Ruth J Hickman, MD – Brain Blogger Health and Science Blog Covering Brain Topics Wed, 30 May 2018 15:00:03 +0000 en-US hourly 1 Current Treatments for Post-Amputation Pain Fri, 26 Jul 2013 11:00:09 +0000 In the US, surgeons perform about 185,000 limb amputations each year, and the majority of these individuals are left with some sort of post-amputation pain. Unfortunately, post-amputation pain syndromes have proven very difficult to treat. A variety of treatments are available, but most of these have not had high quality clinical trials, and only appear beneficial in some cases.

Post-amputation pain falls into two distinct categories: phantom limb pain and residual limb pain. Phantom limb pain refers to unpleasant and painful sensations that seem to the patient to originate from the lost limb, even though the individual consciously understands that the limb is no longer there. One study found that the incidence of phantom limb pain might be as high as 85%. The pain can vary from sharp and shooting sensations to dull, squeezing, or cramping sensations.

An amputee may also perceive residual limb pain (sometimes called “stump” pain) in the part of the body that remains after amputation. It is typically a sharp, burning pain, with a reported incidence of up to 74%. Often, an individual experiences both types of pain syndromes. These pain syndromes are separate from other types of pain an amputee might experience, such as those arising from an incorrectly fitted prosthetic device.

Multiple mechanisms appear to play a role in the development of post-amputation pain, though not all mechanisms may be present in every individual patient. For example, in the brain itself, reorganization in the somatosensory cortex is thought to play a role (this brain area is partly responsible for “mapping” sensations onto the relevant body part). Evidence also points to a role for the spinal cord in post-amputation pain, specifically in a region known as the dorsal horn, which normally receives the incoming sensory information. In some cases, the nerves which were severed in the amputation also appear to contribute to the condition.

Local injection therapy is one of the current mainstays of treatment for individuals with post-amputation pain; for example, injection of the local pain blocker lidocaine at the amputation site. This is more effectual for residual limb pain than for phantom limb pain, and even then the effect is usually temporary. 

Drug treatment is another option. NMDA antagonists like ketamine, opioid drugs like morphine, calcitonin, and anticonvulsant drugs have all shown mixed results in studies. Various types of surgical treatment are sometimes attempted, such as peripheral nerve stimulation, motor cortex stimulation, and deep brain stimulation. These treatments are still experimental, but motor cortex stimulation in particular looks like it may prove beneficial. One study found 53% of phantom limb patients were successfully treated with this method.

Mirror therapy provides another intriguing and cost-effective mode of treatment. In this approach, a mirror is placed adjacent to an intact limb, providing the illusion that the amputated limb is present. Some subjects report immediate lessening or elimination of pain, and multiple studies have demonstrated at least short-term pain reduction using this simple technique. It is believed that this feedback can help somatosensory pathways reorganize, thus reducing pain.

Future developments may involve better classifying patients into subgroups, which may show different response levels to different treatments. Many patients will continue to need multimodal, individualized treatment. Researchers hope to develop better and more proven treatments, partially through a more complete understanding of the multiple potential causes of the condition. New drugs, such as anti-nerve growth factor antibodies, are currently under early development, and may one day provide a new class of medications for the physician’s toolkit.


Chan BL, Witt R, Charrow AP, Magee A, Howard R, Pasquina PF, Heilman KM, & Tsao JW (2007). Mirror therapy for phantom limb pain. The New England journal of medicine, 357 (21), 2206-7 PMID: 18032777

Hsu E, & Cohen SP (2013). Postamputation pain: epidemiology, mechanisms, and treatment. Journal of pain research, 6, 121-36 PMID: 23426608

Image via Alan C. Heison / Shutterstock.

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Math Anxiety – Dealing with Fear of Failure Wed, 10 Jul 2013 11:00:50 +0000 Not everybody loves math. In fact, some people report tension, apprehension, and fear when faced with the need to perform mathematical tasks as a part of everyday life. Not surprisingly, these highly math anxious individuals (HMAs) perform more poorly on math related tasks than individuals with low math anxiety, tending to avoid math classes and math-related career paths. But, understanding more about the neural underpinnings of high math anxiety may help educators develop better strategies for counteracting these tendencies, ultimately opening the door to more diverse career opportunities for HMAs.

Recently, scientists have begun to understand the differences in neural activity that may partially underlie math anxiety. A 2012 study found that when individuals with math anxiety anticipate a math task, they display increased activity bilaterally in the dorso-posterior insula — a region of the brain associated with threat detection and often with the experience of pain itself.

Interestingly, this area did not remain activated during the math task itself: it appears as if the anticipation of math is the painful part, not the actual doing of it. The higher the degree of anxiety, the more this area of the brain appeared to be active. This mechanism helps explain why individuals with high math anxiety avoid math — just thinking about doing it is painful to them!

It’s worth noting that not all individuals with high math anxiety perform poorly on math tasks relative to those with low math anxiety. A 2011 study showed that some individuals with high math anxiety showed increased activity in the inferior frontoparietal regions of the brain relative to individuals with low math anxiety; these same individuals were the ones most likely to perform relatively well on math tasks, even though they were anxious.

