Atrophy of optic nerve detected by transorbital sonography in patients with demyelinating diseases of the central nervous system.

BACKGROUND AND PURPOSE: Transorbital sonography (TOS) has emerged as promising imaging method for the diagnosis and follow-up of acute optic neuritis (ON). Available studies report an increase in the optic nerve diameter (OND) and the optic nerve sheath diameter (ONSD) in the case of a first episode of ON in the affected eye compared to either the contralateral unaffected eye or controls. However, the utility of TOS in the case of recurrent episodes of ON has never been assessed. METHODS: In our prospective cohort study, the diagnostic utility of TOS in patients with demyelinating diseases of the central nervous system was assessed, and the association between TOS, optical coherence tomography (OCT) and visual evoked potentials was examined further. RESULTS: Seventy-eight patients with a history of demyelinating disorders of the central nervous system (mean age 38.2 ± 14.2 years; 24% with acute ON) were included. No differences in the OND (3.2 ± 0.5 mm vs. 3.2 ± 0.4 mm) and ONSD (5.1 ± 0.8 mm vs. 5.1 ± 0.7 mm) measurements were found between patients with and without acute ON. Papillary swelling was more frequent in patients with acute ON (14.2% vs. 1.5%, P = 0.002). Patients with a history of previous ON were found to have lower OND (P < 0.001) and ONSD (P = 0.007) compared to patients without a history of previous ON. TOS measurements were inversely associated with disease duration and positively correlated with OCT findings. No association with visual evoked potential measurements was found. CONCLUSION: No evidence was found for TOS-sensitive differences in the OND and ONSD of patients with demyelinating diseases, according to the presence of acute ON. The association between TOS and OCT measurements deserves further investigation.

MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature.

BACKGROUND: Antibodies to human full-length myelin oligodendrocyte glycoprotein (MOG-IgG) as detected by new-generation cell-based assays have recently been described in patients presenting with acute demyelinating disease of the central nervous system, including patients previously diagnosed with multiple sclerosis (MS). However, only limited data are available on the relevance of MOG-IgG testing in patients with chronic progressive demyelinating disease. It is unclear if patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) should routinely be tested for MOG-IgG. OBJECTIVE: To evaluate the frequency of MOG-IgG among patients classified as having PPMS or SPMS based on current diagnostic criteria. METHODS: For this purpose, we retrospectively tested serum samples of 200 patients with PPMS or SPMS for MOG-IgG using cell-based assays. In addition, we performed a review of the entire English language literature on MOG-IgG published between 2011 and 2017. RESULTS: None of 139 PPMS and 61 SPMS patients tested was positive for MOG-IgG. Based on a review of the literature, we identified 35 further MOG-IgG tests in patients with PPMS and 55 in patients with SPMS; the only reportedly positive sample was positive just at threshold level and was tested in a non-IgG-specific assay. In total, a single borderline positive result was observed among 290 tests. CONCLUSION: Our data suggest that MOG-IgG is absent or extremely rare among patients with PPMS or SPMS. Routine screening of patients with typical PPMS/SPMS for MOG-IgG seems not to be justified.

Headache-attributed burden and its impact on productivity and quality of life in Russia: structured healthcare for headache is urgently needed.

BACKGROUND AND PURPOSE: The study evaluated headache-attributed burden and its impact on productivity and quality of life (QoL) in Russia. Its purpose was to support recommendations for change. METHODS: A countrywide population-based random sample of 2725 biologically unrelated adults (aged 18-65 years) in 35 cities and nine rural areas of Russia were interviewed in a door-to-door survey. The structured questionnaire enquired into symptom burden, functional disability, lost productive time and QoL (applying the WHOQoL-8 question set), as well as willingness to pay (WTP) for adequate headache treatment, if it were available. RESULTS: Mean lost paid-work days due to headache in the previous 3 months were 1.9 ± 4.2, and mean lost household work days were 3.4 ± 5.7. The estimated annual indirect cost of primary headache disorders was USD 22.8 billion, accounting for 1.75% of gross domestic product. QoL was reduced by all types of primary headaches. According to WHOQoL-8, it was significantly lower in those with headache on ≥15 days/month than in those with episodic headache (24.7 ± 4.6 vs. 28.1 ± 5.0; P < 0.05) and lower in those with migraine than in those with tension-type headache (TTH) (27.1 ± 4.9 vs. 28.8 ± 5.0; P < 0.05). Average WTP for adequate headache treatment was RUB 455 ± 494 per month (median RUB 300), a sum sufficient in most cases, and correlated with illness severity (higher for headache on ≥15 days/month than for migraine, and for migraine than for TTH). CONCLUSIONS: Headache is common, burdensome and costly in Russia and, manifestly, poorly mitigated by existing healthcare. Structured healthcare services for headache need to be urgently put in place.

