High-risk syndrome for neuromyelitis optica: a descriptive and comparative study.

BACKGROUND: Neuromyelitis optica (NMO) frequently begins with a monofocal episode of optic neuritis or myelitis. A concept named high-risk syndrome (HRS) for NMO has been proposed for patients with monofocal episodes and NMO-IgG antibodies. OBJECTIVE: To describe HRS patients and compare them with NMO patients. METHODS: We identified 30 patients with HRS: 18 with extensive myelitis (HRM) and 12 with optic neuritis (HRON), in a database pooling patients from 25 centres in France. Clinical, laboratory/magnetic resonance imaging (MRI) data and outcome were analysed and compared with a national cohort of 125 NMO patients extracted from the same database. RESULTS: Mean follow-up was 4.8 years. Mean age at onset was 42.8 years (range: 12.4-70) with a female:male ratio of 0.9. Asymptomatic lesions were report on visual evoked potentials in 4/8 tested HRM patients and on spinal cord MRI in 2/7 HRON patients. Three patients died, two owing to a cervical lesion. HRS and NMO patients had similar clinical/paraclinical data, except for a predominance of men in the HRS group and a later mean age at onset in the HRM subgroup. CONCLUSION: The description of HRS patients is compatible with a monofocal form of NMO. Asymptomatic lesions could be included in a new set of NMO diagnostic criteria.

Clinical course of optic neuritis in patients with relapsing neuromyelitis optica.

OBJECTIVE: To describe the clinical characteristics, course, and prognosis of optic neuritis in recurrent neuromyelitis optica. METHODS: We analyzed 60 patients diagnosed using 1999 Mayo Clinic criteria who were seen between 1985 and 2004 at Hospital da Lagoa (Rio de Janeiro, Brazil). RESULTS: Optic neuritis was the initial feature in 53.3% of patients, most with unilateral disease. Recurrent optic neuritis before myelitis occurred in 18.3%. The visual impairment was severe at nadir of the visual index event in 78.3%, with a high remission rate. In the median disease duration of 8 years (range, 0.5-30 years), 380 relapses (118 optic neuritis, 223 myelitis, 39 optic neuritis and myelitis) occurred. At the last follow-up, 53.3% of patients had bilateral visual impairment and 63.3% were blind in at least 1 eye. A high mortality rate (23.3%) was due to cervical myelitis. Mortality rates were significantly higher among Afro Brazilian patients (58.3%). CONCLUSIONS: Optic neuritis in patients with recurrent neuromyelitis optica has a severe and acute onset, with predominantly unilateral lesions followed by improvement of clinical symptoms. In the long-term, the disease leads to severe bilateral visual impairment. Mortality rates are higher among patients of Afro Brazilian descent.

Prediction of a multiple sclerosis diagnosis in patients with clinically isolated syndrome using the 2016 MAGNIMS and 2010 McDonald criteria: a retrospective study.

BACKGROUND: In 2016, the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS). Changes to the DIS definition included removal of the distinction between symptomatic and asymptomatic lesions, increasing the number of lesions needed to define periventricular involvement to three, combining cortical and juxtacortical lesions, and inclusion of optic nerve evaluation. For DIT, removal of the distinction between symptomatic and asymptomatic lesions was suggested. We compared the performance of the 2010 McDonald and 2016 MAGNIMS criteria for multiple sclerosis diagnosis in a large multicentre cohort of patients with CIS to provide evidence to guide revisions of multiple sclerosis diagnostic criteria. METHODS: Brain and spinal cord MRI and optic nerve assessments from patients with typical CIS suggestive of multiple sclerosis done less than 3 months from clinical onset in eight European multiple sclerosis centres were included in this retrospective study. Eligible patients were 16-60 years, and had a first CIS suggestive of CNS demyelination and typical of relapsing-remitting multiple sclerosis, a complete neurological examination, a baseline brain and spinal cord MRI scan obtained less than 3 months from clinical onset, and a follow-up brain scan obtained less than 12 months from CIS onset. We recorded occurrence of a second clinical attack (clinically definite multiple sclerosis) at months 36 and 60. We evaluated MRI criteria performance for DIS, DIT, and DIS plus DIT with a time-dependent receiver operating characteristic curve analysis. FINDINGS: Between June 16, 1995, and Jan 27, 2017, 571 patients with CIS were screened, of whom 368 met all study inclusion criteria. At the last evaluation (median 50·0 months [IQR 27·0-78·4]), 189 (51%) of 368 patients developed clinically definite multiple sclerosis. At 36 months, the two DIS criteria showed high sensitivity (2010 McDonald 0·91 [95% CI 0·85-0·94] and 2016 MAGNIMS 0·93 [0·88-0·96]), similar specificity (0·33 [0·25-0·42] and 0·32 [0·24-0·41]), and similar area under the curve values (AUC; 0·62 [0·57-0·67] and 0·63 [0·58-0·67]). Performance was not affected by inclusion of symptomatic lesions (sensitivity 0·92 [0·87-0·96], specificity 0·31 [0·23-0·40], AUC 0·62 [0·57-0·66]) or cortical lesions (sensitivity 0·92 [0·87-0·95], specificity 0·32 [0·24-0·41], AUC 0·62 [0·57-0·67]). Requirement of three periventricular lesions resulted in slightly lower sensitivity (0·85 [0·78-0·90], slightly higher specificity (0·40 [0·32-0·50], and similar AUC (0·63 [0·57-0·68]). Inclusion of optic nerve evaluation resulted in similar sensitivity (0·92 [0·87-0·96]), and slightly lower specificity (0·26 [0·18-0·34]) and AUC (0·59 [0·55-0·64]). AUC values were also similar for DIT (2010 McDonald 0·61 [0·55-0·67] and 2016 MAGNIMS 0·61 [0·55-0·66]) and DIS plus DIT (0·62 [0·56-0·67] and 0·64 [0·58-0·69]). INTERPRETATION: The 2016 MAGNIMS criteria showed similar accuracy to the 2010 McDonald criteria in predicting the development of clinically definite multiple sclerosis. Inclusion of symptomatic lesions is expected to simplify the clinical use of MRI criteria without reducing accuracy, and our findings suggest that needing three lesions to define periventricular involvement might slightly increase specificity, suggesting that these two factors could be considered during further revisions of multiple sclerosis diagnostic criteria. FUNDING: UK MS Society, National Institute for Health Research University College London Hospitals Biomedical Research Centre, Dutch MS Research Foundation.

