknown etiology. We individualized 2 sub-populations with poor long-term visual prognosis : CRION and RON with AQP4-antibodies. In contrast, more than 70% of RION without AQP4-antibodies have a visual acuity higher than 0,8 at the end of the follow up. Conclusions: RON is probably a separate entity corresponding to an autoimmune disease different to MS, NMO or vasculitis. Disclosure: Dr. Benoilid has nothing to disclose. Dr. Tilikete has nothing to disclose. Dr. Arndt has nothing to disclose. Dr. Collongues has received personal compensation for activities with Biogen Idec, Bayer Schering Pharma, Teva Neuroscience, Merck-Serono, Sanofi-Aventis Pharmaceuticals, Inc., and Novartis. Dr. Vighetto has nothing to disclose. Dr. Vignal-Clermont has nothing to disclose. Dr. De Seze has received personal compensation for activities with Bayer Schering, Biogen Idec, LFB, Merck Serono, Novartis, Sanofi-Aventis, and Teva Neuroscience.Dr. De Seze has received personal compensation in an editorial capacity for Elsevier.

Multiple sclerosis in Vest-Agder county, Norway

To examine multiple sclerosis (MS) prevalence, rate of immunomodulatory treatment and frequency of Borrelia burgordorferi (Bb) antibodies in Vest-Agder, Norway. Patients in the period 1996-2006 who met the Poser criteria for definitive or probable MS were included. Clinical and demographical data, and presence of Bb antibodies were registered. A total of 295 patients were identified. The crude prevalence was 180 per 100,000 population (95% CI=160.9-218.0), age-adjusted prevalence was 186 per 100,000 population (95% CI=166.3-225.3). The age-adjusted incidence rates were 7.5 and 8.0 for 1996-2000 and 2001-2006, respectively. Thirty-eight per cent were treated with immunomodulatory agents when compared to 28% in the rest of the country. Bb serum antibodies were detected in 7% of patients with MS. Vest-Agder county has the highest prevalence of MS reported in Norway, and a high treatment rate. Bb antibodies were not more prevalent than in healthy individuals.

Prevalence and incidence of multiple sclerosis in Oppland County - a cross-sectional population-based study in a landlocked county of Eastern Norway

OBJECTIVES - We report the prevalence and incidence rates of multiple sclerosis (MS) in Oppland County, Norway. METHODS - Records from all patients diagnosed with MS at the two Oppland County hospitals, Gjøvik and Lillehammer during 1989-2001 were evaluated. In addition, all general practitioners in Oppland County reported their patients into the study. RESULTS - The age-adjusted prevalence rate of definite MS was 174.4/ 100 000 on the prevalence day 1 January 2002. When the probable cases were included, the prevalence rate rose to 185.6/100 000. The highest prevalence rates were detected in the northern mountain areas, thus corroborating the results from previous local surveys 30-50 years ago. The prevalence of MS was statistically significantly associated with climatic, socioeconomic and geographic variables in the county. The age-adjusted incidence of definite and probable MS in Oppland County was 6.6/100 000 during 1989-1993 increasing to 7.6/100 000 during 1994-1998. DISCUSSION - We found the highest prevalence rates of MS ever reported in Norway. Our findings indicate a possible influence of environmental factors.

Clone clusters in autoreactive CD4 T‐cell lines from probable multiple sclerosis patients form disease‐characteristic signatures

We developed a method for selectively propagating disease-related autoreactive T-cell lines (auTCLs) based on their increased resistance to apoptosis. The generated auTCLs homogeneously co-express CD45RO and CD49a, adhere strongly to extracellular matrix proteins and express high interleukin-17 (IL-17) messenger RNA levels, resembling a T-cell subset proposed to transmigrate into tissues and induce systemic and local inflammation in rheumatoid arthritis. The combinations of T-cell oligoclones that comprise probable multiple sclerosis (pMS) disease-related lines use a unique portfolio of T-cell receptor beta-chain variable allele (BV genes) combinations forming 'disease-specific cluster patterns'. The auTCL derived from different patients and from different myelin epitopes display striking similarities in BV gene allele clusters and are derived primarily from a disease-prone hotspot residing in the BV gene locus between Vbeta6 and Vbeta9. Conversely, healthy subject TCLs use different BV gene allele sets, forming 'healthy responder usage formats'. These formats were absent from the pMS patient V-beta gene allele combinations evaluated in this study. Hierarchical clustering of the BV gene combinations, distinguish three pMS auTCL groups, implying existence of up to three disease-related immune response patterns. These subgroup patterns may reflect different disease subclasses or alternatively they may suggest immune reactivity to different aetiological agents. Analyses of clonal-clustering patterns may potentially aid in subclassification of MS or in characterizing aetiological agents of this disease.

