Levetiracetam in the prophylactic treatment of episodic migraine: A prospective open label study.

BACKGROUND: The prophylactic treatment of migraine includes anticonvulsant drugs such as valproic acid and topiramate. However, these substances are often poorly tolerated by migraine patients. So far levetiracetam has hardly been studied as an episodic migraine prophylactic agent in adults. OBJECTIVE: To perform a prospective pilot study for the evaluation of the efficacy and tolerability of levetiracetam in the prophylactic treatment of episodic migraine. METHODS: Fifty patients with episodic migraine were enrolled in this prospective, open label study. After a baseline period of four weeks, patients received 1,000 mg (starting dose 500 mg) bid levetiracetam for 12 weeks. Migraine frequency and accompanying symptoms were recorded in a headache diary. The primary endpoint was the comparison of attack frequency during the baseline with attack frequency during the last four weeks of treatment (treatment period 3). RESULTS: In the Intent-To-Treat analysis, 46% of the patients had a migraine reduction of more than 50% in the third period as compared to the baseline period. The mean number of migraine attacks decreased from 5.2 +/- 2.1 (baseline) to 3.4 +/- 2.7 (period 3). The most frequently reported side effects were somnolence, nausea, and weight gain; all were mild and transient. In a post-hoc comparison, responders to levetiracetam had significantly less migraine attacks at baseline and had significantly more often migraine with aura. CONCLUSION: The data suggest that levetiracetam has some potential in the prophylactic treatment of episodic migraine which seems, however, to be not superior to that of other anticonvulsant drugs. Levetiracetam was well tolerated and showed better efficacy in patients with migraine with aura and in less affected migraine patients. A larger placebo-controlled, double-blind study in adults seems justified on the basis of these data.

Idarucizumab administration in emergency situations: the Munich Registry of Reversal of Pradaxa® in clinical routine (MR REPAIR).

OBJECTIVES: To evaluate daily life management and functional outcome of Idarucizumab administration in case of emergency situations in patients with Dabigatran treatment. DESIGN: Multicenter observational registry study. SETTING: All hospitals with full neurological departments (n = 6) in Munich, Germany INCLUDED PATIENTS: All patients treated with Idarucizumab from 01/2016 to 03/2019. ANALYZED DATA: Indication and application of Idarucizumab, demographics and clinical parameters, and further interventions and treatments; clinical outcome was assessed with the modified Rankin scale (mRS) at 3 months after Idarucizumab administration RESULTS: Idarucizumab was administered to 32 patients for severe bleeding complications and ischemic strokes, more precisely for the following specific indications: intracranial bleeding (17 patients, 53%), ischemic stroke (8 patients, 25%), gastrointestinal bleeding (3 patients, 9%), femoral fracture, aortic dissection, and abdominal trauma and ileus (1 patient each, 3%). Additional coagulation management was performed in 7 patients (22%). Nine patients (28%) underwent emergency surgery. Seven patients (22%) received Idarucizumab before intravenous thrombolysis due to ischemic stroke and 4 of these 7 patients (13%) received mechanical thrombectomy in addition. Indication was mainly based on the history of Dabigatran intake and was irrespective of laboratory testing. At follow-up, 25% of the investigated patients had a mRS 0-2, while 25% had an unfavorable outcome (mRS 4-5). Mortality was 31%. CONCLUSION: In our study, we have shown that the administration of Idarucizumab is a rare intervention and restricted to patients with severe bleeding complications or ischemic stroke. The clinical outcome of patients who received Idarucizumab in emergency situations was poor.

Apheresis therapies for NMOSD attacks: A retrospective study of 207 therapeutic interventions.