Optic neuritis: a population-based study in Olmsted County, Minnesota.

We reviewed the records of all patients with optic neuritis (ON) in Olmsted County, Minnesota, identified through the comprehensive records-linkage system at the Mayo Clinic, and identified 156 ON patients from 1935 to 1991 who had onset of the disease while residing in Olmsted County (incidence cases). Poisson regression analysis revealed that age, gender, and calendar year were associated with incidence. The annual age- and sex-adjusted incidence rate was 5.1 per 100,000 person-years from 1985 to 1991. On December 1, 1991, 128 patients with a documented history of ON resided in Olmsted County (prevalence cohort). The age- and sex-adjusted prevalence rate per 100,000 was 115. The average length of follow-up for the incidence cohort was 13.2 years. Life table analysis showed that 39% of the 95 patients with isolated ON in the incidence cohort had progressed to clinically definite multiple sclerosis (MS) by 10 years of follow-up, that 49% had by 20 years, 54% by 30 years, and 60% by 40 years. There was no difference in the risk of developing MS between men and women. The presence of venous sheathing (p = 0.044) and evidence for recurrent ON (p < 0.0001) were associated with an increased likelihood of developing MS. The estimated 25-year survival rate was 88.3% +/- 5.8% for the incidence cohort with isolated ON, compared with 83.9% for the general US population of similar age and sex.

[A cohort study on deaths from SMON in Japan].

Causes and risk factors of deaths from subacute myelo-optico neuropathy (SMON) were studied in a prospective cohort of 4,329 SMON patients followed for 3 years and 7 months (Sept. 1985-March 1989) with the following findings: (1) Recent excess deaths of SMON patients was estimated as 4% from ratio of O/E (SMR = 104) and deaths due to SMON itself was 6.4%. (2) The ratio of O/E was significantly higher for deaths from cancer of colon/rectum in females, cancer of pancreas in males, hypertension in males, pneumonia/influenza in females, chronic obstructive pulmonary diseases in males, tuberculosis and intestinal obstructive disease in males and females. (3) The ratio of O/E was 1.8 times or greater for those SMON patients with complications of cerebrovascular disease, severe blindness, complete loss of ambulation, and who were bedridden, and who are unable to receive home care from family members or trained home helpers.

[Mortality of SMON patients in relation to their disabilities].

The relationship between mortality and disability, was studied in SMON patients, who had participated in the questionnaire survey in 1980, by following them for 10 years through municipal resident registration information offices. Eighty deaths were observed among 409 subjects during the follow-up period. The effect of each disability on the mortality of SMON was estimated by applying the Cox proportional hazard model. The presence of severe gait disturbance and low levels of activities of daily living (ADL) were associated with significantly higher risk of death after adjustment for age and sex. The relative risk of visual disturbance was not significant after adjusting for age, sex and other kinds of disability. Those who complained of continuous dysesthesia at the time of the initial survey showed better prognosis than those without such dysesthesia. Among subjects who died during the follow-up period, those who had reported low levels of ADL at the time of the initial survey had a greater proportion of deaths attributable to heart failure and pneumonia than those who had reported high levels of ADL.

