Migraines Hurt Your Head but Not Your Brain



The exact cause of migraines is still not well understood, but the problem is considered to be 1) ___ (related to the nervous system). It is believed that brain chemicals, blood vessels, and nerves of the brain are involved. Migraines currently affect about 20% of the female population, and while these headaches are common, there are many unanswered questions surrounding this complex disease. Previous studies have linked this disorder to an increased risk of stroke and structural brain lesions, but it has remained unclear whether migraines had other negative consequences such as dementia or cognitive decline. According to new research from Brigham and Women’s Hospital (BWH), 2) ___ are not associated with cognitive decline. This study is published online by the British Medical Journal (BMJ) on August 8, 2012. “Previous studies on migraines and cognitive decline were small and unable to identify a link between the two. Our study was large enough to draw the conclusion that migraines, while painful, are not strongly linked to 3) ___ decline,” explained Pamela Rist ScD, a research fellow in the Division of Preventive Medicine at BWH, and lead author on this study.


The research team analyzed data from the Women’s Health Study, a cohort of nearly 40,000 women, 45 years and older. In this study, researchers analyzed data from 6,349 women who provided information about migraine status at baseline and then participated in cognitive testing during follow-up. Participants were classified into four groups: no history of migraine, migraine with aura (transient neurology symptoms mostly of the visual field), migraine without 4) ___, and past history of migraine. Cognitive testing was carried out in two year intervals up to three times.

“Compared with women with no history of migraine, those who experienced migraine with or without aura did not have significantly different rates of cognitive decline,” explained Rist. “This is an important finding for both physicians and patients. Patients with migraine and their treating doctors should be reassured that migraine may not have long term 5) ___ on cognitive function.”


There is still a lot that is unknown about migraines. However this study offers promising evidence for patients and their treating physicians. More research needs to be done to understand the consequences of migraine on the 6) ___ and to establish strategies to influence the course of the disease in order to optimize treatment strategies.


A migraine aura is a transient focal neurological phenomena that occurs before or during the 7) ___. They appear gradually over a number of minutes and generally last fewer than 60 minutes. Symptoms can be visual, sensory or motor in nature and many people experience more than one. Visual effects are the most common, occurring in up to 99% of cases and exclusively in more than half. Vision disturbances often consists of a scintillating 8) ___ (an area of partial alteration in the field of vision which flickers.) These typically start near the center of vision and then spread out to the sides with zigzaging lines which have been described to look like fortifications or walls of a castle. Usually the lines are in black and white but some people also see colored lines. Some people lose part of their field of vision known as hemianopsia while other experience blurring. Sensory aura are the second most common occurring in 30-40% of people with auras. Often a feeling of pins-and-9) ___ begins on one side in the hand and arm and spreads to the nose-mouth area on the same side. Numbness usually occurs after the tingling has passed with a loss of position sense. Other symptoms of the aura phase can include: speech or language disturbances, world spinning, and less commonly motor problems. Motor symptoms indicate that this is a hemiplegic migraine and weakness often last longer than one hour unlike other auras. Rarely an aura may occur without a subsequent headache, known as a 10) ___ migraine.


Migraine Aura – Scintillating Scotoma
ANSWERS: 1) neurological; 2) migraines; 3) cognitive; 4) aura; 5) consequences; 6) brain; 7) headache; 8) scotoma; 9) needles; 10) silent



The Head Ache, George Cruikshank (1819)



Migraine is not a new disease. Based on the symptoms, migraine appears to be one of the oldest recorded diseases. Conditions that have been linked to migraine were described in detail in Babylonian writings dating back to 3000 BC. Papyrus scrolls dated around 1550 BC have been found buried alongside a mummy in Thebes containing even more detailed accounts and are remarkably similar to the symptoms of modern migraine sufferers. Father of Medicine, Hippocrates, described what are clearly migraines in 460 BC, when he described a shining light that was typically seen in one eye and followed by severe pain that started in temples and worked its way to encompass the rest of the head and down into the neck. Hippocrates was the first to correlate head pain with exercise and intercourse. Hippocrates also attributed migraines to vapors making their way up to the head from the stomach and thought that the headache pain could be relieved by throwing up.


The Ebers Papyrus, named after George Ebers who discovered it, dating back to at least 1200 BC is an encyclopedic compilation of various prescriptions and medical treatments, including one for shooting pains in the head consistent with modern day migraine headaches. According to the instructions on the papyrus, Egyptians were to use a strip of linen to tie a clay crocodile holding grain in its mouth to the head of the patient. On the linen were written the names of those gods that the Egyptians believed could cure their ailments. As in so many things, the Egyptians may have been preternaturally aware of modern techniques because it is believed that this procedure could possibly have brought relief to the headache sufferer by compressing the scalp and collapsing the blood vessels that were causing the pain. At the very least it made more sense than the previous Egyptian cure for head pain, which was to simply rub a fried fish on the afflicted side of the head.


