Neurology Commons^™

Preventive Treatment Of Migraine, Stephen Silberstein

Department of Neurology Faculty Papers

Migraine is a common episodic pain disorder, the treatment of which can be acute to stop an attack or preventive to reduce the frequency, duration or severity of attacks. Preventive treatment is used when attacks are frequent or disabling. Many different medication groups are used for preventive treatment, including β-blockers, antidepressants and antiepileptic drugs. Their mechanisms of action include raising the threshold to migraine activation, enhancing antinociception, inhibiting cortical spreading depression, inhibiting peripheral and central sensitization, blocking neurogenic inflammation and modulating sympathetic, parasympathetic or 5-HT tone. In this article, I review evidence of the effectiveness of migraine preventive drugs. I …

Botulinum Toxin Type A In The Prophylactic Treatment Of Chronic Tension-Type Headache: A Multicentre, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study, Stephen D. Silberstein, H. Göbel, R. Jensen, A. H. Elkind, R. Degryse, J. M.C.M. Walcott, C. Turkel

Department of Neurology Faculty Papers

We studied the safety and efficacy of 0 U, 50 U, 100 U, 150 U (five sites), 86 Usub and 100 Usub (three sites) botulinum toxin type A (BoNTA; BOTOX); Allergan, Inc., Irvine, CA, USA) for the prophylaxis of chronic tension-type headache (CTTH). Three hundred patients (62.3% female; mean age 42.6 years) enrolled. For the primary endpoint, the mean change from baseline in the number of TTH-free days per month, there was no statistically significant difference between placebo and four BoNTA groups, but a significant difference favouring placebo vs. BoNTA 150 was observed (4.5 vs. 2.8 tension headache-free days/month; P …

Comparison Of Dynamic (Brush) And Static (Pressure) Mechanical Allodynia In Migraine, C. Lopinto, W. B. Young, Avi Ashkenazi

Department of Neurology Faculty Papers

Allodynia has been described in migraine but has not been fully investigated for the different sensory modalities. The aim of this study was to compare the prevalence of dynamic (brush) and static (pressure) mechanical allodynia in migraine patients and to suggest a practical method of testing them in a clinical setting. Patients with International Headache Society-defined episodic migraine (EM) or with transformed migraine (TM) as defined by Silberstein and Lipton were prospectively recruited from the Jefferson Headache Center out-patient clinic. A questionnaire of migraine features and symptoms of allodynia was administered. Brush allodynia (BA) was tested by cutaneous stimulation with …

Light During Darkness And Cancer: Relationships In Circadian Photoreception And Tumor Biology, Samar A. Jasser, David E. Blask, George C. Brainard

Department of Neurology Faculty Papers

The relationship between circadian phototransduction and circadian-regulated processes is poorly understood. Melatonin, commonly a circadian phase marker, may play a direct role in a myriad of physiologic processes. The circadian rhythm for pineal melatonin secretion is regulated by the hypothalamic suprachiasmatic nucleus (SCN). Its neural source of light input is a unique subset of intrinsically photosensitive retinal ganglion cells expressing melanopsin, the primary circadian photopigment in rodents and primates. Action spectra of melatonin suppression by light have shown that light in the 446–477 nm range, distinct from the visual system’s peak sensitivity, is optimal for stimulating the human circadian system. …

Zonisamide For Migraine Prophylaxis In Refractory Patients, Avi Ashkenazi, Adam Benlifer, Jason Korenblit, Stephen D. Silberstein

Department of Neurology Faculty Papers

Zonisamide, a new antiepileptic drug, has been approved in the US as adjunctive therapy for the treatment of partial seizures in adults.^1,2 Chemically a sulfonamide analogue, zonisamide is thought to have several mechanisms of action, including a rate-dependent blockade of voltage-gated sodium channels and reduction of ion flow through T-type calcium channels.^3-5 It is also a weak carbonic anhydrase inhibitor. Zonisamide has a favorable pharmacokinetic profile that includes high oral bioavailability and a long half life (63 hours), permitting a once- or twice-daily dosing regimen.⁶

There are only a limited number of current migraine preventive medications that …

Brain Neprilysin Activity And Susceptibility To Transgene-Induced Alzheimer Amyloids, Troy L. Carter, Steve Pedrini, Jorge Ghiso, Michelle E. Ehrlich, Sam Gandy

Department of Neurology Faculty Papers

Neprilysin (NEP) is a zinc metalloproteinase that degrades enkephalins, endothelins, and the Alzheimer’s disease amyloid ß (Aß) peptides. NEP-deficient mice possess increased levels of brain Aß^1-40 and Aß^1-42. The objective of this study was to determine whether tissue NEP specific activity differs according to age and/or across mouse strains, especially those strains predisposed toward formation of Aß-amyloid plaques following overexpression of the human Alzheimer amyloid precursor protein (APP). The C57Bl/6J mouse strain appears to be relatively susceptible to cerebral amyloidosis, whereas the Swiss Webster (SW) strain appears more resistant. We investigated whether NEP specific activity in brain …

The Effects Of Greater Occipital Nerve Block And Trigger Point Injection On Brush Allodynia And Pain In Migraine, Avi Ashkenazi, William B. Young

Department of Neurology Faculty Papers

Objective: To evaluate the effect of GONB, with or without trigger point injection (TPI), on dynamical mechanical (brush) allodynia (BA) and on head pain in migraine.

Background: Patients with migraine often have cutaneous allodynia, which is related to sensitization of central pain neurons. Greater occipital nerve block (GONB) is an effective treatment for migraine headache, however its effect on cutaneous allodynia in migraine is unknown.