[Course of illness and prognosis of multiple sclerosis. 2: Predictive value of clinical and paraclinical factors]. / Krankheitsverlauf und Prognose der multiplen Sklerose. 2. Teil: Prädiktiver Wert klinischer und paraklinischer Faktoren.

The second part of this review summarizes the predictive value of demographic factors, the early clinical course and paraclinical methods in the prognosis of multiple sclerosis (MS). The chronic progressive course is generally thought to be associated with a worse outcome compared to relapsing-remitting MS. Moderate disability within 5 years, residual pyramidal and cerebellar deficits 6 months following an acute attack, motor, cerebellar and possibly brain stem exacerbations as well as frequent relapses were found to indicate an increased risk for developing severe disability or increased mortality. Magnetic resonance imaging (MRI), evoked potentials and cerebrospinal fluid findings were not found to be predictive in clinically definite MS, although there was a weak association of MRI findings and disability. However, these paraclinical modalities were important methods to predict the further development of clinically isolated demyelinating syndromes. In this regard, MRI was identified as the strongest predictive factor of the conversion to definite MS.

Prognosis of SMON patients.

The following points have become clear on prognosis of SMON through the analysis of 981 cases collected. 1) The prognosis of the old whose ages were 60 year old or over is not favorable, when compared with that of the young. However, there is no prognostic difference between male and female. 2) The cummulative death rate of SMON which was calculated by the life table method is approx twice as much as the generally expected value. 3) Approximately 80% of the patients showed some sort of improvement 7 to 12 months after the onset of the disease. The rate for 13 months or over if nearly the same. 4) The abdominal symptoms found at the time of the onset of the disease decreased markedly in the course of the disease. 5) Among neurological symptoms, the prognosis of motor disorders is more favorable. The complete recovery of sensory disturbances was extremely rare, but approx 60% showed more or less favorable in the course of the illness. Approximately 40% of the cases with visual disturbances completely recovered or showed favorable improvement, whereas 9% of them became worse. As for the prognosis of visual impairment, it is more serious than other symptoms. 6) The patients who had been administered clioquinol over long period displayed a higher rate of severe or moderate motor, sensory and visual disturbances, compared with the group with short-term administration of clioquinol. The death rate was also higher in the former group. 7) The rate of relapse as a whole was 16.7% and 68% of them was seen within 18 months after the onset. There is no difference in relapse according to sex. There was seen a high rate of relapse in the group of longterm administration of clioquinol. 8) A 10.5% of total cases were either unable to walk or in need of assistance in walking, whereas the rate of patients who cannot get dressed or who cannot defecate unassisted was lower. 9) Approximately 65% returned to the job in 12 months or more after the onset. The employment rate was not different according to sex, whereas it was lower along with the age advances. 10) Approximately 20% were not received medical treatment. The rate of non-treated patients is higher in the younger patients. The rate of hospitalized patients was higher in the older patients.

The natural history of non-arteritic anterior ischaemic optic neuropathy.

Seventy one patients with non-arteritic anterior ischaemic optic neuropathy were studied retrospectively. Sixty three (89%) were followed to the end of the study or death, mean follow up time was 5.3 years. Whilst twenty (28%) had diabetes or hypertension, in thirty nine (55%) no predisposing condition was identified. In those who had monocular disease at presentation (68), subsequent involvement of the second eye occurred in seventeen (25%), seven within the first year. Nineteen patients died within the study period. Of these, nine died from myocardial infarction and four from cerebrovascular disease. This is a significant increase above figures calculated from the Office of Population Census and Surveys (p less than 0.001 for all causes, p less than 0.002 for myocardial infarction and cerebrovascular disease). Such an increase in mortality has not been previously reported, and implies that this condition carries a more sinister systemic prognosis than is frequently supposed.

Cytomegalovirus optic neuritis: characteristics, therapy and survival.

Little is known about the natural history of cytomegalovirus (CMV) optic neuritis in the acquired immunodeficiency syndrome. We analyzed the clinical course of CMV optic neuritis in 30 consecutive subjects (35 eyes), and compared the survival of patients with CMV optic neuritis to that of a group having CMV retinitis alone, with both groups matched for ganciclovir therapy. Four untreated eyes had a median final visual acuity of no light perception. The median final visual acuity was 20/100 in treated subjects with a mean follow-up of 6.6 months. Following ganciclovir treatment, 2 eyes showed visual improvement, 17 eyes had unchanged visual acuity, and 12 eyes had marked drop in acuity. Relapse occurred in 4 subjects maintained on single-dose ganciclovir, and was controlled on double-dose ganciclovir. Survival was similar in the group of CMV retinitis alone versus the group of CMV optic neuritis with retinitis. Early recognition and therapy of CMV optic neuritis protects against irreversible visual loss. CMV optic neuritis does not carry a worse prognosis for survival than CMV retinitis alone.