Depressive symptoms and coping in newly diagnosed patients with multiple sclerosis

Background Multiple sclerosis (MS) is a chronic disease with unclear etiology, unpredictable clinical course, and no cure. Patients’ ability to cope with MS moderates the adaptation to the disease. Objectives To compare coping in patients recently diagnosed with MS and healthy controls and to study the association between depressive symptoms and patients' coping styles. Methods A sample of 86 recently diagnosed patients with definite or probable MS and 93 healthy population controls completed questionnaires assessing coping styles and depressive symptoms. Results Compared with healthy controls, patients with MS used significantly less the problem focused strategies including planning, restraint coping, and seeking social support for instrumental reasons, and they used less the emotion-focused strategies seeking social support for emotional reasons, focusing on and venting of emotions, and positive reinterpretation and growth. The mean Beck Depressive symptoms Inventory scores were 10.8 and 4.7 in patients and controls, respectively. In stress situations connected to MS, depressive symptoms in these patients were related to the problem-focused strategies of restraint coping and planning, the emotion-focused strategy of focusing on and venting of emotions, and the avoidance strategies of behavioral- and mental disengagements, and denial.

Visual evoked potentials in normal subjects and patients with multiple sclerosis.

Visual evoked potentials (VEPs) by checkerboard pattern-reversal stimulation were recorded in 70 subjects aged 10--69 years and in 100 patients with definite, probable or possible multiple sclerosis (MS). Longer latencies and smaller amplitudes of the major positive component were found in male subjects, in old subjects and when the amplifier's band-pass was narrowed. Subjects 10--14 years old had longer latencies and higher amplitudes than mature adults. Based on findings in the normal material, the following three criteria were used in evaluating the recordings from patients: the latency, the side difference in latencies and the ratio of amplitudes between the two sides of the major positive component with various limits for the two sexes and different age groups. The incidence of abnormal recordings was 85% for all the patients, 100% in 50 patients with definite, 70% in 50 patients with probable or possible MS, 73% in patients who had a history of spinal symptoms only, 98% if they had and 74% if they had not experienced optic neuritis. The incidence of abnormal findings increased with increasing duration of symptoms. All patients with visual acuity below 0.67 had abnormal VEPs. The high incidence of abnormal recordings confirmed the value of the test in establishing the diagnosis, and suggested that the use of different normative values for sex and age may increase the diagnostic yield without increasing the number of false positive findings.

The hot bath test in multiple sclerosis: comparison with visual evoked responses and oligoclonal bands.

We studied 50 patients with definite, probable, and possible multiple sclerosis (MS), prospectively (20 patients) and retrospectively (30 patients), to determine the value of the hot bath test for diagnosing MS and to compare it to visual evoked responses and oligoclonal bands. The hot bath test was abnormal in 8 of the 23 patients with definite MS (35%), and 4 of the 27 patients with probable or possible MS (15%). Only one patient with an abnormal hot bath test did not also have other evidence of definite multiple sclerosis. Our results suggest that the hot bath test seldom adds diagnostic information, especially when tests for evoked responses and oligoclonal bands are available.

Optic neuritis--a sign of multiple sclerosis or other diseases of the central nervous system.

A neurological and ophthalmological re-examination has been carried out of 116 patients with optic neuritis (ON), who were treated at the eye clinic of the Central Hospital of Turku University during the years 1950–1969. The follow-up period of patients varied from 3 to 22 years (average 10.2 years). Fifty-eight (50.0 per cent) had probable MS (Multiple Sclerosis) and 18 (15.5 per cent) possible MS. Thirty-two (42.1 per cent) earlier undiagnosed cases of MS were found in this material. In most of these cases the patients' neurological symptoms were so mild that they had not consulted a neurologist. This indicates that MS is a more common disease than the selective studies based on patients collected from the hospital records in a neurological clinic would suppose. ON with some cause other than MS was observed in 15 (13.0 per cent) patients, among whom were many cases with a neurological disease other than MS. The etiology of ON remained unknown in 25 (21.6 per cent) patients. Many of these patients had some very mild neurological symptoms, but a diagnosis of MS, based on criteria of the Schumacher committee, could not be made. After a longer follow-up period, even these cases can perhaps be classified as suffering from MS. Neurological and ophthalmological findings in re-examined patients are described and compared with previous reports. Six families with occurrence of MS within the family, and two with Leber's hereditary optic atrophy are reported. Our studies indicate that ON must be considered as an important sign of a disease of the central nervous system and not only as an isolated eye disease.