OBJECTIVE: To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR). METHODS: This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody-seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013. Besides descriptive data analysis of patient and attack characteristics, generalized estimation equation (GEE) analyses were applied to compare the effectiveness of the 2 apheresis techniques. A GEE model was generated to assess predictors of outcome. RESULTS: Two hundred and seven attacks in 105 patients (87% AQP4-ab-antibody seropositive) were treated with at least 1 apheresis therapy. Neither PE nor IA was proven superior in the therapy of NMOSD attacks. CR was only achieved with early apheresis therapy. Strong predictors for CR were the use of apheresis therapy as first-line therapy (OR 12.27, 95% CI: 1.04-144.91, p = 0.047), time from onset of attack to start of therapy in days (OR 0.94, 95% CI: 0.89-0.99, p = 0.014), the presence of AQP4-ab-antibodies (OR 33.34, 95% CI: 1.76-631.17, p = 0.019), and monofocal attack manifestation (OR 4.71, 95% CI: 1.03-21.62, p = 0.046). CONCLUSIONS: Our findings suggest early use of an apheresis therapy in NMOSD attacks, particularly in AQP4-ab-seropositive patients. No superiority was shown for one of the 2 apheresis techniques. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with NMOSD, neither PE nor IA is superior in the treatment of attacks.

OCT-Angiography reveals reduced vessel density in the deep retinal plexus of CADASIL patients.

Optical coherence tomography angiography (OCT-A) represents the most recent tool in ophthalmic imaging. It allows for a non-invasive, depth-selective and quantitative visualization of blood flow in central retinal vessels and it has an enormous diagnostic potential not only in ophthalmology but also with regards to neurologic and systemic diseases. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary vascular small-vessel disease caused by Notch3 mutations and represents the most common form of hereditary stroke disorder. In this study, CADASIL patients prospectively underwent OCT-A imaging to evaluate retinal and choriocapillaris blood flow as well as blood flow at the optic nerve head. The vessel density of the macular region and the size of the foveal avascular zone in the superficial and deep retinal plexus were determined as well as the vessel density at the optic nerve head and in the choriocapillaris. Additionally, cerebral magnetic resonance images were evaluated. The main finding was that vessel density of the deep retinal plexus was significantly decreased in CADASIL patients compared to healthy controls which may reflect pericyte dysfunction in retinal capillaries.

The Use of Digital and Remote Communication Technologies as a Tool for Multiple Sclerosis Management: Narrative Review.

Despite recent advances in multiple sclerosis (MS) care, many patients only infrequently access health care services, or are unable to access them easily, for reasons such as mobility restrictions, travel costs, consultation and treatment time constraints, and a lack of locally available MS expert services. Advances in mobile communications have led to the introduction of electronic health (eHealth) technologies, which are helping to improve both access to and the quality of health care services. As the Internet is now readily accessible through smart mobile devices, most people can take advantage of eHealth apps. The development of digital applications and remote communication technologies for patients with MS has increased rapidly in recent years. These apps are intended to complement traditional in-clinic approaches and can bring significant benefits to both patients with MS and health care providers (HCPs). For patients, such eHealth apps have been shown to improve outcomes and increase access to care, disease information, and support. These apps also help patients to participate actively in self-management, for example, by tracking adherence to treatment, changes in bladder and bowel habits, and activity and mood. For HCPs, MS eHealth solutions can simplify the multidisciplinary approaches needed to tailor MS management strategies to individual patients; facilitate remote monitoring of patient symptoms, adverse events, and outcomes; enable the efficient use of limited resources and clinic time; and potentially allow more timely intervention than is possible with scheduled face-to-face visits. These benefits are important because MS is a long-term, multifaceted chronic condition that requires ongoing monitoring, assessment, and management. We identified in the literature 28 eHealth solutions for patients with MS that fall within the four categories of screening and assessment, disease monitoring and self-management, treatment and rehabilitation, and advice and education. We review each solution, focusing on any clinical evidence supporting their use from prospective trials (including ASSESS MS, Deprexis, MSdialog, and the Multiple Sclerosis Performance Test) and consider the opportunities, barriers to adoption, and potential pitfalls of eHealth technologies in routine health care.

Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients.