Plato thought that head pain was caused by people paying too much attention to the body; and that migraine sufferers complained about unreal pain. Aretaeus of Cappadocia is credited as the “discoverer” of migraines because of his second-century description of the symptoms of a unilateral headache associated with vomiting, with headache-free intervals in between attacks. Galenus of Pergamon used the term “hemicrania” (half-head), from which the word “migraine” derives. He thought there was a connection between the stomach and the brain because of the nausea and vomiting that often accompany an attack. For relief of migraine, Andalusian-born physician Abulcasis, also known as Abu El Qasim, suggested application of a hot iron to the head or insertion of garlic into an incision made in the temple.


Hua T’o was a Chinese surgeon in the second century who is given credit for the invention of anesthetic drugs. He was the first to use acupuncture needles to cure migraines. Hildegard of Bingen was a medieval nun and mystic who began experiencing visions at an early age. Her visions eventually led her to write several books on health and medicine and natural remedies. Both her written accounts and the illustrations she drew, reveal that those visions may have been the result of migraine auras. Her visions were detailed and vivid, as were her descriptions and she has built a significant following who consider her to be the first migraine-inspired artist. The typical treatment of migraines during the Middle Ages consisted of opium and vinegar solutions applied to the skull. The vinegar was thought to open the pores of the scalp so that the opium would be more quickly absorbed.


In the Middle Ages. migraine was recognized as a discrete medical disorder. Followers of Galenus explained migraine as being caused by aggressive yellow bile. Ebn Sina (Avicenna) described migraine in his textbook “El Qanoon fel teb” as “ small movements, drinking and eating, and sounds provoke the pain… the patient cannot tolerate the sound of speaking and light. He would like to rest in darkness alone.” Abu Bakr Mohamed Ibn Zakariya Razi noted the association of headache with different events in the lives of women, “…And such a headache may be observed after delivery and abortion or du”classic migraine” is no longer used, and has been replaced by the term “migraine with aura” Graham and Wolff (1938) published their paper advocating ergotamine tartrate for relieving migraine. Later in the 20th century, Harold Wolff (1950) developed the experimental approach to the study of headache and elaborated the vascular theory of migraine, which has come under attack as the pendulum again swings to the neurogenic theory.


Recently, there has been renewed interest in Wolff’s vascular theory of migraine led by Elliot Shevel, a South African headache specialist, who has published a number of articles providing compelling evidence that Wolff was correct. Trepanation, the deliberate and (usually) nonfatal drilling of holes into a skull, was practiced 9,000 years ago and earlier. Some scholars have (controversially) speculated this drastic procedure might have been a migraine treatment, based on cave paintings and on the fact that trepanation was a historical migraine treatment in 17th-century Europe. In Bibliotheca Anatomica, Medic, Chirurgica, published in London in 1712, five major types of headaches are described, including the “Megrim”, recognizable as classic migraine.


Biomarker May Help Identify Responders to Antidepressant



Previous research had shown that ketamine can lift symptoms of depression within hours in many patients. But side effects hamper its use as a first-line medication. As a result, studies are underway on ketamine’s mechanism of action in hopes of developing a safer agent that works similarly. Ketamine works through a different brain chemical system than conventional antidepressants. It initially blocks a protein on brain neurons, called the NMDA receptor, to which the chemical messenger glutamate binds. However, it is not known if the drug’s rapid antidepressant effects are a direct result of this blockage or of downstream effects triggered by the blockage. A biological marker has now been identified that may help to identify which depressed patients will respond to an experimental, rapid-acting antidepressant. The brain signal, detectable by noninvasive imaging, also holds clues to the agent’s underlying mechanism, which are vital for drug development. The signal is among the latest of several such markers, including factors detectable in blood, genetic markers, and a sleep-specific brain wave. The study was published in Biological Psychiatry (2012; 71: 939-946)


