Susan Kweskin

A new class of injectable monoclonal antibodies directed against calcitonin gene related peptide (CGRP) or its receptor may offer hope to migraineurs who have not found effective prophylactic therapy.

CGRP is a key neuropeptide in the pathophysiology of migraines. Four CGRP inhibitors are currently competing for FDA approval for migraine prevention:

(co-developed by Amgen and Novartis)    


(Teva)                                               


(Eli Lilly)                                             


 (Alder Biopharmaceuticals)                   

Details about these agents can be found in this 

Erenumab binds the CGRP receptor; the others bind the CGRP ligand itself.

, supported by Novartis Pharma AG, will be presented on Wednesday, April 25, at the 

This study included 246 people who had episodic migraine; participants were given injections of either 140 mg of erenumab or a placebo once a month for 3 months. Just over a third of the participants had been treated unsuccessfully with 2 other medications, another third with 3 medications, and a quarter with 4 drugs. Participants experienced an average of 9 migraines a month and used an acute migraine drug 5 times a month.

After 3 months, the erenumab recipients were nearly 3 times more likely to have 50% or more fewer migraine days than placebo recipients; and 30% of those treated with erenumab had half the number of headaches vs 14% in the placebo group. Safety and tolerability of the active drug were similar to those of placebo.

In a statement to the press, study author Uwe Reuter, MD, of The CharitÃ© – University Medicine Berlin in Germany noted, “Our results show that people who thought their migraines were difficult to prevent may actually have hope of finding pain relief. More research is now needed to understand who is most likely to benefit from this new treatment.”

A limitation of the study is its relatively short length of 3 months. More research is needed to determine whether benefits continue.

More information about migraine is available from the 

1. Hackethal V.  CGRP inhibitors reduce migraine frequency, disability. 

Articles

CGRPs: New Help in Migraine Prophylaxis?

Newly approved treatments for several neurologic disorders-including various types of pain, generalized myasthenia gravis, and Parkinson Disease-will be topics of discussion at AAN 2018. Here’s a brief overview of those medications FDA approved within the past 6 months.

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Newly approved medications for various types of pain, generalized myasthenia gravis, and Parkinson disease will be fodder for discussion at AAN 2018. Here’s a brief overview of the therapies the FDA has approved within the past 6 months.

6 New Drugs for Neurologists 

In the last year, the FDA has approved a number of drugs for a variety of neurologic disorders. Here are 8 of the most recent.

The FDA has recently approved a number of drugs for a variety of neurologic disorders, including Parkinson's disease and MS. Here are 8 of the newest.

8 New FDA-Approved Neurology Drugs

Parlez vous francais? Sprechen-sie deutsch? How's your Spanish?

Good news coming out of the University of Ghent for bilingual people: researchers there found evidence to support findings that 

bilingualism contributes to cognitive reserve

 and can postpone symptoms of dementia.

Woumans and colleagues

evaluated 69 monolingual patients and 65 bilingual patients with probable Alzheimer disease (AD) who came to 2 university hospitals in Belgium between March 2013 and May 2014. These researchers determined the age at which AD manifested and was diagnosed in patients in both language groups.

The result? AD manifested itself significantly later in bilinguals -- by 4.6 years. And diagnosis came 4.8 years later than in monolingual patients. In monolinguals, the average ages of AD manifestation and diagnosis were 71.5 and 72.5 years, respectively: in comparison, the average ages in bilinguals were 76.1 and 77.3 years.

When processing a given language, write the authors,"other known, irrelevant languages always get active to a certain degree, and influence processing of the relevant language. This constant competition requires considerable cognitive control specifically imposed on bilinguals." They continue, "Consequently, there are now strong claims that bilinguals show better executive functions and even increased brain plasticity. It is this enhanced executive functioning and plasticity that is assumed to lead to more cognitive reserve in older bilingual adults."

1.Woumans E, Santens P, Sieben A, et al. Bilingualism delays clinical manifestation of Alzheimer’s disease. 

A new study bolsters evidence that bilingualism contributes to cognitive reserve, postpones symptoms of dementia, and delays diagnosis of Alzheimer disease.

Bilingualism Postpones Dementia and Alzheimer

In just 6 weeks -between July 1, 2014 and August 12, 2014 -pubmed posted abstracts of 641 clinical studies on multiple sclerosis. 92 of those abstracts are in English and are accompanied by full text articles.

Only a few of these articles make the headlines. And with the blizzard of publications, the noteworthy and clinically useful information in many of the unsung studies is likely to go unnoticed.

What follows is a brief synopsis of 2 articles that we randomly culled from pubmed-with full text and links - that we thought want to know about, but which you might easily miss.

In coming days, we’ll comb through other recently published articles on MS that may not have made the headlines and will offer synopses here.

HIV and lower risk of multiple sclerosis: beginning to unravel a mystery using a record-linked database study.