Treatment of neuropathic pain (NP) symptoms associated with multiple sclerosis (MS) is frequently insufficient. Yet, cannabis is still rarely offered for treatment of pain. This clinical trial aimed at showing the positive benefit-risk ratio of dronabinol. Two hundred forty MS patients with central NP entered a 16-weeks placebo-controlled phase-III study followed by a 32-weeks open-label period. One hundred patients continued therapy for overall up to 119 weeks. Primary endpoint was change of pain intensity on the 11-point Numerical Rating Scale over a 16-weeks treatment period. Safety was assessed on the basis of adverse reactions (ARs), signs of dependency and abuse. Pain intensity during 16-weeks dronabinol and placebo treatment was reduced by 1.92 and 1.81 points without significant difference in between (p = 0.676). Although the proportion of patients with ARs was higher under dronabinol compared to placebo (50.0 vs. 25.9%), it decreased during long-term use of dronabinol (26%). No signs of drug abuse and only one possible case of dependency occurred. The trial results demonstrate that dronabinol is a safe long-term treatment option.

Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response.

OBJECTIVE: To analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD). DESIGN: This is a retrospective cohort study conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from Cox proportional hazard regression models adjusted for centre effects, important prognostic factors and repeated treatment episodes. RESULTS: 265 treatment episodes with a mean duration of 442 days (total of 321 treatment years) in 144 patients (mean age at first attack: 40.9 years, 82.6% female, 86.1% aquaporin-4-antibody-positive) were analysed. 191 attacks occurred during any of the treatments (annual relapse rate=0.60). The most common treatments were rituximab (n=77, 111 patient-years), azathioprine (n=52, 68 patient-years), interferon-ß (n=32, 61 patient-years), mitoxantrone (n=34, 32.1 patient-years) and glatiramer acetate (n=17, 10 patient-years). Azathioprine (HR=0.4, 95% CI 0.3 to 0.7, p=0.001) and rituximab (HR=0.6, 95% CI 0.4 to 1.0, p=0.034) reduced the attack risk compared with interferon-ß, whereas mitoxantrone and glatiramer acetate did not. Patients who were aquaporin-4-antibody-positive had a higher risk of attacks (HR=2.5, 95% CI 1.3 to 5.1, p=0.009). Every decade of age was associated with a lower risk for attacks (HR=0.8, 95% CI 0.7 to 1.0, p=0.039). A previous attack under the same treatment tended to be predictive for further attacks (HR=1.5, 95% CI 1.0 to 2.4, p=0.065). CONCLUSIONS: Age, antibody status and possibly previous attacks predict further attacks in patients treated for NMOSD. Azathioprine and rituximab are superior to interferon-ß.

Influence of female sex and fertile age on neuromyelitis optica spectrum disorders.

BACKGROUND: Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases. OBJECTIVE: To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)). METHODS: Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset. RESULTS: A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%; p < 0.001). Interval between onset and diagnosis of NMO/SD was longer in women than in men (mean 54 vs 27 months; p = 0.023). In women, attacks occurring ⩽40 years of age were more likely to show complete remission ( p = 0.003) and better response to high-dose intravenous steroids ( p = 0.005) compared to woman at >40 years. CONCLUSION: Our data suggest an influence of sex and age on susceptibility to AQP4-ab-positive NMO/SD. Genetic and hormonal factors might contribute to pathophysiology of NMO/SD.

Variations in multiple sclerosis practice within Europe - Is it time for a new treatment guideline?

In the past 5 years, the combination of developments in diagnostic strategy and approval of new disease-modifying therapies has provided an opportunity to achieve dramatic improvements in patient outcomes in multiple sclerosis (MS). However, across Europe there are several factors that may prevent patients from receiving the best therapy at the appropriate time, and there is variation among countries in terms of which of these factors are most relevant. Here, we review current MS clinical practices in a number of countries in the European Union to identify differences regarding initiation of treatment in patients with clinically isolated syndrome or relapsing-remitting MS, and differences in the timing of treatment switch or escalation. While recognizing that policy is not static in any country, we believe that patients' interests would be better served if a European treatment guideline was developed. Such a guideline could both inform and be informed by national policies, facilitating the dissemination of best clinical practice internationally.

Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses.