To tease apart ketamine’s workings, the authors imaged depressed patients’ brain electrical activity with magnetoencephalography (MEG). Spontaneous activity was monitored while subjects were at rest, and activity evoked by gentle stimulation of a finger, before and 6.5 hours after an infusion of ketamine. It is known that by blocking NMDA receptors, ketamine causes an increase in spontaneous electrical signals, or waves, in a particular frequency range in the brain’s cortex, or outer mantle. Hours after ketamine administration — in the timeframe in which ketamine relieves depression — spontaneous electrical activity in people at rest was the same whether or not the drug lifted their depression. Electrical activity evoked by stimulating a finger, however, was different in the two groups. MEG imaging made it possible to monitor excitability of the somatosensory cortex, the part of the cortex that registers sensory stimulation. Those who responded to ketamine showed an increased response to the finger stimulation, a greater excitability of the neurons in this part of the cortex. Such a change in excitability is likely to result, not from the immediate effects of blocking the receptor, but from other processes downstream, in the cascade of effects set in motion by NMDA. Evidence points to changes in another type of glutamate receptor, the AMPA receptor, raising questions about whether the blocking of NMDA receptors is even necessary for ketamine’s antidepressant effect. If NMDA blockade is just a trigger, then targeting AMPA receptors may prove a more direct way to effect a lifting of depression.


A separate study of ketamine biomarkers adds to evidence that the drug may work, in part, by strengthening neural connections. Thirty treatment resistant depressed patients who received ketamine showed increased sleep-specific slow brainwave activity (SWA) — a marker of such strengthened synapses and of increased synchronization of networks in the cortex. They also had higher blood levels of a key neural growth chemical, brain-derived neurotrophic factor (BDNF), previously linked, in animal studies, to ketamine’s action. Intriguingly, the boosts in BDNF were proportional to those in SWA only among 13 participants whose depressions significantly lifted — suggesting a potential marker of successful treatment.


In another recent study, by-products of the chemical breakdown of ketamine, detectable in blood, helped to sort out responders from non-responders, as well as diagnosis and symptoms. This first study of its kind pinpointed correlates of such downstream ketamine metabolites in 45 treatment resistant depressed unipolar and 22 depressed bipolar patients. Blood levels of one metabolite were higher among bipolar non-responders, indicating that these patients might require a lower dose of the drug for optimal efficacy. Levels of three related metabolites were higher in bipolar patients, with only one, of a different type, elevated in patients with major depression. Higher levels of three metabolites of the former type were also associated with lower scores on measures of psychotic and other side effects, following ketamine treatment. The identification of these downstream metabolites opens the door to possibly developing them into newer treatments that are better tolerated than ketamine.

Brain Hubs Boil When Hoarders Face Pitching Their Own Stuff



Hoarding disorder is a proposed category in psychiatry’s new diagnostic manual, DSM-5, is characterized by avoidance of decision-making about possessions.


According to an article published in the Archives of General Psychiatry (2012;69:832-841), , parts of a decision-making brain circuit patients with hoarding disorder is under-activated when dealing with others’ possessions, but over-activated when deciding whether to keep or discard their own things. Brain scans revealed the abnormal activation in areas of the anterior cingulate cortex and insula known to process error monitoring, weighing the value of things, assessing risks, unpleasant feelings, and emotional decisions. The new findings pinpoint brain circuit activity suspected of underlying the lack of self-insight, indecisiveness, sense that the wrong decision is being made, inflated estimates of the desirability of objects, and exaggerated perception of risk that are often experienced with the disorder.


In the study, brain activity of 43 hoarding disorder patients was compared to that of 31 obsessive compulsive disorder (OCD) patients and 33 healthy controls while they had to decide whether to keep or discard their own or others’ junk mail and newspapers. Notably, such ownership did not appear to differentially affect brain activity in the OCD patients. Hoarding disorder patients, as expected, decided to keep many more items than the other groups.


In hoarding disorder, the implicated brain areas are hubs of a salience network that weighs the emotional significance of things and regulates emotional responses and states. Hoarding patients’ severity of symptoms, self-ratings of indecisiveness, and feeling of things being “not just right” were correlated with the degree of aberrant activity in these hubs. The results add to evidence of impaired decision-making in hoarding disorder and may help to disentangle its brain workings from those of OCD and depression.


The opposite behavior, throwing things out readily without understanding intrinsic value or value to another person, is linked to problems with aggression, and displaced, unconscious anger [editor’s note].

Bacillus-Calmette-Guerin for Treatment of Long-Term Type 1 Diabetes


No targeted immunotherapies reverse type 1 diabetes in humans. However, in a rodent model of type 1 diabetes, Bacillus Calmette-Guerin (BCG) reversed disease by restoring insulin secretion. Specifically, it stimulates innate immunity by inducing the host to produce tumor necrosis factor (TNF), which, in turn, kills disease-causing autoimmune cells and restores pancreatic beta-cell function through regeneration.