 Even though MS and HIV infection are among the two best documented diseases in medicine, there is only a single report of a patient with MS who had been receiving antiretroviral therapy for HIV infection. MS symptoms "resolved completely" for 12 years in this patient immediately after combination antiretroviral therapy was started. Because MS has been linked to human endogenous retroviruses, the authors of the case report hypothesized that antiretroviral HIV therapy may have served as serendipitous Rx for the patient’s MS.

Subsequent studies followed, including the current study by Gold and colleagues,

 who used one of the world’s largest data sets to study the possible link between HIV and MS.

 In their cohort of 21,207 HIV-positive patients and 5,298,496 controls, Gold and colleagues found HIV infection to be associated with a significantly decreased risk of MS. The rate ratio of MS in people with HIV, relative to those without HIV, was 0.38 (95% CI 0.15 to 0.79).

Mechanisms of this observed possibly protective association may include immunosuppression induced by chronic HIV infection and antiretroviral medications. The authors write that if subsequent studies demonstrate that HIV and/or its treatment has a protective effect, “this would be the largest protective effect of any factor yet observed in relation to the development of MS.”

Cognitive Dysfunction in Pediatric Multiple Sclerosis

 Only about 2% to 5% of patients with MS are children or adolescents. The presentation and course of pediatric and adult MS may differ, especially if the onset is at a younger age. Whether the differences are a function of disease pathophysiology or whether the disease processes are expressed on a different substrate (an immature CNS and immune system) is unclear.

These authors did a comprehensive literature review to elucidate differences in pediatric and adult MS.

. Conceptual reasoning is not usually impaired

. Executive functions are more commonly affected (eg, attention deficits, organization, memory)

. Math skills may be vulnerable, despite an average IQ

. Cognitive dysfunctions often appear early in the disease’s course, close to MS diagnosis

. Patterns of MRI lesion distribution differ slightly, possibly due to incomplete myelination

Bottom line: The data suggest that deficits occur early and affect quality of life.  Failure to show age-expected progress is considered a sign of MS progression.

1. Gold J, Goldacre R, Maruszak H, et al. 

2. Suppiej A, Cainelli E. Cognitive dysfunction in pediatric multiple sclerosis. 

Out of the blizzard of recently published clinical studies on multiple sclerosis, we've randomly selected 2 with useful information you might not want to -- but easily could -- miss. Here: brief synopses and links.

What’s New in Multiple Sclerosis? 

Reversible Coma in a Young Postpartum Woman

A 22-year-old woman presented at 36 weeks of gestation with a 1-day history of mild headache, blurred vision, and epigastric pain. She was admitted for severe preeclampia with signs of early labor. Treatment with magnesium sulfate and IV labetolol was started. During labor, however, she experienced multiple generalized tonic clonic seizures. Despite a normal vaginal delivery, she remained postictal.

Neurologic exam was notable for withdrawal of all 4 extremities to painful stimuli. Pupils were mid-position fixed and deep tendon reflexes were 2+ with extensor plantar response bilaterally. She had decorticate posturing. IV levetiracetam was started, and she was transferred to the ICU. Brain CT without contrast showed marked diffuse vasogenic cerebral edema (

). It also showed partial bilateral uncal herniation and effacement of the suprasellar cistern. Bilateral low attenuation of frontal and occipital lobes was noted. This was most likely the result of marked edema presumed to be related to posterior reversible encephalopathy syndrome (PRES).

The development of focal neurologic deficits postpartum is uncommon. Differential diagnoses include seizures, posterior circulation stroke, cerebral venous thrombosis, complicated migraine, eclampsia, encephalitis, vasculitis, cerebral artery dissection, and PRES.

The reported incidence of PRES is approximately 0.01%. PRES is a cliniconeuroradiologic entity. Clinical features include headache, confusion, seizures, cortical visual disturbances, and altered metal status. Radiologic findings include bilateral white and gray matter changes that predominantly affect the posterior cerebral hemispheres. Common causes include hypertension, preeclampsia/eclampsia, uremia, immunosuppressive drugs, transplantation, and SLE.

Eclamptic patients with atypical features such as focal neurologic deficits, markedly depressed mental status, and profound visual disturbances should be evaluated by neuroimaging. CT in this setting may help differentiate PRES from stroke. PRES is a reversible syndrome with excellent recovery in most patients within a few weeks. Early and accurate diagnosis helps ensure optimal outcomes.

Case and photo courtesy of Ranjita Pallavi, MD and Hossam Amin, MD.

For discussion and more details, please click here. .

Patent Foramen Ovale and Paradoxical Stroke in a Young Cyclist

A 42-year-old man presented to the ED after multiple episodes of difficulty in speaking. For 24 hours, he had been unable to formulate his speech for 1 to 2 minutes per episode but was aware of what he wanted to say. He had experienced a similar episode 2 weeks earlier when he lost the ability to verbalize his thoughts for nearly 5 minutes. Three years earlier, he had a DVT that was treated with anticoagulation.

CT angiography of the head was unremarkable and MRA of the neck with contrast found no signs of stenosis, thrombosis, or dissection. Subsequent MRI of the brain with contrast indicated a subacute infarct. An ID workup was normal and ruled out focal encephalitis. MRI spectroscopy verified an ischemic infarct (

). Additional studies to identify the cause of infarct included TEE, which showed a patent foramen ovale (PFO) (

). Lower extremity venous Doppler ultrasonography was negative for DVT.