OBJECTIVE: Neuromyelitis optica (NMO) attacks often are severe, are difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks. METHODS: A retrospective review was made of patient records to assess demographic/diagnostic data, attack characteristics, therapies, and the short-term remission status (complete remission [CR], partial remission [PR], no remission [NR]). Inclusion criteria were NMO according to Wingerchuk's 2006 criteria or aquaporin-4 antibody-positive NMO spectrum disorder (NMOSD). Remission status was analyzed with generalized estimating equations (GEEs), a patient-based statistical approach. RESULTS: A total of 871 attacks in 185 patients (142 NMO/43 NMOSD, 82% female) were analyzed. The 1,153 treatment courses comprised high-dose intravenous steroids (HD-S; n = 810), plasma exchange (PE; n = 192), immunoadsorption (IA; n = 38), other (n = 80), and unknown (n = 33) therapies. The first treatment course led to CR in 19.1%, PR in 64.5%, and NR in 16.4% of attacks. Second, third, fourth, and fifth treatment courses were given in 28.2%, 7.1%, 1.4%, and 0.5% of attacks, respectively. This escalation of attack therapy significantly improved outcome (p < 0.001, Bowker test). Remission rates were higher for isolated optic neuritis versus isolated myelitis (p < 0.001), and for unilateral versus bilateral optic neuritis (p = 0.020). Isolated myelitis responded better to PE/IA than to HD-S as first treatment course (p = 0.037). Predictors of CR in multivariate GEE analysis were age (odds ratio [OR] = 0.97, p = 0.011), presence of myelitis (OR = 0.38, p = 0.002), CR from previous attack (OR = 6.85, p < 0.001), and first-line PE/IA versus HD-S (OR = 4.38, p = 0.006). INTERPRETATION: Particularly myelitis and bilateral optic neuritis have poor remission rates. Escalation of attack therapy improves outcome. PE/IA may increase recovery in isolated myelitis.

Basal Pain Sensitivity does not Predict the Outcome of Multidisciplinary Chronic Pain Treatment.

OBJECTIVES: Individual differences in underlying, "basal" pain sensitivity are large and have clinical implications. Some studies have suggested that basal pain sensitivity may also predict the outcome of pain treatment. Multidisciplinary chronic pain management programs are effective, but treatment success is individually very different. Therefore, identification of predictors of treatment success is important. This study investigated if basal pain sensitivity predicted the outcome of a 4-week outpatient multidisciplinary pain management program. DESIGN: Cohort study. SETTING: Chronic pain outpatient clinic at the Department of Anesthesiology, Intensive Care Medicine and Pain Therapy of the University of Münster. METHODS: Basal pain sensitivity was measured at treatment onset, using comprehensive experimental pain testing (thermal, pressure, and pinprick pain) and the pain sensitivity questionnaire. Primary (clinical pain intensity) and secondary (depression, anxiety, pain-related disability) outcome parameters were assessed at treatment start, at discharge and 6 months later. SUBJECTS: Sixty five adult chronic pain patients with mixed pain diagnoses. RESULTS: There were significant improvements in clinical pain intensity (from 6.1 ± 2.0 to 5.1 ± 1.8 [0-10]), depression and anxiety at discharge (all P < 0.001) and of clinical pain intensity (to 5.3 ± 2.3 [0-10]) and pain-related disability at 6 months (all P < 0.05). However, treatment outcome was not predicted by any of the basal pain sensitivity measures. DISCUSSION: Results show that basal pain sensitivity is not a reliable predictor of treatment outcome in mixed diagnosis multidisciplinary pain management programs, possibly due to the heterogeneity of patients enrolled in such programs. Clinically useful predictors of treatment success in this setting remain to be identified.

Temporal retinal nerve fibre layer thinning in cluster headache patients detected by optical coherence tomography.