Methods: We studied patients with migraine and BA who were treated with GONB with or without TPI. Demographic data, migraine history and headache features were documented. Allodynia was evaluated using a structured …

Involvement Of Beta-Chemokines In The Development Of Inflammatory Demyelination., Ileana Banisor, Thomas P Leist, Bernadette Kalman

Department of Neurology Faculty Papers

The importance of beta-chemokines (or CC chemokine ligands - CCL) in the development of inflammatory lesions in the central nervous system of patients with multiple sclerosis and rodents with experimental allergic encephalomyelitis is strongly supported by descriptive studies and experimental models. Our recent genetic scans in families identified haplotypes in the genes of CCL2, CCL3 and CCL11-CCL8-CCL13 which showed association with multiple sclerosis. Complementing the genetic associations, we also detected a distinct regional expression regulation for CCL2, CCL7 and CCL8 in correlation with chronic inflammation in multiple sclerosis brains. These observations are in consensus with previous studies, and add new …

Referred Cutaneous Allodynia In A Migraine Patient Without Simultaneous Headache, Avi Ashkenazi, Carla Lopinto, William B. Young

Department of Neurology Faculty Papers

Cutaneous allodynia is defined as the perception of pain when a non-noxious stimulus is applied to normal skin. This phenomenon has been demonstrated in migraine patients during an acute attack. It is thought to result from central sensitization of neurons in the trigemino-vascular system and may spread to areas beyond that of the referred head pain.

In a recent study, migraine patients demonstrated increased temporal summation to painful mechanical stimuli in their referred head pain area between attacks. This suggests that changes in physiologic properties of nociceptive neurons may occur in migraine patients between attacks.

We describe a migraine patient …

Periodic Autonomic Dysfunction Without Pain In A Patient With Cluster Headache, Avi Ashkenazi, Stephen Silberstein

Department of Neurology Faculty Papers

Cluster headache (CH) is characterized by episodes of severe unilateral headache accompanied by symptoms of cranial parasympathetic hyperactivity and sympathetic dysfunction that occur in cluster periods. Positron emission tomography (PET) studies have demonstrated evidence of a central generator of CH attacks located in the posterior-inferior hypothalamus. It has been suggested that the autonomic symptoms in CH result from reflex activation of the superior salivatory nucleus secondary to activation of the trigeminal nucleus caudalis (TNC). However, several cases of CH-like symptoms with no head pain have been documented.

We describe a patient who had suffered from typical episodic CH for two …

Dynamic Mechanical (Brush) Allodynia In Cluster Headache, Avi Ashkenazi, William B. Young

Department of Neurology Faculty Papers

Cutaneous allodynia is the perception of pain when a non-noxious stimulus is applied to normal skin. It has been described in patients with migraine. Cutaneous allodynia is caused by sensitization of central nervous system neurons that receive convergent sensory input from both skin and intracranial structures. This phenomenon has not been previously described in patients with cluster headache. Although migraine and cluster headache (CH) may share some clinical features, the pathogenesis of these two primary headaches is different. The aim of this study was to examine the occurrence of dynamic mechanical (brush) allodynia (BA) in patients with CH.

Occipital Nerve Block Rapidly Eliminates Allodynia Far From The Site Of Headache: A Case Report, William B. Young, Valentin Mateos, Avi Ashkenazi

Department of Neurology Faculty Papers

Seventy to 80% of persons with migraine develop allodynia during the course of a severe attack. During a migraine attack, allodynia spreads topographically to extratrigeminal territory. Dynamic mechanical allodynia, otherwise known as brush allodynia (BA), is a subtype of allodynia that is easily tested. Ashkenazi & Young recently reported on the immediate benefits of greater occipital nerve (GON) block on brush allodynia and pain in migraine and in cluster headache. In these studies, testing was performed at fixed sites in the trigeminal and cervical distributions. Allodynia in thoracic dermatomes was not studied.

Headache Management For The Pain Specialist, Avi Ashkenazi, Stephen Silberstein

Department of Neurology Faculty Papers

Headache is a common symptom caused by a wide variety of diseases. Primary headaches include migraine, cluster headache, tension-type headache and other less common diseases. It is important to differentiate these headaches from secondary headaches caused by vascular, neoplastic, infectious, metabolic and toxic disorders. Most primary headaches have a genetic basis, with environmental factors acting as triggers. Recent advances in basic research resulted in the development of more specific and effective therapies. Medication overuse headache is a very common cause of chronic daily headache. Detoxification from the offending drug is essential for headache improvement. Cervicogenic headache is common and needs …

Botulinum Toxin And Other New Approaches To Migraine Therapy, Avi Ashkenazi, Stephen Silberstein

Department of Neurology Faculty Papers

The number of migraine treatments and our understanding of migraine pathophysiology are both increasing. Newer treatments are focusing on migraine prevention. Botulinum toxin (BTX) is a potent neurotoxin that has been used primarily for diseases associated with increased muscle activity. Recently the toxin was found to have antinociceptive effects that are probably independent of its muscle-relaxant action. Recent clinical trials support the efficacy of BTX type-A (and possibly also type-B) in the treatment of migraine. The anticonvulsant topiramate was recently shown to be effective for migraine prevention. With the low doses used for this indication, cognitive side effects are less …

Mitochondrial Myopathy With Atypical Subacute Presentation, Oren Cohen, Israel Steiner, Zohar Argov, Avi Ashkenazi, Judith Diment, Ann Saada, Yaron River

Department of Neurology Faculty Papers

Mitochondrial myopathies usually have a chronic course of progressive limb weakness, exercise induced myalgia without muscle tenderness, and normal or only mildly raised serum creatine kinase. Acute or subacute presentation or exacerbation of nervous system signs is common in Leber's hereditary optic neuropathy (LHON) and in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), but has not been reported for muscle in mitochondrial diseases. We describe a patient who presented with rapidly progressive, subacute muscle weakness due to a mitochondrial disorder.