PFO is not considered a primary cause of stroke. Cardioembolic events account for 19% and carotid disease accounts for 15% of ischemic strokes; the remainder are cryptogenic. Approximately 40% of cryptogenic ischemic strokes are attributed to PFO. PFO can be detected in 10% to 15% of the population by transthoracic echocardiogram.

A number of pathologic manifestations of PFO have been recently identified, including paradoxical systemic embolism. Neurologic decompression illness and migraine with aura also have been associated with PFO but are not common findings. Most patients with PFO remain asymptomatic because under normal physiologic conditions, PFO allows a small amount of left-to-right shunting without causing significant hemodynamic change. Consequently, neurologic deficits associated with PFO are rare.

A 39-year-old woman presented with a 2-month history of progressively worsening headache and right-sided ataxia. She had no significant past medical history and took no medications. Neurologic examination revealed mild dysmetria, and dysdiadochokinesia on the right side. Motor power was grade 5/5 for all extremities. Pain perception and proprioception were intact. MRI of the brain demonstrated a 4.5-cm, non-enhancing, T1 hypointense mass on the right cerebellar hemisphere (

), a finding consistent with Lhermitte-Duclos disease. Histopathology following surgical resection of the mass confirmed this diagnosis.

Also known as dysplastic gangliocytoma of the cerebellum, LDD is a rare, slow-growing, hamartomatous tumor of the cerebellar cortex. It is often asymptomatic in early life but usually becomes clinically apparent in the third and fourth decades. Its manifestations are usually related to a posterior fossa mass-effect and the secondary obstructive hydrocephalus that follows. The most frequent complaints are headaches and ataxia. Cerebellar signs and symptoms are seen in roughly half of patients and may be present for years before diagnosis. One-third of patients have associated cranial nerve palsies and long tract dysfunction. Less commonly presenting features are visual problems, neck stiffness, vertigo, and subarachnoid hemorrhage.

LDD has been linked in 40% of cases to Cowden syndrome. Because of this association, concomitant malignancies, particularly breast and pelvic cancers, need to be excluded.

Case and image courtesy of Wikrom Warunyuwong, MD and colleagues

A 47-year-old man who chronically abused cocaine and alcohol presented with a 3-day history of right-sided weakness and numbness. CT scan of the brain showed a left anterior cerebral artery ischemic stroke.

Examination revealed right facial weakness; motor strength was 4/5 in the right upper extremity and 3/5 in the right lower extremity. Initial lab results were unremarkable. The patient was admitted for observation and later transferred for inpatient rehabilitation, when he became aphasic and lethargic. A second CT brain scan showed a bilateral corpus callosum lesion (

Bilateral strokes of the corpus callosum are uncommon because of the rich blood supply of this structure from 3 main arterial systems-the anterior communicating, anterior cerebral, and posterior cerebral arteries. Also, the corpus callosum is a dense white matter tract, which makes it less sensitive to ischemic injury than gray matter. Moreover, the penetrating arteries of corpus callosum run perpendicular to the parent artery, thus protecting it from emboli.

Corpus callosum infarcts may present acutely or with slowly evolving and non-localizing neurologic signs and symptoms that suggest the diagnosis of tumor rather than infarct. They may exhibit radiologic features more often associated with neoplasm (eg, mass-like enhancement or extension across the midline) that prompt further radiologic imaging, such as MRI or MRA, and in some cases even a brain biopsy for definitive diagnosis.

Biopsy may be avoided if clinicians are aware of this entity and use various radiographic studies such as diffusion-weighted imaging, perfusion imaging, magnetic resonance spectroscopy, and MRA to better delineate the lesions. Keep bilateral corpus callosum stroke in the differential diagnosis of bilateral lesions detected on radiologic imaging in patients who have bilateral neurologic features.

Case and images courtesy Ranjita Pallavi, MD and Shobhana Chaudhari, MD.

Relapsing-remitting Multiple Sclerosis as Seen on MRI

Serial axial T2-weighted (top row) and post-contrast T1-weighted (bottom row) spin-echo MRIs of brain performed at baseline, month 1, and month 2, in a patient with relapsing-remitting MS. Multiple hyperintense lesions, which suggest multifocal white-matter pathology, are visible on T2-weighted image at baseline. On post-contrast T1-weighted examination, some of these lesions are contrast-enhanced, which indicates local disruption of blood–brain barrier. New contrast-enhancing lesions can be observed at month 1 and month 2, which indicate dissemination of disease.

MRI has become central to the diagnosis of MS. Roughly 90% of all MS diagnoses are now based on MRI findings, because of the modality’s high sensensitivy to inflammation and demyelinating plaques.

An unusual cause of postpartum neurologic deficits: MRIs of progressing relapsing-remitting MS; Lhermitte-Duclos disease as a cause of ataxia: here. . . 5 short clinical cases, each with images, that offer take-home messages you can use in your practice.