BACKGROUND: The exact pathophysiology of cluster headache (CH) is still not fully clarified. Various studies confirmed changes in ocular blood flow during CH attacks. Furthermore, vasoconstricting medication influences blood supply to the eye. We investigated the retina of CH patients for structural retinal alterations with optical coherence tomography (OCT), and how these changes correlate to headache characteristics, oxygen use and impaired visual function. METHODS: Spectral domain OCT of 107 CH patients - 67 episodic, 35 chronic, five former chronic sufferers - were compared to OCT from 65 healthy individuals. Visual function tests with Sloan charts and a substantial ophthalmologic examination were engaged. RESULTS: Reduction of temporal and temporal-inferior retinal nerve fibre layer (RNFL) thickness was found in both eyes for CH patients with a predominant thinning on the headache side in the temporal-inferior area. Chronic CH patients revealed thinning of the macula compared to episodic suffers and healthy individuals. Bilateral thinning of temporal RNFL was also found in users of 100% oxygen compared to non-users and healthy controls. Visual function did not differ between patients and controls. DISCUSSION: Our OCT findings show a systemic effect causing temporal retinal thinning in both eyes of CH patients possibly due to attack-inherent or medication-induced frequent bilateral vessel diameter changes. The temporal retina with its thinly myelinated parvo-cellular axons and its more susceptible vessels for the vasoconstricting influence of oxygen inhalation seems to be predisposed for tissue damage-causing processes related to CH.

Contact heat evoked potentials and habituation measured interictally in migraineurs.

BACKGROUND: A lack of habituation of different evoked potential modalities in migraine patients in-between attacks has been suggested. METHODS: This study investigates cortical response after painful stimuli evaluated by contact heat evoked potentials (CHEPs) and quantitative sensory testing (QST) during the migraine-free interval. We enrolled 22 migraine patients and 22 healthy subjects. RESULTS: Cortical potentials after contact heat stimulation of the cheeks and the volar forearm at a temperature of 51°C showed significantly reduced A-δ-amplitudes in patients and healthy controls. When the subjects' attention was drawn to an arithmetic task, a partial lack of habituation of amplitude could be seen in migraine patients. QST did not show any difference between migraineurs and controls. CONCLUSION: Our findings can be primarily deemed to demonstrate that patients and healthy controls show significantly lower amplitudes while performing the calculation task. Without performing the calculation task we could not show the expected lack of habituation in migraineurs. Yet, while performing the calculation task our results partly suggest that hypothesis.

Cutaneous sensory function is not related to depression and anxiety in patients with chronic pruritus with dysesthetic subqualities.

The objective of this study was to examine the subgroup of patients with chronic pruritus with dysesthetic subqualities for the presence of psychiatric comorbidities and to evaluate whether anxiety and depression make a difference in perception of somatosensory stimuli in quantitative sensory testing (QST). Forty-nine patients underwent routine diagnostics, a standardised QST testing battery, a psychosomatic evaluation for psychic comorbidities and filled out 2 questionnaires: the Patient Health Questionnaire for the assessment of depressive mood and the State Trait Anxiety Inventory. Twenty-seven (55.1%) of the sample had at least one psychiatric comorbid diagnosis. QST parameters were not correlated to anxiety and depression levels. We conclude that psychosomatic evaluation should become part of routine diagnostics of these patients in order to detect and treat psychiatric comorbidity. However, research on somatosensory aspects in these patients seems not to be affected by the levels of anxiety and depression.

Multimodal retinal vessel analysis in CADASIL patients.

PURPOSE: To further elucidate retinal findings and retinal vessel changes in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients by means of high resolution retinal imaging. METHODS: 28 eyes of fourteen CADASIL patients and an equal number of control subjects underwent confocal scanning laser ophthalmoscopy (cSLO), spectral-domain optical coherence tomography (SD-OCT), retinal nerve fibre layer (RNFL) measurements, fluorescein and indocyanine angiography. Three vessel measurement techniques were applied: RNFL thickness, a semiautomatic software tool based on cSLO images and manual vessel outlining based on SD-OCT. RESULTS: Mean age of patients was 56.2 ± 11.6 years. Arteriovenous nicking was present in 22 (78.6%) eyes and venous dilation in 24 (85.7%) eyes. Retinal volume and choroidal volume were 8.77 ± 0.46 mm(3) and 8.83 ± 2.24 mm(3). RNFL measurements showed a global increase of 105.2 µm ( CONTROL GROUP: 98.4 µm; p = 0.015). Based on semi-automatic cSLO measurements, maximum diameters of arteries and veins were 102.5 µm (106.0 µm; p = 0.21) and 128.6 µm (124.4 µm; p = 0.27) respectively. Manual SD-OCT measurements revealed significantly increased mean arterial 138.7 µm (125.4 µm; p<0.001) and venous 160.0 µm (146.9; p = 0.003) outer diameters as well as mean arterial 27.4 µm (19.2 µm; p<0.001) and venous 18.3 µm (15.7 µm; p<0.001) wall thicknesses in CADASIL patients. CONCLUSIONS: The findings reflect current knowledge on pathophysiologic changes in vessel morphology in CADASIL patients. SD-OCT may serve as a complementary tool to diagnose and follow-up patients suffering from cerebral small-vessel diseases.