Rapid differentiation of MOGAD and MS after a single optic neuritis.

BACKGROUND: Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS) and myelin-oligodendrocyte-glycoprotein IgG-associated disease (MOGAD). This study evaluated the applicability of optical coherence tomography (OCT) for differentiating between both diseases in two independent cohorts. METHODS: One hundred sixty two patients from seven sites underwent standard OCT and high-contrast visual acuity (HCVA) testing at least 6 months after first ON. Of these, 100 patients (32 MOGAD, 68 MS) comprised the primary investigational cohort, while 62 patients (31 MOGAD, 31 MS) formed a validation cohort. A composite score distinguishing between MOGAD and MS was developed using multivariate logistic regression. RESULTS: Bilateral simultaneous ON occurred more frequently in MOGAD compared to MS (46.9 vs. 11.8%, p < 0.001). OCT revealed more peripapillary retinal nerve fiber layer (pRNFL) atrophy in all segments in MOGAD compared to predominantly temporal pRNFL atrophy in MS (p < 0.001). HCVA was better preserved in MS (p = 0.007). pRNFL thickness in all except for temporal segments was suitable for differentiating MOGAD and MS. Simultaneous bilateral ON and critical atrophy in nasal (< 58.5 µm) and temporal superior (< 105.5 µm) segments were included into the composite score as three independent predictors for MOGAD. The composite score distinguished MOGAD from MS with 75% sensitivity and 90% specificity in the investigational cohort, and 68% sensitivity and 87% specificity in the validation cohort. CONCLUSION: Following a single ON-episode, MOGAD exhibits more pronounced global pRNFL atrophy and lower visual acuity after ON compared to MS. The introduced OCT-based composite score enabled differentiation between the two entities across both cohorts.

Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy.

Recently, the disappearance of oligoclonal bands (OCBs) from the cerebrospinal fluid (CSF) of a few natalizumab-treated patients with multiple sclerosis (MS) has been reported. This is interesting since CSF-restricted OCB are believed to persist in MS. We pooled CSF data from 14 MS centers to obtain an adequate sample size for investigating the suspected changes in central nervous system (CNS)-restricted humoral immune activities in the context of natalizumab therapy. In a retrospective chart analysis, CSF parameters of blood-CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy. At the time of repeat lumbar puncture, local IgG production (according to Reibergram) was significantly reduced (p < 0.0001) and OCB had disappeared in 16% of the patients. We therefore conclude that natalizumab therapy interferes with intrathecal antibody production at least in a significant number of patients.

The prevalence of primary headache disorders in Russia: a countrywide survey.

OBJECTIVE: To estimate the 1-year prevalences of primary headache disorders and identify their principal risk factors in the general population of Russia. METHODS: A countrywide population-based random sample of 2725 biologically unrelated adults in 35 cities and nine rural areas were interviewed in a door-to-door survey using a previously validated diagnostic questionnaire. RESULTS: Of the 2725 eligible adults contacted, 2025 (74.3%) responded (females 52.6%, mean age 39.5 ± 13.4 years). Of these, 1273 (62.9%) reported headache 'not related to flu, hangover, cold, head injury' occurring at least once in the previous year. The gender- and age-standardized 1-year prevalence of migraine was 20.8%. Female gender (odds ratio (OR) = 3.8; 95% confidence interval (CI) 2.8-5.1) and obesity (OR = 1.5; 1.1-2.1) were positively associated with this type of headache. The gender- and age-standardized 1-year prevalence of tension-type headache (TTH) was 30.8%. TTH was more prevalent in urban than in rural areas (OR = 1.6; 1.3-2.0). Headache on ≥15 days/month was reported by 213 (10.5%) respondents (gender- and age-standardized prevalence 10.4%), and associated with low socioeconomic status (OR = 3.4; 2.4-4.9), obesity (OR = 3.0; 2.1-4.3), female gender (OR = 2.9; 2.1-4.1) and age over 40 years (OR = 2.6; 1.9-3.6). The majority of these respondents (68.1%) overused acute headache medications. CONCLUSION: The study demonstrated a high prevalence of migraine and a very high prevalence of headache on ≥15 days/month, and revealed unmet health-care needs of people with headache in Russia.

