CSF Predicts Progression of MS

CSF can predict the future progression of multiple sclerosis (MS), according to a study published online ahead of print May 9 in the Journal of Neurology, Neurosurgery & Psychiatry. CSF and peripheral blood were obtained from patients with clinically isolated syndrome, relapsing-remitting MS, primary progressive MS, or other inflammatory or noninflammatory neurologic diseases who underwent elective diagnostic lumbar puncture. Patients without MS served as controls. CSF samples were analyzed for free and immunoglobulin-associated light chains on B cells and plasmablasts. Clinical follow-up duration was five years. There was an increased median CSF κ:λ free light chain in all groups except controls. This ratio predicted Expanded Disability Status Scale (EDSS) score progression at five years. Median EDSS score was lower among patients with high CSF κ:λ free light chain.

Rathbone E, Durant L, Kinsella J, et al. Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018 May 9 [Epub ahead of print].

First Anti-CGRP Monoclonal Antibody Gains FDA Approval

The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third study evaluated 667 patients with chronic migraine. Over three months, treated patients had, on average, 2.5 fewer monthly migraine days than controls. Aimovig is marketed by Amgen.

APOE Plays a Greater Role in Women Than in Men

There is a stronger association between APOE-ε4 and CSF tau levels among women than among men, according to a study published online ahead of print May 7 in JAMA Neurology. Investigators selected data from 10 longitudinal cohort studies of normal aging and Alzheimer’s disease. Biomarker analyses included CSF levels of β-amyloid 42, total tau, and phosphorylated tau. Of the 1,798 patients in the CSF biomarker cohort, 862 were women, 226 had Alzheimer’s disease, 1,690 were white, and the mean age was 70. Of the 5,109 patients in the autopsy cohort, 2,813 were women, 4,953 were white, and the mean age was 84. After correcting for multiple comparisons using the Bonferroni procedure, investigators observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau and phosphorylated tau.

Hohman TJ, Dumitrescu L, Barnes LL. Sex-specific association of apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol. 2018 May 7 [Epub ahead of print].

FDA Issues Warning About Lamictal

The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.

Is Tenecteplase Better Than Alteplase Before Thrombectomy?

When administered before thrombectomy, tenecteplase is associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset, according to a study published April 26 in the New England Journal of Medicine. Researchers randomly assigned patients with ischemic stroke and occlusion of the internal carotid, basilar, or middle cerebral artery who were eligible for thrombectomy to receive tenecteplase or alteplase within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the initial angiographic assessment. Of 202 patients enrolled, 101 were assigned to receive tenecteplase. The primary outcome occurred in 22% of the tenecteplase group and 10% of the alteplase group.

Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018;378(17):1573-1582.

FDA Approves Gilenya for Pediatric Use

The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.

Lifestyle Factors at Midlife Could Influence Dementia Risk

Demographic and lifestyle factors assessed in midlife could potentially modify the risk of dementia in late adulthood, according to a study published in the March issue of Journal of Alzheimer’s Disease. Researchers used data collected from 1979 until 1983 in the Framingham Heart Study Offspring cohort to examine associations between lifestyle factors in midlife and late-life dementia. They examined the data with decision tree classifier and random forests analysis. Investigators then evaluated model performance by computing area under receiver operating characteristic (ROC) curve. Age was strongly associated with dementia. The analysis also identified widowed status, lower BMI, and less sleep at midlife as risk factors for dementia. The areas under the ROC curves were 0.79 for the decision tree and 0.89 for the random forest model.

Li J, Ogrodnik M, Kolachalama VB, et al. Assessment of the mid-life demographic and lifestyle risk factors of dementia using data from the Framingham Heart Study Offspring Cohort. J Alzheimers Dis. 2018;63(3):1119-1127.

DBS Device Approved for Refractory Epilepsy

The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.

Epilepsy Does Not Affect Women’s Fertility

In women without a history of infertility or related disorders, the likelihood of conceiving and having a live birth is no different between individuals with or without epilepsy, according to a study published online ahead of print April 30 in JAMA Neurology. Researchers examined data from the Women With Epilepsy: Pregnancy Outcomes and Deliveries study to compare fertility rates between women with and without epilepsy. The primary outcome was the proportion of women who achieved pregnancy within 12 months after enrollment. Of the 197 participants, 142 were white. Mean age was 31.9 among the 89 women with epilepsy and 31.1 among the 108 control women. Among women with epilepsy, 60.7% achieved pregnancy, compared with 60.2% among controls. Median time to pregnancy was similar between groups.

Pennell PB, French JA, Harden CL, et al. Fertility and birth outcomes in women with epilepsy seeking pregnancy. JAMA Neurol. 2018 Apr 30 [Epub ahead of print].

FDA Approves Treatment for CIDP

The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.

Sauna Bathing Reduces Stroke Risk

Frequent sauna bathing is associated with a reduced risk of stroke, according to a study published online ahead of print May 2 in Neurology. Researchers assessed baseline habits of sauna bathing in 1,628 adults between ages 53 and 74 (mean age, 62.7) without a known history of stroke. The following sauna bathing frequency groups were defined: once per week, two to three times per week, and four to seven times per week. During a median follow-up of 14.9 years, 155 incident stroke events were recorded. Compared with people who took one sauna bath per week, the risk of stroke was 14% lower among people with two to three sessions and 61% lower among people with four to seven sessions. Controlling for stroke risk factors did not alter the association.

Kunutsor SK, Khan H, Zaccardi F, et al. Sauna bathing reduces the risk of stroke in Finnish men and women: a prospective cohort study. Neurology. 2018 May 2 [Epub ahead of print].

—Kimberly Williams
and Glenn Williams

New and Noteworthy Information—June 2018