This area of the brain includes regions thought to be involved in cognitive control and in dealing with negative emotions in a logical way. In those with high math anxiety, both high performers and low performers showed similar activity in areas of the brain associated with a fear response. Both groups also showed similar activity in regions associated with mathematical calculations. Thus the researchers concluded that the individuals’ cognitive response to their own anxiety may be the most important factor in determining their ultimate performance.

These findings may be used to shape educational strategies for high math anxiety students. The most successful strategies may not be ones that seek to eliminate the anxiety outright. Instead, it may be more effective for educators to teach these students how to utilize their own inner cognitive controls to mitigate the math-anxiety response when it happens — before it has a chance to decrease actual math performance. These individuals might not like doing math any more than before, but they might find themselves able to do it more successfully.


Lyons, I., & Beilock, S. (2012). When Math Hurts: Math Anxiety Predicts Pain Network Activation in Anticipation of Doing Math PLoS ONE, 7 (10) DOI: 10.1371/journal.pone.0048076

Lyons, I., & Beilock, S. (2011). Mathematics Anxiety: Separating the Math from the Anxiety Cerebral Cortex, 22 (9), 2102-2110 DOI: 10.1093/cercor/bhr289

Image via Malota / Shutterstock.

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Ketogenic Diet for Epilepsy and Other Neurological Disorders Wed, 10 Apr 2013 11:00:16 +0000 In recent years, clinicians have utilized a somewhat surprising tool to treat their patients with refractory epilepsy-diet. The majority of people with epilepsy can become free from seizures with the use of antiepileptic medications, but in about 20-30% of people with epilepsy, medications fail to completely control their symptoms. Clinicians and researchers have found the ketogenic diet is an effective way to treat these patients; it is at least as successful as the most recent anticonvulsant drugs designed to treat refractory epilepsy. Researchers have also started exploring the therapeutic potential of the diet in other neurological conditions, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis (ALS), among others.

The ketogenic diet is low in carbohydrates, adequate in protein, and high in fat, and sometimes partially restricted in calories. When following this diet, the brain shifts its main source of energy from glucose to fat. Fats are broken down into ketones, and these ketones are utilized by the brain as its main energy source. This shift in energy source is thought to be related to decreased seizures, though exactly how this happens is not yet clear. Researchers have proposed that the diet may work by altering neurotransmitter function, synaptic transmission, regulation of reactive oxygen species, and mitochondrial dysfunction — pathological mechanisms thought to play a role in a number of neurological diseases.

In Alzheimer’s disease, for example, results from clinical studies have been inconclusive but promising. In one randomized double-blind study, Alzheimer’s patients on a ketogenic diet showed significant cognitive improvement compared to patients not following the diet. In cell cultures, ketone bodies have been shown to be effective against the toxic effects of beta-amyloid, a key pathological feature of the disease. The diet may also help reduce oxidative stress and enhance mitochondrial function.

Mitochondrial dysfunction is also thought to play a contributory role in Parkinson’s disease, with its characteristic movement and cognitive impairment. In one small clinical trial of five patients with Parkinson’s disease, patients on the diet reduced their scores on the Unified Parkinson’s Disease Rating Scale by 43.4%.

The diet may also prove helpful in the treatment of Amyotrophic Lateral Sclerosis, or ALS. Mitochondrial dysfunction is also likely to play role in this devastating disease of the motor neurons. Though human studies have not yet been performed, mouse models of the condition have yielded promising results. In these mouse models, animals given a ketogenic diet showed significant motor improvements compared to animals on a normal diet.

Researchers speculate that the diet may prove helpful in even more neurological conditions, such as recovery from stroke and brain injury. Though the diet is an accepted treatment for refractory epilepsy, in other neurological conditions more clinical trials are needed to see if the diet is truly efficacious. If borne out, the diet may open another therapeutic avenue for the treatment of these diseases.


Griggs RC. Epilepsy. In Andreoli TE, Carpenter CC, Griggs RD, Benjamin IJ, eds. Andreoli and Carpenter’s Cecil Essentials of Medicine. 7th Ed. Philadelphia, PA: Elsevier; 2005: 1120-1128.

Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, & Costantini LC (2009). Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutrition & metabolism, 6 PMID: 19664276

Huffman J, & Kossoff EH (2006). State of the ketogenic diet(s) in epilepsy. Current neurology and neuroscience reports, 6 (4), 332-40 PMID: 16822355

Lee M (2012). The use of ketogenic diet in special situations: expanding use in intractable epilepsy and other neurologic disorders. Korean journal of pediatrics, 55 (9), 316-21 PMID: 23049588

Mackay MT, Bicknell-Royle J, Nation J, Humphrey M, & Harvey AS (2005). The ketogenic diet in refractory childhood epilepsy. Journal of paediatrics and child health, 41 (7), 353-7 PMID: 16014140

Stafstrom CE, & Rho JM (2012). The ketogenic diet as a treatment paradigm for diverse neurological disorders. Frontiers in pharmacology, 3 PMID: 22509165

VanItallie, T., Nonas, C., Di Rocco, A., Boyar, K., Hyams, K., & Heymsfield, S. (2005). Treatment of Parkinson disease with diet-induced hyperketonemia: A feasibility study Neurology, 64 (4), 728-730 DOI: 10.1212/01.WNL.0000152046.11390.45

Image via xpixel / Shutterstock.

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