Characteristic retinal atrophy pattern allows differentiation between pediatric MOGAD and MS after a single optic neuritis episode.

BACKGROUND: Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MSped) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGADped) in children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode. METHODS: Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls. RESULTS: Thirteen MOGADped (10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MSped (14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGADped compared to MSped (pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm, p < 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm3, p < 0.001). Neither other macular layers nor P100 latency differed. MOGADped developed global atrophy affecting all peripapillary segments, while MSped displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGADped). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%, p = 0.016). CONCLUSION: First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.

The burden of headache in Russia: validation of the diagnostic questionnaire in a population-based sample.

BACKGROUND: We report validation of the Russian-language version of the Lifting The Burden headache screening and diagnostic questionnaire in a population-based sample of 501 individuals in four cities (Smolensk, Tchelyabinsk, Nishny Novgorod and Tver) and three rural areas (Tula, Tver and Gornyi) of Russia. METHODS: The structured questionnaire, based on ICHD-II criteria, was applied face to face by trained non-medical interviewers calling at randomly selected households. Response rates were about 73% in cities and 80% in rural areas. RESULTS: Of those responding, 301 reported headache in the previous year; of the total sample, 143 people with and 47 without headache according to the questionnaire were re-interviewed by telephone by one of the two neurologists unaware of the questionnaire diagnoses. Migraine (MIG), either definite (dMIG) or probable (pMIG), was diagnosed by the questionnaire in 72 cases, and tension-type headache (TTH), either definite (dTTH) or probable (pTTH), in 66 cases; the five others with headache were unclassifiable by questionnaire. Physicians diagnosed dMIG or pMIG in 65 cases, dTTH or pTTH in 89 cases and no headache in 31 cases; in five cases, headache was unclassifiable. The questionnaire had sensitivities and specificities of 77% and 82% for MIG (κ=0.58) and of 64% and 91% for TTH (κ=0.56). CONCLUSIONS: We concluded that the questionnaire can be utilized in a population-based countrywide survey of the burden attributable to primary headache disorders in Russia.

Extensive cortical involvement in leptomeningeal carcinomatosis.

We present a 77-year-old previously well patient with facial asymmetry and progressive weakness of the lower extremities. An initial MRI revealed slight contrast enhancement of the meninges. Three consecutive cerebrospinal fluid examinations demonstrated low glucose concentration, marked elevation of total protein and moderate pleocytosis. No tumor cells, fungi, acid-fast bacilli or mycobacterial DNA were found. The patient's level of consciousness deteriorated dramatically, and follow-up MRI showed widespread extensive cortical hyperintensities. The lesions showed restricted diffusion on diffusion-weighted images as well as low values on the corresponding apparent diffusion coefficient maps, the changes consistent with diffuse cytotoxic edema. Neuropathological examination findings were of leptomeningeal carcinomatosis (LMC) with diffuse continuous infiltration of the cerebral cortex, cerebellum and spinal cord. The autopsy revealed a subcentimetre adenocarcinoma of the lung. To our knowledge, this is the first report demonstrating extensive cortical involvement in adenocarcinomatous LMC.

Central sensitization of the trigeminal and somatic nociceptive systems in medication overuse headache mainly involves cerebral supraspinal structures.

Trigeminal and somatic nociceptive systems were studied in controls (n=15), episodic migraine (n=16), analgesics (n=14) and triptan-induced medication overuse headache (MOH) (n=15) before and after withdrawal. Patients with MOH and comorbid depressive symptoms and depression without headache were studied to investigate the influence of depression. Trigeminal nociception was studied by simultaneous registration of pain-related cortical potentials (PREP) and nociceptive blink reflex (nBR) following nociceptive-specific electrical stimulation of the forehead. Somatic nociception was evaluated using PREP of upper limbs. We found facilitation of both trigeminal and somatic PREP but not of nBR in MOH, which normalized after withdrawal. No differences were found comparing analgesics vs. triptan MOH. No differences were observed between controls and patients with episodic migraine and depression without headache. A transient facilitation was found of trigeminal and somatic nociceptive systems in MOH, which was more pronounced on a supraspinal level.