Current perspectives on interferon Beta-1b for the treatment of multiple sclerosis.

Interferon (IFN) beta-1b was the first disease-modifying therapy to be approved for the treatment of multiple sclerosis (MS), and over 21 years of follow-up data demonstrate its efficacy and long-term safety profile. Following recent regulatory approvals in the USA and European Union, IFN beta-1b is now one of the seven disease-modifying therapies [intramuscular IFN beta-1a; subcutaneous (SC) IFN beta-1a; IFN beta-1b SC; glatiramer acetate SC; oral dimethyl fumarate; oral teriflunomide; and intravenous alemtuzumab] indicated for first-line use in relapsing-remitting MS. Here we review the clinical trial and follow-up data for IFN beta-1b and discuss factors that clinicians may consider when selecting this treatment, both at first line in early MS, and later in the disease course.

Vessel labeling in combined confocal scanning laser ophthalmoscopy and optical coherence tomography images: criteria for blood vessel discrimination.

INTRODUCTION: The diagnostic potential of optical coherence tomography (OCT) in neurological diseases is intensively discussed. Besides the sectional view of the retina, modern OCT scanners produce a simultaneous top-view confocal scanning laser ophthalmoscopy (cSLO) image including the option to evaluate retinal vessels. A correct discrimination between arteries and veins (labeling) is vital for detecting vascular differences between healthy subjects and patients. Up to now, criteria for labeling (cSLO) images generated by OCT scanners do not exist. OBJECTIVE: This study reviewed labeling criteria originally developed for color fundus photography (CFP) images. METHODS: The criteria were modified to reflect the cSLO technique, followed by development of a protocol for labeling blood vessels. These criteria were based on main aspects such as central light reflex, brightness, and vessel thickness, as well as on some additional criteria such as vascular crossing patterns and the context of the vessel tree. RESULTS AND CONCLUSION: They demonstrated excellent inter-rater agreement and validity, which seems to indicate that labeling of images might no longer require more than one rater. This algorithm extends the diagnostic possibilities offered by OCT investigations.

Natalizumab use during the third trimester of pregnancy.

IMPORTANCE: Natalizumab reduces multiple sclerosis relapses very effectively; however, severe disease activity may return once natalizumab treatment is withdrawn, as recommended during pregnancy. Sometimes restarting natalizumab treatment may be the best option for the mother, but the consequences for the infant are unknown. Except for a few single case reports, to our knowledge, comprehensive data about third-trimester natalizumab exposure are scant. OBSERVATIONS: In a case series of 12 women with 13 pregnancies and highly active multiple sclerosis who were treated with natalizumab during their third trimester of pregnancy, we assessed the clinical and laboratory effects on the newborns. We observed mild to moderate hematologic alterations in 10 of 13 infants including thrombocytopenia and anemia. In a subsample of 5 mother-child pairs, we analyzed natalizumab levels in the umbilical cord blood. Natalizumab was detectable in all 5 newborns. CONCLUSION AND RELEVANCE: Natalizumab can be a therapeutic option in patients with highly active multiple sclerosis during pregnancy. We recommend that a pediatrician be available at the time of delivery to evaluate for potential complications of anemia and thrombocytopenia in newborns exposed to natalizumab during the third trimester.