As a result, a study published online in PLoS ONE (8 August 2012), administered BCG, a generic vaccine, in a proof-of-principle, double-blind, placebo-controlled trial of adults with long-term type 1 diabetes (mean: 15.3 years) at one clinical center in North America. Six subjects were randomly assigned to BCG or placebo and compared to self, healthy paired controls (n = 6) or reference subjects with (n = 57) or without (n = 16) type 1 diabetes, depending upon the outcome measure. Blood samples were monitored weekly for 20 weeks for insulin-autoreactive T cells, regulatory T cells (Tregs), glutamic acid decarboxylase (GAD) and other autoantibodies, and C-peptide, a marker of insulin secretion.


Results showed that BCG-treated patients and one placebo-treated patient who, after enrollment, unexpectedly developed acute Epstein-Barr virus infection, a known TNF inducer, exclusively showed increases in dead insulin-autoreactive T cells and induction of Tregs. In addition, C-peptide levels (pmol/L) significantly rose transiently in two BCG-treated subjects and the EBV-infected subject in reference diabetic subjects. BCG-treated subjects each had more than 50% of their C-peptide values above the 95th percentile of the reference subjects. The EBV-infected subject had 18% of C-peptide values above this level.


According to the authors, BCG treatment or EBV infection transiently modified the autoimmunity that underlies type 1 diabetes by stimulating the host innate immune response and that this suggests that BCG or other stimulators of host innate immunity may have value in the treatment of long-term diabetes.

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.


FDA Approves First Generic Actos to Treat Type 2 Diabetes


Diabetes is a disease in which blood glucose, or sugar, levels are too high. Glucose comes largely from the food we eat. Insulin is a hormone that helps move glucose into the body’s cells to help them produce energy. In people with type 2 diabetes the body does not make or use insulin well. Without enough insulin, glucose stays in the blood. Over time, too much glucose in the blood can cause serious health problems such as damage to eyes, kidneys, and nerves. Diabetes can also contribute to heart disease, and stroke.


The FDA has approved the first generic version of Actos (pioglitazone hydrochloride) tablets. Along with diet and exercise, pioglitazone is used to improve blood glucose control in adults with type 2 diabetes. Mylan Pharmaceuticals, based in Morgantown, W.Va., gained FDA approval for 15 milligram, 30 mg and 45 mg pioglitazone tablets.


Pioglitazone is dispensed with a patient Medication Guide that provides important instructions about its use and drug safety information. The drug has a Boxed Warning to emphasize that pioglitazone may cause or worsen heart failure, particularly in certain patient populations. Careful monitoring of patients when starting the drug or increasing the dose is recommended. The product label also notes that the use of pioglitazone for more than one year may be associated with an increased risk of bladder cancer.

The most common side effects reported by patients using pioglitazone include cold-like symptoms, headache, sinus infection, muscle pain, and sore throat. Information about the availability of generic pioglitazone can be obtained from the manufacturer.


Generic drugs approved by FDA must be of the same high quality and strength as brand-name drugs. The generic manufacturing and packaging sites must pass the same quality standards as those for brand-name drugs.


Mashed Parsnip-Potato-Carrot Loaf


The recipes posted in this section aim to be:
Very low sodium
Very low fat
Very low calorie
High vitamin/ mineral content
Sugar free
Relatively quick and easy to make




1 1/4 pounds sweet potatoes
1 pound parsnips
1 Container (8 oz) of Tofutti (this is soy cream cheese, available at Fresh Direct and other stores)
2 Tablespoons Canola oil
1 Large carrot
1 packed Tablespoon freshly grated horseradish, divided (or store-bought in glass jar)
Pinch salt, (or no salt)
Pinch black pepper
Sugar-free maple syrup
(optional) 1 Fresh Butternut squash or you can get it frozen.
Garnish loaf with a sprinkling of wheat germ and sliced almonds




  • Preheat oven to 350 degrees.
  • Scrub all the veggies and peel the skin off
  • Place on a cookie sheet and roast for about 40 to 50 minutes or until they have softened.
  • Remove veggies from oven and cut into approximately ¼ inch thick pieces
  • Combine the cut up veggies in a large bowl with the Tofutti, oil, salt, pepper and half of the horseradish
  • In the bowl, mash with a potato masher to desired texture. Leave a few lumps for texture.
  • Stir in the other half of remaining horseradish, making sure to incorporate well.
  • To the mashed veggies, add sugar-free maple sugar, to your taste and spoon the mixture into a loaf pan
  • Sprinkle with wheat germ and sliced almonds and reheat for 5-10 minutes.  Serve hot


This is a wonderful side dish for fish along with a green salad.  This summer we are enjoying light well-chilled Orvieto wine.  Like vodka, chill in the freezer and also chill the glasses (not in the freezer)

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